Did Findings Develop in Utero?
Patient with retinal pigmentary changes reports childhood cardiac problems and maternal infection with German measles while pregnant.
Mark T. Dunbar, O.D.
A 36-year-old white female presented for her routine eye exam. As part of her history, she reported symptoms of dizziness that she had been experiencing for one week. She said that she felt better after eating. She reported no history of nausea, vomiting, visual aura or migraines.
Her medical history was significant for asthma for which she takes albuterol. She was born with a heart murmur and underwent heart valve surgery at age 4. Also, she reported that her mother had German measles when pregnant with the patient. Ocular history was unremarkable, but she said that at prior exams, several doctors commented on how interesting her eyes are.
Best-corrected visual acuity was 20/20 O.U. at distance and near. Pupils were equal and reactive with no afferent pupillary defect. Motility and confrontational fields were full. The anterior segment exam was unremarkable. IOP measured 15mm Hg O.U.
Dilated fundus exam showed a healthy optic nerve with a small cup and good rim coloration O.U. Each macula was flat with yellowish coloration, and vessels appeared normal O.U. Peripheral clinical findings are shown in figures 1 and 2.
1,2. Dilated fundus exam (O.D. left, O.S. right) revealed unusual pigmentary changes.
Take the Retina Quiz
1. How would you describe the fundus findings?
a. Tigroid fundus.
b. Salt and pepper retinopathy.
c. Bone spicule formation.
d. Choroidal folds.
2. What is the likely diagnosis?
a. Retinitis pigmentosa.
b. Congenital rubella retinopathy.
c. Syphilis retinopathy.
d. Ocular albinism.
3. What is the likely etiology?
a. Autoimmune.
b. Virus.
c. Trauma.
d. Bacterial.
4. What additional testing would be most beneficial?
a. Ocular coherence tomography.
b. Electroretinogram.
c. B-scan ultrasonography.
d. Pachymetry.
5. What do the changes around the optic nerve likely represent?
a. Peripapillary atrophy.
b. Myopic crescent.
c. Angioid streaks.
d. Nonspecific changes to the retinal pigment epithelium.
For answers, see bottom of page.
Discussion
The mother’s history of German measles during her pregnancy is evidence that this patient has congenital rubella pigmentary retinopathy.
Rubella infection affects children and young adults but often goes undetected. It results from an RNA virus of the Togaviridae family.
The systemic and ocular complications that manifest with rubella infection in utero are called congenital rubella syndrome (CRS).1 CRS results from primary maternal infection of rubella during the first trimester of the pregnancy. The fetus is most vulnerable to rubella insult in the first 16 weeks of gestation because specific immunity against the virus is undeveloped during the first two trimesters of pregnancy. The virus transplacentally infects the developing fetus and is disseminated in the bloodstream, inhibiting cell growth.
The World Health Organization encourages member countries to eradicate CRS by 2010.1 New CRS cases have been rare since the introduction of the measles-mumps-rubella (MMR) vaccine in 1969.2 The Centers for Disease Control and Prevention recommends vaccinations at age 12 to 15 months and again at age 4 to 6.3
CRS can lead to multisystemic malformations, resulting in severe morbidity and mortality. Malformations most associated with CRS are auditory (sensorineural deafness), cardiac (patent ductus arteriosus) and neurologic (microcephaly and mental retardation).
CRS also can affect almost all ocular structures. CRS can be diagnosed in the presence of these three common signs, either in isolation or in combination, even with a lack of laboratory evidence:2,4
• Congenital cataracts (also known as rubella cataracts). These usually present as dense, symmetrical and bilateral cataracts. The virus enters the lens prior to development of a lens capsule that would otherwise act as a barrier to the virus. Rubella cataracts most commonly occur at the fetal nuclear level.
• Pigmentary retinopathy. A diffuse disturbance of the retinal pigment epithelium (RPE) often has a “salt-and-pepper” appearance. Pigment deposits may vary from fine, powdery, sprinkled or granular shapes throughout the retina. Persistence of the virus in the RPE often causes progression during childhood. This can lead to subretinal neovascularization and subsequent macular scarring, usually in the second decade of life.
• Congenital glaucoma with buphthalmos. This can occur in approximately 10% of infants diagnosed with CRS.3 Glaucoma also can manifest at a later stage in these patients, possibly due to virus-induced trabeculodysgenesis. Delayed-onset glaucoma is more commonly associated with microphthalmos. These patients have a poor visual prognosis.
Less common ocular complications of CRS include iris atrophy, uveal coloboma, nystagmus, strabismus, corneal haze, optic atrophy and high refractive error.
Ancillary testing for patients with CRS may include optical coherence tomography and fluorescein angiography when there is a high suspicion of choroidal neovascularization, visual field exam as part of a standard glaucoma assessment, and electroretinogram (ERG) to aid in the differential diagnosis of CRS and retinitis pigmentosa (RP), which is similar in appearance. ERG is normal in patients who have CRS but abnormal in those who have RP. Our patient’s ERG was normal.
The severity of ocular complications of CRS varies among patients. Our patient only presented with bilateral pigmentary retinopathy. Small angioid streaks were present around the optic nerve, but we believe these were an incidental finding.
Pigmentary retinopathy is common among congenital infections, such as cytomegalovirus, toxoplasmosis and syphilitic retinopathy. Thus, the diagnosis of CRS requires a positive serological finding or history of maternal measles infection, as in our patient. Our patient also presented with congenital cardiac deficits, one of the systemic complications associated with CRS.
We must closely monitor patients who have CRS for the development of glaucoma. Our patient currently has no risk factors for glaucoma. We plan to monitor her annually. We do not know why she experienced dizziness, but we told her to see her primary-care doctor if her symptoms continue.
Written by Neha Patel, O.D., an optometry resident at Bascom Palmer Eye Institute in Miami.
1. Khandekar R, Al Awaidy S, Ganesh A, Bawikar S. An epidemiological and clinical study of ocular manifestations of congenital rubella syndrome in Omani children. Arch Ophthalmol 2004 Apr;122(4):541-5.
2. Weisinger HS, Pesudovs K. Optical complications in congenital rubella syndrome. Optometry 2002 Jul;73(7):418-24.
3. Watson JC, Hadler SC, Dykewicz CA, et al. Measles, mumps, and rubella—vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1998 May 22;47(RR-8):1-57.
4. Vijayalakshmi P, Kakkar G, Samprathi A, Banushree R. Ocular manifestations of congenital rubella syndrome in a developing country. Indian J Ophthalmol 2002 Dec;50(4):307-11.
Answers: 1) b; 2) b; 3) b; 4) b; 5) c.
Jam Gadang.Bukittinggi. Sumatera Barat .Indonesia
24.jpg)
Bung Hatta statue ,Bukittinggi
IKATAN DOKTER INDONESIA (IDI).Sumatera Barat
INDONESIAN MEDICAL ASSOCIATION
dr Firman Abdullah SpOG / OBGYN
USG 3D/4D images (dr Firman Abdullah SpOG/ObGyn picture's )
dr Firman Abdullah SpOG / OBGYN
Monday, June 15, 2009
Childhood Blindness
Childhood Blindness
As the causes of blindness in children differ from those in adults, different control measures are needed. In low-income countries, high proportions of children are blind from preventable causes, which require community-based interventions. In all regions, children with treatable diseases, principally cataract, can have their sight restored. Childrens’ eyes cannot, however, be considered smaller versions of adults’ eyes, and specific expertise and equipment are required. Unlike adults, children require longterm follow-up after surgery, to manage complications and to prevent amblyopia (‘lazy eyes’). The understanding and involvement of parents is critical. In all regions, children with irreversible visual loss must be assessed for low-vision services, early visual stimulation, rehabilitation or special education, depending on their age and level of residual vision.
Current situation
It has been estimated that there are 1.4 million blind children in the world, 1 million of whom live in Asia and 300 000 in Africa (26). The prevalence ranges from 0.3/1000 children aged 0–15 years in affluent countries to 1.5/1000 children in very poor communities. Although the number of blind children is relatively low, they have a lifetime of blindness ahead, with an estimated 75 million blind-years (number blind × length of life), second only to cataract.
The same report showed that 500 000 children become blind each year (nearly one per minute). Many die in childhood from the underlying cause, such as measles, meningitis, RUBELLA , prematurity, genetic diseases and head injuries. Most blind children are either born blind or become blind before their fifth birthday. Owing to demographic differences, the number of children who are blind per 10 million population varies from approximately 600 in affl uent countries to approximately 6000 in very poor communities. About 40% of the causes of childhood blindness are preventable or treatable.
The causes of childhood blindness vary, but the main avoidable causes are:
corneal scarring in Africa and poorer countries in Asia;
cataract everywhere
glaucoma everywhere;
retinopathy of prematurity in high- and middle-income countries and some cities in Asia;
refractive errors everywhere, but particularly in South-East Asia; and
low vision, which encompasses visual impairment and blindness from untreatable causes, in all regions.
The main causes of blindness in children change over time. As a consequence of child survival programmes (for example, integrated management of childhood illness), corneal scarring due to measles and vitamin A defi ciency is declining in many developing countries, so that the proportion due to cataract is increasing. Retinopathy of prematurity is emerging as an important cause in the middle-income countries of Latin America and eastern Europe and is likely to become an important cause in Asia over the next decade. The prevalence of refractive errors, particularly myopia, is increasing in school-age children, especially in South-East Asia
Achievements
Vitamin A deficiency: There are concerted global efforts to control vitamin A deficiency in children and women of child-bearing age. The United Nations Children’s Fund (UNICEF) has estimated (27) that between 1998 and 2000 about 1 million child deaths were prevented by these global efforts, and the Vitamin A Global Initiative led by UNICEF has set the target of eliminating vitamin A deficiency by the year 2010.
Measles: Measles immunization coverage continues to improve, resulting in a lower incidence of measles and measles-related deaths. In 2004, there were 454 000 deaths from measles, a reduction of 48% from 1999. The Measles Initiative (28), a partnership between the American Red Cross, the United States Centers for Disease Control and Prevention, the United Nations Foundation, UNICEF and WHO, is now focusing on 47 countries, mainly in sub-Saharan Africa where 98% of deaths occur, with the goal of reducing deaths from measles by 90% by 2010 from the estimates for 2000. The WHO Region of the Americas has eliminated measles, and three other regions have set elimination targets. Reducing the prevalence of measles will also reduce the number of children with measles-related corneal ulceration and scarring.
Retinopathy of prematurity: Programmes for detecting and treating severe retinopathy in premature infants at risk are expanding throughout Latin America and eastern Europe and are being established in urban areas in China, India and other Asian countries.
Child eye-care centres: Training in paediatric ophthalmology is becoming more prevalent, and tertiary level child eye-care centres are being set up in low-income countries.
Consumables for children: Low-vision devices suitable for children as well as other consumables are available through resource centres in Hong Kong, China, and Durban, South Africa.
Limitations
inadequate population-based data on the prevalence and causes of blindness in children;
lack of awareness among parents and the community about preventive measures and that the vision of children who are blind can often be improved or maximized;
barriers to accessing services, including lack of awareness, distance, cost, fear and competing demands for scarce resources within the family;
shortage of paediatric eye-care professionals and inadequate opportunities for training in paediatric ophthalmology in most low-income countries;
lack of international exchanges in human resource development for paediatric ophthalmology and insufficiently developed postgraduate curricula for training paediatric ophthalmologists in many industrialized countries;
fragmentation of paediatric eye-care services in many countries, so that children who need specialist expertise are managed by general ophthalmologists; and
inadequate provision of special education for children with irreversible visual loss, particularly in low-income countries.
Aim
to eliminate avoidable causes of blindness in children
Objectives
to promote programmes that reduce corneal scarring and visual loss from vitamin A deficiency and measles and
to implement interventions against harmful traditional practices, neonatal conjunctivitis and eye injuries;
to provide services to treat children with cataract, glaucoma, retinopathy of prematurity and corneal ulcer or scarring;
to provide optical services for children with refractive errors, for instance in school eye-health programmes; and to provide services for children with low vision.
Strategies
Provide comprehensive services for children at all levels of service delivery'
In areas where childhood blindness from preventable diseases is common, increase awareness in the community and encourage primary health care, including specific preventive measures at the primary level, through primary eye care, including:
measles immunization, to prevent corneal scarring;
vitamin A supplementation, nutrition education, food supplementation and fortification of commonly eaten foods with vitamin A, to control vitamin A deficiency;
avoidance of harmful traditional practices, to prevent corneal scarring; ocular prophylaxis of newborns, to prevent neonatal conjunctivitis; and
rubella immunization where congenital rubella is an important cause of mortality or morbidity in children, with strategies appropriate to the setting (e.g. schoolgirls aged 12–13 years).
At the secondary level, strengthen diagnosis and management of less complex cases.
At the tertiary level, provide specialist training and services for the management of surgically remediable visual loss from cataract, congenital glaucoma and corneal scarring, including longterm follow up. Examine premature infants at risk of retinopathy of prematurity, treat those with severe disease and promote oxygen monitoring.
As children with cataract often do not present, or present late, undertake active case finding, particularly for girls.
Provide each child eye-care centre with a well-trained team (e.g. paediatric or child-centred ophthalmologist, optometrist, anaesthetist, counsellor, low-vision therapist, mid-level personnel), appropriate equipment and infrastructure and access to consumables for infants and children (e.g. small spectacle frames, high-power intraocular lenses).
Ensure the availability of ophthalmologists experienced in indirect ophthalmoscopy to identify premature infants in intensive neonatal care who require treatment for retinopathy of prematurity.
Ensure that infants at risk have fundus examinations starting 4–6 weeks after birth and that infants with severe disease are treated immediately by laser or cryotherapy.
Develop low-vision services for children with irreversible visual loss at secondary and tertiary levels.
Promote school eye-health programmes:
for the diagnosis and management of common conditions, such as refractive errors, and trachoma and vitamin A deficiency in endemic areas;
to promote a healthy environment; and
to educate children in looking after their eyes as part of the normal school curriculum.
In areas where significant uncorrected refractive errors affect more than 2% of schoolchildren aged 11–15 years (29).
Ensure that children undergo a simple vision screening examination, ideally as part of the school health programme, with provision of spectacles to those who will benefit.
Ensure that all children in special education establishments are examined by an ophthalmologist and receive medical, surgical, optical or low-vision services to maximize their vision.
Ensure good linkages between eye-care services and those providing education and rehabilitation services for incurably blind children.
Targets
By 2011, each country’s national plan will include the control of blindness in children, with achievable targets.
For disease control:
reduction in the global prevalence of blindness in children from 0.75/1000 to 0.4/1000 by the year 2020;
reduction in corneal scarring caused by vitamin A deficiency, measles, neonatal conjunctivitis and the use of traditional eye remedies;
reduction in the proportion of blindness due to retinopathy of prematurity, particularly in countries where it is responsible for more than 10% of blindness in children; and appropriate management of children with cataract, with immediate, effective optical correction in suitably equipped specialist centres.
For human resource development:
prevention of blindness in children an explicit aim of primary health care programmes and included in all primary eye-care training curricula
personnel in secondary-level eye clinics with knowledge and skills necessary to manage less complex eye conditions in children; and
at least one child eye-care centre with a well-trained team for every 20 million population by the year 2011 and one per 10 million by 2020.
For infrastructure and technology
all child eye-care centres have adequate supplies of consumables for children, e.g. paediatric aphakic spectacles and low-power, small-diameter intraocular lenses; and
secondary-level eye clinics have facilities to provide appropriate spectacles for children with refractive errors.
Indicators
prevalence of childhood blindness;
prevalence of avoidable childhood blindness, by cause
number of child eye-care centres per at least 20 million population (recommended);
from other WHO programmes:
proportion of countries with measles immunization coverage > 80%;
proportion of countries with vitamin A deficiency control programmes or with eliminated vitamin A deficiency, in line with global targets; and
proportion of countries with a policy or immunization programme for rubella.
Trachoma
Trachoma, which is the commonest infectious cause of blindness, is caused by Chlamydia trachomatis. Children who have the active stages of the disease are the reservoir of infection, while blindness, which occurs after repeated episodes of infection, principally affects adults. Boys and girls are equally affected by active infection, while blindness is more common in women. Trachoma is a condition of poverty and is a focal disease, affecting communities that have poor water supplies and sanitation and poor health services. The organism is transmitted from person to person through direct and indirect contact and by flies. Blindness can be prevented by surgery to correct inturning of the upper lid (trichiasis),
while the infection and its transmission can be reduced with surgery, antibiotics, facial cleanliness and environmental change (the SAFE strategy).
Current situation
Trachoma is endemic in 55 countries: Afghanistan, Algeria, Australia, Benin, Brazil, Burkina Faso, Cambodia, Cameroon, Central African Republic, Chad, China, Côte d’Ivoire, Djibouti, Egypt, Eritrea, Ethiopia, Fiji, Gambia, Ghana, Guatemala, Guinea, Guinea-Bissau, India, Islamic Republic of Iran, Iraq, Kenya, Kiribati, Lao People’s Democratic Republic, Libyan Arab Jamahiriya, Malawi, Mali, Mauritania, Mexico, Morocco, Mozambique, Myanmar, Namibia, Nepal, Niger, Nigeria, Oman, Pakistan, Papua New Guinea, Senegal, Solomon Islands, Somalia, Sudan, Togo, Uganda, United Republic of Tanzania, Vanuatu, Vietnam, Yemen, Zambia and Zimbabwe. The estimated number of affected people has fallen from 360 million in 1985 to about 80 million today. Trachoma affects the poorest and most remote rural areas of Africa, Asia, Central and South America, Australia and the Middle East (30). Updated reports on 36 countries are available (31), while 19 endemic countries have not yet reported data.
There are approximately 10.6 million people with inturned eyelashes (entropion trichiasis), for which eyelid surgery is needed to prevent blindness. The majority of these people are women. An estimated 5.9 million adults are irreversibly visually impaired from corneal scarring due to trachoma.
Achievements
At national level, political support for trachoma control has increased continually since 1997, the year the WHO Alliance for the Global Elimination of Blinding Trachoma (GET 2020) was created; intersector collaboration is growing, and use of the SAFE strategy for eliminating the disease is increasing.
GET 2020 is active at the global level. It is a public–private partnership, bringing together WHO, national coordinators, nongovernmental organizations, donors and international experts, with support from the pharmaceutical industry. Launched in 1997, it was endorsed by WHA Resolution 51.11, adopted in 1998. A nongovernmental organization task force, the International Coalition for Trachoma Control, has been working since 2004 within the framework of GET 2020 to improve information exchange with governments and to coordinate the efforts of international nongovernmental organizations in countries. The GET 2020 secretariat is responsible for trachoma within the WHO department focusing on neglected tropical diseases. The WHO GET 2020 secretariat is also coordinating the drawing up of guidelines for certification of elimination of blinding trachoma, as requested by several WHO Member States.
Limitations
Not all countries in which blinding trachoma is suspected to be endemic have undertaken a proper assessment of the epidemiological situation of trachoma.
The WHO SAFE strategy does not yet cover 100% of the populations in trachoma-endemiccountries.
International partners who are members of the WHO GET 2020 Alliance do not implement the entire SAFE strategy, but only certain components.
The available resources for trachoma control are not suffi cient to achieve the ultimate intervention goals in all countries.
Aim
Global elimination of blindness due to trachoma by the year 2020 by applying the WHO-recommended SAFE strategy
Objectives
Integrate the SAFE strategy into primary health care in all communities with blinding trachoma.
Certify the elimination of trachoma in countries, where applicable.
Strategies
Identify districts where blinding trachoma is a public health problem
Provide surgical services with trained and certifi ed medical or paramedical staff at community level to operate on cases of trachomatous trichiasis.
Provide mass antibiotic administration (azithromycin or tetracycline ointment) for populations living in districts where the prevalence of active disease (follicular trachoma) in children aged 1–9 years is above 10%. In districts where the prevalence is below 10% but above 5%, community or family treatment might be required. The treatment interventions must be implemented in association with promotion of personal hygiene, with particular focus on facial cleanliness of children under 10 and improvement of environmental hygiene and sanitation as part of primary health care.
During the 10th Meeting of GET 2020 (31), the following recommendations were adopted to facilitate implementation of the SAFE strategy:
All endemic countries should establish collaboration with the WHO GET 2020 Secretaria
All endemic countries, particularly the more populous countries, should continue to assess the distribution and severity of trachoma, e.g. by rapid assessment
Countries should develop their strategic 5-year national trachoma plans, in collaboration with national and international partners, reflecting the commitment to implement the SAFE strategy; these plans should be integrated into their VISION 2020 national plans (WHA Resolution 56.26).
WHO should design methods and tools for assessing the trachoma burden and for certifying elimination of the disease.
Countries should endeavour to increase coverage of all the components of the SAFE strategy to the highest possible level.
In countries in which active trachoma prevalence has declined to < 5%, rapid assessment might be the most useful tool for identifying communities that need trachoma control activities as a priority in order to eliminate remaining pockets of the disease.
Countries should institute an ongoing audit of the quality of trichiasis surgery on the basis of the WHO guidelines for assessment (32)
Increased intersectoral collaboration should be instituted at national and district levels to ensure comprehensive implementation of all components of the SAFE strategy.
WHO and the international development community should advocate and promote trachoma as a marker of poverty and GET 2020 as a model of a public–private partnership for tackling the problem.
Target
By 2020, all 49 countries where endemic trachoma has been confi rmed should have achieved their ultimate intervention goals. The countries with plans for achieving those goals are shown in table 3
Indicators
number of countries with blinding trachoma as a public health problem;
proportion of endemic communities covered by the SAFE strategy;
recommended, where applicable:
• prevalence of trachomatous entropion trichiasis at district level;
• prevalence of active trachoma in 1–9-year-olds at district level; and
• progress in achieving the ultimate intervention goals.
National data are being used to refi ne ultimate intervention goals and annual intervention objectives in countries. The data are included in WHO information on neglected tropical diseases, in the WHO Global Health Atlas and in the WHO Infobase.
As the causes of blindness in children differ from those in adults, different control measures are needed. In low-income countries, high proportions of children are blind from preventable causes, which require community-based interventions. In all regions, children with treatable diseases, principally cataract, can have their sight restored. Childrens’ eyes cannot, however, be considered smaller versions of adults’ eyes, and specific expertise and equipment are required. Unlike adults, children require longterm follow-up after surgery, to manage complications and to prevent amblyopia (‘lazy eyes’). The understanding and involvement of parents is critical. In all regions, children with irreversible visual loss must be assessed for low-vision services, early visual stimulation, rehabilitation or special education, depending on their age and level of residual vision.
Current situation
It has been estimated that there are 1.4 million blind children in the world, 1 million of whom live in Asia and 300 000 in Africa (26). The prevalence ranges from 0.3/1000 children aged 0–15 years in affluent countries to 1.5/1000 children in very poor communities. Although the number of blind children is relatively low, they have a lifetime of blindness ahead, with an estimated 75 million blind-years (number blind × length of life), second only to cataract.
The same report showed that 500 000 children become blind each year (nearly one per minute). Many die in childhood from the underlying cause, such as measles, meningitis, RUBELLA , prematurity, genetic diseases and head injuries. Most blind children are either born blind or become blind before their fifth birthday. Owing to demographic differences, the number of children who are blind per 10 million population varies from approximately 600 in affl uent countries to approximately 6000 in very poor communities. About 40% of the causes of childhood blindness are preventable or treatable.
The causes of childhood blindness vary, but the main avoidable causes are:
corneal scarring in Africa and poorer countries in Asia;
cataract everywhere
glaucoma everywhere;
retinopathy of prematurity in high- and middle-income countries and some cities in Asia;
refractive errors everywhere, but particularly in South-East Asia; and
low vision, which encompasses visual impairment and blindness from untreatable causes, in all regions.
The main causes of blindness in children change over time. As a consequence of child survival programmes (for example, integrated management of childhood illness), corneal scarring due to measles and vitamin A defi ciency is declining in many developing countries, so that the proportion due to cataract is increasing. Retinopathy of prematurity is emerging as an important cause in the middle-income countries of Latin America and eastern Europe and is likely to become an important cause in Asia over the next decade. The prevalence of refractive errors, particularly myopia, is increasing in school-age children, especially in South-East Asia
Achievements
Vitamin A deficiency: There are concerted global efforts to control vitamin A deficiency in children and women of child-bearing age. The United Nations Children’s Fund (UNICEF) has estimated (27) that between 1998 and 2000 about 1 million child deaths were prevented by these global efforts, and the Vitamin A Global Initiative led by UNICEF has set the target of eliminating vitamin A deficiency by the year 2010.
Measles: Measles immunization coverage continues to improve, resulting in a lower incidence of measles and measles-related deaths. In 2004, there were 454 000 deaths from measles, a reduction of 48% from 1999. The Measles Initiative (28), a partnership between the American Red Cross, the United States Centers for Disease Control and Prevention, the United Nations Foundation, UNICEF and WHO, is now focusing on 47 countries, mainly in sub-Saharan Africa where 98% of deaths occur, with the goal of reducing deaths from measles by 90% by 2010 from the estimates for 2000. The WHO Region of the Americas has eliminated measles, and three other regions have set elimination targets. Reducing the prevalence of measles will also reduce the number of children with measles-related corneal ulceration and scarring.
Retinopathy of prematurity: Programmes for detecting and treating severe retinopathy in premature infants at risk are expanding throughout Latin America and eastern Europe and are being established in urban areas in China, India and other Asian countries.
Child eye-care centres: Training in paediatric ophthalmology is becoming more prevalent, and tertiary level child eye-care centres are being set up in low-income countries.
Consumables for children: Low-vision devices suitable for children as well as other consumables are available through resource centres in Hong Kong, China, and Durban, South Africa.
Limitations
inadequate population-based data on the prevalence and causes of blindness in children;
lack of awareness among parents and the community about preventive measures and that the vision of children who are blind can often be improved or maximized;
barriers to accessing services, including lack of awareness, distance, cost, fear and competing demands for scarce resources within the family;
shortage of paediatric eye-care professionals and inadequate opportunities for training in paediatric ophthalmology in most low-income countries;
lack of international exchanges in human resource development for paediatric ophthalmology and insufficiently developed postgraduate curricula for training paediatric ophthalmologists in many industrialized countries;
fragmentation of paediatric eye-care services in many countries, so that children who need specialist expertise are managed by general ophthalmologists; and
inadequate provision of special education for children with irreversible visual loss, particularly in low-income countries.
Aim
to eliminate avoidable causes of blindness in children
Objectives
to promote programmes that reduce corneal scarring and visual loss from vitamin A deficiency and measles and
to implement interventions against harmful traditional practices, neonatal conjunctivitis and eye injuries;
to provide services to treat children with cataract, glaucoma, retinopathy of prematurity and corneal ulcer or scarring;
to provide optical services for children with refractive errors, for instance in school eye-health programmes; and to provide services for children with low vision.
Strategies
Provide comprehensive services for children at all levels of service delivery'
In areas where childhood blindness from preventable diseases is common, increase awareness in the community and encourage primary health care, including specific preventive measures at the primary level, through primary eye care, including:
measles immunization, to prevent corneal scarring;
vitamin A supplementation, nutrition education, food supplementation and fortification of commonly eaten foods with vitamin A, to control vitamin A deficiency;
avoidance of harmful traditional practices, to prevent corneal scarring; ocular prophylaxis of newborns, to prevent neonatal conjunctivitis; and
rubella immunization where congenital rubella is an important cause of mortality or morbidity in children, with strategies appropriate to the setting (e.g. schoolgirls aged 12–13 years).
At the secondary level, strengthen diagnosis and management of less complex cases.
At the tertiary level, provide specialist training and services for the management of surgically remediable visual loss from cataract, congenital glaucoma and corneal scarring, including longterm follow up. Examine premature infants at risk of retinopathy of prematurity, treat those with severe disease and promote oxygen monitoring.
As children with cataract often do not present, or present late, undertake active case finding, particularly for girls.
Provide each child eye-care centre with a well-trained team (e.g. paediatric or child-centred ophthalmologist, optometrist, anaesthetist, counsellor, low-vision therapist, mid-level personnel), appropriate equipment and infrastructure and access to consumables for infants and children (e.g. small spectacle frames, high-power intraocular lenses).
Ensure the availability of ophthalmologists experienced in indirect ophthalmoscopy to identify premature infants in intensive neonatal care who require treatment for retinopathy of prematurity.
Ensure that infants at risk have fundus examinations starting 4–6 weeks after birth and that infants with severe disease are treated immediately by laser or cryotherapy.
Develop low-vision services for children with irreversible visual loss at secondary and tertiary levels.
Promote school eye-health programmes:
for the diagnosis and management of common conditions, such as refractive errors, and trachoma and vitamin A deficiency in endemic areas;
to promote a healthy environment; and
to educate children in looking after their eyes as part of the normal school curriculum.
In areas where significant uncorrected refractive errors affect more than 2% of schoolchildren aged 11–15 years (29).
Ensure that children undergo a simple vision screening examination, ideally as part of the school health programme, with provision of spectacles to those who will benefit.
Ensure that all children in special education establishments are examined by an ophthalmologist and receive medical, surgical, optical or low-vision services to maximize their vision.
Ensure good linkages between eye-care services and those providing education and rehabilitation services for incurably blind children.
Targets
By 2011, each country’s national plan will include the control of blindness in children, with achievable targets.
For disease control:
reduction in the global prevalence of blindness in children from 0.75/1000 to 0.4/1000 by the year 2020;
reduction in corneal scarring caused by vitamin A deficiency, measles, neonatal conjunctivitis and the use of traditional eye remedies;
reduction in the proportion of blindness due to retinopathy of prematurity, particularly in countries where it is responsible for more than 10% of blindness in children; and appropriate management of children with cataract, with immediate, effective optical correction in suitably equipped specialist centres.
For human resource development:
prevention of blindness in children an explicit aim of primary health care programmes and included in all primary eye-care training curricula
personnel in secondary-level eye clinics with knowledge and skills necessary to manage less complex eye conditions in children; and
at least one child eye-care centre with a well-trained team for every 20 million population by the year 2011 and one per 10 million by 2020.
For infrastructure and technology
all child eye-care centres have adequate supplies of consumables for children, e.g. paediatric aphakic spectacles and low-power, small-diameter intraocular lenses; and
secondary-level eye clinics have facilities to provide appropriate spectacles for children with refractive errors.
Indicators
prevalence of childhood blindness;
prevalence of avoidable childhood blindness, by cause
number of child eye-care centres per at least 20 million population (recommended);
from other WHO programmes:
proportion of countries with measles immunization coverage > 80%;
proportion of countries with vitamin A deficiency control programmes or with eliminated vitamin A deficiency, in line with global targets; and
proportion of countries with a policy or immunization programme for rubella.
Trachoma
Trachoma, which is the commonest infectious cause of blindness, is caused by Chlamydia trachomatis. Children who have the active stages of the disease are the reservoir of infection, while blindness, which occurs after repeated episodes of infection, principally affects adults. Boys and girls are equally affected by active infection, while blindness is more common in women. Trachoma is a condition of poverty and is a focal disease, affecting communities that have poor water supplies and sanitation and poor health services. The organism is transmitted from person to person through direct and indirect contact and by flies. Blindness can be prevented by surgery to correct inturning of the upper lid (trichiasis),
while the infection and its transmission can be reduced with surgery, antibiotics, facial cleanliness and environmental change (the SAFE strategy).
Current situation
Trachoma is endemic in 55 countries: Afghanistan, Algeria, Australia, Benin, Brazil, Burkina Faso, Cambodia, Cameroon, Central African Republic, Chad, China, Côte d’Ivoire, Djibouti, Egypt, Eritrea, Ethiopia, Fiji, Gambia, Ghana, Guatemala, Guinea, Guinea-Bissau, India, Islamic Republic of Iran, Iraq, Kenya, Kiribati, Lao People’s Democratic Republic, Libyan Arab Jamahiriya, Malawi, Mali, Mauritania, Mexico, Morocco, Mozambique, Myanmar, Namibia, Nepal, Niger, Nigeria, Oman, Pakistan, Papua New Guinea, Senegal, Solomon Islands, Somalia, Sudan, Togo, Uganda, United Republic of Tanzania, Vanuatu, Vietnam, Yemen, Zambia and Zimbabwe. The estimated number of affected people has fallen from 360 million in 1985 to about 80 million today. Trachoma affects the poorest and most remote rural areas of Africa, Asia, Central and South America, Australia and the Middle East (30). Updated reports on 36 countries are available (31), while 19 endemic countries have not yet reported data.
There are approximately 10.6 million people with inturned eyelashes (entropion trichiasis), for which eyelid surgery is needed to prevent blindness. The majority of these people are women. An estimated 5.9 million adults are irreversibly visually impaired from corneal scarring due to trachoma.
Achievements
At national level, political support for trachoma control has increased continually since 1997, the year the WHO Alliance for the Global Elimination of Blinding Trachoma (GET 2020) was created; intersector collaboration is growing, and use of the SAFE strategy for eliminating the disease is increasing.
GET 2020 is active at the global level. It is a public–private partnership, bringing together WHO, national coordinators, nongovernmental organizations, donors and international experts, with support from the pharmaceutical industry. Launched in 1997, it was endorsed by WHA Resolution 51.11, adopted in 1998. A nongovernmental organization task force, the International Coalition for Trachoma Control, has been working since 2004 within the framework of GET 2020 to improve information exchange with governments and to coordinate the efforts of international nongovernmental organizations in countries. The GET 2020 secretariat is responsible for trachoma within the WHO department focusing on neglected tropical diseases. The WHO GET 2020 secretariat is also coordinating the drawing up of guidelines for certification of elimination of blinding trachoma, as requested by several WHO Member States.
Limitations
Not all countries in which blinding trachoma is suspected to be endemic have undertaken a proper assessment of the epidemiological situation of trachoma.
The WHO SAFE strategy does not yet cover 100% of the populations in trachoma-endemiccountries.
International partners who are members of the WHO GET 2020 Alliance do not implement the entire SAFE strategy, but only certain components.
The available resources for trachoma control are not suffi cient to achieve the ultimate intervention goals in all countries.
Aim
Global elimination of blindness due to trachoma by the year 2020 by applying the WHO-recommended SAFE strategy
Objectives
Integrate the SAFE strategy into primary health care in all communities with blinding trachoma.
Certify the elimination of trachoma in countries, where applicable.
Strategies
Identify districts where blinding trachoma is a public health problem
Provide surgical services with trained and certifi ed medical or paramedical staff at community level to operate on cases of trachomatous trichiasis.
Provide mass antibiotic administration (azithromycin or tetracycline ointment) for populations living in districts where the prevalence of active disease (follicular trachoma) in children aged 1–9 years is above 10%. In districts where the prevalence is below 10% but above 5%, community or family treatment might be required. The treatment interventions must be implemented in association with promotion of personal hygiene, with particular focus on facial cleanliness of children under 10 and improvement of environmental hygiene and sanitation as part of primary health care.
During the 10th Meeting of GET 2020 (31), the following recommendations were adopted to facilitate implementation of the SAFE strategy:
All endemic countries should establish collaboration with the WHO GET 2020 Secretaria
All endemic countries, particularly the more populous countries, should continue to assess the distribution and severity of trachoma, e.g. by rapid assessment
Countries should develop their strategic 5-year national trachoma plans, in collaboration with national and international partners, reflecting the commitment to implement the SAFE strategy; these plans should be integrated into their VISION 2020 national plans (WHA Resolution 56.26).
WHO should design methods and tools for assessing the trachoma burden and for certifying elimination of the disease.
Countries should endeavour to increase coverage of all the components of the SAFE strategy to the highest possible level.
In countries in which active trachoma prevalence has declined to < 5%, rapid assessment might be the most useful tool for identifying communities that need trachoma control activities as a priority in order to eliminate remaining pockets of the disease.
Countries should institute an ongoing audit of the quality of trichiasis surgery on the basis of the WHO guidelines for assessment (32)
Increased intersectoral collaboration should be instituted at national and district levels to ensure comprehensive implementation of all components of the SAFE strategy.
WHO and the international development community should advocate and promote trachoma as a marker of poverty and GET 2020 as a model of a public–private partnership for tackling the problem.
Target
By 2020, all 49 countries where endemic trachoma has been confi rmed should have achieved their ultimate intervention goals. The countries with plans for achieving those goals are shown in table 3
Indicators
number of countries with blinding trachoma as a public health problem;
proportion of endemic communities covered by the SAFE strategy;
recommended, where applicable:
• prevalence of trachomatous entropion trichiasis at district level;
• prevalence of active trachoma in 1–9-year-olds at district level; and
• progress in achieving the ultimate intervention goals.
National data are being used to refi ne ultimate intervention goals and annual intervention objectives in countries. The data are included in WHO information on neglected tropical diseases, in the WHO Global Health Atlas and in the WHO Infobase.
How To Do Pelvic Floor Muscle Exercises (Kegel's)
How To Do Pelvic Floor Muscle Exercises (Kegel's)
Frederick R. Jelovsek MD
Many Women with urinary incontinence can decrease their urinary leakage during coughing, laughing, sneezing, or other activities by exercising the muscles of the pelvic floor. These exercises are often called "Kegel exercises" after the doctor, Arnold Kegel, M.D., who first described them.
To find the muscle you need to exercise, imagine that you have a tampon in your vagina that is falling out and you must tighten your muscle in order to hold it in. The muscle you tighten is the muscle you should exercise. Another way to find the right muscle, the bulbocavernosis muscle, is to sit on the toilet, place one finger in the vagina and contract that muscle around you finger. The muscle you use to tighten around your finger is the muscle you should exercise. Your doctor can help you determine which muscle to contract and make sure you are doing it properly by checking you during a pelvic examination.
Do not make a habit of doing these exercises by starting and stopping your urine flow while voiding! You can teach yourself bad bladder habits and develop voiding difficulty by doing this! Instead, you should practice your exercises at other times. Stopping your urine stream during voiding is taught by others only to help you find the correct muscle to contract .
Pelvic muscle exercises can be done in many different ways. We will give you instructions on how to do the type of exercise described by Dr. Kegel. Since continued vigorous exercise can lead to muscle soreness and fatigue, don't try to start out at maximum exercises all at once. Spread them out over the course of the day. We suggest starting with 25 muscle contractions divided into 3 daily sessions. This should take 5 minutes 3 times a day. You should eventually build up to 20 minutes (100 contractions) 3 times a day. If you do have muscle soreness starting out, try doing the exercises vigorously every other day instead. this will allow your muscle to recover from the fatigue of exercise.
These exercises can be done anywhere and at any time. You may find it helpful to associate an activity with your muscles, such as doing them while stopped at a red light, during a TV commercial, talking on the phone, or doing various household chores such as ironing, washing dishes, cooking, etc. The important think is to get in the habit of doing them!
Initially - Tighten the pelvic floor muscles for count of six and relax for six seconds. Each contraction cycle should last 12 seconds or 5 contractions a minute. Repeat 25 times. Do this 3 times each day - total 75 contractions.
Week 2 - Tighten the pelvic floor muscles for 6 seconds every 12 seconds (5 per minute) for 10 minutes, 50 contractions. Do this 3 times each day - total 150 contractions.
Week 3 - Tighten the pelvic floor muscles for 6 seconds every 12 seconds (5 per minute) for 15 minutes, 75 contractions. Do this 3 times each day - total 225 contractions.
Weeks 4-24 - Tighten the pelvic floor muscles for 6 seconds every 12 seconds (5 per minute) for 20 minutes, 100 contractions. Do this 3 times each day - total 100 contractions.
After 24 months - Continue maintainence at 10 minutes three times a day or 15 minutes twice a day, total of 150 contractions a day.
You may notice some soreness in the pelvic muscles and around the vaginal opening once you start exercising regularly. Do not worry about this - it is only soreness associated with increased muscle activity. The benefits of these exercises will continue ONLY as long as you do them! Use it or lose it! You should expect to have to do these exercises regularly for three months before you notice an improvement in your urine loss. At six months of regular exercise you will get maximum effect.
If at any time you think you are getting headaches, chest discomfort or abdominal muscle discomfort, then you are contracting other muscles in addition to, or instead of the bulbocavernosis muscle. Concentrate on just the perineum, while relaxing all other muscles.
From BackupMD
Frederick R. Jelovsek MD
Many Women with urinary incontinence can decrease their urinary leakage during coughing, laughing, sneezing, or other activities by exercising the muscles of the pelvic floor. These exercises are often called "Kegel exercises" after the doctor, Arnold Kegel, M.D., who first described them.
To find the muscle you need to exercise, imagine that you have a tampon in your vagina that is falling out and you must tighten your muscle in order to hold it in. The muscle you tighten is the muscle you should exercise. Another way to find the right muscle, the bulbocavernosis muscle, is to sit on the toilet, place one finger in the vagina and contract that muscle around you finger. The muscle you use to tighten around your finger is the muscle you should exercise. Your doctor can help you determine which muscle to contract and make sure you are doing it properly by checking you during a pelvic examination.
Do not make a habit of doing these exercises by starting and stopping your urine flow while voiding! You can teach yourself bad bladder habits and develop voiding difficulty by doing this! Instead, you should practice your exercises at other times. Stopping your urine stream during voiding is taught by others only to help you find the correct muscle to contract .
Pelvic muscle exercises can be done in many different ways. We will give you instructions on how to do the type of exercise described by Dr. Kegel. Since continued vigorous exercise can lead to muscle soreness and fatigue, don't try to start out at maximum exercises all at once. Spread them out over the course of the day. We suggest starting with 25 muscle contractions divided into 3 daily sessions. This should take 5 minutes 3 times a day. You should eventually build up to 20 minutes (100 contractions) 3 times a day. If you do have muscle soreness starting out, try doing the exercises vigorously every other day instead. this will allow your muscle to recover from the fatigue of exercise.
These exercises can be done anywhere and at any time. You may find it helpful to associate an activity with your muscles, such as doing them while stopped at a red light, during a TV commercial, talking on the phone, or doing various household chores such as ironing, washing dishes, cooking, etc. The important think is to get in the habit of doing them!
Initially - Tighten the pelvic floor muscles for count of six and relax for six seconds. Each contraction cycle should last 12 seconds or 5 contractions a minute. Repeat 25 times. Do this 3 times each day - total 75 contractions.
Week 2 - Tighten the pelvic floor muscles for 6 seconds every 12 seconds (5 per minute) for 10 minutes, 50 contractions. Do this 3 times each day - total 150 contractions.
Week 3 - Tighten the pelvic floor muscles for 6 seconds every 12 seconds (5 per minute) for 15 minutes, 75 contractions. Do this 3 times each day - total 225 contractions.
Weeks 4-24 - Tighten the pelvic floor muscles for 6 seconds every 12 seconds (5 per minute) for 20 minutes, 100 contractions. Do this 3 times each day - total 100 contractions.
After 24 months - Continue maintainence at 10 minutes three times a day or 15 minutes twice a day, total of 150 contractions a day.
You may notice some soreness in the pelvic muscles and around the vaginal opening once you start exercising regularly. Do not worry about this - it is only soreness associated with increased muscle activity. The benefits of these exercises will continue ONLY as long as you do them! Use it or lose it! You should expect to have to do these exercises regularly for three months before you notice an improvement in your urine loss. At six months of regular exercise you will get maximum effect.
If at any time you think you are getting headaches, chest discomfort or abdominal muscle discomfort, then you are contracting other muscles in addition to, or instead of the bulbocavernosis muscle. Concentrate on just the perineum, while relaxing all other muscles.
From BackupMD
Pelvic Floor Muscle Training (Kegel Exercises)
Pelvic Floor Muscle Training (Kegel Exercises)
What is pelvic floor muscle training?
Why should I do pelvic floor muscle exercises?
How do you do pelvic floor muscle exercises?
Important Tips for pelvic floor muscle exercises
What are the most common mistakes made during pelvic muscle exercises?
When should I use the pelvic floor muscles?
How can I work this new health habit into my everyday life?
What is pelvic floor muscle training?
It is a daily training program for the muscles that support the uterus, bladder and other pelvic organs. It is also called Kegel exercise or pelvic muscle rehabilitation. This exercise will help your pelvic muscles prevent accidental urine leakage.
Back to Top
Why should I do pelvic floor muscle exercises?
Regular pelvic floor muscle exercises make the muscles that support your pelvic organs stronger and helps you use the muscles more effectively. Women who have a problem with urine leakage have been able to eliminate or greatly improve this problem just by doing pelvic floor muscle exercises each day. Pregnant and postpartum women who do pelvic floor muscle exercises have significantly less urine leakage.
Back to Top
How do you do pelvic floor muscle exercises?
When you are doing pelvic floor muscle exercises in a way that will build muscle strength you will feel all the muscles drawing inward and upward. A good way to learn the exercise is to pretend that you are trying to avoid passing intestinal gas. Think about the way you tighten (or contract) the muscles to keep the gas from escaping. Bring that same tightening motion forward to the muscles around your vagina. Then move the contraction up your vagina toward the small of you back. Another good way to understand pelvic floor muscle training can be found in thinking about the vagina being able to clasp the penis during intercourse. This is the same upward and inward motion that helps build strong pelvic muscles.
Back to Top
Important Tips for pelvic floor muscle exercises
Each contraction should involve a concentrated effort to get maximum tightening.
Try to contract only the pelvic muscles. (If you feel your abdomen, thighs or buttocks tightening then relax and aim just for the pelvic muscles by using a less intense muscle contraction. If it seems impossible not to tighten the abdomen, thigh, or buttock muscles, then concentrate on full relaxation and try gentle �flicks� of the pelvic muscles, for example, �flick, flick, flick, relax�--working the muscles to higher layers with each flick.)
Be sure to breathe while holding the muscles contracted.
Practice fully relaxing the muscle for at least 10 seconds between each contraction.
Experiment with contracting the muscles in many different positions (standing upright, lying, sitting, on hands and knees, feet together, feet apart).
Back to Top
What are the most common mistakes made during pelvic muscle exercises?
The most serious mistake women make when doing pelvic muscle exercise is to strain down instead of drawing the muscles up and in. Try doing this on purpose once so you can feel what NOT to do: take a breath, hold it, and push down with your abdomen. You can feel a pushing out around your vagina. It is very important to avoid this straining down.
To keep from straining down when you do a pelvic muscle contraction: exhale gently and keep your mouth open each time you tighten your muscles. Remember to breathe. Rest a hand lightly on your abdomen. If you feel your stomach pushing out against your hand, you are straining down. If you cannot avoid straining down, do not continue with the exercise until you check with your nurse to learn how to do it properly.
Back to Top
When should I use the pelvic floor muscles?
Squeezing the pelvic floor muscles can help you right away to avoid leakage. Practice coordinating contraction of these muscles with an event in which you may be prone to leak urine (i.e., coughing, sneezing, nose-blowing, lifting a heavy object, etc.) You should also contract the muscles when you need to delay going to the toilet.
Back to Top
How can I work this new health habit into my everyday life?
Think about your typical day. Pick a time (about 15 minutes) that you should have time to do pelvic floor muscle training, maybe when you first wake up or maybe during a TV program you almost always watch.
Decide on a way to remind yourself to do pelvic floor muscle training. You might put a note on a mirror you always use in the morning or a sticker on your TV or a special magnet on your refrigerator.
Reward yourself for exercising each time you do it. You might get some special small candies and treat yourself to one each day that you remember. Or you could draw a small flower on your calendar to mark each day you exercise and get yourself a real flower or bouquet when you have drawn 10 or 30 flowers. Any small reward that you know will keep you working on this habit is fine.
Everyone who is making a change like this has lapses. You may forget for several days at a time. Don�t get discouraged and think that you won�t be able to continue the exercise program. When you realize that you have forgotten, just resume the program.
Monitor your progress. You might want to keep a daily diary of whether or not you have had a leaking accident. Over the weeks you should begin to see a decrease in the frequency and amount of unwanted urine loss. Another way to check your progress is to see whether or not you can slow or stop your urine stream when you are going to the bathroom. We recommend that you try this no more than once a week. As your pelvic muscles get stronger you will find that you are able to stop the stream more quickly.
Back to Top
University of Michigan, School of Nursing.
Copyright � 2000. Regents of the University of Michigan. All rights reserved.
Revised: February 07, 2001 .
What is pelvic floor muscle training?
Why should I do pelvic floor muscle exercises?
How do you do pelvic floor muscle exercises?
Important Tips for pelvic floor muscle exercises
What are the most common mistakes made during pelvic muscle exercises?
When should I use the pelvic floor muscles?
How can I work this new health habit into my everyday life?
What is pelvic floor muscle training?
It is a daily training program for the muscles that support the uterus, bladder and other pelvic organs. It is also called Kegel exercise or pelvic muscle rehabilitation. This exercise will help your pelvic muscles prevent accidental urine leakage.
Back to Top
Why should I do pelvic floor muscle exercises?
Regular pelvic floor muscle exercises make the muscles that support your pelvic organs stronger and helps you use the muscles more effectively. Women who have a problem with urine leakage have been able to eliminate or greatly improve this problem just by doing pelvic floor muscle exercises each day. Pregnant and postpartum women who do pelvic floor muscle exercises have significantly less urine leakage.
Back to Top
How do you do pelvic floor muscle exercises?
When you are doing pelvic floor muscle exercises in a way that will build muscle strength you will feel all the muscles drawing inward and upward. A good way to learn the exercise is to pretend that you are trying to avoid passing intestinal gas. Think about the way you tighten (or contract) the muscles to keep the gas from escaping. Bring that same tightening motion forward to the muscles around your vagina. Then move the contraction up your vagina toward the small of you back. Another good way to understand pelvic floor muscle training can be found in thinking about the vagina being able to clasp the penis during intercourse. This is the same upward and inward motion that helps build strong pelvic muscles.
Back to Top
Important Tips for pelvic floor muscle exercises
Each contraction should involve a concentrated effort to get maximum tightening.
Try to contract only the pelvic muscles. (If you feel your abdomen, thighs or buttocks tightening then relax and aim just for the pelvic muscles by using a less intense muscle contraction. If it seems impossible not to tighten the abdomen, thigh, or buttock muscles, then concentrate on full relaxation and try gentle �flicks� of the pelvic muscles, for example, �flick, flick, flick, relax�--working the muscles to higher layers with each flick.)
Be sure to breathe while holding the muscles contracted.
Practice fully relaxing the muscle for at least 10 seconds between each contraction.
Experiment with contracting the muscles in many different positions (standing upright, lying, sitting, on hands and knees, feet together, feet apart).
Back to Top
What are the most common mistakes made during pelvic muscle exercises?
The most serious mistake women make when doing pelvic muscle exercise is to strain down instead of drawing the muscles up and in. Try doing this on purpose once so you can feel what NOT to do: take a breath, hold it, and push down with your abdomen. You can feel a pushing out around your vagina. It is very important to avoid this straining down.
To keep from straining down when you do a pelvic muscle contraction: exhale gently and keep your mouth open each time you tighten your muscles. Remember to breathe. Rest a hand lightly on your abdomen. If you feel your stomach pushing out against your hand, you are straining down. If you cannot avoid straining down, do not continue with the exercise until you check with your nurse to learn how to do it properly.
Back to Top
When should I use the pelvic floor muscles?
Squeezing the pelvic floor muscles can help you right away to avoid leakage. Practice coordinating contraction of these muscles with an event in which you may be prone to leak urine (i.e., coughing, sneezing, nose-blowing, lifting a heavy object, etc.) You should also contract the muscles when you need to delay going to the toilet.
Back to Top
How can I work this new health habit into my everyday life?
Think about your typical day. Pick a time (about 15 minutes) that you should have time to do pelvic floor muscle training, maybe when you first wake up or maybe during a TV program you almost always watch.
Decide on a way to remind yourself to do pelvic floor muscle training. You might put a note on a mirror you always use in the morning or a sticker on your TV or a special magnet on your refrigerator.
Reward yourself for exercising each time you do it. You might get some special small candies and treat yourself to one each day that you remember. Or you could draw a small flower on your calendar to mark each day you exercise and get yourself a real flower or bouquet when you have drawn 10 or 30 flowers. Any small reward that you know will keep you working on this habit is fine.
Everyone who is making a change like this has lapses. You may forget for several days at a time. Don�t get discouraged and think that you won�t be able to continue the exercise program. When you realize that you have forgotten, just resume the program.
Monitor your progress. You might want to keep a daily diary of whether or not you have had a leaking accident. Over the weeks you should begin to see a decrease in the frequency and amount of unwanted urine loss. Another way to check your progress is to see whether or not you can slow or stop your urine stream when you are going to the bathroom. We recommend that you try this no more than once a week. As your pelvic muscles get stronger you will find that you are able to stop the stream more quickly.
Back to Top
University of Michigan, School of Nursing.
Copyright � 2000. Regents of the University of Michigan. All rights reserved.
Revised: February 07, 2001 .
Thursday, May 14, 2009
Health and Nutritional Benefits from Coconut Oil: An Important Functional Food for the 21st Century
--------------------------------------------------------------------------------
A New Look at Coconut Oil
By Mary G. Enig, Ph.D.
Health and Nutritional Benefits from Coconut Oil: An Important Functional Food for the 21st Century
Presented at the AVOC Lauric Oils Symposium, Ho Chi Min City, Vietnam, 25 April 1996
Abstract
Coconut oil has a unique role in the diet as an important physiologically functional food. The health and nutritional benefits that can be derived from consuming coconut oil have been recognized in many parts of the world for centuries. Although the advantage of regular consumption of coconut oil has been underappreciated by the consumer and producer alike for the recent two or three decades, its unique benefits should be compelling for the health minded consumer of today. A review of the diet/heart disease literature relevant to coconut oil clearly indicates that coconut oil is at worst neutral with respect to atherogenicity of fats and oils and, in fact, is likely to be a beneficial oil for prevention and treatment of some heart disease. Additionally, coconut oil provides a source of antimicrobial lipid for individuals with compromised immune systems and is a nonpromoting fat with respect to chemical carcinogenesis.
I. Introduction
Mr. Chairman and members of the ASEAN Vegetable Oils Club, I would like to thank you for inviting me to participate in this Lauric Oils Symposium. I am pleased to have the opportunity to review with you some information that I hope will help redress some of the anti-tropical oils rhetoric that has been so troublesome to your industry.
I will be covering two important areas in my presentation. In the first part, I would like to review the history of the major health challenge facing coconut oil today. This challenge is based on a supposed negative role played by saturated fat in heart disease. I hope to dispel any acceptance of this notion with the information I will present to you today. I will show you how both animal studies and human studies have exonerated coconut oil of causing the problem.
In the second part of my talk I will suggest some new directions where important positive health benefits are seen for coconut oil. These benefits stem from coconut oil's use as a food with major antimicrobial and anticancer benefits. I will present to you some of the rationale for this effect and some of the supporting literature.
The health and nutritional benefits derived from coconut oil are unique and compelling. Although the baker and food processor have recognized the functional advantages of coconut oil in their industries, over most competing oils, for many years, I believe these benefits are underappreciated today by both the producer and the consumer. It is time to educate and reeducate all t hose who harbor this misinformation.
Historically, coconuts and their extracted oil have served man as important foods for thousands of years. The use of coconut oil as a shortening was advertised in the United States in popular cookbooks at the end of the 19th century. Both the health-promoting attributes of coconut oil and those functional properties useful to the homemaker were recognized 100 years ago. These same attributes, in addition to some newly discovered ones, should be of great interest to both the producing countries as well as the consuming countries.
II. Origins of the Diet/Heart Hypothesis
Although popular literature of epidemiological studies usually attribute an increased risk of coronary heart disease (CHD) to elevated levels of serum cholesterol, which in turn are thought to derive from a dietary intake of saturated fats and cholesterol. But, saturated fats may be considered a major culprit for CHD only if the links between serum cholesterol and CHD, and between saturated fat and serum cholesterol are each firmly established. Decades of large-scale tests and conclusions therefrom have purported to establish the first link. In fact, this relationship has reached the level of dogma. Through the years metabolic ward and animal studies have claimed that dietary saturated fats increase serum cholesterol levels, thereby supposedly establishing the second link. But the scientific basis for these relationships has now been challenged as resulting from large-scale misinterpretation and misrepresentation of the data. (Enig 1991, Mann 1991, Smith 1991, Ravnskov 1995)
Ancel Keys is largely responsible for starting the anti-saturated fat agenda in the United States. From 1953 to 1957 Keys made a series of statements regarding the atherogenicity of fats. These pronouncements were:
"All fats raise serum cholesterol; Nearly half of total fat comes from vegetable fats and oils; No difference between animal and vegetable fats in effect on CHD (1953); Type of fat makes no difference; Need to reduce margarine and shortening (1956); All fats are comparable; Saturated fats raise and polyunsaturated fats lower serum cholesterol; Hydrogenated vegetable fats are the problem; Animal fats are the problem (1957-1959)."
As can be seen, his findings were inconsistent.
What was the role of the edible oil industry in promoting the diet/heart hypothesis?
It is important to realize that at that time (1960s) the edible oil industry in the United States seized the opportunity to promote its polyunsaturates. The industry did this by developing a health issue focusing on Key's anti-saturated fat bias. With the help of the edible oil industry lobbying in the United States, federal government dietary goals and guidelines were adopted incorporating this mistaken idea that consumption of saturated fat was causing heart disease. This anti-saturated fat issue became the agenda of government and private agencies in the US and to an extent in other parts of the world. This is the agenda that has had such a devastating effect on the coconut industry for the past decade. Throughout the 1960s, the 1970s, the 1980s, and the 1990s, the anti-saturated fat rhetoric increased in intensity.
What are some of the contradictions to the hypothesis blaming saturated fat?
Recently, an editorial by Harvard's Walter Willett, M.D. in the American Journal of Public Health (1990) acknowledged that even though
"the focus of dietary recommendations is usually a reduction of saturated fat intake, no relation between saturated fat intake and risk of CHD was observed in the most informative prospective study to date."
Another editorial, this time by Framingham's William P. Castelli in the Archives of Internal Medicine (1992), declared for the record that
"...in Framingham, Mass, the more saturated fat one ate, the more cholesterol one ate, the more calories one ate, the lower the person's serum cholesterol... the opposite of what the equations provided by Hegsted at al (1965) and Keys et al (1957) would predict..."
Castelli further admitted that
"...In Framingham, for example, we found that the people who ate the most cholesterol, ate the most saturated fat, ate the most calories, weighed the least, and were the most physically active."
III. Coconut Oil and the Diet/Heart Hypothesis
For the past several decades you have heard about animal and human studies feeding coconut oil that purportedly showed increased indices for cardiovascular risk. Blackburn et al (1988) have reviewed the published literature of coconut oil's effect on serum cholesterol and atherogenesis and have concluded that when ...[coconut oil is] fed physiologically with other fats or adequately supplemented with linoleic acid, coconut oil is a neutral fat in terms of atherogenicity. After reviewing this same literature, Kurup and Rajmohan (1995) conducted a study on 64 volunteers and found ...no statistically significant alteration in the serum total cholesterol, HDL cholesterol, LDL cholesterol, HDL cholesterol/total cholesterol ratio and LDL cholesterol/HDL cholesterol ratio of triglycerides from the baseline values... A beneficial effect of adding the coconut kernel to the diet was noted by these researchers.
How did coconut oil get such a negative reputation?
The question then is, how did coconut oil get such a negative reputation? The answer quite simply is, initially, the significance of those changes that occurred during animal feeding studies were misunderstood. The wrong interpretation was then repeated until ultimately the misinformation and disinformation took on a life of its own.
The problems for coconut oil started four decades ago when researchers fed animals hydrogenated coconut oil that was purposefully altered to make it completely devoid of any essential fatty acids. The hydrogenated coconut oil was selected instead of hydrogenated cottonseed, corn or soybean oil because it was a soft enough fat for blending into diets due to the presence of the lower melting medium chain saturated fatty acids. The same functionality could not be obtained from the cottonseed, corn or soybean oils if they were made totally saturated, since all their fatty acids were long chain and high melting and could not be easily blended nor were they as readily digestible.
The animals fed the hydrogenated coconut oil (as the only fat source) naturally became essential fatty acid deficient; their serum cholesterol levels increased. Diets that cause an essential fatty acid deficiency always produce an increase in serum cholesterol levels as well as an increase in the atherosclerotic indices. The same effect has also been seen when other essential fatty acid deficient, highly hydrogenated oils such as cottonseed, soybean, or corn oils have been fed; so it is clearly a function of the hydrogenated product, either because the oil is essential fatty acid (EFA) deficient or because of trans fatty acids (TFA).
What about the studies where animals were fed with unprocessed coconut oil?
Hostmark et al (1980) compared the effects of diets containing 10% coconut fat and 10% sunflower oil on lipoprotein distribution in male Wistar rats. Coconut oil feeding produced significantly lower levels (p=<0.05) of pre-beta lipoproteins (VLDL) and significantly higher (p=<0.01) alpha-lipoproteins (HDL) relative to sunflower oil feeding.
Awad (1981) compared the effects of diets containing 14% coconut oil, 14% safflower oil or a 5% "control" (mostly soybean) oil on accumulation of cholesterol in tissues in male Wistar rats. The synthetic diets had 2% added corn oil with a total fat of 16% Total tissue cholesterol accumulation for animals on the safflower diet was six times greater than for animals fed the coconut oil, and twice that of the animals fed the control oil.
A conclusion that can be drawn from some of this animal research is that feeding hydrogenated coconut oil devoid of essential fatty acids (EFA) in a diet otherwise devoid of EFA leads to EFA deficiency and potentiates the formation of atherosclerosis markers. It is of note that animals fed regular coconut oil have less cholesterol deposited in their livers and other parts of their bodies.
What about the studies where coconut oil is part of the normal diet of human beings?
Kaunitz and Dayrit (1992) have reviewed some of the epidemiological and experimental data regarding coconut-eating groups and noted that the available population studies show that dietary coconut oil does not lead to high serum cholesterol nor to high coronary heart disease mortality or morbidity. They noted that in 1989 Mendis et al reported undesirable lipid changes when young adult Sri Lankan males were changed from their normal diets by the substitution of corn oil for their customary coconut oil. Although the total serum cholesterol decreased 18.7% from 179.6 to 146.0 mg/dl and the LDL cholesterol decreased 23.8% from 131.6 to 100.3 mg/dl, the HDL cholesterol decreased 41.4% from 43.4 to 25.4 mg/dl (putting the HDL values below the acceptable lower limit) and the LDL/HDL ratio increased 30% from 3.0 to 3.9. These latter two changes would be considered quite undesirable. As noted above, Kurup and Rajmohan (1995) studied the addition of coconut oil alone to previously mixed fat diets and report no significant difference.
Previously, Prior et al (1981) had shown that islanders with high intake of coconut oil showed no evidence of the high saturated fat intake having a harmful effect in these populations. When these groups migrated to New Zealand however, and lowered their intake of coconut oil, their total cholesterol and LDL cholesterol increased, and their HDL cholesterol decreased.
What about the studies where coconut oil was deliberately fed to human beings?
Some of the studies reported thirty and more years ago should have cleared coconut oil of any implication in the development of coronary heart disease (CHD).
For example, when Frantz and Carey (1961) fed an additional 810 kcal/day fat supplement for a whole month to males with high normal serum cholesterol levels, there was no significant difference from the original levels even though the fat supplement was hydrogenated coconut oil.
Halden and Lieb (1961) also showed similar results in a group of hyperchole-sterolemics when coconut oil was included in their diets. Original serum cholesterol levels were reported as 170 to 370 mg/dl. Straight coconut oil produced a range from 170 to 270 mg/dl. Coconut oil combined with 5% sunflower oil and 5% olive oil produced a range of 140 to 240 mg/dl.
Earlier, Hashim and colleagues (1959) had shown quite clearly that feeding a fat supplement to hypercholesterolemics, where half of the supplement (21% of energy) was coconut oil (and the other half was safflower oil), resulted in significant reductions in total serum cholesterol. The reductions averaged -29% and ranged from -6.8 to -41.2%.
And even earlier, Ahrens and colleagues (1957) had shown that adding coconut oil to the diet of hypercholesterolemics lowers serum cholesterol from, e.g., 450 mg/dl to 367 mg/dl. This is hardly a cholesterol-raising effect.
Bierenbaum et al (1967) followed 100 young men with documented myocardial infarction for 5 years on diets with fat restricted to 28% of energy. There was no significant difference between the two different fat mixtures (50/50 corn and safflower oils or 50/50 coconut and peanut oils), which were fed as half of the total fat allowance; both diets reduced serum cholesterol. This study clearly showed that 7% of energy as coconut oil was as beneficial to the 50 men who consumed it as for the 50 men who consumed 7% of energy as other oils such as corn oil or safflower. Both groups fared better than the untreated controls.
More recently, Sundram et al (1994) fed whole foods diets to healthy normo-cholesterolemic males, where approximately 30% of energy was fat. Lauric acid (C12:0) and myristic acid (C14:0) from coconut oil supplied approximately 5% of energy. Relative to the baseline measurements of the subjects prior to the experimental diet, this lauric and myristic acid-rich diet showed an increase in total serum cholesterol from 166.7 to 170.0 mg/dl (+1.9%), a decrease in low density lipoprotein cholesterol (LDL-C) from 105.2 to 104.4 mg/dl (-0.1%), an increase in high density lipoprotein cholesterol (HDL-C) from 42.9 to 45.6 mg/dl (+6.3%). There was a 2.4% decrease in the LDL-C/HDL-C ratio from 2.45 to 2.39. These findings indicate a favorable alteration in serum lipoprotein balance was achieved when coconut oil was included in a whole food diet at 5% of energy.
Tholstrup et al (1994) report similar results with whole foods diets high in lauric and myristic acids from palm kernel oil. The HDL cholesterol levels increased significantly from baseline values (37.5 to 46.0 mg/dl, P<0.01) and the LDL-C/HDL-C ratios decreased from 3.08 to 2.69. The increase in total cholesterol was from 154.7 (baseline) to 170.9 mg/dl on the experimental diet.
Ng et al (1991) fed 75% of the fat ration as coconut oil (24% of energy) to 83 adult normocholesterolemics (61 males and 22 females). Relative to baseline values, the highest values on the experimental diet for total cholesterol was increased 17% (169.6 to 198.4 mg/dl), HDL cholesterol was increased 21.4% (44.3 to 53.8 mg/dl), and the LDL-C/HDL-C ratio was decreased 3.6% (2.51 to 2.42).
When unprocessed coconut oil is added to an otherwise normal diet, there is frequently no change in the serum cholesterol although some studies have shown a decrease in total cholesterol. For example, when Ginsberg et al provided an "Average American" diet with 2-3 times more myristic acid (C14:0), 4.5 times more lauric acid (C12:0), and 1.2 times more palmitic and stearic acid (C16:0 and C18:0) than their "Mono[unsaturated]" diet and the National Cholesterol Education Program "Step 1" diet, there was no increase in serum cholesterol, and in fact, serum cholesterol levels for this diet group fell approximately 3% from 177.1 mg% to 171.8 mg% during the 22 week feeding trial.
It appears from many of the research reports that the effect coconut oil has on serum cholesterol is the opposite in individuals with low serum cholesterol values and those with high serum values. We see that there may be a raising of serum total cholesterol, LDL cholesterol and especially HDL cholesterol in individuals with low serum cholesterol. On the other hand there is lowering of total cholesterol and LDL cholesterol in hypercholesterolemics as noted above.
Studies that supposedly showed a hypercholesterolemic effect of coconut oil feeding, in fact, usually only showed that coconut oil was not as effective at lowering the serum cholesterol as was the more unsaturated fat being compared. This appears to be in part because coconut oil does not drive cholesterol into the tissues as does the more polyunsaturated fats. The chemical analysis of the atheroma shows that the fatty acids from the cholesterol esters are 74% unsaturated (41% is polyunsaturated) and only 24% are saturated. None of the saturated fatty acids were reported to be lauric acid or myristic acid (Felton et al 1994).
Should coconut oil be used to prevent coronary heart disease?
There is another aspect to the coronary heart disease picture. This is related to the initiation of the atheromas that are reported to be blocking arteries. Recent research is suggestive that there is a causative role for the herpes virus and cytomegalovirus in the initial formation of atherosclerotic plaques and the recloging of arteries after angioplasty. (New York Times 1991) What is so interesting is that the herpes virus and cytomegalovirus are both inhibited by the antimicrobial lipid monolaurin; but monolaurin is not formed in the body unless there is a source of lauric acid in the diet. Thus, ironically enough, one could consider the recommendations to avoid coconut and other lauric oils as contributing to the increased incidence of coronary heart disease.
Perhaps more important than any effect of coconut oil on serum cholesterol is the additional effect of coconut oil on the disease fighting capability of the animal or person consuming the coconut oil.
IV. Coconut Oil and Cancer
Lim-Sylianco (1987) has reviewed 50 years of literature showing anticarcinogenic effects from dietary coconut oil. These animal studies show quite clearly the nonpromotional effect of feeding coconut oil.
In a study by Reddy et al (1984) straight coconut oil was more inhibitory than MCT oil to induction of colon tumors by azoxymethane. Chemically induced adenocarcinomas differed 10-fold between corn oil (32%) and coconut oil (3%) in the colon. Both olive oil and coconut oil developed the low levels (3%) of the adenocarcinomas in the colon, but in the small intestine animals fed coconut oil did not develop any tumors while 7% of animals fed olive oil did.
Studies by Cohen et al (1986) showed that the nonpromotional effects of coconut oil were also seen in chemically induced breast cancer. In this model, the slight elevation of serum cholesterol in the animals fed coconut oil was protective as the animals fed the more polyunsaturated oil had reduced serum cholesterol and more tumors. The authors noted that "...an overall inverse trend was observed between total serum lipids and tumor incidence for the 4 [high fat] groups."
This is an area that needs to be pursued.
V. Coconut Oil Antimicrobial Benefits
I would now like to review for you some of the rationale for the use of coconut oil as a food that will serve as the raw material to provide potentially useful levels of antimicrobial activity in the individual.
The lauric acid in coconut oil is used by the body to make the same disease-fighting fatty acid derivative monolaurin that babies make from the lauric acid they get from their mothers= milk. The monoglyceride monolaurin is the substance that keeps infants from getting viral or bacterial or protozoal infections. Until just recently, this important benefit has been largely overlooked by the medical and nutrition community.
Recognition of the antimicrobial activity of the monoglyceride of lauric acid (monolaurin) has been reported since 1966. The seminal work can be credited to Jon Kabara. This early research was directed at the virucidal effects because of possible problems related to food preservation. Some of the early work by Hierholzer and Kabara (1982) that showed virucidal effects of monolaurin on enveloped RNA and DNA viruses was done in conjunction with the Center for Disease Control of the US Public Health Service with selected prototypes or recognized representative strains of enveloped human viruses. The envelope of these viruses is a lipid membrane.
Kabara (1978) and others have reported that certain fatty acids (e.g., medium-chain saturates) and their derivatives (e.g., monoglycerides) can have adverse effects on various microorganisms: those microorganisms that are inactivated include bacteria, yeast, fungi, and enveloped viruses.
The medium-chain saturated fatty acids and their derivatives act by disrupting the lipid membranes of the organisms (Isaacs and Thormar 1991) (Isaacs et al 1992). In particular, enveloped viruses are inactivated in both human and bovine milk by added fatty acids (FAs) and monoglycerides (MGs) (Isaacs et al 1991) as well as by endogenous FAs and MGs (Isaacs et al 1986, 1990, 1991, 1992; Thormar et al 1987).
All three monoesters of lauric acid are shown to be active antimicrobials, i.e., alpha-, alpha'-, and beta-MG. Additionally, it is reported that the antimicrobial effects of the FAs and MGs are additive and total concentration is critical for inactivating viruses (Isaacs and Thormar 1990).
The properties that determine the anti-infective action of lipids are related to their structure; e.g., monoglycerides, free fatty acids. The monoglycerides are active, diglycerides and triglycerides are inactive. Of the saturated fatty acids, lauric acid has greater antiviral activity than either caprylic acid (C-10) or myristic acid (C-14).
The action attributed to monolaurin is that of solubilizing the lipids and phospholipids in the envelope of the virus causing the disintegration of the virus envelope. In effect, it is reported that the fatty acids and monoglycerides produce their killing/inactivating effect by lysing the (lipid bilayer) plasma membrane. However, there is evidence from recent studies that one antimicrobial effect is related to its interference with signal transduction (Projan et al 1994).
Some of the viruses inactivated by these lipids, in addition to HIV, are the measles virus, herpes simplex virus-1 (HSV-1), vesicular stomatitis virus (VSV), visna virus, and cytomegalovirus (CMV). Many of the pathogenic organisms reported to be inactivated by these antimicrobial lipids are those known to be responsible for opportunistic infections in HIV-positive individuals. For example, concurrent infection with cytomegalovirus is recognized as a serious complication for HIV+ individuals (Macallan et al 1993). Thus, it would appear to be important to investigate the practical aspects and the potential benefit of an adjunct nutritional support regimen for HIV-infected individuals, which will utilize those dietary fats that are sources of known anti-viral, anti-microbial, and anti-protozoal monoglycerides and fatty acids such as monolaurin and its precursor lauric acid.
No one in the mainstream nutrition community seems to have recognized the added potential of antimicrobial lipids in the treatment of HIV-infected or AIDS patients. These antimicrobial fatty acids and their derivatives are essentially non-toxic to man; they are produced in vivo by humans when they ingest those commonly available foods that contain adequate levels of medium-chain fatty acids such as lauric acid. According to the published research, lauric acid is one of the best "inactivating" fatty acids, and its monoglyceride is even more effective than the fatty acid alone (Kabara 1978, Sands et al 1978, Fletcher et al 1985, Kabara 1985).
The lipid coated (envelop) viruses are dependent on host lipids for their lipid constituents. The variability of fatty acids in the foods of individuals accounts for the variability of fatty acids in the virus envelop and also explains the variability of glycoprotein expression.
Loss of lauric acid from the American diet
Increasingly, over the past 40 years, the American diet has undergone major changes. Many of these changes involve changes of fats and oils. There has been an increasing supply of the partially hydrogenated trans-containing vegetable oils and a decreasing amount of the lauric acid-containing oils. As a result, there has been an increased consumption of trans fatty acids and linoleic acid and a decrease in the consumption of lauric acid. This type of change in diet has an effect on the fatty acids the body has available for metabolic activities.
VI. Lauric Acid in Foods
The coconut producing countries
Whole coconut as well as extracted coconut oil has been a mainstay in the food supply in many countries in parts of Asia and the Pacific Rim throughout the centuries. Recently though, there has been some replacement of coconut oil by other seed oils. This is unfortunate since the benefits gained from consuming an adequate amount of coconut oil are being lost.
Based on the per capita intake of coconut oil in 1985 as reported by Kaunitz (1992), the per capita daily intake of lauric acid can be approximated. For those major producing countries such as the Philippines, Indonesia, and Sri Lanka, and consuming countries such as Singapore, the daily intakes of lauric acid were approximately 7.3 grams (Philippines), 4.9 grams (Sri Lanka), 4.7 grams (Indonesia), and 2.8 grams (Singapore). In India, intake of lauric acid from coconut oil in the coconut growing areas (e.g., Kerala) range from about 12 to 20 grams per day (Eraly 1995), whereas the average for the rest of the country is less than half a gram. An average high of approximately 68 grams of lauric acid is calculated from the coconut oil intake previously reported by Prior et al (1981) for the Tokelau Islands. Other coconut producing countries may also have intakes of lauric acid in the same range.
The US experience
In the United States today, there is very little lauric acid in most of the foods. During the early part of the 20th Century and up until the late 1950s many people consumed heavy cream and high fat milk. These foods could have provided approximately 3 grams of lauric acid per day to many individuals. In addition, desiccated coconut was a popular food in homemade cakes, pies and cookies, as well as in commercial baked goods, and 1-2 tablespoons of desiccated coconut would have supplied 1-2 grams of lauric acid. Those foods made with the coconut oil based shortenings would have provided additional amounts.
Until two years ago, some of the commercially sold popcorn, at least in movie theaters, had coconut oil as the oil. This means that for those people lucky enough to consume this type of popcorn the possible lauric acid intake was 6 grams or more in a three (3) cup order.
Some infant formulas (but not all) have been good sources of lauric acid for infants. However, in the past 3-4 years there has been reformulation with a loss of a portion of coconut oil in these formulas, and a subsequent lowering of the lauric acid levels.
Only one US manufactured enteral formula contains lauric acid (e.g., Impact7); this is normally used in hospitals for tube feeding; it is reported to be very effective in reversing severe weight loss in AIDS patients, but it is discontinued when the patients leave the hospital because it is not sufficiently palatable for oral use. The more widely promoted enteral formulas (e.g., Ensure7, Nutren7) are not made with lauric oils, and, in fact, many are made with partially hydrogenated oils.
There are currently some candies sold in the US that are made with palm kernel oil, and a few specialty candies made with coconut oil and desiccated coconut. These can supply small amounts of lauric acid.
Cookies such as macaroons, if made with desiccated coconut, are good sources of lauric acid, supplying as much as 6 grams of lauric acid per macaroon (Red Mill). However, these cookies make up a small portion of the cookie market. Most cookies in the United States are no longer made with coconut oil shortenings; however, there was a time when many US cookies (e.g., Pepperidge Farm) were about 25% lauric acid.
Originally, one of the largest manufacturers of cream soups used coconut oil in the formulations. Many popular cracker manufacturers also used coconut oil as a spray coating. These products supplied a small amount of lauric acid on a daily basis for some people.
How much lauric acid is needed?
It is not known exactly how much food made with lauric oils is needed in order to have a protective level of lauric acid in the diet. Infants probably consume between 0.3 and 1 gram per kilogram of body weight if they are fed human milk or an enriched infant formula that contains coconut oil. This amount appears to have always been protective. Adults could probably benefit from the consumption of 10 to 20 grams of lauric acid per day. Growing children probably need about the same amounts as adults.
VII. Recommendations
The coconut oil industry needs to make the case for lauric acid now. It should not wait for the rapeseed industry to promote the argument for including lauric acid because of the increased demand for laurate. In fact lauric acid may prove to be a conditionally essential saturated fatty acid, and the research to establish this fact around the world needs to be vigorously promoted.
Although private sectors need to fight for their commodity through the offices of their trade associations, the various governments of coconut producing countries need to put pressure on WHO, FAO, and UNDP to recognizes the health importance of coconut oil and the other coconut products. Moreover, those representatives who are going to do the persuading need to believe that their message is scientifically correct -- because it is.
Among the critical foods and nutrition "buzz words" for the 21st Century is the term "functional foods." Clearly coconut oil fits the designation of a very important functional food.
References
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Bierenbaum JL, Green DP, Florin A, Fleishman AI, Caldwell AB. Modified-fat dietary management of the young male with coronary disease: a five-year report. Journal of the American Medical Association 202:1119-1123;1967.
Blackburn GL, Kater G, Mascioli EA, Kowalchuk M, Babayan VK, kBistrian BR. A reevaluation of coconut oil's effect on serum cholesterol and atherogenesis. The Journal of the Philippine Medical Association 65:144-152;1989.
Castelli WP. Editorial: Concerning the possibility of a nut... Archives of Internal Medicine 152:1371-2;1992.
Cohen LA, Thompson DO, Maeura Y, Choi K, Blank M, Rose DP. Dietary fat and mammary cancer. I. Promoting effects of different dietary fats on N-nitrosomethylurea-induced rat mammary tumorigenesis. Journal of the National Cancer Institute 77:33;1986.
Cohen LA, Thompson DO, Choi K, Blank M, Rose DP. Dietary fat and mammary cancer. II. Modulation of serum and tumor lipid composition and tumor prostaglandins by different dietary fats: Association with tumor incidence patterns. Journal of the National Cancer Institute 77:43;1986.
Eraly MG. IV. Coconut oil and heart attack. Coconut and Coconut Oil in Human Nutrition, Proceedings. Symposium on Coconut and Coconut Oil in Human Nutrition. 27 March 1994. Coconut Development Board, Kochi, India, 1995, pp 63-64.
Enig MG. Diet, serum cholesterol and coronary heart disease, in Mann GV (ed): Coronary Heart Disease: The Dietary Sense and Nonsense. Janus Publishing, London, 1993, pp 36-60.
Felton CV, Crook D, Davies MJ, Oliver MF. Dietary polyunsaturated fatty acids and composition of human aortic plaques. Lancet, 344:1195-1196;1994.
Fletcher RD, Albers AC, Albertson JN, Kabara JJ. Effects of monoglycerides on mycoplasma pneumoniae growth, in The Pharmacological Effect of Lipids II (JJ Kabara, ed) American Oil Chemists' Society, Champaign IL, 1985, pp.59-63.
Florentino RF, Aquinaldo AR. Diet and cardiovascular disease in the Philippines. The Philippine Journal of Coconut Studies 12:56-70;1987.
Halden VW, Lieb H. Influence of biologically improved coconut oil products on the blood cholesterol levels of human volunteers. Nutr Dieta 3:75-88;1961.
Hashim SA, Clancy RE, Hegsted DM, Stare FJ. Effect of mixed fat formula feeding on serum cholesterol level in man. American Journal of Clinical Nutrition. 7:30-34;1959.
Hegsted DM, McGandy RB, Myer ML, Stare FJ. Quantitative effects of dietary fat on serum cholesterol in man. American Journal of Clinical Nutrition. 17:281-295;1965.
Hierholzer, J.C. and Kabara, J.J. In vitro effects of monolaurin compounds on enveloped RNA and DNA viruses. Journal of Food Safety 4:1-12;1982.
Hostmark AT, Spydevold O, Eilertsen E. Plasma lipid concentration and liver output of lipoproteins in rats fed coconut fat or sunflower oil. Artery 7:367-383, 1980.
Isaacs CE, Thormar H. Membrane-disruptive effect of human milk: inactivation of enveloped viruses. Journal of Infectious Diseases 154:966-971;1986.
Isaacs CE, Thormar H. Human milk lipids inactivated enveloped viruses. in Breastfeeding, Nutrition, Infection and Infant Growth in Developed and Emerging Countries (Atkinson SA, Hanson LA, Chandra RK, eds) Arts Biomedical Publishers and Distributors, St. John's NF, Canada, 1990.
Isaacs CE, Thormar H. The role of milk-derived antimicrobial lipids as antiviral and antibacterial agents in Immunology of Milk and the Neonate (Mestecky J, et al, eds) Plenum Press, New York, 1991.
Isaacs CE, Schneidman K. Enveloped Viruses in Human and Bovine Milk are Inactivated by Added Fatty Acids(FAs) and Monoglycerides(MGs). FASEB Journal. Abstract 5325, p.A1288, 1991.
Isaacs CE, Kashyap S, Heird WC, Thormar H. Antiviral and antibacterial lipids in human milk and infant formula feeds. Archives of Disease in Childhood 65:861-864;1990.
Isaacs CE, Litov RE, Marie P, Thormar H. Addition of lipases to infant formulas produces antiviral and antibacterial activity. Journal of Nutritional Biochemistry 3:304-308;1992.
Kabara JJ. Fatty acids and derivatives as antimicrobial agents -- A review, in The Pharmacological Effect of Lipids (JJ Kabara, ed) American Oil Chemists' Society, Champaign IL, 1978,
Kabara JJ. Inhibition of staphylococcus aureaus in The Pharmacological Effect of Lipids II (JJ Kabara, ed) American Oil Chemists' Society, Champaign IL, 1985, pp.71-75.
Kaunitz H, Dayrit CS. Coconut oil consumption and coronary heart disease. Philippine Journal of Internal Medicine 30:165-171;1992.
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Kurup PA, Rajmohan T. II. Consumption of coconut oil and coconut kernel and the incidence of atherosclerosis. Coconut and Coconut Oil in Human Nutrition, Proceedings. Symposium on Coconut and Coconut Oil in Human Nutrition. 27 March 1994. Coconut Development Board, Kochi, India, 1995, pp 35-59.
Lim-Sylianco CY. Anticarcinogenic effect of coconut oil. The Philippine Journal of Coconut Studies 12:89-102;1987.
Macallan DC, Noble C, Baldwin C, Foskett M, McManus T, Griffin GE. Prospective analysis of patterns of weight change in stage IV hulman immunodeficiency virus infection. American Journal of Clinical Nutrition 58:417-24;1993.
Mann GV. A short history of the diet/heart hypothesis, in Mann GV (ed): Coronary Heart Disease: The Dietary Sense and Nonsense. Janus Publishing, London, 1993, pp 1-17.
Mendis S, Wissler RW, Bridenstine RT, Podbielski FJ. The effects of replacing coconut oil with corn oil on human serum lipid profiles and platelet derived factors active in atherogenesis. Nutrition Reports International 40:No.4;Oct.1989.
New York Times, Medical Science, Tuesday, January 29, 1991. Common virus seen as having early role in arteries' clogging (byline Sandra Blakeslee).
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Prior IA, Davidson F, Salmond CE, Czochanska Z. Cholesterol, coconuts, and diet on Polynesian atolls: a natural experiment: the Pukapuka and Tokelau Island studies. American Journal of Clinical Nutrition 34:1552-1561;1981.
Projan SJ, Brown-Skrobot S, Schlievert PM, Vandenesch F, Novick RP. Glycerol monolaurate inhibits the production of beta-lactamase, toxic shock toxin-1, and other staphylococcal exoproteins by interefering with signal transduction. Journal of Bacteriology. 176:4204-4209;1994.
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About the Author
Mary G. Enig, PhD is an expert of international renown in the field of lipid biochemistry. She has headed a number of studies on the content and effects of trans fatty acids in America and Israel, and has successfully challenged government assertions that dietary animal fat causes cancer and heart disease. Recent scientific and media attention on the possible adverse health effects of trans fatty acids has brought increased attention to her work. She is a licensed nutritionist, certified by the Certification Board for Nutrition Specialists, a qualified expert witness, nutrition consultant to individuals, industry and state and federal governments, contributing editor to a number of scientific publications, Fellow of the American College of Nutrition and President of the Maryland Nutritionists Association. She is the author of over 60 technical papers and presentations, as well as a popular lecturer. Dr. Enig is currently working on the exploratory development of an adjunct therapy for AIDS using complete medium chain saturated fatty acids from whole foods. She is Vice-President of the Weston A Price Foundation and Scientific Editor of Wise Traditions as well as the author of Know Your Fats: The Complete Primer for Understanding the Nutrition of Fats, Oils, and Cholesterol, Bethesda Press, May 2000. She is the mother of three healthy children brought up on whole foods including butter, cream, eggs and meat.
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A New Look at Coconut Oil
By Mary G. Enig, Ph.D.
Health and Nutritional Benefits from Coconut Oil: An Important Functional Food for the 21st Century
Presented at the AVOC Lauric Oils Symposium, Ho Chi Min City, Vietnam, 25 April 1996
Abstract
Coconut oil has a unique role in the diet as an important physiologically functional food. The health and nutritional benefits that can be derived from consuming coconut oil have been recognized in many parts of the world for centuries. Although the advantage of regular consumption of coconut oil has been underappreciated by the consumer and producer alike for the recent two or three decades, its unique benefits should be compelling for the health minded consumer of today. A review of the diet/heart disease literature relevant to coconut oil clearly indicates that coconut oil is at worst neutral with respect to atherogenicity of fats and oils and, in fact, is likely to be a beneficial oil for prevention and treatment of some heart disease. Additionally, coconut oil provides a source of antimicrobial lipid for individuals with compromised immune systems and is a nonpromoting fat with respect to chemical carcinogenesis.
I. Introduction
Mr. Chairman and members of the ASEAN Vegetable Oils Club, I would like to thank you for inviting me to participate in this Lauric Oils Symposium. I am pleased to have the opportunity to review with you some information that I hope will help redress some of the anti-tropical oils rhetoric that has been so troublesome to your industry.
I will be covering two important areas in my presentation. In the first part, I would like to review the history of the major health challenge facing coconut oil today. This challenge is based on a supposed negative role played by saturated fat in heart disease. I hope to dispel any acceptance of this notion with the information I will present to you today. I will show you how both animal studies and human studies have exonerated coconut oil of causing the problem.
In the second part of my talk I will suggest some new directions where important positive health benefits are seen for coconut oil. These benefits stem from coconut oil's use as a food with major antimicrobial and anticancer benefits. I will present to you some of the rationale for this effect and some of the supporting literature.
The health and nutritional benefits derived from coconut oil are unique and compelling. Although the baker and food processor have recognized the functional advantages of coconut oil in their industries, over most competing oils, for many years, I believe these benefits are underappreciated today by both the producer and the consumer. It is time to educate and reeducate all t hose who harbor this misinformation.
Historically, coconuts and their extracted oil have served man as important foods for thousands of years. The use of coconut oil as a shortening was advertised in the United States in popular cookbooks at the end of the 19th century. Both the health-promoting attributes of coconut oil and those functional properties useful to the homemaker were recognized 100 years ago. These same attributes, in addition to some newly discovered ones, should be of great interest to both the producing countries as well as the consuming countries.
II. Origins of the Diet/Heart Hypothesis
Although popular literature of epidemiological studies usually attribute an increased risk of coronary heart disease (CHD) to elevated levels of serum cholesterol, which in turn are thought to derive from a dietary intake of saturated fats and cholesterol. But, saturated fats may be considered a major culprit for CHD only if the links between serum cholesterol and CHD, and between saturated fat and serum cholesterol are each firmly established. Decades of large-scale tests and conclusions therefrom have purported to establish the first link. In fact, this relationship has reached the level of dogma. Through the years metabolic ward and animal studies have claimed that dietary saturated fats increase serum cholesterol levels, thereby supposedly establishing the second link. But the scientific basis for these relationships has now been challenged as resulting from large-scale misinterpretation and misrepresentation of the data. (Enig 1991, Mann 1991, Smith 1991, Ravnskov 1995)
Ancel Keys is largely responsible for starting the anti-saturated fat agenda in the United States. From 1953 to 1957 Keys made a series of statements regarding the atherogenicity of fats. These pronouncements were:
"All fats raise serum cholesterol; Nearly half of total fat comes from vegetable fats and oils; No difference between animal and vegetable fats in effect on CHD (1953); Type of fat makes no difference; Need to reduce margarine and shortening (1956); All fats are comparable; Saturated fats raise and polyunsaturated fats lower serum cholesterol; Hydrogenated vegetable fats are the problem; Animal fats are the problem (1957-1959)."
As can be seen, his findings were inconsistent.
What was the role of the edible oil industry in promoting the diet/heart hypothesis?
It is important to realize that at that time (1960s) the edible oil industry in the United States seized the opportunity to promote its polyunsaturates. The industry did this by developing a health issue focusing on Key's anti-saturated fat bias. With the help of the edible oil industry lobbying in the United States, federal government dietary goals and guidelines were adopted incorporating this mistaken idea that consumption of saturated fat was causing heart disease. This anti-saturated fat issue became the agenda of government and private agencies in the US and to an extent in other parts of the world. This is the agenda that has had such a devastating effect on the coconut industry for the past decade. Throughout the 1960s, the 1970s, the 1980s, and the 1990s, the anti-saturated fat rhetoric increased in intensity.
What are some of the contradictions to the hypothesis blaming saturated fat?
Recently, an editorial by Harvard's Walter Willett, M.D. in the American Journal of Public Health (1990) acknowledged that even though
"the focus of dietary recommendations is usually a reduction of saturated fat intake, no relation between saturated fat intake and risk of CHD was observed in the most informative prospective study to date."
Another editorial, this time by Framingham's William P. Castelli in the Archives of Internal Medicine (1992), declared for the record that
"...in Framingham, Mass, the more saturated fat one ate, the more cholesterol one ate, the more calories one ate, the lower the person's serum cholesterol... the opposite of what the equations provided by Hegsted at al (1965) and Keys et al (1957) would predict..."
Castelli further admitted that
"...In Framingham, for example, we found that the people who ate the most cholesterol, ate the most saturated fat, ate the most calories, weighed the least, and were the most physically active."
III. Coconut Oil and the Diet/Heart Hypothesis
For the past several decades you have heard about animal and human studies feeding coconut oil that purportedly showed increased indices for cardiovascular risk. Blackburn et al (1988) have reviewed the published literature of coconut oil's effect on serum cholesterol and atherogenesis and have concluded that when ...[coconut oil is] fed physiologically with other fats or adequately supplemented with linoleic acid, coconut oil is a neutral fat in terms of atherogenicity. After reviewing this same literature, Kurup and Rajmohan (1995) conducted a study on 64 volunteers and found ...no statistically significant alteration in the serum total cholesterol, HDL cholesterol, LDL cholesterol, HDL cholesterol/total cholesterol ratio and LDL cholesterol/HDL cholesterol ratio of triglycerides from the baseline values... A beneficial effect of adding the coconut kernel to the diet was noted by these researchers.
How did coconut oil get such a negative reputation?
The question then is, how did coconut oil get such a negative reputation? The answer quite simply is, initially, the significance of those changes that occurred during animal feeding studies were misunderstood. The wrong interpretation was then repeated until ultimately the misinformation and disinformation took on a life of its own.
The problems for coconut oil started four decades ago when researchers fed animals hydrogenated coconut oil that was purposefully altered to make it completely devoid of any essential fatty acids. The hydrogenated coconut oil was selected instead of hydrogenated cottonseed, corn or soybean oil because it was a soft enough fat for blending into diets due to the presence of the lower melting medium chain saturated fatty acids. The same functionality could not be obtained from the cottonseed, corn or soybean oils if they were made totally saturated, since all their fatty acids were long chain and high melting and could not be easily blended nor were they as readily digestible.
The animals fed the hydrogenated coconut oil (as the only fat source) naturally became essential fatty acid deficient; their serum cholesterol levels increased. Diets that cause an essential fatty acid deficiency always produce an increase in serum cholesterol levels as well as an increase in the atherosclerotic indices. The same effect has also been seen when other essential fatty acid deficient, highly hydrogenated oils such as cottonseed, soybean, or corn oils have been fed; so it is clearly a function of the hydrogenated product, either because the oil is essential fatty acid (EFA) deficient or because of trans fatty acids (TFA).
What about the studies where animals were fed with unprocessed coconut oil?
Hostmark et al (1980) compared the effects of diets containing 10% coconut fat and 10% sunflower oil on lipoprotein distribution in male Wistar rats. Coconut oil feeding produced significantly lower levels (p=<0.05) of pre-beta lipoproteins (VLDL) and significantly higher (p=<0.01) alpha-lipoproteins (HDL) relative to sunflower oil feeding.
Awad (1981) compared the effects of diets containing 14% coconut oil, 14% safflower oil or a 5% "control" (mostly soybean) oil on accumulation of cholesterol in tissues in male Wistar rats. The synthetic diets had 2% added corn oil with a total fat of 16% Total tissue cholesterol accumulation for animals on the safflower diet was six times greater than for animals fed the coconut oil, and twice that of the animals fed the control oil.
A conclusion that can be drawn from some of this animal research is that feeding hydrogenated coconut oil devoid of essential fatty acids (EFA) in a diet otherwise devoid of EFA leads to EFA deficiency and potentiates the formation of atherosclerosis markers. It is of note that animals fed regular coconut oil have less cholesterol deposited in their livers and other parts of their bodies.
What about the studies where coconut oil is part of the normal diet of human beings?
Kaunitz and Dayrit (1992) have reviewed some of the epidemiological and experimental data regarding coconut-eating groups and noted that the available population studies show that dietary coconut oil does not lead to high serum cholesterol nor to high coronary heart disease mortality or morbidity. They noted that in 1989 Mendis et al reported undesirable lipid changes when young adult Sri Lankan males were changed from their normal diets by the substitution of corn oil for their customary coconut oil. Although the total serum cholesterol decreased 18.7% from 179.6 to 146.0 mg/dl and the LDL cholesterol decreased 23.8% from 131.6 to 100.3 mg/dl, the HDL cholesterol decreased 41.4% from 43.4 to 25.4 mg/dl (putting the HDL values below the acceptable lower limit) and the LDL/HDL ratio increased 30% from 3.0 to 3.9. These latter two changes would be considered quite undesirable. As noted above, Kurup and Rajmohan (1995) studied the addition of coconut oil alone to previously mixed fat diets and report no significant difference.
Previously, Prior et al (1981) had shown that islanders with high intake of coconut oil showed no evidence of the high saturated fat intake having a harmful effect in these populations. When these groups migrated to New Zealand however, and lowered their intake of coconut oil, their total cholesterol and LDL cholesterol increased, and their HDL cholesterol decreased.
What about the studies where coconut oil was deliberately fed to human beings?
Some of the studies reported thirty and more years ago should have cleared coconut oil of any implication in the development of coronary heart disease (CHD).
For example, when Frantz and Carey (1961) fed an additional 810 kcal/day fat supplement for a whole month to males with high normal serum cholesterol levels, there was no significant difference from the original levels even though the fat supplement was hydrogenated coconut oil.
Halden and Lieb (1961) also showed similar results in a group of hyperchole-sterolemics when coconut oil was included in their diets. Original serum cholesterol levels were reported as 170 to 370 mg/dl. Straight coconut oil produced a range from 170 to 270 mg/dl. Coconut oil combined with 5% sunflower oil and 5% olive oil produced a range of 140 to 240 mg/dl.
Earlier, Hashim and colleagues (1959) had shown quite clearly that feeding a fat supplement to hypercholesterolemics, where half of the supplement (21% of energy) was coconut oil (and the other half was safflower oil), resulted in significant reductions in total serum cholesterol. The reductions averaged -29% and ranged from -6.8 to -41.2%.
And even earlier, Ahrens and colleagues (1957) had shown that adding coconut oil to the diet of hypercholesterolemics lowers serum cholesterol from, e.g., 450 mg/dl to 367 mg/dl. This is hardly a cholesterol-raising effect.
Bierenbaum et al (1967) followed 100 young men with documented myocardial infarction for 5 years on diets with fat restricted to 28% of energy. There was no significant difference between the two different fat mixtures (50/50 corn and safflower oils or 50/50 coconut and peanut oils), which were fed as half of the total fat allowance; both diets reduced serum cholesterol. This study clearly showed that 7% of energy as coconut oil was as beneficial to the 50 men who consumed it as for the 50 men who consumed 7% of energy as other oils such as corn oil or safflower. Both groups fared better than the untreated controls.
More recently, Sundram et al (1994) fed whole foods diets to healthy normo-cholesterolemic males, where approximately 30% of energy was fat. Lauric acid (C12:0) and myristic acid (C14:0) from coconut oil supplied approximately 5% of energy. Relative to the baseline measurements of the subjects prior to the experimental diet, this lauric and myristic acid-rich diet showed an increase in total serum cholesterol from 166.7 to 170.0 mg/dl (+1.9%), a decrease in low density lipoprotein cholesterol (LDL-C) from 105.2 to 104.4 mg/dl (-0.1%), an increase in high density lipoprotein cholesterol (HDL-C) from 42.9 to 45.6 mg/dl (+6.3%). There was a 2.4% decrease in the LDL-C/HDL-C ratio from 2.45 to 2.39. These findings indicate a favorable alteration in serum lipoprotein balance was achieved when coconut oil was included in a whole food diet at 5% of energy.
Tholstrup et al (1994) report similar results with whole foods diets high in lauric and myristic acids from palm kernel oil. The HDL cholesterol levels increased significantly from baseline values (37.5 to 46.0 mg/dl, P<0.01) and the LDL-C/HDL-C ratios decreased from 3.08 to 2.69. The increase in total cholesterol was from 154.7 (baseline) to 170.9 mg/dl on the experimental diet.
Ng et al (1991) fed 75% of the fat ration as coconut oil (24% of energy) to 83 adult normocholesterolemics (61 males and 22 females). Relative to baseline values, the highest values on the experimental diet for total cholesterol was increased 17% (169.6 to 198.4 mg/dl), HDL cholesterol was increased 21.4% (44.3 to 53.8 mg/dl), and the LDL-C/HDL-C ratio was decreased 3.6% (2.51 to 2.42).
When unprocessed coconut oil is added to an otherwise normal diet, there is frequently no change in the serum cholesterol although some studies have shown a decrease in total cholesterol. For example, when Ginsberg et al provided an "Average American" diet with 2-3 times more myristic acid (C14:0), 4.5 times more lauric acid (C12:0), and 1.2 times more palmitic and stearic acid (C16:0 and C18:0) than their "Mono[unsaturated]" diet and the National Cholesterol Education Program "Step 1" diet, there was no increase in serum cholesterol, and in fact, serum cholesterol levels for this diet group fell approximately 3% from 177.1 mg% to 171.8 mg% during the 22 week feeding trial.
It appears from many of the research reports that the effect coconut oil has on serum cholesterol is the opposite in individuals with low serum cholesterol values and those with high serum values. We see that there may be a raising of serum total cholesterol, LDL cholesterol and especially HDL cholesterol in individuals with low serum cholesterol. On the other hand there is lowering of total cholesterol and LDL cholesterol in hypercholesterolemics as noted above.
Studies that supposedly showed a hypercholesterolemic effect of coconut oil feeding, in fact, usually only showed that coconut oil was not as effective at lowering the serum cholesterol as was the more unsaturated fat being compared. This appears to be in part because coconut oil does not drive cholesterol into the tissues as does the more polyunsaturated fats. The chemical analysis of the atheroma shows that the fatty acids from the cholesterol esters are 74% unsaturated (41% is polyunsaturated) and only 24% are saturated. None of the saturated fatty acids were reported to be lauric acid or myristic acid (Felton et al 1994).
Should coconut oil be used to prevent coronary heart disease?
There is another aspect to the coronary heart disease picture. This is related to the initiation of the atheromas that are reported to be blocking arteries. Recent research is suggestive that there is a causative role for the herpes virus and cytomegalovirus in the initial formation of atherosclerotic plaques and the recloging of arteries after angioplasty. (New York Times 1991) What is so interesting is that the herpes virus and cytomegalovirus are both inhibited by the antimicrobial lipid monolaurin; but monolaurin is not formed in the body unless there is a source of lauric acid in the diet. Thus, ironically enough, one could consider the recommendations to avoid coconut and other lauric oils as contributing to the increased incidence of coronary heart disease.
Perhaps more important than any effect of coconut oil on serum cholesterol is the additional effect of coconut oil on the disease fighting capability of the animal or person consuming the coconut oil.
IV. Coconut Oil and Cancer
Lim-Sylianco (1987) has reviewed 50 years of literature showing anticarcinogenic effects from dietary coconut oil. These animal studies show quite clearly the nonpromotional effect of feeding coconut oil.
In a study by Reddy et al (1984) straight coconut oil was more inhibitory than MCT oil to induction of colon tumors by azoxymethane. Chemically induced adenocarcinomas differed 10-fold between corn oil (32%) and coconut oil (3%) in the colon. Both olive oil and coconut oil developed the low levels (3%) of the adenocarcinomas in the colon, but in the small intestine animals fed coconut oil did not develop any tumors while 7% of animals fed olive oil did.
Studies by Cohen et al (1986) showed that the nonpromotional effects of coconut oil were also seen in chemically induced breast cancer. In this model, the slight elevation of serum cholesterol in the animals fed coconut oil was protective as the animals fed the more polyunsaturated oil had reduced serum cholesterol and more tumors. The authors noted that "...an overall inverse trend was observed between total serum lipids and tumor incidence for the 4 [high fat] groups."
This is an area that needs to be pursued.
V. Coconut Oil Antimicrobial Benefits
I would now like to review for you some of the rationale for the use of coconut oil as a food that will serve as the raw material to provide potentially useful levels of antimicrobial activity in the individual.
The lauric acid in coconut oil is used by the body to make the same disease-fighting fatty acid derivative monolaurin that babies make from the lauric acid they get from their mothers= milk. The monoglyceride monolaurin is the substance that keeps infants from getting viral or bacterial or protozoal infections. Until just recently, this important benefit has been largely overlooked by the medical and nutrition community.
Recognition of the antimicrobial activity of the monoglyceride of lauric acid (monolaurin) has been reported since 1966. The seminal work can be credited to Jon Kabara. This early research was directed at the virucidal effects because of possible problems related to food preservation. Some of the early work by Hierholzer and Kabara (1982) that showed virucidal effects of monolaurin on enveloped RNA and DNA viruses was done in conjunction with the Center for Disease Control of the US Public Health Service with selected prototypes or recognized representative strains of enveloped human viruses. The envelope of these viruses is a lipid membrane.
Kabara (1978) and others have reported that certain fatty acids (e.g., medium-chain saturates) and their derivatives (e.g., monoglycerides) can have adverse effects on various microorganisms: those microorganisms that are inactivated include bacteria, yeast, fungi, and enveloped viruses.
The medium-chain saturated fatty acids and their derivatives act by disrupting the lipid membranes of the organisms (Isaacs and Thormar 1991) (Isaacs et al 1992). In particular, enveloped viruses are inactivated in both human and bovine milk by added fatty acids (FAs) and monoglycerides (MGs) (Isaacs et al 1991) as well as by endogenous FAs and MGs (Isaacs et al 1986, 1990, 1991, 1992; Thormar et al 1987).
All three monoesters of lauric acid are shown to be active antimicrobials, i.e., alpha-, alpha'-, and beta-MG. Additionally, it is reported that the antimicrobial effects of the FAs and MGs are additive and total concentration is critical for inactivating viruses (Isaacs and Thormar 1990).
The properties that determine the anti-infective action of lipids are related to their structure; e.g., monoglycerides, free fatty acids. The monoglycerides are active, diglycerides and triglycerides are inactive. Of the saturated fatty acids, lauric acid has greater antiviral activity than either caprylic acid (C-10) or myristic acid (C-14).
The action attributed to monolaurin is that of solubilizing the lipids and phospholipids in the envelope of the virus causing the disintegration of the virus envelope. In effect, it is reported that the fatty acids and monoglycerides produce their killing/inactivating effect by lysing the (lipid bilayer) plasma membrane. However, there is evidence from recent studies that one antimicrobial effect is related to its interference with signal transduction (Projan et al 1994).
Some of the viruses inactivated by these lipids, in addition to HIV, are the measles virus, herpes simplex virus-1 (HSV-1), vesicular stomatitis virus (VSV), visna virus, and cytomegalovirus (CMV). Many of the pathogenic organisms reported to be inactivated by these antimicrobial lipids are those known to be responsible for opportunistic infections in HIV-positive individuals. For example, concurrent infection with cytomegalovirus is recognized as a serious complication for HIV+ individuals (Macallan et al 1993). Thus, it would appear to be important to investigate the practical aspects and the potential benefit of an adjunct nutritional support regimen for HIV-infected individuals, which will utilize those dietary fats that are sources of known anti-viral, anti-microbial, and anti-protozoal monoglycerides and fatty acids such as monolaurin and its precursor lauric acid.
No one in the mainstream nutrition community seems to have recognized the added potential of antimicrobial lipids in the treatment of HIV-infected or AIDS patients. These antimicrobial fatty acids and their derivatives are essentially non-toxic to man; they are produced in vivo by humans when they ingest those commonly available foods that contain adequate levels of medium-chain fatty acids such as lauric acid. According to the published research, lauric acid is one of the best "inactivating" fatty acids, and its monoglyceride is even more effective than the fatty acid alone (Kabara 1978, Sands et al 1978, Fletcher et al 1985, Kabara 1985).
The lipid coated (envelop) viruses are dependent on host lipids for their lipid constituents. The variability of fatty acids in the foods of individuals accounts for the variability of fatty acids in the virus envelop and also explains the variability of glycoprotein expression.
Loss of lauric acid from the American diet
Increasingly, over the past 40 years, the American diet has undergone major changes. Many of these changes involve changes of fats and oils. There has been an increasing supply of the partially hydrogenated trans-containing vegetable oils and a decreasing amount of the lauric acid-containing oils. As a result, there has been an increased consumption of trans fatty acids and linoleic acid and a decrease in the consumption of lauric acid. This type of change in diet has an effect on the fatty acids the body has available for metabolic activities.
VI. Lauric Acid in Foods
The coconut producing countries
Whole coconut as well as extracted coconut oil has been a mainstay in the food supply in many countries in parts of Asia and the Pacific Rim throughout the centuries. Recently though, there has been some replacement of coconut oil by other seed oils. This is unfortunate since the benefits gained from consuming an adequate amount of coconut oil are being lost.
Based on the per capita intake of coconut oil in 1985 as reported by Kaunitz (1992), the per capita daily intake of lauric acid can be approximated. For those major producing countries such as the Philippines, Indonesia, and Sri Lanka, and consuming countries such as Singapore, the daily intakes of lauric acid were approximately 7.3 grams (Philippines), 4.9 grams (Sri Lanka), 4.7 grams (Indonesia), and 2.8 grams (Singapore). In India, intake of lauric acid from coconut oil in the coconut growing areas (e.g., Kerala) range from about 12 to 20 grams per day (Eraly 1995), whereas the average for the rest of the country is less than half a gram. An average high of approximately 68 grams of lauric acid is calculated from the coconut oil intake previously reported by Prior et al (1981) for the Tokelau Islands. Other coconut producing countries may also have intakes of lauric acid in the same range.
The US experience
In the United States today, there is very little lauric acid in most of the foods. During the early part of the 20th Century and up until the late 1950s many people consumed heavy cream and high fat milk. These foods could have provided approximately 3 grams of lauric acid per day to many individuals. In addition, desiccated coconut was a popular food in homemade cakes, pies and cookies, as well as in commercial baked goods, and 1-2 tablespoons of desiccated coconut would have supplied 1-2 grams of lauric acid. Those foods made with the coconut oil based shortenings would have provided additional amounts.
Until two years ago, some of the commercially sold popcorn, at least in movie theaters, had coconut oil as the oil. This means that for those people lucky enough to consume this type of popcorn the possible lauric acid intake was 6 grams or more in a three (3) cup order.
Some infant formulas (but not all) have been good sources of lauric acid for infants. However, in the past 3-4 years there has been reformulation with a loss of a portion of coconut oil in these formulas, and a subsequent lowering of the lauric acid levels.
Only one US manufactured enteral formula contains lauric acid (e.g., Impact7); this is normally used in hospitals for tube feeding; it is reported to be very effective in reversing severe weight loss in AIDS patients, but it is discontinued when the patients leave the hospital because it is not sufficiently palatable for oral use. The more widely promoted enteral formulas (e.g., Ensure7, Nutren7) are not made with lauric oils, and, in fact, many are made with partially hydrogenated oils.
There are currently some candies sold in the US that are made with palm kernel oil, and a few specialty candies made with coconut oil and desiccated coconut. These can supply small amounts of lauric acid.
Cookies such as macaroons, if made with desiccated coconut, are good sources of lauric acid, supplying as much as 6 grams of lauric acid per macaroon (Red Mill). However, these cookies make up a small portion of the cookie market. Most cookies in the United States are no longer made with coconut oil shortenings; however, there was a time when many US cookies (e.g., Pepperidge Farm) were about 25% lauric acid.
Originally, one of the largest manufacturers of cream soups used coconut oil in the formulations. Many popular cracker manufacturers also used coconut oil as a spray coating. These products supplied a small amount of lauric acid on a daily basis for some people.
How much lauric acid is needed?
It is not known exactly how much food made with lauric oils is needed in order to have a protective level of lauric acid in the diet. Infants probably consume between 0.3 and 1 gram per kilogram of body weight if they are fed human milk or an enriched infant formula that contains coconut oil. This amount appears to have always been protective. Adults could probably benefit from the consumption of 10 to 20 grams of lauric acid per day. Growing children probably need about the same amounts as adults.
VII. Recommendations
The coconut oil industry needs to make the case for lauric acid now. It should not wait for the rapeseed industry to promote the argument for including lauric acid because of the increased demand for laurate. In fact lauric acid may prove to be a conditionally essential saturated fatty acid, and the research to establish this fact around the world needs to be vigorously promoted.
Although private sectors need to fight for their commodity through the offices of their trade associations, the various governments of coconut producing countries need to put pressure on WHO, FAO, and UNDP to recognizes the health importance of coconut oil and the other coconut products. Moreover, those representatives who are going to do the persuading need to believe that their message is scientifically correct -- because it is.
Among the critical foods and nutrition "buzz words" for the 21st Century is the term "functional foods." Clearly coconut oil fits the designation of a very important functional food.
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Tholstrup T, Marckmann P, Jespersen J, Sandstrom B. Fat high in stearic acid favorably affects blood lipids and factor VII coagulant activity in comparison with fats high in palmitic acid or high in myristic and lauric acids. American Journal of Clinical Nutrition 59:371-377;1994.
Thormar H, Isaacs EC, Brown HR, Barshatzky MR, Pessolano T. Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides. Antimicrobial agents and chemotherapy 1987;31:27-31.
Willett W. Editorial: Challenges for public health nutrition in the 1990s. American Journal of Public Health. 80:1295-1298;1990.
About the Author
Mary G. Enig, PhD is an expert of international renown in the field of lipid biochemistry. She has headed a number of studies on the content and effects of trans fatty acids in America and Israel, and has successfully challenged government assertions that dietary animal fat causes cancer and heart disease. Recent scientific and media attention on the possible adverse health effects of trans fatty acids has brought increased attention to her work. She is a licensed nutritionist, certified by the Certification Board for Nutrition Specialists, a qualified expert witness, nutrition consultant to individuals, industry and state and federal governments, contributing editor to a number of scientific publications, Fellow of the American College of Nutrition and President of the Maryland Nutritionists Association. She is the author of over 60 technical papers and presentations, as well as a popular lecturer. Dr. Enig is currently working on the exploratory development of an adjunct therapy for AIDS using complete medium chain saturated fatty acids from whole foods. She is Vice-President of the Weston A Price Foundation and Scientific Editor of Wise Traditions as well as the author of Know Your Fats: The Complete Primer for Understanding the Nutrition of Fats, Oils, and Cholesterol, Bethesda Press, May 2000. She is the mother of three healthy children brought up on whole foods including butter, cream, eggs and meat.
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Monday, May 11, 2009
Cervical cancers after human papillomavirus vaccination
Cervical cancers after human papillomavirus vaccination.
Beller U, Abu-Rustum NR.
Shaare Zedek Medical Center, Jerusalem, Israel. beller@szmc.org.il
BACKGROUND: Current randomized clinical trials have shown that the quadrivalent human papillomavirus (HPV) vaccine can reduce the morbidity of precancerous lesions associated with HPV infection of vaccine-related subtypes. However, to date, there is no definite evidence showing the vaccine reduces the incidence of invasive cervical carcinoma. CASES: We present two cases--one young, vaccinated woman who developed cervical carcinoma that was unrelated to HPV and another who developed cervical carcinoma secondary to infection with an HPV subtype not covered by the vaccine. Both patients were treated successfully and remained well without evidence of cancer. CONCLUSION: Long-term follow-up data are needed to evaluate the prophylactic effectiveness of the current HPV vaccine. These cases could represent non-vaccine-related HPV infections. Young women must be thoroughly counseled about the efficacy and limitations of the vaccine and about continuing lifelong screening even after vaccination.
PMID: 19155953 [PubMed - in process]
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Beller U, Abu-Rustum NR.
Shaare Zedek Medical Center, Jerusalem, Israel. beller@szmc.org.il
BACKGROUND: Current randomized clinical trials have shown that the quadrivalent human papillomavirus (HPV) vaccine can reduce the morbidity of precancerous lesions associated with HPV infection of vaccine-related subtypes. However, to date, there is no definite evidence showing the vaccine reduces the incidence of invasive cervical carcinoma. CASES: We present two cases--one young, vaccinated woman who developed cervical carcinoma that was unrelated to HPV and another who developed cervical carcinoma secondary to infection with an HPV subtype not covered by the vaccine. Both patients were treated successfully and remained well without evidence of cancer. CONCLUSION: Long-term follow-up data are needed to evaluate the prophylactic effectiveness of the current HPV vaccine. These cases could represent non-vaccine-related HPV infections. Young women must be thoroughly counseled about the efficacy and limitations of the vaccine and about continuing lifelong screening even after vaccination.
PMID: 19155953 [PubMed - in process]
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Influence Of The Menstrual Cycle On The Female Brain
Influence Of The Menstrual Cycle On The Female Brain
ScienceDaily (Feb. 11, 2007) — What influence does the variation in estrogen level have on the activation of the female brain? Using functional Magnetic Resonance Imaging, Jean-Claude Dreher, a researcher at the Cognitive Neuroscience Center (CNRS/Université Lyon 1), in collaboration with an American team from the National Institute of Mental Health (Bethesda, Maryland) directed by Karen Berman, has identified, for the first time, the neural networks involved in processing reward-related functions modulated by female gonadal steroid hormones. This result, which was published online on January 29, 2007 on the PNAS website, is an important step in better comprehension of certain psychiatric and neurological pathologies.
--------------------------------------------------------------------------------
See also:
Health & Medicine
Menopause
Gynecology
Women's Health
Mind & Brain
Gender Difference
Intelligence
Neuroscience
Reference
Functional neuroimaging
Hypothalamus
Androgen
Dementia with Lewy bodies
The human brain has a recompense system that predicts different types of reward (food, money, drugs…). The normal functioning of this system plays a fundamental role in many cognitive processes such as motivation and learning. This reward system, composed of dopaminergic neurons(1) situated in the mesencephalon (a very deep region of the brain) and their projection sites(2), is crucial for neural coding of rewards. Its dysfunction can result in disorders such as addictions and is also implicated in various psychiatric and neurological pathologies, such as Parkinson's disease and schizophrenic disorders. Many studies on animals prove that the dopaminergic(3) system is sensitive to gonadal steroid hormones (estrogen, progesterone). For example, female rats self-administer cocaine (a drug that acts on the dopamine system) in higher doses after estrogens have been administered to them. The influence of gonadal steroid hormones on the activation of the reward system remained to be studied in humans. A better knowledge of this influence should make for better understanding of the differences between men and women, particularly as observed in the prevalence of certain psychiatric pathologies and in vulnerability to drugs, (for which the dopaminergic system plays an important role.) It is known, for example, that the female response to cocaine is greater in the follicular phase of the menstrual cycle(4) than in the luteal phase(5). Moreover, schizophrenia tends to appear later in women than in men.
Estrogens and progesterone are not just sex hormones that influence ovulation and reproduction; they also affect a large number of cognitive and affective functions.
These two observations show that gonadal neurosteroids(6) modulate the female dopaminergic system, but the question remains as to whether these hormones modulate the reward system neuron network.
In order to answer this question, the team developed an experiment using functional Magnetic Resonance Imaging (fMRI). The brain activity of a group of women was examined twice during their menstrual cycle. Each time they went into the MRI, they were presented with virtual slot machines showing different probabilities of winning. When women anticipate uncertain rewards, they activate the brain regions involved in processing emotions, particularly the amygdala and the orbitofrontal cortex, to a greater extent during the follicular phase (4 to 8 days after the start of the period) than during the luteal phase (6 to 10 after the LH(7) hormone surge). These results demonstrate increased reactivity of the female recompense system during the follicular phase, which is also the phase in which the estrogens do not oppose the progesterone. In order to determine the gender-related differences of reward system activation, the same experiment was carried out on a male group. Result: when men anticipate rewards, they mainly activate a region involved in motivation for obtaining rewards, the ventral striatum, whereas in women, it is a region dealing with emotions, the amygdalo-hippocampal region, which is the most highly activated.
These conclusions could be applied to rewards other than monetary. Take receptiveness and desire, for example, two qualities that are supposed to facilitate procreation and are seen during the period of ovulation. It could be envisaged that the increase in activity of certain regions of the female brain during the follicular phase would modulate behavior linked to obtaining rewards, such as approach behavior during reward anticipation and hedonistic behavior when the reward is received.
These results, at the border between neuroendocrinology and neurosciences, provide a better understanding of the fundamental role of gonadal steroid hormones on reward processing, particularly in behavioral processes such as motivation and learning. They also important in understanding the dysfunction of the reward system observed particularly in cases of Parkinson's disease, schizophrenia, normal ageing and drug and gambling addictions.
Adapted from materials provided by CNRS.
ScienceDaily (Feb. 11, 2007) — What influence does the variation in estrogen level have on the activation of the female brain? Using functional Magnetic Resonance Imaging, Jean-Claude Dreher, a researcher at the Cognitive Neuroscience Center (CNRS/Université Lyon 1), in collaboration with an American team from the National Institute of Mental Health (Bethesda, Maryland) directed by Karen Berman, has identified, for the first time, the neural networks involved in processing reward-related functions modulated by female gonadal steroid hormones. This result, which was published online on January 29, 2007 on the PNAS website, is an important step in better comprehension of certain psychiatric and neurological pathologies.
--------------------------------------------------------------------------------
See also:
Health & Medicine
Menopause
Gynecology
Women's Health
Mind & Brain
Gender Difference
Intelligence
Neuroscience
Reference
Functional neuroimaging
Hypothalamus
Androgen
Dementia with Lewy bodies
The human brain has a recompense system that predicts different types of reward (food, money, drugs…). The normal functioning of this system plays a fundamental role in many cognitive processes such as motivation and learning. This reward system, composed of dopaminergic neurons(1) situated in the mesencephalon (a very deep region of the brain) and their projection sites(2), is crucial for neural coding of rewards. Its dysfunction can result in disorders such as addictions and is also implicated in various psychiatric and neurological pathologies, such as Parkinson's disease and schizophrenic disorders. Many studies on animals prove that the dopaminergic(3) system is sensitive to gonadal steroid hormones (estrogen, progesterone). For example, female rats self-administer cocaine (a drug that acts on the dopamine system) in higher doses after estrogens have been administered to them. The influence of gonadal steroid hormones on the activation of the reward system remained to be studied in humans. A better knowledge of this influence should make for better understanding of the differences between men and women, particularly as observed in the prevalence of certain psychiatric pathologies and in vulnerability to drugs, (for which the dopaminergic system plays an important role.) It is known, for example, that the female response to cocaine is greater in the follicular phase of the menstrual cycle(4) than in the luteal phase(5). Moreover, schizophrenia tends to appear later in women than in men.
Estrogens and progesterone are not just sex hormones that influence ovulation and reproduction; they also affect a large number of cognitive and affective functions.
These two observations show that gonadal neurosteroids(6) modulate the female dopaminergic system, but the question remains as to whether these hormones modulate the reward system neuron network.
In order to answer this question, the team developed an experiment using functional Magnetic Resonance Imaging (fMRI). The brain activity of a group of women was examined twice during their menstrual cycle. Each time they went into the MRI, they were presented with virtual slot machines showing different probabilities of winning. When women anticipate uncertain rewards, they activate the brain regions involved in processing emotions, particularly the amygdala and the orbitofrontal cortex, to a greater extent during the follicular phase (4 to 8 days after the start of the period) than during the luteal phase (6 to 10 after the LH(7) hormone surge). These results demonstrate increased reactivity of the female recompense system during the follicular phase, which is also the phase in which the estrogens do not oppose the progesterone. In order to determine the gender-related differences of reward system activation, the same experiment was carried out on a male group. Result: when men anticipate rewards, they mainly activate a region involved in motivation for obtaining rewards, the ventral striatum, whereas in women, it is a region dealing with emotions, the amygdalo-hippocampal region, which is the most highly activated.
These conclusions could be applied to rewards other than monetary. Take receptiveness and desire, for example, two qualities that are supposed to facilitate procreation and are seen during the period of ovulation. It could be envisaged that the increase in activity of certain regions of the female brain during the follicular phase would modulate behavior linked to obtaining rewards, such as approach behavior during reward anticipation and hedonistic behavior when the reward is received.
These results, at the border between neuroendocrinology and neurosciences, provide a better understanding of the fundamental role of gonadal steroid hormones on reward processing, particularly in behavioral processes such as motivation and learning. They also important in understanding the dysfunction of the reward system observed particularly in cases of Parkinson's disease, schizophrenia, normal ageing and drug and gambling addictions.
Adapted from materials provided by CNRS.
Herpesvirus, cytomegalovirus, human sperm and assisted fertilization
Herpesvirus, cytomegalovirus, human sperm and assisted fertilization
Coralie Pallier1, Lamia Tebourbi2, Stéphanie Chopineau-Proust1, Damien Schoevaert3, Patrice Nordmann1, Jacques Testart2 and Anne-Marie Courtot2,4
1 Service de Bactériologie–Virologie–Parasitologie–Hygiène, CHU Bicêtre, Paris-Sud, 78 rue du Général Leclerc, 94275 Le Kremlin–Bicêtre, 2 Institut National de la Santé et de la Recherche Médicale Unité 355 et Institut Fédératif de Recherche sur les Cytokines,32 rue des Carnets, 92140 Clamart and 3 Laboratoire d'Analyse d'Images en Pathologie Cellulaire, Institut Universitaire d'Hématologie, Hopital Saint Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France
Abstract
Top
Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
BACKGROUND: The effect of viral particles on the motility of human sperm and the relationship between sperm and virus are of importance particularly in assisted fertilizations. METHODS: We incubated ejaculated sperm with or without seminal fluid with either herpes simplex virus type 2 (HSV2) or human cytomegalovirus (HCMV). For each experiment, 5x105 sperm were incubated with a viral load of between 104 and 106 plaque-forming units. RESULTS: We detected no apparent variations in the percentage of motile forms when sperm were incubated with either HSV2 or HCMV. Using a computer-aided semen analysis system, a slight difference was reported in the percentage of motile forms when seminal fluid-free sperm were incubated with HSV2 (57.18 versus 64.43 in the control). Although the mean amplitude of lateral head displacement and the curvilinear velocity were significantly higher in infected sperm, the difference in straight line velocity was not statistically significantly different. Few viral particles (HSV2 or HCMV) adhered to the sperm membrane in the presence of seminal fluid. However, more particles stuck when in the absence of seminal fluid, particularly with HSV2 (8% of sperm sections for HSV2; 4% for HCMV). CONCLUSIONS: The relationship between sperm and viruses depends on the type of virus present as well as the presence or absence of seminal fluid. Motility is not a good enough criterion on which to prove the presence of viral elements, either in the medium or on the sperm.
Key words: cytomegalovirus/Herpesviridae/human sperm/motility/seminal fluid
Introduction
Top
Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
Several successful new assisted reproductive techniques have been developed over the last decade. It is now possible to take a selected spermatozoon from a given point in the genital tract and to transfer it into the ooplasm. This technique, known as ICSI, involves the use of micromanipulations to move sperm across the zona pellucida and the plasma membrane. The ICSI technique has enabled sperm that would otherwise be unable to fertilize the oocyte to do so, resulting in successful pregnancies. The sperm can be extracted from different regions of the genital tract, e.g. from the testes or from the epididymal duct (Lewin et al., 1999), or from semen samples. The extraction of testicular sperm followed by ICSI is a convenient way of overcoming non-obstructive azoospermia (Devroey et al., 1996). Several methods can be used to process the extracted sperm. The choice of method depends on the facilities available and the physiological condition of the sperm. These methods include isolating a simple swab in a synthetic medium (De Croo et al., 2000), washing by centrifugation (Devroey et al., 1996), selection on a Percoll gradient (Mercan et al., 2000) and swim-up migration (Marina et al., 1998). Although these techniques can solve many fertility problems, they also raise questions about the risks of transferring viral particles into the oocyte.
Several viruses are present in the genital tract. The most common are the herpes simplex virus type 2 (HSV2) and human cytomegalovirus (HCMV), which are sexually transmissible and can lead to fetal and neonatal anomalies (Huraux et al., 1999; Ranger-Roger et al., 1999). Sperm are formed in seminiferous tubules in the testes, where they are protected from the environmental tissue by the haematotesticular barrier. We previously showed that no viral particles are found within the seminiferous tubules in MCMV-infected murine testes. However, the peritubular cells, Leydig cells and endothelial cells contained high viral loads (Tebourbi et al., 2001). Several other papers have reported the presence of HSV2 (Deture et al., 1976) and of CMV (De Paepe et al., 1990) in the testes, but this does not automatically mean that the seminiferous tubules were contaminated (Baskar et al., 1986; Stephanopoulos et al., 1989). However, viruses may be present in the epididymis (Dalton and Harcourt-Webster, 1991; MacCarthy et al., 1991), deferent duct (Kimura et al., 1993), prostate (Boldogh et al., 1983; Benson and Smith, 1992; Mastroianni et al., 1996) or seminal vesicles (Deture et al., 1976; Kimura et al., 1993). If the virus is present in the annexial glands, it may be discharged in the seminal fluid before coming into contact with sperm. The presence of the virus in the semen indicates a genital tract infection. One study (Moore et al., 1989) found infective HSV2 virus in the semen of a healthy donor with an asymptomatic primary infection, and showed that insemination led to the horizontal transmission of the virus. However, cell culture methods have rarely detected HSV2 in sperm (Deture et al., 1978; MacGowan et al., 1983), because semen contains inhibitors that may interfere with these methods (Deture et al., 1978; Sherman and Morgan, 1989). More sensitive methods, such as PCR and in-situ hybridization (ISH), have made it possible to detect viral DNA in the semen of men with genital HSV2 infection (Kotronias and Kapranos, 1998; Wald et al., 1999) and in the semen of a high-risk population (Tabrizi et al., 2000). HCMV has been identified in sperm (Lang and Kummer, 1972). The prevalence of HCMV elements was found to be variable in men who did not have human immunodeficiency virus (HIV) or other sexually transmitted diseases (Lang and Kummer, 1972; Bantel-Schaal et al., 1993; Shen et al., 1994; Mansat et al., 1997), but it may be high in high-risk populations (Biggar et al., 1983; Leach et al., 1993). Detection rates are generally higher for viral DNA than for infective particles. In a recent study involving men taking part in an IVF programme (Witz et al., 1999), 25% of ejaculates, including those from HCMV-negative men (who may or may not have gone on to become positive), were found to contain viral DNA.
Thus, sperm are protected from viral contact in the upper regions of the genital tract, i.e. the testes, whereas sperm in the semen can easily come into contact with viral particles (in the epididymis, deferent duct and annexial glands). This is important as sperm can be harvested from testicular biopsies for ICSI in cases of azoospermia. This then disrupts the haematotesticular barrier, thus removing the protective effect and placing the sperm in close contact with endothelial cells, Leydig cells and peritubular cells. Sperm can also be harvested from the other genital organs or from the semen. In this case, the fertilizing sperm for ICSI are choosen according to their motility. The relationship between the virus and sperm motility is not very clear and the interaction between sperm and virus are of importance.
Some authors have reported an inverse correlation between the presence of HSV2 in semen and sperm motility (Kotronias and Kapranos, 1998). Similar observations have been reported concerning CMV (Torino et al., 1987). A high concentration of HCMV was detected in the semen of a patient with CMV mononucleosis, and this was associated with a transient decrease in sperm motility (Lang and Kummer, 1972; Lang et al., 1974). We were interested to know whether this decrease in sperm motility was due to a direct effect of high concentrations of the virus on sperm or if these results were due to an indirect effect. Few papers have addressed the viral load of semen (Lang and Kummer, 1972; Biggar et al., 1983). Therefore it is not clear how the virus and sperm interact. No relationship has been found between sperm and HSV2 (Sherman and Morgan, 1989), whereas ISH has been used to demonstrate that there is a close relationship between sperm and HSV2 (Kotronias and Kapranos, 1998). Only one group has found CMV within human sperm (Huang et al., 1986); another group (Baskar et al., 1986) observed virus-like particles in mouse sperm.
We developed experimental models to analyse the effects of viruses on sperm motility and the interaction between viruses and sperm in assisted reproduction indications. On the one hand, we used semen, i.e. sperm plus seminal fluid, which is the physiological environment from which motile sperm are selected for intrauterine insemination, IVF and ICSI. On the other hand, we used sperm without seminal fluid (selected by use of a PureSperm gradient), which corresponds to sperm collected in the epididymis before the formation of seminal fluid or to sperm collected from testicular biopsies in azoospermic men for ICSI. The viruses used were HSV2 and HCMV. This study enabled us to study the relationship between viruses and sperm in different regions of the genital tract and to determine whether the new assisted reproduction techniques (especially ICSI in the case of azoospermia) affect the risks of virus adherence to sperm, leading to the introduction of viral particles into oocytes.
Materials and methods
Top
Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
Preparation of the viral strains
The viral strains, HSV2 (ATCC VR-2019) and HCMV (AD-169), were prepared from human embryo lung cells (MRC5, primary cells; Biomerieux, Lyon, France) in modified Eagle's medium (MEM; Gibco BRL, Life Technologies, Paisley, UK). The viral suspensions were titrated by an enzymatic assay method (visualization of early viral antigens) at a concentration of 2x107 plaque-forming units (PFU)/ml.
Human sperm
Sperm samples were taken from male patients undergoing IVF or who attended the American Hospital in Neuilly (France) with fertility problems. The selected patients all had 50% motile sperm, as tested in seminal fluid (six samples) or after selection on PureSperm (JOD, Lyon, France) gradient (five samples). For PureSperm gradient selection, 0.2–2 ml of semen was passed over two successive layers of PureSperm. The culture medium was used to prepare a 45% dilution of the upper layer and a 90% dilution of the 1 ml lower layer. After centrifugation (600 g for 20 min), the sperm pellet was washed in 10 ml PBS (600 g for 10 min) and then diluted in MEM.
Sperm incubated with virus
Sperm (5x105 sperm in 125 µl of MEM) were incubated with the virus (<104 to 106 PFU for 105 sperm) in a Petri dish (Corning 35 mm, tissue culture) for 1 h at 37°C in a moist atmosphere containing 5% CO2. In the controls, the viral suspension was replaced by the culture medium used to prepare the cells.
Interaction between sperm and virus
Sperm motility
Analysis at the optical level. After 1 h incubation, 50 µl of each sample was placed on a slide and the percentage of motile sperm was assessed under the microscope by three independent observers.
Analysis with a CASA system. We used a CASA system to analyse sperm motility. The system used was composed of a microscope (Olympus BHx200), a high speed video camera (Lhesa-Electronic) with a video recorder (Sony time lapse 168) associated with a sytem consisting of a pentium PC, a digitalized Matrox PIP card and an original Siam-Trac software. The following parameters were studied: percentage of motile sperm, straight line velocity (VSL), curvilinear velocity (VCL), linearity (LIN) mean amplitude of lateral head displacement (ALH) and linear acceleration (LA).
For this analysis, sperm were selected on PureSperm gradient and incubated with HSV2 for 1 h (106 sperm/106 PFU in 125 µl DMEM). The control was treated in the same way but replacing the viral suspension with culture medium.
Ultrastructural analysis
The sperm were then incubated with the viral suspensions for 1 h in a glutaraldehyde solution (2.5% in Sörensen buffer). After washing several times with the same buffer to which 1 mol/l sucrose solution had been added, the sperm were incubated in osmic acid (1% in Sörensen buffer) for 1 h before dehydrating by successive passages in 70°, 90°, 95° (3x10 min) and 100° (3x20 min) ethanol. This was followed by a final incubation in araldite for 3 days at 60°C. Ultrathin sections were recovered on 600 mesh grids, before being stained with uranyl acetate in ethanol and then with lead citrate. The sections were examined under a Hitachi electron microscope at a magnification of x12 000. The sections analysed were 10 µm away from each other. The proportion of sperm sections (95 nm thickness) in which viral particles were attached to the membrane or contained in the cell was determined for each experimental condition.
Paired t-tests were used to compare sperm motility (CASA) parameters of seminal fluid-free sperm incubated with either HSV2 or with culture medium. P 0.05 was considered significant.
Results
Top
Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
Sperm motility
Analysis at the optical level
The percentage of motile sperm was evaluated after incubation with HSV2 (seven samples) or with HCMV (nine samples). Both viruses were tested on samples consisting of sperm plus seminal fluid (HSV2: three samples; HCMV: four samples), and samples of sperm separated from the seminal fluid on PureSperm gradient selection (HSV2: four samples; HCMV: five samples). Several viral concentrations were used (<104, 105 and 106 PFU). Table I summarizes the results obtained with seminal fluid-free sperm incubated with HSV2 culture medium. The percentage of motile sperm in the experimental and control samples did not differ significantly, regardless of the procedure, viral strain or viral concentration used.
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Table I. Comparison of the percentage of motile sperm between seminal fluid-free sperm incubated with HSV2 and with culture medium by optical analysis
Analysis with a CASA system
Table II summarizes the analysis of sperm motility parameters (CASA analysis) of seminal fluid-free sperm incubated with HSV2 or with culture medium alone. A slight but insignificant decrease in the percentage motile sperm was reported when sperm were incubated with HSV2 (57.18 versus 64.43% for control). Although VSL was not different in the two groups (22.97 versus 25.66 µm/s for control), VCL differed (82.90 versus 67.23 µm/s for control; P = 0.05), lowering LIN in the experimental group (0.27 versus 0.38% for control; P = 0.05). ALH was significantly higher when sperm were in the presence of HSV2 (3.48 versus 2.46 µm for control; P = 0.05) as was the linear acceleration (LA; 608.62 versus 474.84 m/s2; P = 0.05).
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Table II. Comparison of the sperm motility parameters with computer-assisted semen analysis between seminal fluid-free sperm incubated with HSV2 and with culture medium
Ultrastructural analysis
Sperm with seminal fluid incubated with HSV2 or HCMV
HSV2. Two samples were subjected to ultrastructural analysis and viral particles were detected in both. The particles observed were in the form of complete virions and isolated capsids, but they were seldom found in contact with the sperm membrane (two particles in 310 sperm (0.6%) for sample 1, none in 154 sperm for sample 2).
HCMV. Two samples underwent ultrastructural analysis. Complete and incomplete viral particles, and dense bodies were found to co-exist. Only a few of the sperm were in close contact with viral particles [two out of 238 sperm for sample 1 (0.8 %), and two out of 319 sperm for sample 2 (0.6 %)].
Sperm without seminal fluid incubated with HSV2 or HCMV
A comparative study was carried out using sperm obtained from the same ejaculate and selected by PureSperm gradient. They were incubated with either HSV2 or HCMV.
HSV2. We found 28 viral particles in close contact with the 350 sperm sections observed (8%). The viral particles were either very near the membrane or directly stuck to the membrane of the sperm head (Figure 1E could correspond to fusion of HSV2 virion with the sperm membrane) or of the flagella (Figure 1B,C,D). We did not detect any viral particles inside the sperm. Viral particles were also observed either in isolation or in clusters in the preparation (Figure 1A), showing that they had not been removed from the sperm sample exposed to HSV2 despite the washes carried out before inclusion in araldite.
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Figure 1. (A) Herpes simplex virus 2 (HSV2) viral particles in the sample. The viruses were present in the form of the complete virion with one or several capsids, or in incomplete forms with a full or empty capsid and thick electron-dense coat. Bar = 500 nm. (B, C) Two sperm with viral particles (arrows) attached to the membrane of the principal piece. Bar = 200 nm. (D) HSV2 viral particle (arrow) attached tothe membrane of the intermediate piece. Bar = 500 nm. (E) Viral particles (arrows) attached to the sperm membrane of the acrosome. Bar = 500 nm.
HCMV. Isolated and clustered viral particles were also observed in the sperm sample incubated with HCMV (Figure 2A). We observed viral particles close to the membrane (Figure 2B) in 15 of the 381 sperm sections analysed (4%), implying that the relationship between the sperm and viral particles may be weaker for HCMV than for HSV2.
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Figure 2. (A) Human cytomegalovirus particles. The viruses were present in the form of complete virions with one capsid, or inincomplete forms with empty isolated capsids, or dense bodies. Bar = 500 nm. (B) Dense body (arrow) attached to the sperm membrane. Bar = 500 nm.
Discussion
Top
Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
We have clearly shown that: (i) high concentrations of HSV2 or HCMV do not have a strong effect on the percentage of motile sperm regardless of the viral concentration used or the method used to prepare the sperm; however, motility parameters detected by CASA differed when HSV2 was added to seminal fluid-free sperm; (ii) there was little interaction between HSV2 or HCMV and human sperm when the viruses were incubated with the semen (sperm plus seminal fluid); HSV2 and HCMV behaved differently when incubated with sperm in the absence of seminal fluid; more HSV2 adhered to sperm than HCMV.
Some studies have shown that the presence of viral particles in the semen is correlated with a lower percentage of motile sperm (Lai et al., 1997; Kotronias and Kapranos, 1998). Our study shows that the presence of HSV2 or HCMV in the sperm suspension does not inhibit sperm motility, regardless of the viral concentrations used and the method used to treat the sperm: sperm with seminal fluid, sperm selected by PureSperm gradient (no seminal fluid), or sperm selected by centrifugation and migration (data not shown). These observations were the same for all the samples studied, and CASA system applied to HSV2 strengthened our results. It would therefore appear that the in-vivo correlation between the reported reduction of percentage of motile sperm and the presence of viral particles (Lai et al., 1997; Kotronias and Kapranos, 1998) is due to indirect interactions between the virus and the sperm rather than to a direct effect on motility. However, we observed modifications of motility parameters such as VCL, LIN, ALH and LA, showing that in the presence of HSV2, sperm moved more rapidly with a greater ALH.
We showed that human sperm do not bind to HSV2 in the presence of seminal fluid, although free viral particles were found in the seminal fluid. These findings are similar to those of other investigators (Sherman and Morgan, 1989) who did not find a close relationship between sperm and HSV2, and those of another study (Deture et al., 1978), which observed free viral particles in the seminal fluid. The seminal fluid seems to impede the adherence of HSV2 with sperm. Sherman and Morgan (1989) hypothesized that spermine phosphate is involved. Seminal fluid contains high molecular weight proteins that could impede the interaction of HSV2 with sperm or behave as a receptor for HSV2 thus preventing further contact by sperm.
Conversely, in the absence of seminal fluid, sperm were able to adhere to HSV2. It was difficult to evaluate the exact percentage of sperm with HSV2 adhering to their surface because we observed sections of sperm (95 nm thick) and not whole sperm (4–5 µm thick). The percentage of sperm bearing viral particles was 8% but may have been as high as 45% if only one viral particle adhered to each sperm. This percentage is within the range described for ISH HSV2 DNA-positive sperm cells (Kotronias and Kapranos, 1998). These results also raised questions about the nature of the relationship between HSV2 and sperm. It may consist of a simple passive attachment that is able to resist the repeated washes. This is highly possible given our results. However, in one spermatozoon, the virus particle seemed to be closer to the sperm membrane, and this could even be a beginning of fusion. Thus, we cannot exclude the possibility that this is a true ligand/receptor relationship that only occurs when sperm have been separated from their seminal fluid. Numerous HSV2 receptors have been identified, including heparan sulphate-like glycosaminoglycans (Trybala et al., 2000), nectins and a receptor belonging to the tumour-necrosis factor family (Campadelli-Fiume et al., 2000). It is possible that the sperm have one of these membrane receptors, which is not accessible to the virus when seminal fluid is present.
In conclusion, sperm motility, which is the parameter used to select sperm for ICSI, is not a good enough criterion on which to prove the presence of viral elements in the medium or on the sperm.
From our experiments with virus and sperm with seminal fluid, we can conclude that when the virus is mixed with semen in the annexial glands in vivo, HSV2 does not interact with the sperm and the virus remains in the seminal fluid. In these conditions, the techniques used in assisted reproduction to eliminate the seminal fluids also eliminate the viral particles and improve the sperm preparation. This means that either PureSperm gradient selection or swim-up migration can be used efficiently.
Sperm inside the seminiferous tubules are protected from viruses by the haematotesticular barrier. When this barrier is ruptured, sperm can come into contact with viral particles. Indeed, this barrier is always destroyed when sperm are collected from the testis. This increases the risk of sperm coming into contact with high local concentrations of HSV2 due to contamination from the blood or interstitial tissues. The washing procedure cannot eliminate viral particles, meaning that they are directly injected into the cytoplasm.
The HCMV virus particle did not interact with the sperm when HCMV was added to the semen. However, the relationship between sperm and virus in the absence of the seminal fluid was not so clear as for HSV2, perhaps due to the fact that this virus binds non-specifically. However, as for HSV2, the viral particle may be accidentally injected into the ooplasm during ICSI, either as a result of passive transport by the sperm or from the surrounding environment as washing did not eliminate the virus from the preparation.
Some studies used sperm as vectors (Perry et al., 1999). These experiments concerned purified DNA or plasmids, and we did not study this aspect of the problem as we focused only on infectious virions visible under the electron microscope.
We have attempted to investigate whether there may be a specific risk of viral infection associated with ICSI. Our main conclusion is that ICSI creates a new risk of contaminating sperm with viruses in cases of ICSI for azoospermia. Sperm inside the seminiferous tubules are protected from viruses by the haematotesticular barrier. When this barrier is ruptured, sperm can come into contact with viral particles. Indeed, this barrier is always destroyed when sperm are collected from the testes. This increases the risk of sperm coming into contact with high local concentrations of HSV2 due to contamination from the blood or interstitial tissues. The washing procedure cannot eliminate viral particles, meaning that they are directly injected into the ooplasm.
Acknowledgements
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Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
We would like to thank Pascal Briaud, from the American Hospital, Neuilly and Claudine Hemon from INSERM U355, Clamart, for providing us with sperm samples for this study and Phillipe Etre for the electron micrographs. Electron microscopic observations were carried out in the Neurology Laboratory of Professor Gerard Said (CHU Bicêtre, Paris Sud) with technical help from Josette Bacci.
Notes
4 To whom correspondence should be addressed. E-mail: anne-marie.courtot@inserm.ipsc.u-psud.fr
References
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Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
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Submitted on October 8, 2001; accepted on January 2, 2002.
Coralie Pallier1, Lamia Tebourbi2, Stéphanie Chopineau-Proust1, Damien Schoevaert3, Patrice Nordmann1, Jacques Testart2 and Anne-Marie Courtot2,4
1 Service de Bactériologie–Virologie–Parasitologie–Hygiène, CHU Bicêtre, Paris-Sud, 78 rue du Général Leclerc, 94275 Le Kremlin–Bicêtre, 2 Institut National de la Santé et de la Recherche Médicale Unité 355 et Institut Fédératif de Recherche sur les Cytokines,32 rue des Carnets, 92140 Clamart and 3 Laboratoire d'Analyse d'Images en Pathologie Cellulaire, Institut Universitaire d'Hématologie, Hopital Saint Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France
Abstract
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Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
BACKGROUND: The effect of viral particles on the motility of human sperm and the relationship between sperm and virus are of importance particularly in assisted fertilizations. METHODS: We incubated ejaculated sperm with or without seminal fluid with either herpes simplex virus type 2 (HSV2) or human cytomegalovirus (HCMV). For each experiment, 5x105 sperm were incubated with a viral load of between 104 and 106 plaque-forming units. RESULTS: We detected no apparent variations in the percentage of motile forms when sperm were incubated with either HSV2 or HCMV. Using a computer-aided semen analysis system, a slight difference was reported in the percentage of motile forms when seminal fluid-free sperm were incubated with HSV2 (57.18 versus 64.43 in the control). Although the mean amplitude of lateral head displacement and the curvilinear velocity were significantly higher in infected sperm, the difference in straight line velocity was not statistically significantly different. Few viral particles (HSV2 or HCMV) adhered to the sperm membrane in the presence of seminal fluid. However, more particles stuck when in the absence of seminal fluid, particularly with HSV2 (8% of sperm sections for HSV2; 4% for HCMV). CONCLUSIONS: The relationship between sperm and viruses depends on the type of virus present as well as the presence or absence of seminal fluid. Motility is not a good enough criterion on which to prove the presence of viral elements, either in the medium or on the sperm.
Key words: cytomegalovirus/Herpesviridae/human sperm/motility/seminal fluid
Introduction
Top
Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
Several successful new assisted reproductive techniques have been developed over the last decade. It is now possible to take a selected spermatozoon from a given point in the genital tract and to transfer it into the ooplasm. This technique, known as ICSI, involves the use of micromanipulations to move sperm across the zona pellucida and the plasma membrane. The ICSI technique has enabled sperm that would otherwise be unable to fertilize the oocyte to do so, resulting in successful pregnancies. The sperm can be extracted from different regions of the genital tract, e.g. from the testes or from the epididymal duct (Lewin et al., 1999), or from semen samples. The extraction of testicular sperm followed by ICSI is a convenient way of overcoming non-obstructive azoospermia (Devroey et al., 1996). Several methods can be used to process the extracted sperm. The choice of method depends on the facilities available and the physiological condition of the sperm. These methods include isolating a simple swab in a synthetic medium (De Croo et al., 2000), washing by centrifugation (Devroey et al., 1996), selection on a Percoll gradient (Mercan et al., 2000) and swim-up migration (Marina et al., 1998). Although these techniques can solve many fertility problems, they also raise questions about the risks of transferring viral particles into the oocyte.
Several viruses are present in the genital tract. The most common are the herpes simplex virus type 2 (HSV2) and human cytomegalovirus (HCMV), which are sexually transmissible and can lead to fetal and neonatal anomalies (Huraux et al., 1999; Ranger-Roger et al., 1999). Sperm are formed in seminiferous tubules in the testes, where they are protected from the environmental tissue by the haematotesticular barrier. We previously showed that no viral particles are found within the seminiferous tubules in MCMV-infected murine testes. However, the peritubular cells, Leydig cells and endothelial cells contained high viral loads (Tebourbi et al., 2001). Several other papers have reported the presence of HSV2 (Deture et al., 1976) and of CMV (De Paepe et al., 1990) in the testes, but this does not automatically mean that the seminiferous tubules were contaminated (Baskar et al., 1986; Stephanopoulos et al., 1989). However, viruses may be present in the epididymis (Dalton and Harcourt-Webster, 1991; MacCarthy et al., 1991), deferent duct (Kimura et al., 1993), prostate (Boldogh et al., 1983; Benson and Smith, 1992; Mastroianni et al., 1996) or seminal vesicles (Deture et al., 1976; Kimura et al., 1993). If the virus is present in the annexial glands, it may be discharged in the seminal fluid before coming into contact with sperm. The presence of the virus in the semen indicates a genital tract infection. One study (Moore et al., 1989) found infective HSV2 virus in the semen of a healthy donor with an asymptomatic primary infection, and showed that insemination led to the horizontal transmission of the virus. However, cell culture methods have rarely detected HSV2 in sperm (Deture et al., 1978; MacGowan et al., 1983), because semen contains inhibitors that may interfere with these methods (Deture et al., 1978; Sherman and Morgan, 1989). More sensitive methods, such as PCR and in-situ hybridization (ISH), have made it possible to detect viral DNA in the semen of men with genital HSV2 infection (Kotronias and Kapranos, 1998; Wald et al., 1999) and in the semen of a high-risk population (Tabrizi et al., 2000). HCMV has been identified in sperm (Lang and Kummer, 1972). The prevalence of HCMV elements was found to be variable in men who did not have human immunodeficiency virus (HIV) or other sexually transmitted diseases (Lang and Kummer, 1972; Bantel-Schaal et al., 1993; Shen et al., 1994; Mansat et al., 1997), but it may be high in high-risk populations (Biggar et al., 1983; Leach et al., 1993). Detection rates are generally higher for viral DNA than for infective particles. In a recent study involving men taking part in an IVF programme (Witz et al., 1999), 25% of ejaculates, including those from HCMV-negative men (who may or may not have gone on to become positive), were found to contain viral DNA.
Thus, sperm are protected from viral contact in the upper regions of the genital tract, i.e. the testes, whereas sperm in the semen can easily come into contact with viral particles (in the epididymis, deferent duct and annexial glands). This is important as sperm can be harvested from testicular biopsies for ICSI in cases of azoospermia. This then disrupts the haematotesticular barrier, thus removing the protective effect and placing the sperm in close contact with endothelial cells, Leydig cells and peritubular cells. Sperm can also be harvested from the other genital organs or from the semen. In this case, the fertilizing sperm for ICSI are choosen according to their motility. The relationship between the virus and sperm motility is not very clear and the interaction between sperm and virus are of importance.
Some authors have reported an inverse correlation between the presence of HSV2 in semen and sperm motility (Kotronias and Kapranos, 1998). Similar observations have been reported concerning CMV (Torino et al., 1987). A high concentration of HCMV was detected in the semen of a patient with CMV mononucleosis, and this was associated with a transient decrease in sperm motility (Lang and Kummer, 1972; Lang et al., 1974). We were interested to know whether this decrease in sperm motility was due to a direct effect of high concentrations of the virus on sperm or if these results were due to an indirect effect. Few papers have addressed the viral load of semen (Lang and Kummer, 1972; Biggar et al., 1983). Therefore it is not clear how the virus and sperm interact. No relationship has been found between sperm and HSV2 (Sherman and Morgan, 1989), whereas ISH has been used to demonstrate that there is a close relationship between sperm and HSV2 (Kotronias and Kapranos, 1998). Only one group has found CMV within human sperm (Huang et al., 1986); another group (Baskar et al., 1986) observed virus-like particles in mouse sperm.
We developed experimental models to analyse the effects of viruses on sperm motility and the interaction between viruses and sperm in assisted reproduction indications. On the one hand, we used semen, i.e. sperm plus seminal fluid, which is the physiological environment from which motile sperm are selected for intrauterine insemination, IVF and ICSI. On the other hand, we used sperm without seminal fluid (selected by use of a PureSperm gradient), which corresponds to sperm collected in the epididymis before the formation of seminal fluid or to sperm collected from testicular biopsies in azoospermic men for ICSI. The viruses used were HSV2 and HCMV. This study enabled us to study the relationship between viruses and sperm in different regions of the genital tract and to determine whether the new assisted reproduction techniques (especially ICSI in the case of azoospermia) affect the risks of virus adherence to sperm, leading to the introduction of viral particles into oocytes.
Materials and methods
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Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
Preparation of the viral strains
The viral strains, HSV2 (ATCC VR-2019) and HCMV (AD-169), were prepared from human embryo lung cells (MRC5, primary cells; Biomerieux, Lyon, France) in modified Eagle's medium (MEM; Gibco BRL, Life Technologies, Paisley, UK). The viral suspensions were titrated by an enzymatic assay method (visualization of early viral antigens) at a concentration of 2x107 plaque-forming units (PFU)/ml.
Human sperm
Sperm samples were taken from male patients undergoing IVF or who attended the American Hospital in Neuilly (France) with fertility problems. The selected patients all had 50% motile sperm, as tested in seminal fluid (six samples) or after selection on PureSperm (JOD, Lyon, France) gradient (five samples). For PureSperm gradient selection, 0.2–2 ml of semen was passed over two successive layers of PureSperm. The culture medium was used to prepare a 45% dilution of the upper layer and a 90% dilution of the 1 ml lower layer. After centrifugation (600 g for 20 min), the sperm pellet was washed in 10 ml PBS (600 g for 10 min) and then diluted in MEM.
Sperm incubated with virus
Sperm (5x105 sperm in 125 µl of MEM) were incubated with the virus (<104 to 106 PFU for 105 sperm) in a Petri dish (Corning 35 mm, tissue culture) for 1 h at 37°C in a moist atmosphere containing 5% CO2. In the controls, the viral suspension was replaced by the culture medium used to prepare the cells.
Interaction between sperm and virus
Sperm motility
Analysis at the optical level. After 1 h incubation, 50 µl of each sample was placed on a slide and the percentage of motile sperm was assessed under the microscope by three independent observers.
Analysis with a CASA system. We used a CASA system to analyse sperm motility. The system used was composed of a microscope (Olympus BHx200), a high speed video camera (Lhesa-Electronic) with a video recorder (Sony time lapse 168) associated with a sytem consisting of a pentium PC, a digitalized Matrox PIP card and an original Siam-Trac software. The following parameters were studied: percentage of motile sperm, straight line velocity (VSL), curvilinear velocity (VCL), linearity (LIN) mean amplitude of lateral head displacement (ALH) and linear acceleration (LA).
For this analysis, sperm were selected on PureSperm gradient and incubated with HSV2 for 1 h (106 sperm/106 PFU in 125 µl DMEM). The control was treated in the same way but replacing the viral suspension with culture medium.
Ultrastructural analysis
The sperm were then incubated with the viral suspensions for 1 h in a glutaraldehyde solution (2.5% in Sörensen buffer). After washing several times with the same buffer to which 1 mol/l sucrose solution had been added, the sperm were incubated in osmic acid (1% in Sörensen buffer) for 1 h before dehydrating by successive passages in 70°, 90°, 95° (3x10 min) and 100° (3x20 min) ethanol. This was followed by a final incubation in araldite for 3 days at 60°C. Ultrathin sections were recovered on 600 mesh grids, before being stained with uranyl acetate in ethanol and then with lead citrate. The sections were examined under a Hitachi electron microscope at a magnification of x12 000. The sections analysed were 10 µm away from each other. The proportion of sperm sections (95 nm thickness) in which viral particles were attached to the membrane or contained in the cell was determined for each experimental condition.
Paired t-tests were used to compare sperm motility (CASA) parameters of seminal fluid-free sperm incubated with either HSV2 or with culture medium. P 0.05 was considered significant.
Results
Top
Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
Sperm motility
Analysis at the optical level
The percentage of motile sperm was evaluated after incubation with HSV2 (seven samples) or with HCMV (nine samples). Both viruses were tested on samples consisting of sperm plus seminal fluid (HSV2: three samples; HCMV: four samples), and samples of sperm separated from the seminal fluid on PureSperm gradient selection (HSV2: four samples; HCMV: five samples). Several viral concentrations were used (<104, 105 and 106 PFU). Table I summarizes the results obtained with seminal fluid-free sperm incubated with HSV2 culture medium. The percentage of motile sperm in the experimental and control samples did not differ significantly, regardless of the procedure, viral strain or viral concentration used.
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Table I. Comparison of the percentage of motile sperm between seminal fluid-free sperm incubated with HSV2 and with culture medium by optical analysis
Analysis with a CASA system
Table II summarizes the analysis of sperm motility parameters (CASA analysis) of seminal fluid-free sperm incubated with HSV2 or with culture medium alone. A slight but insignificant decrease in the percentage motile sperm was reported when sperm were incubated with HSV2 (57.18 versus 64.43% for control). Although VSL was not different in the two groups (22.97 versus 25.66 µm/s for control), VCL differed (82.90 versus 67.23 µm/s for control; P = 0.05), lowering LIN in the experimental group (0.27 versus 0.38% for control; P = 0.05). ALH was significantly higher when sperm were in the presence of HSV2 (3.48 versus 2.46 µm for control; P = 0.05) as was the linear acceleration (LA; 608.62 versus 474.84 m/s2; P = 0.05).
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Table II. Comparison of the sperm motility parameters with computer-assisted semen analysis between seminal fluid-free sperm incubated with HSV2 and with culture medium
Ultrastructural analysis
Sperm with seminal fluid incubated with HSV2 or HCMV
HSV2. Two samples were subjected to ultrastructural analysis and viral particles were detected in both. The particles observed were in the form of complete virions and isolated capsids, but they were seldom found in contact with the sperm membrane (two particles in 310 sperm (0.6%) for sample 1, none in 154 sperm for sample 2).
HCMV. Two samples underwent ultrastructural analysis. Complete and incomplete viral particles, and dense bodies were found to co-exist. Only a few of the sperm were in close contact with viral particles [two out of 238 sperm for sample 1 (0.8 %), and two out of 319 sperm for sample 2 (0.6 %)].
Sperm without seminal fluid incubated with HSV2 or HCMV
A comparative study was carried out using sperm obtained from the same ejaculate and selected by PureSperm gradient. They were incubated with either HSV2 or HCMV.
HSV2. We found 28 viral particles in close contact with the 350 sperm sections observed (8%). The viral particles were either very near the membrane or directly stuck to the membrane of the sperm head (Figure 1E could correspond to fusion of HSV2 virion with the sperm membrane) or of the flagella (Figure 1B,C,D). We did not detect any viral particles inside the sperm. Viral particles were also observed either in isolation or in clusters in the preparation (Figure 1A), showing that they had not been removed from the sperm sample exposed to HSV2 despite the washes carried out before inclusion in araldite.
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Figure 1. (A) Herpes simplex virus 2 (HSV2) viral particles in the sample. The viruses were present in the form of the complete virion with one or several capsids, or in incomplete forms with a full or empty capsid and thick electron-dense coat. Bar = 500 nm. (B, C) Two sperm with viral particles (arrows) attached to the membrane of the principal piece. Bar = 200 nm. (D) HSV2 viral particle (arrow) attached tothe membrane of the intermediate piece. Bar = 500 nm. (E) Viral particles (arrows) attached to the sperm membrane of the acrosome. Bar = 500 nm.
HCMV. Isolated and clustered viral particles were also observed in the sperm sample incubated with HCMV (Figure 2A). We observed viral particles close to the membrane (Figure 2B) in 15 of the 381 sperm sections analysed (4%), implying that the relationship between the sperm and viral particles may be weaker for HCMV than for HSV2.
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Figure 2. (A) Human cytomegalovirus particles. The viruses were present in the form of complete virions with one capsid, or inincomplete forms with empty isolated capsids, or dense bodies. Bar = 500 nm. (B) Dense body (arrow) attached to the sperm membrane. Bar = 500 nm.
Discussion
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Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
We have clearly shown that: (i) high concentrations of HSV2 or HCMV do not have a strong effect on the percentage of motile sperm regardless of the viral concentration used or the method used to prepare the sperm; however, motility parameters detected by CASA differed when HSV2 was added to seminal fluid-free sperm; (ii) there was little interaction between HSV2 or HCMV and human sperm when the viruses were incubated with the semen (sperm plus seminal fluid); HSV2 and HCMV behaved differently when incubated with sperm in the absence of seminal fluid; more HSV2 adhered to sperm than HCMV.
Some studies have shown that the presence of viral particles in the semen is correlated with a lower percentage of motile sperm (Lai et al., 1997; Kotronias and Kapranos, 1998). Our study shows that the presence of HSV2 or HCMV in the sperm suspension does not inhibit sperm motility, regardless of the viral concentrations used and the method used to treat the sperm: sperm with seminal fluid, sperm selected by PureSperm gradient (no seminal fluid), or sperm selected by centrifugation and migration (data not shown). These observations were the same for all the samples studied, and CASA system applied to HSV2 strengthened our results. It would therefore appear that the in-vivo correlation between the reported reduction of percentage of motile sperm and the presence of viral particles (Lai et al., 1997; Kotronias and Kapranos, 1998) is due to indirect interactions between the virus and the sperm rather than to a direct effect on motility. However, we observed modifications of motility parameters such as VCL, LIN, ALH and LA, showing that in the presence of HSV2, sperm moved more rapidly with a greater ALH.
We showed that human sperm do not bind to HSV2 in the presence of seminal fluid, although free viral particles were found in the seminal fluid. These findings are similar to those of other investigators (Sherman and Morgan, 1989) who did not find a close relationship between sperm and HSV2, and those of another study (Deture et al., 1978), which observed free viral particles in the seminal fluid. The seminal fluid seems to impede the adherence of HSV2 with sperm. Sherman and Morgan (1989) hypothesized that spermine phosphate is involved. Seminal fluid contains high molecular weight proteins that could impede the interaction of HSV2 with sperm or behave as a receptor for HSV2 thus preventing further contact by sperm.
Conversely, in the absence of seminal fluid, sperm were able to adhere to HSV2. It was difficult to evaluate the exact percentage of sperm with HSV2 adhering to their surface because we observed sections of sperm (95 nm thick) and not whole sperm (4–5 µm thick). The percentage of sperm bearing viral particles was 8% but may have been as high as 45% if only one viral particle adhered to each sperm. This percentage is within the range described for ISH HSV2 DNA-positive sperm cells (Kotronias and Kapranos, 1998). These results also raised questions about the nature of the relationship between HSV2 and sperm. It may consist of a simple passive attachment that is able to resist the repeated washes. This is highly possible given our results. However, in one spermatozoon, the virus particle seemed to be closer to the sperm membrane, and this could even be a beginning of fusion. Thus, we cannot exclude the possibility that this is a true ligand/receptor relationship that only occurs when sperm have been separated from their seminal fluid. Numerous HSV2 receptors have been identified, including heparan sulphate-like glycosaminoglycans (Trybala et al., 2000), nectins and a receptor belonging to the tumour-necrosis factor family (Campadelli-Fiume et al., 2000). It is possible that the sperm have one of these membrane receptors, which is not accessible to the virus when seminal fluid is present.
In conclusion, sperm motility, which is the parameter used to select sperm for ICSI, is not a good enough criterion on which to prove the presence of viral elements in the medium or on the sperm.
From our experiments with virus and sperm with seminal fluid, we can conclude that when the virus is mixed with semen in the annexial glands in vivo, HSV2 does not interact with the sperm and the virus remains in the seminal fluid. In these conditions, the techniques used in assisted reproduction to eliminate the seminal fluids also eliminate the viral particles and improve the sperm preparation. This means that either PureSperm gradient selection or swim-up migration can be used efficiently.
Sperm inside the seminiferous tubules are protected from viruses by the haematotesticular barrier. When this barrier is ruptured, sperm can come into contact with viral particles. Indeed, this barrier is always destroyed when sperm are collected from the testis. This increases the risk of sperm coming into contact with high local concentrations of HSV2 due to contamination from the blood or interstitial tissues. The washing procedure cannot eliminate viral particles, meaning that they are directly injected into the cytoplasm.
The HCMV virus particle did not interact with the sperm when HCMV was added to the semen. However, the relationship between sperm and virus in the absence of the seminal fluid was not so clear as for HSV2, perhaps due to the fact that this virus binds non-specifically. However, as for HSV2, the viral particle may be accidentally injected into the ooplasm during ICSI, either as a result of passive transport by the sperm or from the surrounding environment as washing did not eliminate the virus from the preparation.
Some studies used sperm as vectors (Perry et al., 1999). These experiments concerned purified DNA or plasmids, and we did not study this aspect of the problem as we focused only on infectious virions visible under the electron microscope.
We have attempted to investigate whether there may be a specific risk of viral infection associated with ICSI. Our main conclusion is that ICSI creates a new risk of contaminating sperm with viruses in cases of ICSI for azoospermia. Sperm inside the seminiferous tubules are protected from viruses by the haematotesticular barrier. When this barrier is ruptured, sperm can come into contact with viral particles. Indeed, this barrier is always destroyed when sperm are collected from the testes. This increases the risk of sperm coming into contact with high local concentrations of HSV2 due to contamination from the blood or interstitial tissues. The washing procedure cannot eliminate viral particles, meaning that they are directly injected into the ooplasm.
Acknowledgements
Top
Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
We would like to thank Pascal Briaud, from the American Hospital, Neuilly and Claudine Hemon from INSERM U355, Clamart, for providing us with sperm samples for this study and Phillipe Etre for the electron micrographs. Electron microscopic observations were carried out in the Neurology Laboratory of Professor Gerard Said (CHU Bicêtre, Paris Sud) with technical help from Josette Bacci.
Notes
4 To whom correspondence should be addressed. E-mail: anne-marie.courtot@inserm.ipsc.u-psud.fr
References
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Abstract
Introduction
Materials and methods
Results
Discussion
Acknowledgements
References
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Submitted on October 8, 2001; accepted on January 2, 2002.
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