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PubMed2002

Newly identified endometrial genes of importance for implantation.

The mammalian uterus is normally not receptive to embryo implantation except during the very limited 'window of implantation'. To identify genes that may be responsible for this phenomenon the technique of RNA differential display (DD-PCR) was applied to implantation and inter-implantation sites on day 4.5 of pregnancy in the mouse, the time at which the blastocyst becomes attached to the endometrium. Three of these genes were identified as splicing factor SC35, calbindin-D9k and monoclonal non-specific suppressor factor beta (MNSFbeta). Expression of SC35 mRNA, which is responsible for removal of introns from pre-mRNA, is much higher in implantation than in interimplantation sites during pregnancy. Expression of alternatively spliced mRNAs for SC35 is differentially regulated by early pregnancy and steroid hormones. By contrast, calbindin-D9k, a regulator of calcium, is upregulated by progesterone and its mRNA increases in the uterus during early pregnancy compared with during the cycle, although it is significantly lower in implantation sites than in interimplantation sites on days 4.5-5.5 of pregnancy, but subsequently becomes barely detectable in both sites. The mRNA for calbindin-D9k is predominantly in endometrial luminal epithelium. MNSFbeta, a cytokine involved in regulation of the immune system, showed lower expression at implantation sites than interimplantation sites on day 4.5 of pregnancy, when embryos first attach to the uterus and initiate implantation, and on day 5.5 when implantation has advanced. Immunohistochemically, the protein was localized to endometrial stromal cells in the non-pregnant uterus, but disappeared as decidualization progressed. The precise roles of these three proteins in the process of embryo implantation remains to be determined. Homologues of the proteins may contribute to the development of the 'window of implantation' in the human and hence be appropriate targets for new post-coital contraceptives or may be manipulated to improve fertility.

Animals↗
PubMed1997

[Mycotic vulvovaginitis].

Vulvovaginitis is the most common clinical manifestation of fungal infections causing human mycoses; the incidence occurs in 10% of women, during pregnancy the incidence achieves 30% of cases. Candida albicans has resulted to be the most commonly isolated agent in patients with fungemia. In fact, Candida appears to be the species recovered in as many as 90% of cases. They are mainly the sexual activity, hormonal contraception and several pathologies such as diabetes mellitus and thyroiditis responsible for the pathogenesis of infection. The first symptom of this infection is usually pruritus associated to leukorrhea, dyspareunia and vulvovaginal irritation. Antifungal therapy may be required in more severe cases of vulvovaginal candidiasis. Candida species can be identified on isolation culture media including agar and on direct examination. Diagnosis can also be made through san immunologic examination. However, the authors confirm that the risk factors together with a correct diagnosis of the Candida etiological agent in the different species (albicans, glabrata, tropicalis, krusei) should be accurately investigated in order to give the correct therapeutical approach.

Antifungal Agents↗
PubMed1975

[The enzymic and immunological determination of coeruloplasmin: sex- and method-dependent differences during the administration of oestrogens (author's transl)].

After 14 days of 1 mug ethinyloestradiol per kg body weight per day, both sexes show highly significant increases in serum coeruloplasmin which are independent of the determination method. Expressed on a percentage basis, the concentrations of coeruloplasmin under oestrogen medication determined by the p-phenylendiamine oxidase reaction are significantly higher than those determined by the immunological-nephelometric method. This is because several coeruloplasmin components, mainly C and DO, take part in the determination with p-phenylendiamine oxidase, whereas the immunological method measures chiefly the coeruloplasmin DO component. The significant sex differences under oestrogen medication shown by the determination with p-phenylendiamine oxidase, can therefore be explained by the presence of C- and D-coeruloplasmins in women, while the serum of men contains almost exclusively D-coeruloplasmins. Under oestrogen medication, the increase occurs primarily in the DO- coeruloplasmin component, and women also show an increase in coeruloplasmin-C. The significant higher enzymatic concentrations in the serum of the women in contrast to the men are thus plausibly explained. With the immunological assay, the sex differences were only probably significant.

Administration, Oral↗
PubMed1989

[Erythema nodosum: epidemiology, etiology, pathogenesis, clinical picture and therapy].

Erythema Nodosum (EN) is a painful nodular syndrome, most likely of immunologic origin, which involves dermis and subcutaneous tissue. Pathologic process is that of vasculitis of the small veins with inflammation of the septa of the fat lobules (septal panniculitis). It is generally agreed that EN represents a hypersensitive reaction to a variety of antigenic stimuli and thus may be observed in the course of several diseases (infections, immunopathies, malignancies) as well as during drug therapy (with halides, sulfonamides, oral contraceptives). In approximately 50 per cent of the cases an underlying etiology is not apparent (idiopathic form). The clinical picture is always that of a nonspecific systemic illness with low-grade fever (in 60%), malaise (in 67%), arthralgias (in 64%) and arthritis (in 31%), while when there is an associated illness, this may dominate the presentation. Laboratory tests show no specific abnormalities except for those related to an underlying disease. Treatment of idiopathic form includes nonsteroidal antiinflammatory agents which usually ease the discomfort. Steroids, although highly effective, are not recommended because of the benign nature of EN and the danger of disseminating an underlying disease.

Erythema Nodosum↗
PubMed1995

[HIV and pregnancy].

Since 1990 216 HIV-infected pregnant women have been enrolled in an ongoing nationwide study named "HIV and Pregnancy" financed by the Swiss Federal Office of Health (No. 90-7007 and 93-7131). Of a total of 228 recorded pregnancies 154 continued to parturition. Until now it has been definitively established whether or not 89 offsprings have been infected with HIV by their mothers. According to clinical and immunological findings most of the pregnant women are still in early, stable stages of HIV-infection (stages II and III of the CDC classification system in 94% of the subjects; mean CD4-cell count around 600/microliters). HIV infection was the consequence of an intravenous substance abuse in two thirds of the women. Detailed interviews revealed an alarming negligence with regard to compliance with safer sex recommendations and contraception. Advisory services of specialized AIDS information centers have very rarely been called on. In our group, the vertical transmission rate shows a statistically significant correlation with low maternal anti-HIV-p24 antibody titers, high serum neopterin- and IgA-concentrations, and also with the use of forceps and vacuum in vaginal delivery. Maternal substance abuse but not HIV infection itself resulted in an incidence of preterm deliveries roughly twice as high as in the normal Swiss population.

Abortion, Induced↗
PubMed1986

Evolution and infant feeding.

The darwinian theory of evolution has been used to justify the statement that breast-milk is ideal for infants. However, a broader interpretation of the theory suggests that the mother-child dyad is the evolutionary unit. For the survival of the species, both mother and child should benefit. Simple arithmetic shows that where there is a conflict of interests, the welfare of the mother outweighs that of the infant. The dyad hypothesis suggests that the maximum evolutionary gain is obtained when protein and energy levels in breast-milk are just high enough to prevent prohibitive infant mortality rates, but low enough to spare the mother. The anti-infective constituents of breast-milk are very small in bulk, so they place a minimum metabolic load on the mother but have a large benefit for the child. The contraceptive effect of breast feeding is pronounced only when the mother is malnourished. A separation of the nutritive from the anti-infective properties of breast-milk suggests that a rational method of infant-feeding for many mothers is to breast-feed for several months to reduce the morbidity rate in the infant, but to give supplementary milks, formulae, and foods when needed to promote the baby's nutritional status.

Biological Evolution↗
PubMed1985

Vitamin C and chiropractic.

A review of the literature relating to possible clinical implications of ascorbic acid (AA) supplementation was conducted. Factors requiring a higher AA intake include smoking, alcohol ingestion, stress, diabetes mellitus, pregnancy, and certain drugs, including oral contraceptives, some antibiotics, acetylsalicylate and anti-inflammatory medications. AA has been found to significantly increase wound healing, reduce the inflammatory response, lessen respiratory distress, enhance immune function and serve to benefit many common conditions including osteoarthritis. It is concluded that vitamin C supplementation could be utilized for many conditions seen by chiropractors.

Age Factors↗
PubMed2000

Erythema nodosum: the underlying conditions.

Erythema nodosum (EN) is a cutaneous reaction consisting of inflammatory, tender nodular lesions and is associated with a wide variety of disease processes. The aim of our study was to investigate the frequency of different aetiologies of EN. One hundred and thirty-two EN patients were investigated in a prospective study during the period 1984-1990. The evaluation of all patients began with a medical and family history and completed with a thorough physical examination and detailed laboratory and immunological work-up. In addition, various diagnostic procedures were performed where and when indicated. One hundred and ten patients (83%) were women. Their mean age was 41.0+/-14.0 years, range 18-79 years. In 35% the cause of EN was not found. Sarcoidosis was revealed in 28% of the patients, infections in 17.3% and tuberculosis in 1.5%. Other aetiologic factors were Adamantiadis-Behçet's syndrome (3.8%), pregnancy (6%), oral contraceptives (3.8%) and other drugs (3.8%). The aetiology of EN was not found in 35% of the patients. Sarcoidosis and infections were frequent causes of EN, whereas autoimmune rheumatic diseases rarely cause EN.

Adolescent↗
PubMed1985

Lack of maternal metabolic, endocrine, and environmental influences in the etiology of cleft lip with or without cleft palate.

We studied metabolic, endocrine, and environmental factors in 59 women who had delivered a child with cleft lip with or without cleft palate (CL +/- CP) and compared these values with those of 56 mothers of unaffected children. There was no significant difference between the two groups with respect to race, age, weight, height, education, parity, menstrual history, medical illnesses, or the use of contraceptives, tobacco, alcohol, or caffeine. All patients had a normal XX karyotype confirmed by the fluorescent banding technique. The two groups demonstrated no significant difference in test results of serum chemistries, glucose tolerance, serum or erythrocyte folate, vitamin A, carotene, corticoids, prolactin T4, free T4, urine 17-ketosteroids, 17-hydroxysteroids, total estrogens, or pregnanediol. Urinalyses revealed no group differences in the presence of barbiturates, amphetamines, salicylates, or benzodiazepines. The percentage of immunologic studies reflecting susceptibility to toxoplasmosis, rubella, cytomegalic inclusion disease, and herpes was not different between the two groups. The only statistically significant metabolic differences between the two groups were serum alkaline phosphatase, creatinine, creatinine clearance, and creatinine clearance/m2. Phenytoin pharmacokinetics and urinary metabolic patterns were compared in a subgroup of ten mothers of affected children and ten mothers from the control group. No significant differences were observed. However, a brief course of phenytoin treatment induced a greater inhibition of the folate tolerance test in controls than in mothers of children with clefts.

Adult↗
PubMed1978

Use of a radioreceptor test for HCG in women practicing contraception.

The importance of a simple, rapid and highly sensitive test for the diagnosis of early pregnancy cannot be overemphasized. In the present times when newer delivery systems of contraceptive agents and menstrual regulation procedures are increasingly used for fertility regulation, it is inevitable that confirmation of early pregnancy poses a severe problem. This radioreceptor test has been found to be very reliable even in early cases. A positive test was 100% accurate for pregnancy whereas the accuracy of a negative test was found to be 94.4%. Confirmation of these results was done by various other parameters like clinical, histological, radioimmunoassay for HCG and biological test for pregnancy.

Abortion, Induced↗
PubMed1990

Buserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical profile.

The gonadotrophin releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); gonadorelin] agonist buserelin is a promising new agent in the treatment of a variety of disorders in gynaecology and andrology, paediatrics and oncology. While a single dose of buserelin stimulates the release of pituitary gonadotrophins, multiple doses produce reversible pituitary desensitisation, and this specific blockade of gonadotrophin support to the gonads provides the basis for the drug's efficacy in conditions dependent on sex hormone secretion. Thus, buserelin provides comparable efficacy to orchidectomy or high dose estrogens in the treatment of hormone-sensitive prostate cancer and exhibits a lower incidence of adverse effects. During the early phase of treatment it may be particularly useful in combination with antiandrogens. Buserelin also appears promising in hormone-sensitive premenopausal breast cancer. Extensive studies have proven the value of buserelin in endometriosis, where it produces a transient remission with gradual recurrence of the disease on cessation of treatment. Surgical intervention is necessary in severe disease after buserelin-induced involution of the lesions. In patients with uterine leiomyoma, preliminary data suggest that buserelin may be beneficial in rendering surgery more conservative by reducing fibroid size, although it appears unlikely to preclude surgical intervention. The use of buserelin to induce a state of reversible hypogonadotrophism before administration of exogenous gonadotrophins is a promising strategy in the treatment of infertility associated with polycystic ovary syndrome and other conditions of infertility with underlying ovarian dysfunction; such a strategy also clearly enhances the efficiency of in vitro fertilisation programmes. Initial studies suggest its potential usefulness as a female contraceptive when administered intermittently in conjunction with a progestogen. Buserelin represents a first-line treatment of central precocious puberty. In endometriosis the adverse effect profile of buserelin is generally favourable, with hypoestrogenic effects such as hot flushes and vaginal dryness, and decreased libido, predominating. There is no apparent detrimental effect on lipid metabolism. The potential for adverse hypoestrogenic effects on bone mineral content with long term administration remains to be clarified. Thus, the GnRH agonist buserelin represents an advance in the treatment of a variety of gynaecological and andrological as well as paediatric and oncological conditions, infertility and other sex-hormone dependent conditions, with a low incidence of adverse treatment effects.

Animals↗
PubMed1993

The safety of vasectomy: recent concerns.

Vasectomy has been accepted for family planning by approximately 42 million couples worldwide, the majority of whom live in developing countries. It is a highly reliable and safe contraceptive method, which has been extensively studied. Recently, however, renewed concerns have been raised about a possible effect between vasectomy and cancer of the prostate many years after the procedure has been performed. These concerns are based on research conducted in the USA, where there is a high and rising incidence of prostate cancer. This review discusses the evidence for this association and its potential impact in developing countries. The factors influencing the development and growth of prostate cancer are poorly understood and complicate any research into risk factors for the disease. Overall incidences of prostate cancer in some developed countries, such as the USA, are fifty times higher than in some developing countries, such as China. The majority of epidemiological studies on the relationship between vasectomy and prostate cancer have been based in the USA, but the findings are inconsistent and the reported associations weak. On the basis of currently available data, no changes in family planning policies with regard to vasectomy are warranted, but the concerns raised by these studies require that research into any possible association be undertaken in developing countries where vasectomy is widely practised.

Contraception↗
PubMed1987

Immunology of recurrent vaginitis.

Recent evidence suggests that recurrent vaginitis can arise as a consequence of a transient and localized inhibition of cell-mediated immunity. Lymphocytes from many women with this disorder manifest a reduced in vitro proliferative response to Candida albicans. The inhibition appears to be due to increased production by the patients' macrophages of prostaglandin E2, which inhibits interleukin-2 production and thereby blocks lymphocyte proliferation. When lymphocyte responses are impaired, C. albicans can readily proliferate and initiate a clinical infection. Prostaglandin E2 production can arise as a consequence of a vaginal allergic response. IgE antibodies to C. albicans, ryegrass, contraceptive spermicides, and seminal plasma have been detected in vaginal fluids from recurrent vaginitis patients. The role of male factors in inducing immune alterations and vaginitis in the female partner has been underestimated. Medications or chemicals ingested by the male and present in his semen may be transmitted to sensitized females by coitus. In addition, male-specific allergic responses may be induced in females through the seminal transfer of specific IgE antibodies. Future efforts both to eliminate clinical vaginal infections and to reduce susceptibility of the host to vaginal immunosuppression should improve the efficacy of treatment for this disorder.

Candida albicans↗
PubMed1992

The situation in Africa.

More than three million women world-wide are infected with HIV, and women will constitute 40% of the new AIDS cases in 1990-1991. Unlike in the industrialized world, HIV in Africa is heterosexually transmitted and thus affects at least as many women as men. Already the leading cause of death in a major African city, HIV may be spreading to rural areas. In spite of improvement in surveillance, under-reporting makes it difficult to project trends, document differences within and between urban and rural areas, and identify at-risk groups. Increasing evidence shows that STDs play a major role in spreading the HIV epidemic. Male-to-female transmission is more efficient owing to factors related to the pathogen and the host. Ulcerative STDs such as chancroid, syphilis and herpes facilitate HIV entry through mucosal discontinuation and recruitment of HIV target cells. The role of non-ulcerative STDs such as gonorrhoeal, chlamydial and trichomonal infections needs further elucidation. Lack of circumcision, traditional healing practices and oral contraceptives may affect the risk of viral transmission, but may not be major or modifiable risk factors. Pregnancy and pregnancy-associated immune alterations do not seem to affect the clinical course of HIV/AIDS in African women or impair immunocompetence. Maternal HIV can adversely affect pregnancy outcome in Africa, causing low birth-weight, prematurity, intrauterine and intrapartum fetal death. The risk for these outcomes is likely to depend on the degree of immunological and clinical deterioration. Breast-feeding does not appreciably increase the risk of HIV transmission to the infant and should be actively promoted in Africa. Control of HIV/AIDS in Africa, in the absence of an effective vaccine, will focus on behavioural changes through health education and condom use. High frequency STD transmitter core groups, mainly prostitutes and their clients, are currently the target of prevention campaigns which are proving to be successful and affordable.

Africa↗
PubMed1983

[alpha 2-Macroglobulin in serum and plasma: reference values with carbobenzoxy-valyl-glycyl-arginine-p-nitroanilide, a chromogenic substrate].

alpha 2-Macroglobulin can be determined using the amidolytic activity of the alpha 2-macroglobulin-trypsin-complex. Reference values are reported using a commercially available kit for continuous assay at 25 degrees C. Reference ranges obtained in a population of 235 children and adults aged between 1 day and 61 years were found to be age-dependent. Reference ranges established for the different age groups of children were grouped together in order to obtain useful guide values. The following values were obtained for serum: 1 to 10 days: 5-11 kU/l 11 days to 18 years: 8-16 kU/l The reference values (5th to 95th percentile) determined for juveniles and adults were as follows: 19 to 25 years: 4.1-12.2 kU/l (serum); 4.0-11.2 kU/l (citrated plasma) greater than or equal to 25 to 61 years: 4.1-8.1 kU/l (serum); 3.7-7.4 kU/l (citrated plasma) No variation according to sex was observed, nor was any difference noted between preprandial and postprandial catalytic concentrations, or between values in smokers and non-smokers or between values in the group of women taking hormonal contraceptives and the group not taking such drugs. If the dilution of the blood sample with citrate solution is taken into account when calculating the catalytic concentrations in citrated plasma, the values in plasma are higher than those in serum (median 11%). Measurement of the alpha 2-macroglobulin-trypsin complex in plasma is assumed to give a more realistic reflection of the in vivo activity than measurement in serum. Comparison with two immunological methods (radial immunodiffusion and kinetic nephelometry) revealed that there is a linear relationship between the measurement of the catalytic concentration of the alpha 2-macroglobulin-trypsin complex and the immunological concentration of alpha 2-macroglobulin. Therefore mutual conversion is possible for the described concentration range.

Adolescent↗
PubMed2005

Tubal occlusion causing infertility due to an excessive inflammatory response in patients with predisposition for keloid formation.

Infertility is a condition that affects approximately 15-25% of couples with the desire to procreate. The integrity of the feminine reproductive tract is essential for this purpose, but the occlusion of the Fallopian tubes occurs in 12-33% of infertile women. The infection by Chlamydia trachomatis is one of the principle causes of tubal injury, which could finally lead to tubal occlusion. The tract infection has also been related to the use of intrauterine device, basically due to the fact that the insertion of the device could carry bacteria to the endometrial cavity. Keloid scars result from alterations in the normal process of wound healing, and it affects principally the population in reproductive age, maybe due to specific hormonal influence. These fibroproliferative alterations may produce significant deformations and alter organ function. The genetic factors have been studied in order to have a better understanding of the pathophysiology of keloid scarring. With these assessments, many other factors have been known to have a relationship with this abnormal healing process. This keloid scarring involves an excess in extracellular matrix production and inhibition of apoptosis, for which a several growth factors and interleukins are needed. One of the most important growth factors is IGF-1, which increases the expression of type I and III procollagen (found in the uterus); the IGF-1 receptor is overexpressed in the fibroblasts of keloids. Based on those previous observations a hypothesis that the chronic and repeated infection, and the use of IUD, generate an exaggerated inflammatory response in patients with a predisposition for keloid formation (which frequently form in childbearing age), in comparison to the patients that do not form this type of scarring, has been proposed. This makes a major frequency of adherences and finally tubal occlusion and infertility. The tendency of excessive scarring could not be exclusive of skin and generate abnormal scarring responses in feminine reproductive tract, leading to a major frequency of infertility. Thus, it could be suggested the use of other contraceptive methods and a more aggressive treatment against infections of the reproductive tract, taking in consideration the pathophysiology of keloid scar formation and its relationship with tubal occlusion.

Chlamydia Infections↗
PubMed2007

Peptide vaccines against cancer, infectious diseases, and conception.

The concept of peptide vaccines is based on identification and chemical synthesis of B-cell and T-cell epitopes which are immunodominant and can induce specific immune responses. B-cell epitope of a target molecule can be coupled to a promiscuous T-cell epitope to make it immunogenic. Our increased understanding of antigen recognition at molecular level has resulted in the development of rationally designed peptide vaccines. The relative ease of construction and production, chemical stability, and lack of oncogenic or infectious potential has made the peptides attractive vaccine candidates. However, several obstacles limit the widespread usefulness of peptide vaccines. These include their low immunogenicity, need for a better adjuvant and carrier, and reliable and simple assays to measure T-cell response. Nonetheless, current efforts are defying these limitations and many promising discoveries are making their way to improve this approach. The peptide vaccines against various cancers have undergone phase I and phase II clinical trials with successful immunological clinical outcome. The peptide vaccination is being examined both for palliative and prophylactic immunotherapy. The current status of many peptide vaccines which are being developed against cancer, infectious diseases, and conception is discussed in this review.

Animals↗
PubMed2004

Why consider vaginal drug administration?

OBJECTIVE: To review the anatomy and physiology of the vagina, the merits of vaginal drug administration, and the currently available vaginal drug-administration systems. DESIGN: Review of basic and clinical research. RESULT(S): Although clinicians commonly use topically administered drugs in the vagina, this route for systemic drug administration is somewhat novel. Experience with a variety of products demonstrates that the vagina is a highly effective site for drug delivery, particularly in women's health. The vagina is often an ideal route for drug administration because it allows for the administration of lower doses, steady drug levels, and less frequent administration than the oral route. With vaginal drug administration, absorption is unaffected by gastrointestinal disturbances, there is no first-pass effect, and use is discreet. Knowledge of anatomy, physiology, histology, and immunology of the vagina should allow clinicians to reassure their patients concerning this mode of delivery. Greater understanding and experience by clinicians should lead to increased use and acceptance of the vagina as a route for drug administration. CONCLUSION(S): The safety and efficacy of vaginal administration have been well established. The vaginal route of drug delivery is acceptable and may even be a preferable route of administration for many drugs, particularly hormones, whether for contraception or postmenopausal estrogen therapy.

Administration, Intravaginal↗