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Humoral hyporesponsiveness to a conjugate contraceptive vaccine and its bypass by diverse carriers using permissible adjuvant.

A contraceptive vaccine directed against human chorionic gonadotropin (hCG) has previously undergone clinical testing that demonstrated the feasibility of the approach in preventing pregnancy in women. Some immunized volunteers however, did not respond with an adequate anti-hCG antibody response despite employing highly immunogenic bacterial toxoids as carriers. Since there is some evidence that T cell responses to a complex protein typically focus on a few immunodominant epitopes, we investigated the responsiveness to hCG in mice of different haplotypes using the protein carrier diphtheria toxoid (DT). Our data showed a differential carrier effect of DT. With the aim of making a more potent immunogen employing promiscuous pathogen-derived Th peptides as carriers, peptide:antigen stoichiometric ratios were optimized. When tested individually using alum as the adjuvant, three such peptide conjugates improved the anti-hCG response, though not consistently to levels higher than the DT conjugate. Immunization with a combination of these synthetic epitopes generated anti-hCG responses higher than those achieved with DT or with the individual peptides. Antibodies were of high affinity and capable of neutralizing the bioactivity of hCG, but were devoid of anti-peptide reactivity. These results support our view that differential hyporesponsiveness in a diverse population may arise from inadequate carrier effect and that it can be overcome by use of pathogen-derived broadly reactive non-B Th epitopes employing only alum, a permissible adjuvant.

Adjuvants, Immunologic↗

Risk factors for Candida vulvovaginitis.

Although Candida vulvovaginitis occurs commonly, the reasons for its occurrence and recurrence are often unclear. Several potential risk factors have been described, including the recent use of antibiotics and oral contraceptives, the presence of diabetes mellitus, dietary practices, gastrointestinal colonization by the organism, clothing and sanitary protection practices, sexual communicability of the organism, and specific immunological defects. However, the data supporting each of these factors are conflicting, and to date none are predictive of infection. In this review, the data evaluating these potential risk factors are described. From this information, implications for clinical practice are discussed.

Candidiasis, Vulvovaginal↗

Identification of people at high risk of genital HPV infections.

Clinical and subclinical genital HPV infection is most prevalent in people aged 20-24 years. HPV-infected women have an earlier debut of sex activity, more partners and more casual relationships and STD than age-matched controls without HPV; although data are not available, the same risk factors probably operate in men. There is no evidence that the presence of non-genital warts affects the incidence of genital lesions. Between 50 and 70% of sex partners of individuals with condylomatous or non-condylomatous genital HPV infection also have lesions. Nothing is yet known about any relationship between infectivity and the number of lesions or their viral content. The infectivity of non-condylomatous HPV infection is uncertain. Immunological factors affect the clinical behaviour of genital warts, and immunosuppression, for example by drugs, radiation and possibly cigarette smoking and the use of oral contraceptives, may increase liability to genital HPV infection. The main risk factors appear to be young age, sexual promiscuity, intercourse with a partner with HPV disease and perhaps deficient immune responses. The identification of people at high risk requires careful clinical examination supplemented by the use of a magnification system, histology and cervical cytology. The identification of HPV genotypes in genital epithelia does not seem to be useful in this context, because they are present in a proportion of normal epithelia.

Adult↗

[Juvenile distal cerebral ischemia: value of pulp biopsy].

Juvenile distal cerebral ischemia has been attributed to small artery atherosclerosis (Arnold, Benoit, Merlen, Dobbelaere, Delandsheer, 1979), based on clinicopathologic findings in one male patient and results of big toe pulp biopsy in three other cases. Pathological findings were obstruction of small artery lumens by hypertrophic endothelium and loose fibrocellular bands, their origin being the result possibly of partial intimalization of media by elastic neogenesis. Appearances were similar to those described by Dahl in human cerebral atherosclerosis in 1976, and approached those of the initial stages of experimental atheroma (Ross, Glomset, 1976). Arterial exiguity was also present in the 4 cases. Results of biologic, metabolic, inflammatory and immunologic examinations were negative. The present study concerns 4 additional cases of juvenile distal encephalic ischemia. One case in a female patient not on oral contraceptives confirmed the hypothesis of intimalization of media of arterioles of big toe pulp. Elastic neogenesis was present in the tunica media in areas where there was a change of direction of myocytes, and was apparent at a distance from the internal elastic layer. The latter was fragmented, sometimes doubles and of variable color. In another case, a woman taking oral contraceptives, there was almost total obstruction of the pulp arteriolar lumens with a very thin tunica media. Elastic neogenesis encircled two very narrow lumens in the center of the vessel and there were also elastic changes common to both.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Giant cell thromboangiitis in a patient taking an oral contraceptive (author's transl)].

Pathological examination in a patient who developed an ischemic cerebrovascular accident while taking an oral contraceptive demonstrated widespread lesions in the right and left carotid regions. Histological examination revealed the presence of an obliterating thromboangiitis in the arterial walls, with subendothelial fibrosis of the intima, arterial thrombosis, and a marked giant cell reaction where the lesions were in contact with the internal elastic layer. Immunological and biological anomalies confirmed the inflammatory nature of the lesion with the presence of anti-ethinyl estradiol antibodies in the serum and circulating blood immune complexes. These biological and histological results suggest the immunological nature of the mechanism of origin of the cerebrovascular accident in this case.

Adult↗

Prostate-specific antigen in vaginal fluid as a biologic marker of condom failure.

Forty women participated in three clinic visits during which they were exposed to their partner's semen (10 microL, 100 microL, and 1 mL). At each visit they took vaginal fluid samples before exposure to their partner's semen, immediately after, and at 1, 24, and 48 h after exposure. PSA was measured with an enzyme-linked immunoassay. The mean PSA level for preexposure swabs ranged between 0.43 and 0.88 ng/mL. The mean PSA levels were 193 immediately after exposure to 10 microL, 472 after 100 microL, and 19,098 after 1 mL. The PSA levels declined within 1 h, and returned to background at 48 h. The findings confirm that our procedure is a sensitive and specific method for detecting recent semen exposure, and indicate that PSA levels depend on exposure intensity and time since exposure. Application of this method in condom efficacy studies provides objective evidence of condom failure that enhances the interpretation of self-report.

Adult↗

[Hpv cofactors in cervical carcinogenesis].

Human papillomavirus (HPV) plays a central rule in uterine cervix carcinogenesis. Other factors direct or indirectly influence the installation of this mechanism in cervical squamous epithelium. Investigations regarding mechanisms of interaction of these factors with viral elements are found in the literature of the last 20 years. The present review article discusses possible co-factors of HPV in the genesis of the squamous carcinoma of uterine cervix, taking into account only the factors whose association with the virus or cervical cancer has been documented by experimental studies, and not based just on clinical or epidemiological data. Among the approached parameters are immunological factors (local and humoral immune response), the association with Acquired Immune Deficiency Syndrome, genetic factors as protein p53 polymorphism, tabagism and the use of oral contraceptives. All these factors interact in variable intensity with oncoproteins and other HPV elements, increasing and facilitating the virus action in host cells, leading to the development of immortalization and carcinogenesis.

Carcinoma, Squamous Cell↗

Reproductive failure and antisperm-antibody production among prostitutes.

Reproductive failure and anti-sperm antibody (ASA) production among prostitutes were investigated. A questionnaire including the subject's age, years of prostitution, date of most recent birth, number of children and contraceptive method used at the beginning of prostitution were asked of 109 prostitutes, but only 53 agreed to complete the questionnaire. ASA was detected by ELISA in the prostitutes (n = 109) and in the control group (n = 40) sera. The tests revealed a high ASA rate (43.1%) among the prostitutes. The difference in the incidence of ASA between controls (5%) and the prostitutes (43.1%) was highly significant (p less than 0.01). It was found that ASA positivity incidence in 27 prostitutes who had never use any contraception method and who became infertile within 9.3 years (average) was 61.3%. These results may be explained by repeatedly inoculations with multiple sperm antigens and/or microorganisms.

Adult↗

Oral contraceptives, sex steroid-induced antibodies and vascular thrombosis: results from 1318 cases.

The role of antiethinyl estradiol antibodies (anti EE Ab) and associated risk factors was evaluated in 1318 cases of venous or arterial thrombosis in oral contraceptives (OC) users, and compared to 61 non-users and 124 healthy current users. Anti EE Ab were absent in non-users and present in 33% of healthy users and 72% of those with thrombosis, either arterial or venous. Age, duration of use, hyperlipidaemia and smoking were factors associated with thrombosis only in women with an arterial disease. While the two predominant factors, anti EE Ab and smoking may be risk factors in their own right, the combination of both was found in 47.7% of women with thrombosis. It is proposed that thrombosis associated with OC use may be explained by an immunological disease in which anti EE Ab and their complexes with the circulating synthetic hormones may be harmful to the vessels, as also suggested by the type of lesions already described in OC users. The determination of anti EE Ab in healthy users may identify a group at risk of thrombosis.

Adult↗

Contraception.

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Adolescent↗

Two new male contraceptives exert their effects by depleting germ cells prematurely from the testis.

The three currently available male contraceptive approaches are 1) the barrier method such as the condom, 2) hormonal methods by disrupting the pituitary-testicular axis so as to impair spermatogenesis, and 3) immunological methods by preparing vaccines against male-specific antigens. We hereby describe an alternative approach in which attachments of developing germ cells onto the seminiferous epithelium are disrupted, thereby inducing their premature release into the tubular lumen. This in turn leads to infertility. A panel of analogues based on the core structure of 1-(2,4-dichlorobenzyl)-indazole-3-carboxylic acid was synthesized. These compounds were subjected to an in vivo screening assay assessing their effects in inducing the expression of testin, a testicular marker whose expression correlates with the integrity of Sertoli-germ cell junctions. An induction of testin expression in the testis signifies a disruption of Sertoli-germ cell junctions that is followed by depletion of germ cells from the seminiferous epithelium. Two compounds, namely 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide (AF-2364) and 1-(2,4-dichlorobenzyl)-indazole-3-acrylic acid (AF-2785), were identified that caused detachment of germ cells, in particular round and elongated spermatids, from the epithelium inducing their premature release into the tubular lumen as confirmed by histological analysis. Adult rats receiving several oral doses of either one of these compounds became infertile within 3-7 wk after the epididymal sperm reserve was exhausted. Depending on the dosing of the administered compound, rats became infertile for 4-14 wk before their fertility gradually bounced back, illustrating the reversibility and efficacy of these new compounds. Also, these compounds did not appear to impair the hypothalamus-pituitary-testicular axis because the serum levels of LH, FSH, and testosterone of the treated animals did not change significantly when compared to control rats. In addition, results of serum microchemistry illustrate that liver and kidney function was not affected in animals treated with both compounds.

Animals↗

Immunogestosis: a new etiologic concept of "essential" EPH gestosis, with special consideration of the primigravid patient; preliminary report of a clinical study.

Evidence for immunologic processes taking part in the pathogenesis of what until now has been called the "essential" form of EPH gestosis is cited. The name of immunogestosis (IG) is introduced. The data of this preliminary study suggest that regular "inoculation" of the female genital tract with allogeneic spermatozoal histocompatibility antigens reduces the incidence of IG. Information about preconceptional sexual habits and contraceptive measures was obtained from 83 selected primigravid patients. Twenty-eight women had mild to moderate IG (Group B);55 did not (Group A). Women in Group B had had less contact with spermatozoa of partners than did women in Group A. Oral contraceptive consumption was less in Group B than in Group A. Women in Group B were younger than women in Group A. All these differences were statistically significant. A new immunoetiologic hypothesis referring to IG, as well as the theoretic and clinical implications arising from it, are discussed. This hypothesis is based on the assumption that spermatozoal histocompatibility antigens can either induce immunologic tolerance or be responsible for the phenomenon of immunologic enhancement in the maternal immunosystem. As the fetus inherits paternal histocompatibility antigens, it is concluded that pre-existing tolerance (or enhancement) exerts an IG-preventive function in a subsequent pregnancy.

Contraceptives, Oral↗

[Pityriasis versicolor--modern views on etiology, pathogenesis and therapy].

Pityriasis versicolor (Tinea versicolor) is a superficial chronic fungal infection caused by Pityrisporum species which are normal "inhabitants" of the cutaneous flora. The morphologic changes from yeast to mycelial hypha form are important in the development of clinical lesions. The onset and course of the disease are under the influence of genetic factors, age, sex, climate, local environmental factors, malnutrition, pregnancy, oral contraceptives, corticosteroid and immunosuppressive treatment. They favorize transformation of saphrophytic to pathogenic form, and are the cause of recurrences and chronicity of the disease. The ultrastructural and immunologic studies which are carried out today would significantly contribute to a better understanding of pathogenesis of the disease. The disease is limited to seborrheic areas of the skin and commonly has three clinical forms: papulosquamous, follicular and inverse. This can make great problems in differential diagnosis. In the treatment of these patients it should be kept in mind that Pityriasis versicolor is not a primary contagious disease and that conversion of Pityrisporum depends on the predisposing factors. Numerous medicaments with local and systemic effect which are used nowaday in the treatment and prevention of pityriasis are reported. Way of application, doses, duration of therapy, advantages and disadvantages are given in detail.

Humans↗