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Timing within the menstrual cycle, sex, and the use of oral contraceptives determine adrenergic suppression of NK cell activity.

Physiological responses that involve adrenergic mechanisms, such as stress-induced changes in cardiovascular indices, were reported to fluctuate along the menstrual cycle. Metastatic development following surgery was also reported to vary according to the menstrual phase during which a primary breast tumour was removed. Natural killer (NK) cells are believed to play an important role in controlling metastases. Our recent studies in rats demonstrated that adrenergic suppression of NK activity and of resistance to metastasis is more profound during oestrous phases characterized by high levels of oestradiol. In the current study in humans, we examined the in vitro impact of a beta-adrenergic agonist, metaproterenol (MP), on NK activity, comparing blood drawn from (a) women tested at 3-4 different phases of their menstrual cycle (n = 10), (b) women using oral contraceptives (OC) (n = 10), and (c) men (n = 7). NK activity in each blood sample was assessed in the presence of 5 different concentrations of MP (10(-8)M to 10(-6)M), and in its absence (baseline). The results indicated marked group differences in the magnitude of NK suppression by MP: EC(50)was 2. 6-fold lower in the luteal phase compared to the follicular phase, and 1.8-fold lower in OC users compared to men, who were least susceptible to the effects of MP. No significant group differences or menstrual effects in baseline levels of NK activity were evident. These findings provide the first empirical evidence for menstrual regulation of adrenergic impact on cellular immune competence. Relevance of these findings to the relation between the timing of breast cancer excision within the menstrual cycle and survival rates is discussed.

Adrenergic beta-Agonists↗

Sex hormones and the immune response. II. Perturbation of antibody production by estradiol 17beta.

The administration of 75 microgram/kg of estradiol 17beta at successively later stages in the immune response of female guinea pigs to penicilloyl-coupled cavian globulins showed that this steroid reduces the rate of attainment of the maximum titer, the magnitude of the titer achieved, and the rate of titer decay. Control titers maximized at the third experimental week and diminished to one third the peak value by the 6th week. When steroid treatment was begun coincidentally with inoculation (week 0), the peak titer was delayed by 3 weeks, and by 2 weeks when hormone priming was begun at week 1 or 2. The highest antibody titers achieved in the presence of estrogen were 25-30% lower than those of sesame oil controls. The greatest immunosuppressive effect was observed when estradiol was given at the peak of the immune response, the titer dropping by 50% and remaining at that level for the next 4 weeks in spite of continued antigen inoculation and steroid treatment. Titer decay after the end of the inoculation course was prevented by estradiol but not by progesterone, CHP, or these same oil vehicle.

Animals↗

Evidence of immunosuppressor factor in the serum of women taking oral contraceptives.

The serum of women taking oral contraceptives is able to inhibit an in vitro cytotoxicity reaction at the cell level. This effect is nonspecific. It seems to be due to the presence of an inhibitor of the lymphocyte activity and acting at the membrane level. This factor looks like that described in expectant mothers except that it exhibits a lower activity. This difference makes it possible to consider that its emergence depends on a specific hormonal impregnation.

Blood Proteins↗

Hyposensitisation in the management of recurring vaginal candidiasis.

Hyposensitisation with a commercially available antigen has been attempted in the treatment of women suffering from recurring monilial vaginitis. Ten women entered the trial, each being used as her own control. Eight of them showed undoubted improvement and the average interval between relapses increased from 5.1 to 15.7 months (p. less than .01). Reasons are given for believing that allergic reactions play a part in recurrent vaginal thrush.

Adult↗

Immunization to regulate fertility: biological and cultural frameworks.

Deliberate immunization to control fertility differs from that to control disease. Those differences can be discussed within various frameworks, e.g., intent, recipient population, biological bases, and immunological targets. Others include differing perspectives of developers, providers and users, and rights of the state to impose programs of control. Almost all of the differences are grounded in the social, economic, and gendered aspects of societies. The intent of providing a fertility-regulating vaccine is to prevent pregnancy. In theory, men as well as women could receive such vaccines; in reality, most are designed for women. Traditional vaccines are intended to prevent disease and are generally given to susceptible individuals whether male or female, child or adult. The biological bases of contraceptive vaccines are molecules specific to reproduction. The immune response generated by most anti-fertility vaccines is directed toward 'self', one's own cells and molecules. In contrast, the bases of traditional vaccines are materials derived from non-self, disease-causing microorganisms; the immunological targets are those microorganisms or their toxic products. From a developer perspective vaccines that regulate fertility differ little from those that control disease; both prevent a particular condition. Developers cite these advantages to contraceptive vaccines: non-invasive, no serious side-effects, easy to use, reduced patient failure, and long-lasting but naturally reversible. Because anti-fertility vaccines have been tested only in small-scale clinical trials, information on user reactions and experiences is limited. Not surprisingly, the perspectives of women's health advocates and of potential users (mostly women) often differ markedly from those of developers. Women cite as disadvantages the cryptic nature of immunity which leaves one without an obvious signal for the beginning of protection (against pregnancy) and its decline, and the inability to 'turn-off' an immune response. Further, long-acting contraception can complicate alleviation and side-effects, and it leaves women always vulnerable to sexual demands. Most women object to the lack of user control and are especially concerned about the enormous potential for misuse and coercion by population control programs should fertility-regulating vaccines become widely available. Many scholars and government officials subscribe to the following logic: the global environmental crisis is due to over-population which necessitates population control programs; thus pregnancy can be considered a disease subject to state control. But pregnancy is not a disease nor is over-population the single major cause of environmental degradation. However, as governments grapple with the economic, social, and ecological consequences of population growth, draconian measures to control fertility will be ever more tempting.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Evaluation of somatic and reproductive immunotoxic effects of the porcine zona pellucida vaccination.

Immunological, immunocytochemical and fertility analyses were performed to determine the potential toxic side effects of porcine zona pellucida (pZP) vaccinations on target animals, including horses and dogs. The study was designed to determine the effect of antibodies, raised against highly purified pZP, on somatic tissues. Immunocytochemical studies performed with fixed tissues showed that rabbit anti-pZP antiserum did not crossreact with brain, heart, lung, kidney, liver, bladder, stomach, small intestine, large intestine, muscle, skin, spleen, pancreas, or lymph node of either the dog or horse. To determine the effect or oral intake on nontarget animals, female rabbits were fed a contraceptive vaccine containing pZP glycoproteins and the synthetic trehalose dicorynomycolate in drakeol (S-TDCM) adjuvant. Enzyme-linked immunoadsorbent assay (LISA) analyses showed that rabbits fed with the adjuvanted pZP proteins did not develop circulating anti-pZP IgG antibodies that crossreacted with pZP. Furthermore, fertility studies performed on rabbits fed with adjuvanted pZP revealed no significant differences in the number of embryos or stage of the embryos produced between the treated and control animals. Results of these studies suggest that the pZP vaccine delivered to dogs or horses in field studies have no recognizable somatic tissue effects. Moreover, there were no side effects on nontarget animals should they eat the vaccine. This substantiates field trials results about the safety of the pZP immunocontraceptive vaccine.

Adjuvants, Immunologic↗

Prospects of zona pellucida glycoproteins as immunogens for contraceptive vaccine.

The zona pellucida (ZP) surrounding a mammalian oocyte mediates the initial recognition and binding of spermatozoon to oocyte in a relatively species-specific manner and plays an important role in the subsequent activation events during the fertilization process. The ZP comprises three biochemically and immunologically distinct glycoproteins termed ZP1, ZP2 and ZP3. The critical role of ZP glycoproteins in reproduction together with their tissue-specific nature have led to their being considered as potential candidate antigens for immunocontraception. Immunization of females with ZP glycoproteins leads to a block of fertility in several animal models. However, it is invariably associated with either a transient or an irreversible alteration in the cyclicity, hormonal profile and follicular development in the ovary. To overcome these problems, attempts are being made to delineate relevant 'B' cell epitopes on ZP proteins so as to design immunocontraceptive vaccines based on synthetic peptides devoid of oophoritogenic 'T' cell epitopes. Monoclonal antibodies capable of inhibiting the gamete interaction are being employed to delineate such regions. Additionally, DNA-recombinant technology has made it feasible to obtain, in reasonably large quantities, the ZP glycoproteins from human and non-human primates. Availability of sequence information of these zona proteins and the availability of recombinant antigens (devoid of other ovarian-associated proteins) will further help in understanding more precisely their functions during fertilization and make it feasible to undertake immunization studies to determine their prospects as immunogens for fertility regulation.

Amino Acid Sequence↗

Ischemic strokes and oral contraception.

The authors describe the epidemiology and the physiopathological aspects of ischemic strokes in patients with a history of oestroprogestogen use. They then study their main radiological correlates: arterial infarcts at CT scan and angiographic non-specific lesions which can be included in the extremely wide framework of arteritis and, much more rarely, venous thrombophlebitis.

Arteritis↗

Oral contraceptives and antithrombin III: variations by dosage and ABO blood group.

A randomized clinical trial of oral contraceptives evaluated 67 women on a regimen of 50 micrograms ethinyl estradiol and 1.0 mg norethindrone, 61 women on a regimen of 35 micrograms ethinyl estradiol and 1.0 mg norethindrone, and 64 women on a regimen of 35 micrograms ethinyl estradiol and 0.5 mg norethindrone. ABO blood group type was determined in all women. At baseline and at 3, 6, and 9 months, plasma antithrombin III levels, by both an immunologic and an activity method, and selected plasma levels of the contraceptive steroids were measured. Antithrombin III levels for all oral contraceptive groups combined decreased from baseline by 19.7% and 28.8% for the immunologic and activity methods, respectively. Analysis of interrelationships among antithrombin III by activity method, oral contraceptive type, and ABO blood group showed larger declines in antithrombin III for type O women using the highest estrogen dose preparation (31.6%) and for non-type O women using the lowest progestin dose preparation (38.9%). Plasma levels of contraceptive steroids also were related to changes in the most extreme levels of antithrombin III.

ABO Blood-Group System↗

Diminished incidence of severe rheumatoid arthritis associated with oral contraceptive use.

It has been suggested that the negative association between rheumatoid arthritis (RA) and oral contraceptive (OC) use might be limited to the more severe forms of RA. To investigate this further, we studied 121 consecutive female patients with definite RA, 52 female patients with probable RA, and 378 female controls. All patients had RA symptoms of recent onset. After a mean followup period of 6 years, patients with definite RA were classified as having either a severe disease course (n = 76) or a mild disease course (n = 45). The negative association between OC use prior to the onset of RA symptoms and the development of RA was limited to those patients with definite RA who had a severe disease course. We therefore conclude that OC use prior to the onset of RA symptoms is only associated with a reduction in the incidence of severe RA. This may explain the divergent results of previous studies.

Adult↗

[Oral contraception and multiple sclerosis].

The uncertain question of the use of oral contraceptives by women with multiple sclerosis is discussed. Reference is made to results observed in animals with experimentally induced allergic encephalitis subjected to oestroprogestin management. The course of M.S. during pregnancy is examined and the effects of blood lipid changes produced by oestrogens and progesterone, on the assumption that M.S. is due to a deficiency of unsaturated fatty acids. Lastly, attention is directed to interference with immunity, clotting, and platelet changes, these being factors in the spread off the disease. The data point to a protective rôle on the part of oestrogens, while the picture for progesterone is less conclusive. It would seem that these biological and immunological findings justify the use of oral contraceptives in subjects with M.S., though due caution is imposed by the absence of clinical and epidemiological data.

Blood Coagulation↗

Predictions of Immunological Cross-Reactions of C-Terminal Peptide of Human Chorionic Gonadotropin beta-Chain Based Contraceptive Vaccine with Autoantigens.

Cross-reactions of anti-human chorionic gonadotropin-beta (HCG-beta) antibody elicited by HCG-beta based antifertility vaccines with other autoantigens may occur due to identical or homologous protein subsequences. I have detected hitherto unreported identity of HCG-beta sequence with tetrapeptides of PECAM-1, galactosyl transferase-associated protein kinase, insulin receptor-related receptor and carboxypeptidase E. A predicted potential epitope of C-terminal peptide (CTP) of HCG-beta was identical to a tetrapeptide stretch of MCSF-1. The first 30 residue stretch of CTP was found to have yet unknown homologies of more than 56% with many auto-antigens including 60.1% with centromere protein C. The last 30 residue stretch of CTP was found for the first time to have 61.4-65.4% homology with subsequences of autoantigens SP-100, PM-SCL, D1 (64 kDa), lupus KU (p86), small nuclear ribonucleoprotein-associated proteins N, B and B', major centromere autoantigen B, centromere protein C, and dihydrolipoamide acetyl transferase component E2 of pyruvate, respectively.

Journal Article↗

Changes in the plasma levels of proteins C and S in young women on low-dose oestrogen oral contraceptives.

The physiological importance of proteins C and S as natural anticoagulants is demonstrated by the increased risk of thromboembolic disease among subjects with hereditary deficiency of both proteins. In the present study the effects were evaluated of low-dose oestrogen oral contraceptives (OC) on the plasma levels of immunological protein S, as free (PS-f), and in reversible complex with C4b-binding protein as well as functional protein C (PC) in a homogeneous group of 20 young healthy women. The participants were randomly given either gestodene (75 micrograms) or desogestrel (150 micrograms) in combination with ethinyl oestradiol (30 micrograms). Blood samples were taken prior to the initiation of the treatment and at the end of the sixth 21-day treatment cycle. The mean concentration of both free and bound PS fell significantly, the decrease still being within the reference range. Conversely, the plasma values for PC rose to a statistically significant extent. There were no significant differences between the two OCs. Hypothetically, the changes in PS-f (active fraction) might be conducive to a procoagulant state, which the increased PC may compensate. The reverse effect of two OCs on the activity of the protein C-protein S anticoagulant system might suggest a different regulation of their synthesis.

Adult↗

[Barrier family planning methods as risk factor which predisposes to preeclampsia].

Preeclampsia is a pregnancy-specific syndrome, it occurs in approximately 5-10% of all pregnancies and the etiology remains unknown, but the primigravida adolescent as such as multigravid older women whom have conceived with a new sexual partner have a greater risk, this has been associated also with the use of barrier contraceptive methods that prevent exposure to sperm with the endometrial cavity. An immunological factor has been suspected because fetal antigen's could cause antigenic reaction with the maternal immunological apparatus, for first exposure at these antigens, since the fetus is considered like an allotransplantation. This is supported in some studies that report that the use of condoms, spermicides and withdrawal are associated with developing of preeclampsia in subsequent pregnancy, and another hand indicate at cohabitation preceded for long period, practiced oral sex and use of contraceptive methods that permit exposure to sperm viable with uterus decreased the prevalence of preeclampsia. To test this hypothesis, we initially used data from two groups of pregnant women, comparing the contraceptive and reproductive history of 73 pregnant women with preeclampsia and 70 pregnant women without preeclampsia. The odds ratio for preeclampsia indicated a 2.52-fold (with 95% confidence interval, 1.17 to 5.44, p < 0.05), increased risk of preeclampsia for users of barrier contraceptives compared with women using nonbarrier contraceptives methods. Other variables like socio-demographic and obstetrics analysis were not different between both groups. This study suggest that nonbarrier contraceptive methods or the exposure of paternal spermatic antigens is protective against development of preeclampsia. Further immunological studies are necessary to determine the role of contraception methods and preeclampsia.

Adult↗

Human sperm-specific peptide vaccine that causes long-term reversible contraception.

A novel dodecamer peptide sequence, YLP(12), was identified on human sperm that is involved in oocyte binding. We investigated its immunocontraceptive effects in a murine model. A vaccine was prepared by conjugating the synthetic YLP(12) peptide with the binding subunit of recombinant cholera toxin. Vaccination of female mice by i.m. or intranasal routes without any additional adjuvant induced a sperm-specific immune response in serum and the vaginal tract that caused a long-term contraceptive state. Fertility was fully regained when antibody reactivity diminished at 305-322 days. The contraceptive effect was also completely reversed voluntarily by intravaginal administration of the peptide. Antibodies affected fertility at the prefertilization stage by inhibiting sperm capacitation and the acrosome reaction, and sperm-oocyte binding. The peptide sequence is an epitope of a 50 +/- 5-kDa membrane protein localized on the acrosome and tail of spermatozoa. Thus, the sperm-specific YLP(12) is an attractive candidate for contraceptive vaccine.

Acrosome Reaction↗

Immunological side effects of some long term taking medicaments.

In view of epidemiologic aspects of AIDS we studied the immunological side-effects of oral hormonal contraceptives and the barbiturates--which are used by many people in Hungary. We studied healthy persons using more than six months one of the above described drugs. We found significant decrease in the number of "O" cells and in the serum concentration of IgG in the O.C. test group. In B test group decreased significantly the number of T, B, T-active, T-helper lymphocytes and the serum concentration of IgM. The amount of IgA and IgD increased in both the test groups. We detected HBV-markers only in 0.83% of control-group but in 4.23% of O.C. group and in 2.28% of the B test group. The data suggests that all of studied medicaments cause increase in susceptibility against infections.

Acquired Immunodeficiency Syndrome↗