Immunization with cytoplasmic repetitive antigen and flagellar repetitive antigen of Trypanosoma cruzi stimulates a cellular immune response in mice.

In previous studies, we demonstrated that CRA and FRA recombinant proteins, used for diagnosis of Chagas' disease, elicited a humoral immune response in susceptible and resistant mice. To understand better the immune response to these proteins, we have evaluated, the cellular immune response in CRA- and in FRA-immunized BALB/c and C57BL/6 mice. A specific cellular lymphoproliferative response was observed in both strains of mice. Spleen cell cultures mainly from CRA-immunized C57BL/6 and FRA-immunized BALB/c mice produced high levels of IFN-y, indicating the induction of a Type 1 immune response. Regarding the T cell subsets, CD4+ T cells were the major source of IFN-y in CRA- and FRA-immunized mice. These results suggest that CRA and FRA are important immunogens in inducing a Type 1 immune response and that they may be considered as potential vaccine antigens.

Effect of previous hormone replacement therapy on endometrial polyps during menopause.

The aim of this study was to evaluate the effect of hormone replacement therapy (HRT) on the expression of Ki-67, bcl-2 and c-erb.B2 in endometrial polyps during menopause. Sixteen patients using HRT and 24 untreated controls with endometrial polyps were enrolled in this study. Polypectomy was carried out by hysteroscopy. The presence of c-erb.B2, bcl-2 and Ki-67 expression was determined by immunohistochemistry. HRT was found to decrease Ki-67 and bcl-2 expression in endometrial polyps without affecting the c-erb.B2 staining reaction. HRT may cause endometrial polyp involution by decreasing proliferation and stimulating apoptosis.

Proliferation kinetics in adenomyosis during the menstrual cycle and during oral contraceptive use.

Our objective was to investigate the presence of focal p53 expression in relation to proliferation rates in adenomyotic lesions during the menstrual cycle and in women on oral contraception. Fifty-nine perimenopausal patients with menorrhagia and adenomyosis were submitted to endometrial resection. The procedure was carried out during menstruation (n = 14), during the proliferative phase (n = 15), during the luteal phase (n = 20) or following the use of oral contraceptives (n = 10). The number of Ki-67-positive cells was low during menstruation, during the luteal phase and following the use of progestins. In the proliferative phase, on the other hand, there was a significant increase in the percentage of Ki-67-positive cells. Focal p53 expression was detected mainly during the proliferative phase of the menstrual cycle when proliferation rates were high. PTEN expression was detected in all cases irrespective of the phase of the menstrual cycle or use of oral contraception. We conclude that proliferation rates in adenomyotic lesions undergo marked cyclic variations and this affects the percentage of cases showing focal p53 expression in the glandular epithelium.

Decreased humoral and pathologic responses in undernourished mice infected with Schistosoma mansoni.

We previously demonstrated that mice subjected to a hypoproteinic diet showed milder chronic lesions on infection with Schistosoma mansoni than normally fed mice. Here we compare the immune response of well-nourished and undernourished mice with chronic S. mansoni infection. The proliferative response and cytokine (IFN-gamma and IL-5) production of splenocytes from undernourished mice against the soluble egg antigen (SEA) of S. mansoni or concanavalin A was similar to that of well-nourished mice. The levels of SEA-specific IgG1, IgG2b and IgG3 antibodies were significantly higher in the sera of well-nourished mice in comparison with undernourished mice. Undernourished animals also exhibited diminished periovular granuloma size compared to well-nourished infected controls. Our results support the importance of host nutritional status in the humoral immune response of mice and its effects on the development of periovular granulomas in malnourished animals infected with S. mansoni.

Efeitos de um implante de acetato de nomegestrol, um derivado de 19-nor-progesterona, na função tireoidiana / Effects of an implant of nomegestrol acetate, a 19-nor-progesterone derivative, on thyroid function

Este estudo foi realizado para avaliar tri-iodotironina (T3), tiroxina (T4), hormônio estimulante da tireóide (TSH), T3 uptake, T3 livre e T4 livre em usuárias do implante de acetato de nomegestrol (Uniplant). Dezoito voluntárias em idade reprodutiva, que desejavam fazer anticoncepção, foram recrutadas para o estudo e investigadas antes do início do tratamento. Amostras de sangue foram obtidas antes da inserção do implante, para análises hormonais. Em seguida, amostras de sangue foram colhidas 3,6,12 e 24 meses após a inserção do Uniplant. Todas as pacientes usaram contraceptivo não hormonal por um período mínimo de 6 meses, antes da inserção do implante. Os resultados observados no estudo mostraram que não houve diferença significante na tri-iodotironina (T3), tiroxina (T4) e hormônio estimulante da tireóide (TSH), durante dois anos de uso do Uniplant. Nenhuma diferença significante foi encontrada nos níveis de T3 livre, durante dois anos de uso do Uniplant. Um decréscimo significante foi abservado no T3 uptake (p<0,05) no 24º mês e no T4 livre (p<0,05) no 3º mês de uso do Uniplant. todas as alterações observadas no estudo foram inconsistentes e todos os níveis estavam dentro dos limites normais.

Proliferation profile of endometrial polyps in post-menopausal women.

OBJECTIVE: To determine whether or not the presence of c-erbB2 over-expression in endometrial polyps affects the percentage of cells positive for Ki-67 proliferation marker. METHODS: Thirty-five patients with endometrial polyps were submitted to polypectomy by hysteroscopy. Ki-67 and c-erbB2 over-expression were investigated in the polyps by immunohistochemistry. RESULTS: The presence of c-erbB2 over-expression by immunohistochemistry was observed in 80% of endometrial polyps and was associated with higher proliferation rates as determined by the number of positive Ki-67 cell nuclei. In c-erbB2-negative polyps, the proliferation rates were low. CONCLUSION: Ki-67 and c-erbB2 over-expression are frequent in endometrial polyps in post-menopausal women.

Morphological aspects of Schistosoma mansoni adult worms isolated from nourished and undernourished mice: a comparative analysis by confocal laser scanning microscopy.

Malnutrition hampers the course of schistosomiasis mansoni infection just as normal growth of adult worms. A comparative morphometric study on adult specimens (male and female) recovered from undernourished (fed with a low protein diet - regional basic diet) and nourished (rodent commercial laboratory food, NUVILAB) white mice was performed. Tomographic images and morphometric analysis of the oral and ventral suckers, reproductive system and tegument were obtained by means of confocal laser scanning microscopy. Undernourished male specimens presented smaller morphometric values (length and width) of the reproductive system (first, third and last testicular lobes) and thickness of the tegument than controls. Besides that, it was demonstrated that the dorsal surface of the male worms bears large tubercles unevenly distributed, but kept grouped and flat. At the subtegumental region, vacuolated areas were detected. It was concluded that the inadequate nutritional status of the vertebrate host has a negative influence mainly in the reproductive system and topographical somatic development of male adult Schistosoma mansoni, inducing some alterations on the structure of the parasite.

Preliminary results on the effects of CD40/CD40L interactions and SAC-induction on IFN-gamma expression in human schistosomiasis.

In this communication the authors analyzed the pattern of expression of IFN-gamma as a surrogate type 1 response in different clinical forms of schistosomiasis in response to stimulation involving T-cell dependent and T-cell independent pathways, to investigate which pathways were functional in human schistosomiasis, and to further characterize the nature of Th1 response impairment in this parasitic disease.

Efficacy, acceptability, and clinical effects of a low-dose injectable contraceptive combination of dihydroxyprogesterone acetophenide and estradiol enanthate.

A total of 1,904 women, aged 15-38, used an injectable contraceptive combination of 90 mg dihydroxyprogesterone acetophenide with 6 mg estradiol enanthate, given once during each menstrual cycle between the 7th and 10th day, and preferably on the 8th day of the cycle, for a total of 17,576 cycles. Of these 1,904 women, 1,197 completed 12 cycles of use of the injectable combination. One subject became pregnant during the trial, resulting in a cumulative pregnancy rate of 0.07%. Principal reasons for discontinuation were personal, non-medical reasons, such as lost to follow-up, no longer wished to continue, protocol violation, desire to change to another contraceptive method, moved away, or other personal reasons. Mean weight of 1,901 subjects at admission to the trial was 53.5 +/- 0.2 kg and this increased to 54.3 +/- 0.3 kg after 12 cycles of use. Approximately 50% of subjects experienced menstrual bleeding similar to normal throughout the study period. The most frequent menstrual abnormality was irregular bleeding, experienced by approximately one-third of subjects.

Gossypol blood levels and inhibition of spermatogenesis in men taking gossypol as a contraceptive. A multicenter, international, dose-finding study.

The safety and efficacy of gossypol continues to be controversial. The aim of this study was to evaluate gossypol as a contraceptive pill for men at doses lower than those previously prescribed and in men from various ethnic origin. A total of 151 men from Brazil, Nigeria, Kenya, and China were divided into two groups. Both groups received 15 mg gossypol/day for 12 or 16 weeks to reach spermatogenesis suppression. Subjects were then randomized to either 7.5 or 10 mg/day for 40 weeks. In addition, 51 men were enrolled as a control group. In all, 81 subjects attained spermatogenesis suppression. Only one man discontinued treatment because of tiredness. Potassium levels fluctuated within the normal range. FSH increased consistently. Testicular volume decreased, but after discontinuation, values returned to levels not statistically different from admission. Of 19 subjects on the 7.5 mg/day dose group, 12 recovered sperm counts >20 million/mL within 12 months of discontinuing gossypol. In the 10 mg/day group, sperm counts recovered in only 10 of 24 subjects. Eight of the 43 patients remained azoospermic 1 year after stopping gossypol. All men diagnosed with varicocele failed to reverse spermatogenesis suppression. Gossypol blood levels indicated that sperm suppression occurs independently of concentration, whereas spermatogenesis recovery appears to be concentration-dependent. Gossypol may become a medical alternative to surgical vasectomy when the delay in onset of infertility is acceptable. When taken for 1 year, gossypol causes no reduction in sexual desire or frequency of intercourse. The possibility of reversal, occurring in 51% of the men on this regimen within 1 year after stopping gossypol, is an advantage of this compound as compared with surgical sterilization in many parts of the world.

PIP: The safety and efficacy of gossypol continues to be controversial. The aim of this study was to evaluate gossypol as a contraceptive pill for men at doses lower than those previously prescribed and in men from various ethnic origin. A total of 151 men from Brazil, Nigeria, Kenya, and China were divided into two groups. Both groups received 15 mg gossypol/day for 12 or 16 weeks to reach spermatogenesis suppression. Subjects were then randomized to either 7.5 or 10 mg/day for 40 weeks. In addition, 51 men were enrolled as a control group. In all, 81 subjects attained spermatogenesis suppression. Only 1 man discontinued treatment because of tiredness. Potassium levels fluctuated within the normal range. FSH increased consistently. Testicular volume decreased, but after discontinuation, values returned to levels not statistically different from admission. Of 19 subjects in the 7.5 mg/day dose group, 12 recovered sperm counts higher than 20 million/ml within 12 months of discontinuing gossypol. In the 10 mg/day group, sperm counts recovered in only 10 of 24 subjects. 8 of the 43 patients remained azoospermic 1 year after stopping gossypol. All men diagnosed with varicocele failed to reverse spermatogenesis suppression. Gossypol blood levels indicated that sperm suppression occurs independently of concentration, whereas spermatogenesis recovery appears to be concentration-dependent. Gossypol may become a medical alternative to surgical vasectomy when the delay in onset of infertility is acceptable. When taken for 1 year, gossypol causes no reduction in sexual desire or frequency of intercourse. The possibility of reversal, occurring in 51% of the men on this regimen within 1 year after stopping gossypol, is an advantage of this compound as compared with surgical sterilization in many parts of the world.

Use of a single implant of elcometrine (ST-1435), a nonorally active progestin, as a long acting contraceptive for postpartum nursing women.

Because of its unique features, the contraceptive effectiveness and tolerance during breast-feeding of 16-methylene-17 alpha-acetoxy-19-nor-4-pregnene-3,20-dione (elcometrine), delivered within a single subdermal capsule of medical grade polydimethylsiloxane, was investigated. Unlike other progestational steroids, elcometrine has no affinity for androgen and estrogen receptors and is inactive by the oral route. A total of 66 breast-feeding women receiving elcometrine by the subdermal route were enrolled in the study, and 69 women who elected to use Copper-T380 intrauterine devices (IUD) served as control subjects. The women and their infants were observed until the end of the first postpartum year. There were no significant differences in growth and development measurements among the infants in the elcometrine and control groups. The percentage of infants continuing to breast-feed at 3 and 6 months was significantly higher in the elcometrine group. There were no significant differences between the concentration of elcometrine in the mother's blood and milk. At 75 days, blood levels of elcometrine in the infants were near the undetectable and were significantly lower than the levels in maternal blood or milk (p < 0.01). In 15 of 25 infants, blood levels of elcometrine were at the limit of assay sensitivity or undetectable. Two pregnancies occurred in women using IUD, whereas none occurred in those using implants. There were menstrual bleeding irregularities in both groups. A single elcometrine capsule placed subcutaneously at 6-monthly intervals appears to be an effective method of contraception for lactating women and results in blood concentrations of nursing infants at or near undetectable levels.

PIP: Discusses the effects of the use of a single implant of elcometrine (ST-1435), a nonorally active progestin, as a long acting contraceptive for postpartum nursing women in Maternidade Climerio de Oliveira in Salvador, Bahia, Brazil. A total of 135 women aged 18-35 years having a singleton term delivery, fully breast-feeding on demand, planning to breast-feed for 6 months postpartum, and requesting effective contraception were recruited. The method was initiated for 6 weeks postpartum. Results showed that 66 breast-feeding women used elcometrine implants, while 69 women preferred an IUD insertion. The contraceptive efficacy of lactation is high for women breast-feeding on demand, particularly in those who remain in amenorrhea during the 6 months postpartum; in these women, elcometrine implant and IUD prevented pregnancy effectively. Breast-feeding was significantly higher (p 0.05) in the elcometrine group at 3 and 6 months, while at 9 and 12 months there was no statistical difference. The differences in type, frequency of supplementary feeding, and anthropometric measures between the two contraceptive groups were not significant. Menstrual irregularities were present in both groups. Thus, elcometrine could be best alternative and the most effective method of contraception for lactating women.

Cytokine production in acute versus chronic human Schistosomiasis mansoni: the cross-regulatory role of interferon-gamma and interleukin-10 in the responses of peripheral blood mononuclear cells and splenocytes to parasite antigens.

The contribution of interleukin (IL)-10 and interferon (IFN)-gamma to the regulation of type 1 and type 2 cytokine responses was investigated in Brazilians with different clinical forms of schistosomiasis mansoni. Cells from members of a family with acute intestinal schistosomiasis responded to schistosomal soluble egg antigen (SEA) or soluble adult worm antigen preparation (SWAP) with greater amounts of IFN-gamma than did cells from several patients with chronic intestinal schistosomiasis; IL-10 levels were similar. Neutralization of IL-10 had no effect on the SEA-specific IFN-gamma response in patients with acute infection, whereas SWAP-induced IFN-gamma was increased in both groups. Anti-IL-10 also up-regulated SEA-specific IFN-gamma protein and mRNA responses in most splenocyte cultures from hepatosplenic schistosomiasis patients but had no effect on antigen-specific IL-4 or IL-5 production. Neutralization of IFN-gamma resulted in a comparable increase in SWAP-specific IL-10 and IL-5, while IL-4 was not affected. These studies demonstrate that early disease in schistosomiasis is associated with a significant IFN-gamma response and that IL-10 contributes to the suppression of that response during both early and chronic infection.

Should nutrition be considered as a supplementary measure in schistosomiasis control?

The most important data on the relationships between nutritional status and schistosomiasis mansoni are reviewed. The probable impact of such findings on the traditional strategies for control of the disease are discussed. In endemic areas, malnutrition and schistosomiasis seem to be associated. Malnutrition impairs the biological development of the parasite. However, like the parasite, it also depresses the host's immune system, and malnutrition and infection can be mutually aggravating. Recent schistosomiasis-control activities, although apparently well designed, have frequently seemed ineffective because of the multiplicity of factors involved, and have not offered a realistic promise of sustainable and definitive control. However, these actions must be continued and even encouraged because they do lead to reductions in the prevalence of infection and, of particular importance, to reductions in the incidence of the more severe forms of the disease. Improvement of the nutritional status of those who inhabit endemic areas, particularly those on low incomes (who are at relatively high risk of malnutrition and of schistosomiasis), is recommended as a supplementary measure.

Nomegestrol acetate contraceptive implant use by women with sickle cell disease.

OBJECTIVE: To assess the contraceptive effectiveness, safety, and potential health benefits of nomegestrol acetate contraceptive implant use by women with homozygous sickle cell disease (hemoglobin SS). METHODS: This was a prospective observation before and after insertion of nomegestrol acetate of 20 women with sickle cell disease (test group) compared with 10 women with similar sociodemographic backgrounds. Changes in hematologic and biochemical parameters and symptoms of sickle cell crisis were measured during 12 months of observation. RESULTS: After use of nomegestrol acetate for 1 to 9 months, the women in the test group had symptomatic improvement, with no crisis that required hospitalization and no deaths. Sickle cell symptoms persisted in the women in the control group, with 1 recorded death. Increases in F-cell and fetal hemoglobin parallel the observed clinical improvement in the treated women. There were no adverse hematologic or biochemical changes associated with the use of nomegestrol acetate implants. CONCLUSION: Nomegestrol acetate appears to be a safe and appropriate contraceptive for women with sickle cell disease, showing evidence of being a "stimulant" for F-cell reactivation, independent of F hemoglobin total production increase.

A long-term intake of a protein hydrolysate seems to increase the risk of encephalopathy in mice infected with Schistosoma mansoni.

Previous investigations showed that Schistosoma mansoni infection aggravates protein malabsorption in undernourished mice and this can be reverted by administration of casein hydrolysate. The present study was undertaken to evaluate the effects of ingestion of casein hydrolysate for long periods. Albino Swiss mice were divided into eight groups. Diets contained 5% (undernourished) or 20% (controls) casein levels. For each group there were sub-groups ingesting whole or hydrolysed casein for 12 weeks. Infection with S. mansoni developed in half of the animals under each diet. All undernourished mice developed malabsorption. Low albuminemia was detected in infected animals independently of the protein level in the diet. However, albuminemia was lower in infected controls than in undernourished non-infected mice, suggesting a deficient liver protein synthesis. Infected mice fed on a 20% protein hydrolysed diet exhibited low weight gain and high mortality rates. On the other hand, non-infected mice ingesting the same diet had the highest body weights. We are investigating the hypothesis that infected mice, even when fed normal diets, are unable to metabolise large amounts of amino acids due to the liver lesions related to schistosomiasis and as a result die of hepatic coma. In some of them, the excessive accumulation of ammonia in the blood enhances the outcome of an encephalopathy.

Polypectomy and endometrial resection in postmenopausal patients.

STUDY OBJECTIVE: To evaluate the therapeutic efficacy of polypectomy associated with endometrial resection for the treatment of polyps in postmenopausal women. DESIGN: Prospective study (Canadian Task Force classification II-2). SETTING: Private urban hospital with facilities for endoscopic surgery. PATIENTS: Sixty-six women with endometrial polyps. INTERVENTIONS: Sixty-four of the 66 patients underwent polypectomy followed by endometrial resection. One patient had hysterectomy because endometrial biopsy showed serous papillary carcinoma. MEASUREMENTS AND MAIN RESULTS: No major complications were associated with the procedure. Histopathology showed hyperplasia in most polyps. One patient had a papillary uterine carcinoma in the polyp that was not detected by preoperative endometrial biopsy. The women were followed with transvaginal sonography for 1 year after surgery. CONCLUSION: Polypectomy followed by endometrial resection is a very low-risk procedure for postmenopausal patients. There was no recurrence after the first year in women who completed follow-up.

Multicenter, double-blind, comparative clinical study on the efficacy and acceptability of a monthly injectable contraceptive combination of 150 mg dihydroxyprogesterone acetophenide and 10 mg estradiol enanthate compared to a monthly injectable contraceptive combination of 90 mg dihydroxyprogesterone acetophenide and 6 mg estradiol enanthate.

Healthy, regularly menstruating women, aged 14-38 years, were enrolled in a comparative, double-blind, phase III, clinical trial to evaluate the contraceptive efficacy and acceptability of a combination of 90 mg dihydroxyprogesterone acetophenide with 6 mg estradiol enanthate compared to the commercially available contraceptive combination of 150 mg dihydroxyprogesterone acetophenide with 10 mg estradiol enanthate. Subjects received the contraceptive combination intramuscularly, between the 7th and 10th day of each menstrual cycle, during 12 consecutive menstrual cycles. Approximately 60% of the subjects in both groups completed the study. Principal reasons for discontinuation were personal, nonmedical reasons. Principal medical reasons for discontinuation were menstrual-related, irregular bleeding being the most frequent. Differences in menstrual patterns between the two groups did not lead to differences in discontinuation rates. Three contraceptive failures occurred during the trial, one in Group A (90/6 mg) and two in Group B (150/10 mg), indicating that the lower dose formulation is at least as efficient as the higher dose.

Administration of medroxyprogesterone acetate after endomyometrial resection.

STUDY OBJECTIVE: To assess the efficacy of endometrial resection for treatment of menorrhagia in women to whom no preoperative agent was given to prepare the endometrium. DESIGN: Retrospective analysis of patients' records for all endometrial resections in which medroxyprogesterone acetate was used postoperatively. SETTING: Hospital day surgery unit. PATIENTS: Seventy patients with menorrhagia. INTERVENTIONS: The women underwent transvaginal sonography, followed by hysteroscopy and endometrial biopsy. The endometrium was removed using the 27F resectoscope followed by coagulation with the rollerball. Medroxy-progesterone acetate was prescribed for 2 months after surgery. MEASUREMENTS AND MAIN RESULTS: All women achieved a reduction in menstrual flow and 50% reported amenorrhea after endometrial resection. In only two was hysterectomy necessary due to recurrence of menorrhagia. CONCLUSION: Preoperative endometrial preparation was unnecessary when endometrial resection was carried out for treatment of menorrhagia. However, the patients received medroxyprogesterone acetate postoperatively.

Pathogenesis of schistosomal 'pipestem' fibrosis: a low-protein diet inhibits the development of 'pipestem' fibrosis in mice.

Mice maintained on a low protein diet for 30 days and then infected with Schistosoma mansoni for 16 weeks completely failed to develop 'pipestem fibrosis' of the liver, whereas 50% of well nourished controls did. Usually mice with relatively mild and prolonged S. mansoni infection develop two different pathological pictures: one consisting of disseminated portal fibrosis caused by periovular granulomas concentrated at the portal spaces (pipestem fibrosis), the other represented by scattered hepatic granulomas. The reason for this dual response is poorly understood. Combined results from parasitological, histopathological, biochemical and morphometric data revealed that peri-ovular granulomas of undernourished mice were smaller, inflammation was less intense and there was minimal fibrosis in comparison with those of controls, which suggest that a vigorous host response is necessary for the pathogenesis of schistosomal portal fibrosis.