Influence of cholecalciferol (Vitamin D3) on the course of experimental systemic lupus erythematosus in F1 (NZBxW) mice

The course of systemic lupus erythematosus (SLE), an autoimmune disease, is markedly affected by hormones such as estrogen and prolactin. It is well known that heavy exposure to sunlight has deleterious effects on SLE, triggering episodes of the disease. Classical explanations for this occurrence suggest that UV radiation damages DNA, which becomes immunogenic, or induces exposure of the Ro antigen in keratinocytes. In recent years, it has been shown that vitamin D3 has important effects on the immune system. Thus, we proposed an alternative hypothesis, suggesting that UV radiation, by promoting vitamin D3 synthesis, could be a factor aggravating the course of SLE after exposure to sunlight. To test this hypothesis, we injected F1(NZBxW) mice, which are prone to developing SLE, with vitamin D3, and we demonstrated a worsening of the histopathological findings in the kidney. (C) 2000 Wiley-Liss, Inc.

Estudo comparativo das complicações terapêuticas no Lúpus Eritematoso Sistêmico e nas glomerulopatias idiopáticas.

PURPOSE: To evaluate the therapeutic complications due to the use of immunosupressors in patients with nephropathy. METHODS: 76 patients who had used steroids and cyclophosphamide were retrospectively studied. The cases were divided into three groups: G1= 15 patients with Systemic Lupus Erythematosus without renal lesion; G2= 33 patients with lupus nephritis and G3= 28 patients with nephrotic syndrome owing to idiopathic glomerulopathy. RESULTS: There were no differences related to time of follow up (G1= 42.4 +/- 51, G2= 52.3 +/- 51, G3= 41.8 +/- 47.8 months), total used dosage of steroids (G1= 20, G2= 28, G3= 16 grams) and time of drug use (G1= 20, G2= 26, G3= 14.5 months). About cyclophosphamide use, there was no difference in the percentage of patients who used it (13% in G1, 51% in G2, 28% in G3), but the patients from G1 received lower total dosage than those from G2 (p<0.05). Cushingoid appearance, epigastric distress, psychiatric disorders, diabetes mellitus and ocular alterations occurred in all the three groups, with no statistically significant differences. The infections complications, those considered more severe clinically, were more frequent in G2 (G1= 6%, G2= 15%, G3= 0% - p<0.05), the same occurring with the deaths (7% in G1, 30% in G2, 0% in G3 - p<0.05). CONCLUSION: In patients with lupus nephritis there were more infections complications owing to prolonged immunosuppresion what may indicate a severity marker of this type of lesion.

A review of antifertility folkloric plants tested in laboratory animals

The use of natural active principals is widespread among a great proportion of the rural population, or by people who do not have easy access to medical assistance. These active principles are used as food or medicines, and even for purposes of contraception. It becomes necessary to establish a relationship between the folklore habits and current information on the nature of anti-fertility substances, and knowledge of their mechanisms. Anti-fertility agents may exert their actions in a number of areas, (hypothalamus, anterior pituitary, oviduct, uterus, and vagina), inhibiting synthesis and/or liberation of hormones (follicle-stimulating, luteinizing, and steroid hormones), ovulation, ovum transportation, and implantation process. Therefore, a review of literature was carried out, including of several plants used by women as abortifacient and anti-fertility agents to compare their effects with those obtained among laboratory animals.

Performance and physiological parameters of broiler chickens subjected to fasting on the neonatal period

Broiler chicks aged 12 h after hatching were allotted according to a block design in a 7 x 2 factorial schedule of 14 treatments and four replications of 50 chicks each one. The main experimental factors were fasting for 0, 6, 12, 18, 24, 30, and 36 h after chick placement and sex. Independent of sex, fasting had a negative linear effect on weight and productivity of broilers at market age (42 d) without affecting feed conversion or mortality index. Groups subjected to 18 and 36 h of fasting after placement, corresponding to 30 and 48 h posthatching fasting, had lower biometrical values for small intestine (length, weight, and size; villus height; and crypt depth) than chicks fed immediately after placement. According to the Pearson test, BW of birds at 21 and 42 d were significantly correlated to BW at 7 d (r = 0.77) and 21 d (r = 0.45), respectively. Males performed better than females but had higher mortality rates. Fasting did not influence serum concentrations of corticosterone or sexual steroid hormones. Nevertheless, early signs of sexual dimorphism arose from the high estradiol (E2) concentration on female serum. Heterophil:lymphocyte ratio was not different among treatments, indicating that early fasting did not seem to be a stress factor 21 or 42 d after fasting. The results suggested a maximum fasting of 24 h after hatching in order to preserve broiler productivity at market age.

Changes in norepinephrine and epinephrine concentrations in adrenal gland of the rats submitted to acute immobilization stress

Catecholamines act as neurotransmitters and hormones. Studies conducted to understand the synthesis and metabolism of these monoamines during stress have been the main concern of many authors. This work proposes to investigate the time course of changes in epinephrine and norepinephrine concentration in adrenal gland obtained from rats submitted to acute immobilization stress. The results of the present study indicate that acute immobilization stress during 5 and 15min did not provoke changes in epinephrine and norepinephrine concentrations in adrenal gland in relation to the control group. Such results are justified due to the short time of the stress, showing that the stress did not provoke physiological alteration. The epinephrine and norepinephrine concentrations in adrenal gland increased significantly after the immobilization session in stressed groups during 30 and 50min as compared to control group. This increase probably is due to the emotional component of the immobilization stress. In this way, we suggested that the immobilization stress provoke increase in the biosynthesis of catecholamines in the adrenal gland from rats. However, the results shows that a maximum increase is reached at 30min of immobilization stress and then a decrement of catecholamines levels starts at 50min of the experimental design. This decline in catecholamines level may be consequence of adaptation to stress situations, an increase of the activity of the uptake systems and/or metabolization of catecholamines. In conclusion, these results suggest an effective participation of the adrenal glands to maintain the homeostasis of organism to the stressful conditions. © 2003 Elsevier Ltd. All rights reserved.

Endocrine Disruptors and Hypothalamic Sexual Differentiation

The so-called endocrine disruptors have been described as compounds which interfere with the estrogen action in their receptors and may exert a crucial role in the development of the reproductive tract and in the brain sexual differentiation. Thus, conducts and/or exposure to these drugs in the perinatal period that apparently do not endanger the neonate may cause side effects. During embrionary development, the gonads, through discharge of a small quantity of reproductive hormones, will guarantee the phenotype of male or female at birth, as well as actuate in specific areas sexual differentiation of the central nervous system. Several experimental models have shown an interference of drugs acting as endocrine disruptors in hypothalamic sexual differentiation. Thus, reproductive function is impaired by exposure to estrogen in the perinatal life of rats and the mechanisms involved in this effect are distinct for males and females. Perinatal exposure to drugs which may be considered endocrine disrupters may induce an incomplete masculinization and defeminization of the central nervous system. Alterations in these processes, if present, generally are perceived only at puberty or adult reproductive life. These later alterations may include anomalies in the process of fertility or in sexual behavior.

Prevalence of yeasts in the oral cavity of children treated with inhaled corticosteroids

The aim of this study was to observe the prevalence of Candida spp. in the oral cavity of children undergoing treatment with inhaled corticosteroids. Thirty children treated with inhaled corticosteroids and thirty control children were studied. Saliva samples were collected through oral rinses with phosphate buffered saline (PBS). The samples were plated on Sabouraud's dextrose agar and incubated at 37 degrees C for 48 h. After this period, the number of colony-forming units per ml (cfu/ml) of saliva was calculated. The isolates were identified by phenotypic characterization. Candida spp. was isolated from 43.33% of the samples of children treated with corticosteroids, with a mean of 780 cfu/ml of saliva, and from 30% of the samples of the control group, with a mean of 560 cfu/ml of saliva. No significant statistical difference was observed between the groups. C. albicans was the prevalent species in both groups, followed by C. guilliermondii, C. parapsilosis and C. stellatoidea. Furthermore, Rhodotorula rubra and C. lusitaniae were also isolated from the treated group. We concluded that there was no significant increase in the prevalence and number of Candida spp. in the oral cavity of children treated with inhaled corticosteroids.

Antenatal corticosteroid use and clinical evolution of preterm newborn infants

Objectives: To describe the use of antenatal corticosteroid and clinical evolution of preterm babies. Methods: An observational prospective cohort study was carried out. All 463 pregnant women and their 514 newborn babies with gestational age ranging from 23 to 34 weeks, born at the Brazilian Neonatal Research Network units, were evaluated from August 1 to December 31, 2001. The data were obtained through maternal interview, analysis of medical records, and follow-up of the newborn infants. Data analysis was performed with the use of chi-square, t Student, Mann-Whitney, and ANOVA tests and multiple logistic regression, with level of significance set at 5%. Results: Treatment was directly associated with the number of prenatal visits, with maternal hypertension and with the antenatal use of tocolytic agents. Babies from treated pregnant women presented better Apgar scores at the 1st and 5th minute, reduced need for intervention in the delivery room and lower SNAPPE II. They were born with higher birth weight, longer gestational age and needed less surfactant use, ventilation, and oxygenation time. After multiple logistic regression, the use of antenatal corticosteroid independently improved birth conditions, decreased ventilation time, being related to increased occurrence of neonatal sepsis. Conclusions: The use of corticosteroid was associated with better prenatal care and birth conditions, better preterm evolution but higher risk of infection. Copyright © 2004 by Sociedade Brasileira de Pediatria.

Conformational basis for the biological activity of TOAC-labeled angiotensin II and bradykinin: Electron paramagnetic resonance, circular dichroism, and fluorescence studies

N-Terminally and internally labeled analogues of the hormones angiotensin (AII, DRVYIHPF) and bradykinin (BK, RPPGFSPFR) were synthesized containing the paramagnetic amino acid 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4- carboxylic acid (TOAC). TOAC replaced Asp 1 (TOAC 1-AII) and Val 3 (TOAC 3-AII) in AII and was inserted prior to Arg 1 (TOAC 0-BK) and replacing Pro 3 (TOAC 3-BK) in BK. The peptide conformational properties were examined as a function of trifluoroethanol (TFE) content and pH. Electron paramagnetic resonance spectra were sensitive to both variables and showed that internally labeled analogues yielded rotational correlation times (TC) considerably larger than N-terminally labeled ones, evincing the greater freedom of motion of the N-terminus. In TFE, τ C increased due to viscosity effects. Calculation of τ Cpeptide/τ CTOAC ratios indicated that the peptides acquired more folded conformations. Circular dichroism spectra showed that, except for TOAC 1-AII in TFE, the N-terminally labeled analogues displayed a conformational behavior similar to that of the parent peptides. In contrast, under all conditions, the TOAC 3 derivatives acquired more restricted conformations. Fluorescence spectra of All and its derivatives were especially sensitive to the ionization of Tyr 4. Fluorescence quenching by the nitroxide moiety was much more pronounced for TOAC 3-AII The conformational behavior of the TOAC derivatives bears excellent correlation with their biological activity, since, while the N-terminally labeled peptides were partially active, their internally labeled counterparts were inactive [Nakaie, C. R., et al., Peptides 2002, 23, 65-70]. The data demonstrate that insertion of TOAC in the middle of the peptide chain induces conformational restrictions that lead to loss of backbone flexibility, not allowing the peptides to acquire their receptor-bound conformation. © 2004 Wiley Periodicals, Inc.

Tamoxifen down-regulates CaMKII messenger RNA levels in normal human breast tissue

Tamoxifen was proven to reduce the incidence of breast cancer by 49% in women at increased risk of the disease in the Breast Cancer Prevention Trial. In order to identify potential candidates to explain the preventive effect induced by tamoxifen on breast cancer, normal breast tissue obtained from 42 fibroadenoma patients, randomly assigned to receive placebo or tamoxifen, was analyzed by the reverse Northern blot and RT-PCR techniques. The cDNA fragments used on Northern blot membranes were generated by the Human Cancer Genome Project funded by the Ludwig Institute for Cancer Research and FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil). Total RNA was obtained from normal breast tissue from patients with clinical, cytological and ultrasound diagnosis of fibroadenoma. After a 50-day treatment with tamoxifen (10 or 20 mg/day) or placebo, normal breast tissue adjacent to the tumor was collected during lumpectomy with local anesthesia. One differentially expressed gene, Calcium/calmodulin-dependent protein kinase II (CaMKII), was found to be down-regulated during TAM treatment. CaMKII is an ubiquitous serine/threonine protein kinase that has been implicated in the diverse effects of hormones utilizing Ca2+ as a second messenger as well as in c-fos activation. These results indicate that the down-regulation of CaMKII induced by TAM might represent alternative or additional mechanisms of the action of this drug on cell cycle control and response to hormones in normal human breast tissue.

Chronic renal failure in male and female rats

Gender influences the progression of chronic renal failure (CRF). We studied male (M) and female (F) Wistar rats for 90 days: castrated (CMc, n=7; CFc, n=6) and non castrated controls (CM, n=9; CF, n=6); castrated (CRFMc, n=8; CRFFc, n=6) and non castrated animals submitted to 5/6 nephrectomy (CRFM, n=13; CRFF, n=6). Data are expressed as mean ± SEM. Proteinuria (PTN) was higher in CRFM (554 ± 69mg/24h) compared to CRFMc (277 ± 85 mg/24h), but not in females (CRFF=193 ± 20mg/24h, CRFFc=164 ± 71mg/24h). Mesangial fractional volume increased in all CRF animals. CRF animals showed an increase of glomerular sclerosis index (GSI) and tubulointerstitial damage (TID) but in a smaller proportion in male castrated animals; the opposite occurred with females: castration induced an increase of these parameters. CRF animals showed increased cortical and glomerular fibronectin (FN) rates. Castration decreased glomerular and cortical FN rates in CRFM but not in females. In conclusion, proteinuria was higher in CRFM and probably led to glomerular and interstitial damage, as well as to FN accumulation, castration seems to protect against development of PTN, TID and FN accumulation in males. Castrated female rats presented mesangial expansion, with no changes in PTN, TID and FN rates. It seems that female sex hormones do not protect against renal disease progression, instead, we suggest that male sex hormones lead to acceleration of CRF.

Diagnosis of 5α-reductase type 2 deficiency: Contribution of anti-Müllerian hormone evaluation

Aim: To evaluate anti-Müllerian hormone (AMH) levels in patients with clinical and molecular diagnosis of 5α-reductase 2 deficiency. Patients and methods: Data from 14 patients whose age ranged from 21 days to 29 years were analyzed according to age and pubertal stage. Sexual ambiguity was rated as Prader III in 11 patients. LH, FSH, testosterone (T), dihydrotestosterone (DHT) and AMH serum levels were measured in all but two patients, who had been previously submitted to gonadectomy; T and DHT were also measured in 20 age-matched controls. Results: Gonadotropin levels were normal in all but one patient who retained gonads (six of whom had reached puberty) and T/DHT ratio was elevated in all patients when compared to controls. All prepubertal patients had AMH levels < -1 SD for age, while most pubertal patients had AMH levels compatible with pubertal stage. Conclusions: Prepubertal patients with 5α-reductase 2 deficiency have AMH values in the lower part of the normal range. These data indicate that T does not need to be converted to DHT to inhibit AMH secretion by Sertoli cells. © Freund Publishing House Ltd., London.

Efficacy of hormone therapy with and without methyltestosterone augmentation of venlafaxine in the treatment of postmenopausal depression: A double-blind controlled pilot study

Objective: This study evaluated the augmentation of venlafaxine with hormone therapy in the treatment of postmenopausal depression. The hormones evaluated were estrogen (0.625 mg) in combination with medroxyprogesterone acetate (2.5 mg) and methyltestosterone (2.5 mg). Design: Seventy-two menopausal women (mean age: 53.6 ± 4.27 years) diagnosed with depression (Montgomery-Åsberg Depression Rating Scale [MADRS] scores ≥ 20) were treated with venlafaxine and one of the following hormone therapy combinations, in a double-blind regimen: estrogen + medroxyprogesterone + methyltestosterone (group 1, n = 20); estrogen + medroxyprogesterone acetate (group 2, n = 20); methyltestosterone only (group 3, n = 16); and no hormone therapy (group 4, n = 16). Study duration was 24 weeks. Primary efficacy outcome was remission according to the MADRS, whereas secondary efficacy measures included the Clinical Global Impression (CGI), Blatt-Kupperman Index, and Women's Health Questionnaire (WHQ). Results: Forty-eight patients completed the study. All groups showed significant improvement from baseline. Group 3 demonstrated significant improvement on the MADRS compared with placebo (group 4) at weeks 20 (P = 0.048) and 24 (P = 0.030); effect size 8.04 (0.83; 15.26) (P = 0.029), but also had the highest dropout rate. Groups 1 and 3 had significant CGI improvement rates compared with placebo: 42.23% (P = 0.012) and 44.45% (P = 0.08), respectively. There were no differences in the WHQ or BKI scores among the groups. Conclusions: Methyltestosterone 2.5 mg had the highest effect size compared with placebo, but the high dropout rate prevented its efficacy from being determined. Estrogen plus medroxyprogesterone, combined with methyltestosterone or otherwise, demonstrated a trend toward increased efficacy of venlafaxine. Further larger-scale clinical trials are needed to elucidate the findings of this pilot study. © 2006 by The North American Menopause Society.

Estados hiperprolactinêmicos - Inter-relações com o psiquismo

Hyperprolactinemia is the most frequent endocrine disorder of the hypothalamus-hypophysis axis observed in women of reproductive age. It is characterized by elevated serum prolactin levels. Prolactin production is regulated by the inhibitory action of a neurotransmitter, dopamine. Clinical manifestations include irregular menstrual cycle, amenorrhea, galactorrhea, infertility and libido decrease, but psychological symptoms, especially anxiety and depression, have also been associated with hyperprolactinemia. Nonetheless, few studies about this condition are available. In the pathogenesis of psychiatric disorders, prolactin may have either a direct action on the central nerve system or an indirect effect via gonadal hormones or function as independent factors as a result of dopamine depletion. Thus, since the prevalence of psychiatric disorders in patients with hyperprolactinemia was detected, it was concluded that further studies are necessary to investigate the basis of a potential relationship between both hyperprolactinemic and psychiatric conditions.

Transtorno bipolar do humor e gênero

Although the bipolar disorder (BD) occurs almost with the same frequency in both genders, the phenomenology and the outcome of the illness differ between them. Nevertheless, there is evidence that women with BD show, more than men, delayed beginning, especially in their fifth decade, more rapid cycling outcome, more depressive episodes, more dysphoric mania, more mixed states and more BD type II. Even so, the findings are not always consistent. Although the risk of comorbidities in BD includes, for both the sorts, excessive alcoholic consumption and drugs, bipolar men would have greater probability of being alcohol dependent, of not seeking treatment and of committing suicide. Suggested hypotheses to explain such differences vary from those centered in cultural or psychological aspects to those that focus on the steroids hormones, and other hormones such as cortisol, thyroid hormones and even on the cerebral anatomy. The reproductive cycle (menstrual cycle, pregnancy and menopause) influences on the BD phenomenology and its relevance to the therapeutical options in the treatment of the BD in women are presented in the last part of this review. Further investigations must to be done in order to clarify this controversy. However, up to now the data indicate that estrogen therapy is not to be primarily indicated to prevent depression, Alzheimer disease or cognition impairment.