Effects of simvastatin on bone regeneration in the mandibles of ovariectomized rats and on blood cholesterol levels.

The purpose of this study was to evaluate the effects of simvastatin on guided bone regeneration in the mandibles of ovariectomized rats, and to observe their blood cholesterol levels. Seventy female rats were divided into two groups: control and treated, both groups containing normal and ovariectomized rats. A month after ovariectomy a bone defect was created in the mandible, and was covered by a polytetrafluoroethylene membrane. The treated groups received simvastatin orally for 15 or 30 days. The rats were sacrificed 15, 30 or 60 days after surgery, at which time a blood sample was extracted for blood cholesterol level analysis and the mandible was extracted for densitometric, histological and morphometric analysis. All specimens underwent analysis of variance. The ovariectomized animals had higher cholesterol levels than the treated normal animals, and no significant difference was found between the different treatment periods and the sacrifice times. The densitometric, histological and morphometric analysis showed that the treated ovariectomized animals developed more new bone than the control ovariectomized rats, but no significant difference was observed between the treatment periods. It can be concluded that the deficiency of estrogen increased the level of blood cholesterol and that the simvastatin aided new bone formation in the ovariectomized animals.

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.

Intraepithelial alterations in the Guinea pig lateral prostate at different ages after estradiol treatment

The prostate is an accessory gland of the mammal reproductive system with great volume and high functional importance. Many works infer that, in addition to the androgenic ones, the estrogen can be associated with benign prostatic hyperplasia and prostatic cancer, but no conclusive evidence exists on the role of estrogen in normal prostatic and neoplastic tissue. The objective of this work was to evaluate the effects of chronic administration of estradiol benzoate on the lateral prostate of guinea pigs in the pre-pubescent, pubescent, post-pubescent and adult phases, with emphasis on the modifications provoked by this hormone on the glandular epithelium. The analyses of the estradiol-treated and control groups were investigated using histological procedures and transmission electron microscopy. The histopathological analysis of the lateral prostate in the treated group revealed areas where epithelial dysplasia was observed, assuming at some places a pattern of epithelial stratification characteristic of prostatic intraepithelial neoplasia. After ultrastructural analysis, the following were observed: enlargement of the internal membranes, heterogeneity in the cellular types, hypertrophy of the basal cells and apparent decrease of cytoplasmic organelles in some cells of the prostatic intraepithelial neoplasia. Still, a loss of cellular polarity was observed, along with nuclei of various forms, sizes and heights - as well as irregular chromatin distribution patterns. Such alterations were found mainly in pubescent, post-pubescent and adult animals subject to the chronic administration of estradiol. These findings reinforce the already existent data in understanding the role of estrogen in the etiology of prostatic diseases.

Low-grade endometrial stromal sarcoma presenting as vaginal nodule

Endometrial stromal sarcoma is a rare neoplasm of the uterus. Extrauterine locations of this neoplasm, excluding metastases or local extension, are even more unusual and are usually associated with the presence of endometriosis. The authors report a case of endometrial stromal sarcoma presenting as a vaginal wall nodule, without any sign of primary uterine tumor after extensive evaluation or presence of endometriosis. The morphology, immunohistochemical profile, differential diagnoses, and pathogenesis are discussed, as well as a review of the literature on this issue. © 2004 Elsevier Inc. All rights reserved.

Síndrome do climatério

The climateric is characterized by progressive hipoestrogenism and by tissue and functional alterations that leads the women to aging. The diagnosis approach needs to consider the symptoms originated by estrogenic deficiency and by the more prevalent chronic diseases in this lifetime, for instance, among others, the cardiovascular and osteoporosis diseases, witch need a systematic screening. The therapeutic management must consider the proposition of healthy life habits and, when indicated, pharmacological treatment for estrogenic deficiency or for anothers comorbidities existent. The estroprogestative hormonal therapeutic is a valuable tool to provide health and better quality of life, once obeyed the individualized criterion of the cases, doses, hormonal composition and mainly of the opportunity of intervention. There are nonhormonal alternatives to treat the menopausal symptoms, as the antidepressives and phytoestrogens. It's also advised to combine with regular physical activities and adequate calcium intake. © Copyright Moreira Jr. Editora. Todos os direitos reservados.

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.

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.

Mensuração de hormônios andrógenos, estrógeno, fosfatase ácida prostática (PAP) e antígeno prostático específico (PSA) em cães adultos com próstata normal e hiperplásica

Prostatic diseases have been a common problem in middle age and older intact male dogs. Among these, benign prostatic hyperplasia (BHP) is the most frequent, age-related and hormonal-dependent condition of human and canine prostate. Blood samples were collected from 37 male intact dogs, tree years old dogs or more to determine androgens, estrogen, prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) according to histopathological aspects. Low levels of estrogen and high levels of prostatic specific antigen (PSA) were founded in dogs with BHP, respectively. Seric and urinary PAP levels were high in dogs with hyperplasia.

Orphan nuclear receptor NGFI-B forms dimers with nonclassical interface

The orphan receptor nerve growth factor-induced B (NGFI-B) is a member of the nuclear receptor's subfamily 4A (Nr4a). NGFI-B was shown to be capable of binding both as a monomer to an extended half-site containing a single AAAGGTCA motif and also as a homodimer to a widely separated everted repeat, as opposed to a large number of nuclear receptors that recognize and bind specific DNA sequences predominantly as homo- and/or heterodimers. To unveil the structural organization of NGFI-B in solution, we determined the quaternary structure of the NGFI-B LBD by a combination of ab initio procedures from small-angle X-ray scattering (SAXS) data and hydrogen-deuterium exchange followed by mass spectrometry. Here we report that the protein forms dimers in solution with a radius of gyration of 2.9 nm and maximum dimension of 9.0 nm. We also show that the NGFI-B LBD dimer is V-shaped, with the opening angle significantly larger than that of classical dimer's exemplified by estrogen receptor (ER) or retinoid X receptor (RXR). Surprisingly, NGFI-B dimers formation does not occur via the classical nuclear receptor dimerization interface exemplified by ER and RXR, but instead, involves an extended surface area composed of the loop between helices 3 and 4 and C-terminal fraction of the helix 3. Remarkably, the NGFI-B dimer interface is similar to the dimerization interface earlier revealed for glucocorticoid nuclear receptor (GR), which might be relevant to the recognition of cognate DNA response elements by NGFI-B and to antagonism of NGFI-B-dependent transcription exercised by GR in cells. Published by Cold Spring Harbor Laboratory Press. Copyright © 2007 The Protein Society.

Efeito do raloxifeno sobre a densidade mamográfica em mulheres na pós-menopausa

PURPOSE: to evaluate changes in mammographic breast density in postmenopausal women using raloxifene. METHODS: in this clinical trial, 80 women (mean age=61.1 years) were studied prospectively. Forty patients received 60 mg/day raloxifene, and 40 women comprised the non-treated group (control), paired by age and time of menopause. The treated group was composed of patients with osteoporosis of the lumbar spine. Those with history of breast surgery and users of hormone therapy up to six months prior to the study were excluded. The breast density was assessed qualitatively (subjective) and quantitatively (objective) in two moments, initial and final, after a 6-month follow-up. The 320 mammograms (craniocaudal and oblique) were interpreted qualitatively by the Breast Imaging Reporting and Data System (BI-RADS) classification and quantitatively by digital scanning and computer-assisted segmentation. For statistical analysis t-test, Wilcoxon Mann-Whitney, Spearman correlation and the kappa index were used. RESULTS: on the initial statistical comparison, the groups were considered homogenous for the variables: analyzed age, time of menopause, parity, breast feeding, previous hormonal therapy and body mass index. Baseline breast density, by qualitative and quantitative methods, correlated negatively with the age in both groups (p<0.05). Concerning the other variables, there was no correlation. After six months, no alteration was observed in the mammographic breast density in 38 women of raloxifene group and 38 of the control group, by qualitative method. However, by quantitative method, no alteration was observed in 30 women of the raloxifene group and 27 controls (p>0.05). It was observed a weak agreement rate (kappa=0.25) between the BI-RADS classification and digital scanning/computer-assisted segmentation. CONCLUSIONS: in post-menopausal women with osteoporosis, submitted to raloxifene treatment for six months, no alterations were observed on the mammographic breast density.

Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients

The risk for venous thromboembolism (VTE) in medical patients is high, but risk assessment is rarely performed because there is not yet a good method to identify candidates for prophylaxis. Purpose: To perform a systematic review about VTE risk factors (RFs) in hospitalized medical patients and generate recommendations (RECs) for prophylaxis that can be implemented into practice. Data sources: A multidisciplinary group of experts from 12 Brazilian Medical Societies searched MEDLINE, Cochrane, and LILACS. Study selection: Two experts independently classified the evidence for each RF by its scientific quality in a standardized manner. A risk-assessment algorithm was created based on the results of the review. Data synthesis: Several VTE RFs have enough evidence to support RECs for prophylaxis in hospitalized medical patients (eg, increasing age, heart failure, and stroke). Other factors are considered adjuncts of risk (eg, varices, obesity, and infections). According to the algorithm, hospitalized medical patients ≥40 years-old with decreased mobility, and ≥1 RFs should receive chemoprophylaxis with heparin, provided they don't have contraindications. High prophylactic doses of unfractionated heparin or low-molecular-weight-heparin must be administered and maintained for 6-14 days. Conclusions: A multidisciplinary group generated evidence-based RECs and an easy-to-use algorithm to facilitate VTE prophylaxis in medical patients. © 2007 Rocha et al, publisher and licensee Dove Medical Press Ltd.

The influence of ovariectomy, simvastatin and sodium alendronate on alveolar bone in rats

Bisphosphonates are currently used in the treatment of many diseases involving increased bone resorption such as osteoporosis. Statins have been widely used for the treatment of hypercholesterolemia and recent studies have shown that these drugs are also capable of stimulating bone formation. The purpose of this study was to evaluate thel influence of an estrogen deficient state and the effects of simvastatin and sodium alendronate therapies on alveolar bone in female rats. Fifty-four rats were either ovariectomized (OVX) or sham operated. A month later, the animals began to receive a daily dose of simvastatin (SIN - 25 mg/kg), sodium alendronate (ALN - 2 mg/kg) or water (control) orally. Thirty-five days after the beginning of the treatment, the rats were sacrificed and their left hemimandibles were removed and radiographed using digital X-ray equipment. The alveolar radiographic density under the first molar was determined with gray-level scaling and the values were submitted to analysis of variance (α = 5%). Ovariectomized rats gained more weight (mean ± standard deviation: 20.06 ± 6.68%) than did the sham operated animals (12.13 ± 5.63%). Alveolar radiographic density values, expressed as gray levels, were lowest in the OVX-water group (183.49 ± 6.47), and differed significantly from those observed for the groups receiving alendronate (sham-ALN: 193.85 ± 3.81; OVX-ALN: 196.06 ± 5.11) and from those of the sham-water group (193.66 ± 4.36). Other comparisons between groups did not show significant differences. It was concluded that the ovariectomy reduced alveolar bone density and that alendronate was efficient for the treatment of this condition.

Recurrent urinary tract infections: Evaluation of the prophylactic efficacy of urinary antiseptics methenamine and methylthioninium chloride

Introduction: Urinary tract infection (UTI) is a very common condition in clinical practice, affecting an estimated 50% of all adult women during a lifetime. The most common causative agent is E. coli; UTI may also be caused by S. saprophyticus, Enterobacteria (Klebsiella sp and Serratia sp.), Enterococcus sp., and P aeruginosa. Recurrent UTIs occur at least twice per semester or three times a year. Prophylactic measures to prevent recurrent UTIs include changes in contraception methods, cranberry products, increased fluid intake, urination after intercourse, vaginal estrogen therapy for post-menopausal women, antibiotics, and urinary tract antiseptic agents. Objectives: To evaluate the use of a combination of methenamine and methyl-thioninium chloride in the prophylaxis of recurrent uncomplicated lower UTIs, with respect to: • Signs and symptoms of UTI • Etiologic agent(s) • Recurrence rates • Need for antibiotic therapy in case of recurrence • Incidence of adverse events associated with the treatment, including any reported alterations of laboratory tests Materials & methods: A descriptive, analytic, restrospective study was performed at Hospital Universitário Constantino Otaviano - UNIFESO. Medical charts from patients presenting recurrent uncomplicated lower UTI attended from 2001-present were analyzed, including the following information: Demographic data (age, gender, weight, ethnicity, living conditions): medical history/signs and symptoms of UTI; identification of treatment and dosing regimens; treatment duration; recurrence rates and need for antibiotic therapy in case of recurrence; other medications prescribed; and records of adverse events. Results: E. coli was identified as etiologic agent in 80% of the patients. Following antibiotic therapy, all patients received prophylactic treatment with the combination of methenamine and methylthioninium chloride. Treatment duration ranged from three to six months. Adverse events were observed in 13/60 patients (21.7%). At the end of the respective treatment periods, a statistically significant (p<0.0001) number of patients showed no UTI recurrence. Conclusion: Based on the results from the collected data, we conclude that an orally administered combination of methenamine and methylthioninium chloride is safe and effective in the prophylactic treatment of recurrent uncomplicated lower urinary tract infection. © Copyright Morelra Jr. Editora.

Tamoxifen inhibits transforming growth factor-α gene expression in human breast carcinoma samples treated with triiodothyronine

Objectives: To examine the effects of triiodothyronine (T3), 17β-estradiol (E2), and tamoxifen (TAM) on transforming growth factor (TGF)-α gene expression in primary breast cancer cell cultures and interactions between the different treatments. Methods and results: Patients included in the study (no.=12) had been newly diagnosed with breast cancer. Fresh human breast carcinoma tissue was cut into 0.3-mm slices. These slices were placed in six 35-mm dishes on 2-ml organ culture medium. Dishes received the following treatments: dish 1: ethanol; dish 2: T3; dish 3: T3+TAM; dish 4: TAM; dish 5: E2; dish 6: E2+TAM. TGF-α mRNA content was normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA levels. All tissues included in this study were positive for estrogen receptor (ER) and thyroid hormone receptor expression. Treatment with T3 for 48 h significantly increased TGF-α mRNA levels compared to controls (15-fold), and concomitant treatment with TAM reduced expression to 3.4-fold compared to controls. When only TAM was added to the culture medium, TGF-α mRNA expression increased 5.3-fold, significantly higher than with all other treatment modalities. Conclusion: We demonstrate that TGF-α mRNA expression is more efficiently upregulated by T3 than E2. Concomitant treatment with TAM had a mitigating effect on the T3 effect, while E2 induced TGF-α upregulation. Our findings show some similarities between primary culture and breast cancer cell lines, but also some important differences: a) induction of TGF-α, a mitogenic protein, by TAM; b) a differential effect of TAM that may depend on relative expression of ER α and β; and c) supraphysiological doses of T3 may induce mitogenic signals in breast cancer tissue under conditions of low circulating E2. ©2008, Editrice Kurtis.