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.

Oral stomatitis induced by endogenous progesterone: Case report

Oral stomatitis induced by endogenous progesterone is a rare clinical condition which may be associated with cutaneous involvement. That is probably due to the peak of progesterone production during the luteal phase of the menstrual cycle. In the present case report, a 21-year-old patient displayed recurrent ulcerative lesions located on the buccal mucosa or the upper lip, on a monthly basis since the age of 15. Such lesions would always manifest themselves on the second day until the end of the menstrual cycle. © 2009 Informa UK Ltd All rights reserved.

Brazilian experience with the medium-term multi-organ bioassay: Scientific and regulatory developments

In 1996 the Brazilian Institute for the Environment (IBAMA) officially adopted a variation of the multiorgan initiation-promotion DMBDD bioassay as a valid source of evidence of the carcinogenic potential of pesticides. The protocol adopted by IBAMA was a modification of the one originally proposed by researchers led by Nobuyuki Ito, from the Nagoya City University Medical School. Among the modifications established in the Brazilian protocol were the use of both sexes of the outbreed Wistar strain of rats and two positive control test chemicals. The adoption of the modified DMBDD protocol was instrumental during the last decade for qualifying technical people and to spread knowledge on chemical carcinogenesis in Brazil.

Intervenções farmacêuticas na atenção à saúde mental: Uma revisão

Uma revisão dirigida foi realizada nas bases de dados IBECS, LILACS e MEDLINE, até fevereiro/2011, para identificar intervenções farmacêuticas (IF) na atenção farmacêutica em saúde mental e os seus resultados. Para a busca utilizaram-se os descritores em saúde: Pharmaceutical Care, Pharmaceutical Services, Medication Adherence, Pharmacists, Mental Health, Mental Health Services, Mental Health Assistance, Community Mental Health Services, Mentally Ill Persons andMental Disorders. Identificaram-se 1686 publicações, das quais 21 contemplaram os critérios de inclusão. Após exploração do material, apenas cinco estudos tratavam-se de IF. Todos foram conduzidos no nível secundário de atenção, com abordagem individual, por meio do acompanhamento da terapia (3), intervenção educativa por cartas a médicos e pacientes (1), aconselhamento farmacêutico presencial e remoto e inserção de terapia com sistema transdérmico de nicotina (1). Os resultados, tais como promoção da adesão e resolução de problemas relacionados a medicamentos foram positivos para a terapêutica. No entanto, é necessário que as IF monitorem os parâmetros clínicos, as mudanças de hábitos, a melhora na qualidade de vida e os aspectos farmacoeconômicos a fim de avaliar os seus impactos. Palavras-chave:Atenção Farmacêutica. Assistência Farmacêutica. Adesão à Medicação. Farmacêuticos. Saúde Mental. ABSTRACT Pharmaceutical interventions in mental health services: a review A directed review was performed in IBECS, LILACS and MEDLINE databases, until February/2011, in order to identify the studies which developed pharmaceutical interventions (PI) in pharmaceutical care in mental health services and estimated their results. The search was carried out using the follow health science descriptors: Pharmaceutical Care, Pharmaceutical Services, Medication Adherence, Pharmacists, Mental Health, Mental Health Services, Mental Health Assistance, Community Mental Health Services, Mentally Ill Persons andMental Disorders. It was identified 1686 manuscripts, of whose 21 contemplated the inclusion criteria. After the content analysis of the eligible manuscripts, only five developed PI. All of them were conducted in the second level of health care, with individual approach, through: therapy follow-up (3), educational interventions by letters to physicians and patients (1), presence or remote pharmaceutical counseling and inclusion of therapy with nicotine transdermal patch (1). The data, such as adherence promotion and solving drug related problems, were positive for the therapeutic. However, it is necessary that the PI monitor the clinical parameters, the habit changes, the improvement in the quality of life and the pharmacoeconomic aspects, in order to assess their impacts. Keywords: Pharmaceutical Care. Pharmaceutical Services. Medication Adherence. Pharmacists. Mental Health. Mental Disorders.

Appendiceal endometriosis as a rare cause of abdominal pain - a case report and literature review

Endometriosis is an estrogen-dependent inflammatory disease, common in young women, characterized by the presence of endometrial tissue outside the uterine cavity. This ectopic endometrial tissue is most commonly found in the ovaries, peritoneum, uterosacral ligaments and rectovaginal cul-de-sac, with extremely rare involvement of the appendix. The main symptom is chronic abdominal pain, and the diagnosis is often made later, after the result of the histopathological examination. This study reports a 34-year-old patient complaining of chronic pelvic pain refractory to medical treatment, having undergone diagnostic laparotomy. During the surgery, we observed the presence of endometrioma fixed to the uterine wall, and the appendix was enlarged, but without evidence of inflammation. Endometrioma resection and appendectomy were performed, with good postoperative recovery. The anatomopathological exam showed endometriosis in the cecal appendix.

Primordial germ cells (spermatogonial stem cells) of bullfrogs express sex hormone-binding globulin and steroid receptors during seasonal spermatogenesis

In vertebrate species, testosterone seems to inhibit spermatogonial differentiation and proliferation. However, this androgen can also be converted, via aromatase, into estrogen which stimulates spermatogonial differentiation and mitotic activity. During seasonal spermatogenesis of adult bullfrogs Lithobates catesbeianus, primordial germ cells (PGCs) show enhanced testosterone cytoplasm immunoexpression in winter; however, in summer, weak or no testosterone immunolabelling was observed. The aim of this study was to confirm if PGCs express stem cell markers-alkaline phosphatase (AP) activity and GFRα1 (glial-cell-line-derived neurotrophic factor)-and verify whether testosterone is maintained in these cells by androgen receptors (ARs) and/or sex hormone-binding globulin (SHBG) in winter. Furthermore, regarding the possibility that testosterone is converted into estrogen by PGCs in summer, the immunoexpression of estrogen receptor (ER)β was investigated. Bullfrog testes were collected in winter and in summer and were embedded in glycol methacrylate for morphological analyses or in paraffin for the histochemical detection of AP activity. GFRα1, AR, SHBG and ERβ expression were detected by Western blot and immunohistochemical analyses. The expression of AP activity and GFRα1 in the PGCs suggest that these cells are spermatogonial stem cells. In winter, the cytoplasmic immunoexpression of ARs and SHBG in the PGCs indicates that testosterone is maintained by these proteins in these cells. The cytoplasmic immunoexpression of ERβ, in summer, also points to an ER-mediated action of estrogen in PGCs. The results indicate a participation of testosterone and estrogen in the control of the primordial spermatogonia during the seasonal spermatogenesis of L. catesbeianus. © 2012 S. Karger AG, Basel.

Fine needle aspirate cell blocks are reliable for detection of hormone receptors and HER-2 by immunohistochemistry in breast carcinoma

Aims: To evaluate the reliability of fine needle aspirate cell blocks in the assessment of oestrogen receptor (ER), progesterone receptor (PR) and HER-2/neu proteins by immunohistochemistry in comparison with surgical specimens. Materials and methods: This is a retrospective study of 62 cases of breast carcinoma diagnosed by fine needle aspiration cytology (FNAC) and confirmed using the surgical specimen. Immunohistochemical tests were performed to assess the presence of oestrogen receptor (ER), progesterone receptor (PR) and HER-2/neu proteins in cell blocks and the corresponding surgical specimens. The cell block method used alcohol prior to formalin fixation. Cases with 10% or more stained cells were considered positive for ER and PR. Positivity for HER-2/neu was assessed on a scale of 0-3+. The criterion for positivity was a score of 3+. Results: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the cell blocks in the investigation of ER, PR and HER-2/neu protein (3+) were (%): ER, 92.7, 85.7, 92.7, 85.7 and 90.3; PR, 92.7, 94.7, 97.4, 87.0 and 93.5; HER-2/neu, 70.0, 100.0, 100.0, 94.5 and 95.2. Discrepancies were seen in cell blocks in the 1+ and 2+ HER-2/neu staining scores: two of 12 cases scoring 2+ and one case of 26 scoring 1+ on cell blocks scored 3+ on surgical specimens. The correlation index between cell block and corresponding surgical specimen varied from 90% to 94%. Conclusion: Cell blocks provide a useful method of assessing ER, PR and HER-2/neu, mainly for inoperable and recurrent cases, but consideration should be given to carrying out FISH analysis on 1+ as well as 2+ HER-2/neu results. © 2012 Blackwell Publishing Ltd.

Cyp17a1 and cyp19a1 in the zebrafish testis are differentially affected by oestradiol

Oestrogens can affect expression of genes encoding steroidogenic enzymes in fish gonads. However, little information is available on their effects at the protein level. In this context, we first analysed the expression of key steroidogenic enzyme genes and proteins in zebrafish testis, paying attention also to other cell types than Leydig cells. Gene expression was analysed by quantitative PCR on fluorescence-activated cell-sorting fractions coupled or not to differential plating, while protein synthesis was studied by immunohistochemistry using specific antibodies against zebrafish Cyp17a1, Cyp19a1a and Cyp19a1b. Furthermore, we have evaluated the effect of oestrogen treatment (17β-oestradiol (E2), 10 nM) on the localization of these enzymes after 7 and 14 days of in vivo exposure in order to study how oestrogen-mediated modulation of their expression is linked to oestrogen effects on spermatogenesis. The major outcomes of this study are that Leydig cells express Cyp17a1 and Cyp19a1a, while testicular germ cells express Cyp17a1 and both, Cyp19a1a and Cyp19a1b. As regards Cyp17a1, both protein and mRNA seem to be quantitatively dominating in Leydig cells. Moreover, E2 exposure specifically affects only Leydig cell Cyp17a1 synthesis, preceding the disruption of spermatogenesis. The oestrogen-induced suppression of the androgen production capacity in Leydig cells is a major event in altering spermatogenesis, while germ cell steroidogenesis may have to be fuelled by precursors from Leydig cells. Further studies are needed to elucidate the functionality of steroidogenic enzymes in germ cells and their potential role in testicular physiology. © 2013 Society for Endocrinology.

Risk of metabolic syndrome in postmenopausal breast cancer survivors

The aim of this study was to assess the risk of metabolic syndrome (MetS) in postmenopausal breast cancer survivors as compared with postmenopausal women without breast cancer. METHODS: In this cross-sectional study, 104 postmenopausal breast cancer survivors were compared with 208 postmenopausal women (controls) attending a university hospital. Eligibility criteria included the following: amenorrhea longer than 12 months and aged 45 years or older, treated for breast cancer, and metastasis-free for at least 5 years. The control group consisted of women with amenorrhea longer than 12 months and aged 45 years or older and without breast cancer, matched by age and menopause status (in a proportion of 1:2 as sample calculation). Clinical and anthropometric data were collected. Biochemical parameters, including total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and C-reactive protein, were measured. Women showing three or more diagnostic criteria were diagnosed as having MetS: waist circumference of 88 cm or larger, blood pressure of 130/85 mm Hg or higher, triglycerides level of 150 mg/dL or higher, high-density lipoprotein cholesterol level lower than 50 mg/dL, and glucose level of 100 mg/dL or higher. For statistical analysis, Student's t test, χ2 test, and logistic regression (odds ratio [OR]) were used. RESULTS: The mean (SD) age of breast cancer survivors was 60.6 (8.6) years, with a mean (SD) follow-up of 9.4 (4.4) years. A higher percentage of breast cancer survivors (46.2%) were obese as compared with controls (32.7%; P < 0.05), and a smaller percentage showed optimal values for low-density lipoprotein cholesterol, glucose, and C-reactive protein versus controls (P < 0.05). MetS was diagnosed in 50% of breast cancer survivors and in 37.5% of control group women (P < 0.05). Among the MetS diagnostic criteria, the most prevalent was abdominal obesity (waist circumference >88 cm), affecting 62.5% and 67.8% of the participants, respectively. In the control group, breast cancer survivors had a higher risk for MetS (OR, 1.66; 95% CI, 1.04-2.68), dysglycemia (OR, 1.05; 95% CI, 1.09-3.03), and hypertension (OR, 1.71; 95% CI, 1.02-2.89). CONCLUSIONS: Postmenopausal breast cancer survivors present a higher risk of developing MetS as compared with women without breast cancer. © 2012 by The North American Menopause Society.

Adjunctive antimicrobial photodynamic treatment of experimentally induced periodontitis in rats with ovariectomy

Background: The aim of this study is to compare antimicrobial photodynamic therapy (aPDT) as an adjunctive therapy to scaling and root planing (SRP) for the treatment of experimentally induced periodontitis in rats with ovariectomy (OVX) that are or are not treated with estrogen replacement. Methods: A total of 270 female rats were divided into three groups: 1) normal rats; 2) rats with OVX; and 3) rats with OVX with estrogen replacement. Periodontal disease was induced through the introduction of a cotton thread around the mandibular left first molar. After 7 days, the ligature was removed, and the rats were randomly divided into the following treatment groups: 1) SRP plus saline solution; 2) SRP plus low-level laser therapy (LLLT); and 3) SRP plus toluidine blue O irrigation followed by LLLT. Ten rats from each group were euthanized at days 7, 15, and 30 after dental treatment. Bone loss (BL) in the furcation region was evaluated using histometric and immunohistochemical analyses. Results: aPDT treatment resulted in reduced BL compared with SRP treatment at all time points. Additionally, rats treated with aPDT exhibited reduced numbers of tartrate-resistant acid-phosphatase-positive cells and more proliferating cell nuclear antigen-positive cells in all treatment groups regardless of estrogen status. Whereas rats treated with aPDT showed weak immunoreactivity to the receptor activator of nuclear factor-k B ligand at day 7 post-treatment, strong osteoprotegerin immunoreactivity was observed at day 15 post-treatment. Conclusion: aPDT is an effective adjunctive therapy for the treatment of periodontitis in rats with OVX that are or are not given estrogen replacement therapy.

Long-term effects of perinatal androgenization on reproductive parameters of male rat offspring androgenization and male rat reproduction

It is known that during sex differentiation, fetal androgens are critical determinants of the male phenotype. Although testosterone is necessary for normal development of male sexual behavior, perinatal androgen treatment can result in disruption of normal male sexual reproduction. Pregnant Wistar rats were administered either corn oil (vehicle) or testosterone propionate at 0.2 mg/kg from gestational day 12 until the end of lactation and the reproductive function of male offspring was evaluated at 90 (adulthood) and 270 (middle age) days of age. Perinatal androgenization in the rat provoked a reduction in sperm production and reserves in adulthood that did not affect fertility and did not persist at more advanced ages, as shown by the results at post-natal day 270. If perinatal androgenization promotes similar effects in humans of reproductive age, the results of the present work can impact male reproduction health, given the less efficient spermatogenesis and lower sperm reserves in the human epididymis, compared to rodents. © Georg Thieme Verlag KG Stuttgart. New York.

Effects of exposure to estradiol and estradiol plus testosterone on the mongolian gerbil (Meriones unguiculatus) female prostate

The female prostate is a differentiated organ found in several mammal species, including humans and rodents. This gland has been related to important functions on female reproductive biology. Although the factors, which regulate prostate's development and activity are not well known, its functionality has been related to steroid hormones. It is well established that cyclic changes of estradiol and progesterone levels promote histophysiological adaptations of the whole female body. In contrast, only a few is found about those adaptations in female prostate. Thus, this study aimed to evaluate the effect of estradiol and estradiol+testosterone association on gerbil female prostate in order to verify, which hormonal associations are necessary to its homeostasis. For this, adult females had the ovaries surgically removed. After recovering, they received estradiol and estradiol+testosterone doses through 30 days, each 48 h. The prostatic tissue underwent morphological and morphometric-estereological analysis. Hormonal restriction caused great gland involution and decreased secretory activity, aspects that were reverted by exposure to estradiol and estradiol+testosterone. However, these hormones were not able to re-establish the normal prostate histoarchitecture. The immunoreaction of steroid receptors (ER-α, ER-β, and AR) responded differently among the experimental and control groups, and PCNA assay showed a decrease in epithelial cell proliferation within groups that had hormone privation. Therefore, we conclude that estradiol and testosterone are able to influence prostate morphophysiology and the maintenance of gland homeostasis depends on a balance among these and other hormones. © 2013 Wiley Periodicals, Inc.

Digit ratio (2D:4D) is associated with gastric cancer

Background: Sex steroid exposure during early human development may influence disease susceptibility. Digit ratio (2D:4D) is a putative marker for prenatal hormone exposure and sensitivity, as well as the action of genes closely related to carcinogenesis. Digit ratio could act as a possible marker for cancer predisposition. Aims: The aim of this study is to investigate the possible correlations between right hand, left hand and right minus left (R. - L) 2D:4D and gastric cancer (GCA) in men and women and assess the correlations with tumor staging and histological diagnosis. Methods: Digital images of the right and left hand palms of patients diagnosed with GCA (n = 57, 42 males, 15 females) and age and sex-matched controls (n = 59, 41 males, 18 females) were obtained. Means for 2D:4D were compared. Data were analyzed by repeated-measures one-way ANOVA and Student's t-test for finger measurements and group comparisons and Pearson's and Spearman's tests for correlations with tumor staging (α = 0.05). Results: GCA group presented significantly higher left 2D:4D, but significantly lower R. - L in comparison to healthy controls, particularly so for males. Digit ratio did not correlate to clinical staging or TNM staging. However, low R. - L was significantly related to adenocarcinomas. Conclusions: Early developmental conditions, including prenatal testosterone seem to play a role on the malignant transformation of gastric lesions. The 2D:4D pattern found for gastric cancer parallels that earlier described for breast cancer. The findings suggest that 2D:4D could add to the list of etiological factors and be a putative marker for the screening of patients' susceptibility to develop gastric cancer. © 2012 Elsevier Ltd.