Histological assessment of ovaries and uterus of rats subjected to nandrolone decanoate treatment

This study aimed to analyze the effects of nandrolone decanoate on the ovaries and uterus of adult females rats. This drug was administered intraperitoneally, at one, two and three doses of 3 mg nandrolone decanoate/kg of body weight, respectively, in the first, second and third week of treatment. The females of the control group received a physiological solution. The rats treated with nandrolone decanoate showed estral acyclicity and there was destruction of follicular units and an absence of corpus luteum in the ovaries. In the uterus, the drug promoted morphological alterations, characterized by vacuolated epithelium and endometrial stroma fibrosis. Ovary, uterus and pituitary weights were not affected by the steroid treatment. Nandrolone decanoate affects the sexual cycle and promotes histological alterations in the ovaries and uterus of adult female rats. (C) 2005 Elsevier B.V. All rights reserved.

Efeitos dos esteroides anabólicos androgênicos sobre o útero e parâmetros reprodutivos de ratas adultas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

OVARIAN HISTOLOGY and FOLLICULAR SCORE IN FEMALE RATS TREATED WITH NANDROLONE DECANOATE and SUBMITTED TO PHYSICAL EFFORT

The study was conducted to analyze the histology of the ovaries of adults rats treated with steroids, and submitted or not to physical effort. The control group consisted of females submitted to physical effort and sedentary females, both of which received a physiological solution of 0.9% saline. Treated females, sedentary or not, received 6 mg/kg of body weight of nandrolone decanoate. The steroid and physiological solution were administered intraperitoneally, with a single injection per week for 4 consecutive weeks. The applied physical effort was swimming (20 minutes daily, 5 days/week, for the 4 weeks of treatment). Serial sections (5 mu m) of ovaries were prepared for histological evaluation and follicular score. The weight of ovaries and hypophysis, the number of antral and atretic follicles, and the area of corpus luteum were all affected by the steroids. In the ovaries of the control groups, well-developed corpus luteum was observed. In the treated groups, the cortical stroma was occupied by ovarian interstitial tissue. The females treated with steroids presented estral acyclicity. The use of nandrolone decanoate, whether associated with physical effort or not, affected the morphological pattern of the ovaries.

Administração experimental de esteróide anabólico androgênico e álcool causa alterações histológicas e morfométricas nos ovários e útero de ratas adultas

Abusive and indiscriminate use of androgenic anabolic steroid is an usual practice among youth and adults of both sex. Usually these substances were utilized simultaneously with others drugs, licit or not, that causes damage to health. The purpose of study was to evaluate the influence of experimental administration of nandrolone decanoate steroid (ND), associated or not to alcohol, in the ovaries and uterus of adult rats. Females with regular estrous cycle (n = 20), were distributed in the groups: a) control (physiological solution); b) ND (7.5 mg/kg BW; intraperitoneal); c) alcohol (0.2 mL/100g BW; oral); d) ND + AL. The teatments were realized by single dose per week, during twelve consecutive weeks. The ovaries of rats in the groups ND, AL and ND + AL presented intense follicular atresia and decrease in the number of antral follicles and corpora lutea. None treatment did affect ovarian weight, but uterine weight was increase (p<0.05) in the ND + AL group. There were alterations in the uterine histology and morphometry at function of each treatment. Isolated or simultaneous use of anabolic steroid and alcohol promotes ovarian and uterine toxicity in adult female rats.

Efeitos do esteróide anabólico nandrolona sobre o músculo sóleo de ratos submetidos a treinamento físico através de natação: estudo histológico, histoquímico e morfométrico

Este estudo teve por objetivo analisar as alterações histológicas, histoquímicas e morfométricas das fibras do músculo sóleo de ratos submetidos a um programa de natação, associado ou não à administração do esteróide anabólico decanoato de nandrolona. Foram utilizados 22 ratos Wistar machos, 12 dos quais receberam injeção intramuscular do esteróide (5mg/kg) e 10, óleo mineral (5mg/kg), duas vezes por semana. Os animais foram submetidos a 42 sessões de natação por nove semanas (de segunda a sexta-feira), com aumento progressivo de carga por meio do tempo de natação. Após o sacrifício, o músculo sóleo esquerdo foi retirado, imerso em n-hexana e acondicionado em nitrogênio líquido. Cortes do terço médio desse músculo foram feitos em micrótomo criostato (-20ºC) e corados pela técnica HE e pelo método histoquímico NADH-TR. Os animais submetidos a treinamento físico e a esteróide (TA) ou óleo mineral (TO) apresentaram fibras musculares com maior diâmetro, quando comparados com os animais-controle (NTA e NTO). Não houve diferença significativa entre as medidas das médias dos diâmetros das fibras dos grupos NTA e NTO e entre TA e TO. Nos grupos TA e NTA notou-se acentuado processo de fagocitose, arredondamento e hialinização das fibras musculares. Já nos grupos TA, TO e NTA observou-se perda da atividade enzimática oxidativa. Os resultados sugerem que a natação produz hipertrofia muscular de forma semelhante, tanto no grupo que recebeu esteróide como no que recebeu óleo mineral. No entanto, o grupo que recebeu esteróide apresentou sinais claros de maior degeneração muscular.

Review of Fluconazole Properties and Analytical Methods for Its Determination

Fluconazole, alpha-(2.4-diflurofenil)-alpha-(1H-triazol-1-methyl)-1H-1,2,4-triazol-1-ethanol, is an antifungal of the triazoles class. It shows activity against species of Candida sp. and it is indicated in cases of oropharyngeal candidiasis, esophageal, vaginal, and deep infection. Fluconazole is a selective inhibitor of ergosterol, a steroid exclusive of the cell membrane of fungal cells. Fluconazole is highly absorbed by the gastrointestinal tract and spreads easily by body fluids. The main adverse reactions related to the use of fluconazole are nausea, vomiting, headache, rash, abdominal pain, diarrhea, and alopecia in patients undergoing prolonged treatment with a dose of 400 mg/day. In the form of raw material, pharmaceutical formulations, or biological material, fluconazole can be determined by methods such as titration, spectrophotometry, and thin-layer, gas, and liquid chromatography. This article discusses the pharmacological and physicochemical properties of fluconazole and also the methods of analysis applied to the determination of the drug.

Neurophysiological patterns of ulnar nerve neuropathy in leprosy reactions

Background: Leprosy neuropathy, despite being primarily demyelinating, frequently leads to axonal loss. Neurophysiological examination of the nerves during Type 1 (T1R) and Type 2 reactions (T2R) may give some insight into the pathophysiological mechanisms.Methods: Neurophysiological examinations were performed in 28 ulnar nerves during a clinical trial of steroid treatment effectiveness, 19 patients with T1R and nine with T2R. The nerves were monitored during a period of 6 months; there were eight assessments per nerve, for a total of 224 assessments. Nine neurophysiological parameters were assessed at three sites of the ulnar nerve. The compound motor action potential amplitudes elicited at wrist, elbow and above, as well as the conduction velocity and temporal dispersion across the elbow, were chosen to focus on the changes occurring in the parameters at the elbow tunnel.Results and Conclusion: Neurophysiological changes indicating axonal and demyelinating processes during both T1R and T2R were detected across the elbow. Changes in demyelination, i.e. a Conduction Block, as a primary event present during T2R, occurring as an acute phenomenon, were observed regularly; in T1R Temporal Dispersion, a subacute phenomenon, was seen. During treatment remyelination occurred after both types of reactions.

Nandrolone androgenic hormone presents genotoxic effects in different cells of mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of estrogen receptor alpha and beta and progesterone receptor expression and correlation with clinicopathologic factors and proliferative marker Ki-67 in breast cancers

To elucidate the molecular profile of hormonal steroid receptor status, we analyzed ER-alpha, ER-beta, and PGR mRNA and protein expression in 80 breast carcinomas using reverse transcriptase polymerase chain reaction (RT-PCR), quantitative RT-PCR, and immunohistochemical analysis. Qualitative analysis revealed positive expression of ER-alpha, ER-beta, and PGR mRNA in 48%, 59%, and 48% of the breast carcinomas, respectively. ER-alpha, ER-beta, and PGR transcript overexpression was observed in 51%, 0%, and 12% of the cases, respectively, whereas moderate or strong protein expression was detected in 68%, 78%, and 49% of the cases, respectively. Tumor grade was negatively correlated with transcript and protein levels of ER-alpha (P = .0169 and P = .0006, respectively) and PGR (P = .0034 and P = .0005, respectively). Similarly, proliferative index Ki-67 was negatively associated with transcript and protein levels of ER-alpha (P = .0006 and P < .0001, respectively) and PGR (P = .0258 and P =. 0005, respectively). These findings suggest that ER-alpha and PGR expression are associated with well-differentiated breast tumors and less directly related to cell proliferation. A significant statistical difference was observed between lymph node status and ER-beta protein expression (P = .0208). In ER-alpha-negative tumors, we detected a correlation between ER-beta protein expression and high levels of Ki-67. These data suggest that ER-beta could be a prognostic marker in human breast cancer. (C) 2008 Elsevier B.V. All rights reserved.

Padrões morfológicos de lesão glomerular e correlação com achados clinicolaboratoriais de 43 crianças com síndrome nefrótica

OBJETIVOS: Avaliar a associação entre os parâmetros clinicolaboratoriais e alteração morfológica de biópsias renais em crianças com síndrome nefrótica. MÉTODOS: Os dados foram obtidos dos prontuários médicos de 43 crianças com síndrome nefrótica submetidas a biópsia renal. RESULTADOS: Vinte e oito pacientes eram do sexo masculino (65,1%), idades entre 1,4 a 12 anos (média de 4,7±3,2). Quarenta e dois pacientes (97,7%) apresentaram edema; 83,7%, oligúria e 32,5%, hipertensão arterial. A média de proteinúria foi 15,3g/1,73m²SC/dia e 55,8% apresentaram hematúria microscópica. As biópsias renais mostraram: glomerulonefrite proliferativa mesangial (GNPM) em 37,2%, glomeruloesclerose segmentar e focal (GESF) em 27,9%, alterações glomerulares mínimas (LM) em 25,6%, glomerulonefrite membranoproliferativa (GNMP) em 7% e glomerulonefrite membranosa (GNM) em 2,3%. Vinte e seis pacientes (60,5%) apresentaram resistência ao corticosteróide. Idade, sexo, hipertensão arterial, oligúria, uréia e creatinina séricas não mostraram diferenças estatísticas significativas entre os pacientes com GNPM, GESF e LM. Os pacientes com GNPM e GESF apresentaram maior freqüência de hematúria microscópica (p < 0,003 e p < 0,03; respectivamente). Os pacientes com GESF apresentaram maiores níveis de proteinúria (p < 0,01 versus LM e p < 0,05 versus GNPM). Os pacientes com LM apresentaram sensibilidade ao corticosteróide (p < 0,001 versus GESF e p = 0,047 versus GNPM). CONCLUSÕES: Sexo, idade, presença de hipertensão arterial ou oligúria e níveis séricos de uréia e creatinina não auxiliaram na diferenciação entre pacientes com GNPM, GESF e LM. Os pacientes com LM apresentaram sensibilidade a corticosteróides e menos probabilidade de apresentar hematúria microscópica. Pacientes com GESF apresentaram maiores níveis de proteinúria.

Progression of articular and extraarticular damage in oligoarticular juvenile idiopathic arthritis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Polymorphisms of CYP17A1, CYP19, and androgen in Brazilian women with uterine leiomyomas

Background: Uterine leiomyomas are common, benign, smooth muscle tumors representing a significant public health problem. The aim of this study was to investigate CYP17A1, CYP19, and androgen (AR) polymorphisms, their relative risks for uterine leiomyomas and possible associations with clinical parameters.Methods: Uterine leiomyoma tissues and blood samples were obtained from 87 patients, as were peripheral blood samples from 68 control women. Clinical data were recorded in both groups. The CYP17A1 (rs743572) polymorphism was analyzed by PCR-RFLP, and the CYP19 [TTTA](n) repeat and AR [CAG](n) repeat were analyzed using PCR-based GeneScan analysis. AR loss of heterozygosity (LOH) and microsatellite instability were also evaluated, while samples exhibiting LOH were analyzed for X inactivation.Results: Clinical parameters related to disease development did not differ between cases and controls. CYP17A1 *A2/*A2 genotype was prevalent in non-white women. CYP17A1, CYP19, and AR genotypes and alleles did not differ between groups. However, alleles presenting [TTTA](7) repeats in intron 4 of CYP19 were more frequent in the control group (p=0.0550). Shorter and longer [CAG]n repeat alleles of AR were exclusive to the leiomyoma group. The LOH assay showed allele losses at AR locus in four informative tumors and X chromosome inactivation analysis revealed that these tumors retained the active allele.Conclusions: The overall lack of association between uterine leiomyomas with polymorphisms involved in steroidogenesis or steroid metabolism is consistent with the hypothesis that these polymorphisms do not substantially contribute to the development of these tumors.

Variations in maternal care alter corticosterone and 17beta-estradiol levels, estrous cycle and folliculogenesis and stimulate the expression of estrogen receptors alpha and beta in the ovaries of UCh rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ultrastructural and proliferative features of the ventral lobe of the prostate in non-obese diabetic mice (NOD) following androgen and estrogen replacement associated to insulin therapy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Vascular adaptive responses to physical exercise and to stress are affected differently by nandrolone administration

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)