Effects of the Chronic Use of Acetaminophen on Pregnant Rats

Purpose: to evaluate the effects of acetaminophen on the pregnancy of female albino rats. Methods: forty pregnant rats were separated into four groups. All the animals received daily by gavage 1 ml of acetaminophen solution from the first day (day zero) until the 20th day of pregnancy: group I - only distilled water (control); groups II, III and IV, respectively, 125, 500 and 1,500 mg/kg body weight of acetaminophen dissolved in distilled water. The animals were weighed on days 0, 7, 15 and 20 of pregnancy. Results: our results showed that the rats that received the medication presented a reduction in weight when compared to the control group. The incidence of reabsorption of the embryos was 2.0, 3.5 and 7.0 times higher than in the control, in groups II, III and IV, respectively. Groups GII and GIV showed a clear reduction in the weight of the concepts. In GIV there was a 50% reduction in weight increase of fetuses and placentas when compared to the control, and 15.7% of external malformations were also found. Conclusions: the continuous use of acetaminophen should be avoided at doses higher than 70 mg/kg per during pregnancy.Objetivos: estudar a ação do acetaminofeno administrado durante toda a prenhez da rata albina. Métodos: 40 ratas albinas prenhes foram distribuídas ao acaso em quatro grupos numericamente iguais: GI - recebeu diariamente 1 ml de água destilada por gavagem (controle); GII, GIII e GIV foram tratadas, respectivamente, com 125, 500 e 1.500 mg/kg de peso corporal de acetaminofeno, dose única, diária, por gavagem, sempre diluído em 1 ml de água destilada, desde o dia zero até o 20º dia de prenhez. O ganho de peso das matrizes foi avaliado nos dias 0, 7, 15 e 20 de prenhez, sendo que no 20º dia todos os animais foram sacrificados. Resultados: nossos achados mostraram sempre menor peso entre as matrizes que receberam o medicamento, quando comparadas com o controle. A incidência de reabsorção dos embriões foi da ordem de 2,0, 3,5 e 7,0 vezes maior que no controle, considerando-se, respectivamente, os grupos GII, GIII e GIV. Os grupos GIII e GIV tiveram redução do peso dos conceptos. No GIV, houve redução de 50% no crescimento de fetos e placentas com relação ao controle; aqui, também foram encontradas 15,7% de malformações externas. Conclusões: deve ser evitado o uso contínuo do acetominofeno em altas doses, superiores a 70 mg/kg por dia, durante o período gestacional.UNISA Faculdade de Medicina de Santo AmaroUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de TocoginecologiaUNIFESP, EPM, Depto. de TocoginecologiaSciEL

Effects of isoflavones on the skin of postmenopausal women: a pilot study

OBJECTIVE: The aim of this study was to evaluate the effects of isoflavones on the skin of postmenopausal women. DESIGN: A prospective study was performed with 30 postmenopausal women before and immediately after the end of treatment with 100 mg/day of an isoflavones-rich, concentrated soy extract for six months. A skin punch was performed in the gluteal region for sample collection before and immediately after the treatment program. Morphometric determination of epidermal thickness, the papillary index (wrinkling), and the amount of dermal elastic and collagen fibers was assessed. In addition, the number of blood vessels in the sample was also evaluated. The paired Student's t-test was used for statistical analysis (P < 0.05). RESULTS: Isoflavone treatment resulted in a 9.46% increase in the thickness of the epidermis in 23 patients. In addition, the papillary index was reduced in 21 women. The papillary index was inversely proportional to skin wrinkling, i.e., there were a large number of papillae after treatment. The amount of collagen in the dermis was increased in 25 women (86.2%). In 22 women (75.8%) we observed that the number of elastic fibers increased. The number of dermal blood vessels was significantly increased in 21 women. CONCLUSION: Our data show that the use of a concentrated, isoflavone-rich soy extract during six consecutive months caused significant increases in epithelial thickness, the number of elastic and collagen fibers, as well as the blood vessels.Federal University of São Paulo Gynecology DepartmentFederal University of São Paulo Morphology DepartmentUniversidade de São Paulo Faculdade de Medicina Laboratório de Ginecologia Estrutural e MolecularUniversidade de São Paulo Faculdade de Medicina Departamento de Obstetrícia e GinecologiaUNIFESP, Gynecology DepartmentUNIFESP, Morphology DepartmentSciEL

Morphological and Morphometrical Study of Permanent Estrus Rat Mammary Gland Treated with Danazol

Purpose: the morphologic and morphometric aspects of the breasts of rats in permanent estrus submitted to danazol were studied. Methods: the animals were divided into three groups: group A (n = 12) received water and was used as control, group B (n = 13) was exposed to 20 mg danazol kg-1 day-1, and group C (n = 10) was exposed to 80 mg danazole kg-1 day-1 for 35 consecutive days. The microscopic study evaluated the ductal and acinar distribution. Histometry of the relationship duct/stroma was based on the principles of stereology with a Zeiss k-10X ocular, with Integrationsplatte I reticulum of Weibel of 25 hits, with 100X magnification. For each studied section, 10 aleatoric fields were counted, with a total of 250 points. The variance analysis test (Kruskal-Wallis) was applied to compare the three groups in relation to the mean number of alveoli and ducts (alpha = 0.05). Results: when submitted to morphological study, all groups presented lobules with alveoli lined with cubic cells with nuclei in their central or basal portion. Small amounts of eosinophilic material were observed in some cases in the lumen, with no differences between the groups. At morphometry, with a magnification of 100X, a mean number of 28.6 ducts/10 fields was found in group A, 28.4 in group B and 29.2 in group C (Kruskal-Wallis test: Hcrit = 0.1). The mean number of alveoli in 10 fields was 5.9, 9.3 and 6.5 in groups A, B and C, respectively (Kruskal-Wallis test: Hcrit = 2.9), with no significant differences between the groups. Conclusion: danazol did not cause any changes in the morphology and morphometry of the permanent estrus mammary epithelium.Objetivo: estudar os efeitos do danazol sobre a mama da rata em estro permanente. Métodos: os animais foram divididos em três grupos: os do grupo A (n = 12) receberam água (placebo), como grupo controle; os do grupo B (n = 13) foram expostos a 20 mg/kg de danazol por dia; os do grupo C (n = 10) foram expostos a 80 mg/kg de danazol por dia. A droga foi administrada durante 35 dias consecutivos. O estudo microscópico dos cortes avaliou a distribuição ductal e acinar. A histometria da relação ducto/estroma foi feita baseada nos princípios da estereologia, com ocular k-10X da Zeiss, com retículo de integração (Integrationsplatte I-retículo de Weibel de 25 hits), com aumento final de 100 vezes. Para cada lâmina estudada, foram contados 10 campos aleatórios, num total de 250 pontos. O teste aplicado foi a análise de variância por postos de Kruskal-Wallis, para comparar os três grupos em relação ao número médio de alvéolos e ductos nas mamas (alfa = 0,05). Resultados: em todos os grupos, os lóbulos apresentaram ao estudo morfológico alvéolos revestidos com células cúbicas com núcleos na sua porção central ou basal. Pequenas quantidades de material eosinofílico foram observadas em alguns casos na sua luz. À morfometria (magnificação de 100X) encontraram-se em média 28,6 ductos/10 campos no grupo A, 28,4 no grupo B e 29,2 no grupo C (análise de Kruskal-Wallis: Hcrit = 0,1). As médias dos números de alvéolos /10 campos foram 5,9 (grupo A), 9,3 (grupo B) e 6,5 (grupo C) (Kruskal-Wallis Hcrit = 2.9), sem diferença significativa entre os grupos. Conclusão: o danazol não causou nenhuma alteração significante na morfologia e morfometria do epitélio das mamas das ratas em estro permanente.Universidade Federal de São Paulo (UNIFESP) EPMUNIFESP, EPMSciEL

Proliferation of the superficial epithelium of ovaries in senile female rats following oral administration of conjugated equine estrogens

OBJECTIVE: To evaluate the effect of different concentrations of estrogen on the ovarian superficial epithelium in senile female rats. Design: Fifty female rats at 15 months of age and with irregular estrous cycles were selected and randomly divided into five experimental groups containing equal numbers of animals in each: GPROP, control group receiving vehicle only; GE0.05mg, group receiving conjugated equine estrogens (CEE) at a dose of 50 µg/kg; GE0.5mg, group receiving CEE at 500 µg/kg; GE1mg, group receiving CEE at 1 mg/kg; and GE2mg, receiving CEE at 2 mg/kg. The length of treatment was 21 days. After this period, the animals were anesthetized and the ovaries were fixed in 10% formaldehyde and processed for routine histology. Histomorphology was analyzed by light microscopy, and histomorphometrics were evaluated using the Imagelab program. RESULTS: In the GPROP and GE0.05mg groups, the superficial epithelium of the ovary had a simple cuboidal shape, and as the estrogen dose increased, the epithelium thickened, with pseudo-stratified or stratified epithelium appearing in the GE2mg group. The animals in the group given the highest estrogen dose (GE2mg) showed the thickest ovarian epithelium and the largest perimeter and surface area of the surface ovarian epithelium (P < 0.01). However, the difference in epithelium thickness between the GE0.5mg and GE1mg groups was only slight. CONCLUSION: Our data suggest that CEE at a dose of 2 mg/kg may induce marked proliferation of rat ovarian epithelium.UNIFESP Morphology Department Histology and Cellular Biology DivisionUniversidade de São Paulo Faculdade de MedicinaUniversidade Federal de São Paulo (UNIFESP) Faculdade de Medicina Gynecology DepartmentUNIFESP, Morphology Department Histology and Cellular Biology DivisionUNIFESP, Faculdade de Medicina Gynecology DepartmentSciEL

Efeito da N-acetilcisteína na lesão hepática por isquemia e reperfusão após 30% de hepatectomia em camundongos

PURPOSE: Evaluate the effect of N-acetylcysteine in liver remnant after hepatectomy associated to ischemia-reperfusion injury in mice. METHODS: Male adult BALB/c mice, weighing 20-22g were used. Animals were anesthetized with ketamine (70 mg/kg) and xylazine (10 mg/kg); received N-acetylcysteine (150 mg/kg, H-IR-NAC group) or vehicle (H-IR group). Surgical procedures were performed under 10X magnification. Partial hepatectomy (30%) was followed by ischemia-reperfusion injury (30 minutes of ischemia and 60 minutes of reperfusion). Blood sample and liver tissue were removed before animal was euthanized. AST and ALT were evaluated in blood samples and histomorphological analyses were performed in remnant liver. Groups were compared by Mann-Whitney test, and it was considered significant when p<0.05. RESULTS: Biochemical evaluations showed reduced levels of ALT in NAC group (H-IR-NAC=376±127U/l vs H-IR=636±39U/l, p=0.023). AST was similar (p=0.456). H-IR group showed hepatic tissue with preserved architecture, large area of steatosis, vascular congestion and rare mitogenic activity. NAC group showed hepatic tissue with small area of steatosis, vascular congestion and elevated mitogenic activity, evidenced by increased binuclear cells (H-IR-NAC=15.88±0.52 vs H-IR=7.4±0.37, p<0.001). CONCLUSION: N-acetylcysteine promotes enzymatic and morphological protection against hepatectomy and ischemia-reperfusion injury.OBJETIVO: Investigar se a N-acetilcisteína promove proteção do remanescente hepático após ressecção associada à isquemia e reperfusão do fígado em camundongos. MÉTODOS: Foram utilizados 12 camundongos BALB/c, machos, pesando entre 20-22g. Os animais foram anestesiados com quetamina (70mg/kg) e xilazina (10mg/kg); receberam a N-acetilcisteína (150mg/kg, grupo H-IR-NAC) ou controle (grupo H-IR). Os procedimentos cirúrgicos ocorreram na magnificação de 10X. A lesão por isquemia e reperfusão (30 minutos de isquemia e 60 minutos de reperfusão) foi precedida pela hepatectomia de 30%. Foram utilizados como parâmetro de avaliação: a bioquímica sangüínea (AST e ALT) e a histologia do fígado (coloração de hematoxilina-eosina). Para avaliação estatística empregou-se o teste de Mann-Whitney e o nível de significância foi 5%. RESULTADOS: Na avaliação bioquímica houve redução no nível de ALT no grupo tratado (H-IR-NAC=376±127 U/l vs H-IR=636±39 U/l, p=0,023). AST foi similar (p=0,456). Na histologia, o grupo H-IR apresentou um tecido hepático com arquitetura preservada, com grandes áreas de infiltração gordurosa, presença de congestão vascular e de alguma atividade mitótica; o grupo com a N-acetilcisteína apresentou menor infiltração gordurosa e congestão vascular, maior atividade mitótica, evidenciada pela quantidade elevada de células binucleadas (H-IR-NAC=15,88±0,52 vs H-IR=7,4±0,37, p<0,001). CONCLUSÃO: A N-acetilcisteína promove proteção ao fígado, do ponto de vista morfológico e enzimático, após hepatectomia associada à isquemia e reperfusão.UNIFESP Division of Operative Technique and Experimental Surgery Department of SurgeryUniversidade Federal de São Paulo (UNIFESP) Department of SurgeryUNIFESP Division of Histology Department of MorphologySão Paulo University Faculty of Medicine Surgical PhysiopathologyUNIFESP, Division of Operative Technique and Experimental Surgery Department of SurgeryUNIFESP, Department of SurgeryUNIFESP, Division of Histology Department of MorphologySciEL

Does Gestrinone Antagonize the Effects of Estrogen on Endometrial Implants Upon the Peritoneum of Rats?

OBJECTIVE: To evaluate the effects of estrogen treatment in combination with gestrinone on an experimental rat model of endometriosis. METHODS: Uterine transplants were attached to the peritoneum of female Wistar rats via a surgical autotransplantation technique. The implanted area was measured during the proestrus phase and after hormonal treatment. We performed morphometric analysis and examined the macroscopic and morphometric alterations of endometrial implants after hormonal treatment in ovariectomized rats. RESULTS: The high dose of estrogen caused macroscopic increases in the endometrial implant group compared with other groups, which were similar to increases in the proestrus phase. The low dose showed morphometric development of implants, such as an increase in number of endometrial glands, leukocyte infiltration and mitosis. Gestrinone antagonized both doses of estrogen. CONCLUSION: Our findings suggest that gestrinone antagonizes estrogen's effects on rat peritoneal endometrial implants

Ultrastructural aspects of the remodeling process of the Corpus albicans in the recent postmenopausal period

To study the cytophysiology of the Corpus albicans in the recent postmenopausal period, the authors analyzed the ovarian ultrastructure of ten patients submitted to oophorectomy due to non-malignant gynecological diseases. Evidence of a remodeling process with connective tissue substitution of the corpora albicantia was observed. The remodeling process appears to depend on the activity of three essential cell types: the fibroblasts, which provide collagen synthesis; the macrophages, which phagocytize the flaky material; and the myofibroblasts, mainly located in the peripheral region of the corpora albicantia, which may have a retracting action on the remodeling site of the Corpus albicans.Os autores analisam a ultra-estrutura dos ovários de dez pacientes na pós menopausa recente submetidas a ooforectomia devido a doenças ginecológicas benignas e descrevem o processo de remodelação do corpo albicante, ou seja, de sua substituição por tecido conjuntivo. Referem que tal processo depende basicamente da atividade de três tipos de células: os fibroblastos, que estariam envolvidos com a síntese das fibras colágenas; os macrófagos, que fagocitariam o material floculento presente nos corpos albicantes, e os miofibroblastos, localizados principalmente na região periférica dos corpos albicantes, e que estariam relacionados com a retração do sítio remodelatório do corpo albicante. Referem ainda que o processo de remodelação dos corpos albicantes do ovário depende dos níveis hormonais vigentes.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of Obstetrics and GynecologyUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of MorphologyUNIFESP, EPM, Department of Obstetrics and GynecologyUNIFESP, EPM, Department of MorphologySciEL

Seminal quality, testicle and epididymis morphology of bulls fed a diet containing gossypol

The objective was to evaluate the effect of intake of free gossypol on sperm quality and morphology of the testicles and epididymis of Nelore bulls. Twelve bulls were fed diets containing 3.3g of free gossypol/bull/day (cottonseed) (Group 1, n = 6) and a diet free of gossypol (Group 2, n = 6), respectively. Semen samples were collected in the beginning and end of the experiment which lasted 73 days. In the end of the study the testes and epididymis of bulls were removed to study the effect of free gossypol on histological characteristics. The average consumption of 3.3g of free gossypol/bull/day (mean 7.1mg of free gossypol/kg/day) reduced motility and sperm concentration and increased the percentage of major and total sperm defects, as well as the animals showing testes with seminiferous tubules of smaller thickness, fewer layers of spermatogenic lineage cells, smaller epididymal epithelium thickness and smaller number of sperm within the epididymal ducts, compared to animals with a diet free of gossypol (Group 2). The consumption of 3.3g of free gossypol/bull/day led to changes in morphology and morphometry of the testes and epididymis and reduced sperm quality of bulls.Objetivou-se avaliar o efeito da ingestão de gossipol livre sobre a qualidade espermática e a morfologia dos testículos e dos epidídimos de touros da raça Nelore. Doze touros receberam dieta contendo 3,3g de gossipol livre/touro/dia (caroço de algodão) (Grupo 1, n=6) e dieta isenta de gossipol (Grupo 2, n=6), respectivamente. Foram realizadas coletas de sêmen no início e no final do experimento, que teve duração de 73 dias. Ao final do estudo, foram retirados os testículos e os epidídimos dos touros para se estudar o efeito do gossipol livre sobre as características histológicas. O consumo médio de 3,3g de gossipol livre/touro/dia (média 7,1mg de gossipol livre/kg/dia) reduziu a motilidade e a concentração espermática e aumentou a porcentagem de defeitos espermáticos maiores e totais. Além disso, os animais apresentaram testículos com túbulos seminíferos de menor espessura de parede, menor número de camadas de células espermatogênicas, menor espessura do epitélio epididimário e menor número de espermatozoide no interior dos ductos epidídimários, em relação aos animais com dieta isenta de gossipol (Grupo 2). O consumo de 3,3g de gossipol livre/touro/dia acarretou alterações na morfologia e na morfometria dos testículos e dos epidídimos e reduziu a qualidade espermática dos touros.Universidade de Cuiabá Faculdade de Medicina VeterináriaUFMS Faculdade de Medicina Veterinária e ZootecniaEpamigUniversidade Federal do Mato GrossoUNIFESP-EPMUNIFESP, EPMSciEL

Effects of tamoxifen and conjugated estrogens on the mammary epithelium of rats in persistent estrus

Purpose: to evaluate the morphologic and morphometric alterations produced by tamoxifen and conjugated estrogens in the mammary epithelium of rats in persistent estrus. Methods: thirty-three adult female rats in persistent estrus induced with 1.25 mg testosterone propionate were divided at random into three groups: GI -- which received only water, control group (n = 12); GII -- treated with 500 mug tamoxifen daily (n = 10); GIII -- treated with 30 mug conjugated estrogens per day (n = 11). The first inguinal-abdominal pair of mammary glands of the animals was extirpated and processed for morphologic and morphometric study. Data were analyzed statistically by the Kruskal-Wallis rank analysis of variance (p < 0.05). Results: the morphologic study revealed signs of epithelial atrophy and the morphometric study showed a statistically significant reduction in the mean number of ducts and alveoli in groups II (10.1 and 1.9, respectively) and III (11.1 and 3.5, respectively) compared to group I (25.0 and 6.6, respectively). There was no significant difference between groups II and III. Conclusions: the results of this study indicate that tamoxifen as well as conjugated estrogens at the tested doses produced mammary epithelial atrophy in rats in persistent estrus.Objetivo: avaliar as alterações morfológicas e morfométricas produzidas pelo tamoxifeno e pelos estrogênios conjugados no epitélio mamário de ratas em estro permanente. Métodos: foram utilizadas 33 ratas adultas, induzidas a estro permanente com 1,25 mg de propionato de testosterona e divididas ao acaso em três grupos: GI -- que receberam apenas água, servindo como controle (n = 12); GII -- tratadas com 500 mig de tamoxifeno diariamente (n = 10); GIII -- tratadas com 30 mig de estrogênios conjugados ao dia (n = 11). O primeiro par mamário abdômino-inguinal dos animais foi extirpado e processado para estudo morfológico e morfométrico. Os dados foram analisados estatisticamente pela análise de variância por postos de Kruskal-Wallis (p < 0,05). Resultados: o estudo morfológico revelou sinais de atrofia epitelial e o estudo morfométrico exibiu redução estatisticamente significante do número médio de ductos e alvéolos nos grupos II (10,1 e 1,9, respectivamente) e III (11,1 e 3,5, respectivamente) em relação ao grupo I (25,0 e 6,6, respectivamente). Não houve diferença estatística entre os grupos II e III. Conclusões: os resultados deste estudo indicam que tanto o tamoxifeno como os estrogênios conjugados, nas doses e no tempo utilizado, produziram atrofia no epitélio mamário de ratas em estro permanente.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL