Abstract Introduction The CA1 region of the hippocampus has an important role in learning and memory. It has been shown that estrogen deficiency may reduce the synaptic density in the region and that hormone replacement therapy may attenuate the reduction. Objectives This study aimed to evaluate the effects of estrogen and raloxifene on the synaptic density profile in the CA1 region of the hippocampus in ovariectomized rats. Methods Sixty ovariectomized three-month-old virgin rats were randomized into six groups (n = 10). Treatments started either three days (early treatment) or sixty days (late treatment) after ovariectomy. The groups received propylene glycol vehicle (0.5 mL/animal/day), equine conjugated estrogens (50 μg/animal/day), or raloxifene (3 mg/kg/day) either early or late after ovariectomy. The drugs were administered orally by gavage for 30 days. At the end of the treatments, the animals were anesthetized and transcardially perfused with ether and saline solution. The brains were removed and prepared for analysis under transmission electron microscopy and later fixed. Results Results showed a significant increase in the synaptic density profile of the hippocampal CA1 region in both the early estrogen (0.534 ± 0.026 µ/m2) and the early raloxifene (0.437 ± 0.012 µ/m2) treatment groups compared to the early or late vehicle-treated control groups (0.338 ± 0.038 µ/m2 and 0.277 ± 0.015 µ/m2 respectively). Conclusions The present data suggest that the raloxifene effect may be lower than that of estrogen, even early or late treatment, on synaptic density in the hippocampus. CA memory reduction threemonthold month old n 10. 10 . 10) ovariectomy 0.5 05 0 5 (0. mL/animal/day, mLanimalday mL/animal/day , mL animal day mL/animal/day) 50 (5 μg/animal/day, μganimalday μg/animal/day μg μg/animal/day) 3 ( mg/kg/day mgkgday mg kg treatments solution fixed 0.534 0534 534 (0.53 0026 026 0.02 µm2 µm µ m2 m 0.437 0437 437 (0.43 0012 012 0.01 vehicletreated treated 0.338 0338 338 (0.33 0038 038 0.03 µ/m 0277 277 0.27 0015 015 respectively. respectively respectively) 1 0. (0 0.53 053 53 002 02 0.0 0.43 043 43 (0.4 001 01 0.33 033 33 (0.3 003 03 027 27 0.2 00 0.4 04 4 0.3 2

SUMMARY OBJECTIVE: To assess the impact of the metoclopramide-induced hyperprolactinemia in cellular death and proliferation in the harderian gland of female mice. METHODS: Twenty female mice were divided into two groups of 10 animals each and treated: 0.2 mL of saline solution (controls, Ctr) and 200 µg of metoclopramide (experimental, hyperprolactinemia), both for 50 consecutive days and at 12:00 a.m. On the 50th day, the female were euthanized, and the harderian glands were removed and processed for immunohistochemistry for detected ki67 and TUNEL method. Data were statistically analyzed by unpaired Student’s t test (p<0.05). RESULTS: The harderian gland of the hyperprolactinemia group showed increase in the immunoexpression of Ki67 and TUNEL compared to the Ctr group (p<0.05), and there was no significant difference in the amount of porphyrin in the HPrl group compared to the Ctr group. CONCLUSION: The hyperprolactinemia led to increased cell death in the acini the harderian gland and cell proliferation in the stroma glandular, fact that suggesting a reduction process of cellular activity and fibrosis, which suggests impairment in the functioning of the lacrimal harderian.

ABSTRACT Purpose: To evaluate the effect of hyperbaric oxygenation (HBO) on angiogenesis in random rat skin flaps, by immunoexpression of vascular endothelial growth factor A (VEGF-A). Methods: Forty adult rats were divided into four groups: GE) epilated; GE/HBO) epilated subjected to HBO; GER) epilated submitted to dorsal skin flap; GER/HBO) epilated subjected to dorsal skin flap + HBO. HBO was performed with rats inside a chamber under atmosphere close to 100% oxygen and pressure of 2.4 absolute atmospheres, 2h per day during seven consecutive days. GE and GER groups were placed in the hyperbaric chamber without HBO. Then, under anesthesia, skin flaps were removed and separated into three portions relative to pedicle fixation. The samples were fixed in formalin and processed for paraffin embedding. Histological sections were submitted to immunohistochemistry for VEGF-A detection. The number of immunostained-blood vessels were counted under light microscopy. Results: GE and GE/HBO groups showed normal and similar skin morphology in the three flap portions. A fibrin-leukocyte crust, along with denatured collagen and intense leukocyte infiltrate, was mainly observed in the dermis of the medial and distal flap portions of GER group. Meanwhile, the GER/HBO group presented more regions with intact collagen and small areas of leukocyte infiltrate in the three flap regions. VEGF-A-immunostained blood vessels were largely seen in all regions of GE and GE/HBO groups, whereas no significant differences were found between these groups. A decrease in vascularization was noticed in GER and GER/HBO groups, which was more evident in the most distal portion of the flaps. However, the number of VEGF-A-immunostained blood vessels in GER/HBO group was significantly higher when compared to GER group. Conclusions: Hyperbaric oxygenation was associated with increased angiogenesis and improved viability of rat skin flaps.

SUMMARY Amyotrophic Lateral Sclerosis (ALS) is a fatal disease characterized by muscle weakness, atrophy, fasciculations, and decreased reflexes due to upper and lower motor neurons death. It can be present in both sexes (55-65 years), but with predominance in males. However, in female patients, ALS presents its first symptoms when they are already postmenopausal, when then the incidence ratio of the disease is practically equal between the sexes, which leads to a probable involvement of sex hormones in the development and protection against ALS. The aim of this systematic review, which used the PRISMA consensus and NOS (New Castle-Ottawa Scale) score, was to evaluate the evidence of the action of hormone therapy in women with ALS. The Medline and Cochrane databases were accessed from March 2019 to June 2019, and only full-text articles in Spanish, English, and Portuguese were included. Only four articles matched our inclusion criteria. Postmenopausal women who used exogenous estrogen did not have the same protective factor as women still under the action of endogenous estrogen in the same age group. There was also no increase in the survival of these women.

RESUMO A melatonina tem propriedades anti-inflamatórias e antioxidantes que podem influenciar o crescimento e a apoptose dos tecidos. Esse aspecto pode influenciar o sucesso do transplante de órgãos. OBJETIVO Avaliar a relação entre a melatonina e o transplante de órgãos. MÉTODO A revisão sistemática foi realizada nas bases de dados do PubMed, usando os termos de pesquisa: “fisiologia da melatonina” ou “terapêutica da melatonina” e “farmacologia do transplante” ou “fisiologia do transplante” ou “terapêutica do transplante” ou “terapia do transplante”. Não foram incluídos os experimentos sobre os órgãos do sistema reprodutivo. Após análise, cinco artigos foram selecionados após a leitura do título e do resumo de 50 manuscritos. Os trabalhos foram divididos em duas vertentes: a) análise da influência do procedimento de transplante de órgão na produção de melatonina; b) ação da melatonina sobre o transplante de órgãos. RESULTADOS O procedimento cirúrgico do transplante cardíaco, a imunossupressão e o enxerto não influenciaram a secreção de melatonina em roedores, mas houve redução significante da melatonina nos casos do procedimento de transplante renal em pacientes com insuficiência renal. A ministração de melatonina em modelos experimentais diminuiu a rejeição e melhorou o sucesso de transplante. CONCLUSÃO Os estudos mostram que a melatonina pode reduzir a dependência da espécie e do órgão e que o emprego da melatonina diminui a rejeição do órgão.

SUMMARY Melatonin has anti-inflammatory and antioxidant properties that can influence tissue growth and apoptosis. This aspect may influence the success of organ transplantation. OBJECTIVE To evaluate the relationship between melatonin and organ transplantation. METHODS A systematic review was performed in PubMed databases using the search terms: “melatonin physiology” or “melatonin therapy” and “transplant pharmacology” or “transplant physiology” or “transplant therapy” or “Transplant therapy”. Experiments on the organs of the reproductive system were not included. After analysis, five articles were selected after reading the title and abstract of 50 manuscripts. The works were divided into two aspects: a) analysis of the influence of the organ transplantation procedure on melatonin production; b) action of melatonin on organ transplantation. RESULTS The cardiac transplantation surgical procedure, immunosuppression, and graft did not influence melatonin secretion in rodents, but there was a significant reduction of melatonin in the renal transplantation procedure in patients with renal insufficiency. Melatonin administration in experimental models decreased rejection and improved transplant success. CONCLUSION Studies show that melatonin can reduce organ and species dependence, and the use of melatonin decreases graft rejection.

RESUMO INTRODUÇÃO Embora a terapia estrogênica seja amplamente utilizada contra sintomas pós-menopausais, ela pode apresentar efeitos adversos, incluindo câncer de mama e endometrial. Assim, as isoflavonas da soja são consideradas uma alternativa possível à terapia estrogênica. No entanto, ainda há controvérsias se estes compostos exercem efeitos tróficos significativos no colo do útero. OBJETIVOS Avaliar as alterações histomorfométricas e imuno-histoquímicas no colo do útero de ratas ovariectomizadas tratadas com isoflavonas da soja (iso). MÉTODOS Quinze ratas Wistar adultas foram ovariectomizadas bilateralmente (Ovx) e separadas em três grupos: Grupo I (Ovx) - veículo (propilenoglicol); Grupo II (Ovx-Iso) - receberam extrato concentrado de Iso (150 mg/kg) e Grupo III (Ovx-E2) - tratado com 17β-estradiol (10 µg/kg); as soluções foram administradas via gavagem por 30 dias consecutivos. Posteriormente, os colos uterinos foram retirados, fixados em formaldeído a 10% tamponado e processados para inclusão em parafina. Cortes (4 µm) foram coradas com hematoxilina e eosina para estudo morfológico e morfométricos, enquanto outros foram submetidos à imuno-histoquímica para detecção de Ki-67 e do fator de crescimento endotelial vascular-A (Vegf-A). Os dados obtidos foram submetidos à análise estatística (p≤0,05). RESULTADOS Observamos a presença de colo uterino atrófico no GI (Ovx), sendo este mais volumoso no GII (Ovx+Iso) e ainda mais volumoso no GIII (Ovx+E2). A espessura da mucosa cervical foi significativamente maior no GIII (Ovx-E2), em comparação ao GI (Ovx) e ao GII (Ovx-Iso). A proliferação celular (Ki-67) foi significativamente mais elevada nos grupos tratados com estradiol e isoflavonas, enquanto a imunoexpressão de Vegf-A foi significativamente maior no GIII (Ovx-E2), em comparação ao GII (Ovx-Iso) e ao GI (Ovx-E2). CONCLUSÕES As isoflavonas da soja causam menos efeitos tróficos e proliferativos no colo do útero de ratas em comparação ao estrogênio.

SUMMARY INTRODUCTION Although estrogen therapy is widely used against post-menopausal symptoms, it can present adverse effects, including endometrial cancer. Soy isoflavones are considered a possible alternative to estrogen therapy. However, there are still concerns whether isoflavones exert trophic effects on the uterine cervix. OBJECTIVES To evaluate the histomorphometric and immunohistochemical alterations in the uterine cervix of ovariectomized rats treated with soy isoflavones (Iso). METHODS Fifteen adult Wistar rats were ovariectomized (Ovx) and divided into three groups: Group I (Ovx), administered with vehicle solution; Group II (OVX-Iso), administered with concentrated extract of Iso (150 mg/kg) by gavage; and Group III (OVX-E2), treated with 17β-estradiol (10 µg/kg), subcutaneously. After 30 days of treatments, the uterine cervix was fixed in 10% formaldehyde and processed for paraffin-embedding. Sections were stained with Hematoxylin and eosin for morphological and morphometric studies or subjected to immunohistochemistry for detections of Ki-67 and vascular endothelial growth factor-A (Vegf-A). The data obtained were subjected to statistical analysis (p ≤ 0.05). RESULTS We noted an atrophic uterine cervix in GI, whereas it was more voluminous in GII and even more voluminous in GIII. The thickness of the cervical mucosa was significantly higher in GIII, as compared to GI and GII. The cell proliferation (Ki-67) was significantly elevated in the estradiol and isoflavones treated groups, whereas Vegf-A immunoexpression was significantly higher in GIII, as compared to groups GII and GI. CONCLUSIONS Soy isoflavones cause less trophic and proliferative effects in the uterine cervix of rats as compared to estrogen.

RESUMO A melatonina é conhecida por seus efeitos no sono e no sistema reprodutivo dos mamíferos. Este último tem receptores de melatonina tipos 1 e 2, que atuam para regular, entre outras coisas, o AMP cíclico. Apesar de todos os dados da literatura, ainda não há um conhecimento sólido ou uma compreensão clara da ação do hormônio na fisiologia das células foliculares ovarianas. OBJETIVO Revisar e avaliar estudos da ação da melatonina na literatura sobre as células internas da granulosa/teca ovariana. MÉTODOS A revisão sistemática foi realizada de acordo com as recomendações do Prisma. As bases de dados primárias Medline e Cochrane foram consultadas com o uso de termos específicos. Não houve bar na língua ou ano de publicação. RESULTADOS Sete artigos sobre a ação da melatonina nas células da granulosa foram selecionados. O que se segue pode ser atribuído aos efeitos do hormônio: a) aumento de progesterona no meio de cultura; b) aumento da produção de estrogênio; c) ação antagônica no estrogênio; d) melhoria na qualidade celular, resultando em melhor embrião e maiores taxas de gravidez; e) melhor proliferação celular via MAPK; f) redução de radicais livres. No entanto, existem artigos controversos relatando redução na produção de progesterona. CONCLUSÃO A melatonina interfere na produção de esteroides sexuais, aumentando a produção de progesterona. Tal ação pode ajudar a melhorar a qualidade do oócito.

SUMMARY Melatonin is known for its effects on both the sleep and reproductive system of mammals. The latter has melatonin receptors type 1 and 2, which act to regulate, among other things, cyclic AMP. Notwithstanding all the literature data, there is still no sound knowledge or a clear understanding of the hormone’s action on the physiology of ovarian follicular cells. OBJECTIVE To review and evaluate studies about melatonin action on the ovarian granulosa/theca interna cells from the literature. METHODS The systematic review was carried out according to the PRISMA recommendations. The MEDLINE and Cochrane primary databases were consulted with the use of specific terms. There was no limitation on language or publication year. RESULTS Seven papers about melatonin action on granulosa cells were selected. The following can be attributed to the hormone’s effects: a) progesterone increase in culture medium; b) increased estrogen production; c) antagonistic action on estrogen; d) improvement in cell quality resulting in improved embryo and higher pregnancy rates; e) improved cell proliferation via MAPK; f) reduction of free radicals. Nevertheless, there are contrarian papers reporting a reduction in progesterone production. CONCLUSION Melatonin interferes in sex steroid production, boosting progesterone output. Such action may help improve oocyte quality.

RESUMO OBJETIVO Avaliar os efeitos ovarianos da melatonina (Mel) em ratas com síndrome dos ovários policísticos (SOP) antes e após a indução do estro-permanente. MÉTODOS Trinta e duas ratas com ciclos estrais regulares foram igualmente divididas em quatro grupos: 1) GCtrl - fase de estro. 2) GSOP - fase de estro-permanente. 3) GMel1 – tratadas por 60 dias com Mel (0,4 mg/kg) durante a indução do estro-permanente e 4) GMel2 – ratas com SOP e tratadas com Mel. Após eutanásia dos animais, os ovários foram processados para inclusão em parafina. Cortes foram corados com H.E ou submetidos à imuno-histoquímica para detecção de Ki-67 e caspase-3 clivada (Casp-3). RESULTADOS O GSOP mostrou ausência de corpos lúteos e vários cistos ovarianos, além de inúmeras células intersticiais. A presença de corpos lúteos e o aumento significativo dos folículos primários e antrais foram observados nos grupos tratados com Mel, os quais também mostraram diminuição no número de cistos ovarianos e na área ocupada pelas células intersticiais. Esses resultados foram mais evidentes no GMel1 do que no GMel2. A porcentagem de células Ki-67 positivas foi significativamente maior no GMel1 e no GMel2, sendo mais evidente no GMel2, em comparação ao GSOP. Por outro lado, a porcentagem de células positivas à Casp-3 foi menor nas células da granulosa do GMel1 e maior nas células intersticiais do GMel2, em comparação ao GSOP. CONCLUSÃO A administração de melatonina previne o estado de estro-permanente em ratas com SOP. Esse efeito é mais eficiente quando a melatonina é administrada após indução do estado de estro-permanente.

SUMMARY OBJECTIVE To evaluate the ovarian effects of melatonin (Mel) in a rat model of polycystic-ovary-syndrome (PCOS) before and after permanent estrus induction. METHODS Thirty-two adult-female rats with regular estrous cycle were equally divided into four groups: 1) GCtrl – at estrous phase. 2) GPCOS - at permanent-estrous phase. 3) GMel1 – treated for 60 days with Mel (0.4 mg/Kg) during permanent estrus induction and 4) GMel2 – rats with PCOS and treated for 60 days with Mel. After that, the animals were euthanized, and the ovaries were removed and processed for paraffin embedding. Sections were stained with H.E. for histomorphometry or subjected to immunohistochemistry for Ki-67 and cleaved caspase-3 (Casp-3) detections. RESULTS The GPCOS showed lack of corpus luteum and several ovarian cysts, as well as interstitial-like cells. The presence of corpus luteum and a significant increase in primary and antral follicles were observed in Mel-treated groups, which also showed a decrease in the number of ovarian cysts and in the area occupied by interstitial-like cells. These results were more evident in GMel1. The percentage of Ki-67-positive cells was significantly higher in the Mel-treated groups, mainly in the GMel2, as compared to GPCOS. On the other hand, the percentage of Casp-3-positive cells was significantly lower in granulosa cells of GMel1, whereas it was significantly higher in the interstitial-like cells of GMel2, in comparison to GPCOS. CONCLUSION Melatonin administration prevents the permanent estrus state in the PCOS rat model. This effect is more efficient when melatonin is administered before permanent estrus induction.

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Abstract Purpose: To evaluate the healing potential of the Ximenia americana hydroalcoholic extract in 10% cream in excisional wound models in rats. Methods: Sixty male adults Wistar rats were submitted to skin and subcutaneous tissue surgery in the right and left thoracic regions, divided into three experimental groups: Standard submitted to treatment with only the base vehicle, Treated wounds treated with hydroalcoholic extract of X. americana applied on 10%, Lanette base and Control, untreated wounds. The treatment was performed daily and the wounds evaluated microscopically by the quantification of fibroblasts, collagen fibers and blood vessels. Results: The histomorphometric analysis showed a significant increase in the number of fibroblasts, collagen fibers and blood vessels in the treated group. Conclusion: The topical action of the cream based on Ximenia americana shows angiogenic effects and improves the replacement of collagen, suggesting its use for the development of herbal remedy in the treatment of cutaneous wound healing.

Abstract Purpose: To analyze the effects of ischemic preconditioning (IPC) in the expression of apoptosis-related genes in rat small intestine subjected to ischemia and reperfusion. Methods: Thirty anesthetized rats underwent laparotomy and were drive into five groups: control (CG); ischemia (IG); ischemia and reperfusion (IRG); IPC and ischemia (IG+IPC); IPC and ischemia and reperfusion (I/RG+IPC). Intestinal ischemia was performed by clamping the superior mesenteric artery for 60 minutes, whereas reperfusion lasted for 120 minutes. IPC was carried out by one cycle of 5 minutes of ischemia followed by 10 minutes of reperfusion prior to the prolonged 60-minutes-ischemia and 120-minutes-reperfusion. Thereafter, the rats were euthanized and samples of small intestine were processed for histology and gene expression. Results: Histology of myenteric plexus showed a higher presence of neurons presenting pyknotic nuclei and condensed chromatin in the IG and IRG. IG+IPC and I/RG+IPC groups exhibited neurons with preserved volume and nuclei, along with significant up-regulation of the anti-apoptotic protein Bcl2l1 and down-regulation of pro-apoptotic genes. Moreover, Bax/Bcl2 ratio was lower in the groups subjected to IPC, indicating a protective effect of IPC against apoptosis. Conclusion: Ischemic preconditioning protect rat small intestine against ischemia/reperfusion injury, reducing morphologic lesions and apoptosis.