Lipoic acid prevents mirtazapine-induced weight gain in mice without impairs its antidepressant-like action in a neuroendocrine model of depression.

Mirtazapine (MIRT) is a multi-target antidepressant used in treatment of severe depression with promising efficacy, but also with important side effects, mainly sedation and weight gain. Thus, the present study aimed to test the effects of the neuroprotective antioxidant lipoic acid (ALA) in the reversal of weight and metabolic changes induced by MIRT in corticosterone-induced depression model in mice, as well as proposed mechanisms for their association antidepressant and pro-cognitive effects. To do these male Swiss mice received Tween 80 (control), corticosterone (CORT 20 mg / kg), MIRT (3 mg / kg) and ALA (100 or 200 mg / kg), alone or associated for 21 days. After this, the animals were subjected to behavioral tests for affective and cognitive domains. Daily weight changes, blood cholesterol fractions and corticosterone were measured. Also, hippocampus (HC) protein expression of the serotonin transporter (SERT), synaptophysin, protein kinase B-Akt (total and phosphorylated) and the cytokines IL-4 and IL-6 were investigated. CORT induced a marked depression-like behavior, memory deficits, metabolic changes (total cholesterol and LDL) and increased serum corticosterone. Also, CORT increased SERT expression in the HC. MIRT alone or combined with ALA sustained its antidepressant-like effect, as well as reversed CORT-induced impairment in spatial recognition memory. Additionally, the association MIRT+ALA200 reversed the weight gain induced by the former antidepressant, as well as reduced serum corticosterone levels and SERT expression in the HC. ALA alone induced significant weight loss and reduced total cholesterol and HDL fraction. Our findings provide promising evidence about the ALA potential to prevent metabolic and weight changes associated to MIRT, without impair its antidepressant and pro-cognition actions. Therefore, ALA+MIRT combination could represent a new therapeutic strategy for treating depression with less side effects.

Peritoneal endometriosis induces time-related depressive- and anxiety-like alterations in female rats: involvement of hippocampal pro-oxidative and BDNF alterations.

Endometriosis is a gynecological condition affecting 10% of women in reproductive age. High rates of depression and anxiety are observed in these patients. The mechanisms underlying endometriosis-induced behavioral alterations are still elusive. Animal models provide a useful tool to study the temporal sequence and biological pathways involved in this disease and comorbid states. Here, we sought to characterize time-related behavioral alterations in rats submitted to endometriosis model (EM) induced by peritoneal auto-transplantation of uterine tissues weekly for three weeks. Corticosterone stress reactivity, oxidative stress markers - reduced glutathione (GSH), lipid peroxidation, activity of superoxide dismutase (SOD) and myeloperoxidase (MPO) - and brain-derived-neurotrophic factor (BDNF) levels in the hippocampus were also evaluated. We observed a progressive increase in anxiety-like behavior from 14th to 21st days post-EM. Despair-like behavior was observed from the 14th day post-EM on, while anhedonia and apathetic-like behaviors accompanied by increased corticosterone stress response were detected on 21 days post-EM. Increased pain sensitivity was observed from the 7th day post-EM and was accompanied by increased endometrioma weight. The pro-oxidative alterations, decreased GSH and increased SOD activity were observed on 21 days post-EM, except for lipid peroxidation that was altered from the 14th day. Decreased BDNF also occurred on the 21st day. Therefore, this study demonstrates that EM is related to several features of clinical depression and proposes the contribution of hippocampal oxidative state and neurotrophic support for the emergence of these changes. Our results support the use of this model as a useful tool to test new strategies for endometriosis-related neuropsychiatric symptoms.

Gastroprotective effects of the essential oil of Hyptis crenata Pohl ex Benth. on gastric ulcer models.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyptis crenata Pohl ex Benth (Lamiaceae), popularly known as "hortelã-brava" or "hortelã do campo", is widely distributed in the northeast of Brazil. In Brazil, the leaves of this plant have been used in traditional medicine for the treatment of gastrointestinal disturbances, including gastric ulcers. In an attempt to experimentally validate this claimed antiulcerogenic activity, the gastroprotective effects of the essential oil extracted from the leaves of the Hyptis crenata Pohl ex Benth (EOHc) were evaluated in recognized gastric ulcer models in mice. MATERIALS AND METHODS: EOHc was obtained by hydrodistillation and analyzed using gas chromatography-mass spectrometry (GC-MS). Swiss male mice (25-30g) were used for the studies. The gastric ulcers were induced by oral administration of absolute ethanol or indomethacin 45min after oral pretreatment with EOHc, vehicle and positive control drugs. One hour after the ulcerative challenges, the stomachs were removed and the area of the lesions was measured. The volume, pH and total acidity of the gastric secretions were determined using the pylorus ligature model. The gastrointestinal motility was measured using gastric emptying and intestinal transit. The ethanol-induced gastric mucus depletion and lipid peroxidation were also analyzed. RESULTS: Our findings are as follows: A significant inhibition of gastric lesions induced by absolute ethanol was observed in the mice pre-treated with EOHc, at a dose of 30 and 100 and 300mg/kg (5.56±1.51, 2.88±0.82 and 1.71±0.54mm(2), respectively) compared to control group (118.03±35.4mm(2)). Also, EOHc (300mg/kg) produced a gastroprotective effect against the gastric lesions induced by indomethacin (16.07±4.68mm(2)) compared to control group (38.64±6.1mm(2)). EOHc pretreatment produced a reduction in the ethanol-induced lipid peroxidation from 3.9±0.22 to 2.4±0.1µmol/mg tissue (EOHc-300mg/kg and control group, respectively). We also observed that EOHc pretreatment decreased the gastric emptying, but did not alter the intestinal transit ratio, ethanol-induced depletion of the gastric wall mucus or secretion parameters (volume, pH and [H(+)]). CONCLUSION: Our data indicate that EOHc exerts a gastroprotective effect, indicated by its significant inhibition of gastric lesions in ethanol- and indomethacin-induced ulcer models, which may be associated with its accelerating effect on gastric emptying and reduction in oxidative damages. Our data suggest a potential therapeutic application for EOHc in the treatment of gastric ulcers.

Comportamento cardíaco dos pacientes com de insuficiência mitral antes e após a reconstrução valvar / Cardiac behavior of patients with mitral regurgitation before and after valve reconstruction

Esta pesquisa buscou avaliar o comportamento cardíaco dos portadores de Insuficiência Mitral antes e após a reconstrução valvar (protocolo de MIRACLE) no Hospital de Messejana do Coração. Tratou-se de um estudo em prontuários, de 10 pacientes, independente do sexo e da idade, que se submeteram à cirurgia no período de 1999 a 2006. Os dados foram coletados através de uma ficha de avaliação, baseada no Formulário de Registro (Plastia/Troca de válvula mitral em pacientes com disfunção severa do ventrículo esquerdo), contendo aspectos sobre o perfil populacional e exames complementares, e analisados pela estatística inferencial. Os resultados do estudo mostraram predominância do sexo feminino e 2 realizaram transplante cardíaco. Observou-se que 4 pacientes permaneceram na mesma classe funcional (CF) no pós-operatório e 6 evoluíram para CF menor. Os diâmetros sistólico e diastólico reduziram 3,70 mm e 0,50 mm, respectivamente. A fração de ejeção aumentou em 4%. Não se observou diferença significativa quanto à análise da variabilidade da freqüência cardíaca através do Eletrocardiograma. Conclui-se que, após a cirurgia de reconstrução valvar, há melhora da CF e diâmetro sistólico. Sugere-se inserir esses pacientes em programa de reabilitação cardíaca para observar maior melhora no comportamento cardíaco.

This study aimed to evaluate the cardiac behavior of patients with mitral regurgitation before and after valve reconstruction (MIRACLE protocol) at the Hospital Messejana do Coração. It was based on a study of 10 patients, regardless of gender and age, who underwent surgery in the period of 1999 to 2006. The data was collected through an evaluation sheet, based on a Register Form (Repair/Change of Mitral Valve in Patients with Severe Left Ventricle Dysfunction), containing population’s profile aspects and complementary exams, and analyzed by inferential statistics. The patients were mainly female and two of the patients had undergone a cardiac transplant. It was observed that 4 patients staid at the same functional class (FC) during the recovering period and 6 developed minor FC. The systolic and diastolic diameters reduced 3,70 mm and 0,50 mm respectively. The ejection fraction raised 4%. It was not observed any significant difference regarding the cardiac frequency variability by means of electrocardiograph monitoring. It was concluded that there is an improvement of FC and systolic diameter after valve reconstruction surgery. It is suggested to place these patients in cardiac rehabilitation program so that the cardiac behavior improvement may be observed.