Clozapine linked to nanocapsules minimizes tissue and oxidative damage to biomolecules lipids, proteins and DNA in brain of rats Wistar.

Clozapine, atypical antipsychotic, can change oxidative stress parameters. It is known that reactive species, in excess, can have a crucial role in the etiology of diseases, as well as, can potentiating adverse effects induce by drugs. The nanocapsules have attracted attention as carriers of several drugs, with consequent reduction of adverse effects. This study aimed to evaluate histopathology and oxidative damage of biomolecules lipids, proteins and DNA in the brain of Wistar rats after treatment with nanocapsules containing clozapine. The study consisted of eight groups of male Wistar rats (n = 6): saline (SAL), free clozapine (CZP) (25 mg/Kg i.p.), blank uncoated nanocapsules (BNC), clozapine-loaded uncoated nanocapsules (CNC) (25 mg/Kg i.p.), blank chitosan-coated nanocapsules (BCSN), clozapine-loaded chitosan-coated nanocapsules (CCSN) (25 mg/Kg i.p.), blank polyethyleneglycol-coated nanocapsules (BPEGN), clozapine-loaded polyethyleneglycol-coated nanocapsules (CPEGN) (25 mg/Kg i.p.). The animals received the formulation once a day for seven consecutive days and euthanized in the eighth day. After euthanasia, the brain was collected and homogenate was processed for further analysis. The histopathology showed less brain tissue damage in nanocapsules-treated groups. The lipid peroxidation and carbonylation of proteins showed a significant increase (p < 0.05) induced by CZP. CNC and CPEGN groups obtained a reduction membrane of lipids damage and nanocapsules-treated groups showed significant improvement protein damage. CZP was able to induce genetic oxidative damage, while the nanocapsules causing less damage to DNA. The findings show that different coatings can act protecting target tissues decreasing oxidative damage, suggesting that the drug when linked to different nanocapsules is able to mitigate the harmful effects of clozapine.

Aqueous extract of pummelo pulp (Citrus maxima) improves the biochemical profile and reduces the inflammation process in Wistar rats with non-alcoholic fatty liver disease.

This study investigated the effect of pummelo extract (Citrus maxima) on biochemical, inflammatory, antioxidant and histological changes in NAFLD rats. Forty male Wistar rats divided into four groups were used: (1) control group; (2) fructose associated with high-fat diet - DHF; (3) normal diet + pummelo extract (50 mg/kg); and (4) FHD + pummelo extract. This was administered at dose of 50 mg/kg of the animal's weight, by gavage, for 45 days. Significant improvement in lipid profile, liver and kidney function, inflammation, oxidative stress markers was identified in group 4 compared to group 2. Regarding TNF-α and IL-1ß, group 2 showed higher values (respectively 142, 5 ± 0.7 and 560.5 ± 2.7 pg/mg protein) compared to group 4 (respectively 91.4 ± 0.9 and 402.1.4 ± 0.9 pg/mg protein), p < 0.05. Significant increases were found in SOD and CAT activities, respectively 0.10 ± 0.06 and 8.62 ± 1.67 U/mg protein for group 2 and respectively 0.28 ± 0.08 and 21.52 ± 2.28 U/mg of protein for group 4. Decreases in triglycerides, hepatic cholesterol and fat droplets in hepatic tissue were observed in group 4 compared to group 2. Results highlight that pummelo extract may be useful for prevent the development of NAFLD.

Association between carriers of the G allele of the + 45T> G variant of the ADIPOQ gene (rs 2241766) and the cardiometabolic profile in sickle cell trait.

AIMS: investigate the association between the +45T > G variant of the ADIPOQ gene and the metabolic syndrome (MS) in patients with sickle cell trait (SCT). 33 patients with SCT and 35 control group participated in the study. Lower levels of HDL and adiponectin were observed in patients with G allele and sickle cell trait. There were no differences between the prevalence of MS between the groups and there was no association between the +45T > G variant of the ADIPOQ gene and MS risk allele. MATERIALS AND METHODS: Participants with and without sickle cell anemia answered a questionnaire, performed anthropometric and laboratory analyzes. They were genotyped for the +45T > G variant of the ADIPOQ gene and evaluated for the presence or absence of metabolic syndrome. The study was approved by the Research Ethics Committee of UNIPAMPA (RS/Brazil). KEY FINDINGS: The GG + TG genetic model, it was associated with lower levels of adiponectin and HDL cholesterol in the SCT group. There was no association between the other studied markers and MS. SIGNIFICANCE: For the first time, an association was demonstrated between the G allele of the +45T > G variant of the ADIPOQ gene and a worse cardiometabolic profile (lower serum concentrations of adiponectin and HDL cholesterol) in patients with sickle cell trait.

Extract of Citrus maxima (pummelo) leaves improve hepatoprotective activity in Wistar rats submitted to the induction of non-alcoholic hepatic steatosis.

Non-alcoholic fatty liver disease is a spectrum of liver changes, ranging from hepatic steatosis to hepatocellular carcinoma. The Citrus maxima (CM) has been shown to be beneficial to the organism, and these activities are attributed to the presence of phytochemical compounds. The objective of this study was to evaluate the n vitro antioxidant potential of the CM leaves extract and on Wistar rats submitted to hepatic steatosis induction by fructose-associated hyperlipid diet (FHD). For the evaluation of in vivo effects, the animals were distributed in G1 (normal diet - ND), G2 (FHD), G3 (ND + extract 50mg/kg) and G4 (FHD + extract 50 mg/kg). All the parameters were determined through classical methodologies. The extract showed a significant antioxidant potential in vitro. In the in vivo analysis, the diet used was able to induce the development of metabolic abnormalities that favored the formation of hepatic steatosis (G2). Changes in inflammatory markers, increase in markers of oxidative damage, and reduction of antioxidant defenses were also observed. In addition, the extract did not cause changes in the animals' weight gain and acted as an anti-inflammatory, since G4 animals exhibited significantly reduced levels of the inflammatory markers. In the liver, the extract significantly decreased the content of fat, cholesterol and triglycerides compared to G2. The extract also showed antioxidant activity (G4) when compared to G2. The results suggest that the extract of CM leaf showed hepatoprotective, hypolipidemic, anti-inflammatory and antioxidant activities and the presence of phenolic compounds is a probable cause for such activities.

Protective effect of the hydroalcoholic extract of Tripodanthus acutifolius in hypercholesterolemic Wistar rats.

Cardiovascular disease (CVD) are a major public health problem, as they are among the leading causes of mortality worldwide. Tripodanthus acutifolius (TA) is a hemiparasite plant used for medicinal purposes with great antioxidant capacity. However, little is known about its hypolipemic effect. Thus, the aim of this study was to evaluate the effects of the hydroalcoholic extract of Tripodanthus acutifolius leaves in hypercholesterolemic Wistar rats. The animals were divided into: (1) NC (Normocaloric Control); (2) HC (Hypercaloric Control); (3) Oral Simvastatin Suspension 10mg/kg (SIM); (4) TA extract 50mg/kg (TA 50mg/kg) and (5) TA 100mg/kg. The in vitro antioxidant activity assay demonstrated that TA shows high antioxidant capacity. The in vivo findings demonstrated that TA supplementation resulted in significant decreases (p<0.05) in Total Cholesterol (TC), Triglycerides (TG) and Low density lipoprotein (LDL) levels, whereas High density lipoprotein (HDL) levels increased significantly in all TA-supplemented groups in relation to the HC group. Hepatic, renal and cardiac function markers improved during supplementation. Serum adiponectin levels increased significantly, whereas C-reactive protein (PCRus) levels decreased in the TA-supplemented in relation to the HC group. Catalase (CAT), superoxide dismutase (SOD) and gluthatione peroxidase (GPx) activities, as well as polyphenols, vitamin C (VitC) and total gluthatione (GSH), increased significantly in the TA-supplemented groups treated when compared to the HC group. Concerning oxidative damage to biomolecules, TA showed a protective effect on lipids, proteins and DNA. Regarding the histological analysis of the aortic artery, TA treatment was able to decrease aortic vasculature. Therefore, TA is rich in antioxidant compounds and may be an alternative for the treatment of hypercholesterolemia.

Interaction between endothelial nitric oxide synthase gene polymorphisms (-786T>C, 894G>T and intron 4 a/b) and cardiovascular risk factors in acute coronary syndromes.

BACKGROUND AND AIMS: Endothelial rupture of coronary plaque can represent the pathomorphological substratum of acute coronary syndrome (ACS). Polymorphisms in the NOS3 gene (eNOS) -786T>C, 894G>T and intron 4 a/b VNTR can be associated with a higher susceptibility for ACS. The present study is focused on the investigation of the interaction of these polymorphisms and cardiovascular risk factors in 135 patients with ACS and 115 control subjects. METHODS: Case-control study where the allele and genotype frequencies of the polymorphisms -786T> C, 894G> T and intron 4 VNTR of the gene encoding eNOS were determined by PCR-RFLP associated with cardiovascular risk factors. RESULTS: An association of the 894TT genotype and 894GT+GG (OR 1.4; 95% CI 1.0-1.8) in ACS has been observed. Subjects without dyslipidemia and intron 4 a/b genotype present a lower chance for ACS development, whereas subjects without diabetes and 894TT genotype show a higher risk for ACS (OR 1.7; 95% CI 1.2-2.3). In patients without dyslipidemia, the 894GG genotype presented a tendency to behave as a protector factor against ACS. Also, the 894GG genotype has been a protective factor for ACS in females (OR 0.5; CI 95% 0.2-0.9). CONCLUSIONS: Our results suggest that eNOS polymorphisms may be an additional risk factor in development of ACS.

Análise do exame citopatológico e captura híbrida em mulheres atendidas em unidades básicas de saúde / Analysis of cytopathologic examination and hybrid capture in women receiving care in basic health units

Cervical cancer is one of the most frequent cancers among Brazilian women and its relationship with the human papillomavirus (HPV) is well established. Objective: To analyze the presence of DNA/HPV using Hybrid Capture method for women in the city of Uruguaiana (RS). Methods: During the period of January to December 2015, 51 cervicovaginal samples were collected from patients who sought care at Basic Health Units in the city. After the collection, conventional and liquid-based cytological analysis was performed. Results: The results of the study indicate the prevalence of genital HPV infection in 5.9% of the samples; low-risk DNA/HPV was detected in 3.9% of patients of reproductive age (PIR); and 2.0% of PIR presented highrisk DNA/HPV. By stratifying the prevalence of HPV in age, we found positivity between 16 and 31 years. Conclusion: Conventional cytology is often inconclusive and, in such cases, using molecular biology methods that detect the DNA/HPV presence would be very useful.

O câncer de colo de útero é um dos mais frequentes entre as mulheres brasileiras e a sua relação com o Papilomavírus Humano (HPV) é bem estabelecida. Objetivo: Analisar a presença de DNA/HPV por meio do método de captura híbrida em mulheres no município de Uruguaiana (RS). Métodos: No período compreendido entre janeiro e dezembro de 2015, foram coletadas 51 amostras cervicovaginais de pacientes que buscaram atendimento nas Unidades Básicas de Saúde do município. Após a coleta, foi realizada a análise citológica convencional e em base líquida. Resultados: Os resultados encontrados no estudo indicam a prevalência de infecção genital por HPV em 5,9% das amostras analisadas, sendo DNA/HPV de baixo risco em 3,9% e DNA/HPV de alto risco em 2,0% das infecções. Ao estratificar a prevalência de HPV por faixa etária, observou-se positividade entre 16 e 31 anos. Conclusão: A citologia convencional pode ser, muitas vezes, inconclusiva e, nesses casos, utilizar uma metodologia de biologia molecular que detecte a presença do DNA/HPV seria muito útil.