Carvacrol, (-)-borneol and citral reduce convulsant activity in rodents

Carvacrol, a monoterpenic phenol present in essential oils of the Labiatae family, has been used through the ages as a source of flavor in food and for medicinal purposes. Borneol is a monoterpene found in several species of Artemisia and Dipterocarpaceae, used for anxiety, pain and anesthesia in traditional Chinese. Citral, a mixture of two geometrical isomers (neral and geranial), is one of the most important compounds in some citrus oils and has central nervous system (CNS) properties. The anticonvulsant effect of carvacrol (CARV), (-)-borneol (BOR) and citral (CIT) was investigated in two animal models of epilepsy. Mice were pretreated with CARV, BOR or CIT (50, 100, and 200 mg/kg, i.p.) 30 min before pentylenetetrazole (PTZ) or maximal electroshock (MES) tests, the two most important animal epilepsy tests. The latency for development of convulsions and protection percentage was recorded. In order to investigate the involvement of GABAergic system, flumazenil was utilized. These monoterpenes, CARV in a higher, but not in a lower dose (p < 0.001), BOR and CIT in all doses (p < 0.05 or p < 0.001), were capable of promoting an increase of latency for the development of convulsions induced by PTZ. Additionally, these compounds were efficient in preventing the tonic convulsions (p < 0.05) induced by MES. However, the GABAergic neurotransmitter system might be involved, at least in BOR effects. Henceforth, our results suggest that CARV, BOR and CIT possess anticonvulsant activity effect against PTZ-induced convulsions and MES.Key words: Carvacrol, (-)-borneol, citral, anticonvulsant activit

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Are environmental pollutants risk factors for low birth weight? Os poluentes ambientais são fatores de risco para o baixo peso ao nascer?

The aim of this study was to assess the association between prenatal exposure to air pollutants and low birth weight in a medium-sized city. An ecological study was performed, using live birth data from São José dos Campos, São Paulo State, Brazil. The environmental data were obtained from the São Paul State Environmental Agency. The study included full-term newborns whose mothers were 20 to 34 years of age and had at least a complete high school education, seven or more prenatal visits, singleton pregnancy, and vaginal delivery, in order to minimize potential confounding from these variables. Logistic regression was used to estimate the effect of each pollutant. Low birth weight was defined as less than 2,500g. The sample included a total of 2,529 data from 2001 that met the inclusion criteria (25.6% of the total). We identified 99 newborns (3.95% of the sample) with low birth weight, and the pollutants sulfur dioxide and ozone were associated with low birth weight. The final model was À(x) = -1.79 + 1.30 (SO2) + 1.26 (O3). Thus, sulfur dioxide and ozone were identified as risk factors for low birth weight in a medium-sized city in Southeast Brazil.<br>O objetivo foi estimar o papel de poluentes no baixo peso ao nascer numa cidade de porte médio. Foi um estudo ecológico com dados obtidos da Declaração de Nascido Vivo relativos a São José dos Campos, São Paulo, Brasil. Os dados ambientais foram fornecidos pela Companhia de Tecnologia de Saneamento Ambiental (CETESB). Foram incluídos no estudo recém-nascidos a termo, com mães entre 20 e 34 anos de idade, segundo grau completo, sete ou mais consultas realizadas no pré-natal, gravidez única e parto normal, para minimizar o efeito de confusão destas variáveis. Utilizou-se regressão logística para estimar o efeito de cada poluente. Baixo peso ao nascer foi considerado aquele inferior a 2.500g. Foram incluídos 2.529 dados de 2001 que atenderam aos critérios de inclusão (25,6% do total). Identificamos 99 recém-nascidos (3,95% dessa amostra) com baixo peso e os poluentes dióxido de enxofre e ozônio como associados ao baixo peso ao nascer. O modelo final foi À(x) = -1,79 + 1,30 (SO2) + 1,26 (O3). Assim, identificou-se o dióxido de enxofre e ozônio como responsáveis pelo baixo peso ao nascer numa cidade de porte médio do Sudeste brasileiro

Depression, anxiety, hopelessness and quality of life in users of cocaine/crack in outpatient treatment

Abstract Objective: To identify symptoms of anxiety, depression, and feelings of hopelessness in patients in outpatient treatment for substance dependency and to test for correlations with various aspects of their quality of life. Methods: A cross-sectional study of a sample of 25 men in recuperation from substance dependency, selected by convenience. We assessed symptoms of depression (Beck Depression Inventory-II), anxiety (Beck Anxiety Inventory), hopelessness (Beck Hopelessness Scale), and quality of life (World Health Organization Quality of Life instrument-Abbreviated version [WHOQOL-Bref]), and also analyzed sociodemographic profile, substance abuse, and family history. Categorical variables were expressed as frequencies and percentages and quantitative variables as means and standard deviations or as medians and interquartile ranges. We also analyzed Spearman correlations to a 5% significance level. Results: The study revealed prevalence rates of 32% for depression, 24% for anxiety, and 12% for hopelessness, at a moderate/severe level. Correlations between Beck scales and WHOQOL-Bref were significant; but impacts differed in the four areas evaluated. Conclusions: Overall, we observe global negative impacts on subjects' lives, affecting their psychiatric symptoms and quality of life and their relationships and occupational factors to a similar degree. The results show that the lower the scores on these scales, the better the quality of life in some areas, indicating that there is a negative correlation between psychiatric symptoms and quality of life