Lifestyle and Sense of Coherence: A comparative analysis among university students in different areas of knowledge.

BACKGROUND: The concept of health has undergone profound changes. Lifestyle Medicine consists of therapeutic approaches that focus on the prevention and treatment of diseases. It follows that the quality of life of university students directly affects their health and educational progress. EXPERIMENTAL METHODOLOGY: Socioeconomic, lifestyle (LS), and Salutogenesis Theory/sense of coherence (SOC) questionnaires were administered to college students from three different areas. The results were analyzed for normality and homogeneity, followed by ANOVA variance analysis and Dunn and Tukey post hoc test for multiple comparisons. Spearman's correlation coefficient evaluated the correlation between lifestyle and sense of coherence; p values < 0.05 were considered statistically significant. RESULTS: The correlation between LS and SOC was higher among males and higher among Medical and Human sciences students compared to Exact sciences. Medical students' scores were higher than Applied sciences and Human sciences students on the LS questionnaire. Exact science students' scores on the SOC questionnaire were higher than Human sciences students. In the LS areas related to alcohol intake, sleeping quality, and behavior, there were no differences between the areas. However, women scored better in the nutrition domain and alcohol intake. The SOC was also higher in men compared to women. CONCLUSION: The results obtained demonstrate in an unprecedented way in the literature that the correlation between the LS and SOC of college students varies according to gender and areas of knowledge, reflecting the importance of actions on improving students' quality of life and enabling better academic performance.

High prevalence of gastroschisis in Brazilian triple side border: A socioenvironmental spatial analysis.

This research investigated the spatial association between socioenvironmental factors and gastroschisis in Brazilian triple side border. A geographic analysis for gastroschisis prevalence was performed considering census sector units using Global Moran Index, Local Indicator of Spatial Association Analysis and Getis Ord statistics. Sociodemographic factors included rate of adolescent and parturients over 35 years; population with no income and above 5 minimum wages; rate of late prenatal; and proximity to power transmission lines. Logistic regression models were applied to verify the association between socio-environmental factors and prevalence of gastroschisis. No global spatial correlation was observed in the distribution of gastroschisis (Moran´s I = 0.006; p = 0.319). However, multiple logistic regression showed census sectors with positive cases had higher probability to power transmission lines proximity (OR 3,47; CI 95% 1,11-10,79; p = 0,031). Yet, spatial scan statistic showed low risk for gastroschisis in southern city region (OR = 0; p = 0.035) in opposite to power transmission lines location. The study design does not allow us to attest the causality between power transmission lines and gastroschisis but these findings support the potential exposure risk of pregnant to electromagnetic fields.

Major birth defects in the Brazilian side of the triple border: a population-based cross-sectional study.

BACKGROUND: Major birth defects increase the risk of fetal death and pediatric hospitalization, which also impact on healthcare costs. Sociodemographic factors can drastically affect reproductive health and be used to discriminate the exposure to hidden risk factors. Foz do Iguassu is a Brazilian city located in the triple-border region of Brazil / Paraguay / Argentina with high rates of birth defects. However no study aimed to verify factors associated with this incidence or preventive care is reported. The current work investigated the prevalence of major birth defects and its association with maternal sociodemographic factors in Foz do Iguassu. METHODS: In this population-based cross-sectional study we used data of all live births occurred in Foz do Iguassu from 2012 to 2017. The associated sociodemographic variables such as maternal age, maternal education, maternal race, country of residence, maternal parity and onset of prenatal care were analyzed. Each major birth defect was described according to absolute and relative frequencies, Kruskal-Wallis and logistic regression models were used to evaluate variables associated with selected birth defects. RESULTS: The most prevalent major birth defects were Cleft Lip and/or Palate (9.5/10,000), gastroschisis (6.93/10,000), spina bifida (5.53/10,000), hydrocephalus (5.53/10,000), hypospadias (4.55/10,000), Down syndrome (4.23/10,000), anencephaly (2.93/10,000), anorectal atresia / stenosis (1.95/10,000), undetermined sex (1.95/10,000), esophageal atresia / stenosis with or without fistula (1.63/10,000) and limb reduction defects (1.30/10,000). Maternal age was associated with gastroschisis and Down syndrome. Only maternal education up to 7 years was statistically associated with major birth defects considering all other sociodemographic variables. CONCLUSION: Cleft Lip and/or Palate and Gastroschisis prevalence were higher than those found in the literature. This findings may suggest a distinct epidemiological behavior regarding major birth defects in the region. The work opens new perspectives for birth defects risk factors in the triple-border.

Treatment with sodium nitroprusside improves the endothelial function in aortic rings with endothelial dysfunction.

PURPOSE: Verify if sodium nitroprusside (SNP) is able to improve endothelial function and if this effect is independent of nitric oxide (NO) release of the compound. METHODS: Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. Intact endothelium aortas were placed in a myograph and incubated with SNP: 0.1nM; 1nM or 10nM during 30min. Cumulative concentration-effect curves for acetylcholine (Ach) were realized to measure the relaxing capacity. Intracellular NO were measured (by DAF-2DA probe) in HUVEC treated with SNP 0.1nM or DETA/NO 0.1µM. The detection of intracellular superoxide radical (O2•-) was obtained by using DHE probe. RESULTS: Treatment of 2K-1C aortic rings with SNP (0.1; 1.0 and 10nM) improved endothelium dependent relaxation induced by acetylcholine. This improvement induced by SNP was verified at the concentration of 0.1nM, which does not release NO, suggesting that this effect was not induced due to NO release by SNP compound. Besides, we show that the cell treatment with 0.1nM of SNP decreased the fluorescence intensity to DHE in cells stimulated with angiotensin II. These results indicate that SNP decreases the concentration of O2•- in HUVEC cells. CONCLUSIONS: The SNP at a concentration that does not release NO inside the cells is able to attenuate endothelial dysfunction. DRUGS AND CHEMICALS: Acetylcholine (Ach) (PubChem CID:6060); angiotensin II human (Ang II) (PubChem CID: 16211177); diethylenetriamine/nitric oxide (DETA-NO) (PubChem CID 4518); dihydroethidium (DHE) (PubChem CID: 128682); phenylephrine (Phe) (PubChem CID: 5284443); sodium nitroprusside (SNP) (PubChem CID: 11963579); Thiazolyl Blue Tetrazolium Bromide (MTT) (PubChem CID: 64965); 4,5-diaminofluorescein diacetate (DAF-2DA); 4-hidroxy-Tempo (Tempol) (PubChem CID: 137994), were purchased from Sigma-Aldrich (St. Louis, MO, USA).

Metabolic profiling of human endothelial cells during autophagy assessed in a biomimetic microfluidic device model.

AIMS: Autophagy is critical to endothelial function. We explored the effects of autophagy induced by serum deprivation on Human Umbilical Vascular Endothelial Cells (HUVEC) metabolome profile and its inhibition by the antimalarial drug chloroquine (CLQ) using a microfluidic biomimetic model. MAIN METHODS: The metabolites secreted by HUVEC into the circulating microfluidics were determined by liquid chromatography mass spectrometry (LC-MS) and further analyzed using Metaboanalyst 3.0 multivariate and pathway analysis tools. KEY FINDINGS: Principal component analysis showed the discrimination of metabolites between treated and control groups. The results also identified alterations in metabolites relevant to endothelial function such as arginine, glutamate and energy metabolism pathways. Interestingly, CLQ mostly reversed the changes induced by serum deprivation. SIGNIFICANCE: The knowledge of endothelial metabolic profile during autophagy may contribute to the identification of clinical biomarkers and potential therapeutic approaches based on the regulation of autophagy.

In vitro Treatment with cis-[Ru(H-dcbpy-)2(Cl)(NO)] Improves the Endothelial Function in Aortic Rings with Endothelial Dysfunction.

PURPOSE: The ruthenium complex cis-[Ru(H-dcbpy-)2(Cl)(NO)] (DCBPY) is a nitric oxide (NO) donor and studies suggested that the ruthenium compounds can inactivate O2-. The aim of this study is to test if DCBPY can revert and/or prevent the endothelial dysfunction. METHODS: Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. To vascular reactivity study, thoracic aortas were isolated, rings with intact endothelium were incubated with: DCBPY: 0.1; 1 and 10µM, DCBPY plus hydroxocobalin (NO scavenger) or tempol during 30 minutes, and concentration effect curves to acetylcholine were performed. The potency values (pD2) and maximum effect (ME) were analyzed. The O2- was generated using hypoxantine xantine oxidase and the reduction of cytochrome c, NO consumption by O2- and the effect in avoid NO consumption was measured. RESULTS: In 2K-1C DCBPY at 0.1; 1 or 10µM improved the relaxation endothelium dependent induced by acetylcholine in aortic rings compared to control 2K-1C, and also improved ME. In rings from 2K incubation with DCBPY (0.1; 1.0 and 10 µM) did not change pD2 or ME. Incubation with 0.1 µM of DCBPY plus hydroxocobalamin did not modify the potency and ME in 2K-1C compared to DCBPY (0.1 µM). DCBPY and SOD inhibits the reduction of cytochrome c and inhibited the NO consumption by O2-, showing that O2- has been removed from the solution. CONCLUSION: Our results suggest that DCBPY at a lower concentration (0.1 µM) is not an NO generator, but can inactivate superoxide and improves the endothelial function.

Inhibition of autophagy by chloroquine stimulates nitric oxide production and protects endothelial function during serum deprivation.

BACKGROUND/AIMS: Autophagy plays a fundamental role in cell survival under stress conditions such as nutrient deprivation. Decreased nitric oxide (NO) production, which may contribute to vascular dysfunction, is one of the consequences of autophagy in endothelial cells. The antimalarial drug chloroquine (CLQ) inhibits autophagy by blocking autophagosome formation and has been proposed as adjuvant chemotherapy in other diseases. METHODS: Autophagy was induced by serum deprivation in Human Umbilical Vascular Endothelial Cells (HUVEC) as demonstrated by formation of Acidic Vesicular Organelles (AVOs), conversion of Microtubule-associated protein 1 light chain (LC3), and Sequestosome-1 (SQTM1/p62) degradation. Using endothelium-dependent vasorelaxation assays, intracellular NO production in an ex vivo rat aortic ring model pre-constricted with phenylephrine was estimated along with DAF-2 DA cell membrane-permeable NO sensitive fluorescent dye. RESULTS: The inhibition of autophagy by CLQ restored NO levels, protected against superoxide generation and preserved morphology as well as proliferation of HUVEC under serum deprivation. Interestingly, the incubation of rat aortic rings with CLQ resulted in endothelium-dependent relaxation mediated by the increase of NO. CONCLUSION: These findings emphasize the importance of autophagy in endothelial function and demonstrate the potential use of autophagy inhibitors to protect vascular function during nutrient deprivation.

Testosterone induces apoptosis in vascular smooth muscle cells via extrinsic apoptotic pathway with mitochondria-generated reactive oxygen species involvement.

Testosterone exerts both beneficial and harmful effects on the cardiovascular system. Considering that testosterone induces reactive oxygen species (ROS) generation and ROS activate cell death signaling pathways, we tested the hypothesis that testosterone induces apoptosis in vascular smooth muscle cells (VSMCs) via mitochondria-dependent ROS generation. Potential mechanisms were addressed. Cultured VSMCs were stimulated with testosterone (10(-7) mol/l) or vehicle (2-12 h) in the presence of flutamide (10(-5) mol/l), CCCP (10(-6) mol/l), mimetic manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP; 3 × 10(-5) mol/l), Z-Ile-Glu(O-ME)-Thr-Asp(O-Me) fluoromethyl ketone (Z-IETD-FMK; 10(-5) mol/l), or vehicle. ROS were determined with lucigenin and dichlorodihydrofluorescein; apoptosis, with annexin V and calcein; O2 consumption, with a Clark-type electrode, and procaspases, caspases, cytochrome c, Bax, and Bcl-2 levels by immunoblotting. Testosterone induced ROS generation (relative light units/mg protein, 2 h; 162.6 ± 16 vs. 100) and procaspase-3 activation [arbitrary units, (AU), 6 h; 166.2 ± 19 vs. 100]. CCCP, MnTMPyP, and flutamide abolished these effects. Testosterone increased annexin-V fluorescence (AU, 197.6 ± 21.5 vs. 100) and decreased calcein fluorescence (AU, 34.4 ± 6.4 vs. 100), and O2 consumption (nmol O2/min, 18.6 ± 2.0 vs. 34.4 ± 3.9). Testosterone also reduced Bax-to-Bcl-2 ratio but not cytochrome-c release from mitochondria. Moreover, testosterone (6 h) induced cleavage of procaspase 8 (AU, 161.1 ± 13.5 vs. 100) and increased gene expression of Fas ligand (2(ΔΔCt), 3.6 ± 1.2 vs. 0.7 ± 0.5), and TNF-α (1.7 ± 0.4 vs. 0.3 ± 0.1). CCCP, MnTMPyP, and flutamide abolished these effects. These data indicate that testosterone induces apoptosis in VSMCs via the extrinsic apoptotic pathway with the involvement of androgen receptor activation and mitochondria-generated ROS.

Divergent role of heme oxygenase inhibition in the pathogenesis of sepsis.

The reduction of neutrophil migration to an infectious focus is associated with a high mortality in severe sepsis. Previously, we showed that heme oxygenase (HO) products downregulate neutrophil recruitment in a noninfectious inflammatory model. The present study was designed to determine the role of HO in sepsis induced by cecal ligation and puncture (CLP) model. We demonstrated that pretreatment, but not the combination of pretreatment plus posttreatment with zinc protoporphyrin IX (ZnPP IX), an HO inhibitor, prevented the reduction of CXCR2 on circulating neutrophils and the failure of intraperitoneal neutrophil migration to the site of infection. Consequently, bacterial dissemination, systemic inflammatory response, and organ injury were prevented. In addition, pretreatment with the HO inhibitor avoided hypotension and consequently increased survival. Moreover, in mice subjected to severe CLP, the pretreatment, but not the combination of pretreatment plus posttreatment with ZnPP IX, prevented the increase of plasmatic free heme observed in nontreated severe CLP. The administration of exogenous hemin to mice subjected to moderate sepsis consistently increased the mortality rate. Furthermore, hemin resulted in a reduction of neutrophil migration both in vivo and in vitro. Altogether, our results demonstrated that pretreatment with the HO inhibitor prevents the pathological findings in severe CLP. However, the combination of pretreatment plus posttreatment with ZnPP IX enhances sepsis severity because of an increase in circulating levels of heme, which is deleterious to the host tissues and also inhibits neutrophil migration.

Dehydromonocrotaline induces cyclosporine A-insensitive mitochondrial permeability transition/cytochrome c release.

Monocrotaline (MCT) is a pyrrolizidine alkaloid present in plants of the genus Crotalaria that causes cytotoxicity and genotoxicity in animals and humans. It is well established that the toxicity of MCT results from its hepatic bioactivation to dehydromonocrotaline (DHM), an alkylating agent, but the exact mechanism of action remains unknown. In a previous study, we demonstrated DHM's inhibition of mitochondrial NADH-dehydrogenase activity at micromolar concentrations, which is an effect associated with a significant reduction in ATP synthesis. As a follow-up study, we have evaluated the ability of DHM to induce mitochondrial permeability transition (MPT) and its associated processes in isolated rat liver mitochondria. In the presence of 10 microM Ca(2+), DHM (50-250 microM) elicited MPT in a concentration-dependent, but cyclosporine A-independent manner, as assessed by mitochondrial swelling, which is associated with mitochondrial Ca(2+) efflux and cytochrome c release. DHM (50-250 microM) did not cause hydrogen peroxide accumulation but did deplete endogenous glutathione and NAD(P)H, while oxidizing protein thiol groups. These results potentially indicate the involvement of mitochondria, via apoptosis, in the well-documented cytotoxicity of monocrotaline.

Enantioselective analysis of oxybutynin and N-desethyloxybutynin with application to an in vitro biotransformation study.

An enantioselective method using liquid-phase microextraction (LPME) followed by HPLC analysis was developed for the determination of oxybutynin (OXY) and its major metabolite N-desethyloxybutynin (DEO) in rat liver microsomal fraction. The LPME procedure was optimized using multifactorial experiments. Under the optimal extraction conditions, the mean recoveries were 61 and 55% for (R)-OXY and (S)-OXY, respectively, and 70 and 76% for (R)-DEO and (S)-DEO, respectively. The validated method was employed to an in vitro biotransformation study using rat liver microsomal fraction. The results demonstrated the enantioselective biotransformation of OXY.

Risco ambiental da aplicação de éteres de difenilas polibromadas como retardantes de chama / Environmental risks involved with the application of polybrominated diphenyl ethers as flame retardants

Flame retardants are additives of combustible materials, such as plastics, textile, electronic circuitry, wood and paper providing resistance to the combustion process when exposed to fire and high temperature. The main flame retardants used are inorganic chemicals (such as antimony oxides), organic phosphate esters with or without halogens, and chlorinated and brominated organic compounds. The brominated flame retardants (BFRs) are largely used due to its efficiency and low cost. The most used flame retardants are the polybrominated diphenyl ethers (PBDEs), produced inlarge-scale whose degradation is very difficult. Thus, they have been found in many different environmental samples. These observations suggest the current destination of these substances is still devoid of recycling or specific treatment. Despite the increased application in oil polymers, little is known about its impact upon the ecosystem. In this review, we provide an overview about the use and risks related to PBDEs as a recognized toxicants found in industries.

Os retardantes de chama, dentre os quais se destacam os éteres de difenilas polibromadas, são aditivos de materiais destinados a torná-los resistentes ao fogo ou a altas temperaturas, inibindo ou suprimindo o processo de combustão, dentre os quais se destacam os éteres de difenilas polibromadas (PBDEs, do inglês, polibromated diphenyl ethers). Devido a sua produção em grande escala e sua difícil degradação, os PBDEs têm sido um contaminante emergente frequentemente encontrados em diferentes amostras ambientais, demonstrando que o processo produtivo, em especial o destino desse material, requer medidas estratégicas que racionalize seu uso. Apesar da ampla utilização desses aditivos em polímeros (na maioria derivados de petróleo) e tecidos inflamáveis comumente utilizados, pouco se sabe a respeito do impacto dessas substâncias sobre o ecossistema. Nessa revisão, uma relação consistente a respeito do risco ambiental resultante do uso indiscriminado desses aditivos, ainda carentes de regulamentação específica, foi estabelecida com base na ação desses compostos bem como a prevalência de algumas classes, reconhecidamente tóxicas em alguns ambientes.