Changes in glutathione-redox balance induced by hexachlorocyclohexane and lindane in CHO-K1 cells

©2008. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted, version of a Published Work that appeared in final form in Xenobiotica. To access the final edited and published work see https://doi.org/10.1080/00498250210000126281. The basal cytotoxic effect of the organochlorine pesticides hexachlorocyclohexane and lindane on CHO-K1 cultures was assessed at fractions of their lethal doses as determined by the neutral red incorporation (NRI) assay (NRI6.25, NRI12.5 and NRI25). The sulphur-redox cycle enzymes glutathione peroxidase, glutathione reductase and glutathione S-transferase, and total and oxidized glutathione were evaluated at several points during the standard growth curve of the cultures. 2. After incubation with each compound for 24h, both glutathione peroxidase and reductase showed a substantial increase at the lowest exposure doses (NRI6.25) - more significantly for lindane than for 1,2,3,4,5,6-hexachlorocyclohexane (HCH) - and dropped at higher doses of both compounds. The reduced and oxidized glutathione content was greatly diminished at the lower exposures, whereas the total glutathione content was higher at NRI12.5 values. 3. Changes in cell membrane integrity were assessed for a wide range of pesticide concentrations with the lactate dehydrogenase release assay and lipid peroxidation. Membrane leakage and peroxide production were significantly enhanced at concentrations of HCH 50µg ml−1, although this effect was not significant at lindane concentrations <200µg ml−1. 4. Lipid peroxidation increased with exposure to HCH at concentrations as low as NRI6.25, whereas in the case of lindane, this increase was only significant at doses of NRI25 and above

Compreender crianças com inibição emocional: Uma abordagem com múltiplos informadores do contexto educacional e familiar

Behavioral inhibition (BI) is a temperament trait characterized by extreme fear in the face of novelty. BI has been associated with the development of mental disorders. However, there is a lack of research examining the socioemotional and behavioral characteristics of behaviorally inhibited children both in family and school settings. For a more comprehensive and in-depth overview of children’s behavior in each of these contexts, this study has collected data from both parents (mother and father – family setting) and from teachers (educational environment). The sample consisted of 109 children aged between four and six years old. Multi-informant approach was used: all fathers, mothers and teachers completed both the Preschool Behavioral Inhibition Scales, the Child Behavior Checklist for parents and teachers, and the Behavior Assessment System for Children and Adolescents. Our findings revealed that children classified as BI exhibit less socioemotional and behavioral adjustments than their uninhibited peers both in family and school contexts. Further, the shyness variable seemed to be strongly associated with behavioral inhibition, regardless of informant and context.A inibição comportamental (IC) é um traço de temperamento caracterizado por medo extremo face a situações novas. A IC tem sido associada ao desenvolvimento de perturbações mentais. No entanto, é escassa a investigação que examina as características socio-emocionais e comportamentais de crianças com inibição comportamental em contextos educacionais e familiares. Para uma visão global mais compreensiva e aprofundada do comportamento da criança em cada um destes contextos, este estudo recolheu dados com os pais (mãe e pai – contexto familiar) e com os professores (contexto educacional). A amostra foi constituída por 109 crianças, entre os quatro e os seis anos de idade. Foi utilizada uma abordagem com múltiplos informadores: todos os pais, mães e professores completaram as Escalas de Inibição Comportamental para o Pré-Escolar, o Questionário de Comportamento da Criança para pais e professores (CBCL e TRF), e o Sistema de Avaliação do Comportamento para Crianças e Adolescentes (BASC). Os resultados revelaram que crianças consideradas com IC apresentavam níveis mais baixos de ajustamento socio-emocional e comportamental comparativamente a crianças não inibidas, tanto no contexto familiar como no contexto educacional. Adicionalmente, a variável de timidez pareceu ser a que mais fortemente se associou à inibição comportamental, independentemente do informador e do contexto

Design and evaluation of countermeasures against fault injection attacks and power side-channel leakage exploration for AES block cipher

Differential Fault Analysis (DFA) and Power Analysis (PA) attacks, have become the main methods for exploiting the vulnerabilities of physical implementations of block ciphers, currently used in a multitude of applications, such as the Advanced Encryption Standard (AES). In order to minimize these types of vulnerabilities, several mechanisms have been proposed to detect fault attacks. However, these mechanisms can have a signi cant cost, not fully covering the implementations against fault attacks or not taking into account the leakage of the information exploitable by the power analysis attacks. In this paper, four different approaches are proposed with the aim of protecting the AES block cipher against DFA. The proposed solutions are based on Hamming code and parity bits as signature generators for the internal state of the AES cipher. These allow to detect DFA exploitable faults, from bit to byte level. The proposed solutions have been applied to a T-box based AES block cipher implemented on Field Programmable Gate Array (FPGA). Experimental results suggest a fault coverage of 98.5% and 99.99% with an area penalty of 9% and 36% respectively, for the parity bit signature generators and a fault coverage of 100% with an area penalty of 18% and 42% respectively when Hamming code signature generator is used. In addition, none of the proposed countermeasures impose a frequency degradation, in respect to the unprotected cipher. The proposed work goes further in the evaluation of the proposed DFA countermeasures by evaluating the impact of these structures in terms of power side-channel. The obtained results suggest that no extra information leakage is produced that can be exploited by PA. Overall, the proposed DFA countermeasures provide a high fault coverage protection with a low cost in terms of area and power consumption and no PA security degradation

Orai1 and TRPC1 Proteins Co-localize with CaV1.2 Channels to Form a Signal Complex in Vascular Smooth Muscle Cells

Voltage-dependent CaV1.2 L-type Ca2 channels (LTCC) are the main route for calcium entry in vascular smooth muscle cells (VSMC). Several studies have also determined the relevant role of store-operated Ca2 channels (SOCC) in vascular tone regulation. Nevertheless, the role of Orai1- and TRPC1-dependent SOCC in vascular tone regulation and their possible interaction with CaV1.2 are still unknown. The current study sought to characterize the co-activation of SOCC and LTCC upon stimulation by agonists, and to determine the possible crosstalk between Orai1, TRPC1, and CaV1.2. Aorta rings and isolated VSMCobtained from wild type or smooth muscle-selective conditional CaV1.2 knock-out (CaV1.2KO) mice were used to study vascular contractility, intracellular Ca2 mobilization, and distribution of ion channels. We found that serotonin (5-HT) or store depletion with thapsigargin (TG) enhanced intracellular free Ca2 concentration ([Ca2 ]i) and stimulated aorta contraction. These responses were sensitive to LTCC and SOCC inhibitors. Also, 5-HT- and TG-induced responses were significantly attenuated in CaV1.2KO mice. Furthermore, hyperpolarization induced with cromakalim or valinomycin significantly reduced both 5-HT and TG responses, whereas these responses were enhanced with LTCC agonist Bay-K-8644. Interestingly, in situ proximity ligation assay revealed that CaV1.2 interacts with Orai1 and TRPC1 in untreated VSMC. These interactions enhanced significantly after stimulation of cells with 5-HT and TG. Therefore, these data indicate for the first time a functional interaction between Orai1, TRPC1, and CaV1.2 channels in VSMC, confirming that upon agonist stimulation, vessel contraction involves Ca2 entry due to co-activation of Orai1- and TRPC1-dependent SOCC and LTCC.Ministerio de Economía y Competitividad BFU2013-45564-C2-1-PMinisterio de Economía y Competitividad BFU2013-45564-C2-2-PInstituto de Salud Carlos III RD12/0042/ 0041Cardiovascular Network “RIC” PI12/00941Junta de Andalucía PI-0108-2012Junta de Andalucía P12- CTS-196

Proposed cut-off points for anthropometric and bioelectrical measures based on overweight and obesity criteria in Spanish institutionalised elderly people

The increasing prevalence of obesity among the institutionalised elderly population and its severe consequences on health requires an early and accurate diagnosis that can be easily achieved in any clinical setting. This study aimed to determine new cut-off values for anthropometric and bioelectrical impedance measures that are superior to body mass index criteria for overweight and obesity status in a sample of Spanish institutionalised elderly population. A total of 211 institutionalised older adults (132 women, aged 84.3 +/- 7.3 years; 79 men, aged 81.5 +/- 7.3 years) were enrolled in the current cross-sectional study. Anthropometric and bioelectrical impedance measures included the body mass index, waist circumference, gluteal circumference, waist-hip ratio, sagittal-abdominal diameter, trunk fat, and visceral-fat ratio. In women, the waist circumference, gluteal circumference, sagittal-abdominal diameter, trunk fat, and visceral-fat index presented strongly significant specificity and sensitivity (area under the curve [AUC], p<0.0001) and elevated discriminative values (receiver operating characteristic [ROC] curves: 0.827 to 0.867) for overweight and obesity status. In men, the waist-hip ratio, waist circumference, gluteal circumference, sagittal-abdominal diameter, trunk fat, and visceral-fat ratio were strongly significant AUC (p<0.0001), with moderate-to-high values (ROC curves: 0.757-0.871). In conclusion, our findings suggest that gluteal circumference, waist circumference, and sagittal-abdominal diameter in women and trunk fat, visceral-fat ratio, and waist circumference in men may represent more suitable cut-off values superior to body mass index criteria for overweight and obesity in the Spanish institutionalised elderly population

Consumption of over-the-Counter Drugs: Prevalence and Type of Drugs

Recently, there has been an increase in the use of over-the-counter (OTC) drugs. The consumption of these medicines can be unsafe, as incorrect self-diagnosis or the ingestion of inappropriate doses can lead to side effects and the occurrence of adverse reactions and drug–drug interactions. A cross-sectional descriptive observational study was carried out, targeting the entire Spanish population by using an online questionnaire. The results showed that 78.9% of the subjects had previously taken or were currently taking OTC drugs. This consumption decreased as the age of the subjects increased, with a prevalence of 36.4% of subjects aged 71 taking OTC drugs. Analgesics were the most consumed OTC drugs (49.1%) especially in women, youngsters with non-formal educational qualifications, and individuals of a low–medium socioeconomic level residing in urban areas. Measures should be implemented to optimize the safe use of OTC drugs in order to avoid the occurrence of secondary events associated with the lack of knowledge related to their the usage

Sex differences for predicting metabolic syndrome by adipose dysfunction markers in institutionalized elderly.

Aims: Recent studies have emphasized that metabolic syndrome (MetS) was the most important modifiable risk factor for cardiovascular and cerebrovascular diseases in the institutionalized elderly. In addition, the occurrence of MetS was higher in those with longer age-adjusted institutionalization time. The present study was conducted to assess predictive value of markers of adipose tissue dysfunction for the early screening of MetS in this population. Methods and results: Two hundred and eleven institutionalized older adults (132 women, aged 74.3 ± 7.3 years; 79 men, aged 71.5 ± 7.3 years) were enrolled in the current cross-sectional study. Lipid accumulation product (LAP), visceral adiposity index (VAI), body adiposity index (BAI), and triglycerides (TG)/high-density lipoprotein (HDL)-cholesterol ratio were determined. The receiver operating characteristic curve was calculated to compare the area under the curve of each index. The total prevalence of MetS was 23.8%. In female group, VAI and TG/HDL ratio presented moderate-high sensitivity (77.78% and 78.38%, respectively) and specificity (77.62% and 73.49%, respectively). In males group, LAP presented moderate-high sensitivity (75%) and specificity (76.9%). Conclusion: Gender played a key role on the prediction of MetS by adipose dysfunction markers in institutionalized elderly. Accordingly, VAI and TG/HDL-cholesterol ratio showed the highest predictive value for MetS in female elderly. LAP was the strongest predictor of MetS in male elderly

Comparación de sistemas de manejo de suelo en olivar en ensayos de simulación de lluvia

El objetivo de este estudio es comparar la influencia de dos sistemas de manejo de suelo utilizados en olivar, cubierta vegetal y laboreo convencional, en la generación y calidad de las aguas de escorrentía y la erosión asociada a estos fenómenos. Se parte de la convicción de que la cubierta vegetal, al reducir el flujo superficial y la pérdida de suelo, ha de disminuir en principio la contaminación de las aguas superficiales

Circulating miR-320a as a Predictive Biomarker for Left Ventricular Remodelling in STEMI Patients Undergoing Primary Percutaneous Coronary Intervention

Restoration of epicardial coronary blood flow, achieved by early reperfusion with primary percutaneous coronary intervention (PPCI), is the guideline recommended to treat patients with ST-segment-elevation myocardial infarction (STEMI). However, despite successful blood restoration, increasing numbers of patients develop left ventricular adverse remodelling (LVAR) and heart failure. Therefore, reliable prognostic biomarkers for LVAR in STEMI are urgently needed. Our aim was to investigate the role of circulating microRNAs (miRNAs) and their association with LVAR in STEMI patients following the PPCI procedure. We analysed the expression of circulating miRNAs in blood samples of 56 patients collected at admission and after revascularization (at 3, 6, 12 and 24 h). The associations between miRNAs and left ventricular end diastolic volumes at 6 months were estimated to detect LVAR. miRNAs were also analysed in samples isolated from peripheral blood mononuclear cells (PBMCs) and human myocardium of failing hearts. Kinetic analysis of miRNAs showed a fast time-dependent increase in miR-133a, miR-133b, miR-193b, miR-499, and miR-320a in STEMI patients compared to controls. Moreover, the expression of miR-29a, miR-29b, miR-324, miR-208, miR-423, miR-522, and miR-545 was differentially expressed even before PPCI in STEMI. Furthermore, the increase in circulating miR-320a and the decrease in its expression in PBMCs were significantly associated with LVAR and correlated with the expression of miR-320a in human failing myocardium from ischaemic origin. In conclusion, we determined the time course expression of new circulating miRNAs in patients with STEMI treated with PPCI and we showed that miR-320a was positively associated with LVAR

TRPC Channels: Dysregulation and Ca2+ Mishandling in Ischemic Heart Disease

Transient receptor potential canonical (TRPC) channels are ubiquitously expressed in excitable and non-excitable cardiac cells where they sense and respond to a wide variety of physical and chemical stimuli. As other TRP channels, TRPC channels may form homo or heterotetramericion channels, and they can associate with other membrane receptors and ion channels to regulate intracellular calcium concentration. Dysfunctions of TRPC channels are involved in many types of cardiovascular diseases. Significant increase in the expression of different TRPC isoforms was observed in different animal models of heart infarcts and in vitro experimental models of ischemia and reperfusion. TRPC channel-mediated increase of the intracellular Ca2+ concentration seems to be required for the activation of the signaling pathway that plays minor roles in the healthy heart, but they are more relevant for cardiac responses to ischemia, such as the activation of different factors of transcription and cardiac hypertrophy, fibrosis, and angiogenesis. In this review, we highlight the current knowledge regarding TRPC implication in different cellular processes related to ischemia and reperfusion and to heart infarction