Food-grade titanium dioxide and zinc oxide nanoparticles induce toxicity and cardiac damage after oral exposure in rats.

BACKGROUND: Metallic nanoparticles (NPs) are widely used as food additives for human consumption. NPs reach the bloodstream given their small size, getting in contact with all body organs and cells. NPs have adverse effects on the respiratory and intestinal tract; however, few studies have focused on the toxic consequences of orally ingested metallic NPs on the cardiovascular system. Here, the effects of two food-grade additives on the cardiovascular system were analyzed. METHODS: Titanium dioxide labeled as E171 and zinc oxide (ZnO) NPs were orally administered to Wistar rats using an esophageal cannula at 10 mg/kg bw every other day for 90 days. We evaluated cardiac cell morphology and death, expression of apoptotic and autophagic proteins in cardiac mitochondria, mitochondrial dysfunction, and concentration of metals on cardiac tissue. RESULTS: Heart histology showed important morphological changes such as presence of cellular infiltrates, collagen deposition and mitochondrial alterations in hearts from rats exposed to E171 and ZnO NPs. Intracellular Cyt-C levels dropped, while TUNEL positive cells increased. No significant changes in the expression of inflammatory cytokines were detected. Both NPs altered mitochondrial function indicating cardiac dysfunction, which was associated with an elevated concentration of calcium. ZnO NPs induced expression of caspases 3 and 9 and two autophagic proteins, LC3B and beclin-1, and had the strongest effect compared to E171. CONCLUSIONS: E171 and ZnO NPs induce adverse cardiovascular effects in rats after 90 days of exposure, thus food intake containing these additives, should be taken into consideration, since they translocate into the bloodstream and cause cardiovascular damage.

TRPV1 Contributes to Modulate the Nitric Oxide Pathway and Oxidative Stress in the Isolated and Perfused Rat Heart during Ischemia and Reperfusion.

The transient vanilloid receptor potential type 1 (TRPV1) regulates neuronal and vascular functions mediated by nitric oxide (NO) and by the calcitonin gene-related peptide (CGRP). Here, we study the participation of TRPV1 in the regulation of myocardial injury caused by ischemia-reperfusion and in the control of NO, tetrahydrobiopterin (BH4), the cGMP pathway, CGRP, total antioxidant capacity (TAC), malondialdehyde (MDA) and phosphodiesterase-3 (PDE-3). Isolated hearts of Wistar rats perfused according to the Langendorff technique were used to study the effects of an agonist of TRPV1, capsaicin (CS), an antagonist, capsazepine (CZ), and their combination CZ+CS. The hearts were subjected to three conditions: (1) control, (2) ischemia and (3) ischemia-reperfusion. We determined cardiac mechanical activity and the levels of NO, cGMP, BH4, CGRP, TAC, MDA and PDE-3 in ventricular tissue after administration of CS, CZ and CZ+CS. Western blots were used to study the expressions of eNOS, iNOS and phosphorylated NOS (pNOS). Structural changes were determined by histological evaluation. CS prevented damage caused by ischemia-reperfusion by improving cardiac mechanical activity and elevating the levels of NO, cGMP, BH4, TAC and CGRP. TRPV1 and iNOS expression were increased under ischemic conditions, while eNOS and pNOS were not modified. We conclude that the activation of TRPV1 constitutes a therapeutic possibility to counteract the damage caused by ischemia and reperfusion by regulating the NO pathway through CGRP.

Incivility in the Occupational Therapy Workplace: A Survey of Practitioners.

IMPORTANCE: Incivility in health care settings has detrimental effects on practitioners' well-being, patient outcomes, and health care costs. OBJECTIVE: To explore the prevalence and types of perceived incivility experienced by occupational therapy practitioners in their workplaces and the relationships between perceived incivility and practitioner demographics. DESIGN: Cross-sectional, online survey. SETTING: Surveys were posted to occupational therapy social media sites. PARTICIPANTS: Occupational therapy practitioners throughout the United States. Outcomes and Measures: The Negative Acts Questionnaire-Revised (NAQ-R) was used to measure incivility and bullying. Participants answered demographic questions, and one-way analyses of variance and t tests were used to examine differences between demographic characteristics and mean scores on the NAQ-R. RESULTS: A total of 1,320 practitioners completed the survey. Although the incidence of incivility was low compared with prior research in other health professions, 11% of respondents reported being victims of bullying in the workplace. Practitioners with less experience and who worked in long-term care and skilled nursing settings were more likely to experience incivility, and occupational therapy practitioners experienced significantly less incivility than occupational therapy assistants. CONCLUSIONS AND RELEVANCE: Practitioners, colleagues, managers, and organizations must collaborate to foster an environment of civility and respect to mitigate the effects of incivility on patient outcomes, practitioners' well-being, and health care costs. What This Article Adds: This survey provides baseline information regarding incivility experienced by occupational therapy practitioners, an important first step in developing evidence-based interventions to promote safe and healthy workplaces.

Kidney dysfunction induced by a sucrose-rich diet in rat involves mitochondria ROS generation, cardiolipin changes, and the decline of autophagy protein markers.

The mechanistic link between obesity and renal failure has been proposed to involve mitochondria reactive oxygen species generation and lipotoxicity. These pathological conditions make mitochondria of particular interest in the regulation of cell function and death by both apoptosis and autophagy. Therefore, this work was undertaken to investigate mitochondria function, autophagy, and apoptosis protein markers in the kidney from a rat model of intra-abdominal obesity and renal damage induced by a high-sucrose diet. Mitochondria from sucrose-fed (SF) kidneys in the presence of pyruvate-malate generated H2O2 at a higher rate than from control (79.81 ± 4.98 vs. 65.84 ± 1.95 pmol·min-1·mg protein-1). With succinate, the release of H2O2 was significantly higher compared with pyruvate-malate, and it remained higher in SF than in control mitochondria (146.4 ± 8.8 vs. 106.1 ± 5.9 pmol·min-1·mg protein-1). However, cytochrome c release from SF kidney mitochondria was lower than from control. In addition, cardiolipin, a mitochondria-specific phospholipid, was found increased in SF mitochondria due to the enhanced amount of both cardiolipin synthase and tafazzin. Cardiolipin was also found enriched with saturated and monounsaturated fatty acids, which are less susceptible to peroxidative stress involved in cytochrome c release. Furthermore, beclin-1 and light chain 3-B, as autophagy protein markers, and caspase-9, as apoptosis protein marker, were found decreased in SF kidneys. These results suggest that the decline of autophagy protein markers and the lack of apoptosis process could be a pathological mechanism of cell dysfunction leading to the progression of renal disease in SF rats.

Early identification of peripheral neuropathy based on sudomotor dysfunction in Mexican patients with type 2 diabetes.

BACKGROUND: Type 2 Diabetes in Mexico has a high prevalence, 16-87% of patients may experience peripheral neuropathy. Early detection can prevent or halt its progression. The performance of Sudoscan in detecting neuropathy was compared to the Michigan Neuropathy Screening Instrument (MNSI). The aim was to identificate small fibers neuropathy. METHODS: Patients type 2 diabetes received both MNSI and sudomotor function assessment through measurement of electrochemical skin conductance (ESC) in the hands and feet. RESULTS: Two hundred twenty-one patients with neuropathy according to MNSI B had lower hands and feet ESC, regardless of diabetes duration. Among the 170 patients who had had diabetes for at least 5 years, 76 of them with normal MNSI B had abnormal hands or feet ESC; this was also the case in 28 out of 51 patients with diabetes than 5 or more years. In contrast, only 5 patients in the first group and 1 in the second group had abnormal MNSI B with normal ESC. Using MNSI B as a reference, abnormal hands or feet ESC (< 60 µS and 70 µS respectively) had a sensitivity of 97%, positive predictive value of 87% to detect neuropathy in patients with longer diabetes duration. The group with shorter diabetes duration, the sensitivity of abnormal hands or feet ESC to detect neuropathy was 91% while the positive predictive value was 88%. CONCLUSIONS: The Sudoscan device, which does not require any preparation, is noninvasive, easy and rapid to perform, can be useful in the early diagnosis peripheral neuropathy in type 2 diabetic.

Neuropathy-specific alterations in a Mexican population of diabetic patients.

BACKGROUND: Neuropathy is one of the major complications of type 2 diabetes mellitus. Our first aim was to determine the clinical characteristics of a population of diabetic patients with different types of neuropathy. Our next goal was to characterize the cytokine profile (IL-6 and IL-10), nerve growth factor (NGF) and circulating cell-adhesion molecules in these patients. Finally, we aimed to compare the renal function among the groups of neuropathic patients. METHODS: In a cross-sectional study, we included 217 diabetic patients classified in three groups: sensory polyneuropathy with hypoesthesia (DShP) or hyperesthesia (DSHP), and motor neuropathy (DMN). Two control groups were included: one of 26 diabetic non-neuropathic patients (DNN), and the other of 375 non-diabetic (ND) healthy subjects. The participants were attending to the Mexican Institute of Social Security. RESULTS: The circulating levels of NGF were significantly lower in diabetic patients, compared to healthy subjects. The range of IL-6 and IL-10 levels in neuropathic patients was higher than the control groups; however, several samples yielded null measurements. Neuropathic patients also showed increased circulating levels of the adhesion molecules ICAM, VCAM, and E-Selectin, compared to the ND group. Moreover, neuropathic patients showed reduced glomerular filtration rates compared to healthy subjects (82-103 ml/min per 1.73 m2, data as range from 25th-75th percentiles), especially in the group with DMN (45-76 ml/min per 1.73 m2). CONCLUSIONS: Some particular alterations in neuropathic patients included -but were not limited to- changes in circulating NGF, cell adhesion molecules, inflammation, and the worsening of the renal function. This study supports the need for further clinical surveillance and interventions considering a neuropathy-related basis.

Screening of TNFα, IL-10 and TLR4 single nucleotide polymorphisms in individuals with asymptomatic and chronic cutaneous leishmaniasis in Colombia: a pilot study.

BACKGROUND: Clinical manifestations of cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) range from asymptomatic infection to self-limited, or chronic (non-healing) cutaneous lesions. Given the critical role of the immune response in the clinical outcome of CL, it is plausible that functional polymorphisms in immune-related genes contribute to define the clinical manifestations of human infection. METHODS: DNA samples from a retrospective cohort of individuals from an endemic area of L. V. panamensis transmission in Colombia were used to determine the frequency of SNPs in TNFα, IL-10 and TLR4 genes. DNA samples were obtained from 74 adult participants: 38 patients presenting chronic cutaneous leishmaniasis (CCL) and 36 individuals with asymptomatic infection. Genotyping of TNFα-308G/A, IL-10-819C/T, and TLR4 Asp299Gly and Thr399Ile SNPs, was conducted by PCR-restriction fragment length polymorphisms. Allele, genotype frequencies and associations between SNPs and clinical groups were evaluated. RESULTS: The A allele in TNFα-308G/A SNP was found more frequently in individuals with asymptomatic infection (16% vs 7%), whereas the CC genotype in IL-10-819 C/T SNP was more frequent in patients with CCL (34% vs. 27% in asymptomatic individuals). No differences in allele frequencies for TLR4 SNPs were found among groups. CONCLUSION: This study provides a reference base for statistical power calculation and design of association studies of genetic polymorphisms in immune response related-genes and the pathogenesis of infections caused by L. V. panamensis.

Cytochrome c release from rat liver mitochondria is compromised by increased saturated cardiolipin species induced by sucrose feeding.

Cytochrome c release from mitochondria has been described to be related to reactive oxygen species (ROS) generation. With ROS generation being increased in fatty liver from sucrose-fed (SF) rats, we hypothesized that cytochrome c release might be positively associated with H2O2 generation from SF mitochondria. Surprisingly, cytochrome c release from mitochondria of SF liver was found to be significantly lower compared with control (C) mitochondria oxidizing pyruvate/malate or succinate. Exposure of mitochondria to exogenous superoxide radical generated by the xanthine/xanthine oxidase system elicits a dose-response cytochrome c release in both control and SF mitochondria, but cytochrome c release remains lower in SF mitochondria compared with C mitochondria. Furthermore, the addition of ebselen, PEG-catalase, or catalase, a H2O2 scavenger, significantly reduces cytochrome c release from C and SF mitochondria. Our results suggest that both intra- and extramitochondrial H2O2 are involved in cytochrome c release, but the persisting difference between C and SF levels can be attributed to the differences in cardiolipin compositions. Indeed, the ratio of palmitic acid-rich cardiolipin species was found to be increased in lipid membrane from SF mitochondria compared with C mitochondria, whereas that of linoleic acid-rich cardiolipin species was found decreased. In addition, the content of tafazzin, a protein responsible for cardiolipin remodeling, was decreased in SF mitochondria. Therefore, we conclude that the changes observed in the composition of cardiolipin molecular species in SF mitochondria may be involved in cytochrome c interaction with mitochondrial inner membrane lipid and in its reduced release from SF mitochondria.

Purinergic signaling in the ovary.

Adenosine triphosphate (ATP) is released from the cell by multiple mechanisms. The extracellular form of this purine is processed by ectonucleotidases, resulting in a variety of dephosphorylated metabolites that can bind to specific receptors found in the membrane of target cells; such purinergic signaling is important as an autocrine-paracrine intercellular communication system that influences tissue physiology. In this review, we summarize the studies analyzing purinergic activity in the ovary, which can modulate cellular physiology-including sensitivity to gonadotropins-in several ovarian cell types, including the cumulus-cell complex, granulosa cells, theca cells, and the ovarian surface epithelium. These functions support a role for ATP as an important intra-ovarian messenger, and open new lines of research that can improve our understanding of mechanisms regulating ovarian function and the fine-tuning of folliculogenesis.

Factors Associated with the Quality of Transient Elastography.

BACKGROUND: Transient elastography is a noninvasive method for the evaluation of fibrosis in chronic liver disease. However, its reliability is variable, and the factors associated with its accuracy have not been identified completely. AIMS: To identify the factors associated with the reliability of transient elastography. METHODS: A total of 2033 transient elastography measurements were taken from March 2009 to October 2013. Reliability was determined according to the interquartile range/median (IQR/M < 0.30 = reliable; IQR/M < 0.10 = very reliable). Other indicators such as the percentage of successful measurements (>60 %), time of performance, and probe size were recorded. Potential factors that could affect the reliability of the procedure were analyzed using multivariate logistic regression. RESULTS: Slightly less than 5 % of the measurements were unsuccessful, and 83 % of the successful measurements were found to be reliable. Factors associated with an unsuccessful measurement were female gender, incorrect probe size, and the presence of HCV infection. Unreliable measurements were associated with use of the procedure as part of a clinical study and success rate. Very reliable evaluations were associated with >10 measurements, the presence of chronic hepatic disease, and a success rate of >60 %. CONCLUSIONS: The operator and clinical and anthropometric characteristics are factors that influence the success and reliability of transient elastography. Improvements in the quality of the procedure are needed to provide better diagnostic accuracy in clinical practice.

[Diversity, structure and regeneration of the seasonally dry tropical forest of Yucatán Peninsula, Mexico]. / Diversidad, estructura y regeneración de la selva tropical estacionalmente seca de la Península de Yucatán, México.

Seasonally dry tropical forests are considered as the most endangered ecosystem in lowland tropics. The aim of this study was to characterize the floristic composition, richness, diversity, structure and regeneration of a seasonally dry tropical forest landscape constituted by mature forest, secondary forest and seasonally inundated forest located in the Northeastern part of the Yucatán Peninsula, Mexico. We used the Gentry's standard inventory plot methodology (0.1 ha per forest type in 2007) for facilitating comparison with other Mesoamerican seasonally dry tropical forests. A total of 77 species belonging to 32 families were observed in the study area. Fabaceae and Euphorbiaceae were the families with the largest taxonomic richness in the three forest types. Low levels of ß diversity were observed among forest types (0.19-0.40), suggesting a high turnover of species at landscape level. The non-regenerative species were dominant (50-51 %), followed by regenerative species (30- 28 %), and colonizer species (14-21 %) in the three forest types. Zoochory was the most common dispersal type in the study area. The 88 % of the observed species in the study area were distributed in Central America. Some floristic attributes of the seasonally dry tropical forest of the Yucatán Peninsula, fall into the values reported for Mesoamerican seasonally dry tropical forests. Natural disturbances contributed to explain the high number of individuals, the low number of liana species, as well as the low values of basal area observed in this study. Our results suggested that the seasonally dry tropical forest of Yucatán Peninsula seems to be resilient to natural disturbances (hurricane) in terms of the observed number of species and families, when compared with the reported values in Mesoamerican seasonally dry tropical forests. Nonetheless, the recovery and regeneration of vegetation in long-term depends on animal-dispersed species. This study highlights the importance of establishing multiple protected areas throughout the Mesoamerican seasonally dry tropical forest in order to conserve both α- and ß- diversity.

Paracrine stimulation of P2X7 receptor by ATP activates a proliferative pathway in ovarian carcinoma cells.

P2X7 is a purinergic receptor-channel; its activation by ATP elicits a broad set of cellular actions, from apoptosis to signals for survival. Here, P2X7 expression and function was studied in human ovarian carcinoma (OCA) cells, and biopsies from non-cancerous and cancer patients were analyzed by immunohistochemistry. Ovarian surface epithelium in healthy tissue expressed P2X7 at a high level that was maintained throughout the cancer. The cell lines SKOV-3 and CAOV-3 were used to investigate P2X7 functions in OCA. In SKOV-3 cells, selective stimulation of P2X7 by 2'(3')-O-(4-benzoylbenzoyl) adenosine-5'-triphosphate (BzATP) induced a dose-dependent increase of intracellular Ca(2+) concentration ([Ca(2+)](i)) but not cell death. Instead, BzATP increased the levels of phosphorylated ERK and AKT (pERK and pAKT), with an EC(50) of 44 ± 2 and 1.27 ± 0.5 µM, respectively; 10 µM BzATP evoked a maximum effect within 15 min that lasted for 120 min. Interestingly, basal levels of pERK and pAKT were decreased in the presence of apyrase in the medium, strongly suggesting an endogenous, ATP-mediated phenomenon. Accordingly: (i) mechanically stimulated cells generated a [Ca(2+)](i) increase that was abolished by apyrase; (ii) apyrase induced a decrease in culture viability, as measured by the MTS assay for mitochondrial activity; and (iii) incubation with 10 µM AZ10606120, a specific P2X7 antagonist and transfection with the dominant negative P2X7 mutant E496A, both reduced cell viability to 70.1 ± 8.9% and to 76.5 ± 5%, respectively, of control cultures. These observations suggested that P2X7 activity was auto-induced through ATP efflux; this increased pERK and pAKT levels that generated a positive feedback on cell viability.

Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats.

The attenuation of oxidative stress could be an important mechanism whereby the incidence of vascular complications in the MS (metabolic syndrome) may be diminished. The present study was undertaken to investigate the mechanism by which glycine, supplemented to the diet of SF (sucrose-fed) rats, modulates glutathione biosynthesis and protects against oxidative stress and altered endothelium-dependent relaxation in isolated aorta. Glycine reduced O2•- (superoxide anion radical) release in the presence of NADPH, and decreased protein carbonyl and lipid peroxidation. This effect of glycine could be because of the increased amount of glutathione synthetase, which may be responsible for increased glutathione (GSH) content in vascular tissue from SF rats. Moreover, glycine increased the amount of Cu,Zn-SOD (copper/zinc superoxide dismutase) and eNOS (endothelial NO synthase) in aorta from SF animals. Finally, it improved the relaxation response to ACh (acetylcholine) found impaired in aortic rings from SF rats. In the presence of NAC (N-acetylcysteine), a precursor of GSH, an improved ACh-mediated aortic relaxation of aortic rings from SF rats was observed, whereas BSO (buthionine sulfoximine), an inhibitor of glutathione biosynthesis, inhibited the relaxing effect of NAC in aortas from both control and SF rats. This experiment emphasizes the role of GSH in endothelial function in SF rats. The present data suggest that glycine rectifies vascular reactivity by increasing the biosynthesis of glutathione. Glutathione protects vascular tissue against oxidative stress, and enhances the availability of NO, which exerts its relaxing effect, thus contributing to the reduction of high BP (blood pressure) in the SF rats.

The day of the week does not affect the adenoma detection rate.

BACKGROUND: The role of operator fatigue on adenoma detection rate (ADR) is still controversial. AIMS: The purpose of this study was to determine if fatigue towards the end of the week affects the ADR. METHODS: A retrospective chart review of consecutive colonoscopies was done at a tertiary care teaching institution. Patients 45 years of age or older undergoing screening or surveillance colonoscopy from June 2007 to August 2010 were included in the study. RESULTS: A total of 3,085 patients were included in the study, with an overall 31 % ADR. ADR was between 31 and 32 % throughout the week, with no statistically significant variation (p = 0.8697). The total number of adenomas and advanced adenomas was also similar throughout the week (p = 0.8, p = 0.59, respectively). CONCLUSIONS: ADR is not influenced by the day of the week in which a colonoscopy is performed.

Tissue-specific differences in Ca2+ sensitivity of the mitochondrial permeability transition pore (PTP). Experiments in male rat liver and heart.

Permeability transition pore (PTP) opening dissipates ion and electron gradients across the internal mitochondrial membrane (IMM), including excess Ca2+ in the mitochondrial matrix. After opening, immediate PTP closure must follow to prevent outer membrane disruption, loss of cytochrome c, and eventual apoptosis. Flickering, defined as the rapid alternative opening/closing of PTP, has been reported in heart, which undergoes frequent, large variations in Ca2+. In contrast, in tissues that undergo depolarization events less often, such as the liver, PTP would not need to be as dynamic and thus these tissues would not be as resistant to stress. To evaluate this idea, it was decided to follow the reversibility of the permeability transition (PT) in isolated murine mitochondria from two different tissues: the very dynamic heart, and the liver, which suffers depolarizations less frequently. It was observed that in heart mitochondria PT remained reversible for longer periods and at higher Ca2+ loads than in liver mitochondria. In all cases, Ca2+ uptake was inhibited by ruthenium red and PT was delayed by Cyclosporine A. Characterization of this phenomenon included measuring the rate of oxygen consumption, organelle swelling and Ca2+ uptake and retention. Results strongly suggest that there are tissue-specific differences in PTP physiology, as it resists many more Ca2+ additions before opening in a highly active organ such as the heart than in an organ that seldom suffers Ca2+ loading, such as the liver.

Food-grade titanium dioxide (E171) and zinc oxide nanoparticles induce mitochondrial permeability and cardiac damage after oral exposure in rats.

Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are found in diverse products for human use. E171 is used as whitening agent in food and cosmetics, and ZnO NPs in food packaging. Their potential multi-organ toxicity has raised concerns on their safety. Since mitochondrial dysfunction is a key aspect of cardio-pathologies, here, we evaluate the effect of chronic exposure to E171 and ZnO NPs in rats on cardiac mitochondria. Changes in cardiac electrophysiology and body weight were measured. E171 reduced body weight more than 10% after 5 weeks. Both E171 and ZnO NPs increased systolic blood pressure (SBP) from 110-120 to 120-140 mmHg after 45 days of treatment. Both NPs altered the mitochondrial permeability transition pore (mPTP), reducing calcium requirement for permeability by 60% and 93% in E171- and ZnO NPs-exposed rats, respectively. Treatments also affected conformational state of adenine nucleotide translocase (ANT). E171 reduced the binding of EMA to Cys 159 in 30% and ZnO NPs in 57%. Mitochondrial aconitase activity was reduced by roughly 50% with both NPs, indicating oxidative stress. Transmission electron microscopy (TEM) revealed changes in mitochondrial morphology including sarcomere discontinuity, edema, and hypertrophy in rats exposed to both NPs. In conclusion, chronic oral exposure to NPs induces functional and morphological damage in cardiac mitochondria, with ZnO NPs being more toxic than E171, possibly due to their dissociation in free Zn2+ ion form. Therefore, chronic intake of these food additives could increase risk of cardiovascular disease.

Association of the polymorphisms rs179008 (TLR7), rs2004640 (IRF5), rs1800795 (IL-6) and rs2280788 (CCL5) with systemic lupus erythematosus in women of Mayan ethnicity from Yucatan.

Introduction: IFN-α is the main cytokine in SLE, and single nucleotide polymorphisms (SNP) in different genes could induce it. Aim: To determine the association of rs2004640 (IRF5), rs179008 (TLR7), rs1800795 (IL-6) and rs2280788 (CCL5) with SLE in Mexican women with Mayan ethnicity. Methods: DNA and RNA were isolated from the peripheral blood of 110 patients and 200 healthy control subjects. SNP genotyping and gene expression analysis of IRF5, TLR7, IL-6 and IFN-α were determined by real-time PCR and analyzed with SNP Stat, Stata 10.1 and Graph Pad Prism v5. Results: rs2004640, rs179008, and rs1800795 in both groups were according to Hardy-Weinberg equilibrium. Risk alleles rs179008T and rs2004640T frequencies were higher in controls (p = 0.015 and p = 0.028, respectively), whereas rs179008A frequency was higher in patients (p = 0.015). Allelic combination AGT frequency was higher in patients (p = 0.001). IL-6 rs1800795C > G and CCL5 rs2280788G > C frequencies did not show significant differences (p > 0.05), being rs2280788G (CCL5) monomorphic in controls. SLE patients showed higher TLR7, IRF5, IL6, and IFN-α mRNA levels. IRF5 expression was higher in SLE patients homozygous for rs2004640T (IRF5). Conclusion: This work showed the contribution of TLR7 and IRF5 in SLE pathogenesis in Mayan females from Yucatan.

Sorcin modulates mitochondrial Ca(2+) handling and reduces apoptosis in neonatal rat cardiac myocytes.

Sorcin localizes in cellular membranes and has been demonstrated to modulate cytosolic Ca(2+) handling in cardiac myocytes. Sorcin also localizes in mitochondria; however, the effect of sorcin on mitochondrial Ca(2+) handling is unknown. Using mitochondrial pericam, we measured mitochondrial Ca(2+) concentration and fluxes in intact neonatal cardiac myocytes overexpressing sorcin. Our results showed that sorcin increases basal and caffeine-stimulated mitochondrial Ca(2+) concentration. This effect was associated with faster Ca(2+) uptake and release. The effect of sorcin was specific for mitochondria, since similar results were obtained with digitonin-permeabilized cells, where cytosolic Ca(2+) flux was disrupted. Furthermore, mitochondria of cardiac myocytes in which sorcin was overexpressed were more Ca(2+)-tolerant. Experiments analyzing apoptotic signaling demonstrated that sorcin prevented 2-deoxyglucose-induced cytochrome c release. Furthermore, sorcin prevented hyperglycemia-induced cytochrome c release and caspase activation. In contrast, antisense sorcin induced caspase-3 activation. Thus, sorcin antiapoptotic properties may be due to modulation of mitochondrial Ca(2+) handling in cardiac myocytes.

Lipotoxicity, glucotoxicity and some strategies to protect vascular smooth muscle cell against proliferative phenotype in metabolic syndrome.

Metabolic syndrome (MetS) is a risk factor for the development of cardiovascular disease (CVD) and atherosclerosis through a mechanism that involves vascular smooth muscle cell (VSMC) proliferation, lipotoxicity and glucotoxicity. Several molecules found to be increased in MetS, including free fatty acids, fatty acid binding protein 4, leptin, resistin, oxidized lipoprotein particles, and advanced glycation end products, influence VSMC proliferation. Most of these molecules act through their receptors on VSMCs by activating several signaling pathways associated with ROS generation in various cellular compartments. ROS from NADPH-oxidase and mitochondria have been found to promote VSMC proliferation and cell cycle progression. In addition, most of the natural or synthetic substances described in this review, including pharmaceuticals with hypoglycemic and hypolipidemic properties, attenuate VSMC proliferation by their simultaneous modulation of cell signaling and their scavenging property due to the presence of a phenolic ring in their structure. This review discusses recent data in the literature on the role that several MetS-related molecules and ROS play in the change from contractile to proliferative phenotype of VSMCs. Hence the importance of proposing an appropriate strategy to prevent uncontrolled VSMC proliferation using antioxidants, hypoglycemic and hypolipidemic agents.

Assessment of potential risks to human health associated with trace elements in three commercially important shark species captured in the Central Mexican Pacific.

Shark meat is a popular protein source worldwide. However, existing national control policies for ensuring the safety and quality of shark meat are minimal. There are concerns about the sustainability of shark populations, which bioaccumulate and biomagnify potentially toxic elements at higher rates than non-predatory fish, posing a risk to human health. In this study, the contributions of essential elements to the Recommended Dietary Allowance (RDA) and potentially toxic elements to the Reference Dose (RfD) linked to shark consumption (200 g per week) were investigated for three shark species in the Central Mexican Pacific. We estimated risks and benefits for women, children, and men. Our results suggest that the three shark species are sources of Se, Co, Cr, Cu, Fe, and Zn, but poor sources of Mn for women and men aged 19-50 years. A weekly ingestion of 200 g of shark meat exceeded the RfD-As by 4-14 times and the RfD-Pb by 1.1-1.7 times for adults, indicating a potential risk to human health. The three shark species were also significant sources of potentially toxic elements for children, including Hg, Cd, Cr, and Pb. An excessive intake of Se was observed, with levels at 8.4-10.6 and 4.3-5.3 times the RDA for children aged 1-8 and 9-13 years, respectively. Although shark meat can be a good source of essential nutrients, the lack of controls in the commercialization process indicates that it should be consumed in moderation due to the potential risks associated with excessive exposure to potentially toxic elements. This caution is particularly important for children and pregnant women, who are at higher risk of health complications from consuming contaminated food.