Memantine prevents cardiomyocytes nuclear size reduction in the left ventricle of rats exposed to cold stress

OBJECTIVES: Memantine is an N-methyl-d-aspartate (NMDA) glutamate receptor antagonist used to treat Alzheimer's disease. Previous studies have suggested that receptor blockers act as neuroprotective agents; however, no study has specifically investigated the impact that these drugs have on the heart. We sought to evaluate the effects of memantine on nuclear size reduction in cardiac cells exposed to cold stress. METHOD: We used male EPM-Wistar rats (n=40) divided into 4 groups: 1) Matched control (CON); 2) Memantine-treated rats (MEM); 3) Rats undergoing induced hypothermia (IH) and 4) Rats undergoing induced hypothermia that were also treated with memantine (IHM). Animals in the MEM and IHM groups were treated by oral gavage administration of 20 mg/kg/day memantine over an eight-day period. Animals in the IH and IHM groups were submitted to 4 hours of hypothermia in a controlled environment with a temperature of - 8ºC on the last day of the study. RESULTS: The MEM group had the largest cardiomyocyte nuclear size (151 ± 3.5 μm³ vs. CON: 142 ± 2.3 μm³; p<0.05), while the IH group had the smallest mean value of nuclear size. The nuclear size of the IHM group was preserved (125 ± 2.9 μm³) compared to the IH group (108 ± 1.7 μm³; p<0.05). CONCLUSION: Memantine prevented the nuclear size reduction of cardiomyocytes in rats exposed to cold stress.

What are the similarities between stress, sudden cardiac death in Gallus gallus and sudden unexpected death in people with epilepsy

Individuals with epilepsy are at higher risk of sudden unexpected death in epilepsy (SUDEP), responsible for 7.5% to 17% of all deaths in epilepsy. Many factors are current associated with SUDEP and possible effect of stress and cardiac arrhythmia are still not clear. Sudden death syndrome (SDS) in chickens is a disease characterized by an acute death of well-nourished and seeming healthy Gallus gallus after abrupt and brief flapping of their wings, similar to an epileptic seizure, with an incidence estimated as 0.5 to 5% in broiler chickens. A variety of nutritional and environmental factors have been included: but the exactly etiology of SDS is unknown. Studies had suggested that the hearts of broiler chickens are considerably more susceptible to arrhythmias and stress may induce ventricular arrhythmia and thus, sudden cardiac death. In this way, SDS in Gallus gallus could be an interesting model to study SUDEP.

Effect of n-3 polyunsaturated fatty acids on oxidative stress in rats supplemented with different doses of fish oil

The diet and plasma lipid patterns associated with lipid oxidation susceptibility in rats fed different doses of polyunsaturated fatty acids (n-3 PUFA) from fish oil were evaluated. Wistar rats were assigned into three groups and received diets containing 8% soybean oil (SOY), 4% soybean oil + 4% fish oil (SOY-FISH) and 8% fish oil (FISH) for 21 days. Linoleic, oleic and ?-linolenic acids in SOY diets were substituted by myristic, palmitic, palmitoleic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in SOY-FISH and FISH diets reducing the n-6/n-3 ratio and increasing the peroxidability index (PI). Increased dietary EPA and DHA were observed in SOY-FISH and FISH plasma at the expense of linoleic and arachidonic acid levels. Saturated fatty acids, which were significantly different between the three diets (P < 0.01), were found at the same concentration in the plasma (P = 0.23). No changes were observed in oxidative stress as measured by the concentration of thiobarbituric acid reactive substances (TBARS) expressed in brain homogenates. However, TBARS concentration in the plasma of the SOY-FISH group was higher than the other two groups (P = 0.02). The major differences between these three groups were the n-3 PUFA content (0.4, 1.8 and 3.2 g/100 g diet) and the saturates/polyunsaturates ratio (0.3, 0.5 and 0.8) for SOY, SOY-FISH, and FISH groups, respectively. Thus, n-3 PUFA intake from fish oil only when followed by a decrease in saturated/polyunsaturated fatty acids ratio increased oxidative susceptibility in rats measured by plasma TBARS concentration

Stress at work among electric utility workers

In the last decades there was an increase in stress at work and its effects on workers' health. These issues are still little studied in the electric utility sector. This study aims to evaluate factors associated with stress at work and to verify its associations with health status among workers of an electric company in São Paulo State, Brazil. A cross-sectional study was conducted with 474 subjects (87.5% of the eligible workers). Data were collected using self-reported questionnaires. A descriptive analysis, a multiple linear hierarchical regression analysis and a correlation analysis were performed. The majority of participants were males (91.1%) and the mean age was 37.5 yr. The mean score of stress level was 2.3 points (scale ranging from 1.0 to 5.0). Hierarchical multiple analyses showed that: regular practice of physical activities (p=0.025) and individual monthly income (p=0.002) were inversely associated with stress level; BMI was marginally associated with the stress level (p=0.074). The demographic characteristics were not associated with stress. Stress at work was significantly associated with physical and mental health status (p<0.001). To improve health of electric utility workers, actions are suggested to decrease stress by remuneration and an appropriate practice of physical activity aiming reduction of BMI

Augmented muscle vasodilatory responses in obese children with Glu27 beta(2)-adrenoceptor polymorphism

This study examined forearm vasodilatation during mental challenge and exercise in 72 obese children (OC; age = 10 +/- 0.1 years) homozygous with polymorphism in the allele 27 of the beta(2)-adrenoceptors: Gln27 (n = 61) and Glu27 (n = 11). Forearm blood flow was recorded during 3 min of each using the Stroop color-word test (MS) and handgrip isometric exercise. Baseline hemodynamic and vascular measurements were similar. During the MS, peak forearm vascular conductance was significantly greater in group Glu27 (Delta = 0.35 +/- 0.4 vs. 0.12 +/- 0.1 units, respectively, p = .042). Similar results were found during exercise (Delta = 0.64 +/- 0.1 vs. 0.13 +/- 0.1 units, respectively, p = .035). Glu27 OC increased muscle vasodilatory responsiveness upon the MS and exercise.

No evidence for an association between the-36A > C phospholamban gene polymorphism and a worse prognosis in heart failure

Background: In Brazil, heart failure leads to approximately 25,000 deaths per year. Abnormal calcium handling is a hallmark of heart failure and changes in genes encoding for proteins involved in the re-uptake of calcium might harbor mutations leading to inherited cardiomyopathies. Phospholamban (PLN) plays a prime role in cardiac contractility and relaxation and mutations in the gene encoding PLN have been associated with dilated cardiomyopathy. In this study, our objective was to determine the presence of the -36A>C alteration in PLN gene in a Brazilian population of individuals with HF and to test whether this alteration is associated with heart failure or with a worse prognosis of patients with HF. Methods: We genotyped a cohort of 881 patients with HF and 1259 individuals from a cohort of individuals from the general population for the alteration -36A>C in the PLN gene. Allele and genotype frequencies were compared between groups (patients and control). In addition, frequencies or mean values of different phenotypes associated with cardiovascular disease were compared between genotypic groups. Finally, patients were prospectively followed-up for death incidence and genotypes for the -36A>C were compared regarding mortality incidence in HF patients. Results: No significant association was found between the study polymorphism and HF in our population. In addition, no association between PLN -36A>C polymorphism and demographic, clinical and functional characteristics and mortality incidence in this sample of HF patients was observed. Conclusion: Our data do not support a role for the PLN -36A>C alteration in modulating the heart failure phenotype, including its clinical course, in humans.

Phase transformation and residual stress probed by Raman spectroscopy in diamond-turned single crystal silicon

Single-point diamond turning of monocrystalline semiconductors is an important field of research within brittle materials machining. Monocrystalline silicon samples with a (100) orientation have been diamond turned under different cutting conditions (feed rate and depth of cut). Micro-Raman spectroscopy and atomic force microscopy have been used to assess structural alterations and surface finish of the samples diamond turned under ductile and brittle modes. It was found that silicon undergoes a phase transformation when machined in the ductile mode. This phase transformation is evidenced by the creation of an amorphous surface layer after machining which has been probed by Raman scattering. Compressive residual stresses are estimated for the machined surface and it is observed that they decrease with an increase in the feed rate and depth of cut. This behaviour has been attributed to the formation of subsurface cracks when the feed rate is higher than or equal to 2.5 mu m/rev. The surface roughness was observed to vary with the feed rate and the depth of cut. An increase in the surface roughness was influenced by microcrack formation when the feed rate reached 5.0 mu m/rev. Furthermore, a high-pressure phase transformation induced by the tool/material interaction and responsible for the ductile response of this typical brittle material is discussed based upon the presented Raman spectra. The application of this machining technology finds use for a wide range of high quality components, for example the creation of a micrometre-range channel for microfluidic devices as well as microlenses used in the infrared spectrum range.

Importance of considering a material micro-failure criterion in the numerical modelling of the shot peening process applied to parabolic leaf springs

Shot peening is a cold-working mechanical process in which a shot stream is propelled against a component surface. Its purpose is to introduce compressive residual stresses on component surfaces for increasing the fatigue resistance. This process is widely applied in springs due to the cyclical loads requirements. This paper presents a numerical modelling of shot peening process using the finite element method. The results are compared with experimental measurements of the residual stresses, obtained by the X-rays diffraction technique, in leaf springs submitted to this process. Furthermore, the results are compared with empirical and numerical correlations developed by other authors.

Heat and chemical stress modulate the expression of the alpha-RYR gene in broiler chickens

The biological cause of Pork Stress syndrome, which leads to PSE (pale, soft, exudative) meat, is excessive release of Ca(2+) ions, which is promoted by a genetic mutation in the ryanodine receptors (RyR) located in the sarcoplasmic reticulum of the skeletal muscle cells. We examined the relationship between the formation of PSE meat under halothane treatment and heat stress exposure in chicken alpha RYR hot spot fragments. Four test groups were compared: 1) birds slaughtered without any treatment, i.e., the control group (C); 2) birds slaughtered immediately after halothane treatment (H); 3) birds slaughtered immediately after heat stress treatment (HS), and 4) birds exposed to halothane and to heat stress (H+HS), before slaughtering. Breast muscle mRNA was extracted, amplified by RT-PCR, and sequenced. PSE meat was evaluated using color determination (L*value). The most common alteration was deletion of a single nucleotide, which generated a premature stop codon, resulting in the production of truncated proteins. The highest incidence of nonsense transcripts came with exposure to halothane; 80% of these abnormal transcripts were detected in H and H+HS groups. As a consequence, the incidence of abnormal meat was highest in the H+HS group (66%). In HS, H, and C groups, PSE meat developed in 60, 50, and 33% of the samples, respectively. Thus, halothane apparently modulates alpha RYR gene expression in this region, and synergically with exposure to heat stress, causes Avian Stress syndrome, resulting in PSE meat in broiler chickens.

Behavior and viability of spontaneous oxidative stress-resistant Lactococcus lactis mutants in experimental fermented milk processing

Previously, we isolated two strains of spontaneous oxidative (SpOx2 and SpOx3) stress mutants of Lactococcus lactis subsp cremoris. Herein, we compared these mutants to a parental wild- type strain (J60011) and a commercial starter in experimental fermented milk production. Total solid contents of milk and fermentation temperature both affected the acidification profile of the spontaneous oxidative stress- resistant L. lactis mutants during fermented milk production. Fermentation times to pH 4.7 ranged from 6.40 h (J60011) to 9.36 h (SpOx2); V(max) values were inversely proportional to fermentation time. Bacterial counts increased to above 8.50 log(10) cfu/mL. The counts of viable SpOx3 mutants were higher than those of the parental wild strain in all treatments. All fermented milk products showed post-fermentation acidification after 24 h of storage at 4 degrees C; they remained stable after one week of storage.

Proteasome Inhibition Represses Unfolded Protein Response and Nox4, Sensitizing Vascular Cells to Endoplasmic Reticulum Stress-Induced Death

Background: Endoplasmic reticulum (ER) stress has pathophysiological relevance in vascular diseases and merges with proteasome function. Proteasome inhibition induces cell stress and may have therapeutic implications. However, whether proteasome inhibition potentiates ER stress-induced apoptosis and the possible mechanisms involved in this process are unclear. Methodology/Principal Findings: Here we show that proteasome inhibition with MG132, per se at non-lethal levels, sensitized vascular smooth muscle cells to caspase-3 activation and cell death during ER stress induced by tunicamycin (Tn). This effect was accompanied by suppression of both proadaptive (KDEL chaperones) and proapoptotic (CHOP/GADD153) unfolded protein response markers, although, intriguingly, the splicing of XBP1 was markedly enhanced and sustained. In parallel, proteasome inhibition completely prevented ER stress-induced increase in NADPH oxidase activity, as well as increases in Nox4 isoform and protein disulfide isomerase mRNA expression. Increased Akt phosphorylation due to proteasome inhibition partially offset the proapoptotic effect of Tn or MG132. Although proteasome inhibition enhanced oxidative stress, reactive oxygen species scavenging had no net effect on sensitization to Tn or MG132-induced cell death. Conclusion/Relevance: These data indicate unfolded protein response-independent pathways whereby proteasome inhibition sensitizes vascular smooth muscle to ER stress-mediated cell death. This may be relevant to understand the therapeutic potential of such compounds in vascular disease associated with increased neointimal hyperplasia.

Factor (NF) kappa B polymorphism is associated with heart function in patients with heart failure

Background: Cardiac remodeling is generally an adverse sign and is associated with heart failure (HF) progression. NFkB, an important transcription factor involved in many cell survival pathways, has been implicated in the remodeling process, but its role in the heart is still controversial. Recently, a promoter polymorphism associated with a lesser activation of the NFKB1 gene was also associated with Dilated Cardiomyopathy. The purpose of this study was to evaluate the association of this polymorphism with clinical and functional characteristics of heart failure patients of different etiologies. Methods: A total of 493 patients with HF and 916 individuals from a cohort of individuals from the general population were investigated. The NFKB1-94 insertion/deletion ATTG polymorphism was genotyped by High Resolution Melt discrimination. Allele and genotype frequencies were compared between groups. In addition, frequencies or mean values of different phenotypes associated with cardiovascular disease were compared between genotype groups. Finally, patients were prospectively followed-up for death incidence and genotypes for the polymorphism were compared regarding disease onset and mortality incidence in HF patients. Results: We did not find differences in genotype and allelic frequencies between cases and controls. Interestingly, we found an association between the ATTG(1)/ATTG(1) genotype with right ventricle diameter (P = 0.001), left ventricle diastolic diameter (P = 0.04), and ejection fraction (EF) (P = 0.016), being the genotype ATTG(1)/ATTG(1) more frequent in patients with EF lower than 50% (P = 0.01). Finally, we observed a significantly earlier disease onset in ATTG(1)/ATTG(1) carriers. Conclusion: There is no genotype or allelic association between the studied polymorphism and the occurrence of HF in the tested population. However, our data suggest that a diminished activation of NFKB1, previously associated with the ATTG(1)/ATTG(1) genotype, may act modulating on the onset of disease and, once the individual has HF, the genotype may modulate disease severity by increasing cardiac remodeling and function deterioration.

The Borg Scale as an Important Tool of Self-Monitoring and Self-Regulation of Exercise Prescription in Heart Failure Patients During Hydrotherapy - A Randomized Blinded Controlled Trial

Background: The Borg Scale may be a useful tool for heart failure patients to self-monitor and self-regulate exercise on land or in water (hydrotherapy) by maintaining the heart rate (HR) between the anaerobic threshold and respiratory compensation point. Methods and Results: Patients performed a cardiopulmonary exercise test to determine their anaerobic threshold/respiratory compensation points. The percentage of the mean HR during the exercise session in relation to the anaerobic threshold HR (%EHR-AT), in relation to the respiratory compensation point (%EHR-RCP), in relation to the peak HR by the exercise test (%EHR-Peak) and in relation to the maximum predicted HR (%EHR-Predicted) was calculated. Next, patients were randomized into the land or water exercise group. One blinded investigator instructed the patients in each group to exercise at a level between ""relatively easy and slightly tiring"". The mean HR throughout the 30-min exercise session was recorded. The %EHR-AT and %EHR-Predicted did not differ between the land and water exercisegroups, but they differed in the %EHR-RCP (95 +/- 7 to 86 +/- 7. P<0.001) and in the %EHR-Peak (85 +/- 8 to 78 +/- 9, P=0.007). Conclusions: Exercise guided by the Borg scale maintains the patient's HR between the anaerobic threshold and respiratory compensation point (ie, in the exercise training zone). (Circ J 2009; 73: 1871-1876)

Cardiomyopathy, adult valve disease and heart failure in South America

Continued assessment of temporal trends in mortality and epidemiology of specific cardiovascular diseases in South America is needed to provide a scientific basis for rational allocation of the limited healthcare resources and introduction of strategies to reduce risk and predict the future burden of cardiovascular disease. The epidemiology of cardiomyopathies, adult valve disease and heart failure (HF) in South America is reviewed here. Diseases of the circulatory system are the main cause of death based on data from about 50% of the South American population. Among the cardiovascular causes of death, cerebrovascular disease is predominant followed by ischaemic heart disease, other heart diseases and hypertensive disease. Of note, cerebrovascular disease is the main cause of death in women, and race also influenced cardiovascular mortality rates. HF is the most important cardiovascular reason for admission to hospital due to cardiovascular disease of ischaemic, idiopathic dilated cardiomyopathic, valvular, hypertensive and chagasic aetiologies. Also, mortality due to HF is high, especially owing to Chagas' disease. HF and aetiologies associated with HF are responsible for 6.3% of deaths. Rheumatic fever is the leading cause of valvular heart disease. The findings have important public health implications because the allocation of healthcare resources, and strategies to reduce the risk of HF should also consider controlling Chagas' disease and rheumatic fever in South American countries.

ACE as a Mechanosensor to Shear Stress Influences the Control of Its Own Regulation via Phosphorylation of Cytoplasmic Ser(1270)

Objectives: We tested whether angiotensin converting enzyme (ACE) and phosphorylation of Ser(1270) are involved in shear-stress (SS)-induced downregulation of the enzyme. Methods and Results: Western blotting analysis showed that SS (18 h, 15 dyn/cm(2)) decreases ACE expression and phosphorylation as well as p-JNK inhibition in human primary endothelial cells (EC). CHO cells expressing wild-type ACE (wt-ACE) also displayed SS-induced decrease in ACE and p-JNK. Moreover, SS decreased ACE promoter activity in wt-ACE, but had no effect in wild type CHO or CHO expressing ACE without either the extra-or the intracellular domains, and decreased less in CHO expressing a mutated ACE at Ser(1270) compared to wt-ACE (13 vs. 40%, respectively). The JNK inhibitor (SP600125, 18 h), in absence of SS, also decreased ACE promoter activity in wt-ACE. Finally, SS-induced inhibition of ACE expression and phosphorylation in EC was counteracted by simultaneous exposure to an ACE inhibitor. Conclusions: ACE displays a key role on its own downregulation in response to SS. This response requires both the extra- and the intracellular domains and ACE Ser(1270), consistent with the idea that the extracellular domain behaves as a mechanosensor while the cytoplasmic domain elicits the downstream intracellular signaling by phosphorylation on Ser(1270).