Iron concentrations in atherosclerotic plaque and serum in patients with carotid atherosclerosis

The aim of this study was to investigate the iron concentrations in serum and carotid plaque in patients with different morphology of carotid atherosclerotic plaque and compared with other metal ions. Carotid endarterectomy due to the significant atherosclerotic stenosis was performed in 91 patients. Control group consisted of 27 patients, without carotid atherosclerosis. Atherosclerotic plaques were divided into four morphological groups, according to ultrasonic and intraoperative characteristics. Iron, copper and zinc concentration in plaque, carotid artery and serum were measured by spectrophotometry. Serum iron concentrations were higher in patients with hemorrhagic plaques in comparison to the control group (4.7 μmol/l ± 1.2 vs. 2.1 μmol/l ± 0.8, p < 0.05). Iron concentrations were higher in patients with hemorrhagic plaques in comparison to fibrolipid plaques (72.1 ± 14.3 μg/g vs. 39.3 ± 22.9 μg/g; p < 0.05). Negative significant correlation was found for zinc in serum and plaque iron concentration in patients (p < 0.05). We also demonstrated positive significant correlation for copper and iron in serum (p < 0.05). The data obtained in the current study are consistent with the hypothesis that high iron levels may contribute to atherosclerosis and its complications as factors in a multifactorial disease

Heart rate variability before and after cycle exercise in relation to different body positions

The purpose of this study was to assess the effect of three different body positions on HRV measures following short-term submaximal exercise. Thirty young healthy males performed submaximal cycling for five minutes on three different occasions. Measures of HRV were obtained from 5-min R to R wave intervals before the exercise (baseline) and during the last five minutes of a 15 min recovery (post-exercise) in three different body positions (seated, supine, supine with elevated legs). Measures of the mean RR normal-to-normal intervals (RRNN), the standard deviation of normal-to-normal intervals (SDNN), the root mean square of successive differences (RMSSD) and the low-frequency (LF) and the high-frequency (HF) spectral power were analyzed. Post-exercise RRNN, RMSSD were significantly higher in the two supine positions (p 0.05). Post-exercise time domain measures of HRV (RRNN, SDNN, RMSSD) were significantly lower compared with baseline values (p < 0.01) regardless body position. Post-exercise ln LF and ln HF in all three positions remained significantly reduced during recovery compared to baseline values (p < 0.01). The present study suggests that 15 minutes following short-term submaximal exercise most of the time and frequency domain HRV measures have not returned to pre-exercise values. Modifications in autonomic cardiac regulation induced by body posture present at rest remained after exercise, but the post-exercise differences among the three positions did not resemble the ones established at res

Dietary nitrate does not modify blood pressure and cardiac output at rest and during exercise in older adults : a randomised cross over study

Dietary nitrate (〖NO〗_3^-) supplementation has been associated with improved vascular and metabolic health. We conducted a double-blind, cross-over, placebo-controlled RCT to investigate the effects of 7-day consumption of beetroot juice compared with placebo on 1) blood pressure (BP) measured in resting conditions and during exercise, 2) cardiac and peripheral vascular function and 3) biomarkers of inflammation, oxidative stress and endothelial integrity. Twenty non-smoking healthy participants aged 60-75y and BMI 20.0-29.9kg/m2 were recruited. Measurement were conducted before and after each 7-day intervention period. Consumption of 〖NO〗_3^- had no effect on resting systolic and diastolic BP. 〖NO〗_3^- consumption did not improve indexes of central and peripheral cardiac function responses during cardiopulmonary exercise testing. Dietary 〖NO〗_3^- supplementation did not modify biomarkers of inflammation, oxidative stress and endothelial integrity. This study do not support the short-term benefits of dietary 〖NO〗_3^- supplementation on physiological and biochemical markers of vascular health in older healthy adults. Trial Registration: ISRCTN1906495

The role of hydrogen sulfide in homocysteine-induced cardiodynamic effects and oxidative stress markers in the isolated rat heart

This study aimed to assess the role of H2S in homocysteine-induced cardiodynamic effects in the isolated rat heart. The hearts were retrogradely perfused according to the Langendorff technique. The maximum and minimum rates of pressure in the left ventricle (dp/dt max, dp/dt min), systolic and diastolic left ventricular pressures (SLVP, DLVP), heart rate (HR), and coronary flow (CF) were measured. A spectrophotometrical method was used to measure the following oxidative stress markers: index of lipid peroxidation (thiobarbituric acid reactive substances, TBARS), nitrite level (NO2−), superoxide anion radicals (O2•−), and hydrogen peroxide (H2O2) concentrations. The administration of 10 µmol/l DL-homocysteine (DL-Hcy) alone decreased dp/dt max, SLVP, and CF but did not change any oxidative stress parameters. The administration of 10 µmol/l DL-propargylglycine (DL-PAG) decreased all cardiodynamic parameters and increased the concentration of O2•−. The co-administration of DL-Hcy and DL-PAG induced a significant decrease in all estimated cardiodynamic parameters and decreased the concentration of NO2− and O2•− but increased the levels of TBARS and H2O2. Homocysteine shows a lower pro-oxidative effect in the presence of hydrogen sulfide (H2S), which indicates a potential anti-oxidative capacity of H2S

A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus

Generally, the second messenger bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-diGMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be—at least partially—functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus

Metabolic effects of bezafibrate in mitochondrial disease.

Funder: Medical Research Council (MRC): Confidence in Concept award to Newcastle UniversityMitochondrial disorders affect 1/5,000 and have no cure. Inducing mitochondrial biogenesis with bezafibrate improves mitochondrial function in animal models, but there are no comparable human studies. We performed an open-label observational experimental medicine study of six patients with mitochondrial myopathy caused by the m.3243A>G MTTL1 mutation. Our primary aim was to determine the effects of bezafibrate on mitochondrial metabolism, whilst providing preliminary evidence of safety and efficacy using biomarkers. The participants received 600-1,200 mg bezafibrate daily for 12 weeks. There were no clinically significant adverse events, and liver function was not affected. We detected a reduction in the number of complex IV-immunodeficient muscle fibres and improved cardiac function. However, this was accompanied by an increase in serum biomarkers of mitochondrial disease, including fibroblast growth factor 21 (FGF-21), growth and differentiation factor 15 (GDF-15), plus dysregulation of fatty acid and amino acid metabolism. Thus, although potentially beneficial in short term, inducing mitochondrial biogenesis with bezafibrate altered the metabolomic signature of mitochondrial disease, raising concerns about long-term sequelae

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations