Characteristics and clinical outcome of 458 patients with acute myocardial infarction requiring mechanical ventilation. Results of the BEAT registry of the ALKK-study group

Background  

Information about the clinical course of patients with acute myocardial infarction requiring mechanical ventilation is scarce. We sought to evaluate the clinical outcome of a large cohort of such patients in clinical practice.     

Cytokine gene polymorphisms and graft-versus-host disease in children after matched sibling hematopoietic stem cell transplantation: a single-center experience

Various polymorphisms in cytokine genes have recently been investigated as candidate risk factors in allogeneic hematopoetic stem cell transplantation (allo-HSCT). We retrospectively analyzed specific polymorphisms in genes for interleukin (IL)-10, IL-6, tumor-necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in a pediatric cohort of 57 histocompatibility leucocyte antigen (HLA)-identical sibling myeloablative transplants. Both recipient and donor genotypes were tested for association with graft-versus-host disease (GVHD) by statistical methods including Cox regression analysis. We found a significant association between the IL-10 promoter haplotype polymorphisms at positions -1082, -819 and -592 with the occurrence of severe (grades III-IV) acute GVHD (aGVHD). Recipients with the haplotype GCC had a statistically significant decreased risk of severe aGVHD (hazard risk (HR)=0.20, 95% confidence interval (CI): 0.06-0.67) in comparison with patients with other IL-10 haplotypes (P=0.008). Transplant-related mortality at 1 year was significantly lower in recipients with this haplotype (HR=0.17, 95% CI: 0.012-0.320) versus other IL-10 haplotypes (P=0.03), whereas overall survival was not influenced by IL-10 haplotype polymorphisms. In multivariate analysis, the presence of the IL-10 GCC haplotype was found as the only variable associated with a statistically significant decreased hazard of severe aGVHD development (P=0.02, HR=0.21, 95% CI: 0.05-0.78). These results suggest that pediatric patients possessing the IL-10 GCC haplotype may be protected from the occurrence of severe aGVHD in the setting of matched sibling HSCT.     

Glutamine, ornithine, citrulline and arginine levels in children with phenylketonuria: The diet effect

BackgroundPhenylketonuria (PKU) therapeutic diet is characterized by the great replacement of natural protein with a phenylalanine-free formula.AimTo investigate the effect of diet on the amino acid serum levels in PKU patients and their total antioxidant status (TAS).MethodsThirty-seven poorly controlled patients (group A), 43 patients who strictly adhered to their diet (group B) and 50 controls were included in the study. In patients and controls blood chemistry, TAS and serum amino acid level determinations were performed.ResultsPhenylalanine levels significantly differed among the groups. Glutamine and ornithine levels were significantly higher in group A, while TAS (416 ± 30 vs 228 ± 23 μmol/L, p < 0.001), citrulline (39 ± 15 vs 26 ± 5 μmol/L, p < 0.001) and arginine levels (61 ± 11 vs 80 ± 12 μmol/L, p < 0.001) were higher in group B. The other determined amino acid serum levels did not differ among the groups of patients and controls.ConclusionsThe high glutamine and ornithine levels in group A may reflect the high natural protein intake. High phenylalanine levels in these patients may locally affect the hepatocyte, enterocyte, and/or renal function resulting in low citrulline and arginine levels contributing to their low TAS.     

Maternal chronic hepatitis B virus is implicated with low neonatal paraoxonase/arylesterase activities

BACKGROUND: Paraoxonase/arylesterase activities are closely implicated with liver function and antiatherogenetic process. AIM: To evaluate whether maternal chronic hepatitis B virus, disease (HBV) affect serum neonatal paraoxonase/arylesterase activities. PATIENTS AND METHODS: 28 pregnant women with HBV and 28 healthy pregnant women (controls) in the delivery room and their newborns (cord blood) underwent laboratory examinations. Serological virus tests and liver function tests and paraoxonase (PON 1) activities were measured with the Siemens Advia 1650 Clinical Chemistry System, while total antioxidant capacity (TAC) levels and paraoxonase-arylesterase (PON-aryl) activities were measured spectrophotometrically. RESULTS: Serological HBV tests and HBV DNA showed chronic HBV (precore mutant G1896A) in the diseased mothers whereas anti-HBc and anti-HBe were detected in their neonates. Liver function parameters were found normal in controls and both groups of newborns. Moderately increased transaminase levels were measured in HBV mothers, whereas TAC levels were decreased in hepatic mothers and their newborns. Interestingly albumin levels did not differ among the studied groups. PON 1 and PON-aryl activities in the diseased mothers (148+/-14 U/mL/min, 130+/-16 KU/mL/min) and their infants (32+/-6 U/mL/min, 24+/-5 KU/mL/min) were significantly lower as compared to those of control mothers (217+/-16 U/mL/min, 196+/-14 KU/mL/min p<0.001) and their newborns (57+/-6 U/mL/min, 48+/-8 UK mL/min p<0.001). Inverse significant correlations were found between the studied enzyme activities and liver enzymes in all the groups of study except in infants born from HBV mothers and positive with TAC in all the studied groups. CONCLUSIONS: Decreased PON 1 and PON-aryl activities were measured in infants born from hepatic mothers probably as a consequence of their low TAC. Infants born from HBV mothers are at risk for developing LDL oxidation perinatally.     

L-cysteine supplementation prevents exercise-induced alterations in human erythrocyte membrane acetylcholinesterase and Na+,K+-ATPase activities.

BACKGROUND: L-Cysteine (L-Cys) is implicated in the reduction of free radical production. The aim of this study was to investigate whether L-Cys supplementation prevents modulation of the activities of erythrocyte membrane acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)-ATPase induced by free radicals in basketball players during training. METHODS: Blood was obtained from 10 basketball male players before (group A) and after a game (group B) and after 1 week of L-Cys (0.5 g/24 h orally) supplementation before (group C) and after training (group D). Lactate, pyruvate and total antioxidant status (TAS) were measured using commercial kits and the enzyme activities were determined spectrophotometrically. RESULTS: Both lactate and pyruvate levels remarkably increased after exercise. In contrast, TAS levels significantly decreased in group B, increased in group C and then declined (group D), reaching those of group A. AChE activity was statistically increased post-exercise (3.98+/-0.04 Delta OD/min x mg protein) compared with pre-training (2.90+/-0.05 Delta OD/min x mg protein, p<0.01). Na(+),K(+)-ATPase activity was also higher post-exercise (1.27+/-0.05 micromol Pi/h x mg protein) than that pre-exercise (0.58+/-0.04 micromol Pi/h x mg protein, p<0.001). When the players were supplemented with L-Cys, both AChE and Na(+),K(+)-ATPase activities remained unaltered post-exercise. Mg(2+)-ATPase activities were unchanged in all groups studied. CONCLUSIONS: L-Cys supplementation may protect the enzyme activities studied against stimulation induced by free radical production during training in athletes by ameliorating their total antioxidant capacity.     

Alterations in the heart mitochondrial proteome in a desmin null heart failure model

Desmin, the major muscle-specific intermediate filament (IF) protein, is essential for mitochondrial behavior and function and maintenance of healthy muscle. Mice null for desmin develop dilated cardiomyopathy characterized by extensive cardiomyocyte death, fibrosis, calcification and eventual heart failure. We sought to investigate the heart mitochondrial proteome of wild type and desmin null mice in order to understand the cardiac and skeletal myopathy phenotype of desmin deficiency. The proteins were analyzed by 2-D electrophoresis, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Three hundred and eighty different gene products were identified, about 50% of which were enzyme subunits. Cytoskeletal and muscle-specific proteins, calcium-binding proteins, proteins with various other functions and about 70 unknown, hypothetical or poorly described gene products, were also identified. We have observed differences in most metabolic pathways, in apoptosis, calcium homeostasis, calcification and fibrosis and in different signaling pathways linked or not to mitochondrial function. The most significant changes were observed in ketone body and acetate metabolism, NADH shuttle proteins, amino-acid metabolism proteins and respiratory enzymes. Several of these changes are consistent with the known phenotype of desmin deficiency.     

Improvement in Cardiovascular Indices After Roux-en-Y Gastric Bypass or Sleeve Gastrectomy for Morbid Obesity

Background

Morbidly obese patients display cardiac abnormalities which are partially reversed after weight loss. The aim of the present study was to assess the potential difference in cardiovascular disease indices between patients who underwent either gastric bypass surgery or sleeve gastrectomy.

Methods

Thirty-seven morbidly obese patients who underwent either Roux-en-Y gastric bypass (RYGB) (n?=?14) or SG (n?=?23) were examined before, 3 and 6 months after surgery. Indices of cardiac autonomic nervous system activity were evaluated, namely baroreflex sensitivity (BRS) and heart rate variability (HRV). A complete echocardiographic study was performed in a subgroup of 17 patients (RYGB 8, SG 9) preoperatively and 6 months after surgery, evaluating epicardial fat thickness, aortic distensibility, left ventricular (LV) Tei index, left atrium diameter, ejection fraction, and LV mass.

Results

All subjects experienced significant (p?<?0.001) and similar weight loss independently of the type of operation. BRS and HRV indices improved significantly and to the same degree after surgery in both groups. In the echocardiographic study, all parameters improved significantly at 6 months in comparison with the baseline values. In addition, the RYGB group displayed significantly greater reduction in epicardial fat thickness (p?=?0.007) and also tended to have a better LV performance as expressed by the lower values of the Tei index (p?=?0.06) compared to the SG group 6 months after surgery.

Conclusions

Both RYGB and SG exert comparable effects on weight loss and improvement of cardiovascular parameters. RYGB displays a more beneficial influence on epicardial fat thickness and left ventricular performance than SG.     

Cardiac I-1c Overexpression With Reengineered AAV Improves Cardiac Function in Swine Ischemic Heart Failure

Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 10¹³ vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 10¹² vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure–volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF.