Ageing is associated with a decrease in the number of sarcolemmal ATP-sensitive K+ channels in a gender-dependent manner

The opening of sarcolemmal K(ATP) channels is considered to be an important endogenous cardioprotective mechanism. On the other hand, age-dependent changes in the myocardial susceptibility to ischemia and hypoxia have been observed in different species, including humans. Here, we have hypothesized that aging might be associated with the changes in sarcolemmal K(ATP) channels. Therefore, the main objective of the present study was to establish whether aging changes expression of cardiac sarcolemmal ATP-sensitive K+ (K(ATP)) channels. RT-PCR using primers specific for K(ATP) channel subunits, Kir6.2, Kir6.1 and SUR2A subunits was performed using total RNA from guinea-pig ventricular tissue. Whole cell electrophysiology was done on isolated guinea-pig ventricular cardiomyocytes. Western blotting using anti-Kir6.2 and anti-SUR2A antibodies was performed on cardiac membrane fraction. Tissue and cells were harvested from young and old, male and female guinea-pigs. RT-PCR analysis did not reveal significant age-related changes in levels of Kir6.1 or Kir6.2 mRNAs. However, levels of SUR2A were significantly lower in old than in young females. Such age-differences were not observed with cardiac tissue from male animals. In both old and young males, pinacidil (100 microM) induced outward currents. The difference between current density of pinacidil-sensitive component in females, but not males, was statistically significant. Western blotting analysis revealed higher levels of Kir6.2 and SUR2A proteins in cardiac membrane fraction from young than old females. The present study demonstrates that in females, but not males, aging is associated with decrease in number of cardiac K(ATP) channels which is due to decrease in levels of the SUR2A subunit.     

A der(14)t(1;14)(q12;p11) in chronic myelomonocytic leukemia

Duplication of the long arm of chromosome 1 (1q) is widely reported in human neoplasia, including the myelodysplastic syndromes (MDS). So far, it has not been described as a single aberration in the chronic myelomonocytic leukemia (CMML), a subtype of MDS. Rather, trisomy 1q was always a part of complex chromosome changes affecting the subtypes of MDS other than CMML. We report on a patient with CMML with an unbalanced translocation of the entire 1q onto the short arm of chromosome 14 as a sole cytogenetic abnormality. Fluorescence in situ hybridization (FISH) analysis with an alpha-satellite probe for the paracentric region of the long arm of chromosome 1 confirmed the presence of trisomy 1q in a derivative chromosome, der(14)t(1;14)(q12;p11). The discrepant results between the metaphase cytogenetics (100% abnormal) and interphase cytogenetic (71% nuclei with 3 signals) suggest that trisomy 1q, even in the absence of additional cytogenetic changes, has a sufficient leukemogenic potential to confer a proliferative advantage on hematopoietic cells committed to monocyte stemline both in vitro and in vivo. The literature data on partial and complete trisomy 1q in CMML is reviewed.     

Sarcolemmal K(ATP) channels in ageing

This review highlights some recent research addressing sarcolemmal K(ATP) channels in ageing. These channels are abundant in cardiac myocytes where they are essential in coupling the cellular metabolic state with membrane excitability. The opening of sarcolemmal ATP-sensitive K+ (K(ATP)) channels occurs during ischaemia and protect the heart against injury. Age-dependent changes in the myocardial susceptibility to ischemia have been observed in different species, including humans. Recent research has demonstrated that ageing is associated with decrease in numbers of sarcolemmal K(ATP) in hearts from females, but not males. This phenomenon seems to be associated with age-dependent decrease in concentration of circulating estrogens. In the heart, SUR2A, a regulatory subunit of K(ATP) channels, is present in excess over Kir6.2, a pore-forming K(ATP) channel subunit. The consequence of this is that SUR2A is a subunit that controls the number of sarcolemmal K(ATP) channels. Estrogens specifically up-regulate SUR2A and, thereby, control the number of sarcolemmal K(ATP) channels. Age-dependent loss of sarcolemmal K(ATP) channels creates a cardiac phenotype more sensitive to ischaemia, which may explain, at least in part, an ageing-associated decrease of myocardial tolerance to stress that occurs in elderly women.     

The Impact of Diet and Fibre Fractions on Plasma Adipocytokine Levels in Prediabetic Adults

The impact of diet and fibre fractions on adipocytokines in obese subjects with a risk of diabetes has not been investigated in detail yet. The purpose of the study is to evaluate the effects of a 12-month lifestyle intervention with different fibre profiles (resistant starch (RS)—rich fibre, or ordinary food fibre profiles) on adipocytokine levels. Fifty participants are divided into two groups (RS group and Fibre group). The groups differ only in the percentage of the recommended level of the RS consumed as a fraction of the same total fibre amount. The applied dietary intervention includes intake of 7531 KJ/daywith a total fibre portion of 25–35 g/dayfor both groups that includes 15 g/day of RS for the RS group only. The levels of leptin, adiponectin, apelin, resistin, tumor necrosis factor (TNF)-alpha and C-reactive protein (CRP) are measured, and their relationship to anthropometric and biochemical parameters is estimated. Along with significant body weight loss, only leptin is significantly reduced by 13% in the RS group while in the Fibre group, apelin levels are significant (−21%). Polynomial regression shows a negative correlation between RS intake and adiponectin (R2 = 0.145) and resistin level (R2 = 0.461) in the RS group. This study indicates the possibility that fibre fractions differently influence the outcome of lifestyle interventions, as well as their adipocytokine levels, in obese prediabetic adults.     

Supplementation with Octacosanol Affects the Level of PCSK9 and Restore Its Physiologic Relation with LDL-C in Patients on Chronic Statin Therapy

Dietary supplementation with sugar cane derivates may modulate low-density lipoprotein cholesterol (LDL-C) and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. The purpose of this study was to determine if dietary supplement (DS), containing Octacosanol (20 mg) and vitamin K2 (45 µg), could restore the disrupted physiologic relation between LDL-C and serum PCSK9. Double-blind, randomized, placebo-controlled, single-center study including 87 patients on chronic atorvastatin therapy was conducted. Eighty-seven patients were randomized to receive DS (n = 42) or placebo (n = 45), and followed for 13 weeks. Serum PCSK9 levels, lipid parameters and their relationship were the main efficacy endpoints. The absolute levels of PCSK9 and LDL-C were not significantly different from baseline to 13 weeks. However, physiologic correlation between % change of PCSK9 and % change of LDL-C levels was normalized only in the group of patients treated with DS (r = 0.409, p = 0.012). This study shows that DS can restore statin disrupted physiologic positive correlation between PCSK9 and LDL-C. Elevated PCSK9 level is an independent risk factor so controlling its rise by statins may be important in prevention of cardiovascular events.     

Hepatoprotective Effect of Mixture of Dipropyl Polysulfides in Concanavalin A-Induced Hepatitis

The main biologically active components of plants belonging to the genus Allium, responsible for their biological activities, including anti-inflammatory, antioxidant and immunomodulatory, are organosulfur compounds. The aim of this study was to synthetize the mixture of dipropyl polysulfides (DPPS) and to test their biological activity in acute hepatitis. C57BL/6 mice were administered orally with DPPS 6 h before intravenous injection of Concanavalin A (ConA). Liver inflammation, necrosis and hepatocytes apoptosis were determined by histological analyses. Cytokines in liver tissue were determined by ELISA, expression of adhesive molecules and enzymes by RT PCR, while liver mononuclear cells were analyzed by flow cytometry. DPPS pretreatment significantly attenuated liver inflammation and injury, as evidenced by biochemical and histopathological observations. In DPPS-pretreated mice, messenger RNA levels of adhesion molecules and NADPH oxidase complex were significantly reduced, while the expression of SOD enzymes was enhanced. DPPS pretreatment decreased protein level of inflammatory cytokines and increased percentage of T regulatory cells in the livers of ConA mice. DPPS showed hepatoprotective effects in ConA-induced hepatitis, characterized by attenuation of inflammation and affection of Th17/Treg balance in favor of T regulatory cells and implicating potential therapeutic usage of DPPS mixture in inflammatory liver diseases.     

Point-of-care measured serum cholinesterase activity predicts patient outcome following severe burns

Risk stratification is of utmost importance in burn therapy. However, suitable bedside biomarkers to evaluate the emerging inflammatory response following burn injuries are missing. Serum cholinesterase (butyrylcholinesterase, BChE) has been shown to be a clinically relevant biomarker in acute inflammatory diseases including burns.In this observational cohort study BChE activity was measured by using point-of-care testing (POCT), a novel method in acute burn care. POCT measurements were performed at emergency room admission (ERA) of 35 patients and repeated 12, 24 and 48 h later. All patients or their legal designees gave informed consent.Patients with burn injuries showed sustained BChE activity reduction following hospital admission. BChE activity correlated negatively with burn injury severity, organ failure severity and intensive care unit resource requirements. BChE activity measured at ERA and 12 h later identified survivors and predicted 28-day patient outcome with noninferior efficacy compared to the abbreviated burn severity index (ABSI) scoring. Finally, POCT-measured BChE activity might complement ABSI scoring and possibly improve early risk stratification in acute burn care therapy.     

Mesangial expansion at 5 years predicts death and death‐censored graft loss after renal transplantation

Death with a functioning graft and death‐censored renal allograft failure remain major problems for which effective preventative protocols are lacking. The retrospective cohort study aimed to determine whether histologic changes on a 5‐year surveillance kidney biopsy predict adverse outcomes after transplantation in recipients who had: both Type 2 diabetes (T2DM) and obesity (BMI ≥ 30 kg/m²) at the time of transplantation (T2DM/Obesity, n = 75); neither (No T2DM/No obesity, n = 78); No T2DM/Obesity (n = 41), and T2DM/No obesity (n = 47). On 5‐year biopsies, moderate‐to‐severe mesangial expansion was more common in the T2DM/Obesity group (Banff mm score ≥2 = 49.3%; Tervaert classification MS ≥ 2b = 26.7%) compared to the other groups (p < .001 for both scores). Risk factors included older age, higher BMI, HbA1C, and triglycerides at 1‐year post‐transplant. Moderate‐to‐severe mesangial expansion correlated with death with function (HR 1.74 (1.01, 2.98), p = .045 Banff and 1.89 (1.01, 3.51) p = .045 Tervaert) and with death‐censored graft loss (HR 3.2 (1.2, 8.8), p = .02 Banff and HR 3.8 (1.3, 11.5), p = .01 Tervaert) over a mean of 11.6 years of recipient follow‐up post‐transplant. These data suggest that mesangial expansion in recipients with T2DM and obesity may reflect systemic vascular injury and might be a novel biomarker to predict adverse outcomes post renal transplant.     

Human V5/MT+: comparison of functional and cytoarchitectonic data

To date, the delineation of the human visual “motion area” still relies on functional paradigms originally devised to identify monkey area MT. Using fMRI, we have identified putative human area V5/MT+ in normals by modelling the BOLD responses to alternating radially moving and stationary dot patterns. Functional activations were compared with cytoarchitectonic probability maps of its putative correlate area hOc5, which was calculated based upon data from histological sections of ten human post-mortem brains. Bilateral visual cortex activations were seen in the single subject dynamic versus stationary contrasts and in the group random-effects analysis. Comparison of group data with area hOc5 revealed that 19.0%/39.5% of the right/left functional activation was assigned to the right/left hOc5. Conversely, 83.2%/53.5% of the right/left hOc5 was functionally activated. Comparison of functional probability maps (fPM) with area hOc5 showed that 28.6%/18.1% of the fPM was assigned to hOc5. In turn, 84.9%/41.5% of the area hOc5 was covered by the respective fPM. Thus, random-effects data and fPMs yielded similar results. The present study shows for the first time the correspondence between the functionally defined human V5/MT+ and the post-mortem cytoarchitectonic area hOc5.