The slow component of the delayed rectifier potassium current in undiseased human ventricular myocytes

Objective: The purpose of this study was to investigate the properties of the slow component of the delayed rectifier potassium current (I-Ks) in myocytes isolated from undiseased human left ventricles. Methods: The whole-cell configuration of the patch-clamp technique was applied in 58 left ventricular myocytes from 15 hearts at 37 degreesC. Nisoldipine (1 muM) was used to block inward calcium current (I-Ca) and E-4031 (1-5 muM) was applied to inhibit the rapid component of the delayed rectifier potassium current (I-Ks). Results: In 31 myocytes an E-4031 insensitive, but L-735,821 and chromanol 293B sensitive, tail current was identified which was attributed to the slow component of I-K (I-Ks). Activation of I-Ks was slow (tau = 903 +/- 101 ms at 50 mV, n = 24), but deactivation of the current was relatively rapid ( tau =122.4 +/- 11.7 ms at -40 mV, n = 19). The activation of I-Ks was voltage independent but its deactivation showed clear voltage dependence. The deactivation was faster at negative voltages (about 100 ms at -50 mV) and slower at depolarized potentials (about 300 ms at 0 mV). In six cells, the reversal potential was -81.6 +/- 2.8 mV on an average which is close to the K+ equilibrium potential suggesting K+ as the main charge carrier. Conclusion: In undiseased human ventricular myocytes, I-Ks exhibits slow activation and fast deactivation kinetics. Therefore, in humans I-Ks differs from that reported in guinea pig, and it best resembles I-Ks described in dog and rabbit ventricular myocytes

N-acetyl-l-aspartic acid-N'-methylamide with side-chain orientation capable of external hydrogen bonding

In this study, we generated and analyzed the side-chain conformational potential energy hyper-surfaces for each of the nine possible backbone conformers for N-acetyl-L-aspartic acid-N' methylamide. We found a total of 27 out of the 81 possible conformers optimized at the B3LYP/6-31G(d) level of theory. The relative energies, as well as the stabilization energies exerted by the side-chain on the backbone, have been calculated for each of the 27 optimized conformers at this level of theory. Various backbone-backbone (N-(HO)-O-...=C) and backbone-side-chain (N-(HO)-O-...=C; N-(HOH)-O-...) hydrogen bonds were analyzed. The appearance of the notoriously absent epsilon(L) backbone conformer may be attributed to such side-chain-backbone (SC/BB) and backbone-backbone (BB/BB) hydrogen bonds

Haptoglobin Polymorphism: A Novel Genetic Risk Factor for Celiac Disease Development and Its Clinical Manifestations

Background: Haptoglobin (Hp) α-chain alleles 1 and 2 account for 3 phenotypes that may influence the course of inflammatory diseases via biologically important differences in their antioxidant, scavenging, and immunomodulatory properties. Hp1-1 genotype results in the production of small dimeric, Hp2-1 linear, and Hp2-2 cyclic polymeric haptoglobin molecules. We investigated the haptoglobin polymorphism in patients with celiac disease and its possible association to the presenting symptoms. Methods: We studied 712 unrelated, biopsy-proven Hungarian celiac patients (357 children, 355 adults; severe malabsorption 32.9%, minor gastrointestinal symptoms 22.8%, iron deficiency anemia 9.4%, dermatitis herpetiformis 15.6%, silent disease 7.2%, other 12.1%) and 384 healthy subjects. We determined haptoglobin phenotypes by gel electrophoresis and assigned corresponding genotypes. Results: Hp2-1 was associated with a significant risk for celiac disease (P = 0.0006, odds ratio [OR] 1.54, 95% CI 1.20–1.98; prevalence 56.9% in patients vs 46.1% in controls). It was also overrepresented among patients with mild symptoms (69.2%) or silent disease (72.5%). Hp2-2 was less frequent in patients than in controls (P = 0.0023), but patients having this phenotype were at an increased risk for severe malabsorption (OR 2.21, 95% CI 1.60–3.07) and accounted for 45.3% of all malabsorption cases. Celiac and dermatitis herpetiformis patients showed similar haptoglobin phenotype distributions. Conclusions: The haptoglobin polymorphism is associated with susceptibility to celiac disease and its clinical presentations. The predominant genotype in the celiac population was Hp2-1, but Hp2-2 predisposed to a more severe clinical course. The phenotype-dependent effect of haptoglobin may result from the molecule’s structural and functional properties

Modulation of Cosmogenic Tritium in Meteoric Precipitation by the 11-year Cycle of Solar Magnetic Field Activity

The relationship between the atmospheric concentration of cosmogenic isotopes, the change of solar activity and hence secondary neutron flux has already been proven. The temporal atmospheric variation of the most studied cosmogenic isotopes shows a significant anti-correlation with solar cycles. However, since artificial tritium input to the atmosphere due to nuclear-weapon tests masked the expected variations of tritium production rate by three orders of magnitude, the natural variation of tritium in meteoric precipitation has not previously been detected. For the first time, we provide clear evidence of the positive correlation between the tritium concentration of meteoric precipitation and neutron flux modulated by solar magnetic activity. We found trends in tritium time series for numerous locations worldwide which are similar to the variation of secondary neutron flux and sun spot numbers. This variability appears to have similar periodicities to that of solar cycle. Frequency analysis, cross correlation analysis, continuous and cross wavelet analysis provide mathematical evidence that the correlation between solar cycle and meteoric tritium does exist. Our results demonstrate that the response of tritium variation in precipitation to the solar cycle can be used to help us understand its role in the water cycle

Megaphylogeny resolves global patterns of mushroom evolution

Mushroom-forming fungi (Agaricomycetes) have the greatest morphological diversity and complexity of any group of fungi. They have radiated into most niches and fulfil diverse roles in the ecosystem, including wood decomposers, pathogens or mycorrhizal mutualists. Despite the importance of mushroom-forming fungi, large-scale patterns of their evolutionary history are poorly known, in part due to the lack of a comprehensive and dated molecular phylogeny. Here, using multigene and genome-based data, we assemble a 5,284-species phylogenetic tree and infer ages and broad patterns of speciation/extinction and morphological innovation in mushroom-forming fungi. Agaricomycetes started a rapid class-wide radiation in the Jurassic, coinciding with the spread of (sub)tropical coniferous forests and a warming climate. A possible mass extinction, several clade-specific adaptive radiations and morphological diversification of fruiting bodies followed during the Cretaceous and the Paleogene, convergently giving rise to the classic toadstool morphology, with a cap, stalk and gills (pileate-stipitate morphology). This morphology is associated with increased rates of lineage diversification, suggesting it represents a key innovation in the evolution of mushroom-forming fungi. The increase in mushroom diversity started during the Mesozoic-Cenozoic radiation event, an era of humid climate when terrestrial communities dominated by gymnosperms and reptiles were also expanding

Coronary-Artery Bypass Surgery in Patients with Ischemic Cardiomyopathy

BACKGROUND: The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear. METHODS: From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy alone (medical-therapy group, 602 patients). The primary outcome was death from any cause. Major secondary outcomes included death from cardiovascular causes and death from any cause or hospitalization for cardiovascular causes. The median duration of follow-up, including the current extended-follow-up study, was 9.8 years. RESULTS: A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in 398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P=0.02 by log-rank test). A total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006 by log-rank test). Death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524 patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82; P<0.001 by log-rank test). CONCLUSIONS: In a cohort of patients with ischemic cardiomyopathy, the rates of death from any cause, death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes were significantly lower over 10 years among patients who underwent CABG in addition to receiving medical therapy than among those who received medical therapy alone. (Funded by the National Institutes of Health; STICH [and STICHES] ClinicalTrials.gov number, NCT00023595.)

Cryptocapsinepoxide-type Carotenoids from Red Mamey, Pouteria sapota

Three new carotenoids, cryptocapsin-5,6-epoxide, 3ʹ-deoxycapsanthin-5,6-epoxide, and cryptocapsin-5,8-epoxides, have been isolated from the ripe fruits of red mamey (Pouteria sapota). Cryptocapsin-5,6-epoxide was prepared by partial synthesis via epoxidation of cryptocapsin and the (5R,6S)- and (5S,6R)-stereoisomers were identified by HPLC-ECD analysis. Spectroscopic data of the natural (anti) and semisynthetic (syn) derivatives obtained by acid-catalyzed rearrangement of cryptocapsin-5,8-epoxide stereoisomers were compared for structural elucidation. Chiral HPLC separation of natural and semisynthetic samples of cryptocapsin-5,8-epoxides was performed and HPLC-ECD analysis allowed configurational assignment of the separated stereoisomers

A felső és alsó endoszkópiák indikációja, a diagnózisok megoszlása és minőségi mutatók 2010–2011-ben a Semmelweis Egyetem I. Belgyógyászati Klinikáján

Absztrakt: Bevezetés és célkitűzés: A Semmelweis Egyetem I. Belgyógyászati Klinikájának endoszkópos laboratóriumában vizsgálták a felső és alsó endoszkópiák indikációit, a diagnózisok megoszlását indikációk szerint, valamint a kolonoszkópiák minőségi mutatóit. Módszer: 2010. január 1. és 2011. december 31. között 2987 beteg felső és alsó endoszkópos vizsgálatának adatait elemezték (férfi/nő: 1361/1626, átlagéletkor: 60,7 év, SD: 16,7 év) a fekvő- és járóbeteg-megjelenések riportjaiból. Eredmények: A felső endoszkópiák során a jóindulatú fekélybetegség, nyelőcső-varicositas, gyomorpolip és gyomorrák előfordulási gyakorisága 10,8%, 4,5%, 6,1% és 2,9% volt. Az alsó endoszkópos vizsgálatok vastagbélpolipot, diverticulosist, daganatot és gyulladásos bélbetegséget 29,9%, 22,4%, 6,9% és 9,7%-ban írtak le. A betegek 26,3%-át vizsgálták okkult/manifeszt GI-vérzés indikációjával. A vérzés indikációjával vizsgált betegek idősebbek voltak (p<0,01), több volt a férfi (p<0,001, OR: 1,64), gyakrabban szedtek acenocoumarol- vagy heparinkészítményeket (p<0,001), gyakoribb volt a jóindulatú fekélybetegség (p<0,001, OR: 2,83) és nyelőcső-varicositas (p<0,001, OR: 2,79), a gasztroszkópiák, valamint a kolonoszkópiák során a colorectalis daganat (p<0,001, OR: 3,27). A kolonoszkópiák 81%-a volt komplett. Az inkomplett vizsgálat hátterében elégtelen előkészítés (38,2%), technikai nehézség (25,1%) és daganat miatti szűkület (20,5%) állt. Következtetés: A diagnózisok megoszlása és a minőségi mutatók (adenomatalálat, komplettálási arány) megfeleltek az adott populációban várhatónak. Orv. Hetil., 2016, 157(52), 2074–2081. | Abstract: Introduction and aim: The aim was to assess the incidence of endoscopic findings based on the indication of the procedures in upper/lower endoscopies, and measuring quality indicators of colonoscopies at the 1st Department of Medicine, Semmelweis University, Budapest. Method: Data of 2987 patients (male/female:1361/1626, mean age: 60.7 years(y), SD: 16.7y) between 01.01.2010 and 31.12.2011 were analyzed. Both inpatient and outpatient records were collected. Results: Incidence of peptic ulcer disease, esophageal varices, gastric polyps and gastric cancer were 10.8%, 4.5%, 6.1%, 2.9% in upper endoscopies, respectively. In colonoscopies colorectal polyps, diverticulosis, colorectal cancer and IBD were found in 29.9%, 22.4%, 6.9%, 9.7%, respectively. In patients having upper endoscopy with GI bleeding indication, older age (p<0.001), male gender (p<0.001, OR: 1.64), acenocoumarol/heparin use (p<0,001, peptic ulcers and esophageal varices were more frequent (p<0.001, OR: 2.83 and p<0.001, OR: 2.79), while in colonoscopies colorectal cancer had higher incidence (p<0.001, OR:3.27). 81% of colonoscopies were complete. Causes of incomplete procedures were ineffective bowel preparation (38.2%), technical difficulties (25.1%) and strictures (20.5%). Conclusion: The endoscopic findings and quality indicators (adenoma detection rate, coecal intubation rate) were in line with that reported in published series. Orv. Hetil., 2016, 157(52), 2074–2081