Cellular remodeling in heart failure disrupts K(ATP) channel-dependent stress tolerance

ATP-sensitive potassium (K(ATP)) channels are required for maintenance of homeostasis during the metabolically demanding adaptive response to stress. However, in disease, the effect of cellular remodeling on K(ATP) channel behavior and associated tolerance to metabolic insult is unknown. Here, transgenic expression of tumor necrosis factor alpha induced heart failure with typical cardiac structural and energetic alterations. In this paradigm of disease remodeling, K(ATP) channels responded aberrantly to metabolic signals despite intact intrinsic channel properties, implicating defects proximal to the channel. Indeed, cardiomyocytes from failing hearts exhibited mitochondrial and creatine kinase deficits, and thus a reduced potential for metabolic signal generation and transmission. Consequently, K(ATP) channels failed to properly translate cellular distress under metabolic challenge into a protective membrane response. Failing hearts were excessively vulnerable to metabolic insult, demonstrating cardiomyocyte calcium loading and myofibrillar contraction banding, with tolerance improved by K(ATP) channel openers. Thus, disease-induced K(ATP) channel metabolic dysregulation is a contributor to the pathobiology of heart failure, illustrating a mechanism for acquired channelopathy.     

Contents Volume 26 (2000)

Volume Contents

Contents Volume 26 (2000)     

Mutants ofPhycomyceswith Decreased Gallic Acid Content

Weinkove, D., Poyatos, J. A., Greiner, H., Oltra, E., Avalos, J., Fukshansky, L., Barrero, A. F., and Cerdá-Olmedo, E. 1998. Mutants ofPhycomyceswith decreased gallic acid content.Fungal Genetics and Biology25, 196–203. Most plants and some fungi accumulate phenols. Two hydroxybenzoic acids, gallic and protocatechuic acids, are abundant in the giant sporangiophores of the zygomycetePhycomyces blakesleeanus,much more so than in the basal mycelium or the culture medium. The actual concentrations vary with illumination, age of the culture, and composition of the medium. We devised a simple screening procedure to isolatehbamutants whose sporangiophores contained less gallic acid than the wild type. The most useful mutant had very low concentrations of hydroxybenzoic acids in the sporangiophores, but about the same as the wild type in the basal mycelium and the medium. The mutant was only slightly different from the wild type in growth and morphology. Mutant and wild-type sporangiophores grew away from ultraviolet C sources (260 nm) equally well. Contrary to previous conjectures, ultraviolet tropism does not depend on the ultraviolet absorption of gallic acid or other free hydroxybenzoic acids in the sporangiophore. Against expectations, phenols did not impair DNA extraction: sporangiophores produced better DNA preparations than basal mycelia and thehbamutant only slightly better than the wild type.     

Epidemiology of venous thromboembolism (VTE) associated with pregnancy

This review is focused on the epidemiology of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), associated with pregnancy. Superficial vein thrombosis, a less hazardous and less studied type of thrombosis in pregnant women, is beyond the scope of this review. This study discusses the VTE incidence rate in women from developed countries for both antepartum and postpartum periods and for subpopulations of women affected by additional risk factors, such as thrombophilias, circulatory diseases, preeclampsia of varying degrees of severity, and Caesarean section. To minimize bias due to historical changes in medical and obstetric practices, lifestyle, diet, etc., this review is generally limited to relatively recent studies, i.e., those that cover the last 35 years. The absolute risk or incidence rate was used to ascertain risk of VTE associated with pregnancy. For the studies where the direct incidence rates of VTE were not reported, we calculated an estimate of the observed but not reported absolute incidence rates using the data presented in respective articles. Birth Defects Research (Part C) 105:167–184, 2015. © 2015 Wiley Periodicals, Inc.     

Stereotactic body radiation therapy (SBRT) of adrenal gland metastases in oligometastatic and oligoprogressive disease

BackgroundStereotactic body radiation therapy (SBRT) as a form of noninvasive treatment that is becoming increasingly used to manage cancers with adrenal gland metastases. There is a paucity of data on safety and efficacy of this modality. The aim of the study was to evaluate the safety and efficacy of adrenal gland SBRT in oligometastatic and oligoprogressive disease.Materials and methodsIn this retrospective study, we performed a single-institution analysis of 26 adrenal lesions from 23 patients with oligometastatic or oligoprogressive disease treated from 2013 to 2019 with the goal of achieving durable local control. Palliative cases were excluded. Radiation dosimetry data was collected. Kaplan Meier product estimator and Cox proportional hazards regression analysis were used for statistical analysis.ResultsThe median dose was 36 Gy in 3 fractions (range: 24–50 Gy and 3–6 fractions) with a median biologically effective dose (BED10) of 72 (range: 40–100). 1-year local control rate was 80% and median local control was not achieved due to a low number of failures. 1- and 2-year overall survival rates were 66% and 32%. Toxicity was mild with only one case of grade 2 nausea and no grade 3–5 toxicity. Higher neutrophil to lymphocyte ratio was associated with worse overall survival and a trend toward worse progression-free survival. In addition, worse performance status and lower BED10 were associated with worse survival. No such association could be shown for primary tumor location, histology, size or stage.ConclusionAdrenal SBRT for oligometastatic or oligoprogressive disease is a safe and effective form of treatment.     

Glucose sensing in the pancreatic beta cell: a computational systems analysis

Background  

Pancreatic beta-cells respond to rising blood glucose by increasing oxidative metabolism, leading to an increased ATP/ADP ratio in the cytoplasm. This leads to a closure of K_ATP channels, depolarization of the plasma membrane, influx of calcium and the eventual secretion of insulin. Such mechanism suggests that beta-cell metabolism should have a functional regulation specific to secretion, as opposed to coupling to contraction. The goal of this work is to uncover contributions of the cytoplasmic and mitochondrial processes in this secretory coupling mechanism using mathematical modeling in a systems biology approach.     

Voltammetric studies of glutathione transfer across arrays of liquid–liquid microinterfaces for sensing applications

Amino Acids - The simple and facilitated transfer of tripeptide glutathione across the water/2-nitrophenyl octhyl ether interface was studied via cyclic voltammetry at interface between two...