Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation.

Hydropersulfide and hydropolysulfide metabolites are increasingly important reactive sulfur species (RSS) regulating numerous cellular redox dependent functions. Intracellular production of these species is known to occur through RSS interactions or through translational mechanisms involving cysteinyl t-RNA synthetases. However, regulation of these species under cell stress conditions, such as hypoxia, that are known to modulate RSS remain poorly understood.

Methamphetamine causes cardiovascular dysfunction via cystathionine gamma lyase and hydrogen sulfide depletion.

Methamphetamine (METH) is an addictive illicit drug used worldwide that causes significant damage to blood vessels resulting in cardiovascular dysfunction. Recent studies highlight increased prevalence of cardiovascular disease (CVD) and associated complications including hypertension, vasospasm, left ventricular hypertrophy, and coronary artery disease in younger populations due to METH use. Here we report that METH administration in a mouse model of 'binge and crash' decreases cardiovascular function via cystathionine gamma lyase (CSE), hydrogen sulfide (HS), nitric oxide (NO) (CSE/HS/NO) dependent pathway.

Decreased bioavailability of hydrogen sulfide links vascular endothelium and atrial remodeling in atrial fibrillation.

Oxidative stress drives the pathogenesis of atrial fibrillation (AF), the most common arrhythmia. In the cardiovascular system, cystathionine γ-lyase (CSE) serves as the primary enzyme producing hydrogen sulfide (HS), a mammalian gasotransmitter that reduces oxidative stress. Using a case control study design in patients with and without AF and a mouse model of CSE knockout (CSE-KO), we evaluated the role of HS in the etiology of AF.

Nitric Oxide and Hydrogen Sulfide Regulation of Ischemic Vascular Growth and Remodeling.

Ischemic vascular remodeling occurs in response to stenosis or arterial occlusion leading to a change in blood flow and tissue perfusion. Altered blood flow elicits a cascade of molecular and cellular physiological responses leading to vascular remodeling of the macro- and micro-circulation. Although cellular mechanisms of vascular remodeling such as arteriogenesis and angiogenesis have been studied, therapeutic approaches in these areas have had limited success due to the complexity and heterogeneous constellation of molecular signaling events regulating these processes.

Total sulfane sulfur bioavailability reflects ethnic and gender disparities in cardiovascular disease.

Hydrogen sulfide (HS) has emerged as an important physiological and pathophysiological signaling molecule in the cardiovascular system influencing vascular tone, cytoprotective responses, redox reactions, vascular adaptation, and mitochondrial respiration. However, bioavailable levels of HS in its various biochemical metabolite forms during clinical cardiovascular disease remain poorly understood. We performed a case-controlled study to quantify and compare the bioavailability of various biochemical forms of HS in patients with and without cardiovascular disease (CVD).

The Type 1 Diabetes-Resistance Locus Controls Trafficking of Autoreactive CTLs into the Pancreatic Islets of NOD Mice.

Type 1 diabetes (T1D) has a strong genetic component. The () locus was identified in crosses of T1D-susceptible NOD mice with the strongly T1D-resistant ALR strain. The NODcALR-()/Mx (NOD-) recombinant congenic mouse strain was generated in which NOD mice carry the full confidence interval.

Assessment of counselling for acute diarrhoea in German pharmacies: a simulated patient study.

Objectives: The aim of this study was to assess the quality of counselling provided for acute diarrhoea and to evaluate the role of the patient's approach and different user groups in determining the outcome of counselling.

Methods: The simulated patient methodology was used in all 21 community pharmacies in a north-eastern German city. Four different scenarios related to self-medication of acute diarrhoea were developed and used in all the pharmacies (a total of 84 visits).

Role of thiosulfate in hydrogen sulfide-dependent redox signaling in endothelial cells.

Recent reports have revealed that hydrogen sulfide (HS) exerts critical actions to promote cardiovascular homeostasis and health. Thiosulfate is one of the products formed during oxidative HS metabolism, and thiosulfate has been used extensively and safely to treat calcific uremic arteriopathy in dialysis patients. Yet despite its significance, fundamental questions regarding how thiosulfate and HS interact during redox signaling remain unanswered.

[Using the simulated patient methodology to assess counselling for acute diarrhoea - evidence from Germany].

Objectives: First, to assess the quality of counselling for acute diarrhoea; second, to evaluate the patient's approach and different user groups as a determinant of counselling.

Methods: The simulated patient methodology was used in all 21 community pharmacies in a north-eastern German city with a population of about 63,000. Four scenarios related to self-medication for acute diarrhoea were developed and used in all pharmacies (total: 84 visits).

Plasma free H2S levels are elevated in patients with cardiovascular disease.

Background: Hydrogen sulfide (H2S) has been implicated in regulating cardiovascular pathophysiology in experimental models. However, there is a paucity of information regarding the levels of H2S in health and cardiovascular disease. In this study we examine the levels of H2S in patients with cardiovascular disease as well as bioavailability of nitric oxide and inflammatory indicators.

SDF-1-CXCR4 differentially regulates autoimmune diabetogenic T cell adhesion through ROBO1-SLIT2 interactions in mice.

Aims/hypothesis: We had previously reported that stromal cell-derived factor 1 (SDF-1) mediates chemorepulsion of diabetogenic T cell adhesion to islet microvascular endothelium through unknown mechanisms in NOD mice. Here we report that SDF-1-mediated chemorepulsion occurs through slit homologue (SLIT)2-roundabout, axon guidance receptor, homologue 1 (Drosophila) (ROBO1) interactions.

Methods: C-X-C receptor (CXCR)4 and ROBO1 protein expression was measured in mouse and human T cells.

Temporal genome expression profile analysis during t-cell-mediated colitis: identification of novel targets and pathways.

Background: T cells critically regulate inflammatory bowel disease (IBD), with T-cell-dependent experimental colitis models gaining favor in identifying potential pathogenic mechanisms; yet limited understanding of specific pathogenic molecules or pathways still exists.

Methods: In this study we sought to identify changes in whole genome expression profiles using the CD4CD45Rbhi T-cell transfer colitis model compared to genome expression differences from Crohn's disease (CD) tissue specimens. Colon tissue was used for histopathological and genome expression profiling analysis at 0, 2, 4, or 6 weeks after adoptive T-cell transfer.

VEGF₁₆₄ isoform specific regulation of T-cell-dependent experimental colitis in mice.

Background: Inflammatory bowel disease (IBD) consists of Crohn's disease (CD) and ulcerative colitis (UC), two widespread diseases of unknown, multifactorial etiology. Colitis pathology involves a pathological angiogenic response where increases in vascular density participate in colitis histopathology. Vascular endothelial growth factor-A (VEGF-A) is a potent angiogenesis stimulator known to be involved in pathological angiogenesis in several diseases including colitis.

VEGF₁₆₄ differentially regulates neutrophil and T cell adhesion through ItgaL- and ItgaM-dependent mechanisms.

Leukocyte recruitment to inflamed tissues is the cornerstone of inflammatory responses and the driving force behind the establishment of inflammatory bowel disease, consisting of Crohn's disease and ulcerative colitis. It has been reported that angiogenic cytokines contribute to this inflammatory response that facilitates the chronic nature of disease. We have previously reported (Goebel S, Huang M, Davis WC, Jennings M, Siahaan TJ, Alexander JS, Kevil CG.

Genetic deficiency of Itgb2 or ItgaL prevents autoimmune diabetes through distinctly different mechanisms in NOD/LtJ mice.

Objective: Insulitis is an important pathological feature of autoimmune diabetes; however, mechanisms governing the recruitment of diabetogenic T-cells into pancreatic islets are poorly understood. Here, we determined the importance of leukocyte integrins beta(2)(Itgb2) and alphaL (ItgaL) in developing insulitis and frank diabetes.

Research Design And Methods: Gene-targeted mutations of either Itgb2 or ItgaL were established on the NOD/LtJ mouse strain.

Multicenter, randomized controlled trial of pain-related behaviors following routine neutering in dogs.

Objective: To evaluate the degree of postoperative pain in dogs undergoing elective castration or ovariohysterectomy (OHE); determine whether an association exists between surgeon experience, incision length, or surgery duration and degree of postoperative pain; and determine whether analgesic treatment decreases expression of postoperative pain behaviors.

Design: Randomized controlled clinical trial.

Animals: 426 client-owned dogs undergoing OHE or castration.

Stromal cell-derived factor-1/CXCL12 stimulates chemorepulsion of NOD/LtJ T-cell adhesion to islet microvascular endothelium.

Objective: Diabetogenic T-cell recruitment into pancreatic islets facilitates beta-cell destruction during autoimmune diabetes, yet specific mechanisms governing this process are poorly understood. The chemokine stromal cell-derived factor-1 (SDF-1) controls T-cell recruitment, and genetic polymorphisms of SDF-1 are associated with early development of type 1 diabetes.

Research Design And Methods: Here, we examined the role of SDF-1 regulation of diabetogenic T-cell adhesion to islet microvascular endothelium.

Influence of channel width on alignment of smooth muscle cells by high-aspect-ratio microfabricated elastomeric cell culture scaffolds.

Engineered smooth muscle tissue requires ordered configurations of cells to reproduce native function, and microtechnology offers possibilities for physically and chemically controlling cell organization with high spatial resolution. In this work, poly(dimethylsiloxane) microchannel scaffolds, modified by layer-by-layer self-assembly of polyelectrolytes to promote cell adhesion, were evaluated for use as substrates for the culture of aligned smooth muscle cells. The hypothesis that narrower channels would result in better alignment was tested using channel width dimensions of 20, 30, 40, 50, and 60 microm, in addition to flat (control) surfaces.