MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Clinical Science' source. Mon, 06 Feb 2012 14:00:59 +0100 http://www.medworm.com/index.php?rid=5664045&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110662 Obese adipose tissue (AT) exhibits increased macrophage number. Pro-inflammatory CD16+ peripheral monocyte numbers are also reported to increase with obesity. The current study was undertaken to simultaneously investigate obesity-associated changes in CD16+ monocytes and adipose tissue macrophages (ATM). In addition, a pilot randomised placebo controlled trial using the peroxisome proliferator-activated receptor (PPAR) agonists, pioglitazone and fenofibrate was performed to determine their effects on CD14+/CD16+ monocytes, ATM and cardiometabolic and adipose dysfunction indices. Obese glucose-tolerant men (n=32) were randomised to placebo, pioglitazone (30 mg/day) and fenofibrate (160 mg/day) for 12 weeks. A blood sample was taken to assess levels of serum infla... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5664045 Mon, 06 Feb 2012 05:00:00 +0100 5664045 http://www.medworm.com/index.php?rid=5656202&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110584 A previous expression profiling of visceral adipose tissue (VAT) revealed that the thymic stromal lymphopoietin (TSLP) gene was less expressed in severely obese men with (n=7) vs. without (n=7) the metabolic syndrome (MS). We hypothesized that TSLP single nucleotide polymorphisms (SNPs) are associated with TSLP gene expression in VAT and with MS phenotypes. Following validation of lower TSLP expression (p=0.003) in VAT of severely obese men and women with (n=70) vs. without (n=60) MS, a detailed genetic investigation was performed at the TSLP locus by sequencing its promoter, exons and intron-exon splicing boundaries using DNA of 25 severely obese subjects. Five tagging SNPs were genotyped in the 130 subjects from the expression analysis to test whether these SNPs contributed to TSLP expre... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5656202 Fri, 03 Feb 2012 05:00:00 +0100 5656202 http://www.medworm.com/index.php?rid=5643686&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110403 Conclusions: This work demonstrates that ACE2 regulates renal ANP via the generation of angiotensin 1-7. This is a new mechanism whereby ACE2 counterbalances the renal effects of angiotensin II and which explains why targeting ACE2 may be a promising strategy against kidney diseases, including diabetic nephropathy. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5643686 Mon, 30 Jan 2012 05:00:00 +0100 5643686 http://www.medworm.com/index.php?rid=5624506&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110272 This study aims to evaluate if cord blood stem cells (CBSCs) can be new source of dendritic cells (DCs) which can generate more potent antigen-specific immune responses and anti-tumor effects. The CBSCs and peripheral blood mononuclear cells (PBMCs) were collected, cultured and differentiated into DCs. Surface markers, secreting cytokines, antigen presentation activity, antigen-specific cell-mediated immunity and cytotoxic killing effects induced by these two origins of DCs were evaluated and compared. The CBSCs expanded for ~17-fold by ex vivo culture. The expressions of surface markers in CBSC-derived DCs were higher than those in PBMC-derived DCs treated with LPS. The CBSC-derived DCs mainly secreted IL-6, IL-10, and TNF-a, while PBMC-derived DCs mainly secreted IL-5 and IFN-γ. T... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5624506 Mon, 23 Jan 2012 05:00:00 +0100 5624506 http://www.medworm.com/index.php?rid=5603718&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110520 Abstract Glutamine depletion is demonstrated to be an independent predictor of hospital mortality in ICU patients. Today glutamine supplementation is recommended to ICU patients on parenteral nutrition. In addition to glutamine, glutathione may be a limiting factor in ICU patients with multiple organ failure. To study the prevalence of glutamine and glutathione depletion an observational study was performed. The results were analysed in relation to mortality and the conventional predictors of mortality outcome, APACHE II and SOFA. Consecutive patients admitted to the ICU at Karolinska University Hospital Huddinge were studied. Patient admissions scoring of APACHE II and SOFA were registered as well as mortality up to 6 months. Plasma glutamine concentration and whole blood glutathione st... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5603718 Tue, 17 Jan 2012 05:00:00 +0100 5603718 http://www.medworm.com/index.php?rid=5603719&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110501 This study has examined the role of gap junctions in the delayed anti-arrhythmic effect of cardiac pacing, with particular reference to the time-course changes in connexin43 (Cx43) expression both after pacing (4x5 min, at a rate of 240 beats min-1) and 24h later, when the dogs were subjected to a 25 min occlusion and reperfusion of the left anterior descending coronary artery. Compared to the sham-paced controls (n=20), in dogs paced 24h previously (n=16) there were reductions in arrhythmia severity (e.g. number of ventricular premature beats during occlusion 294±78 vs. 63±25; survival from the combined ischaemia/reperfusion insult 20% vs. 78%), and in other ischaemic changes (epicardial ST-segment, total activation time, tissue impedance). Pacing also prevented the ischaemi... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5603719 Mon, 16 Jan 2012 05:00:00 +0100 5603719 http://www.medworm.com/index.php?rid=5592743&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110557 In conclusion, baseline cTnT levels are higher in patients with MPI evidence of reversible myocardial ischemia than those without reversible ischemia. However, while cTnT levels increase during exercise stress testing in patients without evidence of reversible ischemia, this response appears to be blunted in patients with evidence of reversible ischemia. Mechanisms other than reversible myocardial ischemia may play a role for acute exercise-induced increases in circulating cTnT levels. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5592743 Thu, 12 Jan 2012 05:00:00 +0100 5592743 http://www.medworm.com/index.php?rid=5592744&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110523 Activation of Toll-like receptors (TLR) induces gene expression of proteins involved in the immune system response. TLR4 has been implicated in the development and progression of cardiovascular diseases. Innate and adaptive immunity contribute to hypertension-associated end-organ damage, although the mechanism by which this occurs remains unclear. In the present study we hypothesize that inhibition of TLR4 decreases blood pressure and improves vascular contractility in resistance arteries from spontaneously hypertensive rats (SHR). TLR4 protein expression in mesenteric resistance arteries was higher in 15 weeks-old SHR than in same age Wistar controls or in 5 weeks-old SHR. In order to decrease activation of TLR4, 15 weeks-old SHR and Wistar rats were treated with anti-TLR4 antibody or non... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5592744 Tue, 10 Jan 2012 05:00:00 +0100 5592744 http://www.medworm.com/index.php?rid=5568599&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110517 By inducing bradykinin-stimulated adrenomedullary catecholamine release, bolus injection of the β-fragment of activated plasma coagulation FXIIa (β-FXIIa) transiently elevates blood pressure (BP) and heart rate (HR) of anesthetized, vagotomized, ganglion-blocked, captopril treated bioassay rats. We hypothesized that intravenous infusion of β-FXIIa into intact untreated rats would elicit a qualitatively similar and vasoconstrictor response. Brown Norway (BN) rats received for 60 min either: 1) saline (control; n=10); 2) β-FXIIa (85 ng/min/kg; n=9); or 3) β-FXIIa after bilateral adrenalectomy (2ADX; n=9). Left ventricular volume and aortic BP were recorded before (30 min baseline), during (60 min), and after (30 min recovery) the infusion. Total peripheral... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5568599 Thu, 05 Jan 2012 05:00:00 +0100 5568599 http://www.medworm.com/index.php?rid=5568600&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110631 Hepatitis C virus infection is a serious health-care problem that affects more than 170 million people worldwide. Viral clearance depends on the development of a successful cellular immune response against the virus. Interestingly, such a response is altered in chronically infected patients, leading to chronic hepatitis that can result in liver fibrosis, cirrhosis and hepatocellular carcinoma. Among the mechanisms that have been called as responsible for the immune suppression caused by the virus, regulatory T cells are emerging as an essential component. In the present work we aim to study the effect of HCV core protein in the development of T cells with regulatory-like function. Using a third generation lentiviral system to express HCV core in CD4+ Jurkat T cells, we describe that... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5568600 Tue, 03 Jan 2012 05:00:00 +0100 5568600 http://www.medworm.com/index.php?rid=5532997&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110323 In conclusion, inducible ischemia is associated with a decrease in whole blood TLR-2 and -4 response. These results point to a regulating role of TLRs in order to prevent excessive inflammatory events known to occur during acute ischemia. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5532997 Thu, 22 Dec 2011 05:00:00 +0100 5532997 http://www.medworm.com/index.php?rid=5512149&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110622 The present study was undertaken to evaluate the effects of chronic treatment with cis-4-[4-(3-adamantan-1-yl-ureido)cyclohexyl-oxy]benzoic acid (c-AUCB), a novel inhibitor of soluble epoxide hydrolase (sEH), which is responsible for the conversion of biologically active epoxyeicosatrienoic acids (EETs) to biologically inactive dihydroxyeicosatrienoic acids (DHETEs), on blood pressure (BP) and myocardial infarct size in male heterozygous Ren-2 transgenic rats (TGR) with established hypertension. Normotensive Hannover Sprague-Dawley (HanSD) rats served as controls. Myocardial ischemia was induced by coronary artery occlusion. Systolic BP was measured in conscious animals by tail-plethysmography. c-AUCB was administrated in drinking water. Renal and myocardial concentrations of EETs and DHET... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5512149 Fri, 16 Dec 2011 05:00:00 +0100 5512149 http://www.medworm.com/index.php?rid=5482794&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110374 Diabetes is a strong risk factor for premature and severe stroke. The glucagon-like peptide-1 receptor agonist Exendin-4 is a drug for the treatment of type 2 diabetes that may also have neuroprotective effects. The aim of this study was to determine the efficacy of Exendin-4 against stroke in diabetes by using a diabetic animal model, a drug administration paradigm and a dose that mimic a diabetic patient on Exendin-4 therapy. Furthermore, we investigated inflammation and neurogenesis as potential cellular mechanisms underlying the Exendin-4 efficacy. Seven-nine month-old type 2 diabetic Goto-Kakizaki rats were treated peripherally for 4 weeks with 0.1,1 or 5 µg/kg Exendin-4 before inducing stroke by transient middle cerebral artery occlusion and for 2-4 weeks thereafter. The seve... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5482794 Wed, 07 Dec 2011 05:00:00 +0100 5482794 http://www.medworm.com/index.php?rid=5482795&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110366 In humans there is a large inter-individual variability in the evolution of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH). To investigate this issue, NASH was induced with a methionine-choline deficient (MCD) diet in C57BL/6 and Balb/c mice that are characterized by different biases in T-lymphocyte (Th-1/Th2) and macrophage (M1/M2) responses. Following 4 weeks on the MCD diet steatosis and lobular inflammation were prevalent in C57BL/6 (Th-1, M1 oriented) than in BALB/c (Th-2, M2 oriented) mice. Consistently, hepatic TNF-a mRNA expression and circulating TNF-a levels were higher in MCD-fed C57BL/6 than in MCD-fed BALB/c mice. Th-1/Th-2 bias did not account for the increased NASH severity, as in both strains MCD feeding did not significantly modify the liver mRNA expr... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5482795 Tue, 06 Dec 2011 05:00:00 +0100 5482795 http://www.medworm.com/index.php?rid=5482796&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110412 The flavone acetic acid derivative 5,6-dimethylxanthenone-4-acetic acid (DMXAA, Vadimezan, ASA404) is a drug that displayed vascular disrupting activity and induced hemorrhagic necrosis and tumour regression in preclinical animal models. Both immune-mediated and non-immune-mediated effects contributed to the tumour regression. The vascular disruption was less in human tumours with immune-mediated effects being less prominent but none the less DMXAA showed promising effects in phase-II clinical trials in non-small cell lung cancer. However these effects were not replicated in phase-III clinical trials. It has been difficult to understand the differences between preclinical findings and later clinical trials as the molecular targets for the agent have never been clearly established. To inves... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5482796 Mon, 05 Dec 2011 05:00:00 +0100 5482796 http://www.medworm.com/index.php?rid=5437139&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110434 In conclusion, TGF-beta1 –IL-6 axis possessed the predictive power in the prognosis of oral cancer, and targeting TGF-beta1 could represent a promising treatment strategy. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5437139 Tue, 22 Nov 2011 05:00:00 +0100 5437139 http://www.medworm.com/index.php?rid=5437140&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110257 Inhibition of glycosphingolipid (GSL) synthesis reduces amyloid-beta (Ab) production in vitro. Previous studies indicate that glucosylceramide synthase (GCS) inhibitors modulate phosphorylation of extracellular signal-regulated kinase 1/2 (ERK) and that the ERK pathway may regulate some aspects of Ab production. It is not clear if there is a causative relationship linking GSL synthesis inhibition, ERK phosphorylation, and Ab production. Here we treated CHO cells and SH-SY5Y neuroblastoma cells that both constitutively express human wild type amyloid precursor protein (APP), and process this to produce Ab, with GSL-modulating agents to explore this relationship. We found that three related ceramide analogue GSL inhibitors, based on the D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propano... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5437140 Mon, 21 Nov 2011 05:00:00 +0100 5437140 http://www.medworm.com/index.php?rid=5417239&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110483 In conclusion, AM5 has significant haemodynamic, endocrine and renal actions in experimental HF likely to be protective and compensatory in this setting. These results suggest AM5 may have potential as a therapeutic agent in human HF. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5417239 Thu, 17 Nov 2011 05:00:00 +0100 5417239 http://www.medworm.com/index.php?rid=5417238&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110234 Animal studies implicate the AP-1 pro-inflammatory pathway as a promising target in the treatment of atherosclerotic disease. It is however unclear whether these observations apply to human atherosclerosis. Therefore, we evaluated the profile of AP-1 activation through histological analysis and tested the potential benefit of AP-1 inhibition in a clinical trial. AP-1 activation was quantified by phospho-c-Jun nuclear translocation (immunohistochemistry) on a biobank of aortic wall samples from organ donors. The effect of AP-1 inhibition on vascular parameters was tested through a double blind, placebo-controlled cross-over study of 28 days doxycycline or placebo in patients with symptomatic peripheral artery disease. Vascular function was assessed by brachial dilation as well as by plasma ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5417238 Thu, 17 Nov 2011 05:00:00 +0100 5417238 http://www.medworm.com/index.php?rid=5396528&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20090464 Glucagon-like peptide 1 (GLP-1) and its mimetic Exendin-4 are used against type 2 diabetes. C-peptide has also proven promising to enhance insulin action. Since insulin secretion in vivo can be rapidly tuned by changes in islet microcirculation, we evaluated the influence of GLP-1, Exendin-4 and C-peptide on pancreatic islet blood flow (IBF), and dynamic changes in insulin secretion and glycemia in the rat. Adult male Wistar rats were divided into four groups given i.v. saline, GLP-1, Exendin-4 or C-peptide, respectively, and administered either saline or 30 % glucose. We furthermore investigated the effect of i.v. infusion of different doses of Exendin-4 into either the femoral vein or the portal vein on islet microcirculation. A non-radioactive microsphere technique was adopted to measu... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5396528 Mon, 07 Nov 2011 05:00:00 +0100 5396528 http://www.medworm.com/index.php?rid=5343394&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110482 In conclusion, despite significant recoveries of BAs and C4 in HDL and despite the metabolic relationships between RCT and BA formation, monogenic disorders of HDL metabolism do not lead to altered serum concentrations of BAs and C4. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5343394 Thu, 20 Oct 2011 04:00:00 +0100 5343394 http://www.medworm.com/index.php?rid=5321260&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110303 In conclusion, the mesenteric innervation may participate in the development of the characteristic hyperdynamic circulation observed in short-term PH through the joint action of decreased adrenergic influence, and increased nitrergic and sensory innervations influences. The participation of each innervation normalizes under conditions of long-term PH. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5321260 Fri, 14 Oct 2011 04:00:00 +0100 5321260 http://www.medworm.com/index.php?rid=5321261&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110378 In this study, we tested the hypothesis that maternal stress can affect mTOR signalling at term, and as a result, influence placental growth. We first investigated the expression of DEPTOR, mTOR, rictor and raptor from human placentae (n=23) using quantitative RT-PCR (Q-PCR), and correlated these data to days of pregnancy, maternal stress as well as placental and fetal weight. Maternal and fetal cortisol levels were also measured. JEG-3 and BeWo cells were used as placental in vitro models treated with cortisol and DEPTOR expression was assessed using Q-PCR. DEPTOR appears to be the predominant transcript in the human placenta compared with mTOR, rictor and raptor in both term (n=13) and preterm (n=10) placentas as assessed by Q-PCR. There was a significantly lower level only of Log-DEPTOR... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5321261 Thu, 13 Oct 2011 04:00:00 +0100 5321261 http://www.medworm.com/index.php?rid=5292628&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110205 In conclusion, the risk alleles of CYBA and GSTP1, their haplotypes, and gene-gene interactions associated with imbalanced oxidative stress and thereby with high-altitude adaptation and mal-adaptation. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5292628 Thu, 06 Oct 2011 04:00:00 +0100 5292628 http://www.medworm.com/index.php?rid=5292629&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110199 Mitochondrial diseases (MDs) are a clinically heterogeneous group of disorders characterized by impairment of the respiratory chain function with altered oxidative phosphorylation. We tested the hypothesis that the function of vascular endothelium is affected by increased oxidative stress in MDs. Twelve patients with MDs and pair-matched controls were studied. Endothelial function was assessed measuring flow-mediated vasodilatation (FMD) of brachial and common femoral arteries. The test was repeated after vitamin C (500 mg bid) and E (400 mg od) supplementation for 30 days and 90 days after vitamins withdrawal. FMD was reduced in patients compared to controls [mean±SEM; AUC/t brachial artery: 1.05±0.24% vs. 4,19±0.59%, P<0.001; femoral artery: 0.98±0.19% vs... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5292629 Wed, 05 Oct 2011 04:00:00 +0100 5292629 http://www.medworm.com/index.php?rid=5281255&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110266 Sodium retention has been proposed as the cause of hypertension in the maternal low protein (LP) rat model of developmental programming because of increased renal Na+:K+:2Cl- type 2 transporter expression. However, we have shown that LP rats excrete more rather than less sodium than controls, leading us to hypothesize that LP rats ingest more salt in order to maintain sodium balance. Rats were fed either a 9% (low) or 18% (control) protein diet during pregnancy; male and female offspring were studied at 4 weeks of age. LP rats of both sexes held in metabolism cages excreted more sodium and urine than controls. When given water to drink LP rats drank more and ate more food than controls, hence sodium intake matched excretion. However, when given a choice between saline and wat... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5281255 Mon, 03 Oct 2011 04:00:00 +0100 5281255 http://www.medworm.com/index.php?rid=5281254&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110369 We examined whether the erythropoietin analogue darbepoetin improves flow mediated dilatation (FMD), a measure of endothelium-derived NO, and whether this is influenced by preceding ischaemia-reperfusion. Thirty six patients (50-75 years) with stable coronary artery disease were randomized to receive a single dose of darbepoetin 300 µg or saline placebo. FMD was measured at the brachial artery using high resolution ultrasound. CD133+/CD34+/VEGFR2+ circulating EPC were enumerated by flow cytometry. Measurements were made immediately before darbepoetin/placebo and at 24h, 72h and 7 days. At 24h FMD was repeated after 20 minutes ischaemia-reperfusion of the upper limb. A further group of 11 patients were studied according to the same protocol, all receiving darbepoetin, with omission o... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5281254 Mon, 03 Oct 2011 04:00:00 +0100 5281254 http://www.medworm.com/index.php?rid=5281253&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110312 Sex differences in Ca2+-dependent signaling and homeostasis in the vasculature of hypertensive rats are well characterized. However, sex-related differences in store-operated calcium entry (SOCE) have been minimally investigated. We hypothesized that vascular protection in females reflects decreased Ca2+ mobilization due to diminished activation of Orai1/ stromal interaction molecule 1 (STIM1). In addition, we investigated if female ovariectomy may affect the activation of Orai1/STIM1 pathway. Endothelium-denuded aortic rings from male and female Stroke Prone Spontaneously Hypertensive (SHRSP) and Wistar-Kyoto (WKY) rats and from ovariectomized (OVX) or sham SHRSP and WKY female rats were used to functionally evaluate Ca2+ influx-induced contractions. Compared to femal... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5281253 Mon, 03 Oct 2011 04:00:00 +0100 5281253 http://www.medworm.com/index.php?rid=5281257&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110493 Editor: We appreciate the comments made by Drs. Wen-Jun Tu and Hui Chen about our article [1] published in the Journal Clinical Science. In their letter, they suggest that the results shown in our article were caused by gender, rather than acute ischemic stroke. It is well known that gender influences the type of stroke and also the outcome; for example, in female patients, the rate of atrial fibrillation and cardioembolic stroke is higher, and many of them present bigger ischemic volume and worse outcome. Moreover, stroke in women usually appears in advanced age. However, we do not agree with the idea that molecular mechanisms of stroke involved in the human clinic and in elderly population depend on the gender. The comments suggested by Drs. Wen-Jun Tu and Hui Chen are based on two s... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5281257 Fri, 30 Sep 2011 04:00:00 +0100 5281257 http://www.medworm.com/index.php?rid=5281256&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110426 NA (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5281256 Fri, 30 Sep 2011 04:00:00 +0100 5281256 http://www.medworm.com/index.php?rid=5268397&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100519 Interleukin(IL)-1beta plays an important role in cartilage extracellular matrix degradation and bone resorption in osteoarthritis through the induction of degradative enzymes and pro-inflammatory mediators. In the present study, we have determined the consequences of heme oxygenase-1 (HO-1) induction on markers of inflammation and senescence in the functional unit cartilage-subchondral bone stimulated with IL-1beta. Cartilage-subchondral bone specimens were obtained from the knees of osteoarthritic patients. Treatment with the HO-1 inducer cobalt protoporphyrin IX (CoPP) counteracted the stimulatory effects of IL-1beta on IL-6, nitrite, prostaglandin E2 (PGE2), transforming growth factor(TGF)beta2, TGFbeta3, and osteocalcin. Immunohistochemical analyses indicated that CoPP treatment of exp... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5268397 Wed, 28 Sep 2011 04:00:00 +0100 5268397 http://www.medworm.com/index.php?rid=5268398&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110270 Postprandial hypotension leading to increased morbidity, and mortality, is an important clinical problem, particularly in the elderly and individuals with autonomic dysfunction. The magnitude of the postprandial fall in blood pressure (BP) appears to be dependent on the rate of nutrient entry into the small intestine and may be related to changes in splanchnic blood flow and sympathetic nerve activity. We aimed to determine the comparative effects of different intraduodenal (ID) glucose loads on BP, heart rate (HR), superior mesenteric artery (SMA) flow and vascular conductance and plasma noradrenaline (NA) in ‘young’ and ‘older’ subjects. Twelve ‘young’ (6M,6F; age 22.2±2.3yr) and twelve ‘older’ (6M,6F; age 68.7±1.0yr) ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5268398 Tue, 27 Sep 2011 04:00:00 +0100 5268398 http://www.medworm.com/index.php?rid=5233154&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110241 Chronic Fatigue Syndrome (CFS) is commonly co-morbid with Postural Tachycardia Syndrome (POTS). Individuals with CFS/POTS experience unrelenting fatigue, tachycardia during orthostatic stress, and ill-defined neurocognitive impairment, often described as mental fog. We hypothesized that orthostatic stress causes neurocognitive impairment in CFS/POTS related to decreased cerebral blood flow velocity (CBFV). 16 CFS/POTS and 20 control subjects underwent graded tilt table testing (at 0, 15, 30, 45, 60, and 75°) with continuous cardiovascular, cerebrovascular, and respiratory monitoring and neurocognitive testing using a N-back task at each angle. The N-back task tests working memory, concentration, attention, and information processing. The N-back imposes increasing cognitive challenge... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5233154 Thu, 15 Sep 2011 04:00:00 +0100 5233154 http://www.medworm.com/index.php?rid=5217527&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110200 In conclusion, fatigue and CFS-defining symptoms are common in POTS patients. The majority of them met criteria for CFS. CFS-POTS patients have higher markers of sympathetic activation but are part of the spectrum of POTS. Targeting this sympathetic activation should be considered in the treatment of these patients. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5217527 Mon, 12 Sep 2011 04:00:00 +0100 5217527 http://www.medworm.com/index.php?rid=5203904&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110176 Conclusion: Ruboxistaurin can ameliorate myocardial hypertrophy and dysfunction in diabetes, which may represent a novel therapy in the prevention of diabetes cardiovascular complications. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5203904 Mon, 05 Sep 2011 04:00:00 +0100 5203904 http://www.medworm.com/index.php?rid=5191009&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110355 Cardiac power output is a direct measure of overall cardiac function that integrates both flow- and pressure- generating capacities of the heart. The present study assessed the reproducibility of cardiac power output and other more commonly reported cardiopulmonary exercise variables in patients with chronic heart failure. Metabolic, ventilatory, and non-invasive (inert gas rebreathing) central hemodynamic measurements were undertaken at rest and near maximal exercise of the modified Bruce protocol in 19 patients with stable chronic heart failure. The same procedure was repeated seven days later in order to assess reproducibility. Cardiac power output was calculated as the product of cardiac output and mean arterial pressure. Resting central haemodynamic variables demonstrate low coefficie... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5191009 Wed, 31 Aug 2011 23:00:00 +0100 5191009 http://www.medworm.com/index.php?rid=5191011&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110233 In conclusion, the dramatic muscle wasting seen in critically ill patients with sepsis is due to increased protein degradation. This is facilitated by increased activities of both the proteasome and lysosomal proteolytic systems. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5191011 Tue, 30 Aug 2011 23:00:00 +0100 5191011 http://www.medworm.com/index.php?rid=5191010&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110178 In conclusion, hypoxia and reoxygenation significantly increased PV arrhythmogenesis and induced different electrophysiological responses in the RA and LA, which may play a role in the pathophysiology of AF. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5191010 Tue, 30 Aug 2011 23:00:00 +0100 5191010 http://www.medworm.com/index.php?rid=5155360&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110284 We examined the effects of angiotensin receptor blocker (ARB) therapy (losartan 100 mg daily on insulin sensitivity and endothelial function in fifty-three subjects with stage one hypertension, abdominal obesity and impaired fasting glucose. The study design was a randomized, double-blinded, parallel design, placebo-controlled multicenter trial of 8 weeks duration. We used the euglycemic hyperinsulinemic clamp technique to measure insulin sensitivity (expressed as the ‘M/I’ value), and reactive hyperemia-peripheral arterial tonometry (RH-PAT) to measure endothelial function. Additional measures included HOMA-B, an index of pancreatic beta cell function, and markers of inflammation (e.g. CRP) and oxidative stress (e.g. F2-isoprostanes). ARB therapy did not alter insulin sensit... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5155360 Tue, 23 Aug 2011 23:00:00 +0100 5155360 http://www.medworm.com/index.php?rid=5155361&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110143 In conclusion, high body temperature within the first 24 hours after ischemic stroke is a risk factor for HT in patients non-treated with rtPA. This effect is independent of some biological signatures of BBB damage. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5155361 Mon, 22 Aug 2011 23:00:00 +0100 5155361 http://www.medworm.com/index.php?rid=5094017&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110114 In conclusion, Ang II induces leptin expression in human VSMCs and atorvastatin could inhibit the leptin expression induced by Ang II. The inhibitory effect of atorvastatin on Ang II-induced leptin expression was mediated by Rac, ROS, and JNK pathway. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5094017 Mon, 01 Aug 2011 23:00:00 +0100 5094017 http://www.medworm.com/index.php?rid=5068448&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110295 In conclusion, our study demonstrated that transgenic expression of human MMP-1 decreased proliferation of smooth muscle cells and prevented excessive deposition of collagen in the pulmonary arterial tree. Our results indicate that upregulation of MMP-1 could attenuate the debilitation of human PAH and provide an option for therapeutic intervention. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5068448 Tue, 26 Jul 2011 23:00:00 +0100 5068448 http://www.medworm.com/index.php?rid=5048104&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110013 Methylarginines have been shown to interfere with nitric oxide (NO) formation by inhibiting NO synthase (asymmetric dimethylarginine, ADMA) and cellular L-arginine uptake into the cell (ADMA, and symmetric dimethylarginine, SDMA). In a recent study elevation of SDMA was related to long term mortality in patient recruited 30 days after a stroke event. In the present study we aimed to investigate the association of SDMA and adverse clinical outcome in the early phase (first 30 days) after acute ischemic stroke. 137 patients were recruited immediately upon admission to the emergency unit with an acute ischemic stroke. Plasma levels of methylarginines were determined by a validated LC/MS-MS method. Patients were prospectively followed for 30 days. 25 patients (18.2 %) experienced the primary c... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5048104 Wed, 20 Jul 2011 23:00:00 +0100 5048104 http://www.medworm.com/index.php?rid=5048105&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110181 The activity of angiotensin-converting enzyme (ACE) in the aorta of senescent rats and rats treated with nitric oxide (NO) synthase inhibitor - Nω-nitro-L-arginine methyl ester (L-NAME) or dexamethasone and the effect of low doses of ethanol (0.2–1.2 g/kg of body weight, daily for 8-12 days) on this activity have been studied. We found that ACE activity increases with age and in response to L-NAME and dexamethasone. Ethanol at a dose of 0.4 g/kg per day decreases the ACE activity in the aorta of aged rats and of rats treated with L-NAME or dexamethasone down to the level of ACE activity in young control rats. The optimal ethanol dose (the dose inducing a maximum decrease in the ACE activity) increases with increasing dose of dexamethasone: 0.4 g/kg per day at 30 µg/kg ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5048105 Sun, 17 Jul 2011 23:00:00 +0100 5048105 http://www.medworm.com/index.php?rid=5026695&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110077 In this study, we tested the hypothesis that there is diurnal variation of orthostatic HR & BP in patients with POTS and healthy controls. Patients with POTS (n=54) and healthy volunteers (n=26) were admitted to the Clinical Research Center. Supine and standing (5 min) HR & BP were obtained on the evening on the day of admission and in the following morning. Overall, standing HR was significantly higher in the morning than the evening (102±3 bpm [AM] vs. 93±2 bpm [PM]; P<0.001). Standing HR was higher in the morning in both POTS patients (108±4 bpm [AM] vs. 100±3 bpm [PM]; P=0.012) and controls (89±3 bpm [AM] vs. 80±2 bpm [PM]; P=0.005), when analyzed separately. There was no diurnal variability in orthostatic BP in POTS. More subjects met the P... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5026695 Wed, 13 Jul 2011 23:00:00 +0100 5026695 http://www.medworm.com/index.php?rid=5026694&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110230 This study investigated whether Src kinase is a potential drug target for treating oesophageal squamous cell carcinoma. Compared to the human immortalized esophageal epithelial cell line SHEE, oesophageal squamous cell carcinoma cells have increased tyrosine phosphorylation activities. Here, we explore the therapeutic potential of dasatinib, a small-molecule inhibitor that targets multiple cytosolic and membrane-bound tyrosine kinases for the treatment of oesophageal squamous cell carcinoma. We examined the effects of dasatinib on proliferation, invasion, apoptosis, spindle checkpoint, cell-cycle arrest, and kinase activity in vitro using three human oesophageal carcinoma cell lines KYSE30, KYSE180 and EC109. In nude mouse models, dasatinib treatment effectively inhibits expression of acti... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5026694 Wed, 13 Jul 2011 23:00:00 +0100 5026694 http://www.medworm.com/index.php?rid=5116933&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110236 Conclusion: Our data support a role for RBCs in buffering plasma S1P and identify a disturbance in the capacity after transfusion. Changes in S1P content may contribute to an RBC storage lesion. Further studies should investigate the clinical significance of alterations in circulating S1P levels and the potential value of enriching stored RBC with S1P. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5116933 Tue, 12 Jul 2011 23:00:00 +0100 5116933 http://www.medworm.com/index.php?rid=5026696&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110236 Conclusion: Our data support a role for RBCs in buffering plasma S1P and identify a disturbance in the capacity after transfusion. Changes in S1P content may contribute to an RBC storage lesion. Further studies should investigate the clinical significance of alterations in circulating S1P levels and the potential value of enriching stored RBC with S1P. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5026696 Tue, 12 Jul 2011 23:00:00 +0100 5026696 http://www.medworm.com/index.php?rid=5017649&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110144 Nitric oxide (NO) may be involved in fluid homeostasis. We hypothesized that increases in NO synthesis contribute to acute, saline-induced natriuresis which, therefore, should be blunted when NO availability is stabilized. Young men were studied during simultaneous infusions of Nω-nitro-L-arginine methyl ester (L-NAME, 750 µg·(kg body weight)-1 bolus and 8.3 µg·kg-1·min-1) and sodium nitroprusside, the latter at a rate preventing the L-NAME from increasing total peripheral resistance (‘NO-clamping’). Slow volume expansion (saline, 20 µmol NaCl·kg-1·min-1 for 3 h) was performed with and without concomitant NO-clamping. NO-clamping per se decreased renal plasma flow (RPF, P ~0.02) and tended to decrease arterial ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5017649 Mon, 11 Jul 2011 23:00:00 +0100 5017649 http://www.medworm.com/index.php?rid=5017650&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110033 This study examined the relationship between glycaemia during pregnancy and small artery function and structures some 2 years post-partum. Women were originally enrolled in the HAPO study from which they were classified by their glycaemic distribution during pregnancy as controls (in the lower half of the distribution), upper quartile (UQ - in the upper quartile of the glycaemic distribution) or having had overt GDM. Sub-cutaneous arteries from gluteal fat biopsy taken at follow-up 2 years later were examined using wire myography. Small artery structure, stiffness and vasoconstrictor responses were similar across groups. Maximal endothelium-dependent dilation to carbachol was impaired in arteries from both GDM (43.3%, n=8, p=0.01) and UQ (51.7%, n=13, p=0.04) women despite generally ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=5017650 Sun, 10 Jul 2011 23:00:00 +0100 5017650 http://www.medworm.com/index.php?rid=5017651&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100590 In conclusion, propranolol pre-incubation enhanced the portal-systemic collateral AVP responsiveness in portal hypertensive rats, which was related to Gαq and Gα11 upregulation. In contrast, the attenuated AVP responsiveness by chronic propranolol treatment was related to Gαs upregulation. Gα protein signaling pathway may be a therapeutic target to control variceal bleeding and portal pressure in portal hypertension. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5017651 Thu, 07 Jul 2011 23:00:00 +0100 5017651 http://www.medworm.com/index.php?rid=5006177&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110043 In conclusion, we describe a murine model of GV. GV causes an impairment of ischemia-induced angiogenesis in diabetes, likely to be independent of changes in average blood glucose levels, and this impaired collateral vessel formation is associated with an alteration of the VEGF pathway. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=5006177 Mon, 04 Jul 2011 23:00:00 +0100 5006177 http://www.medworm.com/index.php?rid=4951182&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110018 In cirrhosis, the development of ascites and the response to diuretics are determined by by the renin-angiotensin-aldosterone system (RAAS) and renal sodium handling system. We hypothesized that single nucleotide polymorphisms affecting the candidate genes of the RAAS and renal sodium handling pathway may influence initial diuretics responsiveness and affect clinical outcome in non-azotemic cirrhotic patients with moderate ascites. We prospectively recruited 176 patients and 245 controls and determined their genetic polymorphisms for 24 SNPs of ten genes involved in RAAS and renal-sodium-handling pathway. In cirrhotic patients with moderate ascites, multivariate analysis showed that diuretics unresponsiveness was predicted by high basal plasma aldosterone, by a high aldosterone/renin ratio... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4951182 Mon, 20 Jun 2011 23:00:00 +0100 4951182 http://www.medworm.com/index.php?rid=4951183&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110215 Conclusion: This study highlights the elevation in CYP450 metabolites of arachidonic acid and oxidative stress in acute ischaemic stroke patients. Further investigation of the effect this has on long-term clinical outcome or whether this can be modified by treatment is warranted. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4951183 Sun, 19 Jun 2011 23:00:00 +0100 4951183 http://www.medworm.com/index.php?rid=4931966&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110108 Chronic kidney disease (CKD) has become a public health problem. The therapeutic approaches have been able to reduce proteinuria, but have not been successful in limiting disease progression. In this setting, cell therapies, associated with regenerative effects are becoming of increasing interest. We evaluated the effect of mesenchymal stem cell (MSC) in the progression of CKD and the expression of molecular biomarkers associated with regenerative effects. Adult male Sprague-Dawley submitted to 5/6 nephrectomy (NPX) received a single intravenous infusion of 0.5x106 MSC or culture medium. A sham group, submitted to the same injection was used as control. Rats were sacrificed 5 weeks after MSC infusion. Dye tracking of MSCs was followed by immunofluorescence. Kidney function was evaluated ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4931966 Wed, 15 Jun 2011 23:00:00 +0100 4931966 http://www.medworm.com/index.php?rid=4931967&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110259 Statins can have beneficial cholesterol-independent effects on vascular contractility which may involve increases in the bioavailability of nitric oxide (NO) as a result of phosphorylation of endothelial NO synthase. While this has been attributed to phosphorylation of Akt, studies in cultured cells have shown that statins can phosphorylate AMPK; it is unknown whether this has functional effects in intact arteries. Thus, we investigated the acute effects of simvastatin on resistance arterial contractile function, evaluating the involvement of NO, Akt and AMPK. Isolated rat mesenteric resistance arteries were mounted on a wire myograph. The effects of incubation (1 and 2 hours) with simvastatin (0.1 or 1 μM) on contractile responses were examined in the presence and absence of N-Ni... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4931967 Mon, 13 Jun 2011 23:00:00 +0100 4931967 http://www.medworm.com/index.php?rid=4919892&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110207 MicroRNA-31 (miR-31) is frequently altered in numerous cancers. The purpose of this study was to investigate the role of miR-31 in esophageal squamous cell carcinoma (ESCC). We measured miR-31 in 45-paired ESCC tissues and 523 serum samples using real-time RT-PCR. The serum samples were divided into a discovery group (120 ESCCs and 121 normal controls), a validation group (81 ESCCs and 81 controls), and a final group comprising six other common tumors (colorectal, liver, cervical, breast, gastric and lung cancers; total n=120). The Mann–Whitney test and Wilcoxon matched pairs test were used for statistics. MiR-31 was found up regulated in 77.8% of the ESCC tissues. Serum miR-31 levels in ESCC patients were significantly higher than normal controls (P<0.001). It yielded a under re... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4919892 Thu, 09 Jun 2011 23:00:00 +0100 4919892 http://www.medworm.com/index.php?rid=4870582&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110153 Conclusions/Significance: We conclude that maternal stress and exaggerated fetal glucocorticoid exposure enhance sex-specific stress responses, as well as alterations in aortic reactivity. Because concurrent tempol attenuated conditioned fear and stress reactivity even among the offspring of saline injected dams, we speculate antenatal stressors program offspring stress reactivity in a cycle that may be broken by antenatal antioxidant therapy. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4870582 Wed, 25 May 2011 23:00:00 +0100 4870582 http://www.medworm.com/index.php?rid=4861044&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110069 We tested whether inhibition of mitochondrial membrane potential dissipation by cyclosporine A would prevent doxorubicin-induced myocardial and mitochondrial dysfunction. Acute and sub-chronic models of doxorubicin exposition were performed in mice with either a single intra peritoneal bolus (10 mg/kg, i.p.) or one injection of 4 mg/kg per week during five weeks. Follow-up was 1.5 week and 16 weeks in acute and sub-chronic models, respectively. Mice received either cyclosporine A (1mg/kg i.p. on alternate days) or saline until follow-up. Heart function was evaluated by echocardiography. Mitochondrial measurements included oxygen consumption, membrane potential and externally added calcium-induced mitochondrial permeability transition. Mitochondrial mass was evaluated by transmission electr... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4861044 Mon, 23 May 2011 23:00:00 +0100 4861044 http://www.medworm.com/index.php?rid=4847156&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100607 Conclusion The hemodynamic changes following CSM have a distinct temporal pattern that is characterised by an initial fall in cardiac output (driven by heart rate), followed by a later fall in total peripheral resistance even though sympathetic withdrawal is immediate. This pattern is independent of body position. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4847156 Thu, 19 May 2011 23:00:00 +0100 4847156 http://www.medworm.com/index.php?rid=4839481&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110227 (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4839481 Tue, 17 May 2011 23:00:00 +0100 4839481 http://www.medworm.com/index.php?rid=4819482&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110008 Whether brachial artery flow-mediated dilation (FMD) is altered in pregnancy by 28-35 weeks compared to non-pregnant women remains controversial. The controversy may be due to limitations of previous studies which include failing to: 1) test non-pregnant controls in the mid-late luteal phase, 2) account for effects of pregnancy on the dilatory shear stimulus, 3) account for physical activity, or 4) control for inter-individual variation in the time to peak FMD. Brachial artery FMD was measured in 17 active and 8 sedentary pregnant women (34.1±1.6 weeks gestation), and in 19 active and 11 sedentary non-pregnant women (mid-late luteal phase). Decreased vascular tone secondary to increased shear stress contributes minimally to pregnancy-induced increases in baseline brachial artery dia... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4819482 Wed, 11 May 2011 23:00:00 +0100 4819482 http://www.medworm.com/index.php?rid=4811831&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110243 Hepatic ischaemia reperfusion injury is an important clinical problem complicating liver surgery and transplantation. Ischaemic preconditioning (IPC) is a strategy whereby brief episodes of ischaemia-reperfusion (IR) in an organ can induce an adaptive response to protect against subsequent prolonged IR injury. However, trauma to vessels supplying the target organ is unavoidable using the technique of direct IPC. One amenable strategy would be to apply the protective, preconditioning stimulus to an organ distant or remote from the target organ of interest called remote ischaemic preconditioning (RIPC). In this issue of Clinical Science, Abu-Amara et al utilise hindlimb RIPC as a novel therapeutic strategy against liver IRI and investigate the mechanistic contribution of NO to hepatoprotecti... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4811831 Mon, 09 May 2011 23:00:00 +0100 4811831 http://www.medworm.com/index.php?rid=4801534&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110072 Conclusion: HgCl2 treatment increased vasoconstrictor response to EFS as a result, at the least, of reduced NO bioavailability and increased adrenergic function. These findings offer further evidence that mercury, even at low concentrations, is an environmental risk factor for cardiovascular disease. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4801534 Sun, 08 May 2011 23:00:00 +0100 4801534 http://www.medworm.com/index.php?rid=4801533&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110032 The cytotoxic functions of natural killer cells (NKs) are critical in enabling the immune system to cope efficiently with malignancy. This investigation compared how various exercise regimens with/without hypoxia influence phenotypic characteristics of NK subsets and cytotoxicity of NKs to nasopharyngeal carcinoma cells (NPCs). Sixty sedentary males were randomly divided into five groups. Each group (n=12) underwent one of five interventions: normoxic (21%O2) resting, hypoxic (15%O2) resting, normoxic exercise (50% maximal work-rate under 21%O2, N-E), hypoxic-relative exercise (50% maximal heart rate reserve under 15%O2, H-RE), or hypoxic-absolute exercise (50% maximal work-rate under 15%O2, H-AE) for 30 minutes/day, five days/week for four weeks. The results showed that hypoxic exercise r... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4801533 Sun, 08 May 2011 23:00:00 +0100 4801533 http://www.medworm.com/index.php?rid=4788020&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110036 In this study we have used HEK-293 cells stably transfected with either the AT1R or the AT2R to perform a systematic analysis of binding affinities of all the major Ang peptides. Additionally, we tested the novel AT2R agonist, Compound 21, as well as the MasR agonist and antagonist, AVE0991 and A779 respectively, for their ability to bind to the AT1R or the AT2R. Candesartan, CGP42214 and PD123319 were used as reference compounds. Binding studies using [125I]-Sar1Ile8Ang II on the AT1R transfected HEK-293 cells revealed only Ang II, Ang III and candesartan to have high affinity for the AT1R. In the AT2R transfected HEK-293 cells, competition for [125I]-Sar1Ile8Ang II binding was observed for all ligands except candesartan, AVE0991 and A-779, the latter 2 compounds having negligible affinit... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4788020 Tue, 03 May 2011 23:00:00 +0100 4788020 http://www.medworm.com/index.php?rid=4779599&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110129 Conclusions: Plasma PCSK9 is a heritable trait associated with both FCHL diagnostic hallmarks. These results combined with the significant rise in PCSK9 levels after statin therapy warrant further studies to unravel the exact role of PCSK9 in the pathogenesis and treatment of this highly prevalent genetic dyslipidemia. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4779599 Mon, 02 May 2011 23:00:00 +0100 4779599 http://www.medworm.com/index.php?rid=4762154&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110063 Heart Rate Turbulence (HRT) describing the heart rate changes following a premature ventricular contraction, has been regarded as an indirect index of baroreflex function. However limited data are available on its relation to invasive assessment by phenylephrine injection (Phe_Slope). We therefore compared these methodologies in a series of heart failure (HF) patients in which both measures together with clinical and hemodynamic data were available. HRT parameters (turbulence onset, TO and turbulence slope, TS, were measured from 24-hour Holter recordings obtained within one week from baroreflex sensitivity assessment and right heart hemodynamic evaluation (Swan-Ganz catheter). HRT was computable in 135 out of 157 (86%) patients who had both phenylephrine test and hemodynamic evaluati... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4762154 Wed, 27 Apr 2011 23:00:00 +0100 4762154 http://www.medworm.com/index.php?rid=4731883&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100529 Hypertension and diabetes mellitus (DM) are common chronic disorders that often coexist. DM and peroxisome proliferator-activated receptors (PPAR)-gamma agonists may directly impair heart functions. However, the effects of DM and PPAR-g agonists on hypertensive myocardium are not known. Hence, the objective of this study was to investigate whether DM and a PPAR-gamma agonist (rosiglitazone, RGZ) can modulate the effects of hypertension on myocardial expressions of PPAR isoforms. Cardiac PPAR isoforms, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 were evaluated by real-time PCR and Western blotting in spontaneously hypertensive rat (SHR), diabetic SHR, diabetic SHR treated with RGZ (5 mg/kg), and Wistar-Kyota control rats. Cardiac nicotinamide adenine dinucleotide phosphate (NA... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4731883 Mon, 18 Apr 2011 23:00:00 +0100 4731883 http://www.medworm.com/index.php?rid=4731882&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100597 Increased dietary long-chain n-3 polyunsaturated fatty acid (LCn-3PUFA) intake stimulates muscle protein anabolism in individuals who experience muscle loss due to aging or cancer cachexia. However, it is not known whether LCn-3PUFA elicit similar anabolic effects in healthy individuals. To answer this question we evaluated the effect of 8 weeks of LCn-3PUFA supplementation (4 g·d-1 of Lovaza®) in nine 25-45 y old healthy subjects on the rate of muscle protein synthesis (by using stable isotope labelled tracer techniques) and the activation (phosphorylation) of elements of the mTOR-p70s6k pathway during basal, postabsorptive conditions and during a hyperinsulinemic-hyperaminoacidemic clamp. We also measured the concentrations of protein, RNA, and DNA in muscle to obtain indic... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4731882 Mon, 18 Apr 2011 23:00:00 +0100 4731882 http://www.medworm.com/index.php?rid=4682666&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110027 In conclusion, over a wide range of HRV magnitudes during experimental endotoxaemia, neither paced breathing, nor mild hyperventilation affected HRV indices. Moreover, paced breathing did not result in a significant reproducibility improvement. Therefore, employing a paced breathing protocol is not required to obtain valid HRV data during endotoxaemia. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4682666 Tue, 05 Apr 2011 23:00:00 +0100 4682666 http://www.medworm.com/index.php?rid=4675827&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100598 In conclusion, NO is an essential mediator of the protection afforded by hindlimb RIPC against liver IR injury. The mechanisms underlying this protection involve preservation of the sinusoidal structure and maintenance of blood flow through the hepatic microcirculation. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4675827 Sun, 03 Apr 2011 23:00:00 +0100 4675827 http://www.medworm.com/index.php?rid=4657799&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110060 Hepatic metabolism of methionine is the source of cysteine, the precursor of glutathione, the major intracellular antioxidant in the body. Methionine also is the immediate precursor of s-adenosylmethionine (SAM) the key methyl donor for phosphotidylcholine synthesis required for the export of VLDL triglycerides from the liver. We have examined the kinetics of methionine, its transmethylation and transsulfuration with estimates of whole body rate of protein turnover and urea synthesis in clinically stable biopsy confirmed subjects with non-alcoholic steatohepatitis (NASH). Subjects with NASH were more insulin resistant and had significantly higher plasma concentration of usCRP, TNF alpha and other inflammatory cytokines. There was no significant effect of insulin resistance and NASH on whol... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4657799 Tue, 29 Mar 2011 23:00:00 +0100 4657799 http://www.medworm.com/index.php?rid=4657798&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100596 Hypobaric hypoxia preconditioning (HHP) caused overexpression of heat shock protein (HSP)-70 as well as tolerance to cerebral ischemia. We hypothesize that HHP protects against high altitude exposure (HAE)-induced acute lung injury and edema via promoting the appearance of HSP-70 in lungs prior to onset of HAE. Two weeks after the start of HHP, animals were exposed to a simulated HAE of 6,000 m in a hypobaric chamber for 24 hours. Right after being taken out to the ambient, the non-HHP animals displayed higher scores of alveolar edema, neutrophil infiltration and hemorrhage, acute pleurisy (e.g., increased exudates volume, increased numbers of polymorphonuclear cells, and increased lung myeloperoxidase activity), increased proinflammatory cytokines (e.g., tumor necrosis factor-α, in... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4657798 Tue, 29 Mar 2011 23:00:00 +0100 4657798 http://www.medworm.com/index.php?rid=4651880&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100601 Conclusion. Obesity is associated with an enhanced TLR response in patients suffering from established atherosclerotic disease. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4651880 Mon, 28 Mar 2011 23:00:00 +0100 4651880 http://www.medworm.com/index.php?rid=4610142&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110002 In this study we investigate a mechanism whereby HSCs modulate the migratory activity of HCC cells. We used primary cultures of human HSCs to investigate their effect on Hep3B, Alexander, HLE and HLF HCC cells. The expression of Laminin-5 (Ln-) was documented at transcript and protein levels both in vitro and in vivo. HCC cells strongly adhere, migrate and spread in the presence of HSCs conditioned media and of co-culture. HSCs produce and secrete Ln-5 in the conditioned medium. The electrophoretic pattern of secreted Ln-5 is consistent with that of a migratory substrate, showing the presence of the g2x fragment. Blocking antibodies against Ln-5 inhibit HCC migration in the presence of HSCs conditioned media. HCC cells migrate very poorly in the presence of Ln-5 immuno-depleted HSCs condit... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4610142 Fri, 18 Mar 2011 00:00:00 +0100 4610142 http://www.medworm.com/index.php?rid=4569953&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100611 Suppression of lipolysis by acipimox is known to improve insulin-stimulated glucose disposal and this is an important phenomenon. The mechanism has been assumed to be enhancement of glucose storage as glycogen, but no direct measurement has tested this concept nor its possible relationship to the reported impairment in insulin-stimulated muscle ATP production. Isoglycaemic-hyperinsulinaemic clamps with 13C-glucose infusion were performed on type 2 diabetes subjects and matched controls with measurement of glycogen synthesis by 13C magnetic resonance spectroscopy (MRS) of muscle. 31P saturation transfer MRS was used to quantify muscle ATP turnover rates. Glucose disposal rates were restored to near-normal in diabetic subjects after acipimox (6.2 ± 0.8 vs. 4.8 ± 0.6 mg/kgffm/mi... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4569953 Thu, 10 Mar 2011 00:00:00 +0100 4569953 http://www.medworm.com/index.php?rid=4511577&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100448 Conclusions DSS, microcirculatory function and endothelium-independent vasodilatation in response to GTN, are important determinants that impact on the magnitude of FMD response, and are impaired in patients with type 1 diabetes mellitus. Impaired FMD response is multifactorial in origin and cannot be attributed solely to a diminished Nitric Oxide (NO) bioavailability. Clinical trials no: NCT01045005 (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4511577 Wed, 23 Feb 2011 00:00:00 +0100 4511577 http://www.medworm.com/index.php?rid=4494347&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20110006 This study examined the glucose-lowering and insulinotropic properties of acylated GLP-1 and GIP peptides in type 2 diabetes and obesity. GLP-1, GIP, Liraglutide, N-AcGIP(Lys37Myr), a simple combination of both peptides, and an overnight preparation of Liraglutide and N-AcGIP(Lys37Myr) (Lira-AcGIP preparation) were incubated with DPP-IV to assess peptide stability and BRIN-BD11 cells were used to evaluate cAMP production and insulin secretion. Acute glucose-lowering and insulinotropic actions were evaluated in Swiss TO mice. Sub-chronic studies on glucose homeostasis, insulin secretion, food intake and bodyweight were evaluated in ob/ob mice. Liraglutide, N-AcGIP(Lys37Myr), a simple combination of both peptides and Lira-AcGIP preparation demonstrated improved DPP-IV resistance (P < 0.00... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4494347 Fri, 18 Feb 2011 00:00:00 +0100 4494347 http://www.medworm.com/index.php?rid=4459159&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100595 In conclusion, an unfavorable NOS substrate/inhibitor ratio may contribute to the reduced NO bioavailability associated with inflammation. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4459159 Thu, 10 Feb 2011 00:00:00 +0100 4459159 http://www.medworm.com/index.php?rid=4459158&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100564 Conclusions: Plasma copeptin is elevated after NSTEMI and higher levels are associated with worse outcomes. Copeptin used in conjunction with the GRACE score improves risk stratification enabling more accurate identification of high risk individuals. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4459158 Thu, 10 Feb 2011 00:00:00 +0100 4459158 http://www.medworm.com/index.php?rid=4436287&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100589 Conclusion: A dysregulated MGP system could be involved in left ventricular dysfunction in patients with chronic HF. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4436287 Fri, 04 Feb 2011 00:00:00 +0100 4436287 http://www.medworm.com/index.php?rid=4432593&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100435 Conclusions: Joint isoflurane preconditioning and propofol anesthesia regimen synergistically attenuated myocardial reperfusion injury in patients. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4432593 Thu, 03 Feb 2011 00:00:00 +0100 4432593 http://www.medworm.com/index.php?rid=4428379&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100534 In conclusion, maternal overnutrition induced permanent changes in adipose tissue metabolism of the offspring. These preexisting alterations in offspring were worsened under a high-fat diet from weaning to adulthood. Consequently, adipose adipokines and enzymes could provide a potential therapeutic target, and new investigations in this field could constitute strategies to improve the impact of early life overnutrition. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4428379 Wed, 02 Feb 2011 00:00:00 +0100 4428379 http://www.medworm.com/index.php?rid=4418427&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100527 Conclusion: MET-induced enhancement of myocardial fatty acid oxidation had neutral effect on cardiac function and survival. Recently reported cardioprotective effects of MET may not be universal to all forms of HF and may require AMPK activation or ATP depletion. No increase in mortality on MET supports its safe use in diabetic HF. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4418427 Mon, 31 Jan 2011 00:00:00 +0100 4418427 http://www.medworm.com/index.php?rid=4404855&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100588 In conclusion, eszopiclone increases the arousal threshold and lowers the apnea/hypopnea index in obstructive sleep apnea patients that do not have marked overnight hypoxemia. The greatest reductions in the apnea/hypopnea index occurred in those with a low arousal threshold. The results of this single night physiological study suggest that certain sedatives may be of therapeutic benefit for a definable subgroup of patients. However, additional treatment strategies are likely required to achieve elimination of apnea. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4404855 Thu, 27 Jan 2011 00:00:00 +0100 4404855 http://www.medworm.com/index.php?rid=4398759&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100427 ABSTRACT Ischemic stroke is associated with an excessive release of glutamate in brain. Glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) are two enzymes that are able to metabolize blood glutamate facilitating the lowering of extracellular levels of brain glutamate. Our aim was to study the association between blood levels of both enzymes and stroke outcome in the patients with acute ischemic stroke. We prospectively studied 365 patients with first ischemic stroke <12 hours. Glutamate, GOT and GPT levels were determined in blood samples obtained at admission. We considered functional outcome at 3 months (good outcome: mRS ≤2; poor outcome mRS <2), early neurological deterioration (END) in the first 72 h (Increment ≥4 points in ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4398759 Wed, 26 Jan 2011 00:00:00 +0100 4398759 http://www.medworm.com/index.php?rid=4342229&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100460 This study investigated whether blood flow to skeletal muscle and/or the liver was increased in the postprandial period after exercise, relative to a control trial, and whether this resulted from increased cardiac output or redistribution of flow. Eight overweight, inactive males, aged 49.4 ± 10.5 years (mean ± SD) acted as their own controls in a counter-balanced design, either walking briskly for 90 minutes at 60% VO2max, or resting in the lab, on the evening of day 1. The following morning a fasting blood sample was collected, participants consumed a high-fat breakfast and further venous blood samples were drawn hourly for 6 h. Immediately after blood sampling, Doppler ultrasound was used to measure cardiac output and blood flow through both the femoral artery of one leg a... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4342229 Thu, 13 Jan 2011 00:00:00 +0100 4342229 http://www.medworm.com/index.php?rid=4336934&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100277 We investigated an effect of uraemia on structural and functional features of human resistance vasculature. Arteries (around 0.2 mm) isolated from subcutaneous fat biopsies obtained from 35 end-stage renal disease (ESRD) patients starting peritoneal dialysis and 30 matched controls were studied using isolated small artery bioassays. Flow-mediated dilatation was attenuated in ESRD patients vs. controls. Nitric oxide (NO) contribution to flow was lacking in ESRD patients, but present in the controls. Asymmetrical dimethyl L-arginine (ADMA) levels were higher in the ESRD group vs. control group. Dilatation to acetylcholine was reduced in ESRD patients vs. controls, but response to NO-donor was similar. Expression of nitrotyrosine and heat shock proteins 70 and 27, but not 90, was increased ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4336934 Tue, 11 Jan 2011 00:00:00 +0100 4336934 http://www.medworm.com/index.php?rid=4317770&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100417 The regulation of human Th17 cell effector function by regulatory T (T reg) cells is poorly understood. Here we report that human T reg (CD4+CD25+) cells inhibit the proliferative response of Th17 cells but not their capacity to secrete IL-17. However they could inhibit proliferation and cytokine production by Th1 and Th2 cells as determined by IFN-g and IL-5 biosynthesis. Currently as there is interest in the role of IL-17 producing cells and T reg cells in chronic inflammatory diseases in humans we investigated the presence of CD4+CD25+ T cells and IL-17 in inflammation in the human lung. Transcripts for IL-17 were expressed in mononuclear cells and purified T cells from lung tissue of patients with chronic pulmonary inflammation and when activated these cells... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4317770 Thu, 06 Jan 2011 00:00:00 +0100 4317770 http://www.medworm.com/index.php?rid=4248451&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100475 Endothelin (ET)-1, a potent vasoconstrictor peptide released by the endothelium, plays an important role in vasomotor regulation and has been linked to diminished endothelial vasodilator capacity in several pathologies associated with human aging, including hypertension, type 2 diabetes, and coronary artery disease. However, it is currently unknown whether the decline in endothelial vasodilation with advancing age, per se, is due to elevated ET-1 vasconstrictor activity. Accordingly, we tested the hypothesis that the age-related impairment in acetylcholine-mediated endothelium-dependent vasodilation is due, at least in part, to increased ET-1-mediated vasoconstrictor tone. Forearm blood flow (FBF) responses to acetylcholine (ACh), sodium nitroprusside (SNP), and BQ-123 (ETA receptor blocke... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4248451 Fri, 10 Dec 2010 00:00:00 +0100 4248451 http://www.medworm.com/index.php?rid=4248450&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100440 Conclusions: Our data suggest that reduced blood DC counts in CAD are, at least partly, due to impaired DC differentiation from bone marrow progenitors. Decreased mDCs are presumably also explained by activation and subsequent migration to atherosclerotic plaques or lymph nodes. Although mDCs are functioning normally, pDCs from patients seemed to be both numerically and functionally impaired. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4248450 Fri, 10 Dec 2010 00:00:00 +0100 4248450 http://www.medworm.com/index.php?rid=4241038&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100466 Remote ischemic preconditioning (rIPC) has been shown to invoke potent myocardial protection in animal studies and recent clinical trials. While the important role of phosphatidylinositol-3-kinase (PI3K)/Akt activation in the cardioprotection afforded by local IPC is well described, our understanding of the intracellular signaling of rIPC remains incomplete. We therefore examined the hypothesis that the myocardial protection afforded by rIPC is mediated via the PI3K/Akt/Glycogen synthase kinase 3β (GSK-3β) signaling pathway, activation of which is associated with nuclear accumulation of β-catenin. rIPC was induced in mice using 4 cycles of 5 minutes ischemia and 5 minutes reperfusion of the hindlimb using a torniquet. This led to reduced infarct size (rIPC: 19±4... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4241038 Wed, 08 Dec 2010 00:00:00 +0100 4241038 http://www.medworm.com/index.php?rid=4182408&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100280 This study assessed the effect of Ang 1-7 on blood pressure and cardiac remodelling in a rat model of renal mass ablation. Male Sprague Dawley rats underwent subtotal nephrectomy (STNx) and were treated for 10 days with vehicle, the ACE inhibitor, ramipril (oral, 1 mg/kg/d) or Ang 1-7 (s.c 24 µg/kg/h) (all, n=15 /gp). A control group (n=10) of sham-operated rats were also studied. STNx rats were hypertensive (P<0.01) with renal impairment (P<0.001), cardiac hypertrophy (P<0.001) and fibrosis (P<0.05), and increased cardiac ACE (P<0.001) and ACE2 activity (P<0.05). Ramipril reduced blood pressure (P<0.01), improved cardiac hypertrophy (P<0.001), and inhibited cardiac ACE (P<0.001). By contrast, Ang 1-7 infusion in STNx was associated with further increases ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4182408 Fri, 19 Nov 2010 00:00:00 +0100 4182408 http://www.medworm.com/index.php?rid=4178506&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100553 Hepatitis C virus (HCV) represents one of the major health problems worldwide, as almost 170 million are infected and most of patients develop a chronic disease, often with progression to cirrhosis and its complications. The study by Iwata and colleagues [1] reports an association between a variant of a gene regulating bile acid levels, ABCB11 1331T<C, and progression to cirrhosis in patients with HCV, but not in fatty liver patients. They correlate this genetic variant with increased serum bile acid levels, as marker of cholestasis. These findings have important implications for researchers working to dissect the molecular mechanisms underlying liver fibrogenesis and disease progression. Implications for clinical hepatologists are less immediate. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4178506 Thu, 18 Nov 2010 00:00:00 +0100 4178506 http://www.medworm.com/index.php?rid=4171349&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100504 Conclusion Serum CRP was associated with lung function cross-sectionally however CRP polymorphisms were not associated with lung function or decline, suggesting that the CRP-lung function relationship is either due to reverse causality, unmeasured confounding factor or only has modest causal effect. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4171349 Tue, 16 Nov 2010 00:00:00 +0100 4171349 http://www.medworm.com/index.php?rid=4158249&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100416 Common polymorphisms within the fat mass and obesity associated (FTO) gene correlate with increased BMI and a rising risk of type 2 diabetes. FTO is highly expressed in the brain but has also been detected in peripheral tissues including the endocrine pancreas, although its function there is unclear. The current work aimed to investigate the role of FTO in pancreatic β-cells using a conditional expression system developed in INS-1 cells. INS-1 cells were stably transfected with haemagluttinin-tagged FTO (FTO-HA) incorporated under the control of a tetracycline-inducible promoter. Induction of FTO resulted in localisation of the tagged protein to the nucleus. The level of FTO-HA protein achieved in transfected cells was tightly regulated and experiments with selective inhibitors reve... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4158249 Thu, 11 Nov 2010 00:00:00 +0100 4158249 http://www.medworm.com/index.php?rid=4132329&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100521 Saturated fatty acids are toxic to pancreatic β-cells. By inducing apoptosis, they contribute to a decrease in β-cell mass, a hallmark of type 2 diabetes. In this issue of Clinical Science, Keane and co-workers show that the polyunsaturated fatty acid arachidonic acid protects the β-cell against the toxic effects of palmitate. As type 2 diabetes is characterised by subclinical inflammation, and arachidonic acid and metabolites thereof are produced during states of inflammation, it is possible that pancreatic β-cells use arachidonic acid as a compound for self-protection. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4132329 Tue, 02 Nov 2010 00:00:00 +0100 4132329 http://www.medworm.com/index.php?rid=4116892&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100355 Conclusions: Obesity associated or not with type 2 diabetes alters human peri-umbilical adipose tissue arterioles in terms of structure, function and biochemsitry, including diminished eNOS expression and reduced levels of IRS-1, IRS-2, PI3-kinase and AKT in insulin-signaling pathway. Key words: arterioles, obesity, type 2 diabetes, insulin signaling, endothelial dysfunction. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4116892 Wed, 27 Oct 2010 23:00:00 +0100 4116892 http://www.medworm.com/index.php?rid=4116893&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100311 Red wine polyphenols (RWPs) exert antihypertensive effects and improve endothelial function by reducing the plasma levels of endothelin-1 (ET-1) and the subsequent vascular production of superoxide (O2.-). Our present study was designed to evaluate if RWPs act directly in the vascular wall improving endothelial dysfunction and O2.- production induced by ET-1 and to analyze the compounds responsible for these protective effects. We incubated rat isolated aortic rings in the presence or absence of ET-1 (10 nM) and RWPs (10-4 g/L to 10-2 g/L) or catechin (0.2 μM), epicatechin (10 μM) and resveratrol (0.1 μM). ET-1 reduced the relaxant responses to acetylcholine, increased intracellular O2.- production, NADPH oxidase activity, and protein expression of NADPH oxidase subuni... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4116893 Mon, 25 Oct 2010 23:00:00 +0100 4116893 http://www.medworm.com/index.php?rid=4072849&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100441 In this study, we have investigated the metabolic effects of a mixture of these three herbal extracts (SK0506) in a rodent model of metabolic syndrome induced by high fat diet (HFD). SD rats that were fed HFD for 4 weeks gained 33% more weight compared with chow fed rats (P <0.05). 4 weeks treatment with SK0506 prevented weight gain with decreased visceral fat (P <0.01 vs. vehicle treatment). SK0506 also significantly reduced plasma triglycerides, NEFAs and cholesterol. SK0506 exerted similar effects to rosiglitazone on impaired glucose intolerance SK0506 also significantly enhanced glucose uptake and glycogen synthesis in adipose tissue during hyperinsulinaemic-euglycaemic clamp. Western blotting analysis revealed SK0506 enhanced GLUT4 expression in adipose tissue and rosiglitazone ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4072849 Thu, 14 Oct 2010 23:00:00 +0100 4072849 http://www.medworm.com/index.php?rid=4072850&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100366 Conclusion This is the first report showing a potential role for the serine protease Proteinase 3 in determining mortality and incidence of heart failure following AMI, independent of established conventional risk factors. Proteinase 3 may represent a clinically useful marker of prognosis after an AMI as part of a multimarker strategy. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4072850 Wed, 13 Oct 2010 23:00:00 +0100 4072850 http://www.medworm.com/index.php?rid=4044250&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100387 In conclusion, hepatic expression of LXRalpha and its related lipogenic and inflammatory genes is abnormally increased in NAFLD and HCV patients with steatosis, suggesting a potential role of LXRalpha in the pathogenesis of hepatic steatosis in these chronic liver diseases. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4044250 Thu, 07 Oct 2010 23:00:00 +0100 4044250 http://www.medworm.com/index.php?rid=4035589&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100369 Conclusion: Reduction of peroxynitrite-induced nitrooxidative stress subsequent to the inhibition of iNOS represents a major mechanism whereby postconditioning confers cardioprotection in vivo. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=4035589 Mon, 04 Oct 2010 23:00:00 +0100 4035589 http://www.medworm.com/index.php?rid=4017506&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100246 Chronic hepatitis C (HCV)-associated cirrhosis represents a major indication for liver transplantation. Bile acids (BA) contribute to hepatic stellate cell activation as a key event in fibrogenesis. Aim of this study was to investigate the role of BA and polymorphisms in BA level-regulating genes on fibrosis progression. 206 patients with chronic HCV infection were included for ABCB11 1331T<C and NR1H4 -1G<T genotyping, 178 of which were analyzed for fibrosis stage. Exclusion criteria were HBV or HIV coinfection, alcohol <40 g/day and morbid obesity. 358 patients with non-alcoholic fatty liver disease (NAFLD) were genotyped for comparison with a non-viral liver disease. 110 Caucasian individuals undergoing liver resection for focal hepatic metastasis served as controls. The ABC... Clinical Science journals http://www.medworm.com/rss/comments.php?id=4017506 Wed, 29 Sep 2010 23:00:00 +0100 4017506 http://www.medworm.com/index.php?rid=3980103&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100388 Monitoring of heart failure (HF) with intracardiac pressure, intrathoracic impedance and/or natriuretic peptide levels has been advocated. We aim to investigate possible differences in the response patterns of each of these monitoring modalities during HF decompensation that may impact the potential for early therapeutic intervention. Six sheep were implanted with a left atrial pressure (LAP) sensor and a cardiac resynchronization therapy defibrillator (CRT-D) capable of monitoring impedance along six lead configuration vectors. An estimate of LAP from admittance (ALAP) was determined by linear regression. HF was induced by rapid ventricular pacing at 180bpm and 220bpm for a week each, followed by a third week with daily pacing suspensions for increasing durations (1-5hours). Incrementa... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3980103 Thu, 16 Sep 2010 23:00:00 +0100 3980103 http://www.medworm.com/index.php?rid=3968505&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100282 Chronic exposure of pancreatic β-cells to saturated non-esterified fatty acids can lead to inhibition of insulin secretion and apoptosis. Several previous studies have demonstrated that saturated fatty acids such as palmitic acid (PA) are detrimental to β-cell function compared to unsaturated fatty acids. Here, we describe the effect of the polyunsaturate arachidonic acid (AA) on the function of the clonal pancreatic β-cell line BRIN-BD11 and demonstrate AA dependent attenuation of PA effects. When added to β-cell incubations at 100uM AA can stimulate cell proliferation and chronic (24 h) basal insulin secretion. Microarray analysis and/or real time PCR indicated significant AA dependent up-regulation of genes involved in proliferation and fatty acid metabolism ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3968505 Mon, 13 Sep 2010 23:00:00 +0100 3968505 http://www.medworm.com/index.php?rid=3953170&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100137 In conclusion, during acute psychological stress BRS is higher in healthy subjects treated with non-selective β-adrenergic blockade with significantly lower HR but comparable BP. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3953170 Wed, 08 Sep 2010 23:00:00 +0100 3953170 http://www.medworm.com/index.php?rid=3932530&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100297 Circulating microRNAs (miRNAs) are emerging as promising biomarkers for several pathological conditions, and the aim of this study was to investigate the feasibility of using serum miRNAs as biomarkers for liver pathologies. Real-time quantitative PCR-based TaqMan MicroRNA arrays were first employed to profile miRNAs in serum pools from patients with hepatocellular carcinoma (HCC) or liver cirrhosis (LC) and from healthy controls. Five miRNAs (i.e. miR-885-5p, 574-3p, -224, -215 and miR-146a) that were up-regulated in the HCC and LC serum pools were selected and further quantified using RT-qPCR in patients with HCC, LC, chronic hepatitis B (CHB) or gastric cancer (GC) and in normal controls. The present study revealed that more than 110 miRNA species in the serum samples and wide distribut... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3932530 Thu, 02 Sep 2010 23:00:00 +0100 3932530 http://www.medworm.com/index.php?rid=3932529&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100206 Conclusions: Although marathon running leads to a transient increase of cardiac biomarkers, no detectable myocardial necrosis was observed as evidenced by LGE MRI. Endurance exercise induces an augmented systolic wringing motion of the myocardium and increased diastolic filling velocities. The stress of marathon running seems to be better described as a burden of myocardial overstimulation rather than cardiac injury. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3932529 Thu, 02 Sep 2010 23:00:00 +0100 3932529 http://www.medworm.com/index.php?rid=3932528&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100223 Conclusion: Although there were gender differences in vascular function and structure in the young adult population examined in this study many of the differences were eliminated simply by adjusting for artery diameter. However, the lower EID observed in males could not be explained by artery diameter. Future studies need to continue to examine influence of gender on EID and other measures of vascular function. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3932528 Thu, 02 Sep 2010 23:00:00 +0100 3932528 http://www.medworm.com/index.php?rid=3906850&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100372 The aim of this study was to test the effect of sitagliptin and exendin-4 upon metabolic alterations, β-cell mass decrease and hepatic steatosis induced by F (fructose) in rats. Normal adult male Wistar rats received a standard commercial diet without (C) or with 10% F in the drinking water (F) for 3 weeks; animals from each group were randomly divided into three subgroups: untreated (C and F) and simultaneously receiving either sitagliptin (CS and FS; 115.2 mg/day/rat) or exendin-4 (CE and FE; 0.35 nmol/kg body wt, ip). Water and food intake, oral glucose tolerance, plasma glucose, triglyceride, insulin and fructosamine concentration, HOMA-IR, HOMA-β and liver triglyceride content were measured. Pancreas immunomorphometric analyses were also performed. IGT (impaired glucose ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3906850 Wed, 25 Aug 2010 23:00:00 +0100 3906850 http://www.medworm.com/index.php?rid=3906849&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100226 In conclusion, resistin increases migration and proliferation of VSMCs and expression of resistin in carotid artery significantly increases after injury. Resistin siRNA attenuates neointimal formation after carotid injury partly through anti-oxidative mechanism. Resistin may play a pivotal role in the pathogenesis of neointimal thickening after mechanical injury. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3906849 Wed, 25 Aug 2010 23:00:00 +0100 3906849 http://www.medworm.com/index.php?rid=3888511&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100256 In conclusion, despite an increase in full-length RAGE expression, esRAGE expression was down-regulated in the diabetic patients, and serum sRAGE and esRAGE was also reduced. Hence, increased full-length RAGE levels are not associated with a similar increase in soluble RAGE isoforms levels. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3888511 Thu, 19 Aug 2010 23:00:00 +0100 3888511 http://www.medworm.com/index.php?rid=3801798&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100254 Doxorubicin (DOX), an antibiotic used in oncologic treatments, is limited by a dose-related cardiotoxicity, against which acute exercise is protective. However, the mechanisms related to this protection involving mitochondria remain unknown. Therefore, we aimed to determine the effects of an acute endurance exercise bout performed 24h before Doxorubicin (DOX) treatment on heart and liver mitochondrial function. Twenty adult Wistar-male rats were divided as follows: non-exercised saline (NE+SAL), non-exercised DOX (NE+DOX), exercised-saline (EX+SAL) and exercised-DOX (EX+DOX). The animals performed a 60 min exercise bout on a treadmill or remained sedentary 24h before receiving either a 20 mg.kg-1 DOX bolus or saline. Heart and liver mitochondrial function (oxyg... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3801798 Wed, 28 Jul 2010 23:00:00 +0100 3801798 http://www.medworm.com/index.php?rid=3779814&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100367 Abstract Sepsis and the severe systemic response syndrome are very common illnesses that are responsible for a great amount of morbidity and death. These closely related conditions are characterized by a remarkable increase of the prohormone, procalcitonin (ProCT). ProCT is both a marker of sepsis and a harmful mediator of the disease. In elegant in rats with endotoxin shock, Drs. Tavares and Minano used an antibody to a segment of the N-ProCT that is part of the ProCT molecule and confirmed that immunoneutralization of ProCT saves the animals from this severe illness. Furthermore, they extensively studied the epiphenomena associated with this immunoneutralization. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3779814 Wed, 21 Jul 2010 23:00:00 +0100 3779814 http://www.medworm.com/index.php?rid=3766686&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100174 Brachial artery flow-mediated dilation (FMD) is impaired with aging and is associated with increased risk for cardiovascular disease (CVD). We determined if regular aerobic exercise improves brachial artery FMD in middle-aged/older (MA/O) men and postmenopausal women. In sedentary MA/O adults (age 55 - 79 years) without CVD, 8 weeks of brisk walking (6 days/week for ~50 min/day; randomized, controlled design) increased treadmill time ~20% in both MA/O men (n=11) and postmenopausal women (n=15) (P<0.01), without altering body composition or circulating CVD risk factors. Brachial artery FMD increased < 50% in the MA/O men (4.6 ± 0.6 to 7.1 ± 0.6%, P < 0.01), but did not change in the postmenopausal women (5.1 ± 0.8 vs. 5.4 ± 0.7%, P = 0.50). No changes oc... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3766686 Sun, 18 Jul 2010 23:00:00 +0100 3766686 http://www.medworm.com/index.php?rid=3757198&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100363 Derangements in systemic and local metabolism develop in patients with chronic heart failure and contribute to the progression of the disease. Impaired skeletal muscle metabolism, morphology and function leading to exercise intolerance are hallmarks of the syndrome of chronic heart failure. These changes result in abnormal glucose and lipid metabolism and the associated insulin resistance which contribute to progression of skeletal muscle catabolism and the development of muscle atrophy in patients with advanced heart failure. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3757198 Wed, 14 Jul 2010 23:00:00 +0100 3757198 http://www.medworm.com/index.php?rid=3729363&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100190 Conclusion: In our study in renal transplant recipients suggests the TLR system to be involved in both acute rejection and MACE. Modulation of the TLR system may be promising targets in future therapeutic strategies. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3729363 Mon, 05 Jul 2010 23:00:00 +0100 3729363 http://www.medworm.com/index.php?rid=3721360&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100241 A fundamental concern for all new biological therapeutics is the possibility of inducing an immune response. We have recently demonstrated that a ligand-receptor fusion (LR-fusion) of growth hormone generates a potent long-acting agonist, however the immunogenicity and toxicity of these molecules have not been tested. To address these issues we have designed molecules with low potential as immunogens and undertaken immunogenicity and toxicology studies in Macaca fascicularis and pharmacokinetic and pharmacodynamic studies in rats. Two variants of the LR-fusion, one with a flexible linker (GH-LRv2) and the other without (GH-LRv3), were tested. Comparison was made with native human GH. GH-LRv2 and GH-LRv3 demonstrated similar pharmacokinetics in rats, showing reduced clearance compared to ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3721360 Thu, 01 Jul 2010 23:00:00 +0100 3721360 http://www.medworm.com/index.php?rid=3705961&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100147 Mesenchymal Stromal Cells (MSC) can differentiate into renal adult cells, and have anti-inflammatory and immune-modulating activity. We investigated whether MSC have protective/reparative effects in anti-Thy 1 disease, an antibody-induced mesangiolysis resulting in mesangioproliferative nephritis. We studied five groups of rats. A: rats injected with anti-Thy Ab on day 0. B: rats injected with anti-Thy Ab on day 0 + MSC on day 3. C: rats injected with anti-Thy Ab on day 0 + mesangial cells on day 3. D: rats injected with saline on day 0 + MSC on day 3. E: rats injected with saline on day 0. Rats were sacrificed on days 1, 3, 7, 14. MSC prevented the rise in serum creatinine, proteinuria, glomerular monocyte influx and glomerular histopathological injury. Furthermore, M... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3705961 Sun, 27 Jun 2010 23:00:00 +0100 3705961 http://www.medworm.com/index.php?rid=3694726&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100162 Conclusions: Active CMV infection occurs, though uncommonly, in patients with AHF, and may be a marker of disease severity. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3694726 Wed, 23 Jun 2010 23:00:00 +0100 3694726 http://www.medworm.com/index.php?rid=3690334&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100007 Severe sepsis and septic shock are an important cause of mortality and morbidity. These illnesses can be triggered by the bacterial endotoxin lipopolysaccharide (LPS) and proinflammatory cytokines, particularly tumor necrosis factor (TNF)-a and interleukin (IL)-1b. Severity and mortality of sepsis have also been associated with high concentrations of aminoprocalcitonin (N-PCT), a 57-amino acid neuroendocrine peptide derived from procalcitonin. Prior studies in a lethal model of porcine polymicrobial sepsis have revealed that immunoneutralization with IgG that is reactive to porcine N-PCT significantly improves short-term survival. To further explore the pathophysiological role of N-PCT in sepsis, we developed an antibody raised against a highly conserved amino acid sequence of human N-PCT ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3690334 Tue, 22 Jun 2010 23:00:00 +0100 3690334 http://www.medworm.com/index.php?rid=3647858&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100053 The renin-angiotensin system (RAS) is classically involved in blood pressure regulation and water-electrolyte balance, and in the central nervous system it has been mostly associated with homeostatic processes, such as thirst, hormone secretion and thermoregulation. Epilepsies are chronic neurological disorders characterized by recurrent epileptic seizures that affect 1-3% of the world’s population, and the most commonly used anticonvulsants are described to be effective for ≈70% of the population with this neurological alteration. Using a rat model of epilepsy we found that components of the RAS, namely angiotensin I converting enzyme (ACE) and the angiotensin type 1 (AT1) receptor are upregulated in the brain (2.6- and 8.2-fold, respectively) following repetitive seizures. ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3647858 Wed, 09 Jun 2010 23:00:00 +0100 3647858 http://www.medworm.com/index.php?rid=3647859&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100110 Patients with chronic heart failure (HF) experience muscle atrophy during the course of the disease. The mechanisms underlying muscle atrophy in HF, however, are not understood. Thus, we evaluated leg phenylalanine balance and kinetics in HF patients and controls following a brief fast (24 hr) and under euglycemic-hyperinsulinemic-hyperaminoacidemic conditions to determine if HF increases muscle protein catabolism in response to nutritional deprivation and/or diminishes the anabolic response to meal-related stimuli (insulin and amino acids) and whether alterations in protein metabolism correlate to circulating cytokine levels. No differences in phenylalanine balance, rate of appearance or rate of disappearance were found between patients and controls under fasting conditions. However, the ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3647859 Tue, 08 Jun 2010 23:00:00 +0100 3647859 http://www.medworm.com/index.php?rid=3644169&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20090554 AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and AT1 receptor are associated with the inflammatory process and microvascular dysfunction of AKI (acute kidney injury) induced by renal I (ischemia) and R (reperfusion). However, Ang(1-7) (angiotensin-(1-7)), ACE2 and Mas receptor also play a role in renal disease models. Therefore, in this study we have examined the renal profile of Ang(1-7), ACE2 and Mas receptor in renal I/R and compared to AngII, ACE and AT1 receptor. Male Wistar rats were submitted to left nephrectomy and I (45 min) followed by R (2 or 4 h) in the right kidney. At 4 h of R, renal AngII was increased (p < 0.01) and renal Ang(1-7) intensively decreased (p < 0.05), although plasma levels of both angiotensins were unchanged. In addition, renal I/R decre... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3644169 Mon, 07 Jun 2010 23:00:00 +0100 3644169 http://www.medworm.com/index.php?rid=3640130&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100230 In this study we show that long-lived postnatal low protein (PLP) mice were protected from developing albuminuria whereas short-lived recuperated mice demonstrated an age-dependent increase in albuminuria in old age. Microarray analysis of 21 day old kidneys revealed that gene expression profiles were differentially affected depending on whether protein restriction was imposed during pregnancy or lactation. The differentially expressed genes were involved in diverse biological functions such as cytoprotective functions, vitamin D synthesis, protein homeostasis, regulation of antioxidant enzymes and cellular senescence. Significantly, up-regulation of heme oxygenase 1 in PLP kidneys suggests that tissues of long-lived mice are equipped with a better cytoprotective function. In contrast up-r... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3640130 Mon, 07 Jun 2010 23:00:00 +0100 3640130 http://www.medworm.com/index.php?rid=3640131&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100043 We examined gene expression in whole blood of 12 patients with coronary artery disease (CAD) and 12 healthy control subjects. Furthermore, 10 patients with CAD underwent whole blood gene expression analysis before and after completion of a cardiac rehabilitation programme following surgical coronary revascularisation. mRNA and miRNA were isolated for expression profiling. Gene expression analysis identified 365 differentially expressed genes in CAD vs controls (175 up and 190 down regulated in CAD), and 645 in CAD rehabilitation patients (196 up and 449 down regulated post rehabilitation). Biological pathway analysis identified a number of canonical pathways, including oxidative phosphorylation and mitochondrial function, as being significantly and consistently modulated across the groups.... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3640131 Sun, 06 Jun 2010 23:00:00 +0100 3640131 http://www.medworm.com/index.php?rid=3628845&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100003 This study included 66 patients with CAD and 33 subjects without CAD (non-CAD). Patients with CAD were randomized to 12 months of combined treatment with atorvastatin and telmisartan (ARB) or atorvastatin and enalapril (ACEI). Peripheral blood mononuclear cells (PBMCs) were obtained from peripheral blood at baseline and after 12 months. Levels of miR-146a / b, IRAK1, TRAF6 and TLR4 were significantly higher in the CAD group than in the non-CAD group (all P < 0.01). Levels of miR-146a / b were positively correlated with IRAK1 and TRAF6 levels. After 12 months of treatment, these levels were markedly decreased in the ARB and ACEI groups, with the decrease in the ARB group being greater than that in the ACEI group (all P < 0.05). In our 12-month follow-up study, high levels of miR-146a... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3628845 Thu, 03 Jun 2010 23:00:00 +0100 3628845 http://www.medworm.com/index.php?rid=3628844&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100008 Conclusion: Adiponectin levels are decreased in patients with NAFLD. Adiponectin levels correlate positively with surrogate markers of hepatic fibrosis (transient elastography, fasting serum bile acids and hyaluronate) and are significantly elevated in case of cirrhosis. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3628844 Thu, 03 Jun 2010 23:00:00 +0100 3628844 http://www.medworm.com/index.php?rid=3624750&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100151 In conclusion, our results suggest that rs4065 might be a previously unknown genetic risk factor for MI in Chinese Han population. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3624750 Wed, 02 Jun 2010 23:00:00 +0100 3624750 http://www.medworm.com/index.php?rid=3624749&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100066 Appropriate blood vessel function is important to cardiovascular health. Adipose tissue plays an important role in metabolic homeostasis. Subcutaneous abdominal ATBF (adipose tissue blood flow) is responsive to nutritional stimuli. This response is impaired in obesity, suggesting parallels with endothelial function. We assessed whether regulation of ATBF is related to the regulation of endothelial function, assessed by FMD (flow-mediated vasodilatation) of the brachial artery. Impaired FMD is a marker of atherosclerotic risk so we also assessed relationships between ATBF and a marker of atherosclerosis, common carotid artery IMT (intima-media thickness). Since ATBF is responsive to sympatho-adrenal stimuli we also investigated relationships to HRV (heart rate variability). Seventy-nine hea... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3624749 Wed, 02 Jun 2010 23:00:00 +0100 3624749 http://www.medworm.com/index.php?rid=3620921&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100087 Abnormal glucocorticoid metabolism contributes to vascular dysfunction and cardiovascular disease. Cortisol activation of vascular mineralocorticoid and glucocorticoid receptors is regulated by 11-β hydroxysteroid dehydrogenase type 2 and type 1, respectively (11β-HSD2, 11β-HSD1). We hypothesized that inhibition of 11β-HSD would attenuate vascular function in healthy humans. Fifteen healthy subjects were treated with the selective 11β-HSD inhibitor glycyrrhetic acid or matching placebo in a randomized, double-blinded crossover trial. 11β-HSD activity was assessed by the ratio of urinary cortisol:cortisone, and vascular function was measured using strain-gauge plethysmography. Endothelial function was measured through incremental brachial artery adm... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3620921 Mon, 31 May 2010 23:00:00 +0100 3620921 http://www.medworm.com/index.php?rid=3606869&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100161 The aim of this study was to compare the effect of pioglitazone or glimepiride on erythrocyte deformability in T2DM. The study covered 23 metformin treated T2DM patients with an HbA1c above 6.5%. Patients were randomized to receive either 15 mg Pioglitazone (PIO) bid. or 1 mg Glimepiride (GLIM) bid. in combination with 850 mg Metformin bid. for 6 months. Blood samples were taken for the measurement of fasting glucose, HbA1c, fasting insulin, intact proinsulin, adiponectin, and heamatocrit (Hct). In addition, the erythrocyte elongation index (EI) was measured using laserdiffractoscopy. Both treatments significantly improved HbA1c levels (PIO -0.9 ± 1.1%; GLIM -0.6 ± 0.4%; p<0.05 respectively) and end up in comparable HbA1c levels after 6 months (PIO 6.5 ± 1.2; GLI... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3606869 Thu, 27 May 2010 23:00:00 +0100 3606869 http://www.medworm.com/index.php?rid=3602881&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100113 Although pioglitazone, a PPAR-γ agonist, was shown to prolong survival of two rapidly progressive pkd1 knock-out mice models through disparate mechanisms, these studies lacked data on therapeutic strategy and long-term safety because of a short observation period. Here we used another potent PPAR-γ agonist, rosiglitazone, to treat Han:SPRD rats, a slowly progressive ADPKD animal model, and confirmed that short-term treatment was able to delay the progression of kidney cysts and protect renal function, which may relate to down-regulating the abnormally activated β-catenin signaling pathway and its anti-inflammatory, anti-fibrosis effects. Long-term administration was able to prolong the survival of SPRD rats significantly. Moreover, early therapy on rats with normal ren... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3602881 Wed, 26 May 2010 23:00:00 +0100 3602881 http://www.medworm.com/index.php?rid=3588503&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100266 This study demonstrates that transient over-expression of STARD3 (MLN64), endosomal cholesterol transporter and member of the ‘START’ family of lipid trafficking proteins, induces significant increases in macrophage ATP binding cassette transporter A1 (ABCA1) mRNA and protein, enhances [3H]cholesterol efflux to apolipoprotein (apo)AI, and reduces biosynthesis of cholesterol, cholesteryl ester, fatty acids, triacylglycerol and phospholipids from [14C]acetate, compared with controls. Notably, over-expression of STARD3 prevents increases in cholesterol esterification in response to acetylated LDL, blocking cholesteryl ester deposition. Thus, enhanced endosomal trafficking via STARD3 induces an anti-atherogenic macrophage lipid phenotype, positing a potentially therapeutic strate... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3588503 Thu, 20 May 2010 23:00:00 +0100 3588503 http://www.medworm.com/index.php?rid=3563268&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100153 Conclusion Statin treatment did not impede exercise performance or tolerance, mitochondrial function or mass. In addition, training-induced improvements in glucose homeostasis were preserved in ST. Strikingly, the insulin sensitizing effect of training was more prominent in ST than in C. The combined prescription of statins along with exercise training is safe and should be considered for subjects prone to develop insulin resistance. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3563268 Wed, 12 May 2010 23:00:00 +0100 3563268 http://www.medworm.com/index.php?rid=3551648&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20090536 Our study examines, in mesenteric resistance arteries, possible vasodilation alterations, and the role of NO and COX-derivates in cirrhosis. Vasodilator response to acetylcholine was analysed in segments from control and cirrhotic rats. The effects of the unspecific COX inhibitor indomethacin, of the specific COX-1 inhibitor SC-560 and of the specific COX-2 inhibitor NS-398 were analysed in segments from both groups of rats. NO release was measured and eNOS, phosphorylated eNOS (P-eNOS), iNOS, COX-1 and COX-2 expressions were also analysed. The effects of TP receptor antagonist SQ 29548, TxA2 synthesis inhibitor furegrelate, of PGI2 synthesis inhibitor TCP or of TCP-plus-furegrelate were only determined in segments from cirrhotic rats. Vasodilator response to acetylcholine was higher in se... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3551648 Mon, 10 May 2010 23:00:00 +0100 3551648 http://www.medworm.com/index.php?rid=3541854&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100084 Hypoxic injury to cardiomyocytes is a stress that causes cardiac pathology through cardiac-restricted gene expression. Serum response factor (SRF) and myocardin are important for cardiomyocyte growth and differentiation in response to myocardial injuries. Previous studies indicated that angiotensin II (Ang II) stimulated both myocardin expression and cardiomyocyte hypertrophy. We evaluated the expression of myocardin and Ang II after hypoxia in regulating genetic transcription to neonatal cardiomyocytes. Cultured rat neonatal cardiomyocytes experienced hypoxia, and the expression of myocardin and Ang II were evaluated. Different signal transduction inhibitors were used to identify the pathway of myocardin expression. Electrophoretic motility shift assay (EMSA) was used to identify the bind... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3541854 Wed, 05 May 2010 23:00:00 +0100 3541854 http://www.medworm.com/index.php?rid=3529140&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100234 This study suggests that even in patients with extra-cardiac diseases, high-sensitive troponin assays could lead to better risk stratification of patients in whom conventional cTnI assays show values within the 'normal range'. These data support the hypothesis that increased levels of cTnI and cTnT are an index of cardiac tissue damage even in patients with extra-cardiac diseases, thus enabling appropriate diagnosis and, when necessary and available, specific treatment. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3529140 Mon, 03 May 2010 23:00:00 +0100 3529140 http://www.medworm.com/index.php?rid=3507503&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100015 Previous evidences support the concept that increased oxidative stress may play an important role in the metabolic syndrome (MetS)-related manifestations. Dietary fat quality has been proposed to be critical in oxidative stress and the pathogenesis of the MetS. We investigated whether oxidative stress parameters are affected by diets with different fat quantity and quality during the postprandial state in subjects with the MetS. Patients were randomly assigned to one of four isoenergetic diets distinct in fat quantity and quality: high-saturated fatty acid (HSFA); high-monounsaturated fatty acid (HMUFA) and two low-fat, high complex carbohydrate (diets, supplemented with 1.24 g/day of long chain n-3 polyunsaturated fatty acid (LFHCC n-3) or with placebo (LFHCC) for 12 weeks. HMUFA diet enh... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3507503 Sun, 25 Apr 2010 23:00:00 +0100 3507503 http://www.medworm.com/index.php?rid=3501178&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100061 In conclusion, all treatments were effective in controlling metabolic syndrome. The best results were achieved using Telmisartan and Sitagliptin as monotherapies or as a dual treatment, combining partial PPAR-gamma agonism and PPAR-alpha activation in the liver with extended incretin action. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3501178 Thu, 22 Apr 2010 23:00:00 +0100 3501178 http://www.medworm.com/index.php?rid=3493717&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100014 Conclusions. In pulmonary hypertension patients, the novel biomarker high-sensitive troponin T is associated with death and advanced WHO class, and related to systolic right ventricular dysfunction and impaired six minute walk distance. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3493717 Wed, 21 Apr 2010 23:00:00 +0100 3493717 http://www.medworm.com/index.php?rid=3490016&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20090656 In conclusion, the A allele of rs3766871 in RyR2 not only associates with ventricular arrhythmias but also serves as an independent predictor of sudden cardiac death, and the A allele of rs790896 in RyR2 is a protective factor against sudden cardiac death in patients with chronic heart failure. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3490016 Tue, 20 Apr 2010 23:00:00 +0100 3490016 http://www.medworm.com/index.php?rid=3462974&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100011 Inflammation and extracellular matrix (ECM) remodeling play important roles in left ventricular (LV) remodeling following acute myocardial infarction (MI). Previous studies show elevated plasma matrix metalloproteinase (MMP) levels in patients with acute MI, but their sources are not clear. The recruitment of mononuclear cells into the infarcted myocardium is critical for inflammatory responses, but their exact roles in LV remodeling are not fully investigated since it is difficult to isolate and study the function of regional inflammatory cells. To address these questions, we isolated peripheral blood mononuclear cells (PBMCs) from blood samples of patients with acute MI or stable angina or healthy controls (n=14, 8, 12, respectively). PBMCs were cultured for 24 h and MMP-9 level ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3462974 Mon, 12 Apr 2010 23:00:00 +0100 3462974 http://www.medworm.com/index.php?rid=3453070&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20090634 In conclusion these results demonstrated that low (<2 pg/ml) circulating levels of IL-6, as present in non-inflamed ESRD patients, are sufficient to activate some inflammatory pathways and can differently regulate hepcidin and fetuin-A gene expression. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3453070 Thu, 08 Apr 2010 23:00:00 +0100 3453070 http://www.medworm.com/index.php?rid=3403197&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20090559 Tetrahydrobiopterin (BH4) supplementation improves endothelial function in models of vascular disease by maintaining endothelial nitric oxide synthase coupling and nitric oxide bioavailability. However, the cellular mechanisms through which enhanced endothelial function leads to reduced atherosclerosis remain unclear. We have used a pharmaceutical BH4 formulation to investigate the effects of BH4 supplementation on atherosclerosis progression in ApoE-KO mice. Single oral dose pharmacokinetic studies revealed rapid BH4 uptake into plasma and organs. Plasma BH4 levels returned to baseline by 8 hours after oral dosing, but remained markedly increased in aorta at 24 hours. Daily oral BH4 supplementation in 8 week old chow-fed ApoE-KO mice for 8 or 12 weeks had no effect on plasma lipids or ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3403197 Thu, 25 Mar 2010 00:00:00 +0100 3403197 http://www.medworm.com/index.php?rid=3377663&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20100096 This study was designed to determine the validity of measurement of Nε-(Carboxymethyl)Lysine (CML) levels in ELF for the assessment of small airways inflammation in COPD. Ten non-smokers, 10 current smokers, and 16 COPD patients were included in this study. Concentrations of CML, 8-isoprostane, and interleukin-8 (IL-8) were measured in ELF separately from the central or peripheral airways. CML levels in central airways did not significantly differ, but were markedly higher in peripheral than in central airways in the three groups. However, CML levels in peripheral airways of COPD patients were significantly higher than those in non-smokers and current smokers. In COPD patients, CML level in peripheral airways was significantly correlated with FEV1 (r = -0.82, p = 0.002) and FEV1/FVC... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3377663 Thu, 18 Mar 2010 00:00:00 +0100 3377663 http://www.medworm.com/index.php?rid=3358223&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20090661 Conclusions: We identified functionally active HCV core-specific Tregs in patients with chronic hepatitis C, which share their epitopes with conventional T cells and require the continued presence of antigen to maintain their functional differentiation. Thus, HCV core-specific Tregs may contribute to the immunoregulatory balance in chronic hepatitis C. (Source: Clinical Science) Clinical Science journals http://www.medworm.com/rss/comments.php?id=3358223 Fri, 12 Mar 2010 00:00:00 +0100 3358223 http://www.medworm.com/index.php?rid=3349681&cid=s_37623_61_f&fid=37623&url=http%3A%2F%2Fwww.clinsci.org%2Fcs%2Fimps%2Frefer.htm%3FMSID%3DCS20090645 MicroRNAs (miRNAs) precipitate in many diseases including cardiovascular disease. In contrast to our original thought, miRNAs exist in circulating blood and they are relatively stable due to binding with other materials. The current translational study is to establish a method to determine the absolute amount of a miRNA in blood and to determine the potential applications of circulating cell-free microRNA-1 (miR-1) in acute myocardial infarction (AMI). The results revealed that miR-1 is the most abundant miRNA in the heart and is also a heart and muscle specific miRNA. In a cardiac cell necrosis model induced by Triton-100 in vitro, we found that cardiac miR-1 can be released into cultured medium and is stable at least for 24 h. In a rat model of AMI induced by coronary ligation, we found ... Clinical Science journals http://www.medworm.com/rss/comments.php?id=3349681 Wed, 10 Mar 2010 00:00:00 +0100 3349681