Clinical Science via MedWorm.com

Increased levels of N{epsilon}-(Carboxymethyl)Lysine in epithelial lining fluid from peripheral airways in patients with chronic obstructive pulmonary disease: a pilot study

Clinical Science — Thu, 18 Mar 2010 00:00:00 +0100

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...

Core-specific adaptive regulatory T cells in different outcomes of hepatitis C

Clinical Science — Fri, 12 Mar 2010 00:00:00 +0100

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)

A translational study of circulating cell-free microRNA-1 in acute myocardial infarction

Clinical Science — Wed, 10 Mar 2010 00:00:00 +0100

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 ...

Increased plasma concentrations of anterior gradient 2 protein are positively associated with ovarian cancer

Clinical Science — Fri, 05 Feb 2010 00:00:00 +0100

Ovarian cancer is often asymptomatic and is diagnosed at an advanced stage with poor survival rates, thus, there is an urgent need to develop biomarkers for earlier detection of ovarian cancer. Here, we demonstrate for the first time that the previously-reported metastasis-inducing protein, anterior gradient protein 2 (AGR2), can be detected in the blood of ovarian cancer patients. Using a newly developed ELISA test, we show significantly increased concentrations of AGR2 protein in plasma from cancer patients relative to normal controls. Plasma AGR2 concentrations were highest in stage II and stage III ovarian cancer patients and were similarly elevated in patients with both serous and non-serous tumours. The identification of elevated plasma concentrations of AGR2 may provide a useful bio...

Administration of a low dose of sildenafil for one week decreases intrahepatic resistance in rats with biliary cirrhosis: The role of NO bioavailability

Clinical Science — Fri, 05 Feb 2010 00:00:00 +0100

Conclusions: Sildenafil treatment improves endothelial dysfunction by augmenting NO bioavailability in hepatic microcirculation. (Source: Clinical Science)

Myriocin-mediated upregulation of hepatocyte apoA-I synthesis is associated with ERK inhibition

Clinical Science — Tue, 26 Jan 2010 00:00:00 +0100

Sphingolipids including sphingomyelin have been implicated as potential atherogenic lipids. Studies in apolipoprotein-E (apoE) null mice have revealed that the serine palmitoyl transferase inhibitor myriocin reduces plasma levels of sphingomyelin, ceramide, sphingosine-1-phosphate and glycosphingolipids, and that this is associated with potent inhibition of atherosclerosis. Interestingly, hepatic apolipoprotein A-I (apoA-I) synthesis and plasma high density lipoprotein cholesterol levels were also increased in apoE null mice treated with myriocin. Since myriocin is a known inhibitor of ERK phosphorylation, we assessed the possibility that myriocin may be acting to increase hepatic apoA-I production via this pathway. To address this, HepG2 cells and primary mouse hepatocytes were treated wi...

Angiotensin II infusion promotes ascending aortic aneurysms: attenuation by CCR2 deficiency in apoE -/- mice

Clinical Science — Fri, 15 Jan 2010 00:00:00 +0100

Angiotensin II (AngII) induces atherosclerosis and abdominal aortic aneurysms (AAA) through multiple proposed mechanisms, including chemotaxis. Therefore, we determined the effects of whole body deficiency of the chemokine receptor, CCR2, on these diseases. To meet this objective, apoE -/- mice, that were either CCR2 +/+ or -/-, were infused with either saline or AngII (1,000 ng/kg/min) for 28 days via mini-osmotic pumps. Deficiency of CCR2 markedly attenuated both atherosclerosis and AAAs, unrelated to systolic blood pressure or plasma cholesterol concentrations. During the course of this study, we also observed that AngII infusion led to large dilations that were restricted to the ascending aortic region of apoE -/- mice. The aortic media in most of the dilated area was thi...

Reduced nephron endowment due to fetal uninephrectomy impairs renal sodium handling in male sheep

Clinical Science — Tue, 12 Jan 2010 00:00:00 +0100

This study investigated whether a nephron deficit, induced by fetal uninephrectomy at 100d gestation (term=150 days), resulted in 1) altered renal sodium handling both under basal conditions and in response to an acute 0.9% saline load, (50 ml/kg/30minutes); 2) hypertension; and 3) altered expression of renal channels/transporters in male sheep at 6 months of age. Uninephrectomised animals had significantly elevated arterial pressure (90.1±1.6 vs 77.8±2.9; P<0.001) whilst glomerular filtration rate and renal blood flow (per gram of kidney weight) were 30% lower than that of the sham animals. Total kidney weight was similar between the groups. Renal gene expression of apical NHE3, ENaC (β and γ) subunits and basolateral Na+/K+ ATPase (β an...

Impact of catheter insertion using the radial approach on vasodilation in humans

Clinical Science — Fri, 08 Jan 2010 00:00:00 +0100

The aim of this study was to determine the impact of catheter sheath insertion, a model of endothelium disruption in humans, on the conventional flow-mediated dilation (FMD) response in vivo. Seventeen subjects undergoing transradial catheterization were recruited and assessed prior to, the day after, and 3-4 months post-catheterization. The catheter sheath’s external diameter was 27mm and the average pre-procedure internal radial artery diameter was 28mm, indicating a high likelihood of endothelial denudation as a consequence of sheath placement. Radial artery flow-mediated and endothelium-derived nitric oxide (NO)-dependent function (FMD) was assessed within the region of sheath placement (sheath site) and also above the sheath (catheter site). Glyceryl trinitrate (GTN) endotheliu...

Fenofibrate improves endothelial function in the brachial artery and forearm resistance arterioles of statin-treated type 2 diabetic patients

Clinical Science — Tue, 05 Jan 2010 00:00:00 +0100

Dyslipidemia contributes to endothelial dysfunction and cardiovascular disease (CVD) in type 2 diabetes mellitus. While statin therapy reduces CVD in these patients, residual risk remains high. Fenofibrate corrects atherogenic dyslipidemia, but it is unclear whether adding fenofibrate to statin therapy lowers CVD risk. We investigated whether fenofibrate improves endothelial dysfunction in statin-treated type 2 diabetic patients. In a crossover study, 15 statin-treated type 2 diabetic patients, with LDL-cholesterol <2.6mmol/L and endothelial dysfunction (brachial artery flow-mediated dilatation (FMD) <6.0%), were randomized, double-blind, to fenofibrate 145mg/day or matching placebo for 12 weeks, with 4 weeks washout between treatment periods. Brachial artery FMD and endothelium-inde...

Combined inhibition of 20-hydroxyeicosatetraenoic acid formation and of epoxyeicosatrienoic acids degradation attenuates hypertension and hypertension-induced end-organ damage in Ren-2 transgenic rats

Clinical Science — Tue, 05 Jan 2010 00:00:00 +0100

Recent studies have shown that the renal cytochrome P-450 metabolites of arachidonic acid: the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE), and the vasodilator epoxyeicosatrienoic acids (EETs) play an important role in the pathophysiology of angiotensin II (ANG II)-dependent forms of hypertension and the associated target organ damage. The present studies were performed in Ren-2 renin transgenic rats (TGR) to evaluate the effects of chronic selective inhibition of 20-HETE formation or elevation of the level of EETs, alone or in combination, on the course of hypertension and hypertension-associated end-organ damage. Both young (30 days of age) prehypertensive TGR and adult (190 days of age) TGR with established hypertension were examined. Normotensive Hannover Sprague-Dawley (...

{beta}-arrestin 1 contributes to primary biliary cirrhosis

Clinical Science — Mon, 21 Dec 2009 00:00:00 +0100

This study broadens the correlation of barr1 overexpression in experimental allergic encephalomyelitis and multiple sclerosis to a third autoimmune disease, PBC. Further investigations on barr1 modulation in autoimmune disease are warranted. (Source: Clinical Science)

Effects of GIK (glucose-insulin-potassium) on stress-induced myocardial ischemia

Clinical Science — Tue, 15 Dec 2009 00:00:00 +0100

Despite the evidence in experimental animal models that insulin - or GIK (glucose-insulin-potassium) - improves left ventricular function and perfusion during both acute and chronic ischaemia, clinical studies have generated conflicting results. We tested the hypothesis that pretreatment with GIK attenuates the vascular and functional effects of stress-induced myocardial ischaemia in man. Twenty-two patients with evidence of inducible myocardial ischaemia were enrolled; 11 patients with normal ventricular function underwent two dypiridamole echocardiography tests and 11 with regional contractility defects from previous myocardial infarction were submitted to two ECG exercise tests combined with 201Tl myocardial perfusion scintigraphy; the tests were preceded by 60 minutes of either normal ...

Ethanol -induced vasoconstriction is mediated via redox-sensitive, cyclooxygenase-dependent mechanisms.

Clinical Science — Thu, 03 Dec 2009 00:00:00 +0100

The present study investigated the role of reactive oxygen species (ROS) and cyclooxygenase in ethanol-induced contraction and elevation of intracellular Ca2+ ([Ca2+]i). Vascular reactivity experiments, using standard muscle bath procedures, showed that ethanol (1 – 800 mmol/l) induced contraction in endothelium-intact (EC50: 306 ± 34 mmol/l) and denuded (EC50: 180 ± 40 mmol/l) rat aortic rings. Endothelial removal enhanced ethanol-induced contraction. Pre-incubation of intact rings with L-NAME (non selective NOS inhibitor, 100 μmol/l), 7-nitroindazole (selective nNOS inhibitor, 100 μmol/l), oxyhaemoglobin (NO scavenger, 10 μmol/l) and ODQ (selective inhibitor of guanylyl cyclase enzyme inhibitor, 1 μmol/l) increased ethanol-in...

Countervailing vascular effects of rosiglitazone in high cardiovascular risk mice: Role of oxidative stress and PRMT-1

Clinical Science — Tue, 01 Dec 2009 00:00:00 +0100

We tested the hypothesis that the PPAR-γ activator rosiglitazone improves vascular structure and function in aged hyperhomocysteinemic methylene tetrahydrofolate reductase gene (MTHFR) heterozygous knockout mice (mthfr+/-) fed a high cholesterol diet (HCD), a model of high cardiovascular risk. One year-old mthfr+/- were fed or not HCD (6 mg/Kg/day) and treated or not with rosiglitazone (20 mg/Kg/day) for 90 days, and compared to wild-type mice. Endothelium dependent relaxation of carotid arteries was significantly impaired (-40%) only in rosiglitazone treated HCD-fed mthfr+/-. Carotid media-to-lumen ratio (M/L) and cross-sectional area (CSA) were increased (2-fold) in mthfr+/- fed or not HCD compared to wild-type mice (P<0.05). Rosiglitazone reduced M/...

Hypoxia and non alcoholic fatty liver disease

Clinical Science — Tue, 10 Nov 2009 00:00:00 +0100

Non alcoholic fatty liver disease (NAFLD) represents a spectrum of fatty liver diseases associated with increased risk of type 2 diabetes and cardiovascular disease. The spectrum of fatty liver diseases, comprises simple steatosis, steatosis with inflammation (i.e. non alcoholic steatohepatitis or NASH), fatty liver disease with inflammation and fibrosis (severe NASH) and cirrhosis. The molecular mechanisms contributing to NASH are the subject of considerable investigation, as a better understanding of the pathogenesis of NASH will lead to novel therapies for a condition that hitherto remains difficult to treat. In this edition of the Journal Piquet et al have investigated the effects of hypoxia in the PTEN deficient mouse, a mouse model that develops NAFLD. Piquet et al show that a short ...

Effects of auricular electrical stimulation on vagal activity in healthy men: Evidence from a three-armed randomized trial

Clinical Science — Mon, 09 Nov 2009 00:00:00 +0100

The activity of the vagus nerve is negatively associated with risk factors such as stress and smoking, morbidity, and mortality. In contrast it is also a target of therapeutic intervention. Vagus nerve stimulation is used in depression and epilepsy. Due to its high invasivity and exclusive application to therapy-resistant patients, there is interest in less invasive methods affecting the vagus nerve. Several studies examining acupuncture report beneficial effects on vagal activity. However, findings are inconsistent and applied methods are heterogeneous resulting in difficulties in interpretation. The purpose of the present study was evaluation of the effects of acupuncture on vagal activity in a three-armed randomized trial while controlling several disturbing factors. Fourteen healthy me...

Clopidogrel application: beyond coronary artery disease

Clinical Science — Wed, 04 Nov 2009 00:00:00 +0100

Dual antiplatelet therapy with aspirin and clopidogrel, a P2Y12 antagonist, is a cornerstone for treatment of patients with stroke, peripheral arterial disease, and acute coronary artery disease followed with or without percutaneous coronary intervention. Giachini and colleagues found that clopidogrel could normalize the increased phenylephrine-induced vascular contraction and impaired acetylcholine-induced vasodilatation in mesenteric arteries from angiotensin II-infused Sprague-Dawley rats. This might develop a new area for clopidogrel application. However, whether clopidogrel can improve the arterial function in patients with hypertension or diabetes, or whether clopidogrel outweighs the beneficial effect aspirin in those patients, remains an open field for future inquiry. (Source: Clin...

Early life nutrition influences thymic growth in male mice that may be related to the regulation of longevity

Clinical Science — Thu, 29 Oct 2009 00:00:00 +0100

Nutrition and growth rate during early life can influence later health and lifespan. We previously demonstrated that low birth weight resulting from maternal protein restriction during pregnancy followed by catch-up growth in rodents was associated with shortened lifespan whereas protein restriction and slow growth during lactation increased lifespan. The underlying mechanisms by which these differences arise are unknown. Here we report that maternal protein restriction in mice influences thymic growth in early adult life. Offspring of dams fed a low protein diet during lactation (PLP offspring) showed significant thymic growth from 21 days to 12 weeks of age whereas this was not observed in control mice or offspring of dams fed a low protein diet during pregnancy (recuperated offspring). ...

The development of hepatic fibrosis occurs normally in AMPK deficient mice

Clinical Science — Mon, 26 Oct 2009 00:00:00 +0100

Inhibition or blockade of hepatic stellate cells (HSCs), the main matrix producing cells involved in would healing response, represents an attractive strategy for the treatment of liver fibrosis. In vitro studies have shown that activation of the AMP-activated protein kinase (AMPK), a key player in the regulation of cellular energy homeostasis, inhibits proliferation of myofibroblasts derived from HSC. If AMPK is a true regulator of fibrogenesis then defective AMPK activity would enhance fibrogenesis and hepatic fibrosis. To test this, in vitro studies were performed on mouse primary HSCs treated or not with AMPK activator AICAR or isolated from mice lacking the AMPKα1 catalytic subunit (AMPKα1-/-) or their littermates (AMPKα1+/+). Liver fibrosis was indu...

Central and cerebrovascular effects of leg crossing in humans with sympathetic failure

Clinical Science — Thu, 15 Oct 2009 23:00:00 +0100

In conclusion, leg crossing improves cerebral perfusion and oxygenation both in patients with sympathetic failure and in healthy subjects. However, in healthy subjects cerebral perfusion and oxygenation improve by a rise in CO without significant changes in TPR or MAP, whereas in patients with sympathetic failure cerebral perfusion and oxygenation improve through a rise in MAP due to increments in both CO and TPR. (Source: Clinical Science)

Hypoxia aggravates nonalcoholic steatohepatitis in mice lacking hepatocellular PTEN

Clinical Science — Wed, 14 Oct 2009 23:00:00 +0100

Conclusion. The findings demonstrate that hypoxia alone aggravates and accelerates the progression of NASH by upregulating the expression of lipogenic genes, by down-regulating genes involved in lipid metabolism and by decreasing insulin sensitivity. (Source: Clinical Science)

Prognostic value of admission blood glucose concentration and diabetes diagnosis on survival after acute myocardial infarction; Results from 4702 index cases in routine practice

Clinical Science — Mon, 12 Oct 2009 23:00:00 +0100

The diagnosis of diabetes and admission blood glucose concentration are associated with adverse outcome after acute coronary syndromes. We compared the relative association with survival after ST-elevation acute myocardial infarction of admission blood glucose concentration and of diabetes diagnosis. We carried out a retrospective cohort study in 4702 consecutive patients with ST elevation AMI (STEMI) occurring April 1st 1993 - December 31st 2005, assessed for mortality at 30 days and 1 year. Patients were classified according to antecedent diabetes, and by blood glucose concentration at admission (quartile 1, <7mmol/L; quartile 2, 7 - 8.2 mmol/L; quartile 3, 8.3 - 10.9 mmol/L; quartile 4, ≥11 mmol/L). Multivariable models were constructed for determinants of mortality, includi...

Clopidogrel, independent of vascular P2Y12 receptor, improves the arterial function in small mesenteric arteries from Ang II-hypertensive rats

Clinical Science — Tue, 06 Oct 2009 23:00:00 +0100

The P2Y12 receptor antagonist clopidogrel blocks platelet aggregation, improves systemic endothelial nitric oxide bioavailability, and has anti-inflammatory effects. Since P2Y12 receptors have been identified in the vasculature, we hypothesized that clopidogrel ameliorates angiotensin II (Ang II) -induced vascular functional changes by blockade of P2Y12 receptors in the vasculature. Male Sprague Dawley rats were infused with Ang II (60 ng.min-1) or vehicle for 14 days. The animals were treated with clopidogrel (10mg•kg-1•day-1) or vehicle. Vascular reactivity was evaluated in second-order mesenteric arteries. Clopidogrel treatment did not change systolic blood pressure [(mmHg) control-vehicle, 117±7.1 vs. control- Clopidogrel, 125±4.2; AngII-vehicle, 197±...

DNA damage and repair in a model of rat vascular injury

Clinical Science — Sun, 04 Oct 2009 23:00:00 +0100

Restenosis rate following vascular interventions still limits their long-term success. Oxidative stress plays a relevant role in this pathophysiological phenomenon, but less attention has been devoted to its effects on DNA damage and to the subsequent mechanisms of repair. We analysed in a model of arteriotomy-induced stenosis in rat carotids the time-dependent expression of DNA damage markers and of DNA repair genes, together with the assessment of proliferation and apoptosis indexes. The expression of the oxidative DNA damage marker 7,8-dihydro-8-oxo-2’-deoxyguanosine was increased at 3 and 7 days after arteriotomy, with immunostaining distributed in the injured vascular wall and in perivascular tissue. The expression of the DNA damage marker phospho-H2A.X was less relevant but...

Activation of a novel natriuretic endocrine system in humans with heart failure.

Clinical Science — Tue, 22 Sep 2009 23:00:00 +0100

Conclusions: Plasma proguanylin and prouroguanylin are elevated in patients with heart failure. Elevated plasma proguanylin and prouroguanylin levels are associated with hypertension, renal impairment and increasing severity of heart failure. This novel endocrine system may contribute to the pathophysiology of heart failure. (Source: Clinical Science)

Protein metabolism in leg muscle following an endotoxin injection in healthy volunteers

Clinical Science — Sun, 13 Sep 2009 23:00:00 +0100

The human endotoxin model has been used to study the early phase of sepsis. The aim of the present study was to assess leg muscle protein kinetics after an endotoxin challenge given to healthy human volunteers. Six healthy male subjects were studied in the post-absorptive state before and during 4 hours following an intravenous endotoxin bolus (4 ng / kg body weight). Primed continuous infusion of [2H5]phenylalanine and [2H3]3-methylhistidine in combination with sampling from artery, femoral vein and muscle tissue were used to assess leg muscle protein kinetics. Both 2 and 3-compartment models were used to calculate protein kinetics. In addition 26S proteasome activity and protein ubiquitination were assessed. Results showed an increased net release of phenylalanine from the leg fo...

Statins have beneficial effects on platelet free radical activity and intracellular distribution of GTPases in hyperlipidaemia

Clinical Science — Tue, 08 Sep 2009 23:00:00 +0100

Conclusion: This study shows altered nitric oxide/superoxide production following statin therapy. A potential mechanism for this is the change in distribution of intracellular GTPases which was felt to be secondary to decreases in isoprenoid intermediates, suggesting that activity of the former had been affected by atorvastatin. (Source: Clinical Science)

Obesity is the major contributor to vascular dysfunction and inflammation in high fat diet hypertensive rats

Clinical Science — Wed, 02 Sep 2009 23:00:00 +0100

Obesity and hypertension are the two major risk factors that contribute to the progression of end-stage renal disease. To examine whether hypertension further exacerbates oxidative stress and vascular dysfunction and inflammation in obese rats, four groups of male Sprague Dawley rats were fed either normal (7% fat) or high fat (36% fat) diet for 6 weeks and osmotic pumps were implanted to deliver angiotensin II (ANG) or vehicle for four additional weeks. High fat diet treatment did not alter ANG-induced hypertension compared to normal diet (174±6 vs. 170±5 mmHg, respectively). High fat diet treatment increased body weight gain and plasma leptin levels and induced insulin resistance in normotensive and ANG hypertensive rats. Plasma TBARs, a measure of oxidative stress, was ele...

Relation of circulating progenitor cells to vascular function and oxidative stress with long term training and short term detraining in older men

Clinical Science — Mon, 31 Aug 2009 23:00:00 +0100

Exercise may contribute to the maintenance of vascular function via enhanced liberation and action of bone marrow-derived progenitor cells. Activity-related changes in oxidative stress may also influence the number and function of these cells. We sought to determine whether adaptations in reactive hyperemic forearm blood flow (FBF) response associated with long-term endurance exercise and short-term detraining were related to resting putative progenitor cell number and function and to determine whether oxidative stress affected these factors. Participants included men with greater than 30 years of moderate- to high-intensity exercise (HI) history and healthy low active age- and BMI- matched control subjects (LO). Vascular reactive hyperemic FBF response, resting CD34+ and CD34...

Reduction in renal ACE2 expression in subtotal nephrectomy is ameliorated with ACE inhibition

Clinical Science — Thu, 20 Aug 2009 23:00:00 +0100

Alterations within the renin-angiotensin system (RAS) are pivotal for the development of renal disease. Angiotensin-converting enzyme (ACE) 2 is expressed in the kidney, and converts the vasoconstrictor angiotensin (Ang) II to Ang 1-7, a peptide with vasodilatory and anti-fibrotic actions. Whilst the expression of ACE2 in the diabetic kidney has been well studied, little is known about its expression in non-diabetic renal disease. We assessed ACE2 in rats with acute kidney injury induced by subtotal nephrectomy (STNx). STNx and Control rats received vehicle or ramipril (1 mg/kg/d), and measured renal ACE, ACE2 and mas receptor gene and protein expression 10 days later. STNx rats were characterised by polyuria, proteinuria, hypertension and elevated plasma ACE2 activity (all P<0.01), and...

Enhanced circulating retinol and nonesterified fatty acids in pregnancies complicated with intrauterine growth restriction

Clinical Science — Wed, 05 Aug 2009 23:00:00 +0100

In conclusion, the increased circulating retinol and NEFA in maternal plasma are negatively associated with birth and placental weights, which may reflect an impaired placental transfer in IUGR pregnancies. Since retinoids have been involved in the control of gene transcription, it is proposed that a decreased placental transfer of retinol could underlie the metabolic dysfunction of IUGR pregnancies. (Source: Clinical Science)

Exercise training reduces circulating adiponectin levels in patients with chronic heart failure

Clinical Science — Wed, 05 Aug 2009 23:00:00 +0100

Conclusions: Circulating adiponectin concentrations are higher in CHF patients compared to healthy subjects and increase with disease severity. Four months exercise training lowers circulating adiponectin levels. (Source: Clinical Science)

Regulation of resistin by cyclic mechanical stretch in cultured rat vascular smooth muscle cell

Clinical Science — Thu, 16 Jul 2009 23:00:00 +0100

In conclusion, cyclic mechanical stretch increases the resistin expression in cultured rat VSMCs. The stretch-induced resistin is mediated through ROS, p38 MAP kinase and STAT3 pathway. The resistin induced by cyclic stretch may contribute to the pathogenesis of atherosclerosis under hemodynamic overload. (Source: Clinical Science)

Homocysteine and stroke: another brick in the wall

Clinical Science — Mon, 13 Jul 2009 23:00:00 +0100

After a long debate, due to conflicting data from clinical studies, homocysteine is now largely accepted as a risk factor for cardiovascular diseases including stroke. To date, the role of elevated homocysteine values in stroke recurrences has not been evaluated and consequently we acknowledge the paper by Zhang et al. that proves that patients with high homocysteine values have an increased risk for stroke recurrence and for all-cause mortality with respect to patients with lower values. Remarkably, in their study high homocysteine values were associated with an increased risk of stroke recurrence and of all-cause mortality in patients included for an atherothrombotic stroke and an intracerebral hemorrhage but not in patients who were included for a lacunar stroke. The study by Zhang et a...

Central sympathetic outflow to skeletal muscle: the major link between non-esterified fatty acids and elevated blood pressure?

Clinical Science — Sun, 12 Jul 2009 23:00:00 +0100

Sympathetic nervous system activation is a hallmark of several conditions associated with an adverse prognosis including hypertension and the metabolic syndrome. Proposed mediators of increased sympathetic drive include hyperinsulinemia, leptin, non-esterified fatty acids (NEFA), proinflammatory cytokines, baroreflex impairment, and others. The role of NEFAs appears to be of particular importance given the increased levels observed in human obesity and the experimental data linking the NEFA induced pressor response to sympathetic activation. Data from human studies yielded conflicting results with regards to a sympathetically mediated association between NEFA and elevated arterial blood pressure. In the current issue of the journal Florian and Pawelczyk present some interesting data obtain...

Matrix Metalloproteinase-2 predicts mortality in patients with acute coronary syndrome.

Clinical Science — Tue, 07 Jul 2009 23:00:00 +0100

Conclusions This is the first single centre study that identifies MMP2 as an independent predictor of all cause mortality post ACS however, NT proBNP and the GRACE Score are superior for risk stratification in this cohort. (Source: Clinical Science)

Evaluation of the relation between hyperinsulinaemia and myocardial ischaemia-reperfusion injury in a rat model of depression

Clinical Science — Sun, 05 Jul 2009 23:00:00 +0100

In conclusion, FSL rats had larger infarct sizes and were found to be hyperinsulinaemic compared to SD rats but seemed to have a maintained cardioprotective mechanism against ischaemia-reperfusion injury as IPC reduced infarct size in these rats. This animal model may be useful in future studies when examining the mechanisms that contribute to the cardiovascular complications associated with depression. (Source: Clinical Science)

Chronic fatigue syndrome: comments on deconditioning, blood volume, and resulting cardiac function

Clinical Science — Wed, 17 Jun 2009 23:00:00 +0100

Cardiovascular and autonomic dysfunction have been suggested to underly the symptoms accompanying CFS (chronic fatigue syndrome). In the present issue of Clinical Science, Hurwitz and colleagues have investigated whether deficits were present in cardiac output and blood volume in a cohort of patients with CFS and whether these were linked to illness severity and sedentary lifestyle. The results clearly demonstrated reduced cardiac stroke volume and cardiac output in more severely afflicted patients with CFS, which is primarily attributable to a measurable reduction in blood volume. Similar findings are observed in microgravity and bedrest deconditioning, in forms of orthostatic intolerance, and to a lesser extent in sedentary people. The circulatory consequences of reduced cardiac output m...

Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats

Clinical Science — Thu, 11 Jun 2009 23:00:00 +0100

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a physiological tetrapeptide hydrolized by angiotensin converting enzyme. In experimental model of hypertension, Ac-SDKP has antifibrotic effects in the heart. The role of Ac-SDKP in diabetic cardiomyopathy is presently unknown. The aim of the study was to evaluate the effect of Ac-SDKP on cardiac systolic and diastolic function, interstitial and perivascular fibrosis in the heart of diabetic rats. Diabetes was induced in 55 Sprague Dawley rats by streptozotocin injection. Control rats (n=18) underwent only buffer injection. Out of 55 diabetic rats, 19 were chronically treated with insulin and 13 with the angiotensin converting enzyme inhibitor (ACEi), ramipril (3mg/kg/day). Two months after the onset of diabetes, Ac-SDKP (1mg/kg/day) w...

Skeletal muscle metabolic recovery following submaximal exercise in chronic heart failure is limited more by O2 delivery than O2 utilization

Clinical Science — Thu, 11 Jun 2009 23:00:00 +0100

In conclusion, prolonged metabolic recovery in CHF patients is associated with an even slower muscle tissue re-oxygenation, indicating a lower O2 delivery relative to metabolic demands. Therefore, we postulate that the impaired ability to perform repetitive daily activities in these patients depends more on a reduced muscle blood flow than on limitations in O2 utilization. (Source: Clinical Science)

Transient decrease in circulating dendritic cell precursors after acute stroke {-} potential recruitment into the brain

Clinical Science — Tue, 09 Jun 2009 23:00:00 +0100

In conclusion, acute stroke leads to a decrease in circulating DCP. Potentially, circulating DCP are recruited from the blood into the infarcted brain, and probably trigger cerebral immune reactions there. (Source: Clinical Science)

High plasma homocysteine levels contribute to the risk of stroke recurrence and all-cause mortality in a large prospective stroke population

Clinical Science — Tue, 09 Jun 2009 23:00:00 +0100

Plasma homocysteine concentration has been associated with the risk of stroke, but its relevance to secondary vascular events and mortality after stroke remains unclear because of inconsistent results from clinical trials. We aimed to investigate whether plasma homocysteine levels and methylenetetrahydrofolate reductase (MTHFR) variant C677T contributed to the risk of stroke recurrence and all-cause mortality in a large prospective cohort of stroke patients in Chinese population. A total of 1,823 stroke patients (35-74 years) were recruited during 2000-2001 and prospectively followed up for a median of 4.5 years. During the follow-up, 347 recurrent strokes and 323 deaths from all-causes were documented. After adjustment for age, gender, and other cardiovascular risk factors, high homocyste...

Reliability of heart rate variability measurements in patients with a history of myocardial infarction

Clinical Science — Tue, 09 Jun 2009 04:00:00 +0100

In this study we assessed the reliability of short-term HRV indexes in post myocardial infarction (MI) patients. We studied 61 MI patients (50 males, mean age±SD: 59±8 yrs, LVEF: 46±6 %), who underwent a 5+5min ECG recording during spontaneous and paced breathing, on two consecutive days. Standard time- (SDNN, RMSSD) and frequency-domain (LF and HF power and LF/HF) indices of HRV were computed. Absolute and relative reliability were assessed respectively by the 95% limits of random variation and by the intraclass correlation coefficient (ICC). The agreement between the two measurements in classifying patients at low or high risk, according to different cut-points, and the sample size needed to detect a clinically relevant change, were also assessed. During spon...

The haplotype of growth-differentiation factor-15 gene is associated with left ventricular hypertrophy in human essential hypertension

Clinical Science — Mon, 08 Jun 2009 04:00:00 +0100

Growth-differentiation factor-15 (GDF-15) is a novel antihypertrophic factor which is induced in the heart in response to pressure overload and plays an important regulatory role in the process of hypertrophy. We sought to access the relationship between GDF-15 gene variants and left ventricular hypertrophy in human essential hypertension. A community-based hypertensive population sample of 1527 individuals (506 men and 1,021 women) was genotyped for three GDF-15 genetic variants, including one tag-variant -3148C>G (rs4808793) and two exonic variant +157A>T (rs1059369) and +2438C>G (rs1058587). The effects of variants on gene expression were studied by use of luciferase reporter assays and by the determination of plasma GDF-15 levels. Only the tag-variant -3148G show...

Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function

Clinical Science — Tue, 26 May 2009 04:00:00 +0100

This study examined whether deficits in cardiac output and blood volume in a Chronic Fatigue Syndrome (CFS) cohort were present and linked to illness severity and sedentary lifestyle. Follow-up analyses assessed whether differences between CFS and control groups in cardiac output levels were corrected by controlling for cardiac contractility and total blood volume (TBV). The 146 participants were subdivided into two CFS groups based on symptom severity data, severe (n=30) vs. non-severe (n=26), and two healthy non-CFS control groups based on physical activity, sedentary (n=58) vs. non-sedentary (n=32). Controls were matched to CFS participants using age, sex, ethnicity and body mass. Echocardiographic measures indicated that the severe CFS participants displayed 10.2% lower cardiac volume ...

Effect of weight loss on HDL-apoA-II kinetics in the metabolic syndrome

Clinical Science — Thu, 21 May 2009 04:00:00 +0100

In conclusion, in obese men with MetS, short-term weight loss with a low-fat, low-caloric diet lowers plasma apoA-II concentration by decreasing both production and catabolism of HDL-apoA-II. The cardiometabolic significance of this effect on HDL metabolism remains to be further investigated. (Source: Clinical Science)

C type natruiretic peptide production by the human kidney is blunted in chronic heart failure

Clinical Science — Mon, 18 May 2009 04:00:00 +0100

C-type natriuretic peptide (CNP) is a vasodilatory peptide produced by vascular endothelium and human heart with a short half-life. CNP has been identified within the human kidney. Few data are available on whether the human kidney is a systemic source of CNP. The aim of the current study was to establish whether CNP is secreted by human kidney and whether synthesis is blunted in chronic heart failure (CHF). 20 male subjects (age 57±2 years, mean±SEM) undergoing CHF assessment (n=13) or investigation of paroxysmal supraventricular arrhythmia (n=7, normal left ventricular function, in sinus rhythm during procedure) were recruited. Renal CNP production was determined from concomitant plasma concentration in aorta and renal vein. When considering all subjects, a significant ste...

Delivery by Caesarean section, rather than vaginal delivery, promotes hepatic steatosis in piglets

Clinical Science — Fri, 15 May 2009 04:00:00 +0100

There has been a marked increase in the number of babies born by elective caesarean section (CS). Following CS, the lack of normal stimuli that occur at birth alters the thermogeneic response but any effects on hepatic metabolism had not been identified. We compared the effect of delivery on hepatic metabolism in piglets, born either by CS or vaginal delivery (VD) and fed by total parenteral nutrition, by measuring lipid metabolism and enzyme activity coupled with metabolomic and genomic approaches. Hepatic lipid in the CS piglets 7 days post-partum was in excess of 5mg/g of liver consistent with hepatic steatosis whereas in the VD piglets the amount of lipid was markedly lower (3mg/g) and below the threshold for a diagnosis of steatosis. Metabolomic analysis indicated that CS resulted in ...

Non-esterified fatty acids increase arterial pressure via central sympathetic activation in humans

Clinical Science — Fri, 08 May 2009 04:00:00 +0100

Previous studies have shown that acute increases in plasma non-esterified fatty acids (NEFAs) raise systemic vascular resistance (SVR) and blood pressure (BP). However, these studies fail to distinguish between central nervous system (CNS) mechanisms that raise sympathetic activity and paracrine mechanisms that increase SVR directly independent of CNS involvement. The purpose of the study was to directly determine whether the sympathetic nervous system contributes to the pressor response to NEFAs. On 2 days separated by at least 2 wks 17 lean, healthy volunteers (10M/7F; 22±1 yrs; BMI: 23±1; mean±SEM) received a 4-h i.v. infusion of Intralipid 20% or placebo (single-blind, randomized, balanced order). Muscle sympathetic nerve activity (MSNA), heart rate (HR), BP (oscil...

Limb-specific and cross-transfer effects of arm-crank exercise training in patients with symptomatic peripheral arterial disease

Clinical Science — Thu, 23 Apr 2009 04:00:00 +0100

Arm-cranking is a useful alternative exercise modality for improving walking performance in patients with intermittent claudication. However, the mechanisms of such an improvement are poorly understood. The main aim of this study was to investigate the effects of arm-crank exercise training on lower-limb oxygen delivery in patients with intermittent claudication. Fifty-seven claudicants (age 70 ± 8 y; mean ± SD) were randomised to an arm-crank exercise group or a non-exercise control group. The exercise group trained twice weekly for 12 weeks. At baseline and 12 weeks, patients completed incremental tests to maximum exercise tolerance on both an arm-crank ergometer and on a treadmill. Respiratory variables were measured breath-by-breath to determine peak oxygen uptake (peak V...

Effects of androgens on endothelial progenitor cells in vitro and in vivo

Clinical Science — Fri, 17 Apr 2009 04:00:00 +0100

Beneficial or detrimental effects of androgens on the cardiovascular system are debated. Endothelial progenitor cells are bone marrow-derived cells involved in endothelial healing and angiogenesis, which promote cardiovascular health. Estrogens are potent stimulators of endothelial progenitor cells, and previous data indicated that androgens may improve biology of these cells, as well. Herein, we show that testosterone and its active metabolite dihydrodrotestosterone exert no effects on expansion and function of late endothelial progenitors isolated from peripheral blood of healthy human adult males, while they positively modulate early "monocytic" endothelial progenitors. In parallel, we show that castration in rats is followed by a decrease in circulating endothelial progenitor cells, bu...

Long QT syndrome and associated gene mutation carriers in Japanese children: Results from ECG screening examination

Clinical Science — Thu, 16 Apr 2009 04:00:00 +0100

Conclusion: These results demonstrate that, in a random sample of healthy Japanese children, the prevalence of a high probability of LQTS is 0.038% (3/7961), and that LQTS mutation carriers can be identified in at least 0.038% (1/2653). Further, large-scale genetic studies will be needed to clarify the real prevalence of LQTS by gene carrier status, since the present study may have underestimated it. (Source: Clinical Science)

Angiotensin 1-7, an alternative metabolite of the renin-angiotensin system, is upregulated in human liver disease and has antifibrotic activity in the bile duct ligated rat

Clinical Science — Thu, 16 Apr 2009 04:00:00 +0100

Angiotensin 1-7 (Ang-(1-7)) a peptide product of the recently described angiotensin converting enzyme (ACE) homologue, ACE2, opposes the harmful actions of angiotensin II (Ang II) in cardiovascular tissues, but its role in liver disease is unknown. Our objective was to assess plasma levels of Ang-(1-7) in human liver disease and determine its effects in experimental liver fibrosis. Angiotensin peptide levels were measured in cirrhotic and non-cirrhotic patients with hepatitis C. The effects of Ang-(1-7) on experimental fibrosis were determined using the rat bile duct ligation (BDL) model. Liver histology, hydroxyproline quantification and expression of fibrosis related genes were assessed. Expression or renin-angiotensin system components and the effects of Ang-(1-7) were examined in rat h...

New statistical methods for evaluation of cardiovascular risk markers: what the clinician should know

Clinical Science — Tue, 07 Apr 2009 04:00:00 +0100

Calculation of odds ratios or hazard ratios by multivariate logistic regression or Cox regression analyses have traditionally been used to show that candidate risk markers provide prognostic information independently of conventional risk markers, but it has become increasingly clear that a statistical significant increase in risk in multivariate models may not represent a clinically meaningful improvement in overall prediction. This observation has prompted the development of more clinically relevant statistical methods, including tests of the ability to provide incremental discrimination compared to traditional risk markers by calculation of the C-statistic (corresponding to the area under the receiver-operating curve) of the model and methods for evaluating improvement in risk classifica...

Overexpression of the malate-aspartate NADH shuttle member Aralar1 in the clonal beta cell line BRIN BD11 enhances amino acid stimulated insulin secretion and cell metabolism

Clinical Science — Fri, 03 Apr 2009 04:00:00 +0100

We have investigated the effects of transduction with recombinant adenovirus AdCA-Aralar1 (aspartate/glutamate carrier 1) on the metabolism, function and secretory properties of the glucose and amino acid responsive clonal insulin secreting cell line BRIN BD11. Aralar1 overexpression increased long-term (24hr) and acute (20min) glucose and amino acid stimulated insulin secretion, cellular glucose metabolism, L-alanine and L-glutamine consumption, cellular ATP and glutamate concentrations and stimulated glutamate release. However, cellular triacylglycerol and glycogen contents were decreased as was lactate production. These data indicate that increased malate-aspartate shuttle activity positively shifted ?beta-cell metabolism, thereby increasing glycolysis capacity, stimulus-secretion coupl...

Angiopoietin-2 promotor haplotypes confer increased risk of stroke in Han Chinese

Clinical Science — Thu, 02 Apr 2009 04:00:00 +0100

Angiopoietin-2 is an important mediator of angiogenesis. We hypothesized that genetic variants of angiopoietin-2 would result in abnormal angiogenesis and contribute to stroke susceptibility. To test our hypothesis, we investigated the association of variants in the promoter of the angiopoietin-2 gene with stroke in a multi-center case-control study. We found that allele C of rs3739390 conferred a 1.42 fold risk for lacunar infarction (adjusted odds ratio [OR], 1.42 [95% confidence interval {CI}, 1.08-1.87]; P = 0.012) and a 2.10-fold higher transcriptional activity than did the corresponding G allele, rs3739390G. The haplotype G-G-T conferred a 1.54 fold risk for atherothrombotic stroke and a 1.64 fold risk for hemorrhagic stroke, while the haplotype G-C-C conferred about a 2.0-fold risk ...

Short chain fatty acids stimulate migration of neutrophils to inflammatory site

Clinical Science — Wed, 01 Apr 2009 04:00:00 +0100

In this study, the effect of the SCFAs (acetate, propionate and butyrate) on neutrophil chemotaxis and migration was investigated. Experiments were carried out in rats and in vitro. The following parameters were measured: rolling, adherence, expression of adhesion molecules in neutrophils (L-selectin and β2-integrin), transmigration, air pouch influx of neutrophils and production of cytokines (CINC-2αβ, IL-1β, MIP-1α and TNF-α). SCFAs induced in vivo neutrophil migration and increased the release of CINC-2αβ into air pouch. These fatty acids increased the number of rolling and adhered cells as evaluated by intravital microscopy. SCFAs raised L-selectin expression on neutrophil surface and L-selectin mRNA levels, but had no effect on e...

Incremental prognostic value of combining left ventricular lead position and systolic dyssynchrony in predicting long-term survival after cardiac resynchronization therapy

Clinical Science — Wed, 01 Apr 2009 04:00:00 +0100

In conclusion, the placement of LV lead at a PL position provides additional value to baseline dyssynchrony in predicting a lower all-cause and cardiovascular mortality during long-term follow up after CRT. (Source: Clinical Science)

Long-term portal hypertension increases the vasodilator response to acetylcholine in rat aorta. Role of prostaglandin I2

Clinical Science — Mon, 30 Mar 2009 04:00:00 +0100

In conclusion, the increased vasodilation to acetylcholine is maintained in long-term portal hypertension. While the participation of endothelial NO remained unmodified, the COX-2 derivate PGI2 does participate through an increased vasodilator response. (Source: Clinical Science)

Glutathione and amino acid concentrations in human liver during short warm ischemia and reperfusion: A pilot study

Clinical Science — Mon, 30 Mar 2009 04:00:00 +0100

Glutathione is a major antioxidant. In the present study we investigated if a clinical model of short warm ischemia and reperfusion of the human liver during surgery would influence glutathione and amino acid metabolism. Previous studies on man have demonstrated that ischemia and reperfusion in skeletal muscle up to 120 minutes have no major effect on muscle glutathione concentration. Liver ischemia and reperfusion in animals have demonstrated diverging results concerning glutathione metabolism. In the present study six patients with malignancies of the liver, undergoing liver resection during warm ischemia were included. Liver biopsies were obtained from healthy-appearing liver tissue from both lobes before ischemia and at maximal ischemia, and from the remaining liver lobe after 5, 10,...

Eicosapentaenoic acid stimulates AMP-activated protein kinase and increases visfatin secretion in cultured murine adipocytes

Clinical Science — Wed, 18 Mar 2009 04:00:00 +0100

Visfatin is an adipokine highly expressed in visceral adipose tissue (AT) of humans and rodents, the production of which seems to be dysregulated in excessive fat accumulation and conditions of insulin resistance. Eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid (PUFA), has been demonstrated to exert beneficial effects within obesity and insulin resistance conditions, which have been further linked to its reported ability to modulate adipokine production by adipocytes. TNF-α is a pro-inflammatory cytokine whose production is increased in obesity and involved in the development of insulin resistance. Control of adipokine production by some insulin-sensitizing compounds has been associated with the stimulation of AMP-activated protein kinase (AMPK). The aim of this study...

Sympatho-vagal responses in patients with sleep and typical vasovagal syncope

Clinical Science — Thu, 12 Mar 2009 04:00:00 +0100

Sleep syncope is a recently-described form of vasovagal syncope which interrupts sleep. The pathophysiology of this condition is uncertain but a “central” non-baroreflex mediated trigger has been suggested. We tested the hypothesis that patients with sleep syncope, have abnormal sympatho-vagal responses to non-baroreflex, but normal responses to baroreflex stimuli. We collected historical data from patients with a history of vasovagal syncope with (SS, n=16) and without sleep syncope (NSS, n=35), including demography, triggers and symptoms during syncope. We compared mean blood pressure (MBP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) in SS patients to NSS patients and matched controls (n=16) during hand grip (HG), cold pressor tests (CPT), head-up tilt (H...

Dexamethasone decreases neuronal nitric oxide release in mesenteric arteries from hypertensive rats through decreased protein kinase C activation

Clinical Science — Fri, 06 Mar 2009 05:00:00 +0100

In conclusion, results obtained here indicate that PKC activity positively modulates the neuronal NO release in MAs from SHR. They also reveal that by PKC inhibition, through activation of glucocorticoid receptors, dexamethasone reduces neuronal NO release in these arteries. (Source: Clinical Science)

Hemodialysis acutely reduces the plasma levels of asymmetric dimethylarginine (ADMA) without reversing impaired nitric oxide dependent vasodilation

Clinical Science — Thu, 05 Mar 2009 05:00:00 +0100

Patients with end stage renal disease have endothelial dysfunction and high plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO)-synthase. The actual link between these abnormalities is controversial. Therefore, we investigated whether hemodialysis (HD) impacts acutely on NO-dependent vasodilation and on plasma ADMA in these patients. Twenty-four patients undergoing maintenance HD (HD-group) and 24 age- and sex-matched healthy controls were enrolled (Control-group). The increase in forearm skin blood flow (SkBF) caused by local heating to 41°C (SkBF41), known to depend on endothelial NO production, was determined with laser Doppler imaging. SkBF41 was expressed as % of the vasodilatory reserve, obtained from the maximal SkBF induced by lo...

Circulating and muscle glutathione turnover in human endotoxemia

Clinical Science — Thu, 05 Mar 2009 05:00:00 +0100

Conclusions: During the initial phase of sepsis as represented by an intravenous endotoxin challenge to healthy volunteers, plasma concentration of total glutathione decreased, while glutathione status and synthesis rate in skeletal muscle and whole blood remained unaltered. However, due to the variation in the synthesis measures, larger studies are needed to confirm these findings. (Source: Clinical Science)

Common genetic variation in DDAH2 is associated with intracerebral hemorrhage in Chinese population: a multicenter case-control study in China

Clinical Science — Fri, 27 Feb 2009 05:00:00 +0100

Conclusions- Our results suggest that the DDAH2 common variant may play a protective role in the development of intracerebral hemorrhage, implicating that DDAH2/ADMA pathway acts as a critical regulator of cerebral small vessel disorders. (Source: Clinical Science)

Programming of growth, insulin resistance and vascular dysfunction in offspring of late gestation diabetic rats

Clinical Science — Mon, 09 Feb 2009 05:00:00 +0100

The offspring of diabetic mothers (ODM) have an increased risk of developing metabolic and cardiovascular dysfunction. However, few studies have focused on susceptibility to disease in offspring of mothers developing diabetes during pregnancy. We developed an animal model of late-gestation diabetic pregnancy and characterized metabolic and vascular function in the offspring. Diabetes was induced by streptozotocin (50 mg/kg, i.p.) in pregnant rats on gestational day 13 and partially controlled by twice-daily injections of insulin. At 2 months of age, ODM had slightly better glucose tolerance than controls (p < 0.05), however, by 6 months of age this trend reversed. Hyperinsulinemic-euglycemic clamp revealed insulin resistance in male ODM (p < 0.05). In 6-8 mo old female ODM, aortas sh...

Association between the PDE4D gene and ischemic stroke in Han Chinese population

Clinical Science — Thu, 05 Feb 2009 05:00:00 +0100

This study adds further support to the role of PDE4D in stroke. (Source: Clinical Science)

Role of matrix metalloproteinases and their tissue inhibitors as potential biomarkers of left ventricular remodelling in the athlete{'}s heart

Clinical Science — Thu, 05 Feb 2009 05:00:00 +0100

The aim of the present study was to verify whether plasma MMPs and TIMPs could be used as potential markers of paraphysiological remodelling in the athlete’s heart, and to correlate these matrix parameters with echocardiographic signs of left ventricular remodelling. Plasma MMP-2 and MMP-9 were measured by zymography, TIMP-1 and TIMP-2 were measured by ELISA in 42 veteran marathoners (AH), and in 25 sedentary healthy subjects (CTL). All subjects were submitted to clinical examination and 2D color Doppler echocardiography together with the measure of circulating NT-proBNP; GGT was evaluated as a marker of cardiovascular disease. Veteran athletes had significant elevation in LV dimensions and calculated LV mass index. Diastolic and systolic functions were normal for both groups. MMP-9...

Transient limb ischemia remotely preconditions through a humoral mechanism acting directly on the myocardium: evidence suggesting cross-species protection

Clinical Science — Wed, 28 Jan 2009 05:00:00 +0100

In conclusion, in vivo transient limb ischemia releases a low molecular weight (< 15kDa), hydrophobic, circulating factor(s) which induce(s) a potent protection against myocardial ischemia/reperfusion injury in Langendorff perfused hearts and isolated cardiomyocytes in the same species. This cardioprotection is transferable across species, independent of local neurogenic activity, and requires opioid receptor activation. (Source: Clinical Science)

Serial changes in adiponectin and BNP in ACS patients: paradoxical associations with each other and with prognosis

Clinical Science — Wed, 28 Jan 2009 05:00:00 +0100

In conclusion, increases in plasma adiponectin (rather than absolute levels) after ACS are related to risk of adverse outcome, but this relationship is not independent of BNP levels. Our results allude to a potential direct or indirect relationship between adiponectin and BNP post-ACS that requires further investigation. (Source: Clinical Science)

N-terminal pro B type natriuretic peptide complements the GRACE risk score in predicting early and late mortality following acute coronary syndrome

Clinical Science — Tue, 27 Jan 2009 05:00:00 +0100

Conclusion: NT-proBNP gives complementary information to GRACE risk score for predicting early and late mortality. The inclusion of the NT-proBNP blood test is useful in risk stratifying patients after an acute coronary syndrome. (Source: Clinical Science)

Comparison of the retinal microvasculature in European and African-Caribbean people with diabetes

Clinical Science — Tue, 27 Jan 2009 05:00:00 +0100

Conclusions: In the presence of diabetes, a relationship between BP and retinal arteriolar diameter is not evident and implies impaired small artery remodelling in the presence of diabetes. African Caribbean people with diabetes have wider retinal arterioles and this could contribute to enhanced microvascular damage in this ethnic group. (Source: Clinical Science)

The second meal phenomenon is associated with enhanced muscle glycogen storage in humans

Clinical Science — Fri, 23 Jan 2009 05:00:00 +0100

Conclusion: The second meal effect is associated with priming of muscle glycogen synthesis consequent upon sustained suppression of plasma FFA concentrations. (Source: Clinical Science)

Circulating CD34+KDR+ endothelial progenitor cells are reduced in chronic heart failure patients as a function of Type D personality

Clinical Science — Fri, 23 Jan 2009 05:00:00 +0100

Conclusions: Reduced EPC numbers might explain impaired cardiovascular outcome in Type D patients. The observed larger increase in circulating EPC in these patients suggests that acute exercise elicits a more pronounced stimulus for endothelial repair. (Source: Clinical Science)

Titin isoform expression in aortic stenosis

Clinical Science — Tue, 20 Jan 2009 05:00:00 +0100

Conclusion: Expression of less N2BA and more N2B titin in response to pressure overload will result in the generation of higher passive tension upon stretch at a given sarcomere length and thus affect cardiac performance. (Source: Clinical Science)

Programming of hypothalamic energy balance gene expression in rats by maternal diet during pregnancy and lactation

Clinical Science — Tue, 20 Jan 2009 05:00:00 +0100

This study investigates potential underlying mechanisms. Rats were established as follows: (a) controls (offspring of control dams fed a 20% protein diet), (b) recuperated animals (offspring of dams fed an isocaloric low-protein (8%) diet during pregnancy, nursed by control dams) and (c) postnatal low-protein animals (offspring of control dams nursed by low-protein dams). Serum and brains were collected from fed and fasted animals at weaning. Expression of hypothalamic energy balance genes was assessed using in situ hybridisation. Recuperated pups were smaller at birth, but caught up with controls by day 21 and gained more weight than controls between weaning and 12 weeks of age (p (Source: Clinical Science)

A common variant of eNOS gene (Glu298Asp) is an independent risk factor for left ventricular hypertrophy in human essential hypertension

Clinical Science — Thu, 08 Jan 2009 05:00:00 +0100

Background and objectives: Endothelial nitric oxide synthase (eNOS) plays a critical role in the development of ventricular remodeling and cardiac hypertrophy. The purpose of the study was to determine whether three common variants in the eNOS gene (NOS3) are associated with risk of left ventricular hypertrophy (LVH) in patients with essential hypertension. Methods: Three NOS3 genetic variants, -T786C (rs2070744), eNOS4a/b and +G894T (rs1799983) were genotyped in two independent case-control studies: the first study consisted of 1,061 hypertensive patients with LVH and 1,118 hypertensive patients without LVH, and the second sample consisted of 120 patients with LVH and 223 patients without LVH. Echocardiographic measurements were obtained in all the hypertensive patients. Results: Only th...

Prenatal programming of renal sodium handling in the rat

Clinical Science — Wed, 07 Jan 2009 05:00:00 +0100

Prenatally programmed hypertension induced by maternal protein restriction is associated with increased expression of the renal tubular Na+:K+:2Cl- co-transporter (NKCC2) and the Na+:Cl- co-transporter (NCC). This has led to the suggestion that renal sodium retention contributes to the development of hypertension in the low protein (LP) rat. However, this hypothesis has not been tested in vivo. Renal clearance measurements in hypertensive 4 week old male and female LP rats showed that while glomerular filtration rate remained unaltered, urine flow (P (Source: Clinical Science)

Effects of HCV co-infection on apoptosis of CD4+ T cells in HIV-positive patients

Clinical Science — Wed, 07 Jan 2009 05:00:00 +0100

Conclusions: Our results suggest that HCV co-infection sensitizes CD4+ T cells towards apoptosis in untreated HIV-positive patients. However, this effect is rapidly lost under effective antiretroviral therapy. (Source: Clinical Science)

Effect of ischemic exercise training of normal limb on angiogenesis of pathological ischemic limb in rabbit

Clinical Science — Tue, 06 Jan 2009 05:00:00 +0100

In conclusion, angiogenesis associated with up-regulation of VEGF expression in pathological ischemic limb may be facilitated by 4 weeks of physiological ischemic exercise training in normal limb. (Source: Clinical Science)

Arginine, citrulline, and nitric oxide metabolism in sepsis

Clinical Science — Tue, 23 Dec 2008 05:00:00 +0100

The objective of this study was to investigate whole-body, in vivo arginine and citrulline metabolism and nitric oxide synthesis rates and their relationships to protein breakdown in patients with sepsis or septic shock and in healthy volunteers. Endogenous leucine flux, an index of whole-body protein breakdown rate, was measured in 13 critically-ill patients with sepsis or septic shock and 7 healthy controls using an intravenous infusion of 1-13C-leucine. Arginine flux, citrulline flux, and the rate of conversion of arginine to citrulline (an index of nitric oxide synthesis) were measured with intravenous infusions of 15N2-guanidino-arginine and 5,5-2H2-citrulline. Plasma concentrations of nitrite plus nitrate, arginine, citrulline, and asymmetric dimethylarginine were measured. Compared ...

Intramyocellular lipid levels are associated with peripheral but not hepatic insulin sensitivity in normal healthy subjects

Clinical Science — Thu, 18 Dec 2008 05:00:00 +0100

Conclusion: Our data suggest that IMCL accumulation may be a sensitive marker for attenuations in peripheral but not hepatic SI in normal populations. Given the close relation of IMCL levels to whole-body and central abdominal fat mass, relative increases in the flux of lipids from adipose tissue to the intramyocellular compartment may be an integral part of the mechanisms underlying reductions in SI. (Source: Clinical Science)

Effect of intensive lipid-lowering therapy on telomere erosion in endothelial progenitor cells obtained from patients with coronary artery disease

Clinical Science — Wed, 17 Dec 2008 05:00:00 +0100

This study included 100 patients with stable CAD and 25 subjects without CAD as controls. CAD patients were randomized to 12 months of intensive LLT with atorvastatin or moderate LLT with pravastatin. EPCs were obtained from peripheral blood at baseline and after 12 months of statin therapy. Telomere length in EPCs was measured by fluorescence in situ hybridization and oxidative DNA damage by flow cytometry of oxidized DNA bases. EPC telomere length was shorter in the CAD group than in the controls. Oxidative DNA damage to EPCs was higher in the CAD group compared to controls. After 12 months of therapy, changes in lipid profiles were greater in intensive LLT group than in moderate LLT group. Intensive LLT markedly increased EPC number and decreased oxidative DNA damage in EPCs (both P < ...

Increased expression of TGF-beta type I receptor in brain tissues of patients with temporal lobe epilepsy

Clinical Science — Tue, 16 Dec 2008 05:00:00 +0100

This study aimed to further understand the potential effects of TβRs in human epilepsy. Tissue samples of temporal neocortices from 30 patients with temporal lobe epilepsy were prepared for detecting TβR-I protein expression using immunohistochemistry, immunofluorescence and western blot. We compared these tissues against 8 histological normal temporal lobes from controls. TβR-I immunoreactive staining was increased in patient group compared to controls using immunohistochemistry, this finding was consistently observed with western blot analysis. Immunofluorescence showed that TβR-I fluorescence stain mainly accumulated in the cytoplasm of astrocytes. Our findings demonstrate that an up-regulation of TGF-beta receptor type I is present in patients with temporal ...

Extracellular matrix metalloproteinase inducer (EMMPRIN) is present in smooth muscle cells of human aneurysmal aorta and is induced by Angiotensin II in vitro

Clinical Science — Mon, 15 Dec 2008 05:00:00 +0100

CONCLUSION: This is the first report on the expression of EMMPRIN in aortic aneurysmal diseases. We speculate that EMMPRIN may be important in the pathogenesis of aortic aneurysmal diseases. Whether these abnormalities are potential therapeutic targets deserves further investigation. (Source: Clinical Science)

QT interval prolongation and decreased heart rate variability in cirrhotic patients: relevance of hepatic venous pressure gradient and serum calcium

Clinical Science — Wed, 10 Dec 2008 05:00:00 +0100

A prolongation of QT interval has been shown in patients with cirrhosis and it is considered as part of the definition of the so-called “cirrhotic cardiomyopathy”. The aim of the present study was to assess the determinants of QT interval prolongation in cirrhotic patients. Forty-eight male patients with different stages of liver disease were divided in three subgroups according to Child-Pugh classification. All patients underwent a 24-hours electrocardiogram (ECG) Holter recording. The 24-hours mean of QT intervals corrected for heart rate (QTc) and the slope of the regression line QT/RR were calculated. Heart rate variability (HRV), plasma calcium and potassium concentration and hepatic venous pressure gradient (HVPG) were measured. QTc was progressively prolonged from Chil...

The role of vitamin D in upregulating VEGF and reducing the risk of pre-eclampsia

Clinical Science — Wed, 10 Dec 2008 05:00:00 +0100

(Source: Clinical Science)

Interval exercise is a path to good health but how much, how often, and for whom?

Clinical Science — Wed, 10 Dec 2008 05:00:00 +0100

Interval exercise training has now been examined in a wide variety of individuals ranging from elite athletes to patients with severe cardiovascular disease. The advantages of interval exercise training in comparison to constant intensity exercise programs are that they seem to deliver superior improvements in several cardiovascular risk factors, fitness and performance. Depending on the program design, some interval exercise programs result in a range of benefits even though the time commitment may be dramatically less that more traditional continuous intensity programs. The study by Tjonna et.al. demonstrates that aerobic interval training may also be a powerful tool in combating the increased cardiovascular risk observed in overweight adolescents. (Source: Clinical Science)

Magic angle spinning magnetic resonance - a novel method opening up translational research into NAFLD?

Clinical Science — Thu, 04 Dec 2008 05:00:00 +0100

Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are of increasing importance, both in connection with insulin resistance and with the development of liver cirrhosis. Histological samples are still the “gold standard” for that diagnosis; however, because of the risks of a liver biopsy, non-invasive methods are needed. Magic angle spinning (MAS) is a special type of nuclear magnetic resonance (NMR) that allows for a characterization of intact, excised tissue without a need for additional extraction steps. Because clinical magnetic resonance imaging (MRI) and spectroscopy (MRS) are based on the same physical principle as NMR, translational research is feasible from excised tissue to non-invasive examinations in humans. A study in three animal strains sufferi...

Systemic hypoxia enhances bactericidal activities of human polymorphonuclear leukocytes

Clinical Science — Wed, 03 Dec 2008 05:00:00 +0100

Reactive oxygen species generated by hypoxia facilitate vascular inflammatory response, whether systemic hypoxia influences leukocyte bactericidal activity by modulating circulatory redox status remains unclear. This investigation elucidates how various hypoxic interventions influence bactericidal activity of polymorphonuclear leukocyte (PMN) following treatment with an antioxidant vitamin E (d-α-tocopheryl acetate). Forty healthy sedentary men were randomly assigned to vitamin E (n=20) and placebo (n=20) groups. One hour following oral administering of 1000 IU vitamin E or placebo, each subject in the two groups was randomly exposed to 12%, 15%, 18% and 21% O2 for two hours in a normobaric hypoxia chamber. The results demonstrated that exposure to 12% O2 in the placebo group increa...

The role of pravastatin in pulmonary hypertension in chronic obstructive pulmonary disease

Clinical Science — Thu, 27 Nov 2008 05:00:00 +0100

In this issue of Clinical Science Lee et al report a placebo-controlled study of 53 patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) on echocardiography, in which six-months of pravastatin treatment was associated with a significant increase in exercise time (660 to 1006s, p (Source: Clinical Science)

Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria

Clinical Science — Tue, 25 Nov 2008 05:00:00 +0100

Exposure to an adverse intrauterine environment is recognized as an important risk factor for the development of cardiovascular disease later in life. While oxidative stress has been proposed as a mechanism for the fetal programming phenotype, the role of mitochondrial superoxide production has not been explored. To determine whether mitochondrial reactive oxygen species production is altered by in utero programming, pregnant ewes were given a 48-hr dexamethasone (dex-exposed, 0.28 mg/kg/d) or saline (control) infusion at 27-28 days gestation (term = 145 d). Intact left ventricular mitochondria and freeze-thaw mitochondrial membranes were studied from offspring at 4-mo of age. AmplexRed used to measure hydrogen peroxide (H2O2) production. Activities of the antioxidant enzymes manganese sup...

Angiogenic factors and preeclampsia: an early marker is needed

Clinical Science — Tue, 25 Nov 2008 05:00:00 +0100

Preeclampsia, a pregnancy complication characterized by hypertension and proteinuria, is still a major cause of neonatal and maternal mortality and acute and long-term morbidities for both, mother and neonate. There is mounting evidence that an imbalance between angiogenic factors such as VEGF or PlGF and factors inhibiting angiogenesis such as sFlt1 and sEng are closely related to the pathogenesis of preeclampsia. In the present issue of Clinical Science, Bills and co-workers report that VEGF165b, an alternative splice variante of the VEGF-pre-mRNA, is upregulated in women with normal pregnancy and that this increase delayed or diminished in women who develop preeclampsia. Thus, this protein could serve (alone or in combination with other parameters) as a new marker for risk assessment in...

Desferroxamine infusion increases cerebral blood flow: a potential association with hypoxia-inducible transcription factor 1

Clinical Science — Tue, 18 Nov 2008 05:00:00 +0100

Finding an effective means to improve cerebral perfusion during hypoxic-ischemic stress is essential for neuroprotection. Studies in animal models of stroke have shown that Desferroxamine activates hypoxia inducible transcription factor-1, reduces brain damage and promotes functional recovery. Our study was designed to investigate the effects of Desferroxamine infusion on the cerebral circulation in humans. Fifteen volunteers were enrolled in a randomized double-blinded placebo controlled crossover study. We measured cerebral blood flow velocity by transcranial Doppler ultrasonography in the middle cerebral artery, arterial blood pressure, end-tidal CO2, as well as hypoxia inducible transcription factor-1 protein and serum lactate dehydrogenase concentrations in response to 8 hours of Desf...

Difference in upper airway collapsibility during wakefulness between men and women in response to lower body positive pressure

Clinical Science — Fri, 14 Nov 2008 05:00:00 +0100

Fluid shift from the legs to the neck induced by lower body positive pressure (LBPP) increases upper airway (UA) collapsibility in healthy men. Rostral fluid displacement during recumbency may therefore contribute to the pathogenesis of obstructive sleep apnea (OSA). There is a higher prevalence of OSA in men than in women. We therefore hypothesized that UA collapsibility increases more in men in response to rostral fluid displacement than in women. UA collapsibility was assessed in healthy, non-obese men and women while awake by determining UA critical closing pressure (Pcrit) during application of different suction pressures to the UA. Subjects were randomized to 5-minute control or LBPP arms after which they crossed-over into the other arm following a 30-minute washout. LBPP was applied...

Altered plasma proteome during an early phase of peritonitis-induced sepsis

Clinical Science — Thu, 13 Nov 2008 05:00:00 +0100

Sepsis is a systemic response to infection commonly found in critically ill patients and is associated with multi-organ failure and high mortality rate. Its pathophysiology and molecular mechanisms are complicated and remain poorly understood. We performed a proteomics study to characterize early host responses to sepsis as determined by altered plasma proteome in a porcine model of peritonitis-induced sepsis, which simulated several clinical characteristics of human sepsis syndrome. Hemodynamics, oxygen exchange, inflammatory responses, oxidative and nitrosative stress, and other laboratory parameters were closely monitored. Plasma samples were obtained from 7 pigs before and 12-h after an induction of sepsis, and plasma proteins were resolved with two-dimensional gel electrophoresis (n =...

Mediators of mineralocorticoid receptor-induced profibrotic inflammatory responses in the heart

Clinical Science — Thu, 06 Nov 2008 05:00:00 +0100

Coronary, vascular and perivascular inflammation in rats following mineralocorticoid receptor (MR) activation plus salt is a well-characterized precursor for the appearance of cardiac fibrosis. Endogenous corticosterone, in the presence of the 11βHSD2 inhibitor carbenoxolone (CBX) plus salt, produces similar inflammatory responses and tissue remodeling via activation of MR. MR-mediated oxidative stress has previously been suggested to account for these responses. We thus postulated that when 11βHSD2 is inhibited, endogenous corticosterone bound to unprotected MR in the vessel wall may similarly increase early biomarkers of oxidative stress. Uninephrectomized rats received either deoxycorticosterone (DOC), CBX or CBX plus the MR antagonist eplerenone (EPL) together with 0.9% s...

Time course of changes in serum oxidant/antioxidant status in overfed obese rats and their offspring

Clinical Science — Wed, 05 Nov 2008 05:00:00 +0100

In conclusion, excessive maternal fat and energy intake can play an important role in the development of metabolic disorders in the offspring. Maternal oxidative stress may be amongst the responsible factors. Fetal oxidative stress may present an additional confounding influence and probably contributes to additional disorders, aggravating metabolic syndrome features. An improvement of maternal oxidant/antioxidant status during pregnancy and lactation, with adequate nutrition, could have beneficial effects in the progeny. (Source: Clinical Science)

Tryptophan degradation in multiple trauma patients: survivors versus non-survivors

Clinical Science — Wed, 05 Nov 2008 05:00:00 +0100

This study investigated whether tryptophan degradation is associated with outcome of patients post trauma. Tryptophan and kynurenine concentrations were measured by HPLC in serum specimens of 15 patients post-trauma during 12-14 days of follow up. Of every patient up to 5 specimens within this observation period were included in this analysis, in total 69 specimens were available. For further comparisons, concentrations of immune activation marker neopterin were measured. Compared to healthy controls, average kyn/trp and kynurenine were increased in patients, and tryptophan concentrations were decreased. During follow-up, increasing kyn/trp and kynurenine concentrations (all p (Source: Clinical Science)

Immuno-inflammatory predictors of stroke at follow-up in patients with chronic non-valvular atrial fibrillation (NVAF)

Clinical Science — Mon, 03 Nov 2008 05:00:00 +0100

Conclusion: Baseline plasma levels of TNF-α, IL-6 and vWF are predictors of new onset ischemic stroke at follow-up in patients with chronic non valvular atrial fibrillation (NVAF). (Source: Clinical Science)

The DGAT2 gene is a candidate for dissociation between fatty liver and insulin resistance in humans

Clinical Science — Mon, 03 Nov 2008 05:00:00 +0100

The enzyme acyl-CoA:diacylglycerol acyltransferase (DGAT) catalyzes the final step of triglyceride synthesis. Mice overexpressing hepatic DGAT2, fed a high-fat diet, develop fatty liver, but not insulin resistance, suggesting that DGAT2 induces dissociation between fatty liver and insulin resistance. We investigated whether such a phenotype also exists in humans. For this purpose, we determined the relationships of genetic variability in the DGAT2 gene with changes in liver fat and in insulin sensitivity in 187 extensively phenotyped subjects during a lifestyle intervention with diet modification and increase in physical activity. Changes in body fat composition [magnetic resonance (MR) tomography], liver fat and intramyocellular fat (1H-MR spectroscopy) and insulin sensitivity (OGTT and e...

Statins for heart failure: still caught in no man{'}s land?

Clinical Science — Wed, 29 Oct 2008 04:00:00 +0100

Statins are well-known for their ability to lower serum cholesterol levels, but have properties beyond mere cholesterol reduction. These pleiotropic effects include an improvement in endothelial dysfunction, release of endothelial progenitor cells, anti-inflammatory properties, and a number of antitumour activities. In the present issue of Clinical Science, Stunpf et al. show that a 4-week treatmentcourse with the lipophilic atorvastatin ameliorates left ventricular remodelling and function, reduces serum levels of TNFα, IL-6, and monocyte chemoattractant protein-1, and increases both serum and myocardial levels of IL-10. The authors hypothesize that this shift from a pro- to an anti-inflammatory response might be beneficial in the clinical setting, because patients with low levels ...

Reliability of dynamic cerebral autoregulation measurement using spontaneous fluctuations in blood pressure

Clinical Science — Wed, 22 Oct 2008 04:00:00 +0100

Spontaneous fluctuations in blood pressure (BP) and subsequent change in cerebral blood flow velocity (CBFV) in the middle cerebral artery (MCA) can be used to assess dynamic cerebral autoregulation using transfer function analysis. However the reliability of this technique has not been assessed, in particular the contribution of intra-subject variability relative to inter-subject variability. Three bilateral CBFV, BP and R-R interval recordings were performed in ten healthy volunteers on four separate occasions over a 2-week period. Data were analysed to provide autoregulatory index (ARI), CBFV, resistance-area product (RAP), and critical closing pressure (CrCP). We also measured systolic and diastolic BP, and resting heart rate (HR). We calculated the standard error of measurement (SEM)...

Muscle acylcarnitines during short-term fasting in lean healthy men

Clinical Science — Wed, 22 Oct 2008 04:00:00 +0100

The transition from the fed to the fasted resting state is characterized by, amongst others, changes in lipid metabolism and peripheral insulin resistance. Acylcarnitines have been suggested to play a role in insulin resistance besides other long-chain fatty acid metabolites. Plasma levels of long-chain acylcarnitines increase during fasting, but this is unknown for muscle long-chain acylcarnitines. We studied whether muscle long-chain acylcarnitines increase during fasting and their relation with glucose/fat oxidation and insulin sensitivity in lean healthy humans. After 14 and 62 hours of fasting, glucose fluxes, substrate oxidation, plasma and muscle acylcarnitines were measured before and during a hyperinsulinemic euglycemic clamp. Hyperinsulinemia decreased long-chain muscle acylcarni...

Total leukocyte count but not C-reactive protein predicts one-year mortality in patients with acute coronary syndromes treated with percutaneous coronary intervention

Clinical Science — Tue, 14 Oct 2008 04:00:00 +0100

Although an association between elevated white blood cells (WBC) count and mortality in patients with acute coronary syndromes (ACS) has been established, the independence of this association from coronary risk factors and C-reactive protein has been inadequately studied. This prospective registry included 4329 patients with ACS treated with percutaneous coronary intervention (PCI): 1059 patients with ST-segment elevation acute myocardial infarction, 1753 patients with non-ST-segment elevation acute myocardial infarction and 1517 patients with unstable angina. Blood samples were obtained before angiography for WBC count and C-reactive protein measurements. The primary outcome of this analysis was 1-year mortality. At one year, 345 patients (8%) died: 45 patients in the 1st tertile, 93 pati...

Deterioration in cardiac systolic and diastolic function late in normal human pregnancy

Clinical Science — Tue, 14 Oct 2008 04:00:00 +0100

Conclusion: By term pregnancy, an increase in ventricular wall stress is accompanied by deterioration in cardiac function. (Source: Clinical Science)

A comprehensive assessment of endothelial function in overweight women with and without polycystic ovary syndrome

Clinical Science — Mon, 13 Oct 2008 04:00:00 +0100

Conclusion: Women with PCOS are hyperandrogenic, dyslipidaemic and IR and have risk factors for cardiovascular disease and diabetes including increased circulating markers of endothelial function (ADMA, PAI-1) and a trend towards worse FMD as a global marker of endothelial function. In PCOS, deterioration in endothelial function is related to IR, hyperandrogenism and other factors. (Source: Clinical Science)

More knocks to the oxidation hypothesis for vascular disease?

Clinical Science — Fri, 10 Oct 2008 04:00:00 +0100

The oxidation hypothesis for coronary heart disease (CHD) is attractive. However, the almost universal failure of antioxidant vitamin supplementation as a CVD risk modifier challenges the oxidation hypothesis, at least as a concept that easily ‘translates’ into clinical benefit for the population. At the same time, quality prospective data on lipid or protein oxidation markers as predictors of vascular events is spare. In this issue of the journal, Woodward and colleagues provide much needed prospective data examining the relationship between markers of oxidative damage and CHD outcome in a general population. Despite noting the expected associations between several established CHD risk factors and CHD events, no significant link was seen between measured oxidation markers a...

Effects of pravastatin on functional capacity in patients with chronic obstructive pulmonary disease and pulmonary hypertension

Clinical Science — Fri, 03 Oct 2008 04:00:00 +0100

Pulmonary hypertension (PH) often complicates the course of patients with chronic obstructive pulmonary disease (COPD), and portents a worse prognosis. We assessed whether pravastatin administration is effective in improving PH and exercise capacity in COPD patients with PH, and whether the pulmonary protection is mediated by inhibiting endothelin-1 production. In a double-blind, and parallel design, 53 COPD patients with PH were randomly assigned to receive either placebo or pravastatin (40 mg per day) over a period of 6 months in a medical center. Baseline characteristics were similar in both groups. The exercise time remained stable throughout the study in the placebo group. After 6 months, exercise time significantly increased by 52% from 660 ± 352 sec to 1006 ± 316 sec (...

Failure to upregulate VEGF165b in maternal plasma is a first trimester predictive marker for pre-eclampsia

Clinical Science — Wed, 01 Oct 2008 04:00:00 +0100

Pre-eclampsia is a pregnancy related condition characterised by hypertension, proteinuria and endothelial dysfunction. VEGF165b, formed by alternative splicing of vascular endothelial growth factor (VEGF) pre-mRNA inhibits VEGF165 mediated vasodilatation and angiogenesis, but has not been quantified in pregnancy. Enzyme-linked immunoassays (ELISA) were used to measure mean±SEM plasma VEGF165b, soluble endoglin (sEng) and soluble Flt1 (sFlt-1). At 12 weeks gestation the plasma VEGF165b concentration was significantly upregulated in plasma from women who maintained normal blood pressure throughout their pregnancy (normotensive group 4.90 ±1.6 ng/ml, p0.1 compared with pre-eclampsia). Patients with a lower than median plasma VEGF165b at 12 weeks, had elevated soluble fms-like ty...

Hyperbaric oxygen activates discoidin domain receptor 2 via tumor necrosis factor-{alpha} and p38 pathway to increase vascular smooth muscle cells migration through matrix metalloproteinase 2

Clinical Science — Fri, 26 Sep 2008 04:00:00 +0100

In conclusion, HBO activates DDR2 expression in cultured rat SMCs. HBO-induced DDR2 is mediated by TNF-α and at least in part through p38 MAP kinase and Myc pathway. (Source: Clinical Science)

IGF-I/IGFBP- 3 ratio: a mechanistic insight into the metabolic syndrome

Clinical Science — Wed, 24 Sep 2008 04:00:00 +0100

We examined 3,281 subjects (1,463 men; 1,818 women aged 20 to 49 years), otherwise healthy adults, who participated in the Third National Health and Nutrition Examination Survey (NHANES III) and had the recently released measurements of IGF-I and IGFBP-3. Insulin resistance was estimated using the computer homeostatic model assessment (HOMA-2). The updated ATP-III definition of the metabolic syndrome was used. We applied adjusted logistic and linear regression models. After adjusting for age and race, men and women in the lowest quartile of the IGF-I/IGFBP-3 ratio were 3 times more likely to meet the ATP-III definition of the metabolic syndrome and twice as likely to be insulin resistant. Mean values of the IGF-I/IGFBP-3 ratio decreased significantly as the number of metabolic syndrome com...

Predictive value of the decrease in circulating dendritic cell precursors in stable coronary artery disease

Clinical Science — Tue, 23 Sep 2008 04:00:00 +0100

In conclusion, we show that patients with stable CAD have significantly lower numbers of circulating DCP than healthy individuals. Their decrease seems to be an independent predictor of the presence and consecutive therapeutical procedure in stable CAD. (Source: Clinical Science)

Effects of bradykinin on venous capacitance in health and treated chronic heart failure.

Clinical Science — Thu, 18 Sep 2008 04:00:00 +0100

We investigated the effects of basal and intra-arterial infusion of bradykinin on unstressed forearm vascular volume (a measure of venous tone) and blood flow in health (G1, n=20) and in chronic heart failure patients treated with angiotensin converting enzyme (ACE) inhibitors (G2, n=16) and angiotensin receptor blockers (ARB) (G3, n=14). We used radionuclide plethysmography to examine the effects of bradykinin and of the bradykinin antagonists B9340 (B1/B2 antagonist) and HOE140 (B2 antagonist). Bradykinin infusion increased unstressed forearm vascular volume in a similar dose dependent manner in G1 and G3 (G1 maximum 12.3±2.1%; p (Source: Clinical Science)

Oral antioxidants and cardiovascular health in the exercise trained and untrained elderly: a radically different outcome

Clinical Science — Tue, 16 Sep 2008 04:00:00 +0100

Both antioxidant supplementation and exercise training have been identified as interventions which may reduce oxidative stress and thus improve cardiovascular health, but the interaction of these interventions on arterial blood pressure and vascular function has not been studied in older humans. Thus, in six older (71 ± 2 yrs) mildly hypertensive men, arterial blood pressure was evaluated non-invasively at rest and during small muscle mass (knee-extensor) exercise with and without a pharmacologic dose of oral antioxidants (Vitamins C, E, and alpha-lipoic acid). The efficacy of the antioxidant intervention to decrease plasma free radical concentration was verified via electron paramagnetic resonance (EPR) spectroscopy, while changes in endothelial function in response to exercise tra...

Angiotensin II modulates CD40 expression in vascular smooth muscle cells

Clinical Science — Thu, 11 Sep 2008 04:00:00 +0100

The signaling pathway CD40-CD40L plays an important role in atherosclerotic plaque formation and rupture. Angiotensin II (ANGII), which induces oxidative stress and inflammation, is also implicated in the progression of atherosclerosis. In the present study we tested the hypothesis that ANGII increases CD40-CD40L activity in vascular cells and that reactive oxygen species (ROS) are part of the signaling cascade that controls CD40-CD40L expression. Human coronary artery smooth muscle cells (CASMCs) in culture exposed to IL-1β or TNF-α showed increased superoxide generation and enhanced CD40 expression, detected by electron paramagnetic resonance and immunoblotting, respectively. Both phenomena were abolished by previous incubation with membrane-permeable antioxidants or cell ...

Basal adipose tissue and hepatic lipid kinetics are not affected by a single exercise bout of moderate duration and intensity in sedentary women

Clinical Science — Wed, 27 Aug 2008 04:00:00 +0100

Hypertriglyceridemia is an important risk factor for cardiovascular disease. In men we have shown that the effects of evening exercise on basal very low-density lipoprotein (VLDL) metabolism are dose-dependent: a single, prolonged bout of aerobic exercise (2 h at 60% of peak oxygen consumption, VO2 peak) reduces fasting plasma triglyceride (TG) concentrations, via enhanced clearance of VLDL-TG from the circulation, whereas the same exercise performed for 1 h has no effect on VLDL-TG metabolism and concentration. We hypothesized that women are more sensitive to the TG-lowering effect of exercise because they reportedly use more intramuscular TG as energy source during exercise and depletion of muscle TG stores has been linked to reciprocal changes in skeletal muscle lipoprotein lipase (LPL)...

Prolonged L-alanine exposure induces changes in metabolism, Ca2+ handling and desensitization of insulin secretion in clonal pancreatic beta-cells

Clinical Science — Thu, 14 Aug 2008 04:00:00 +0100

This study examined the effects of prolonged exposure of beta cells to the metabolizable amino acid, L-alanine. Basal insulin release or cellular insulin content were not significantly altered by alanine culture, but acute alanine-induced insulin secretion was suppressed by 74% (p (Source: Clinical Science)

Phenotyping murine models of non-alcoholic fatty liver disease through metabolic profiling of intact liver tissue

Clinical Science — Tue, 12 Aug 2008 04:00:00 +0100

This study aimed to characterise murine models of NAFLD by metabolic profiling of intact liver tissue. Mice of three strains (BALB/c, C3H and the novel mutant, Gena/263) were fed a control or high fat diet. Biometric, biochemical and histological analysis demonstrated a spectrum of NAFLD from normal liver to steatohepatitis. Metabolic profiling of intact liver tissue, using magic angle spinning proton magnetic resonance spectroscopy (MAS MRS), showed an increase in total lipid-to-water ratio, a decrease in polyunsaturation indices and a decrease in total choline with increasing disease severity. Principal components analysis and partial least squares discriminant analysis showed separation of each model from its control and of each model from the total dataset. Class membership from the wh...

Phosphodiesterase 4D gene polymorphism is associated with ischemic and hemorrhagic stroke

Clinical Science — Tue, 12 Aug 2008 04:00:00 +0100

It has been reported that the variants of phosphodiesterase 4D gene (PDE4D) are associated with stroke, especially with the combination of cardioembolic and carotid stroke in Icelandic population, but it is still very controversial on whether PDE4D is a susceptible gene for stroke in other populations. We tested whether PDE4D gene variation also confers stroke risk in Chinese population. Our hypothesis was tested in a case-control study of Chinese population comprising of 639 patients with stroke (including 253 cerebral thrombosis, 171 lacunar infarct and 215 intracerebral hemorrhage) and 887 healthy controls. Three single nucleotide polymorphisms (SNPs) (rs966221, rs456009, rs2910829) in PDE4D were chosen based on significant association with stroke reported previously in western populati...

The additive prognostic value of the cardiopulmonary exercise test in elderly patients with heart failure

Clinical Science — Tue, 12 Aug 2008 04:00:00 +0100

Conclusions: In elderly HF patients, a steeper VE/VCO2 slope provides additional information for risk stratification across the spectrum of ventricular function and identifies a high risk population, commonly not considered in exercise test guidelines. (Source: Clinical Science)

Left ventricular systolic and diastolic dyssynchrony in coronary artery disease with preserved ejection fraction

Clinical Science — Wed, 06 Aug 2008 04:00:00 +0100

In conclusion, LV mechanical dyssynchrony is evident in CAD patients with preserved EF, though it was less prevalent than those with depressed EF. Also, mechanical dyssynchrony occurred in CAD patients without prior MI and narrow QRS complexes. (Source: Clinical Science)

Aerobic interval training reduces cardiovascular risk factors more than a multi treatment approach in overweight adolescents

Clinical Science — Fri, 01 Aug 2008 04:00:00 +0100

Aims: To compare effects of a multidisciplinary approach (MTG) and aerobic interval training (AIT) on cardiovascular risk factors in overweight adolescents. Research design and methods: Sixty-two overweight and obese adolescents from Trøndelag County in Norway, referred to medical treatment at St. Olav’s Hospital (Trondheim, Norway), were invited to participate. Fifty-four adolescents (14.0±0.3yrs) were randomized to either AIT (4x4-minutes intervals at 90% of maximal heart rate, each interval separated by 3-minutes at 70%, 2/week for 13-weeks) or to MTG (exercise, dietary and psychological advice, 2/month for 12-months). Follow-up testing occurred at three- and twelve-month. Results: VO2max increased more after AIT vs. MTG, both at three- (11% vs. 0%) and twelve-mont...

Gender and renal function influence plasma levels of copeptin in healthy individuals

Clinical Science — Tue, 22 Jul 2008 04:00:00 +0100

This study sought to identify confounding factors for the interpretation of copeptin levels in healthy individuals. The natriuretic peptides are recognised as diagnostic and prognostic tools in heart failure (HF). Interpretation of BNP and NTproBNP levels is multifaceted as their secretion is influenced by many variables. A newly identified glycopeptide called copeptin is comparable to the natriuretic peptides in diagnosis and prognosis of HF and as a prognostic biomarker after acute myocardial infarction (AMI). Copeptin, derived from the C-terminal portion of the precursor to arginine vasopressin (AVP), is secreted stoichiometrically with vasopressin, hence can be used as a surrogate marker of the AVP system. 706 healthy volunteers were recruited from a local HF screening study. Participa...

The angiotensin-converting enzyme I/D polymorphism is associated with phagocytic NADPH oxidase-dependent superoxide generation: potential implication in hypertension

Clinical Science — Tue, 22 Jul 2008 04:00:00 +0100

In conclusion, we reported for the first time an association of the DD genotype of the ACE I/D polymorphism with phagocytic NADPH oxidase-mediated •O2- overproduction. Within the group of hypertensive patients, DD cases also associated with increased blood pressure values and with enhanced plasma levels of MMP-9. (Source: Clinical Science)

Human tribbles homolog 2 is expressed in unstable regions of carotid plaques and regulates macrophage IL-10 in vitro

Clinical Science — Mon, 21 Jul 2008 04:00:00 +0100

In this study, a screen for mRNA species specifically regulated in vulnerable regions of human atherosclerotic plaque demonstrated upregulation of both Trb1 and Trb2, the latter by more than 8-fold. In vitro experiments in primary human monocyte-derived macrophages showed that Trb2 expression was upregulated by treatment with oxidised low density lipoprotein (LDL), and that expression of recombinant Trb2 specifically reduced macrophage levels of IL-10 mRNA. Our results thus identify Trb2 as a highly regulated gene in vulnerable atherosclerotic lesions, and demonstrate inhibition of macrophage IL-10 biosynthesis as a potential pro-inflammatory consequence of high Trb2 expression that may contribute to plaque instability. (Source: Clinical Science)

MicroRNA profile in peripheral blood T cells of patients with primary biliary cirrhosis

Clinical Science — Thu, 17 Jul 2008 04:00:00 +0100

This study provides insight into PBC pathogenesis. (Source: Clinical Science)

RNA interference targeting ACE gene reduced blood pressure and improved myocardial remodeling in SHR

Clinical Science — Tue, 08 Jul 2008 04:00:00 +0100

Objectives: To investigate the effects of RNA interference (RNAi) targeting angiotensin- converting enzyme (ACE) on blood pressure and myocardial hypertrophy in spontaneously hypertensive rats (SHR). Methods: SHRs were treated with normal saline as vehicle controls, with Ad5-EGFP as vector controls, and with recombinant adenoviral vectors Ad5-EGFP-ACE-shRNA carrying shRNA for ACE as ACE-RNAi. WKY rats were taken as normotensive controls treated with normal saline. Systolic blood pressure of the caudal artery was recorded. Serum levels of ACE and angiotensin II (Ang II) were determined with ELISA. ACE mRNA and ACE protein level were determined in aorta, myocardium, kidney and lung. On day-32 of the experiment, heart was pathologically examined. The ratio of heart weight to and left ventricu...

Effect of different antihypertensive treatments on Ras / MAPKinases / Akt activation in hypertension and diabetes

Clinical Science — Mon, 30 Jun 2008 04:00:00 +0100

Ras GTPases function as transducers of extracellular signals regulating many cell functions, and they seem to be involved in the development of hypertension. We have evaluated whether the antihypertensive treatment with angiotensin II receptor blockers (ARB), angiotensin converting enzyme inhibitors (ACEi), and diuretics induce changes in Ras activation and in some of its effectors (Erk and Akt) in lymphocytes from hypertensive and diabetic patients. ACEi treatment transiently reduced Ras activation in the first month of treatment, but diuretics induced a sustained increase in Ras activation throughout the 3 months of the study. In diabetic-hypertensive patients, ARB, ACEi and diuretics increased Ras activation only during the first week. ACEi treatment increased phospho-Erk expression dur...

Ischemia and insulin, but not ischemia and contraction, act synergistic in stimulating muscle glucose uptake in vivo in humans

Clinical Science — Fri, 20 Jun 2008 04:00:00 +0100

Ischemia, like muscle contraction, has been reported to induce skeletal muscle glucose uptake in in vitro models. This stimulating effect appears independent of insulin and is likely mediated by activation of AMPK. We hypothesized that in vivo in humans, ischemia- and insulin-induced glucose uptake are additive, and that the combined impact of ischemia and contraction on glucose uptake is of a similar magnitude when each is applied separately. We assessed the effects of ischemia with and without euglycemic hyperinsulinemia (clamp, protocol 1) and with and without muscle contraction (protocol 2) on muscle forearm glucose uptake (FGU) in healthy subjects. Furthermore, we assessed the impact of ischemia on forearm blood flow (FBF, plethysmography). In protocol 1, ischemia increased FGU from 0...

A single bout of whole-body resistance exercise augments basal VLDL-triacylglycerol removal from plasma in healthy untrained men

Clinical Science — Fri, 13 Jun 2008 04:00:00 +0100

A single bout of prolonged aerobic exercise lowers plasma triacylglycerol (TAG) concentrations the next day by increasing the efficiency of very low-density lipoprotein (VLDL)-TAG removal from the circulation. The effect of resistance exercise on VLDL-TAG metabolism is not known. Therefore, we evaluated VLDL-TAG kinetics by using stable isotope labeled tracers in 8 healthy untrained men (age: 25±1 years, body mass index: 24.5±0.6 kg/m2) in the post-absorptive state in the morning, on two separate occasions: once after performing a single 90-min bout of strenuous isokinetic resistance exercise (3 sets x 10 repetitions, 12 exercises at 80% of maximum peak torque production, with a 2-min rest interval between sets) on the preceding afternoon and once after an equivalent period o...

Fructose modifies the hormonal response and modulates lipid metabolism in aerobic exercise after glucose supplementation

Clinical Science — Thu, 05 Jun 2008 04:00:00 +0100

The metabolic response, when aerobic exercise is performed after the ingestion of glucose plus fructose, is unclear. To compare the hormonal and lipid responses provoked by the ingestion of glucose plus fructose in relation to glucose alone, during aerobic exercise and the recovery phase, we administered two beverages containing glucose plus fructose or glucose in a randomised crossover design, to twenty healthy, aerobically trained volunteers. After a 15-minute resting period they performed 30 minutes of moderate aerobic exercise. Urinary and blood samples were taken at baseline (t-15), during the exercise (t0; t15; t30) and during the recovery phase (t45; t75; t105). Plasma insulin concentrations were higher half-way through the exercise period and during acute recuperation (t15 and t75;...

Injury to rat carotids causes time-dependent changes in gene expression in contralateral uninjured arteries

Clinical Science — Tue, 03 Jun 2008 04:00:00 +0100

Vascular surgery aimed at stenosis removal induces local reactions often leading to restenosis. While extensive analysis has been focused on pathways activated in injured arteries, little attention has been devoted to associated systemic vascular reactions. Aim of this study was to analyse changes occurring in contralateral uninjured rat carotids in the acute phase following unilateral injury. WKY rats were submitted to unilateral carotid arteriotomy. Contralateral uniunjured carotids were harvested from 4 hrs to 7 days after injury. Carotids were also harvested from sham-operated rats and from uninjured rats. Carotid morphology and morphometry were examined. Affymetrix microarrays were used for differential analysis of gene expression. A subset of data was validated by Real-Time RT-PCR an...

Heat-shock protein gene polymorphisms and the risk of nephropathy in type 2 diabetes patients

Clinical Science — Fri, 30 May 2008 04:00:00 +0100

Heat-shock proteins (HSPs) are molecular chaperones synthesized under stress conditions. HSPs are involved in renal cell survival and matrix remodeling in acute and chronic renal diseases. We investigated whether the HSP70 gene polymorphisms affect susceptibility to nephropathy in type 2 diabetes patients.The study group consisted of 240 patients with nephropathy. Two control subgroups involved: 275 healthy individuals and 132 patients with type 2 diabetes lasting ≥ 10 years, free of nephropathy. Subjects were genotyped for the HSP70-1 +190 G/C and -110 A/C, HSP70-2 +1267 A/G and HSP70-hom +2437 T/C polymorphisms by polymerase chain reaction (PCR) followed by digestion with restriction endonucleases. There were no statistically significant differences in genotype distribution betwee...

The association between both lipid and protein oxidation and the risk of fatal or non-fatal coronary heart disease in a human population

Clinical Science — Wed, 28 May 2008 04:00:00 +0100

Background: The role of oxidative damage in the etiology of coronary disease remains controversial; clinical trials investigating the effect of antioxidants have not generally been positive. Methods and Results: 227 coronary cases, identified from a cohort study, were matched, by age and sex, with 420 controls in a nested case-control design. Stored plasma samples were analyzed for F2-isoprostanes by stable isotope dilution mass spectrometry, and specifically oxidized forms of apolipoprotein A I by high performance liquid chromatography analysis of high-density lipoprotein. Median values of F2-isoprostanes were higher in plasma samples that contained oxidized apolipoprotein A I compared to samples with undetectable oxidized apolipoprotein A I (1542 v 1165 pmol/L). F2-isoprostanes were sig...

Effect of acute variations of insulin and glucose on plasma concentrations of asymmetric dimethylarginine in young people with type 1 diabetes

Clinical Science — Thu, 22 May 2008 04:00:00 +0100

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is considered a major risk factor for cardiovascular disease and progression of renal disease. In the present study we aim to investigate the effect of acute variations in plasma glucose and insulin on plasma ADMA levels in young people with type 1 diabetes (T1D). Fifteen young patients (10 males) with T1D, median age 18.3 (13.2-24.4) years, HbA1c 9% (6.4-13.6), underwent an overnight (18:00-08:00 h) variable insulin infusion for euglycemia, followed by a hyperinsulinemic euglycemic clamp (08:00-12:00 h). Blood samples were collected every 15 minutes for determination of ADMA, symmetric dimethylarginine (SDMA), valine, phenylalanine, arginine, creatinine and glucose. Insulin levels were assessed every 30...

Chronic administration of ursodeoxycholic acid decreases portal pressure in rats with biliary cirrhosis

Clinical Science — Wed, 14 May 2008 04:00:00 +0100

This study investigates the effects of one-month anti-oxidants-ursodeoxycholic acid (UDCA)-administration in bile-duct-ligation (BDL)-cirrhotic rats. Splanchnic hemodynamics, IHR, hepatic levels of thiobarbituratic acid-reactive substance (TBARS), glutathione (GSH), activity of superoxide dismutase (SOD), nitrite, N-terminal of propeptide of type III procollagen (PIIINP) and collagen deposition, histological examination of liver, mRNA expressions of PIIIP-{alpha}1, transforming growth factor-{beta}1 (TGF-{beta}1), protein expressions of thromboxane synthase (TXS) and inducible nitric oxide synthase (iNOS), and thromboxane A2 (TXA2) production in liver perfusates were measured. The current study showed that portal pressure and IHR, hepatic levels of PIIINP, hepatic collagen deposition, mRNA...

Hypovolaemia after glucose-insulin infusions in volunteers

Clinical Science — Fri, 09 May 2008 04:00:00 +0100

High-dose intravenous infusion of glucose 5% promotes rebound hypoglycaemia and hypovolaemia in healthy volunteers. To study whether such effects occur in response to glucose-insulin, 12 healthy firemen (mean age 39 years) received 3 infusions over 1-2 hours that contained 20 ml/kg of glucose 2.5%, 5 ml/kg of glucose 10% with rapid-acting insulin 0.05 U/kg, and 4 ml/kg of glucose 50% with 1 U/kg of insulin. The plasma glucose concentration and plasma dilution were compared at 5-10 min intervals during 4 hours. Regardless of the amount of administered fluid and whether insulin was given, the plasma glucose concentration decreased to hypoglycaemic levels within 30 min after the infusion ended. Plasma dilution closely mirrored plasma glucose and became negative by about 5%, which indicates a ...

Administration of a substituted adamantly-urea inhibitor of soluble epoxide hydrolase protects the kidney from damage in hypertensive Goto-Kakizaki rats

Clinical Science — Wed, 07 May 2008 04:00:00 +0100

Hypertension and type II diabetes are co-morbid diseases that lead to the development of nephropathy. Soluble epoxide hydrolase (sEH) inhibitors are reported to provide protection from renal injury. We hypothesized that the sEH inhibitor 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA) protects the kidney from the development of nephropathy associated with hypertension and type II diabetes. Hypertension was induced in spontaneously diabetic Goto-Kakizaki rats using angiotensin II and a high salt diet. Hypertensive Goto-Kakizaki rats were treated for two weeks with either AUDA or its vehicle added to drinking water. Mean arterial pressure increased from 118 ± 2 mmHg to 182 ± 20 and 187 ± 6 mmHg for vehicle and AUDA treated hypertensive Goto-Kakizaki rats, respectively. AUD...

Atorvastatin enhances interleukin-10 levels and improves cardiac function in rats after acute myocardial infarction

Clinical Science — Tue, 06 May 2008 04:00:00 +0100

Left ventricular (LV) remodeling is the basic mechanism of heart failure (HF) following myocardial infarction (MI). Whereas there is evidence that pro-inflammatory cytokines (including TNF-{alpha} and IL-6) are involved in the remodeling process, only little is known about the role of anti-inflammatory cytokines, such as IL-10. Since accumulating evidence revealed that statins possess anti-inflammatory properties, the goal of the present study was to elucidate the effect of atorvastatin on the modulation of the anti-inflammatory cytokine IL-10 and its effect on LV function in rats with HF subsequent to MI. Rats with MI, induced by permanent left anterior descending (LAD) branch ligation, were treated for 4 weeks with atorvastatin (10 mg/kg/d via oral gavage) starting on the first day after...

Coronary vasomotor and blood flow responses to isoflavone-intact soy protein in subjects with coronary heart disease or risk factors for coronary heart disease

Clinical Science — Mon, 28 Apr 2008 04:00:00 +0100

Animal data suggest favourable coronary vasomotor actions of isoflavones however the effects of isoflavones on the human coronary circulation are undetermined. We therefore investigated the effects of short-term isoflavone-intact soy protein ingestion on basal coronary arterial tone and stimulated vasoreactivity and blood flow in patients with coronary heart disease (CHD) or risk factors for CHD. Seventy-one subjects were randomised, double-blind, to isoflavone-intact soy protein (active; n=33, mean±SD, aged 58±8 years) or isoflavone-free placebo (n=38, aged 61±8 years) for 5 days prior to coronary angiography. In 25 of these subjects stimulated coronary blood flow was calculated from flow velocity, measured using intracoronary Doppler, and coronary luminal diameter before a...

Relationship between birth weight and arterial compliance in childhood

Clinical Science — Mon, 07 Apr 2008 04:00:00 +0100

There is a considerable debate about the potential influence of "fetal programming" on cardiovascular diseases in adulthood. This prospective epidemiological cohort study assessed the relationship between birth weight and arterial elasticity in 472 children from 5 to 8 years of age. The large artery elasticity index-LAEI, the small artery elasticity index-SAEI, and blood pressure were assessed by the HDI/Pulse WaveTM CR-2000. Blood concentrations of glucose, total cholesterol and fractions (LDL-c,HDL-c), and triglycerides were determined by automated enzymatic methods. Insulin was assessed by a chemiluminescent method, insulin resistance by the Homeostasis Model Assessment (HOMA), and C-reactive protein (CRP) by immunonephelometry. Two linear regression models were applied to inv...

Immune regulator cells: circulating biomarker factories in cardiovascular disease

Clinical Science — Thu, 03 Apr 2008 04:00:00 +0100

Toll Like receptors are the first line of defence of the innate immune system. These receptors recognise not only exogenous but also endogenous ligands that are expressed following arterial injury and atherosclerotic disease. Expression of the Toll like receptors 2 and 4 is observed in macrophages and different vascular cells and is increased in atherosclerotic disease. It is suggested that Toll Like receptor expression and functional responsiveness following ligation could serve as biomarkers for atherosclerotic disease progression. Recently published research papers support the concept that the Toll Like receptors are fast responders upon arterial injury. In the current issue of Clinical Science new evidence emerges that point to the potential prognostic properties of the Toll like Recep...

Significant immunomodulatory effects of Pseudomonas aeruginosa quorum-sensing signal molecules: possible link in human sepsis

Clinical Science — Tue, 25 Mar 2008 04:00:00 +0100

Pathogenic bacteria use quorum-sensing signal molecules to coordinate the expression of virulence genes. Animal-based studies have demonstrated the immunomodulatory effects of quorum-sensing signal molecules. We have examined the impact of these molecules on normal human immune function in vitro, and compared this with immune changes in patients with sepsis where quorum-sensing signal molecules were detected in patients' sera. Quorum-sensing signal molecules inhibited normal dentritic cell and T cell activation and proliferation, down-regulated expression of co-stimulatory molecules on dendritic cells; in mixed lymphocyte dendritic cell reactions (MLDCRs), secretion of IL-4 and IL-10 was enhanced, but TNF-{alpha}, IFN-{gamma} and IL-6 was reduced. Quorum-sensing signal molecules induced ap...

Dynamic cerebral autoregulatory capacity is affected early in type 2 diabetes mellitus

Clinical Science — Tue, 18 Mar 2008 04:00:00 +0100

Type 2 diabetes is associated with an increased risk of endothelial dysfunction and microvascular complications with impaired autoregulation of tissue perfusion. Both microvascular disease and cardiovascular autonomic neuropathy may affect cerebral autoregulation. We tested the hypothesis that in absence of cardiovascular autonomic neuropathy, cerebral autoregulation is impaired in subjects with type 2 diabetes with microvascular complications but intact in subjects without complications. Dynamic cerebral autoregulation and the steady state cerebrovascular response to postural change were studied in subjects with type 2 diabetes with (DM+) and without (DM-) microvascular complications in absence of cardiovascular autonomic neuropathy and in healthy subjects (CTRL). The relationship between...

Increased plasma urotensin-II levels are associated with diabetic retinopathy and carotid atherosclerosis in type 2 diabetes mellitus

Clinical Science — Fri, 14 Mar 2008 04:00:00 +0100

Human urotensin-II (U-II), the most potent vasoconstrictor peptide identified to date, is associated with cardiovascular disease. Single-nucleotide polymorphism of U-II gene (S89N) is associated with onset of type 2 diabetes mellitus and insulin resistance in the Japanese population. In the present study, we demonstrated a relationship between plasma U-II levels and progression of diabetic retinopathy and vascular complications in patients with type 2 diabetes mellitus. Eye fundus, intima-media thickness (IMT) and plaque score in the carotid artery, blood pressure (BP), fasting plasma glucose (FPG), hemoglobin A1c, U-II, angiogenesis stimulating factors, such as vascular endothelial growth factor (VEGF) and heregulin-{beta}1, and lipid profiles were determined in 64 diabetic patients and 2...

Heme oxygenase-1 gene transfer protects retinal ganglion cells from ischemia-reperfusion injury

Clinical Science — Fri, 14 Mar 2008 04:00:00 +0100

This study aimed to evaluate the role of heme oxygenase-1 (HO-1) in the retina against ischemia-reperfusion (IR) injury. Adenovirus-mediated HO-1 gene transfer (Adv-HO-1) was carried out by injection into the vitreous body to induce HO-1 overexpression. Three weeks after transfection, levels of HO-1 expression as measured by Western blots, immunohistochemical staining, and activity assay were drastically upregulated. Transient retinal ischemia was induced by raising the intraocular pressure to 150 mmHg for 60 min. Untreated IR caused a significant decrease in retinal ganglion cell (RGC) numbers 3 and 7 days after reperfusion (76.1 and 67.2% of control eyes with sham IR, respectively, P < 0.001). Eyes pretreated with Adv-HO-1 showed less RGC loss on day 3 and day 7 following reperfusion,...

Both aerobic endurance and strength training programs improve cardiovascular health in obese adults

Clinical Science — Thu, 13 Mar 2008 04:00:00 +0100

Conclusions: High-intensity aerobic interval training was better than moderate-intensity aerobic training for improving aerobic work capacity and endothelial function. An important contribution toward improved aerobic work capacity, endothelial function and cardiovascular health originates from strength training, which may serve as a substitute when whole-body aerobic exercise is contra-indicated or difficult to perform. (Source: Clinical Science)