bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of BMI on Lifetime Risk for Diabetes in the U.S.
Authors: Narayan K.M.V. , Boyle James P. , Thompson Theodore J. , Gregg Edward W. , Williamson David F. 
Published: May 2007

OBJECTIVE—At birth, the lifetime risk of developing diabetes is one in three, but lifetime risks across BMI categories are unknown. We estimated BMI-specific lifetime diabetes risk in the U.S. for age-, sex-, and ethnicity-specific subgroups.
RESEARCH DESIGN AND METHODS—National Health Interview Survey data (n = 780,694, 1997–2004) were used to estimate age-, race-, sex-, and BMI-specific prevalence and incidence of diabetes in 2004. U.S. Census Bureau age-, race-, and sex-specific population and mortality rate estimates for 2004 were combined with two previous studies of mortality to estimate diabetes- and BMI-specific mortality rates. These estimates were used in a Markov model to project lifetime risk of diagnosed diabetes by baseline age, race, sex, and BMI.
RESULTS—Lifetime diabetes risk at 18 years of age increased from 7.6 to 70.3% between underweight and very obese men and from 12.2 to 74.4% for women. The lifetime risk difference was lower at older ages. At 65 years of age, compared with normal-weight male subjects, lifetime risk differences (percent) increased from 3.7 to 23.9 percentage points between overweight and very obese men and from 8.7 to 26.7 percentage points for women. The impact of BMI on diabetes duration also decreased with age.
CONCLUSIONS—Overweight and especially obesity, particularly at younger ages, substantially increases lifetime risk of diagnosed diabetes, while their impact on diabetes risk, life expectancy, and diabetes duration diminishes with age.
Heterobimetallic complexes containing iron (II) and hexa-coordinated organosilicon
Authors: Malhotra Rajesh , Mehta Jyoti , Puri J. 
Published: May 2007

Abstract
Heterobimetallic complexes of the type R2Si(HL)Cl2 and R2SiL2 (where R = Me, Et, Ph; L = ferrocenyl aroylhydrazone) have been synthesized at 40 °C to 50 °C and at room temperature (25 °C), respectively, and characterized by elemental analysis, molar conductance, infrared and NMR (1H, 13C and 29Si) spectral data. The ligands behave as bidentate, coordinating through the azomethine nitrogen and the oxygen in the amidic and the imidic acid forms of the ligand at low temperature and at room temperature, respectively. The ligands and their organosilicon complexes have been evaluated for the antifungal activity against Alternaria alternata, Fusarium oxysporum and Rhizoctonia solani, as well as antibacterial activity against gram negative, Escherichia coli and gram positive, Bacillus subtilis, at 28 °C. Organosilicon complexes of ferrocenyl aroylhydrazone were found to be more potent than the parent ligands.
The antithrombotic effect of angiotensin-(1—7) closely resembles that of losartan
Authors: Kucharewicz Iwona , Chabielska Ewa , Pawlak Dariusz , Matys Tomasz , Rólkowski Roland , Buczko Wlodzimierz 
Published: May 2007

Angiotensin-(1-7) [Ang-(1-7)] is the bioactive peptide which may be responsible for some of the pharmacological effects of losartan. Our previous study has demonstrated the antithrombotic action of losartan in a model of experimental thrombosis. In the present study, we compared the antithrombotic action of losartan and Ang-(1-7). Acute (10 mg/kg, p.o.) and chronic (10 mg/kg, p.o., three weeks) losartan administration to spontaneously hypertensive rats (SHR) induced a decrease in thrombus weight (1.6±0.6 mg and 1.2±0.3 mg respectively vs. control 2.9±0.8 mg; p<0.05, p<0.05). A similar reduction was observed in two-kidney, one-clip hypertensive rats (2K-1C) receiving acute losartan administration (1.39±0.29 mg vs. 3.25±0.62 mg; p<0.01). Infusion of Ang-(1-7) to 2K-1C rats also reduced the thrombus weight (1.01±0.34 mg, 1.23±0.38 mg and 2.17±0.36 mg for 1, 10, 100 pmol/kg/min, respectively vs. 3.58±0.6 mg control; p<0.01, p<0.01, p<0.05). Losartan produced a decrease in systolic blood pressure (BP) in SHR as well as in 2K-1C rats, while Ang-(1-7) infusion had no effect on BP. Acute losartan dosing to 2K-1C rats decreased platelet adhesion to fibrillar collagen (24.9±1.0% vs. control 31.5±1.1%, p<0.001). The incubation of platelet samples with Ang-(1-7) (10-6 and 10 —5 M) also reduced adhesion to fibrillar collagen (38.4±0.1% and 33.8±0.8% respectively vs. control 40.0±0.6%; p<0.05, p<0.001). There were no apparent changes in prothrombin time, activated partial thromboplastin time and euglobulin clot lysis time in losartan and Ang-(1-7)-treated groups. We conclude that, like losartan, Ang-(1-7) is able to act as an antithrombotic agent.
Saving lives: Long-term morbidity and mortality trials with selective angiotensin receptor blocker therapy
Authors: McInnes Gordon T 
Published: May 2007

Summary Prospective randomised trials have demonstrated convincingly the benefits of drug treatment of hypertension. Treatment with conventional antihypertensive agents reduces the incidence of cardiovascular events by about that which would be expected from epidemiological data for the achieved difference in blood pressure. Newer agents, such as angiotensin II receptor blockers, have potential for benefits beyond blood pressure reduction. This rationale is under evaluation in a number of long-term morbidity and mortality trials which will report over the next few years, with the largest, VALUE, due to provide results in 2004. The findings from these trials will be decisive in determining the future role of this important new class of drugs.
New basic science initiatives with the angiotensin II receptor blocker valsartan
Authors: de Gasparo Marc 
Published: May 2007

SummaryAngiotensin II (Ang II) plays a key role in the regulation of blood pressure and fluid homeostasis. Valsartan is a highly selective Ang II receptor blocker that specifically and selectively blocks Ang II at the AT1-receptor. In animal models, valsartan has shown positive effects on vasoconstriction, proliferation, remodelling, endothelial function and thrombogenesis, inflammation and atherosclerosis. These data are likely to be confirmed by the results of current clinical trials and valsartan is set to provide improved cardiovascular therapy in the future.
Transforming growth factor-β1 induces angiotensin-converting enzyme synthesis in rat cardiac fibroblasts during their differentiation to myofibroblasts
Authors: Petrov Victor V , Fagard Robert H , Lijnen Paul J 
Published: May 2007

Objectives Appearance of angiotensin-converting enzyme (ACE) in fibrotic tissue can be the result of the action either of one particular growth factor or of cross-talk between multiple factors. Transforming growth factor-β1 (TGF-β 1) is an effective inducor of the differentiation of cultured fibroblasts to myofibroblasts, which are heterogeneous cells with different phenotypes. The present study investigated whether TGF-β1 is able to induce, in vitro, the differentiation of cultured fibroblasts to myofibroblasts with a phenotype containing ACE. Design Adult rat cardiac ventricular fibroblasts were obtained from hearts perfused with collagenase. Cells from second passage were always used. Rat cardiac ventricular fibroblasts were incubated with TGF-β1 (10 ng/ml) for seven days. Cell characterisation was performed using light microscopy and indirect immunostaining. Presence of vimentin, desmin, factor VIII, α-smooth muscle actin, and ACE was checked with both immunostaining and Western blotting. ACE activity was measured fluorometrically with hippuryl-histidyl-leucine as substrate. Synthesis of DNA was measured as 3H-thymidine incorporation. Results Fibroblasts contained two types of activity of hip-his-leu degradation, namely a lisinopril-dependent activity (ACE activity) and a lisinopril-independent activity (`ACE-like' activity) which is performed by peptidase(s) other than ACE. The ACE activity constituted approximately 30% of the total activity. TGF-β1 induced an increase in both ACE activity and ACE protein (detected by immunoblotting) by 4.5 ± 0.9- and 6.9 ± 2.0-fold, respectively (p<0.05). This induction of ACE was accompanied by a profound modification of the fibroblasts phenotype, which consisted of a change in cell morphology, an enlargement of cell volume and an increase in cell protein content. TGF-β1 profoundly inhibited 3H-thymidine incorporation and the number of cells in growing cultures. The induction of α-smooth muscle actin by TGF-β 1 (6.8 ± 2.8-fold increase, p<0.05) simultaneously with these modifications in cell morphology and proliferation indicates the appearance of myofibroblasts. These myofibroblasts did not contain desmin. Conclusion TGF-β 1 is able to induce the appearance of ACE in cultures of adult rat cardiac ventricular fibroblasts. The appearance of the enzyme is accompanied by the differentiation of fibroblasts to myofibroblasts.
Interaction of ACE inhibitors and AT1-receptor blockers on maximum blood pressure response in spontaneous hypertensive rats
Authors: Morgan Trefor , Griffiths Cory , Delbridge Lea 
Published: May 2007

This study in spontaneous hypertensive rats (SHR) was designed to determine whether a greater fall in blood pressure (BP) could be achieved with the combination of an angiotensin-converting enzyme inhibitor (ACE-I) and an AT1-receptor blocking drug than with higher doses of either drug alone. The peak effect of captopril occurred 3—4 hours post-dose and a plateau response was achieved with 10 mg/kg. The peak effect of losartan occurred 7—8 hours post-dose and a plateau response was achieved with 10 mg/kg. Increasing the dose of either drug caused no greater fall in BP, but increased the duration of the effect. Captopril, 10 mg/kg, administered with losartan 10 mg/kg caused a greater fall in BP than captopril or losartan, 20 mg/kg. This was present after acute doses or after one week of daily therapy. The combination of ACE-I and AT1-blocking drugs is more effective than either therapy alone and may be a useful combination to manage hypertension and/or cardiac failure.
Oxidative stress increases the expression of the angiotensin-II receptor type 1 in mouse peritoneal macrophages
Authors: Keidar Shlomo , Heinrich Ronit , Kaplan Marielle , Aviram Michael 
Published: May 2007

Angiotensin II (Ang II) has been shown to accelerate atherogenesis, and the cellular Ang II type 1 (AT1) -receptor mediates most of Ang II-induced proatherogenic effects. In this study we have examined the effect of macrophage oxidative stress on cellular AT1-receptor expression. Mouse peritoneal macrophages (MPM) from apolipoprotein-E deficient (E0) mice at increasing ages (1—6 months) demonstrated an age-dependent increase in cellular lipid-peroxides (PD) content. In parallel, the AT1-receptor mRNA and protein levels both increased by up to 3.7-fold and 1.7-fold, respectively, in MPM from 6-month old mice compared with 1-month old mice. Vitamin E supplementation to E0 mice significantly decreased the MPM PD content and macrophage AT1-receptor mRNA expression compared with placebo-treated mice. The role of oxidative stress in the cellular expression of AT1-receptors was further demonstrated by manipulation of macrophage glutathione content. Buthionine-sulfoximine, a glutathione synthesis inhibitor, increased MPM PD content and AT1receptor mRNA expression, whereas L-2-oxothiazolidine-4-carboxylic acid, that contributes to glutathione synthesis, reduced macrophage PD and AT1receptor mRNA expression. Incubation of MPM with oxidised low-density lipoproteins (LDL) led to a significant, dose-dependent and time-dependent increase in macrophage AT1-receptor mRNA and protein expression, compared with control cells. In contrast, native LDL or acetylated LDL did not significantly affect macrophage AT1-receptor mRNA expression. In conclusion, our findings suggest that oxidative stress in macrophages induces AT1-receptor expression. This phenomenon can stimulate the interaction of Ang II with macrophages and hence accelerate macrophage foam cell formation and early atherogenesis.
Acute and long-term effects of ACE inhibition on renal haemodynamics in glomerular and interstitial nephropathies
Authors: Guidi Ettore , Minetti Enrico E , Cozzi Maria Grazia 
Published: May 2007

Background Angiotensin-converting enzyme (ACE) inhibitors are the drugs of choice for the treatment of hypertension in patients with non-diabetic nephropathies. However, not every trial has reported better results with ACE inhibitors (ACE-I) than with other drugs. This study investigates whether the acute and chronic effects of ACE inhibition on renal and glomerular haemodynamics are similar in glomerular and interstitial nephropathies. Methods We studied 20 hypertensive patients, on their usual diet, with mild-to-moderate chronic renal failure secondary to non-diabetic nephropathy. After a three-week wash out period, we determined plasma clearances of para-amino-hippurate and inulin before, and after acute oral administration of either enalapril or ramipril. This same test was carried out after one and two years of treatment with the same drug. Results Acute ACE inhibition causes a decrease of renal perfusion, glomerular filtration and pressure with an increase of afferent resistances. Long-term ACE inhibition is associated only with a decrease in renal perfusion, with a non-significant tendency to higher filtration fraction and lower afferent resistances. All the renal haemodynamic modifications mentioned above are present only in patients with glomerular diseases. Conclusions Renal and glomerular haemodynamic responses are not similar after acute and chronic ACE inhibition. Only patients with glomerular diseases show acute or long-term responses to ACE inhibition.
The renin-angiotensin system does not contribute to the endothelial dysfunction and increased infarct size in rats exposed to second hand smoke
Authors: Zhu Bo-qing , Sievers Richard E , Browne Amanda EM , Hillman Robert T , Chair Kamel , Lee Randall J , Chatterjee Kanu , Glantz Stanton A , Parmley William W 
Published: May 2007

Introduction Both second hand smoke (SHS) and the renin-angiotensin system (RAS) contribute to endothelial dysfunction and increased infarct size in a rat ischaemia-reperfusion model. However, the potential interaction between SHS and the RAS is unknown. Methods Eighty-four rats were randomised into four groups: group C was a normal control; L was given 40 mg/kg/day of losartan in drinking water; SC and SL were exposed to SHS (smoking chamber) and given regular water or 40 mg/kg/day of losartan in drinking water, respectively. After six weeks of pre-treatment, rats were subjected to 17 minutes of left coronary artery occlusion and 2 hours of reperfusion with haemodynamic and ECG monitoring. Results Haemodynamics were not significantly different among the four groups. Losartan increased the threshold for ventricular fibrillation (p=0.0001) and reduced spontaneous ventricular arrhythmias (p=0.002) during ischaemia-reperfusion, while SHS did not (p=0.713, 0.110), and there was no interaction between losartan and SHS. The maximal endothelium-dependent vasorelaxation induced by a calcium ionophore (A23187) was increased by losartan (p=0.007). Myocardial infarct size was smaller in the losartan groups (p=0.032), larger in the SHS groups (p=0.0001), and there was no significant interaction. Conclusion In conclusion, losartan decreased infarct size and increased endothelium-dependent vasorelaxation. SHS exposure impaired endothelial function and increased infarct size. The effects of losartan and SHS were consistently independent of each other. These results suggest that the RAS does not contribute to the adverse effects of SHS.
Lack of rapid aldosterone effects on forearm resistance vasculature in health
Authors: Gunaruwan Prasad , Schmitt Matthias , Taylor Justin , Lee Leong , Struthers Allan , Frenneaux Michael 
Published: May 2007

Objectives Systemic infusions of aldosterone cause an acute increase in systemic vascular resistance (SVR) in healthy subjects. It is not clear whether this is due to a direct effect on the vasculature or the result of increased sympathetic tone. We investigated the short-term effects of locally infused aldosterone on the forearm resistance bed. Methods In this dose response study, we assessed the effects of incremental doses (10, 50, 100 ng/minute) of intrabrachial aldosterone on forearm blood flow (FBF), using conventional strain gauge plethysmography. Arterial blood pressure was monitored continuously, using finger photo-plethysmography. Forearm vascular resistance (FVR) was calculated. FBF and FVR were also measured in the non-infused arm. Changes in FBF and FVR in the infused arm were corrected for those occurring in the control arm. Results Plasma aldosterone levels in the venous effluent of the infused arm increased in a dose-dependent fashion, from 113.3±17.9 pg/ml at baseline to 297.8±51.8 pg/ml at 10 ng/minute (p=<0.01), 743.9±105.9 pg/ml at 50 ng/min (p=<0.001 vs. baseline) and 1230.6±73.7 pg/ml at 100 ng/min (p=<0.0005 vs. baseline). Plasma concentrations of aldosterone in the control arm did not change significantly vs. baseline. The corrected FBF (+4.1±10.3%) and corrected FVR (+4.3±11.3%) did not change significantly even at peak infusion rates. Conclusions Local intra-arterial infusion of aldosterone had no acute effect on forearm resistance vessels in healthy male volunteers.
Transforming growth factor-β1-mediated collagen gel contraction by cardiac fibroblasts
Authors: Lijnen Paul , Petrov Victor , Fagard Robert 
Published: May 2007

Objective Myofibroblasts and transforming growth factor-β1 (TGF-β1) are key elements of cardiac tissue fibrosis development. The aim of this study was to determine whether the ability of TGF-β1 to affect the contractile activity of cardiac fibroblasts depends on their differentiation into myofibroblasts. Methods Cardiac fibroblasts (from male adult Wistar rats) from passage two were cultured to confluency and incubated on a hydrated collagen gel with and without TGF-β1 (0, 20, 40, 100, 200, 400 or 600 pmol/L) for one, two and three days in a Dulbecco's Modified Eagle's Medium without foetal bovine serum. Results TGF-β1 dose-dependently increased the contraction of collagen gel mediated by cardiac fibroblasts, reaching a maximal effect at 100 pmol/L TGF-β1. TGF-β 1 also stimulated 3H-thymidine incorporation and total protein content in cardiac fibroblasts in the collagen gel lattice . TGF-β 1 dose-dependently induced an increase in αsmooth muscle actin, a marker of myofibroblasts. The TGF-β1-induced reduction of area of the collagen gel was negatively correlated to the TGF- R β 1-evoked appearance of α-smooth muscle actin in the collagen gel matrix. Conclusion Our data demonstrate that TGF-β1 increased the contractile activity of adult rat cardiac fibroblasts and their ability to differentiate into myofibroblasts. Because contractile activity was correlated with differentiation, the influence of TGF-β1 on cardiac fibroblast-induced collagen gel contraction might depend on the promotion of myofibroblast differentiation.
Biphasic effects of angiotensin (1-7) and its interactions with angiotensin II in rat aorta
Authors: Haulica Ion , Bild Walther , Mihaila Christian N , Ionita Teodor , Boisteanu Corneliu P , Neagu Bogdan 
Published: May 2007

Using isolated rat aortic rings perfused with Krebs-Henseleit saline, the vascular effects of angiotensin (1-7) (Ang [1-7]) and its interactions with angiotensin II (Ang II) were investigated. Ang (1-7) induced endothelium-dependent relaxation and vasodilating effects in preparations precontracted with phenylephrine. Without preconstriction, Ang (1-7) at high doses (10 -6—10-5 M) produced either a significant inhibition of Ang IIinduced vasoconstriction or a non-tachyphylactic vasopressor response. While losartan inhibited the vasoconstriction induced by Ang (1-7), A779 blocked only its relaxation. Unlike losartan, blockade of AT2-receptors with PD 123319 had no effect. Taking into account the biphasic effects of angiotensin (1-7), we propose that it is one of the active components of the renin-angiotensin system, which is involved as a modulator both in the counter-regulatory actions of Ang II and in the self-regulation of its own vasodilating effects.
Effect of chronic treatment with the vasopeptidase inhibitor AVE 7688 and ramipril on endothelial function in atherogenic diet rabbits
Authors: Weckler Nadine , Leitzbach Daniela , Kalinowski Leszek , Malinski Tadeusz , Busch Andreas E , Linz Wolfgang 
Published: May 2007

Cardiovascular disease is the major cause of death in Western nations, although improved possibilities regarding diagnosis and therapy now exist. Endothelial dysfunction is triggered by cardiovascular risk factors such as hypercholesterolaemia, hypertension, adiposity and smoking, contributing to the common endpoint of atherosclerosis. This study examined the pharmacological effects of angiotensin-converting enzyme (ACE) and combined ACE-neutral endopeptidase (NEP) (vasopeptidase) inhibitors on endothelial dysfunction in the model of hyperlipidaemic rabbits. The focus of the study was to assess endothelial function after treatment with the ACE-NEP inhibitor AVE 7688 (30 mg/kg/day) in comparison to the ACE inhibitor (ACE-I) ramipril (1 mg/kg/day). Different parameters, such as endothelial function, blood pressure (BP), expansion of plaques, endothelial nitric oxide (NO) and superoxide (O2 ) release and plasma levels of various lipidaemic parameters were analysed. Control groups consisted of one group fed only with normal diet, one group fed only with atherogenic diet and the direct control group fed with varied diets (six weeks atherogenic diet followed by 12 weeks normal diet). Since for the treatment of atherosclerosis, a change in feeding is absolutely necessary, in the present study, at the start of the treatments with AVE 7688 and ramipril, the rabbits food was changed to a normal diet. At the end of the study, mean arterial blood pressure (MAP) was measured in the anaesthetised animals. The values in standard, atherogenic and varied diet-fed rabbits were around 73±2 mmHg. Angiotensin I (Ang I) given intravenous (i.v.) induced a strong increase in MAP of about 20%. In both the treated groups Ang I-induced BP increase was inhibited. In contrast, i.v. bradykinin led to a strong reduction in MAP in both the treated groups of around 50%. Six weeks' feeding with an atherogenic diet in the rabbits induced an enduring endothelial dysfunction despite the food subsequently being changed to a normal chow. All measured parameters indicated a significant favourable effect on endothelial dysfunction as a result of the two treatment regimens. Endothelial function measured in the organ chamber showed somewhat greater improvement in the ACE-NEP treated group than in the ACE-I treated group. The treatment with ramipril, as well as with AVE 7688, restored endothelial function by increasing the ratio of NO to O2- concentration and bioavailability of NO. In this study, a similar protective effect on endothelial function was shown by ACE-NEP inhibition as already seen with ACE inhibitors in an animal model of atherosclerosis.