bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylenetetrahydrofolate reductase polymorphism (C-677T) and coronary artery disease
Authors: MALIK N. M. , SYRRIS P. , SCHWARTZMAN R. , KASKI J. C. , CROSSMAN D. C. , FRANCIS S. E. , CARTER N. D. , JEFFERY S. 
Published: August 2015

1.Many studies have shown that hyperhomocysteinaemia is a risk factor for atherosclerotic vascular disease. A mutation (C-677T) in the gene coding for the methylenetetrahydrofolate reductase (MTHFR) enzyme has been shown to produce a thermolabile form of the enzyme. Homozygosity for this mutation has been correlated with an elevated plasma homocysteine concentration. The present study aimed to determine whether this mutation was a risk factor for coronary artery disease (CAD). This was achieved by comparing the frequency of the C-677T mutation in patients with angiographically proven CAD against angiographically normal patients in two separate U.K. samples. The analysis was repeated with CAD patients split into those with ⩾ 99% stenosis of arteries and those without, to establish whether the C-677T mutation could be correlated with severity of CAD.
2.Two patient groups were selected from London and Sheffield. The London group comprised 174 cases and 148 controls. The Sheffield group comprised 93 cases and 85 controls. The DNA samples of the patients were genotyped by polymerase chain reaction and restriction enzyme digestion.
3.For London the homozygous C-677T frequencies were: 0.07 (controls), 0.09 (CAD without ⩾ 99% stenosis) and 0.10 (CAD with ⩾ 99% stenosis). For Sheffield the homozygous C-677T frequencies were: 0.08 (controls), 0.10 (CAD without ⩾ 99% stenosis) and 0.11 (CAD with ⩾ 99% stenosis). No association was found between the C-677T mutation and CAD in our sample geographical groups. Statistical comparison by genotype distribution for 0 ;VD (no vessel disease, i.e. 0% diameter reduction in all epicardial arteries) versus CAD without ⩾ 99% stenosis: London, P = 0.19; Sheffield, P = 0.53; 0 ;VD versus CAD with ⩾ 99% stenosis: London, P = 0.23; Sheffield, P = 0.55.
Diminished insulin clearance during late pregnancy in patients with Type I diabetes mellitus
Authors: BJÖRKLUND Anders O. , ADAMSON Ulf K. C. , LINS Per-Eric S. , WESTGREN L. Magnus R. 
Published: August 2015

1.Intensive insulin treatment of patients with Type I diabetes mellitus during pregnancy is associated with a high frequency of serious hypoglycaemic events. A potential change in insulin metabolism during pregnancy may affect both the frequency and the severity of insulin-induced hypoglycaemia.
2.In 10 patients with Type I diabetes, during the third trimester of pregnancy and 5 to 13 months after delivery, hypoglycaemia was induced by the hyperinsulinaemic hypoglycaemic clamp technique. A constant high-dose intravenous insulin infusion was administered for 150 ;min and arterial blood glucose was clamped at 2.2 ;mmol/l by counterregulation with intravenous glucose. During the experiment venous samples were collected for later analysis of free plasma insulin, whereby the metabolic clearance rate of insulin could be calculated.
3.The desired blood glucose level was approached after approximately 60 ;min of insulin infusion. After just 30 ;min the insulin levels were significantly higher during pregnancy compared with after delivery. In addition, the steady-state insulin level from 90 to 150 ;min was significantly higher during pregnancy.
4.From the steady-state insulin levels at 90 to 150 ;min, the metabolic clearance rate of insulin was calculated, being 24% higher after delivery.
5.We conclude that there is a decreased metabolic clearance rate of insulin during pregnancy. This might be due to altered blood-flow distribution, decreased hepatic insulin extraction and relative increase in body fat during pregnancy. A decreased clearance of insulin will contribute to the risk for serious hypoglycaemic events in patients with Type I diabetes during pregnancy.
Stimulation of apoptosis by sulindac and piroxicam
Authors: WADDELL William R. 
Published: August 2015

1.Sulindac, cis-5-fluoro-2-methyl-1-(p-methylsulphinylbenzylidene)indene-3-acetic acid, inhibits growth of colon polyps and cancers. This effect has been attributed to inhibition of prostaglandin synthesis but more recent observations indicate that, in vitro, cells that do not have cyclo-oxygenase nor RNA for synthesis of such enzymes are affected by sulindac. Therefore the presumptive effect is probably not correct.
2.It has also been found that sulindac stimulates apoptosis. It is herein postulated that in tumour cells such effects may be due to interaction of the anionic form of the drug with protons in the intermembrane space of mitochondria to disrupt the potential across the inner mitochondrial membrane and thereby initiate apoptosis. Normal cells are not affected.
Renal arginine metabolism in fasted rats with subacute short bowel syndrome
Authors: DEJONG Cornelis H. C. , WELTERS Carlo F. M. , DEUTZ Nicolaas E. P. , HEINEMAN Erik , SOETERS Peter B. 
Published: August 2015

1.Arginine can be produced in the kidney from citrulline. An important source of circulating citrulline is the intestinal breakdown of glutamine. Consequently, partial enterectomy leads to decreased plasma citrulline levels. The aim of the present study was to investigate the effect of diminished arterial citrulline levels on renal arginine production and total-body free arginine pools.
2.Renal amino acid metabolism was studied 24 ;h after 75% small bowel resection in rats fasted overnight (16 ;h) (n = 12; total fast 40 ;h). Sham-operated (n = 9) and non-operated 16-h and 40-h fasted controls were studied in parallel (n = 8/n = 7). During anaesthesia, l-(2,3-3H)-arginine and para-aminohippuric acid were infused until steady state. Subsequently, arterial and renal venous blood samples were taken. Concentrations of para-aminohippurate and amino acids and specific activity of arginine and citrulline were measured to calculate renal plasma flow, net renal uptake or release, and unidirectional influx or efflux of arginine and citrulline, as well as whole-body arginine turnover.
3.Arterial citrulline was decreased in enterectomized rats compared with sham-operated rats (23±3 versus 44±6 ;μM). Net renal citrulline uptake and arginine release were almost stoichiometric (-36±7 and 38±6 ;nmol·min-1·100 ;g-1 body weight respectively in sham-operated rats) and were both diminished by 50% in enterectomized versus sham-operated rats. In all groups, net renal arginine production accounted for less than 10% of whole-body rate of arginine appearance (488 ;nmol·min-1·100 ;g-1 body weight in the sham group). Despite decreased net renal citrulline consumption and renal arginine production in enterectomized rats, whole-body rate of arginine appearance and arterial arginine did not change significantly.
4.In conclusion, net renal arginine production is reduced 24 ;h after 75% enterectomy in fasted rats. However, this does not have important effects on whole-body arginine production.
A comparison of the development of renal hypertension in male and female rats
Authors: OKUNIEWSKI Rachel , DAVIS Elizabeth A. , JARROTT Bevyn , WIDDOP Robert E. 
Published: August 2015

1.The objective of this study was to determine the influence of gender on the development of renal hypertension in Sprague–Dawley rats using the Goldblatt two-kidney, one-clip (2K1C) model. In addition, this study examined the effect of ovariectomy upon the development of hypertension in female rats.
2.At 10 weeks of age, male, intact female and ovariectomized female rats underwent clipping of the right renal artery or sham operation. Tail-cuff plethysmography was used to monitor the systolic blood pressure of all animals for 7 weeks post-clipping or sham operation. Rats were sub-grouped according to whether or not they developed hypertension (systolic blood pressure ⩾ 150 ;mmHg).
3.Within 2 to 3 weeks of clipping, hypertension was induced in only 53% (n = 120) of the intact female 2K1C rats, but in 83% (n = 18) of the male and 78% (n = 18) of the ovariectomized female rats.
4.Seven weeks after right renal artery clipping, plasma renin activity was determined in a subset of each group and was found to be 5–6 fold higher in male (17.29±4.04 ;ng angiotensin I·h-1·ml-1) and ovariectomized female (9.71±1.25 ;ng angiotensin I·h-1·ml-1) hypertensive rats compared with their respective normotensive or sham-operated counterparts (3.39±0.58 ;ng angiotensin I·h-1·ml-1 and 1.60±0.41 ;ng angiotensin I·h-1·ml-1 respectively) (P< 0.05, analysis of variance). In contrast, the plasma renin activity measured in intact female hypertensive rats was not significantly different from that measured in the corresponding 2K1C normotensive or sham-operated groups.
5.These results indicate that the success rate of inducing renal hypertension in Sprague–Dawley rats is higher in males than in intact females. Furthermore, these results suggest that the induction of 2K1C hypertension may be influenced by ovarian hormones.
Arrhythmogenic effect of ventriculography in patients with left ventricular dilation and/or hypertrophy
Authors: SERAFI Abdulhalim S. , EVANS Stephen J. , JONES John V. 
Published: August 2015

1.This study examined the effect of an acute injection of contrast medium on generation of arrhythmias in diseased hearts in man.
2.Subjects were 100 patients in sinus rhythm undergoing cardiac catheterization in whom good quality echocardiograms could be obtained. The subjects comprised 78 males and 22 females aged 37–83 years.
3.Arrhythmia induced by left ventricular angiography ranged from nil to brief bursts of ventricular tachycardia. There was a strongly positive relationship between left ventricular internal dimension in diastole (LVIDd) and induced arrhythmia. Out of 26 patients, 25 developed arrhythmia when LVIDd ⩾ 5 ;cm (96%), but only 24 out of 74 patients developed arrhythmia when LVIDd < 5 ;cm (32%) (P< 0.001). In non-dilated hearts where K+ < 4.0 ;mmol/l, arrhythmia developed in 100% (10 out of 10) of those with left ventricular hypertrophy (LVH), but in only 40% (8 out of 20) without LVH (P< 0.005). Where K+ ⩾ 4.0 ;mmol/l, no arrhythmia occurred in patients with LVH but was present in 52% (31 out of 60) of patients without LVH (P< 0.005). There were no relationships with age, end-diastolic pressure, blood pressure, ischaemic heart disease or sex of patient.
4.These data support the view that acute injection of contrast medium in humans induces arrhythmias dependent upon the underlying state of the heart, with potentially complex interplay between left ventricular dimension, hypertrophy and potassium status, supporting similar observations in experimental animals.
Porcine hepatic response to sepsis and its amplification by an adrenergic receptor α1 agonist and a β2 antagonist
Authors: TIGHE D. , MOSS R. , BENNETT D. 
Published: August 2015

1.We investigated the effect of adrenergic receptor stimulation or inhibition on the hepatic ultrastructural changes in a porcine faecal peritonitis model of multi-organ failure. We infused either the α1 adrenergic receptor agonist methoxamine or the β2 adrenergic receptor antagonist ICI 118551 during 8 ;h of the study.
2.Anaesthetized pigs (25–30 ;kg) were divided into four non-septic groups (control, non-septic, non-septic methoxamine and non-septic ICI 118551) and three septic groups (septic, septic methoxamine and septic ICI 118551).
3.Changes in hepatic ultrastructure were measured by morphometric analysis. The septic group was significantly worse than all the non-septic groups. Septic methoxamine and septic ICI 118551 were significantly worse than the septic group.
4.Septic methoxamine and septic ICI 118551 had a significantly increased perisinusoidal space; septic methoxamine had significant hepatocyte vacuolation.
5.Hepatic ultrastructural changes were independent of hepatic blood flow.
6.Septic methoxamine had significant myocardial depression.
7.The α1 adrenergic receptor agonist methoxamine or the β2 antagonist ICI 118551 both amplified the hepatic injury normally found during sepsis in our porcine model.
8.These findings suggest that during sepsis a protective endogenous β2 adrenergic receptor-mediated anti-inflammatory response is activated via cell membrane transduction to stimulate the trimeric G-protein complex Gs and activate the second cell messenger cAMP.
9.In addition, it is likely that α1 adrenergic receptor agonists amplify the inflammatory response by stimulating the cell-surface receptor-linked trimeric G-protein complex to activate Gq and the second cell messenger phospholipase C.
Randomized clinical trial comparing the effectiveness of two dietary interventions for patients with hyperlipidaemia
Authors: MHURCHÚ Cliona NÍ , MARGETTS Barrie M. , SPELLER Viv 
Published: August 2015

1.Intervention trials in free-living populations have shown relatively small reductions in risk factors for cardiovascular disease, including lipid levels, and have led some to question whether diet is an effective treatment for hyperlipidaemia. However, behaviour change is a complex process and it is possible that standard intervention methods fail to motivate people sufficiently to comply with dietary advice.
2.This study applied motivational interviewing, a style of behaviour change counselling, to dietary education for people with hyperlipidaemia. One-hundred and twenty-one patients with hyperlipidaemia who had been referred to a hospital dietetic department for dietary advice were randomized to receive either standard or motivational dietary interventions for a period of 3 months. Outcomes assessed included dietary knowledge, stage of change, dietary intakes, lipid levels and body mass indices.
3.From baseline, both methods of dietary intervention resulted in self-reported changes in dietary habits and knowledge, statistically significant reductions in intake of total fat (from 32.8% to 28.4%), saturated fat (from 11.4% to 9.2%) and energy intakes [-239 ;kcal (-999.98 ;kJ)/day], and in body mass indices (-0.45 ;kg/m2). Serum cholesterol did not change significantly in either intervention group.
4.Motivational and standard dietary interventions achieved statistically significant changes in reported dietary knowledge and behaviour, and led to a reduction in body weight, but not serum cholesterol. Whether this lack of effect is real or due to subjects overestimating true dietary change cannot be determined. Change in body weight was associated with a reported change in energy intake; this provides some support for there having been a real change in intake.
Contractile response of isolated human hepatic arteries to α-adrenoceptor agonists is not impaired in patients with cirrhosis
Authors: HADOKE Patrick W. F. , DILLON John F. , JOHN Timothy G. , WALKER Simon W. , HAYES Peter C. , WILLIAMS Brent C. 
Published: August 2015

1.Impaired vasoconstriction in animals with cirrhosis is maintained in isolated vessels in vitro, indicating an intrinsic alteration in function or structure of the cells in the vascular wall. This may be due to receptor down-regulation, a defect in post-receptor signal transduction or overproduction of vasodilator compounds. This investigation examined the role of these mechanisms in modulating α-adrenoceptor-mediated contraction in hepatic arteries from patients with advanced cirrhosis.
2.Hepatic arteries were obtained from subjects with and without cirrhosis for functional investigation in vitro. Endothelial cell function was assessed using endothelium-dependent (acetylcholine) and independent (3′-morpholinosydnonimine) vasodilators. α-Adrenoceptor-mediated contraction was assessed by constructing cumulative concentration–response curves to the α1-selective agonist phenylephrine, the non-selective adrenoceptor agonist noradrenaline and the receptor-independent vasoconstrictor potassium chloride.
3.None of the vessels used in this study had an intact endothelium but endothelium-independent relaxation was not different in arteries from subject with (79.5±10.16%; n = 23) and without (84.45±18%; n = 20) cirrhosis. Phenylephrine, noradrenaline and potassium chloride produced contractions that were of similar size (P> 0.05) in arteries from subjects with (10.10±0.97 ;g, 8.85±1.03 ;g and 8.56±0.65 ;g respectively) and without (10.42±1.23 ;g, 9.58±1.39 ;g and 8.62±0.98 ;g respectively) cirrhosis. The sensitivities (pD2) of the responses to these agonists were also similar (P< 0.05) in arteries from patients with cirrhosis (5.45±0.10, 5.60±0.12 and 1.57±0.03 respectively) and those from non-cirrhotic donors (5.58±0.11, 5.67±0.11 and 1.54±0.05 respectively).
4.Contraction of the denuded hepatic artery was unaffected by cirrhosis indicating that vascular abnormalities in this condition in man are not due to an intrinsic alteration of smooth muscle cell function in hepatic conduit arteries.
Measurement and significance of circulating natriuretic peptides in cardiovascular disease
Authors: SAGNELLA G. A. 
Published: August 2015

1.The major cardiovascular and renal actions of α-atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and the fact that the heart is strategically located to sense changes in intravascular volume indicate the importance of these peptides in the overall control of the extracellular fluid volume under normal and pathophysiological conditions.
2.This review examines the clinical and diagnostic significance of the measurement of plasma natriuretic peptides in diseases of the cardiovascular system with particular emphasis on the assessment of patients with heart failure.
3.Raised plasma levels of ANP and BNP have repeatedly been found in patients with heart disease originating from diverse causes including tachycardias, valvular stenosis or ventricular dysfunction. The raised circulating levels of natriuretic peptide (ANP, N-terminal proANP and BNP in particular) are associated with (i) raised atrial and pulmonary wedge pressures; (ii) reduced ventricular systolic and diastolic function; (iii) presence (and possibly geometric form) of left ventricular hypertrophy; and (iv) severe myocardial infarction. Although both plasma ANP and BNP are raised in the presence of left ventricular hypertrophy, BNP appears to be a better index of left ventricular hypertrophy.
4.Several situations where the measurement of natriuretic peptides may be of benefit in the overall assessment of heart disease are discussed. However, it is emphasized that the measurement of plasma natriuretic peptides alone appears to be of limited value as a specific diagnostic tool, given that raised levels are a consequence of haemodynamic and structural abnormalities arising from diverse pathological processes. Despite these limitations, the major value of plasma natriuretic peptides in the examination of patients with suspected heart disease rests on the premise that: (i) a normal value would not be consistent with cardiac disease; (ii) the presence of markedly raised levels may help to target those for subsequent detailed assessment of underlying cardiac dysfunction; and (iii) markedly raised levels of plasma natriuretic peptides after myocardial infarction can identify those at high risk of death.
Regional plasma levels of cardiac peptides and their response to acute neutral endopeptidase inhibition in man
Authors: LAINCHBURY J. G. , NICHOLLS M. G. , ESPINER E. A. , IKRAM H. , YANDLE T. G. , RICHARDS A. M. 
Published: August 2015

1.The cardiac natriuretic peptides, atrial natriuretic peptide and brain natriuretic peptide, are degraded via clearance receptors and the enzyme neutral endopeptidase (EC 3.4.24.11). We studied the regional plasma concentrations of these peptides and their response to acute neutral endopeptidase inhibition in a consecutive series of patients with a broad spectrum of severity of cardiac dysfunction who were undergoing diagnostic right and left heart catheterization (24 patients, mean age 62.6 years).
2.Baseline blood samples were obtained for hormone analysis from femoral artery, femoral vein, renal vein, hepatic vein, superior vena cava, coronary sinus and pulmonary artery, and initial haemodynamic measurements were made. Twelve patients then received a neutral endopeptidase inhibitor (SCH 32615, 200 ;mg intravenously) and 12 received vehicle alone. The cardiac catheterization procedure was then completed and haemodynamic and hormone measurements were repeated.
3.Haemodynamic status was similar at baseline in both groups, and at repeated measurement (post-procedure after placebo or active drugs) haemodynamic variables were not significantly different from baseline values. Plasma levels of atrial and brain natriuretic peptides exhibited an arteriovenous increment (344% and 124% respectively) across the heart (femoral artery to coronary sinus) and decrement (by 28–54% and 9–16% respectively) across all other tissue beds (P&lt; 0.05 for all) except the lung (no change). Final levels of atrial natriuretic peptide rose above initial levels at all sites in both groups (P&lt; 0.05) except coronary sinus levels in the vehicle group (no change). The increase was consistently greater in the inhibitor group at all sites (P&lt; 0.05 versus placebo). Levels of brain natriuretic peptide rose at all sites in the inhibitor group only (P&lt; 0.05). The transcardiac step-up in atrial natriuretic peptide was markedly augmented after the administration of neutral endopeptidase inhibitor. Other tissue gradients were not significantly altered by neutral endopeptidase inhibitor.
4.Atrial and brain natriuretic peptides in plasma are degraded by a number of tissues, and respond differently to cardiac catheterization. Neutral endopeptidase has a significant role in determining plasma levels of natriuretic peptides, in part perhaps by influencing the amount of intact peptide reaching the circulation after secretion from the heart.
Increased Na+ and decreased Mg2+ intracellular concentrations in vascular smooth muscle cells from spontaneously hypertensive rats
Authors: KISTERS Klaus , KREFTING Ernst-Rudolf , SPIEKER Claus , ZIDEK Walter , DIETL Karl Heinz , BARENBROCK Michael , RAHN Karl Heinz 
Published: August 2015

1.Although in blood cells decreased magnesium concentrations and increased sodium concentrations in essential hypertension have often been described, only sparse data exist on cellular magnesium or sodium content and exchange in vascular smooth muscle cells.
2.Therefore in aortic smooth muscle cells from 10 spontaneously hypertensive rats (SHR) of the Münster strain and 10 normotensive Wistar–Kyoto rats (WKY) aged 3 and 8–10 months, the intracellular magnesium and sodium content was measured.
3.Electron-probe X-ray microanalysis was used to determine intracellular Mg2+ and Na+ concentrations in aortic cryosections 3 ;μm thick. The Mg2+ content was 47±13 ;mmol/kg dry weight in SHR versus 48±19 ;mmol/kg dry weight in WKY aged 3 months, and 37±6 ;mmol/kg dry weight in SHR versus 47±4 ;mmol/kg dry weight in WKY aged 8–10 months (P&lt; 0.05). Vascular smooth muscle Na+ content was 283±59 ;mmol/kg dry weight in WKY and 402±123 ;mmol/kg dry weight in SHR aged 3 months (P&lt; 0.05), and 289±17 ;mmol/kg dry weight in WKY versus 548±39 ;mmol/kg dry weight in SHR aged 8–10 months (P&lt; 0.05).
4.Aortic smooth muscle cells from SHR are characterized by a markedly lower intracellular Mg2+ content in 8–10-month-old animals and increased Na+ concentrations compared with normotensive cells in 3- and 8–10-month-old rats. The results may be due to genetically determined disturbances in transmembrane Mg2+ and Na+ transport. Cellular magnesium and sodium handling may be disturbed in SHR aortic smooth muscle as it is in hypertensive blood cells. In addition, it is concluded that vascular smooth muscle cell Mg2+–Na+ exchanger can be altered in a subgroup of SHR.