bluuebunny/crossref_metadata_2025_split huggingface dataset:
Splanchnic and systemic haemodynamic response to volume changes in patients with cirrhosis and portal hypertension
Authors: VLAVIANOS Panagiotis , MAC MATHUNA Padraik , WILLIAMS Roger , WESTABY David 
Published: August 2015

We investigated the haemodynamic response to volume depletion and subsequent repletion in patients with cirrhosis and portal hypertension. Twelve patients with compensated cirrhosis and portal hypertension were included in the study. The haemodynamic changes occurring after removal of approx. 15% of the blood volume, and subsequently after isovolume repletion with colloid, were assessed. Baseline haemodynamic measurements showed increased cardiac output and a systemic vascular resistance at the lower limit of normal. The hepatic venous pressure gradient (HVPG) was increased, at 18 mmHg. After depletion, arterial pressure, cardiac output and all right-heart-sided pressures decreased, and systemic vascular resistance increased. HVPG decreased to 16.0 mmHg. All the above changes were statistically significant. After blood volume restitution, the haemodynamic values returned to baseline. In particular, an increase in HVPG was shown in four out of the twelve patients (two with ascites and two without), which was small in three of them. However, HVPG remained the same as or lower than the baseline in the other eight patients. Patients with cirrhosis and portal hypertension exhibit an abnormal haemodynamic response to blood volume depletion. After volume repletion, no increase in the portal pressure was noted in this group of patients as a whole, although four out of the twelve patients did show an increase, possibly due to extensive collateral circulation.
Relationship between erythropoietin and nitric oxide in the contraction of rat renal arcuate arteries and human umbilical vein endothelial cells
Authors: WU Xiao Chun , JOHNS Edward J. , RICHARDS Nicholas T. 
Published: August 2015

We have investigated the effects of recombinant human erythropoietin (EPO) on the responses of rat renal arcuate arteries to dopamine, noradrenaline and acetylcholine and on the release of NO from human umbilical vein endothelial cells (HUVEC) in culture. Noradrenaline induced a concentration-dependent constriction and acetylcholine a concentration-dependent relaxation of the vessels. The effects of dopamine were concentration-dependent, leading to relaxation of the vessels at low concentrations and contraction of the vessels at high concentrations. NG-Nitro-L-arginine methyl ester (L-NAME; 0.1 mM) did not change the vasoconstrictor responses to noradrenaline and dopamine, but inhibited the acetylcholine- and dopamine-induced vasorelaxation. Neither 0.1 nor 20 units·ml-1 EPO affected noradrenaline-induced constriction, or dopamine- or acetylcholine-induced relaxation, of the vessels. EPO at 20 units·ml-1 attenuated dopamine-induced constriction of the vessels. This effect was blunted by application of L-NAME, suggesting that EPO may stimulate dopamine-mediated NO release from these vessels. EPO stimulated NO release from the resting HUVEC in a concentration- and time-dependent manner, an effect that was inhibited by the presence of NG-nitro-L-arginine. These data suggest that, in vitro, EPO is able to stimulate NO release from rat renal arcuate arteries and HUVEC in culture. Whether these acute short-term actions can be related to the longer-term actions of EPO remains to be resolved.
Splanchnic and extrasplanchnic extraction of insulin following oral and intravenous glucose loads
Authors: BRUNDIN Tomas 
Published: August 2015

In the basal state, approx. 60–70% of the insulin released from the pancreas is extracted by the liver; the remaining 30–40% is extracted by extrasplanchnic organs. Carbohydrate ingestion is known to stimulate pancreatic insulin release and to inhibit whole-body insulin extraction. The present study was undertaken to obtain a quantitative assessment of the degree to which early postprandial insulinaemia in peripheral blood is due to the inhibition of splanchnic as opposed to extrasplanchnic insulin extraction. By means of catheterization, which allowed frequent analyses of insulin and C-peptide in arterial and hepatic venous blood and estimates of splanchnic plasma flow (indocyanine), insulin extraction by splanchnic and extrasplanchnic tissues was studied in 16 healthy volunteers at timed intervals before and after or during oral (n = 8) and intravenous (n = 8) isoglycaemic glucose loads. Splanchnic insulin extraction (66±2% in the basal state) fell significantly during the 10 min after oral glucose to a minimum of 45±8%; during 5–20 min of intravenous glucose administration it rose significantly to a maximum of 72±2%. Extrasplanchnic extraction of insulin fell from 90–100% in the basal state to a minimum of 3±6% (P< 0.001) after oral glucose; during the first 5 min of intravenous glucose infusion it fell in relative but not in absolute terms. It is concluded that the early postprandial increase in peripheral insulinaemia largely (> 85% during the first 30 min) reflects a marked inhibition of insulin extraction. It is suggested that intestinal hormones and/or splanchnic blood flow may be involved in the mechanisms governing the postprandial inhibition of insulin extraction.
Serum carnitine concentrations in patients with idiopathic hypertrophic cardiomyopathy: relationship with impaired myocardial fatty acid metabolism
Authors: NAKAMURA Tomoki , SUGIHARA Hiroki , KINOSHITA Noriyuki , ITO Kazuki , ADACHI Yoshihiko , HIRASAKI Satoshi , MATSUO Akiko , AZUMA Akihiro , KODO Naoki , NAKAGAWA Masao 
Published: August 2015

We evaluated the clinical significance of serum carnitine concentrations in determining the severity of impaired myocardial fatty acid metabolism in idiopathic hypertrophic cardiomyopathy (HCM). We studied 56 asymptomatic or mildly symptomatic patients with HCM. Serum levels of free carnitine and acylcarnitine were measured by the enzymic cycling method. Myocardial scintigraphy with 123I-labelled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) was performed, and the images were analysed quantitatively and semi-quantitatively. Serum free carnitine levels were significantly higher in HCM patients than in normal subjects (52.5±9.5 and 42.3±5.5 nmol/ml respectively; P< 0.0001). On the other hand, serum acylcarnitine levels and acyl/free carnitine ratios were lower in HCM patients than in normal subjects (10.2±4.0 nmol/ml and 0.19±0.08, compared with 13.2±3.9 nmol/ml and 0.32±0.11 respectively; P< 0.0001). Clinical characteristics were not significantly different between the patients showing high and normal free carnitine levels, although female patients with high free carnitine levels were few (P = 0.02). Both quantitative and semi-quantitative analyses revealed that the severity of decreased myocardial BMIPP uptake was significantly correlated with serum free carnitine levels (quantitative analysis: r = -0.422, P< 0.0012; semi-quantitative analysis: r = 0.633, P< 0.0001). In the presence of reduced carnitine uptake into the myocardium in HCM, there may also be reduced transport of acylcarnitines out of the myocardium into the plasma. Although inborn errors of fatty acid metabolism and carnitine deficiencies are reported to provoke secondary HCM and are associated with low serum carnitine concentrations, this study has revealed that the levels of carnitine are, in contrast, increased in idiopathic HCM. Moreover, serum carnitine concentrations are a sensitive indicator of the severity of impaired myocardial fatty acid metabolism even in asymptomatic patients with HCM.
Muscle protein degradation and amino acid metabolism during prolonged knee-extensor exercise in humans
Authors: VAN HALL G. , SALTIN B. , WAGENMAKERS A. J. M. 
Published: August 2015

The aim of this study was to investigate whether prolonged one-leg knee-extensor exercise enhances net protein degradation in muscle with a normal or low glycogen content. Net amino acid production, as a measure of net protein degradation, was estimated from leg exchange and from changes in the concentrations of amino acids that are not metabolized in skeletal muscle. Experiments were performed at rest and during one-leg knee-extensor exercise in six subjects having one leg with a normal glycogen content and the other with a low glycogen content. Exercise was performed for 90 min at a workload of 60–65% of maximal one-leg power output, starting either with the normal-glycogen or the low-glycogen leg, at random. The net production of threonine, lysine and tyrosine and the sum of the non-metabolized amino acids were 9–20-fold higher (P< 0.05) during exercise of the normal-glycogen leg than at rest. Total amino acid production was also 10-fold higher during exercise compared with that at rest (difference not significant). The net production rates of threonine, glycine and tyrosine and of the sum of the non-metabolized amino acids were about 1.5–2.5-fold higher during exercise with the leg with a low glycogen content compared with the leg with a normal glycogen content (P< 0.05). Total amino acid production was 1.5-fold higher during exercise for the low-glycogen leg compared with the normal-glycogen leg (difference not significant). These data indicate that prolonged one-leg knee-extensor exercise leads to a substantial increase in net muscle protein degradation, and that a lowering of the starting muscle glycogen content leads to a further increase. The carbon atoms of the branched-chain amino acids (BCAA), glutamate, aspartate and asparagine, liberated by protein degradation, and the BCAA and glutamate extracted in increased amounts from the blood during exercise, are used for the synthesis of glutamine and for tricarboxylic-acid cycle anaplerosis.
Use of opposing reflex stimuli and heart rate variability to examine the effects of lipophilic and hydrophilic β-blockers on human cardiac vagal control
Authors: VAILE Julian C. , FLETCHER Janine , AL-ANI Muzahim , ROSS Hamish F. , LITTLER William A. , COOTE John H. , TOWNEND Jonathan N. 
Published: August 2015

Evidence from animal studies suggests that β-blockers can act within the central nervous system to increase cardiac vagal motoneuron activity. We have attempted to determine whether such an effect is evident in healthy humans, by examining the effects of lipophilic and hydrophilic agents on heart rate variability and cardiac vagal reflexes. A total of 20 healthy volunteers took part in the study. Autonomic studies were performed after 72 h of treatment with placebo, atenolol or metoprolol in a blinded cross-over design. ECG recordings were taken at rest and during mental and orthostatic stress. Heart rate variability was measured in the time and frequency domains. The effects on heart rate of two opposing cardiac vagal reflexes were examined. Trigeminal stimulation causing vagal stimulation, and isometric forearm muscle contraction (‘muscle heart reflex’) causing vagal inhibition, were performed alone and simultaneously. At rest, during mental stress and during trigeminal stimulation, β-blocker therapy was associated with significantly increased high-frequency beat-to-beat heart rate variability when compared with placebo. There were no significant differences in effects on heart rate or heart rate variability between atenolol and metoprolol. Analysis of the muscle heart reflex, alone and with simultaneous trigeminal stimulation, showed that the magnitude of the R–R interval response was significantly greater after β-blocker therapy compared with placebo, but the effects of atenolol and metoprolol were equivalent. β-Blocker therapy increased cardiac vagal activity, as shown by measures of high-frequency heart rate variability and reflex studies. Lipophilic and hydrophilic β-blockers appeared to be equally efficacious in increasing the cardiac vagal modulation of heart rate.
Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat
Authors: SHERMAN Rachel C. , LANGLEY-EVANS Simon C. 
Published: August 2015

Epidemiological evidence from diverse human populations, supported by experimental evidence from animal models, suggests that maternal nutrition during pregnancy is an important fetal programming influence upon cardiovascular disease. Experiments with a low-protein-diet model of rat pregnancy suggest a role for the renin–angiotensin system in the programming mechanism, since fetal undernutrition permanently elevates pulmonary and plasma angiotensin-converting enzyme activity. Long-term beneficial effects of captopril on blood pressure in this model require further investigation in order to clarify the role of angiotensin II. Pregnant rats were fed a control diet containing 18% (w/w) casein as the protein source or a low-protein diet containing 9% (w/w) casein. Between the ages of 2 and 4 weeks postnatally, mothers and their pups were treated with losartan or nifedipine. All pups in the study had blood pressure determined at 4 and 12 weeks of age using a tail cuff. Animals exposed to the low-protein diet in utero and not subjected to drug treatment had elevated blood pressure relative to control rats (mean increase of 27 mmHg; P < 0.001). Treatment of rats exposed to the control diet in utero with either nifedipine or losartan between 2 and 4 weeks of age did not alter their blood pressure. Nifedipine had no effect upon the blood pressure of low-protein-exposed pups, but losartan prevented the blood pressure elevation in these animals. Between 4 and 12 weeks of age, blood pressure increased significantly in all groups (P < 0.001). The pattern of blood pressure among the groups was identical to that observed at 4 weeks, suggesting that the observed early effects of losartan would be maintained into adult life. The data are consistent with the hypothesis that angiotensin II plays a major role in the prenatal programming of hypertension. The action of angiotensin II at the AT1 receptor between 2 and 4 weeks of age may be critically up-regulated by fetal factors, including exposure to glucocorticoids of maternal origin.
Effects of proinsulin C-peptide on nitric oxide, microvascular blood flow and erythrocyte Na+,K+-ATPase activity in diabetes mellitus type I
Authors: FORST T. , DUFAYET DE LA TOUR D. , KUNT T. , PFÜTZNER A. , GOITOM K. , POHLMANN T. , SCHNEIDER S. , JOHANSSON B. L. , WAHREN J. , LÖBIG M. , ENGELBACH M. , BEYER J. , VAGUE P. 
Published: August 2015

This study was conducted to evaluate the influence of proinsulin C-peptide on erythrocyte Na+,K+-ATPase and endothelial nitric oxide synthase activities in patients with type I diabetes. In a randomized double-blind study design, ten patients with type I diabetes received intravenous infusions of either human C-peptide or physiological saline on two different occasions. C-peptide was infused at a rate of 3 pmol·min-1·kg-1 for 60 min, and thereafter at 10 pmol·min-1·kg-1 for 60 min. At baseline and after 60 and 120 min, laser Doppler flow (LDF) was measured following acetylcholine iontophoresis or mild thermal stimulation (44 °C), and venous blood samples were collected to determine plasma cGMP levels and erythrocyte membrane Na+,K+-ATPase activity. The LDF response to acetylcholine increased during C-peptide infusion and decreased during saline infusion [18.6±19.2 and -13.2±9.4 arbitrary units respectively; mean±S.E.M.; P < 0.05). No significant change in LDF was observed after thermal stimulation. The baseline plasma concentration of cGMP was 5.5±0.6 nmol·l-1; this rose to 6.8±0.9 nmol·l-1 during C-peptide infusion (P < 0.05). Erythrocyte Na+,K+-ATPase activity increased from 140±29 nmol of Pi·h-1·mg-1 in the basal state to 287±5 nmol of Pi·h-1·mg-1 during C-peptide infusion (P < 0.01). There was a significant linear relationship between plasma C-peptide levels and erythrocyte Na+,K+-ATPase activity during the C-peptide infusion (r = 0.46, P < 0.01). No significant changes in plasma cGMP levels or Na+,K+-ATPase activity were observed during saline infusion. This study demonstrates an effect of human proinsulin C-peptide on microvascular function, which might be mediated by an increase in NO production and an activation of the erythrocyte Na+,K+-ATPase. These mechanisms are compatible with the previous observed microvascular effects of C-peptide in patients with type I diabetes.
Effects of adenosine receptor antagonists on the responses to contrast media in the isolated rat kidney
Authors: OLDROYD Simon D. , FANG Lu , HAYLOR John L. , YATES Michael S. , EL NAHAS A. Meguid , MORCOS Sameh K. 
Published: August 2015

Contrast media can induce both a decrease in renal blood flow and a reduction in glomerular filtration rate (GFR) when administered to both experimental animals and humans. In the present study we have examined the role of adenosine in mediating these effects using the isolated perfused rat kidney. Kidneys were perfused with a 6.7%-(w/v)-albumin-based perfusate supplemented with glucose and amino acids (n = 6 per group). They were exposed to diatrizoate [20 mg of iodine (mgI)/ml; osmolality 1650 mOsm/kg of water] or iotrolan (20 mgI/ml; osmolality 320 mOsm/kg of water) in the presence or absence of theophylline (10.8 µg/ml), or to diatrizoate in the presence or absence of a specific adenosine A1 receptor antagonist (KW-3902; 2 µg/ml) or a specific A2 receptor antagonist (KF17837; 6 µg/ml). Diatrizoate (n = 6) produced a fall in GFR from 0.65±0.04 to 0.42±0.03 ml·min-1·g-1 (P < 0.05); renal perfusate flow (RPF) also declined, from 36.5±3.8 to 22.0±3.2 ml·min-1·g-1 (P < 0.05). Iotrolan (n = 6) produced a fall in GFR from 0.64±0.02 to 0.48±0.04 ml·min-1·g-1 (P < 0.05) and in RPF from 33.3±3.8 to 24.0±3.0 ml·min-1·g-1 (P < 0.05). Theophylline (10.8 µg/ml) prevented the fall in GFR caused by either diatrizoate (baseline, 0.63±0.05 ml·min-1·g-1; diatrizoate+theophylline, 0.60±0.04 ml·min-1·g-1) or iotrolan (basline, 0.64±0.04 ml·min-1·g-1; iotrolan+theophylline, 0.67±0.05 ml·min-1·g-1), but did not affect the decreases in RPF caused by either agent. KW-3902 (2 µg/ml) also prevented the fall in GFR produced by diatrizoate (baseline, 0.66±0.05 ml·min-1·g-1; diatrizoate+KW-3902, 0.61±0.05 ml·min-1·g-1), while the fall in RPF remained unaffected. KF17837 (6 µg/ml) had no effect on the decreases in either GFR or RPF induced by diatrizoate (n = 6 per group). The results suggest a role for adenosine acting at the A1 receptor in mediating the decrease in GFR induced by contrast media. This effect is independent of a change in renal vascular resistance, and possibly secondary to mesangial cell contraction causing a decrease in the ultrafiltration coefficient.
Does a high concentration of calcium in the urine cause an important renal concentrating defect in human subjects?
Authors: LAM George S. S. , ASPLIN John R. , HALPERIN Mitchell L. 
Published: August 2015

The objective of this study was to evaluate the hypothesis that a high concentration of ionized calcium in the lumen of the medullary collecting duct causes an osmole-free water diuresis. The urine flow rate and osmolality were measured in normal human subjects, as well as in patients with a history of nephrolithiasis who excreted more than 5 mmol of calcium per 24 h. There was an inverse relationship between the concentration of calcium in the urine and the 24 h urine volume both in normal subjects and in patients with a history of nephrolithiasis. When the concentration of calcium in the urine was greater than 5 mmol/l, the urine volume was less than 1 litre per day in the majority of subjects. After 16 h of water deprivation, when the concentration of calcium in the urine was as high as 17 mmol/l (ionized calcium 7.4 mmol/l), urine osmolality was 1258 mOsm/kg of water and the urine flow rate was 0.30 ml/min. We conclude that, although a calcium receptor may be present in the lumen of the medullary collecting duct in human subjects, an extremely high concentration of urinary total and ionized calcium does not cause a clinically important defect in the renal concentrating process.
Myocardial tissue oxygen supply and utilization during coronary artery bypass surgery: evidence of microvascular no-reflow
Authors: AL-OBAIDI Mohamed K. , ETHERINGTON Philip J. , BARRON David J. , WINLOVE Peter C. , PEPPER John R. 
Published: August 2015

The supply and utilization of oxygen by the myocardium reflect the dynamic efficiency of the microcirculation. The present study examines these parameters during coronary artery bypass surgery. We used a voltammetric microelectrode technique to assess regional variations in myocardial tissue partial pressure of oxygen (PO2) and myocardial tissue perfusion (MTP) in patients undergoing coronary artery bypass surgery. A total of 29 myocardial regions were studied in 17 patients to assay tissue PO2, and 13 regions in 10 patients to measure MTP. There was an increase in MTP from 53±9 ml·min-1·100 g-1 before cardiopulmonary bypass to 72±13 ml·min-1·100 g-1 after (means±S.E.M.; P = 0.05). Tissue PO2 showed an overall increase from a baseline level of 45±8 mmHg to a final level of 88±10 mmHg (P< 0.0001). Following release of the aortic cross-clamp there was a variable time delay before a change in tissue PO2 was observed. There was an immediate response in five regions, whereas in 20 regions the response was delayed by between 0.5 and 32 min. In the remaining four regions there was no change in tissue PO2. The duration of the delay in response was correlated positively with the cross-clamp time (r = 0.45, P < 0.05) and negatively with the final tissue PO2 (r =-0.5, P < 0.05). Voltammetric methods for monitoring changes in oxygen supply and utilization offer new insights into the changes that occur during ischaemia and reperfusion. A delay in the delivery of oxygen to the myocardium occurs in many patients following coronary artery bypass surgery.
Effects of pre- and post-absorptive factors on the lactulose/rhamnose gut permeability test
Authors: VAN NIEUWENHOVEN M. A. , DE SWART E. A. M. , VAN EIJK H. M. , DEUTZ N. E. P. , BROUNS F. , M. BRUMMER R.-J. 
Published: August 2015

It is assumed that the outcome of the lactulose/rhamnose gut permeability test is not influenced by pre- or post-absorptive factors. The aim of our study was to investigate the role of a pre-absorptive factor, i.e. small-intestinal transit, and a post-absorptive factor, i.e. renal clearance. Ten healthy male subjects were studied. Urinary lactulose and rhamnose excretion was measured after intraduodenal administration of lactulose and rhamnose following induction of increased intestinal permeability using chenodeoxycholic acid (chenodiol), in the absence and in the presence of accelerated intestinal transit. Urinary sugar excretion was measured after intravenous administration of either a regular dose (50 mg/50 mg) or a high dose (250 mg/250 mg) of lactulose/rhamnose. The intraduodenal experiments showed that a combination of accelerated small-bowel transit and increased permeability did not lead to significant differences in the recovery of lactulose (P = 0.647) or rhamnose (P = 0.889), or in the lactulose/rhamnose ratio, compared with those under conditions of increased permeability alone (P = 0.68). However, lactulose recovery was significantly lower (P = 0.025) after intravenous administration of a high dose of the sugars. There was no significant difference in urinary rhamnose recovery (P = 0.575) between the high and the regular doses. This resulted in a significantly lower lactulose/rhamnose ratio (P = 0.021) after intravenous administration of a high dose, compared with a regular dose, of the sugars. In conclusion, the assumption that post-absorptive processes do not influence the outcome of the lactulose/rhamnose permeability test appears not to be valid.