bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical Fitness and Insulin Sensitivity in Human Subjects with a Low Insulin Response to Glucose
Authors: Pigon Jan , Karlsson Jan , Östenson Claes-Göran 
Published: August 2015

1. We have assessed insulin secretion, insulin sensitivity, exercise capacity and muscle fibre composition in healthy men with a low insulin response to glucose (low insulin responders and endurance-trained subjects) and in healthy men with a normally high insulin response. Low insulin responders have been considered as prediabetic subjects.
2. During glucose infusion, low insulin responders and endurance-trained subjects had acute-phase (0-10 min) insulin responses that were 26% (P &lt; 0.001) and 31% (P &lt; 0.001), and C-peptide responses that were 35% (P &lt; 0.001) and 42% (P &lt; 0.01), respectively of the responses in high insulin responders. Also, the late-phase (10-60 min) insulin and C-peptide responses were lower in low insulin responders and endurance-trained subjects. Endurance-trained subjects, compared with high and low insulin responders, had higher insulin sensitivity (blood glucose concentration during a somatostatin-insulin-glucose infusion test 3.6 ± 0.4 versus 6.3 ± 0.6 mmol/l in high insulin responders, P &lt; 0.01, and 5.5 ± 0.4 mmol/l in low insulin responders, P &lt; 0.01), exercise capacity (4.2 ± 0.2 versus 3.0 ± 0.2 W/kg body weight, P &lt; 0.001, and 2.8 ± 0.1 W/kg body weight, P &lt; 0.001) and a higher percentage of slow-twitch fibres (58.2 ± 5.2 versus 38.5 ± 3.5%, P &lt; 0.01 and 40.9 ± 3.0%, P &lt; 0.001).
3. In conclusion, we demonstrate that low insulin responders exhibited decreased insulin and C-peptide responses to glucose, despite normal insulin sensitivity and exercise capacity. Thus, the low insulin response in low insulin responders reflects a true impairment of insulin release and not a compensatory decrease due to increased insulin sensitivity. The insulin response to glucose in endurance-trained subjects was also decreased, probably due to increased insulin sensitivity.
Effect of Sepsis on Mucosal Protein Synthesis in Different Parts of the Gastrointestinal Tract in Rats
Authors: Higashiguchi Takashi , Noguchi Yoshifumi , O'Brien William , Wagner Kenneth , Fischer Josef E. , Hasselgren Per-Olof 
Published: August 2015

1. In a previous study we found that the protein synthesis rate was increased by 50–60% in the mucosa of the jejunum and ileum during sepsis in rats. It is not known if sepsis affects protein turnover in other parts of the gastrointestinal tract as well.
2. In the present study, the influence of sepsis on mucosal protein synthesis in different parts of the gastrointestinal tract, from the stomach to the rectum, was determined in rats.
3. Sepsis was induced by caecal ligation and puncture; control rats underwent sham-operation. Protein synthesis rate was measured in vivo after administration of a flooding dose of [14C]leucine.
4. Basal mucosal protein synthesis rates were lower in the colon than in the rest of the gastrointestinal tract. Sixteen hours after caecal ligation and puncture, the protein synthesis rates were increased by 40–85% in the mucosa of the small and large intestine and the rectum, whereas in the gastric mucosa, the protein synthesis rate was reduced by approximately 40%.
5. The results suggest that mucosal protein synthesis rates differ in the various regions of the gastrointestinal tract, and that the metabolic response to sepsis is different in the stomach than in the rest of the gastrointestinal tract. The finding of a reduced protein synthesis rate in the gastric mucosa may partly explain the tendency to gastric stress ulcers and bleeding seen clinically in sepsis.
Haemodynamic and Neurohumoral Effects of Caffeine in Elderly Patients with Symptomatic Postprandial Hypotension: A Double-Blind, Randomized, Placebo-Controlled Study
Authors: Lipsitz Lewis A. , Jansen Rene W. M. M. , Connelly Carolyn M. , Kelley-Gagnon Margaret M. , Parker Anthony J. 
Published: August 2015

1. The aim of this study was to determine the effects of caffeine on haemodynamic and neurohumoral responses to meal ingestion in elderly patients with a history of symptomatic postprandial hypotension.
2. Postprandial hypotension is a common disorder of blood pressure regulation in the elderly, associated with falls and syncope. The pathophysiological mechanism is thought to be related to impaired vascular compensation for splanchnic blood pooling after a meal. Since caffeine inhibits vasodilatory adenosine receptors in the splanchnic circulation, we postulated that caffeine would reduce splanchnic blood pooling and prevent the development of postprandial hypotension.
3. We conducted a randomized, double-blind, placebo-controlled, cross-over study in nine elderly patients [age 76 ± 9 (SD) years] with histories of symptomatic postprandial hypotension. Standardized 1674 kJ liquid meals with 250 mg of caffeine or placebo were given on two occasions, at least 1 week apart. Blood pressure, heart rate, forearm vascular resistance (by venous occlusion plethysmography), and plasma caffeine and catecholamine levels were measured. Cardiac and splanchnic blood volume were determined by radionuclide scans.
4. By 30 min after both caffeine and placebo meal studies, supine mean arterial blood pressure fell significantly (P = 0.006) by 31 ± 7 and 19 ± 6 mmHg, respectively (mean ± SEM, between group difference was not significant). Heart rate, cardiac output and splanchnic blood volume increased significantly, but to a similar extent, after caffeine and placebo. Forearm vascular resistance was unchanged after both meals.
5. Oral caffeine given with a meal does not reduce splanchnic blood pooling nor prevent postprandial hypotension in symptomatic elderly patients.
l-Arginine Infusion Decreases Peripheral Arterial Resistance and Inhibits Platelet Aggregation in Healthy Subjects
Authors: Bode-Böger S. M. , Böger R. H. , Creutzig A. , Tsikas D. , Gutzki F.-M. , Alexander K. , Frölich J. C. 
Published: August 2015

1. L-Arginine is the physiological precursor of nitric oxide which induces vasodilatation and inhibits platelet aggregation by the formation of cyclic GMP.
2. In the present study we investigated the effects of an intravenous infusion of L-arginine (30 g, 30 min) compared with placebo on blood pressure, heart rate and peripheral haemodynamics in ten healthy male subjects. Cyclic GMP, NO−2 and NO−3 were determined in plasma and urine to assess NO production in vivo by a new, highly specific and sensitive gas chromatography-mass spectrometry method.
3. L-Arginine significantly decreased mean arterial blood pressure and increased heart rate. The effect was more pronounced on diastolic than on systolic blood pressure. This was due to a decreased peripheral arteriolar resistance, as in femoral artery Doppler sonography the arterial diameter was unchanged but blood flow was increased. These haemodynamic effects were not observed after placebo administration.
4. Urinary excretion of cyclic GMP increased by 65.4% after L-arginine and by 25.1% after placebo. Urinary NO−2 excretion was near the threshold of detection. Urinary NO−3 excretion increased by 79.7% after L-arginine. Plasma arginine levels increased nearly ten-fold after the L-arginine infusion, and plasma cyclic GMP increased by a similar rate as in urine. However, plasma NO−2 and NO−3 remained unchanged after both treatments, as did plasma α-atrial natriuretic peptide levels.
5. Platelet aggregation was inhibited by 32.7% after L-arginine (P &lt; 0.05), but was unchanged after placebo. Platelet intracellular cyclic GMP was increased by 43.0% after L-arginine, but not after placebo (P &lt; 0.05).
6. We conclude that intravenous L-arginine decreases peripheral arteriolar tone and inhibits platelet aggregation in healthy human subjects by enhancing nitric oxide formation and, concomitantly, cyclic GMP formation.
Plasma Cysteine and Sulphate Levels in Patients with Cirrhosis of the Liver
Authors: Davies M. H. , Klovrza L. , Waring R. H. , Elias E. 
Published: August 2015

1. Fasting levels of plasma cysteine, plasma sulphate and the plasma cysteine/sulphate ratio were measured in patients with primary biliary cirrhosis and compared with those in patients with other liver disease, general intensive therapy unit patients and healthy subjects.
2. Plasma cysteine was significantly elevated in patients with primary biliary cirrhosis (median 0.364 nmol/mg of protein, P &lt; 0.0001) and patients with other liver disease (median 0.445 nmol/mg of protein, P &lt; 0.0001), compared with healthy control subjects (median 0.125 nmol/mg of protein) and increased progressively with the severity of liver disease. Plasma cysteine was also elevated in intensive therapy unit patients (median 1.564 nmol/mg of protein) compared with healthy control subjects (P &lt; 0.0001) and patients with other liver disease (P &lt; 0.0001).
3. Plasma sulphate was reduced significantly only in patients with primary biliary cirrhosis (median 0.822 nmol/mg of protein) compared with healthy control subjects (median 1.37 nmol/mg of protein, P &lt; 0.05). There was no significant difference in plasma sulphate between disease groups.
4. The plasma cysteine/sulphate ratio was significantly elevated in patients with primary biliary cirrhosis (median 0.448, P &lt; 0.0001) and patients with other liver diseases (median 0.394, P &lt; 0.0001) compared with healthy control subjects (median 0.095). The ratio was also elevated in intensive therapy unit patients (median 1.650, P &lt; 0.0001) compared with healthy control subjects and liver disease groups (P &lt; 0.0001).
5. In conclusion, plasma cysteine rises in primary biliary cirrhosis and other forms of liver disease. This effect is not specific to liver disease, since cysteine is elevated in an heterogeneous group receiving intensive care. Impairment of trans-methylation and trans-sulphuration pathways does not explain the finding of increased plasma cysteine. Since cysteine is elevated in non-hepatic disease, it may reflect the effect of muscle breakdown and the catabolic state. Impaired activity of cysteine dioxygenase and impaired mitochondrial function may be contributory, but this requires further study. These metabolic changes may reflect progressively diminished detoxification capacity within the liver and other tissues.
Metabolic Abnormalities in Skeletal Muscle after Myocardial Infarction in the Rat
Authors: Thompson C. H. , Kemp G. J. , Rajagopalan B. , Radda G. K. 
Published: August 2015

1. The effect of experimental myocardial infarction on exercise and recovery of rat skeletal muscle was studied using 31P n.m.r. 4 weeks post-operatively.
2. Myocardial infarction (12 ± 3% of left ventricular volume), insufficient to produce haemodynamic manifestations of heart failure, was without significant effect on exercise bioenergetics of skeletal muscle.
3. Citrate synthase activity was reduced by 17% in the infarcted animals and there was a marked slowing of the rate of phosphocreatine recovery after infarction (half-time 0.7 ± 0.1 min to 1.6 ± 0.2 min) in the absence of evidence of left ventricular failure or hypertrophy.
4. The study of recovery bioenergetics could provide a more sensitive measure of mitochondrial function than exercise, where no bioenergetic abnormality was detected.
5. Myocardial infarction can produce evidence of mitochondrial abnormality in skeletal muscle in the absence of haemodynamic compromise.
Glomerular Charge Selectivity in Primary Glomerulopathies
Authors: Fox J. G. , Quin J. D. , O'Reilly D. St. J. , Boulton-Jones J. M. 
Published: August 2015

1. Glomerular charge selectivity was assessed using the ratio of the clearance of pancreatic isoamylase to the clearance of the more anionic salivary isoamylase (CPAm/CSAm) in 53 patients with primary glomerulopathies (minimal change nephropathy, idiopathic membranous nephropathy, IgA nephropathy) and a wide range of albumin excretion rates and in 31 healthy subjects. Fractional clearances of pancreatic and salivary isoamylases (FCPAm, FCSAm) and of albumin (FCAlb) were also measured.
2. CPAm/CSAm and FCPAm were negatively correlated with FCAlb for the whole patient group (rs = −0.56 and rs = −0.65, respectively, P &lt; 0.0001 for both), but there was no correlation of FCSAm with FCAlb.
3. For patients with near-normal albumin excretion rates (&lt; 100 mg/24 h), there was no difference in CPAm/CSAm between the three types of glomerulopathy or between patients and healthy subjects.
4. These data suggest that glomerular charge selectivity at the size of amylase (which is smaller than albumin) is progressively lost as albuminuria increases from normal to the nephrotic range. Size restriction progressively increases until albuminuria is very heavy. When the albumin excretion rate is near normal, charge selectivity is also normal in the three main forms of primary glomerulopathy.
Plasma Endogenous Digoxin-Like Substance Levels are Dependent on Blood O2 in Man
Authors: Ferri Claudio , Bellini Cesare , Coassin Simonetta , De Angelis Claudio , Perrone Alessandro , Santucci Anna 
Published: August 2015

1. Recently, we have demonstrated that hypoxic breathing is followed by an increase in plasma digoxin-like substance in normal men.
2. This study was undertaken in order to evaluate whether or not a low arterial O2 partial pressure is combined with an increase in plasma digoxin-like substance in chronic pathological conditions also.
3. Sixteen male patients (mean age 53.1 ± 3.7 years) affected by chronic obstructive pulmonary disease of a mild stage were studied. They were further subdivided according to their arterial O2 partial pressure into ‘mild hypoxic’ (n = 8, mean age 52.5 ± 2.7 years), with an arterial O2 partial pressure between 66 and 75 mmHg, and ‘severe hypoxic’ (n = 8, mean age 54.3 ± 5.1 years), with an arterial O2 partial pressure 65 mmHg, groups. Seven healthy men (mean age 48.5 ± 4.8 years) voluntarily participated as the control group.
4. Plasma digoxin-like substance levels were significantly higher in ‘severe hypoxic’ patients (203.5 ± 9.9 pg/ml) than in both ‘mild hypoxic’ patients (169.5 ± 31.4 pg/ml, P &lt; 0.02) and normal subjects (158.9 ± 12.4 pg/ml, P &lt; 0.0001) and were directly correlated with urinary Na+ excretion (severe hypoxic group, r = 0.756, P &lt; 0.007; mild hypoxic group, r = 0.789, P &lt; 0.02). Considering the two hypoxic groups together, plasma digoxin-like substance levels were negatively correlated with arterial O2 partial pressure (r = −0.740, P &lt; 0.001). However, when patients were subdivided according to the degree of hypoxia, the negative correlation between arterial O2 partial pressure and plasma digoxin-like substance persisted only in severe hypoxic patients (r = −0.761, P &lt; 0.03).
5. These results indicate a clear linkage between blood O2 and endogenous digoxin-like substance regulation. In particular, hypoxia may be regarded as an important stimulus for the release of the endogenous digoxin-like substance in man.
Intraluminal Colonic Release of Immunoreactive Tumour Necrosis Factor in Chronic Ulcerative Colitis
Authors: Casellas F. , Papo M. , Guarner F. , Antolín M. , Armengol J. R. , Malagelada J.-R. 
Published: August 2015

1. Tumour necrosis factor is a proinflammatory macrophage-derived polypeptide cytokine. Its participation in disease processes has been usually inferred from data obtained from experiments in vitro or from measurements of its plasma circulating levels. To investigate its role in chronic ulcerative colitis, we have quantified in vivo the steady-state release of tumour necrosis factor into the colonic lumen.
2. We studied 19 patients with untreated active ulcerative colitis and seven patients with irritable bowel syndrome as controls. A group of seven patients with active ulcerative colitis were studied before and after 4 weeks on treatment with oral 5-aminosalicylic acid. By means of an intracolonic double-lumen perfusion tube, an isotonic solution was continuously infused 50 cm from the anal verge at a rate of 5 ml/min, and was recovered 30 cm distally by siphonage. Effluents were assayed for tumour necrosis factor by a specific e.l.i.s.a. and for prostaglandin E2 and leukotriene B4 by specific r.i.a.s.
3. The intracolonic release of tumour necrosis factor was undetectable in patients with irritable bowel syndrome, whereas measurable release occurred in 15 out of 19 patients with active ulcerative colitis (P &lt; 0.01). Prostaglandin E2 and leukotriene B4 release were also increased in active ulcerative colitis by comparison with irritable bowel syndrome (P &lt; 0.01). Five out of seven patients with colitis improved with 5-aminosalicylic acid treatment, and tumour necrosis factor release became undetectable or decreased markedly (P &lt; 0.05 compared with before treatment). However, tumour necrosis factor release remained high in the non-responder patients.
4. These findings indicate that intracolonic immunoreactive tumour necrosis factor release is enhanced in active chronic ulcerative colitis, becoming undetectable when mucosal lesions are healed. These results suggest that the luminal release of tumour necrosis factor may serve as an objective index of inflammatory activity in patients with chronic ulcerative colitis.
Multiple Transcripts of the Neurofibromatosis Type I Gene in Human Brain and in Brain Tumours
Authors: Takahashi Kazuhiro , Suzuki Hiroyuki , Kayama Takamasa , Suzuki Youichi , Yoshimoto Takashi , Sasano Hironobu , Shibahara Shigeki 
Published: August 2015

1. Neurofibromatosis type 1 is a common hereditary disorder characterized by the presence of multiple neurofibromas and café-au-lait spots, and is frequently associated with intellectual handicaps and brain tumours. The gene responsible for neurofibromatosis (the NF1 gene) codes for a protein of 2818 amino acids, termed neurofibromin, which has a domain related to mammalian ras GTPase-activating protein.
2. The NF1 gene gives rise to multiple transcripts generated by alternative splicing, that encode neurofibromin and its isoforms. These include type I mRNA coding for neurofibromin, type II mRNA coding for neurofibromin containing the insertion of 21 amino acids in the GTPase-activating protein-related domain and mRNA coding for an N-terminal isoform lacking the GTPase-activating protein-related domain (N-isoform).
3. In the present study, the relative levels of mRNAs encoding type I, type II and N-isoform were determined by S1-nuclease mapping analysis in human brain tissue and in primary brain tumours obtained from patients with tumours unrelated to neurofibromatosis type 1.
4. These three mRNAs were expressed in all ten brain tumours and in every region of the brain examined, with the highest levels found in the cerebellum. Type I mRNA was the predominant form in the human brain except for the pons, whereas type II mRNA was predominantly expressed in eight out of ten primary brain tumours.
5. In contrast, N-isoform mRNA was similarly expressed in normal brain tissue and brain tumours.
6. These findings suggest that neurofibromin and its isoforms have important physiological roles in the human brain and that the altered expression of type I and type II mRNAs in brain tumours may be related to the tumorigenesis.
Absence of Mutations in the Gsα and Gi2α Genes in Sporadic Parathyroid Adenomas and Insulinomas
Authors: Vessey S. J. Rupert , Jones Philip M. , Wallis Simon C. , Schofield John , Bloom Stephen R. 
Published: August 2015

1. Activating mutations of the α-subunits of the Gs and Gi2 proteins give rise to the oncogenes gsp and gip2, respectively, which are found in a variety of endocrine tumours.
2. In this study the polymerase chain reaction and direct sequencing have been used to screen a small sample of parathyroid adenomas and insulinomas for these mutations.
3. No mutations were identified in nine insulinomas and 13 parathyroid adenomas screened for gsp, and 11 parathyroid adenomas and four insulinomas screened for gip2. In addition, two gastrinomas from patients with multiple endocrine neoplasia type 1 were found to be negative for both oncogenes.
4. This is the first report of screening for gip2 in parathyroid adenomas and gsp/gip2 in insulinomas, and it extends the range of tumours examined for these oncogenes.
Dietary Salt Extremes and Renal Function in Rats: Effect of Atrial Natriuretic Factor
Authors: Honrath U. , Chong C. K. , Wilson D. R. , Sonnenberg H. 
Published: August 2015

1. Chronic reduction of salt intake can reduce the natriuretic effect of exogenously administered atrial natriuretic factor. The purpose of this study was to elucidate the intrarenal site(s) of such atrial natriuretic factor resistance. Renal clearance and collecting duct microcatheterization experiments were made before and during infusion of atrial natriuretic factor in three groups of rats: group 1 consisted of rats fed a high salt diet (8% NaCl) for 1 week before the experiment; group II were fed a low salt diet (&lt; 0.008%); group III received the same low salt diet, but were acutely replenished with salt at the time of experiment.
2. Baseline sodium chloride excretion was 6480 ± 810 nmol min−1g−1 kidney weight in group 1 compared to 99 ± 16 in group 1. Fractional re-absorptions in the medullary collecting duct were 37 ± 6% and 95 ± 2% of delivered load, respectively (P &lt; 0.05). The fractions of filtered sodium remaining at the beginning of the medullary duct were 6.6 ± 1.0% of filtered load in group 1 and 2.7 ± 0.7% in group II (P &lt; 0.05), indicating increased tubular reabsorption in group II, not only in the medullary duct, but also in upstream nephron segments.
3. During infusion of atrial natriuretic factor, marked saluresis (13240 ± 750 nmol min−1 g−1 kidney weight), together with decreased fractional reabsorption at both sites (duct, −13 ± 9%; upstream remainder, 7.9 ± 0.7%; P &lt; 0.05 each, compared to corresponding control values) was found in group 1, whereas the excretory (150 ± 28 nmol min−1 g−1 kidney weight), and the tubular transport (duct = 84 ± 3%; upstream remainder =2.2 ± 0.4%) changes were quantitatively insignificant in group II. Glomerular filtration rate was increased in group 1 from 1.07 ± 0.03 to 1.26 ± 0.04 ml min−1g−1 kidney weight (P &lt; 0.05), but not in group II (0.93 ± 0.07 to 0.96 ± 0.09, not significant).
4. In group III, acute salt replenishment was associated with increased excretion (1940 ± 440 nmol mm−1 g−1 kidney weight, P &lt; 0.05 compared to group II) and with reduction of tubular reabsorption in the collecting duct only (69 ± 8%, P &lt; 0.05). Infusion of atrial natriuretic factor in this group further increased natriuresis (7810 ± 780 nmol min−1 g−1 kidney weight) and decreased tubular reabsorption in the duct (−32 ± 22%, P &lt; 0.05 compared to the corresponding control value).
5. We conclude that chronic salt deprivation can effectively prevent, via a rapidly reversible counter-regulatory mechanism, the expected actions of atrial natriuretic factor on sodium reabsorption in the medullary collecting duct. Operation of such a mechanism may explain salt retention despite elevated endogenous levels of atrial natriuretic factor in pathological states such as congestive heart failure and liver cirrhosis.