bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Insulin Sensitivity in Man: A Comparison of Minimal Model- and Euglycaemic Clamp-Derived Measures in Health and Heart Failure
Authors: Swan Jonathan W. , Walton Christopher , Godsland Ian F. 
Published: August 2015

1. Simplified protocols for the measurement of insulin resistance will facilitate studies of this potentially important variable.
2. Using the euglycaemic clamp as the reference technique, we have assessed the validity of the insulin sensitivity index (inversely related to insulin resistance) obtained using a high-dose (500 mg/kg), unmodified intravenous glucose tolerance test with a 16 point sampling schedule and analysis using the minimal model of glucose disappearance. The two methods were compared in 10 clinically normal subjects and five patients with severe heart failure secondary to coronary heart disease.
3. The insulin sensitivity index of the minimal model was compared with four clamp-derived measures. Correlation coefficients of 0.72–0.92 (P &lt; 0.01−P &lt; 0.001) were obtained between the two methods over a wide range of insulin sensitivity [model values 1.03–14.63 min−1/(pmol/l) × 10−5]. Patients with heart failure had the lowest measures of insulin sensitivity.
4. The high-dose, unmodified intravenous glucose tolerance test with minimal model analysis is a straightforward and economical clinical procedure and provides a valid measure of insulin sensitivity, in health and disease.
Production of Interleukin-6 and Tumour Necrosis Factor-α in Vitro Is Reduced in Whole Blood of Severely Malnourished Children
Authors: Doherty J. F. , Golden M. H. N. , Remick D. G. , Griffin G. E. 
Published: August 2015

1. Cytokine production in vitro was assessed in 16 malnourished children, before and after nutritional recovery.
2. Tumour necrosis factor-α and interleukin-6 were measured in whole blood after lipopolysaccharide stimulation.
3. The total amount of both cytokines was significantly less after 24 h incubation among malnourished children when compared with the same children after nutritional rehabilitation.
4. Cytokine production in vitro is impaired in severely malnourished children.
Acute Sodium Loading in Patients with Uncomplicated Diabetes Mellitus: Renal and Hormonal Effects
Authors: Beretta-Piccoli Carlo , Elshater-Zanetti Francesca , Shaw Sidney , Cusi Daniele , Weidmann Peter 
Published: August 2015

1. Diabetes mellitus is associated with high body sodium, but the pathogenetic mechanism is still unknown. The possibility that an abnormal renal handling of sodium, an abnormal responsiveness of sodium-modulating factors or a shift in the set point for sodium metabolism may contribute to or be associated with sodium retention was tested with an acute saline infusion.
2. A consecutive sample of 33 patients with stable non-azotaemic diabetes mellitus (24 insulin-dependent patients) and 30 normal control subjects was studied. Two litres of a 0.9% NaCl infusion were infused over 4 h. The urinary sodium excretion during the infusion and the next 18 h was analysed in relation to blood pressure, creatinine and lithium clearances, Na+−K+ co-transport, Na+−Li+ countertransport, plasma levels of renin, angiotension II, aldosterone, noradrenaline, adrenaline, atrial natriuretic factor and digoxin-like factor.
3. Diabetic patients and control subjects did not differ in blood pressure, body mass index, clearances of creatinine, sodium or lithium, intracellular sodium, Na+−K+ co-transport and Na+−Li+ countertransport, urinary and plasma levels of digoxin-like factor, plasma renin activity, angiotensin II, aldosterone, noradrenaline, adrenaline and atrial natriuretic factor. The intravenous saline infusion caused a similar natriuresis in diabetic patients and normal subjects; the renin—angiotension-aldosterone system was suppressed to a higher degree in diabetic patients than in normal subjects, whereas atrial natriuretic factor was stimulated to a similar extent; plasma digoxin-like activity was unchanged in both groups.
4. The natriuretic response to saline infusion was comparable between patients with insulin-dependent and non-insulin-dependent diabetes mellitus, those with lower or higher HbA1c levels and those with positive or negative family history of essential hypertension.
5. Using an acute saline infusion to study sodium-modulating factors, no abnormality can be detected which could represent a pathogenetic mechanism for sodium retention in diabetes mellitus. The normal natriuretic response to acute sodium loading in diabetic patients indicates that the set point for sodium homoeostasis may be normal despite the presence of high exchangeable sodium.
Acute Effects of Intravenous Ouabain in Healthy Volunteers
Authors: Pidgeon G. B. , Richards A. M. , Nicholls M. G. , Lewis L. K. , Yandle T. G. 
Published: August 2015

1. The influence of single-dose intravenous ouabain on haemodynamics, renal function and vasoactive hormones was investigated in healthy subjects.
2. After ouabain injection there was a significant reduction in minimum and average hourly heart rates. Diastolic blood pressure fell immediately after ouabain, without a significant change in systolic blood pressure.
3. There was no change in renal blood flow, glomerular filtration rate, hourly urine volume or sodium and potassium excretion.
4. Ouabain injection was associated with a fall in plasma angiotensin II levels and a rise in plasma adrenaline levels, but plasma noradrenaline levels were unchanged. Both plasma atrial and brain natriuretic peptide levels were increased after ouabain administration.
5. The present study demonstrates that ouabain has significant although minor, acute effects on plasma levels of vasoactive hormones. It fails, however, to confirm that ouabain is an acute pressor or natriuretic substance. If it has an important influence on electrolyte and haemodynamic homoeostasis, its actions are likely to be slowly developed.
Effects of Vasopressin V1 and V2 Receptor Antagonists on Progressive Renal Failure in Rats
Authors: Okada Hirokazu , Suzuki Hiromichi , Kanno Yoshihiko , Yamamura Yoshitaka , Saruta Takao 
Published: August 2015

1. The relationship between vasopressin and the progression of renal failure has been proposed, but not intensively investigated because of a lack of orally available, selective vasopressin antagonists.
2. The effects of novel, orally available vasopressin V1 and V2 receptor antagonists on several indices of the progression of chronic renal failure, i.e. blood pressure, urinary protein excretion, sodium balance and renal histopathology, were investigated by using Wistar rats with adriamycin-induced nephropathy accelerated by deoxycorticosterone acetate-salt hypertension. Groups 2 and 3 were treated with V1 and V2 antagonists, respectively, while the untreated group 1 served as the control. To block the effects of vasopressin efficaciously, V1 and V2 antagonists were simultaneously administered (group 4).
3. At week 6, 2 weeks after the beginning of administration of deoxycorticosterone acetate-salt and vasopressin antagonists after the second injection of adriamycin, V1 and V2 antagonists given either alone or in combination significantly reduced the systolic blood pressure as compared with the control, and urine volume was increased in groups 3 and 4. The proteinuria was also decreased at week 10 in groups 2, 3 and 4. Differences in sodium excretion between all groups were not significant. Histopathological alterations in the kidneys of group 4 were significantly ameliorated.
4. These results suggest that a combination of V1 and V2 antagonists can have therapeutic effects in certain types of chronic renal failure.
Blood Pressure Response to Physical Exercise in Healthy Adolescents and Adolescents with Insulin-Dependent Diabetes Mellitus
Authors: Nordgren H. , Freyschuss U. , Persson B. 
Published: August 2015

1. Reference values for systolic blood pressure during exercise are provided for 88 healthy adolescents (12–22 years of age) of both sexes. Data were related to oxygen uptake, heart rate, blood lactate concentration, rate of perceived exertion, age, sex, body size and physcial fitness.
2. The same variables were measured in 55 adolescents of both sexes with insulin-dependent diabetes mellitus of about 12 years duration and were analysed with respect to the healthy control group, to degree of metabolic control and to late diabetic complications.
3. In healthy adolescents the pressure response was not related to sex or age. When compared with control subjects diabetic patients had a higher diastolic blood pressure at rest and a more marked blood pressure increase, 23 versus 19 mmHg W−1 kg−1 body weight, during exercise with no sex difference. The blood pressure rise was not related to metabolic control, glomerular hyperfiltration or physical fitness.
4. Prolonged exercise tests were no more informative regarding the blood pressure response to exercise than the stepwise increased load test. Analysing the blood pressure increase versus relative work load (W/kg body weight) during exercise reveals blood pressure differences otherwise not noted. A diabetic patient with blood pressure above the 97.5% confidence limit during exercise seems to have a higher risk of developing incipient nephropathy 5 years later.
Sodium Status Affects Gc-B Natriuretic Peptide Receptor mRNA Levels, but Not Gc-A Or C Receptor Mrna Levels, in the Sheep Kidney
Authors: Fraenkel Margaret B. , Aldred G. Peter , McDougall John G. 
Published: August 2015

1. In humans and experimental animals the natriuresis and diuresis resulting from infusion of atrial natriuretic peptide varies with the sodium status of the subject. Tissue binding studies have suggested that this may be related to changes in the renal receptors for the hormone.
2. In order to establish whether these changes are under transcriptional control, we examined the levels of mRNA for the three natriuretic peptide receptors [GC-A, GC-B and clearance (C) receptors] in renal cortex and medulla from six sodium-loaded, six sodium-depleted and four control sheep. cDNA probes specific to each receptor were generated using the polymerase chain reaction.
3. GC-B receptor mRNA levels were increased approximately two-fold in the renal cortex of sodium-depleted animals, whereas there was no influence on GC-B receptor mRNA levels in the renal medulla. There was no significant difference in mRNA levels for the GC-A and C receptors.
4. At present the role of the GC-B receptor and its natural ligand C-type natriuretic peptide in the control of renal function is unknown. The present experiments imply some intrarenal function for the GC-B receptor and its natural ligand, although the site of any such function, e.g. renal vasculature or tubules, remains unclear. In addition, we have shown that if GC-A and C receptor levels in the sheep are modulated by sodium, the regulation occurs beyond the level of gene transcription.
Post-Exercise Doppler-Echocardiographic Haemodynamics in Idiopathic Dilated Cardiomyopathy after Metoprolol Infusion
Authors: Perchet Hervé , Pouillart Frédéric , Duval-Moulin Anne Marie , Heintz Jean François , Hittinger LUC , Castaigne Alain , Dubois-Randé Jean Luc 
Published: August 2015

1. The physiological effects of the acute administration of a β-adrenoceptor antagonist in patients with idiopathic dilated cardiomyopathy were assessed by performing post-exercise Doppler-echocardiography study. Eleven patients and six control subjects were studied. According to a double-blind randomized protocol, 5 mg of metoprolol or placebo was administered before cycloergometer exercise.
2. In patients, after metopolol, a significant decrease in heart rate and systolic blood pressure, as well as in peak aortic acceleration and cardiac output, was observed 2 min after exercise. Left ventricular end-diastolic diameter did not change from baseline values either after placebo or metoprolol. In normal subjects, as compared with placebo, a decrease in heart rate and peak aortic acceleration was observed after metoprolol, whereas systolic blood pressure did not change. A similar increase in cardiac output occurred after metoprolol, as compared with placebo, associated with an increase in left ventricular end-diastolic diameter and stroke volume.
3. Post-exercise Doppler echocardiography is a means of assessing haemodynamic changes occurring during exercise in patients with congestive heart failure. Although acute metoprolol administration does not provide beneficial haemodynamic effects, a decrease in the energy requirements of the heart and a faster recovery after exercise may participate in the long-term beneficial action of β-adrenoceptor antagonists.
Waveform Shape Analysis: Extraction of Physiologically Relevant Information from Doppler Recordings
Authors: Ramsay Margaret M. , Pipkin Fiona Broughton , Rubin Peter C. , Skidmore Robert 
Published: August 2015

1. Doppler recordings were made from the brachial artery of healthy female subjects during a series of manoeuvres which altered the pressure—flow characteristics of the vessel.
2. Changes were induced in the peripheral circulation of the forearm by the application of heat or icepacks. A sphygmomanometer cuff was used to create graded occlusion of the vessel above and below the point of measurement. Recordings were also made whilst the subjects performed a standardized Valsalva manoeuvre.
3. The Doppler recordings were analysed both with the standard waveform indices (systolic/diastolic ratio, pulsatility index and resistance index) and by the method of Laplace transform analysis.
4. The waveform parameters obtained by Laplace transform analysis distinguished the different changes in flow conditions; they thus had direct physiological relevance, unlike the standard waveform indices.
Augmented Thermic Effect of Amino Acids under General Anaesthesia: A Mechanism Useful for Prevention of Anaesthesia-Induced Hypothermia
Authors: Selldén EVA , Brundin Tomas , Wahren John 
Published: August 2015

1. Intravenous infusion of amino acids stimulates energy expenditure and heat accumulation in normal man. To find out whether such stimulation also occurs during general anaesthesia, thermogenesis was measured in 21 patients before, during and after anaesthesia and surgery.
2. Ten patients received a mixture of 19 amino acids (240 kJ/h) infused intravenously throughout the anaesthesia. The other 11 patients, serving as controls, received saline. Using catheters previously inserted into the pulmonary and a systemic artery, cardiac output, arteriovenous oxygen difference, pulmonary oxygen uptake and mixed blood temperature were measured.
3. During anaesthesia and surgery, the blood temperature fell by 0.67 ± 0.09 °C/h in the control patients and by 0.38 ± 0.06 C/h in the amino acid-treated patients. Anaesthesia during 34 ± 4 min before surgery reduced the pulmonary oxygen uptake by 145 ± 9 ml/min in the control patients and by 81 ± 10 ml/min in the amino acid-treated patients, corresponding to reductions in total energy expenditure of 47 W in the control group and 26 W in the amino acid-treated group. The difference, 21 W, illustrates the thermogenic action of the amino acids. This value may be compared with that of 4 W, observed in unanaesthetized individuals subjected to 30 min of identical amino acid infusions.
4. At awakening after the anaesthesia, the oxygen consumption rose to 71 ± 21% above the pre-anaesthesia level in the amino acid-treated patients, who, without shivering, rapidly returned to normothermia, whereas in the control patients the oxygen uptake remained slightly below the pre-anaesthesia level, despite sustained hypothermia and vigorous shivering.
5. It is concluded that general anaesthesia augments five-fold the thermic effect of amino acids and that peroperative infusion of amino acids effectively prevents anaesthesia-induced hypothermia.
Potential Role for Interleukin-1 in the Pathophysiology of Ulcerative Colitis
Authors: Wardle T. D. , Turnberg L. A. 
Published: August 2015

1. Biopsies of colonic mucosa from patients with ulcerative colitis liberated more interleukin-1β, prostaglandin E2, leukotriene C4 and platelet-activating factor into the medium in which they were cultured than biopsies from patients with irritable bowel syndrome and histologically normal mucosa.
2. Addition of interleukin-1 stimulated release of greater quantities of all these inflammatory mediators, including interleukin-1 itself, from inflamed and normal mucosa.
3. Blockade of cyclo-oxygenase with indomethacin or of lipoxygenase with ICI 207968 or of phospholipase A2 with mepacrine inhibited release of prostaglandin E2 or leukotriene C4 or both of these plus platelet-activating factor, respectively.
4. Interleukin-1 stimulated the short-circuit current across isolated rat colonic mucosa mounted in flux chambers in a dose-dependent manner (Km 2 × 10−11 mol/l). This stimulation was markedly inhibited by the removal of chloride from the bathing media.
5. Indomethacin or ICI 207968 inhibited the short-circuit current response to interleukin-1 and a combination of these antagonists produced a greater inhibition. Mepacrine caused an even greater inhibition whereas tetrodotoxin plus mepacrine inhibited the current completely.
6. These data indicate that interleukin-1, released in excess from inflamed colonic mucosa, stimulates the release of a range of inflammatory mediators as well as of more interleukin-1. It probably acts by stimulating phospholipase A2 in inflammatory cells, probably lymphocytes, and can do so in normal and inflamed mucosa. Since, in rat colonic mucosa it stimulated an electrical response in very low concentrations, it is feasible that it is involved in the chloride secretion, and hence the diarrhoea, which may occur in inflammatory reactions. Hence treatment with mepacrine seems a prospect worth pursuing.
Short-Term Starvation Alters the Free Amino Acid Content of the Human Intestinal Mucosa
Authors: Ahlman BO , Andersson Kerstin , Leijonmarck Carl-Eric , Ljungqvist Olle , Hedenborg Lennart , Wernerman JAN 
Published: August 2015

1. The effects of short-term starvation and refeeding on the free amino acid concentrations of the intestinal mucosa were characterized in male subjects (n = 6), using endoscopically obtained biopsy specimens from the duodenum and from all four segments of the colon.
2. The alterations in the amino acid concentrations in response to short-term starvation were overall uniform in both duodenal and colonic mucosa as well as in plasma. Most amino acids decreased, whereas branched-chain amino acids increased.
3. In the colon, glutamic acid and glutamine decreased during the starvation period, whereas they remained unaltered in the duodenum. This was the major difference in response to short-term starvation between the amino acid concentrations in the intestinal mucosa of the duodenum and colon.
4. Refeeding for 3 days normalized the amino acid concentrations except for glutamic acid, asparagine and histidine, which remained low in the colon, and threonine, which showed an overshoot in both parts of the intestine.
5. The changes in mucosal amino acid concentrations seen in response to starvation and refeeding were uniform in the four segments of the colon. This suggests that sampling from the rectum/sigmoid colon will give representative values for the free amino acid concentrations of the entire large intestine.
The Rat SA Gene Shows Genotype-Dependent Tissue-Specific Expression
Authors: Kaiser Michael A. , Lodwick David , Samani Nilesh J. 
Published: August 2015

1. SA is a recently identified gene implicated in blood pressure regulation in rodent models of genetic hypertension. In this study we have examined, by Northern blotting, its expression in tissues of the spontaneously hypertensive rat, the Wistar-Kyoto rat and F2 rats, derived from a cross of the spontaneously hypertensive rat with the Wistar-Kyoto rat.
2. We demonstrate that the gene is expressed in a tissue-specific manner. Expression was detected in four sites: kidney, liver, brain and testes.
3. In the kidney and liver expression was higher in the spontaneously hypertensive rat than in the Wistar-Kyoto rat, whereas in the brain and testes the pattern was reversed.
4. In the F2 rats, the levels of SA mRNA in the liver, brain and testes were found to be primarily determined by the genotype at the SA gene locus.
5. The findings suggest the presence of strain-specific cis- and more than one tissue-specific trans-acting factors regulating the expression of the rat SA gene.
Serum Levels, Absorption Efficiency, Faecal Elimination and Synthesis of Cholesterol during Increasing Doses of Dietary Sitostanol Esters in Hypercholesterolaemic Subjects
Authors: Vanhanen H. T. , Kajander J. , Lehtovirta H. , Miettinen T. A. 
Published: August 2015

1. Serum cholesterol reduction and changes in cholesterol metabolism were studied during rapeseed oil feeding without and with increasing amounts of sitostanol trans-esterified with rapeseed oil fatty acids and dissolved in rapeseed oil mayonnaise. Fifteen mildly hypercholesterolaemic subjects replaced 50 g of their usual dietary fat by 50 g of rapeseed oil fat mayonnaise for 6 weeks followed by randomization so that eight subjects continued on rapeseed oil mayonnaise alone (control group) for 15 weeks and seven on rapeseed oil mayonnaise with a small dose of sitostanol ester (800 mg/day of sitostanol) for 9 weeks followed by 6 weeks with higher dose of sitostanol ester (2000 mg/day of sitostanol).
2. During the rapeseed oil period the reduction in serum low-density lipoprotein cholesterol was 14% from the home diet. The control-adjusted reduction by the low sitostanol ester dose was 7.4% (not significant) and by the higher dose it was 15.7%.
3. The low dose of sitostanol ester had no consistent effect on cholesterol precursors or cholestanol in serum, reduced serum levels of campesterol and sitosterol by 28.2% and 23.6%, respectively, and reduced cholesterol absorption efficiency significantly from 28.7% to 23.4%. In accordance, faecal excretion of neutral and particularly endogenous neutral sterols increased (16.7% and 19.7%, respectively), but faecal cholesterol elimination and cholesterol synthesis were only insignificantly increased.
4. During the high dose of sitostanol ester the high-density lipoprotein- to low-density lipoprotein-cholesterol ratio increased. Serum levels of cholesterol precursor sterols, indicators of cholesterol synthesis, increased up to 12%, whereas those of cholestanol were slightly decreased and those of campesterol and sitosterol values were further reduced by 30% and 25.6%, respectively.
5. Associations of serum plant sterols and cholesterol precursors with cholesterol absorption efficiency and synthesis and the sitostanol-ester-induced changes in serum campesterol and lathosterol proportions with those in serum low-density lipoprotein-cholesterol suggest that reduced cholesterol absorption efficiency was the main reason for cholesterol reduction and that there was a compensatory increase in cholesterol synthesis.
6. The findings indicate that sitostanol ester dissolved in dietary fat is apparently unabsorbable and interferes with sterol absorption so that the serum levels of cholesterol and low-density lipoprotein-cholesterol are reduced to the extent that sitostanol ester-fat mixture in reasonable daily amounts can be recommended to replace dietary fat for lowering of serum cholesterol.