bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrocardiographic changes during steady mild hypothermia and normothermia in patients with poikilothermia
Authors: MacKenzie Marius A. , Aengevaeren Wim R. M. , Hermus Ad R. M. M. , van der Werf Tjeerd , Pieters Gerlach F. F. M. , Smals Anthony G. H. , Kloppenborg Peter W. C.
Published: August 2015

1. ECG changes observed in short-term induced and accidental hypothermia are well known. To assess the influence of steady-state spontaneous hypothermia on the ECG, we subjected four patients with acquired poikilothermia (severe thermolability) to 24 h ECG recording, exercise testing and thermal stress.

2. Twenty-four hour Holter monitoring showed a significant reduction in heart rate and a prolongation of the QT interval during steady-state mild hypothermia (rectal temperature 33.9 ± 0.7°C, mean ± sd) compared with during normothermia; no significant changes occurred in the PR interval, QRS complex and QTc interval (QT interval corrected for heart rate).

3. Unlike during normothermia, during steady hypothermia atrioventricular Wenckebach blocks were observed in two patients, whereas another patient showed markedly more atrioventricular Wenckebach blocks during hypothermia.

4. During steady hypothermia the heart rate variability was significantly enhanced in comparison with normothermia.

5. Exercise tolerance was similar during mild hypothermia and normothermia.

6. Heat exposure (ambient temperature 40°C) induced significantly greater changes in rectal temperature, heart rate and PR interval, QRS complex and QT interval in the patients than in the control subjects (n = 8).

7. The present study reveals that even mild steady spontaneous hypothermia can elicit ECG changes, presumably mediated by relatively enhanced cardiac vagal tone. Hence, spontaneous abnormalities in core temperature should be taken into account in interpreting the ECG in clinical practice.
Effect of haemodialysis on plasma levels of brain natriuretic peptide in patients with chronic renal failure
Authors: Lang Chim C. , Maria Anna , Choy J. , Henderson Iain S. , Coutie Wendy J. , Struthers Allan D.
Published: August 2015

1. Plasma human brain natriuretic peptide-like immunoreactivity (hBNP-li) was measured in ten patients with chronic renal failure before and after 4 h of haemodialysis.

2. Plasma hBNP-li was elevated in all patients before dialysis (mean ± sem 21.0 ± 3.8 pmol/l) compared with healthy control subjects (1.3 ± 0.2 pmol/l, n = 11), but showed considerable inter-patient variability. Before dialysis plasma hBNP-li bore no relationship to the serum creatinine level or to the mean blood pressure.

3. Plasma hBNP-li fell significantly (P = 0.04) during 4 h of haemodialysis. The fall in plasma hBNP-li correlated significantly with the degree of postural blood pressure drop (r2 = 0.44, P = 0.05) and with the fall in body weight (r2 = 0.64, P<0.01) after haemodialysis. In all patients, plasma hBNP-li at the end of treatment remained above that in healthy subjects.

4. There was no significant correlation between the fall in plasma hBNP-li and the fall in serum creatinine level, and between the fall in plasma hBNP-li and the fall in supine systolic or diastolic blood pressure, during haemodialysis.

5. We have shown that plasma hBNP-li is elevated in patients with chronic renal failure and is decreased during haemodialysis. The fact that the plasma hBNP-li was not reduced to normal by haemodialysis despite restoration to normovolaemia gives tentative support to the view that, in addition to hypervolaemia, another factor may also be responsible for the elevated plasma hBNP-li seen in these patients.
Differences in ouabain-induced natriuresis between isolated kidneys of Milan hypertensive and normotensive rats
Authors: Foulkes Roland , Ferrario Romana G. , Salvati Patricia , Bianchi Giuseppe
Published: August 2015

1. Several observations support the hypothesis that in rats of the Milan hypertensive strain elevated levels of a circulating ouabain-like factor might normalize the elevated Na+ reabsorption, but, on the other hand, might contribute to the development of hypertension.

2. As the receptor occupancy of this endogenous factor seems to be reversible, the aim of our study was to test, in vitro, the hypothesis of its presence in isolated kidneys from Milan hypertensive rats by studying the response to exogenous ouabain before and after prolonged washing.

3. The kidneys were isolated from adult Milan hypertensive rats and from age-matched normotensive controls and ouabain was given at two different experimental time intervals: shortly (15 min) after washout or after a further 60 min of washout (75 min in total). Comparative experiments with the diuretic hydrochlorothiazide were performed using the same protocol.

4. Ouabain given after 15 min of perfusion caused an increase in renal vascular resistance, diuresis and natriuresis; these haemodynamic and tubular responses were similar in kidneys from both Milan hypertensive and Milan normotensive rats. If given after the washout period, ouabain caused a comparable increase in renal vascular resistance, but a significantly greater natriuresis in kidneys from Milan hypertensive rats as compared with kidneys from Milan normotensive rats. On the other hand, hydrochlorothiazide caused similar natriuresis in kidneys from both strains after washout.

5. These results support the hypothesis that a factor, capable of interacting with the ouabain receptor on the Na+/K+−ATPase of tubular cells, is present in the kidney of adult Milan hypertensive rats and that it can be removed by prolonged washout.
Kinetics of sodium-lithium countertransport activity in patients with uncomplicated type I diabetes
Authors: Rutherford Peter A. , Thomas Trevor H. , Carr Susan J. , Taylor Roy , Wllklnson Robert
Published: August 2015

1. Increased erythrocyte sodium-lithium countertransport activity has been reported to be associated with nephropathy in type 1 diabetes and linked to a family history of essential hypertension.

2. This study aimed to determine the mechanism of increased sodium-lithium countertransport activity. Sodium-lithium countertransport kinetics were measured in uncomplicated and hyperlipidaemic type 1 diabetic patients.

3. In the nine out of 31 uncomplicated type 1 diabetic patients who had high sodium-lithium countertransport activity, the sodium affinity (Km) was normal but the maximum velocity (Vmax.) was increased.

4. Hyperlipidaemia, when present in diabetic patients, was associated with increased sodium-lithium countertransport activity, but could not explain the high activity in uncomplicated type 1 diabetic patients in whom plasma lipid concentrations were normal.

5. Sodium-lithium countertransport activity is increased in type 1 diabetes by a mechanism different to that in essential hypertension, where the mechanism is a low Km (increased sodium affinity). Hence familial hypertension cannot explain the raised sodium-lithium countertransport activity in type 1 diabetes.
Extent of ischaemia caused by hepatic vascular exclusion as evaluated in a canine model
Authors: Egawa Hiroto , Morimoto Taisuke , Takeuchi Toshihiko , Yamaoka Yoshio , Ozawa Kazue , Yamaguchi Tetsuya , Yamamoto Naritaka
Published: August 2015

1. The difference in the extent of liver ischaemia between a hepatic vascular exclusion model and an inflow occlusion model were investigated by determining Indocyanine Green retention and hepatic mitochondrial redox state during 2 h of ischaemia in 10 mongrel dogs. The splanchnic venous bed and/or the infra-hepatic inferior vena cava were decompressed by pump-driven veno-venous bypass.

2. The Indocyanine Green retention test revealed that there was no hepatic blood flow in the hepatic vascular exclusion model during ischaemia (96.8 ± 0.73% retention of the dye after 20 min), whereas hepatic blood perfusion was still present significantly in the inflow occlusion model (78.1 ± 1.19% retention of the dye after 20 min) (P <0.01).

3. The mitochondrial redox potential of the liver in the dogs with hepatic vascular exclusion decreased immediately after the induction of ischaemia and remained fixed at extremely low levels. By contrast, in the dogs with inflow occlusion the redox potential decreased gradually after induction and was maintained significantly higher than that in dogs with hepatic vascular exclusion during 2 h of ischaemia (P<0.01).

4. It is concluded that the extent of liver ischaemia in the hepatic vascular exclusion model with pump-driven shunt is significantly different from that in the inflow occlusion model with shunt.
Exercise training reduces the sympathetic component of the blood pressure-heart rate baroreflex in man
Authors: Kingwell Bronwyn A. , Dart Anthony M. , Jennings Garry L. , Korner Paul I.
Published: August 2015

1. Exercise training reduces resting sympathetic activity, but the effects on sympathetic activation or withdrawal during baroreflex responses to blood pressure perturbations are controversial. The purpose of this study was to investigate the effects of training on both the vagal and sympathetic reflex heart rate responses to blood pressure changes.

2. Using 10 healthy males in a randomized cross-over design, we examined the effects of three 30 min cycling sessions at 70% of maximal capacity for 4 weeks on the steady-state reflex heart rate responses to perturbations in mean arterial pressure induced with injections of nitroprusside and phenylephrine. The method provides a sigmoidal relationship between changes in heart rate and blood pressure. The upper plateau (maximum tachycardia in response to blood pressure reduction) and lower plateau (maximum bradycardia in response to blood pressure elevation) are mainly mediated by the cardiac sympathetics and vagus, respectively. The slope of the relationship is a measure of reflex gain.

3. Training, which increased maximal oxygen consumption by 13 ± 2% (mean ± standard error of the difference), reduced supine and standing blood pressures by 3 ± 1 / 3 ± 1 mmHg (P < 0.05) and 4 ± 1/2 ± 2 mmHg (P < 0.05 for systolic), respectively, whereas resting heart rate was lowered by 6 ± 1 beats/min (P < 0.05). Reflex sensitivity in the presence of functioning vagus and sympathetics was not altered with training, but the vagal component of sensitivity, as assessed after sympathetic blockade with propranolol, was significantly reduced. The maximal tachycardiac responses to blood pressure decreases were consistently reduced with training (sedentary, 106 beats/ min; trained, 97 ± 1 beats/min; P < 0.05). This attenuation was not evident in the presence of propranolol, suggesting a sympathetic origin.

4. Exercise training thus reduced the sympathetic contribution to reflex tachycardia induced by blood pressure reduction and diminished the vagal contribution to reflex sensitivity. These effects of training may be of relevance to individuals with elevated sympathetic activity who may be at risk of myocardial ischaemia, serious ventricular arrhythmias or sudden cardiac death.
Effect of diet-induced weight loss on total body bone mass
Authors: Compston J. E. , Laskey M. A. , Croucher P. I. , Coxon A. , Kreitzman S.
Published: August 2015

1. Total body areal bone mineral density was measured by dual-energy X-ray absorptiometry in eight women before and 10 weeks after a very-low-calorie diet [405 kcal (1701 kJ)/day].

2. The mean weight loss of 15.6 kg was accompanied by a statistically significant reduction in total body bone mineral density from 1.205 ± 0.056 to 1.175 ± 0.058 g/cm2 (mean ± sd, P < 0.005).

3. After cessation of the diet, weight gradually increased and by 10 months was similar to baseline values. Total body bone mineral density also increased after stopping the diet and mean values obtained 10 months after the diet did not differ significantly from initial values. Throughout the study total body bone mineral density values in all subjects were well within the range reported for normal subjects.

4. These data indicate that diet-induced weight loss is associated with rapid bone loss, subsequent weight gain being accompanied by increases in bone mass. Further studies are required to establish the clinical significance of these findings and, in particular, the skeletal distribution of bone loss.
Accumulation of calcium by normal and dystrophin-deficient mouse muscle during contractile activity in vitro
Authors: McArdle A. , Edwards R. H. T. , Jackson M. J.
Published: August 2015

1. Accumulation of calcium by extensor digitorum longus muscles from dystrophin-deficient mdx and control C57BL/10 mice has been studied in vitro by measurements of total muscle calcium and by following the retention of 45Ca resulting from the incubation of muscles with the isotope for up to 2 h.

2. The rate of influx of calcium, calculated from the retention of 45Ca, was linear over 2 h in muscles at rest with no significant difference between mdx and control muscles.

3. Repetitive tetanic stimuli caused a substantial increase in 45Ca flux into both mdx and control muscles. This elevated rate of influx was maintained by control muscle, but not by mdx muscle after stimulation resulting in a significantly smaller total calcium flux into mdx muscle compared with control muscle by 1 h after stimulation. Similar changes were also seen in the total muscle calcium content of mdx and control muscles. Comparison of these results with those for loss of cytosolic creatine kinase previously reported (McArdle, A., Edwards, R.H.T. & Jackson, M.J. Clin. Sci. 1991; 80, 367-71) [1] indicate that control and dystrophin-deficient muscles release equivalent amounts of intracellular creatine kinase in response to the same accumulation of intracellular calcium.

4. These results therefore do not support the hypotheses that dystrophin deficiency in muscle leads to increased calcium influx during contractile activity, or that dystrophin-deficient muscle shows any inherent increased permeability to cytosolic proteins.
Plasma platelet-activating factor degradation in patients with severe coronary artery disease
Authors: Graham Ross M. , Stephens Charlene J. , Sturm Marian J. , Taylor Roger R.
Published: August 2015

1. Platelet-activating factor is inactivated in plasma by the action of a specific acetylhydrolase that cleaves the acetate moiety from the sn-2 position. Degradation was determined under optimized conditions and under conditions closer to those which may occur in vivo. The latter, or platelet-activating factor half-life, was measured by a modified method that is simple, inexpensive and reliable.

2. A hyperbolic relationship was found to exist between the two measures of degradation, the values in both normal subjects and patients with coronary artery disease falling on the tail of the hyperbola. Thus, there is an increase in platelet-activating factor half-life associated with a lowering of acetylhydrolase activity, but this increase is relatively small.

3. There were significant direct linear relationships between acetylhydrolase activity and serum total cholesterol and low-density-lipoprotein-cholesterol concentrations in both subject groups. Although acetylhydrolase activity was most closely associated with the low-density-lipoprotein-cholesterol fraction, the activity for a given serum level of low-density-lipoprotein-cholesterol was higher in patients with coronary artery disease.
High-voltage pulsed galvanic stimulation: effects of frequency of current on blood flow in the human calf muscle
Authors: Heath Martha E. , GIBBS Susan Bleck
Published: August 2015

1. Twelve healthy subjects received high-voltage pulsed galvanic stimulation (115–475V d.c.) delivered in separate treatments of 2, 32 and 128 pulses/s for 10 min at the subject's maximum tolerable voltage while calf muscle blood flow was measured by non-invasive Whitney strain-gauge venous occlusion plethysmography.

2. The high-voltage pulsed galvanic stimulation was administered with negative polarity by an intermittent mode of 30 s on, 30 s off. Measurements of calf muscle blood flow were made during each 30 s period when the stimulus was off. The effect of one 30 s maximum isometric contraction of the calf muscles on blood flow was used as a standard for evaluating the effectiveness of high-voltage pulsed galvanic stimulation on calf muscle blood flow.

3. Significant (paired t-tests; P < 0.05) increases in calf muscle blood flow over the preceding baseline levels occurred for the isometric contraction (322%) and for frequencies of 2 pulses/s (33.5%) and 128 pulses/s (13.36%), but not for a frequency of 32 pulses at which calf muscle blood flow increased in only six of 12 subjects. The mean increases in calf muscle blood flow at 2 and 128 pulses/s represented 11.63% and 4.0%, respectively, of that resulting from the isometric contraction.

4. A clear positive correlation between voltage level and the magnitude of increase in calf muscle blood flow was demonstrated but differed for each frequency used.

5. It is concluded that high-voltage pulsed galvanic stimulation results in a measurable increase in calf muscle blood flow when it is applied at frequencies of 2 or 128 pulses/s on intermittent mode and at maximum tolerable voltages, but the magnitude of the increase in blood flow is small compared with that stimulated by a maximal isometric contraction.
Cutaneous blood flow during a hypoglycaemic clamp in insulin-dependent diabetic patients and healthy subjects
Authors: Åman J. , Berne C. , Ewald U. , Tuvemo T.
Published: August 2015

1. A marked cutaneous vasodilatation has been shown to occur in healthy subjects, but not in insulin-dependent diabetic patients, in response to hypoglycaemia induced by a rapid intravenous bolus injection of insulin.

2. In the present study cutaneous blood flow in response to a gradual decline in blood glucose concentration was investigated in eight young adult diabetic patients and in eight age- and sex-matched control subjects. After a hyperinsulinaemic euglycaemic clamp for 40 min, hypoglycaemia was induced (plasma glucose concentration 2 mmol/l) by a standardized stepwise reduction in the intravenous glucose infusion

3. Blood flow was measured by using a laser Doppler sensor and a cutaneous O2 electrode placed on the medial aspect of the forearm, and a laser Doppler sensor placed on the forehead.

4. No significant change in cutaneous blood flow occurred during euglycaemic hyperinsulinaemia.

5. In control subjects a marked increase in blood flow during hypoglycaemia was observed in the forearm by both methods. No corresponding change was observed in the forehead.

6. In the diabetic patients the increase in cutaneous blood flow was absent in both the forearm and forehead.

7. It is concluded that hypoglycaemia, but not hyperinsulinaemia, is associated with a regional cutaneous vasodilatation in healthy control subjects. This cutaneous vasodilatation is absent in diabetic patients.
Ion transport characteristics of the murine trachea and caecum
Authors: Smith S. N. , Alton E. W. F. W. , Geddes D. M.
Published: August 2015

1. The basic defect in cystic fibrosis relates to abnormalities of ion transport in affected tissues, such as the respiratory and gastrointestinal tracts. The identification of the cystic fibrosis gene has enabled studies on the production of a cystic fibrosis transgenic mouse to be undertaken. Knowledge of normal ion transport will be necessary for the validation of any such animal model. We have therefore characterized selected responses of the murine trachea and caecum mounted in ‘mini’ Ussing chambers under open-circuit conditions.

2. Basal values for the trachea were: potential difference, 1.1 mV (sem 0.2; n=18); equivalent short-circuit current, 20.4 μA/cm2 (3.6); conductance, 18.2 mS/cm2 (1.7). Corresponding values for the caecum were: potential difference, 0.7 mV (0.1; n=18); equivalent short-circuit current, 11.0 μA/cm2 (1.6); conductance, 14.5 mS/cm2 (1.4).

3. Amiloride (10 μmol/l) produced a significant (P < 0.001) fall in potential difference of 43.0% (5.7) in the trachea, but had no significant effect in the caecum.

4. Subsequently, one of three protocols was used to assess the capacity of either tissue for chloride secretion. Addition of a combination of forskolin (1 μmol/l) and zardaverine (10 μmol/l) produced rises in the potential difference of 873% (509) in the trachea and 399% (202) in the caecum. Both A23187 (10 μmol/l) and phorbol dibutyrate (10 nmol/l) increased tracheal potential difference by 350% (182) and 147% (47), respectively. Neither had a significant effect in the caecum.

5. Subsequent addition of bumetanide caused a fall in the stimulated potential difference of between 39.8% and 71.7%, depending on secretagogue and tissue type.

6. When a homozygous transgenic cystic fibrosis mouse becomes available, these responses should allow such an animal to be distinguished from normal or heterozygous mice.
Hepatic glutamine metabolism in the septic rat
Authors: Salleh M. , Ardawi M.
Published: August 2015

1. The hepatic metabolism of glutamine, alanine, ammonia, urea, glutathione and glucose was studied in rats made septic by caecal ligation and puncture and was compared with that in rats that had undergone sham operation (laparotomy).

2. Sepsis resulted in increases in the plasma activities of γ-glutamyltransferase (P < 0.001), alanine aminotransferase (P < 0.001) and aspartate aminotransferase (P < 0.001), the serum total and direct bilirubin concentrations (P < 0.001), and the blood lactate (P < 0.01), glutamine (P < 0.05), alanine (P < 0.001) and urea (P < 0.05) concentrations, but produced decreases in the blood ketone body (P < 0.001) and glutathione (P < 0.05) concentrations and in the plasma cholesterol concentration (P < 0.05). These changes were associated with marked negative nitrogen balance in septic rats.

3. Sepsis increased total hepatic blood flow (by 22.7%) together with hepatic arterial flow (by 25.8%) and portal venous flow (by 18.7%). Sepsis resulted in marked increases in the net rates of hepatic extraction of glutamine (by 164%), alanine (by 138%) and ammonia (by 259%) with concomitant increases in the net rates of hepatic release of glutamate (by 105%), glutathione (by 87.5%), glucose (by 70.1%) and urea (by 100.4%).

4. Sepsis increased the activities of liver carbamoyl-phosphate synthase (by 16.4%), ornithine transcarbamylase (by 29.8%), argininosuccinate synthase (by 28.1%) and arginase (by 33.8%).

5. Septic rats exhibited marked increases in hepatic protein (by 46.0%), RNA (by 43.4%) and DNA (by 37.7%) contents. These changes were accompanied by marked increases in the activity of thymidine kinase (by 35.9%).

6. It is concluded that the enhanced hepatic glutamine extraction in response to sepsis could be attributed to increases in hepatic ureagenesis, gluconeogenesis, proliferative and synthetic activities, and glutathione production.
Physiological basis for an animal model of the renal Fanconi syndrome: use of succinylacetone in the rat
Authors: Wyss Peter A. , Boynton Sandra B. , Chu Judith , Spencer Robert F. , Roth Karl S.
Published: August 2015

1. The biochemical basis for the human renal Fanconi syndrome, including glucosuria, phosphaturia and aminoaciduria, remains enigmatic. This is due, in part, to the lack of an appropriate animal model. Since there is an association between the human genetic disease hereditary tyrosinaemia, for which urinary excretion of the compound succinylacetone constitutes a biochemical marker, and a renal Fanconi syndrome, we have examined the relationship between succinylacetone and renal tubular function in the rat.

2. Intraperitoneal injection of succinylacetone for 3 consecutive days into adult male Sprague-Dawley rats resulted in succinylacetone plasma concentration of 3 mmol/l. This concentration was associated with glucosuria, aminoaciduria, polyuria, reduced renal phosphate reabsorption and normal creatinine clearance. In addition, urinary porphobilinogen and total porphyrin excretions were markedly reduced. In animals permitted to recover for 7 days after succinylacetone administration, these renal functional changes remitted partially or completely. Ultrastructural examination of the kidneys after the 3 days of treatment showed no fine structural changes.

3. We conclude that the physiological alterations produced in normal rat renal tubules by succinylacetone provide the basis for the study of the biochemical changes underlying the human renal Fanconi syndrome.
Effect of l-alanine infusion on 31P nuclear magnetic resonance spectra of normal human liver: towards biochemical pathology in vivo
Authors: Dagnelie P. C. , Menon D. K. , Cox I. J. , Bell J. D. , Sargentoni J. , Coutts G. A. , Urenjak J. , Iles R. A.
Published: August 2015

1. 31P n.m.r. spectroscopy in vivo was used to study the effect of l-alanine infusion on the concentrations of gluconeogenic intermediates in normal human liver. Studies were performed in six healthy male subjects (34–44 years, fasted overnight) using a chemical shift imaging pulse sequence on a whole-body n.m.r. system operating at 1.6T. Hepatic 31P n.m.r. spectra were obtained from 10 min before to 70 min after intravenous administration of 0.70 (n = 2), 1.40 (n = 3) or 2.80 (n = 5) nmol of l-alanine/kg body weight over 4.5 min. Concentrations of phosphomonoesters, Pi and phosphodiesters relative to ATP were calculated from peak areas in the n.m.r. spectra, using the β-ATP peak as a reference.

2. Dose-dependent spectral changes were observed for [phosphomonoesters]/[ATP] and [Pi]/[ATP]. At the highest dose given, maximal changes in [phosphomonoesters]/[ATP] (mean ± sem: 98 ± 12%, P<0.005) and [Pi]/[ATP] (−33 ± 3%, P<0.001) were observed approximately 45 min after the l-alanine infusion. [Phosphodiesters]/[ATP] showed a maximal increase of 24 ± 6% (P<0.05), which was independent of the l-alanine dose. Hepatic ATP levels and pH did not change.

3. To identify the metabolites responsible for the changes observed in vivo, male Wistar rats were infused with 11.2 mmol of l-alanine/kg body weight. After 15 min, livers were freeze-clamped and were extracted according to standard procedures. In vitro, 31P n.m.r. spectra obtained at 8.4 or 11.7 T revealed sharp increases in the concentrations of 3-phosphoglycerate and phosphoenolpyruvate after l-alanine infusion. No significant increases in other metabolites contributing to the phosphomonoester or phosphodiester resonances in vivo were observed, suggesting that the rise in [phosphomonoesters] observed in vivo was caused by increasing concentrations of 3-phosphoglycerate, and that phosphoenolpyruvate contributed to the rise in [phosphodiesters].

5. These results show that l-alanine infusion leads to consistent changes in the 31P n.m.r. spectra of the human liver owing to increased concentrations of gluconeogenic intermediates. The ‘n.m.r.-alanine test’ may constitute a useful tool for studies of gluconeogenesis and hepatic biochemical pathology in vivo.
Absorption of non-haem iron in normal women measured by the incorporation of two stable isotopes into erythrocytes
Authors: Barrett J. F. R. , Whittaker P. G. , Williams J. G. , Lind T.
Published: August 2015

1. Iron absorption has been quantitatively measured as the incorporation of physiological doses of stable iron isotopes into erythrocytes. Five milligrams of 57Fe (orally) and 250 μg of 58Fe (intravenously) were given to five healthy women on 2 consecutive days. Fourteen days later the changes in the 57Fe/56Fe and 58Fe/56Fe ratios in the erythrocytes of each subject were measured using an inductively coupled plasma mass spectrometer. Isotope ratios were also measured in two subjects who were not given any enriched isotope. Concomitant measurements of plasma volume using a dye-dilution technique enabled the estimation of body iron mass and the calculation of iron absorption.

2. The mean coefficients of variation for the 57Fe/56Fe ratio and the 58Fe/56Fe ratio were 0.22% and 0.47%, respectively. This precision allowed enrichments of basal ratios to be reliably detected in all cases. The mean change in the 57Fe/56Fe ratio was 0.00116 (sd 0.00052, P<0.001) and the mean change in the 58Fe/56Fe ratio was 0.00035 (sd 0.00004, P<0.001). Control subjects showed no enrichment.

3. The calculated iron absorption ranged from 10% to 34%, and the amount of absorption was related to the iron stores of the subjects. Percentage iron absorption was identical when estimates of the plasma volume (derived from a body mass equation) were used instead of the plasma volume determined by dye-dilution measurements. Incorporation of intravenous iron into erythrocytes was on average 81% (range 68–93%).

4. The method is especially applicable to the study of iron absorption during pregnancy when incorporation into erythrocytes cannot be predicted.
Expression of adhesion molecules on circulating leucocytes in patients with inflammatory bowel disease
Authors: Greenfield S. M. , Hamblin A. , Punchard N. A. , Thompson R. P. H.
Published: August 2015

1. The expression of leucocyte antigens CD11/CD18 and complement receptor 1 was studied on the circulating leucocytes of 13 patients with inflammatory bowel disease and 13 age- and sex-matched healthy control subjects.

2. Monoclonal antibodies against CD11/CD18 and complement receptor 1 were added to leucocyte suspensions from patients and control subjects. Antibody binding was detected using a fluorescein-conjugated rabbit anti-mouse antibody and flow cytometry. The proportions of lymphocytes, monocytes and granulocytes expressing these molecules and the density of antigen expression, measured as mean fluorescence intensity, were determined.

3. There were no differences between patients and control subjects in the mean fluorescence intensity of antibody staining of surface molecules or in the proportion of cells expressing each molecule for any cell type. Analysis of subgroups of patients according to disease type, severity or treatment also showed no difference compared with control subjects.

4. We conclude that failure to identify a population of circulating leucocytes whose adhesion molecules or complement receptors are upregulated may arise because cells are only activated locally within the gut vasculature. Alternatively, structural changes in these molecules, rather than an increase in their number or the expression of other surface glycoproteins, may be more important in mediating adhesive interactions in inflammatory bowel disease.
Pathophysiology of unilateral high-grade carotid artery stenosis: evaluation of intracranial haemodynamics by analysis of velocity waveforms from the middle cerebral artery
Authors: Fürst Heinrich , Hartl Wolfgang H. , Jansen Ingrid , Fink Barbara , Piepgras Axel , Lauterjung Lutz , Schildberg Friedrich W.
Published: August 2015

1. Transcranial flow velocity waves were measured via Doppler sonography of the middle cerebral artery during hypo-, hyper- and normo-capnia. Applying the principle of vascular impedance, flow velocity waves were analysed in 30 young subjects, 37 elderly subjects and 18 patients with high-grade unilateral internal carotid artery disease.

2. There was evidence that the relative peak-to-peak velocity in the middle cerebral artery could serve as an index of peripheral wave reflection and cerebral resistance (CRi). The response of CRi to changes in arterial CO2 concentration (CRi reactivity) showed a clear age-dependency. However, the absolute side-to-side asymmetry of CRi reactivity (ΔR) did not vary with age and could be used to define a normal range (0–4%CRi/vol.%CO2).

3. Selective angiography demonstrated no cerebral cross-flow through the anterior part of the circle of Willis in nine patients with carotid artery stenosis whose absolute ΔR was above the normal range and whose CRi reactivity of the affected hemisphere was lower than that of the healthy opposite hemisphere. Conversely, another group of nine patients, whose ipsilateral CRi reactivity was higher than the contralateral CRi reactivity, demonstrated cross-flow through the anterior part of the circle of Willis.

4. ΔR may be used to identify patients who have high-grade internal carotid artery stenosis and present with low cerebral vascular resistance owing to poor intracerebral collaterals.
Contribution of soluble aluminium species to absorption of aluminium from the rat gut in situ
Authors: Partridge Neil A. , Regnier Fred E. , Reed Willie M. , White Joe L. , Hem Stanley L.
Published: August 2015

1. Rat gut perfusion studies in vivo at pH 4, 6 or 8 using aluminium chloride or equimolar aluminium chloride and sodium citrate showed that elevated plasma aluminium concentrations were associated with aluminium solubility in the perfusion. Elevated plasma aluminium levels and soluble aluminium in the perfusate occurred with perfusion of equimolar aluminium chloride and sodium citrate at all three pH values.

2. Partitioning studies in vitro, utilizing water and ethyl acetate, revealed that uncomplexed aluminium exhibited maximum partitioning into the ethyl acetate phase at pH 2.5. When complexed with citrate, aluminium exhibited partitioning over a much broader pH range, pH 2.5–8.0.

3. A direct linear relationship was observed between the soluble aluminium concentration of the perfusate and the increase in the plasma aluminium level, suggesting that soluble aluminium is absorbed by a passive diffusion mechanism.
Plasma concentrations of immunoreactive-endothelin in patients with chronic renal failure treated with recombinant human erythropoietin
Authors: Takahashi Kazuhiro , Totsune Kazuhito , Imai Yutaka , Sone Masahiko , Nozuki Mitsuru , Murakami Osamu , Sekino Hiroshi , Mouri Toraichi
Published: August 2015

1. Elevation of blood pressure is one of the major side effects of recombinant human erythropoietin therapy in haemodialysis patients.

2. We investigated the possible involvement of endothelin in the pathogenesis of this recombinant human erythropoietin-induced blood pressure elevation in 51 patients undergoing maintenance haemodialysis.

3. Blood haemoglobin level increased from 7.1 ± 0.1 to 8.8 ± 0.1g/dl (means ± SEM) after 8 weeks of treatment with recombinant human erythropoietin (3000–4500 units/week). An increase in mean blood pressure was found in 19 patients (37%) (n = 9, by 0–10 mmHg; n = 10, by > 10 mmHg).

4. Plasma immunoreactive-endothelin concentration significantly increased from 2.26 ± 0.18 to 3.14 ± 0.31 pmol/l in the 10 patients whose mean blood pressure increased by more than 10 mmHg (P < 0.05), but not in the other patients. Moreover, the increase in plasma immunoreactive-endothelin concentration showed a significant positive correlation with the change in mean blood pressure in 19 patients with elevated mean blood pressure (r = 0.47, P < 0.05).

5. There was no significant correlation between the change in plasma immunoreactive-endothelin concentration and the change in blood haemoglobin level or the change in body weight.

6. These results suggest the possibility that endothelin may contribute to the recombinant human erythropoietin-related rise in blood pressure in some haemodialysis patients.
Possible link between vitamin D and hyperoxaluria in patients with renal stone disease
Authors: Giannini Sandro , Nobile Martino , Castrignano Rocco , Pati Tecla , Tasca Andrea , Villi Giorgio , Pellegrini Federico , D'Angelo Angela
Published: August 2015

1. Vitamin D seems to play an essential role in the pathogenesis of idiopathic hypercalciuria at least in part via intestinal hyperabsorption of calcium. Hyper-absorption of calcium, in turn, might enhance the intestinal uptake of free oxalate, thus leading to hyperoxaluria. To verify this hypothesis we studied 75 calcium-stone-formers subdivided as follows: group 1 (15 patients) with isolated hyperoxaluria; group 2 (25 patients) with hyperoxaluria and hypercalciuria; group 3 (22 patients) with isolated hypercalciuria; group 4 (12 patients) with no metabolic abnormalities.

2. As expected, urinary calcium excretion differed in the various groups (P < 0.001), being highest in groups 2 and 3; urinary oxalate excretion, by definition highest in groups 1 and 2, was even more pronounced in group 2 than in group 1 (P < 0.05). Although in the normal range, the serum 1,25-dihydroxyvitamin D concentration was higher (P < 0.001) in the two hypercalciuric groups (2 and 3), showing peak levels in group 2.

3. When the data from the 75 stone-formers were pooled, there was a positive correlation between the serum concentration of 1,25-dihydroxyvitamin D and urinary calcium excretion (P < 0.001) and urinary oxalate excretion (P < 0.003), the latter relationship also being present when only the two hypercalciuric groups (groups 2 and 3) were considered together (P < 0.05).

4. Our data seem to confirm a relevant role for the vitamin D system in the pathogenesis of calcium nephrolithiasis due to increased intestinal calcium absorption, but also because this in turn induces a greater intestinal absorption of oxalate, thus leading to the occurrence or exacerbation of hyperoxaluria.
Assessment of the mathematical issues involved in measuring the fractional synthesis rate of protein using the flooding dose technique
Authors: Chinkes David L. , Rosenblatt Judah , Wolfe Robert R.
Published: August 2015

1. The fractional synthesis rate of protein is commonly measured by either the constant infusion method or the flooding dose method. The two methods often give different results.

2. An underlying assumption of the traditional flooding dose formula is that the protein synthesis rate is not stimulated by the flooding dose. A new formula for calculation of the fractional synthesis rate is derived with the alternative assumption that the protein synthesis rate is stimulated by an amount proportional to the change in the intracellular concentration of the infused amino acid. The alternative formula is:

where EB and EF are the enrichments of bound and free amino acid, respectively (atom per cent excess), and C=1-(EF/EI), where EI is the enrichment of the infusate. This approach defines the lowest possible value for the fractional synthesis rate. The traditional equation gives a maximal value for the fractional synthesis rate.

3. When data from the literature are considered, the fractional synthesis rate of muscle protein as calculated by the constant infusion technique falls between the values of fractional synthesis rate calculated by the two flooding dose formulae when leucine is the tracer, suggesting that a flooding dose of leucine exerts a stimulatory effect on the rate of protein synthesis, but that the increase is not as great as the increase in the intracellular concentration of leucine.

4. The precision of the formula for the calculation of fractional synthesis rate is limited by the accuracy of the underlying assumptions regarding the effect of the flooding dose on the fractional synthesis rate. At present, the best approach would appear to be the use of both equations to calculate the upper and lower bounds of the true fractional synthesis rate.
Elevated total body noradrenaline spillover in normotensive members of hypertensive families
Authors: Ferrier Claudia , Cox Helen , Esler Murray
Published: August 2015

1. In prehypertension, abnormalities in cardiovascular control mechanisms have been described. It has been postulated that this may involve hereditary disturbances in the sympathetic regulation of blood pressure. Since the neurochemical methods used to test sympathetic nervous system activity have been rather imprecise, in the present study we have applied noradrenaline plasma kinetic methodology to evaluate sympathetic activity in normotensive subjects with a familial predisposition to essential hypertension.

2. Total body noradrenaline spillover to plasma, an index of integrated sympathetic nerve firing rates, was calculated during infusion of l-[7-3H] noradrenaline in 11 normotensive offspring of essential hypertensive parents and 11 age-, height- and weight-matched normotensive offspring of normotensive parents.

3. The resting arterial plasma noradrenaline concentration was higher in healthy subjects with a family history of essential hypertension (1.41 ± 0.15 nmol/l, mean ± SEM, P < 0.002) than in normotensive subjects with no family history of essential hypertension (0.82 ± 0.07 nmol/l). The overall rate of spillover of noradrenaline to plasma was also elevated in the normotensive offspring of hypertensive parents (4.34 ± 0.54 nmol/min) compared with subjects with a negative family history of essential hypertension (2.02 ± 0.20 nmol/min). Similarly, the arterial plasma concentration of the noradrenaline precursor 3,4-dihydroxyphenylalanine was higher in subjects with a positive family history of essential hypertension (7.55 ± 0.24 nmol/l) than in normotensive control subjects (5.97 ± 0.30 nmol/l, P < 0.001). Despite this apparent evidence of relative sympathetic nervous activation in the subjects with a positive family history of hypertension, their blood pressure and heart rate were only marginally, and non-significantly, higher.

4. Biochemical indices of sympathetic function in normotensive offspring of hypertensive parents suggest a familial disturbance in sympathetic nervous system activity, which may be a predictor for the development of hypertension in adult life.
Free-radical scavengers, thiol-containing reagents and endothelium-dependent relaxation in isolated rat and human resistance arteries
Authors: Sunman W. , Hughes A.D. , Sever P.S.
Published: August 2015

1. Small arteries were isolated from either rat mesentery or human subcutaneous fat, and mounted in a myograph for the measurement of isometric force.

2. Superoxide dismutase, either in the presence or absence of catalase, relaxed noradrenaline-induced tone. This effect was abolished by removal of the endothelium or incubation with an inhibitor of NO synthase, N-ω-nitro-L-arginine methyl ester. Catalase alone had a negligible effect on noradrenaline-induced tone.

3. Captopril, an angiotensin-converting enzyme inhibitor and putative free-radical scavenger, did not relax pre-contracted isolated vessels. N-Acetylcysteine caused an endothelium-independent relaxation of rat vessels. Similar effects were observed in human vessels.

4. Acetylcholine induced a concentration-dependent relaxation of isolated resistance arteries, which was inhibited by removal of the endothelium or N-ω-nitro-L-arginine methyl ester, but unaffected by indomethacin. Preincubation with captopril, N-acetylcysteine or catalase alone did not alter the acetylcholine concentration-response relationship, but superoxide dismutase in combination with catalase enhanced responses to acetylcholine, causing a six-fold increase in potency.

5. Superoxide dismutase causes endothelium-dependent relaxation of resistance arteries and potentiates responses to acetylcholine. This action is probably due to the ability of the enzyme to scavenge superoxide anions which inhibit endothelium-dependent relaxation.

6. N-Acetylcysteine causes an endothelium-independent relaxation of resistance arteries which is probably unrelated to the putative ability of this compound to scavenge superoxide radicals and may reflect a direct action on vascular smooth muscle.
Assessment of Glomerular Charge Selectivity in Man by Differential Clearance of Isoamylases
Authors: Fox J. G. , Quin J. D. , O'reilly D. Stj. , 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 30 normal subjects, 14 patients with minimal proteinuria and 23 patients with heavy proteinuria due to primary glomerulopathies. Seven patients with minimal change nephropathy were studied in relapse and remission.

2. CPAm/CSAm exceeded 2.0 (range 2.1-6.1) in all normal subjects, indicating that the normal glomerular capillary wall possesses charge selectivity at the molecular size of amylase (molecular mass 56 kDa). 3. CPAm/CSAm was significantly lower in patients with heavy proteinuria than in normal subjects or patients with minimal proteinuria. CPAm/CSAm was low in patients with minimal change nephropathy in relapse and rose into the normal range with steroid-induced remission.

4. These data suggest that heavy proteinuria in primary glomerulopathies is accompanied by loss of glomerular charge selectivity. Remission of minimal change nephropathy is associated with restoration of normal charge selectivity.
Intravenous Infusion of Tridihomo-γ-Linolenoyl-Glycerol Reduces Leukotriene B4 Production in the Rat and Rabbit
Authors: Nakamura Norio , Hamazaki Tomohito , Taki Hirofumi , Yamazaki Katsuya , Kobayashi Masashi
Published: August 2015

1. We have formulated an infusible emulsion of 10% tridihomo-γ-linolenoyl-glycerol (94% pure) and investigated the effects of its infusion on leukotriene B4 production.

2. We infused the emulsion into the ear veins of two rabbits in a dose of 0.8 g of tridihomo-γ-linolenoyl-glycerol/kg. Polymorphonuclear leucocytes were obtained from rabbits before the infusion, and 6, 24, 72 and 168 h after. The ionophore-stimulated leukotriene B4 production by polymorphonuclear leucocytes was reduced to about 50% of baseline as early as 6 h after the infusion and remained reduced until 24 h after the infusion.

3. To closely investigate the changes in leukotriene B4 production at 6 h after the infusion, we infused 1.0 g of tridihomo-γ-linolenoyl-glycerol/kg into the tail veins of eight male Wistar rats. Six hours later, peritoneal macrophages were obtained from four rats for the analysis of ionophore-stimulated leukotriene B4 production. Peritoneal cells and blood samples were also obtained from the remaining rats for fatty acid analysis. Another eight rats were used without prior infusion for baseline determination.

4. The production of leukotriene B4 by macrophages was significantly reduced to 42% of baseline, and the plasma free dihomo-γ-linolenic acid was markedly increased from 0.26 to 4.82 mol%, in 6 h.

5. We conclude that the infusion of a tridihomo-γ-linolenoyl-glycerol emulsion is able to decrease leukotriene B4 production and to increase the dihomo-γ-linolenic acid concentrations in the plasma and peritoneal cells of rats in 6 h.
What is the Blood Flow to Resting Human Muscle?
Authors: Elia M. , Kurpad A.
Published: August 2015

1. An investigation was carried out in five healthy lean adults to assess whether forearm and calf plethysmography largely reflect muscle blood flow as measured by 133Xe and whether there is substantial variability in the blood flow to muscles located at different sites in the body.

2. Blood flow to forearm and calf flexors and extensors, biceps, triceps and quadriceps was assessed using the 133Xe clearance technique. Blood flow to forearm skin and subcutaneous adipose tissue was also measured using the 133Xe clearance technique, whereas blood flow to the forearm and calf was measured using strain gauge plethysmography.

3. The mean blood flow to different muscles ranged from 1.4 ± 0.6 (gastrocnemius) to 1.8 ± 0.7 (forearm extensor) ml min−1 100 g−1 muscle (1.4 ± 0.6 and 1.9 ± 0.8 ml min−1 100 ml−1 muscle, respectively) but there were no significant differences between them. Forearm and calf blood flows (2.7 ± 0.3 and 3.0 ± 0.7 ml min−1 100 ml−1 limb tissue, respectively) were about 50% to more than 100% greater (P <0.025) than blood flow to the muscles within them (1.7 ± 0.5 and 1.4 ± 0.5ml min−1 100g−1 muscle, respectively, or 1.8 ± 0.6 and 1.5 ± 0.5 ml min−1 100 ml−1 muscle, respectively). In contrast, the blood flows to 100 g of forearm skin (9.1 ± 2.6 ml min−1 100 g−1) and adipose tissue (3.8 ± 1.1 ml min−1 100 g−1) were higher than the blood flow to 100 g of forearm (P <0.01 and not significant, respectively).

4. Although several possibilities can explain the discrepancy between muscle blood flow measured by 133Xe and blood flow to the distal limbs measured by plethysmography, the results suggest that non-muscular blood flow, especially that to skin, is substantially greater than muscular blood flow. Indeed, the overall blood flow to the forearm could be accounted for by summation of blood flows to individual constituent tissues, which were assumed to be present in proportions typical of lean subjects. The results have important implications in the use of arteriovenous catheterization studies for assessing flux of oxygen, carbon dioxide and metabolites across muscle.