bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II regulates the metabolism but not the secretion of vasoactive intestinal peptide in the rabbit
Authors: Davis R. E. , MacDonald G. J. , Duggan K. A.
Published: August 2015

1. We have previously demonstrated that the metabolism and secretion of vasoactive intestinal peptide are affected by both acute and chronic dietary sodium. Sodium concentrations in portal and systemic plasma were unaffected by differing levels of sodium intake or administration of an acute gastric sodium load. We sought, therefore, to determine whether other hormones involved in sodium homoeostasis (such as angiotensin II) might be involved in regulating the metabolism and secretion of vasoactive intestinal peptide. We determined the metabolic clearance rate and theoretical secretion rate of vasoactive intestinal peptide in rabbits on low sodium (high circulating angiotensin II) and high sodium (low circulating angiotensin II) diets with and without simultaneous angiotensin II infusion.

2. The metabolic clearance rate of vasoactive intestinal peptide was significantly higher in rabbits on the high sodium diet during both vehicle control (P<0.01) and angiotensin II (P<0.05) infusion. Angiotensin II infusion decreased the metabolism of vasoactive intestinal peptide in rabbits on both low (P<0.01) and high (P<0.01) sodium diets.

3. Although there was a significant difference in secretion rates between the two dietary groups (P<0.025) under basal conditions, infusion of angiotensin II did not alter the secretion rate significantly in either group.

4. We conclude that angiotensin II regulates the metabolism of vasoactive intestinal peptide in the rabbit, but does not regulate its secretion.
Whole-body and site-specific bone remodelling in patients with previous femoral fractures: relationships between reduced physical activity, reduced bone mass and increased bone resorption
Authors: Wand J. S. , Smith T. , Green J. R. , Hesp R. , Bradbeer J. N. , Reeve J.
Published: August 2015

1. A new tracer method is described for the noninvasive measurement of bone formation in the proximal femur. The method is based on our previously described whole-body method using 85Sr as the tracer (Reeve, J., Hesp, R. & Wootton, R. Calcif. Tissue Res. 1976; 22, 191–206). It allows correction to be made for long-term exchange processes within the skeleton.

2. The method has been applied in a study of regional and whole-body bone formation in 12 rehabilitated patients who had previously suffered a fracture of the proximal femur. Twelve healthy control subjects were studied, who were selected for their good health and continued physical activity. The aim was to explore the relationship between bone formation and physical activity.

3. Bone formation was similar in the two groups, both regionally and in the whole body. Based on analyses of four cadaver specimens, bone formation in the proximal femur was about one and two-thirds times that in the whole skeleton when related to mass of calcium in the region of interest.

4. Whole-body bone resorption, estimated from five measurements per subject of hydroxyproline excretion in relation to creatinine excretion, was significantly higher in the fracture patients (P<0.01, Wilcoxon's test).

5. Estimates of current physical activity (and immediate pre-fracture physical activity) were made with a newly devised questionnaire. Historical levels of physical activity (at ages 15–45 years) were determined with Astrom's questionnaire. No bone formation index correlated with any index of physical activity. Urinary hydroxyproline excretion correlated inversely both with current physical activity and historical physical activity (for both regression coefficients P<0.01).

6. The results are discussed in the light of our current understanding of the control of bone remodelling by the discrete basic multicellular units of bone. The opportunity to study regional bone resorption by the additional use of serial dual X-ray absorptiometry of the same region will in future allow the direct monitoring of the effects of therapeutic interventions which have been designed to prevent contralateral hip fracture.
Quantitative autoradiography reveals higher densities of specific calcitonin-gene-related peptide receptors in small intramyocardial compared with large epicardial coronary arteries
Authors: Sun Bing , Davenport Anthony P. , Brown Morris J.
Published: August 2015

1. Binding sites for calcitonin-gene-related peptide were localized and characterized in porcine coronary arteries using quantitative autoradiography, and the density of binding sites was compared between large epicardial and small intramyocardial coronary arteries.

2. A single class of binding sites for calcitonin-gene-related peptide with a dissociation constant of 2.1 ± 0.2 nmol/l was detected in both the large and small coronary arteries. The density of specific binding sites was higher (maximum binding site density 231 ± 14 fmol/mg of protein) in the small coronary arteries than in the large epicardial coronary arteries (maximum binding site density 108 ± 5 fmol/mg of protein). β-Human calcitonin-gene-related peptide showed higher affinity than α-human calcitonin-gene-related peptide for the binding sites. Most of the specific binding sites for both peptides in the large coronary artery were localized in the intima and media.

3. In coronary artery from patients with coronary heart disease, there were more binding sites for calcitonin-gene-related peptide in the smooth muscle layer of atheromatous segments (7.2 ± 0.7 amol/mm2) than in that of normal segments (3.0 ± 0.3 amol/mm2, P < 0.002).

4. The present findings lend further support to the theory of regional variation in the vasodilator response to calcitonin-gene-related peptide in porcine coronary arteries, which seems to be due to different densities of a single type of receptor for calcitonin-gene-related peptide.
Augmented portal flow in the isolated perfused cirrhotic rat liver: a haemodynamic and morphological study
Authors: Cardoso Jorge E. , Calmus Yvon , Legendre Claire , Cherruau Brigitte , Jeyaraj Prema Raj , Crougneau Simone , Habib Nagy , Houssin Didier
Published: August 2015

1. Isolated perfused cirrhotic rat livers were used to study the effects of an increase in portal perfusion pressure and portal flow on the microcirculation and viability of the hepatocytes. Cirrhosis was induced by CCl4, and Krebs-Ringer bicarbonate buffer solution was used as the perfusate. Portal perfusion pressures were increased incrementally between 25 and 45 cm H2O. The viability of the livers was assessed and histological studies were performed under light and electron microscopy.

2. An increase in portal perfusion pressure induced an increase in hepatic flow in all the experiments (P < 0.05). Hepatic flow was 2.52 ml min−1 g−1 of liver (SD 0.67; n = 5) at basal pressure compared with 4.19 ml min−1g−1 of liver (SD 0.93; n = 5) and 5.91 ml min−1g−1 of liver (SD 0.63; n = 5) when pressures were raised to 25 and 45 cm HzO, respectively. Portal perfusion pressure and hepatic flow were correlated (r = 0.908; P < 0.001; n = 30).

3. Production of the enzyme alanine aminotransferase (EC 2.6.1.2) increased significantly from 5.69 i.u. ml−1min g-l of liver (SD 3.62; n = 5) to 23.53 i.u. ml−1min g−1 of liver (SD 16.7; n = 5) when the perfusion pressure was raised from baseline to 30 cm H2O. In all the cases the porto-caval gradient of enzyme production was within the normal range. No correlation existed between the release of enzyme and portal perfusion pressures

4. Histological studies demonstrated sinusoidal dilatation in one case out of five in the control group compared with nine cases out of 25 in the high perfusion pressure groups. Dead sinusoidal cells coloured by Trypan Blue were observed in one case out of five in the control group compared with nine cases out of 25 in the high perfusion pressure groups. With electron microscopy, occasional lesions such as detachment of endothelial cells or blebs were found. No relationship existed between portal perfusion pressures and histological lesions.

5. This study shows that a brief increase in portal perfusion pressure in the isolated perfused cirrhotic rat liver induces an increase in hepatic flow without a change in the viability of the liver and without significant histological alterations.
Lack of effect of peripheral nervous blockade on nocturnal fluctuations in lower-leg subcutaneous blood flow in man
Authors: Sindrup J. H. , Petersen L. J. , Kastrup J. , Wroblewski H. , Kristensen J. K.
Published: August 2015

1. The local subcutaneous adipose tissue blood flow was measured simultaneously in the right and left lower legs of 10 normal human subjects under outpatient nocturnal conditions. The 133Xe-wash-out technique, portable CdTe(Cl) detectors and a portable data-storage unit were used for the measurement of blood flow.

2. The purpose of the study was to unveil the possible role of centrally controlled nerve fibres to the measurement area as mediators of a previously described nocturnal subcutaneous hyperaemia of 2 h duration. Therefore, before the sleeping period, a local nervous blockade was applied immediately proximal to the isotope depot on the right lower leg by the injection of approximately 15 ml of bupivacaine (5 mg/ml) subcutaneously.

3. Control experiments revealed blockade of the baroreceptor vasoconstrictor reflex activity 4 h after application of the local nervous blockade in three subjects examined.

4. Identical nocturnal isotope-wash-out curves were recorded from the two legs. Subcutaneous blood flow was found to increase significantly (P <0.0001) after approximately 1 h of sleep and the hyperaemia persisted for 2 h.

5. A significant positive correlation was detected between the latency periods from going to bed until the onset of the hyperaemia in the right and left lower legs (P <0.001, r = 0.95).

6. No significant difference could be detected between the relative blood flow increase during the hyperaemic phase in the right and left lower legs (P = 0.83).

7. It is concluded that the present data seem to rule out a central nervous factor(s) as the eliciting mechanism of the nocturnal subcutaneous hyperaemia. A circulating humoral factor(s) might be involved, although modification by local metabolic factors cannot be excluded. The possible physiological significance of the nocturnal hyperaemia is discussed.
Effect of Posture and Acute Glycaemic Control on the Excretion of Retinol-Binding Protein in Normoalbuminuric Insulin-Dependent Diabetic Patients
Authors: Catalano Carlo , Winocour Peter H. , Gillespie Susan , Gibb Ian , Alberti K. George M. M.
Published: August 2015

1. It has been suggested that tubular damage may precede gomerular damage at the onset of diabetic nephropathy. This may be reflected by increased urinary excretion of low-molecular-mass proteins, such as retinol-binding protein.

2. We have measured the urinary excretion rate of retinol-binding protein overnight, during orthostasis and during a hyperinsulinaemic euglycaemic clamp (blood glucose concentration 7.0 mmol/l) with stable diuresis in 34 normotensive, normoalbuminuric insulin-dependent diabetic patients and in 10 normal control subjects. Normal control subjects were not clamped. A further four normoalbuminuric insulin-dependent diabetic patients were rendered euglycaemic without a water load.

3. Overnight retinol-binding protein excretion rate was 58 (16-157) [median(range)] ng/min in patients with insulin-dependent diabetes and 32 (15-72) ng/min in control subjects (P < 0.01). The excretion rate did not change during orthostasis [patients with insulin-dependent diabetes, 67 (3-173) ng/min; control subjects, 23 (5-78) ng/min]. During the euglycaemic clamp retinol-binding protein excretion rate increased to 383 (78-4897) ng/min in patients with insulin-dependent diabetes (P < 0.01). An average increment in retinol-binding protein excretion rate of greater than 4000% was noted after acute euglycaemia in those patients with insulin-dependent diabetes who were not water-loaded.

4. In insulin-dependent diabetes, both overnight and orthostatic retinal-binding protein excretion was not correlated with fasting blood glucose concentration, HbA1, fructosamine or duration of diabetes. The absolute and incremental excretion rates of retinol-binding protein during the clamp were, however, correlated with both fasting blood glucose concentration and glucose excretion rate (rs = 0.41-0.48, P < 0.01).

5. The study demonstrates that retinol-binding protein excretion is increased in insulin-dependent diabetes in the absence of microalbuminuria and that this increase in retinol-binding protein excretion is particularly pronounced after acute euglycaemia. Acute tubular dysfunction related to acute changes in glucose control appears to be the most likely explanation, but established tubular damage could also be implicated. Postural variation in retinol-binding protein excretion was not detected.
Enzymuria in Non-Insulin-Dependent Diabetic Patients: Signs of Tubular Cell Dysfunction
Authors: Ikenaga Hideki , Suzuki Hiromichi , Ishii Naohito , Itoh Hajime , Saruta Takao
Published: August 2015

1. To evaluate tubular damage in diabetic patients, we measured the 24 h urinary excretion of five enzymes (N-acetyl-β-D-glucosaminidase, γ-glutamyl transpeptidase, dipeptidyl aminopeptidase IV, alanine aminopeptidase and alkaline phosphatase) that originate in renal proximal tubular cells.

2. Studies were performed on 118 non-insulin-dependent diabetic patients, 59 non-diabetic patients with chronic renal disease and 47 normal control subjects. First, the correlation between renal function, glycaemic control and urinary enzyme excretion was investigated. Secondly, the subjects were treated by controlled diet therapy to assess the effects of better glycaemic control on urinary enzyme excretion.

3. Regardless of a diabetic or non-diabetic cause of renal dysfunction, all of the five enzymes showed abnormal urinary excretion in patients with renal insufficiency (serum creatinine concentration < 2.0 mg/dl). In diabetic patients, however, an increase in N-acetyl-β-D-glucosaminidase excretion and a decrease in γ-glutamyl transpeptidase excretion were noted even in those who had no signs of renal dysfunction, including microalbuminuria. Moreover, the excretion of these two enzymes had a higher degree of correlation with glycaemic control and renal function than did that of the other three enzymes. Multiple regression analysis revealed that excretion of N-acetyl-β-D-glucosamindase is best correlated with urinary protein (r2 = 0.35), whereas excretion of γ-glutamyl transpeptidase is closely associated with glomerular filtration rate (r2 = 0.33).

4. In diabetic patients, diet therapy improved glycaemic control but had no effects on renal function, microalbumin excretion and β2-microglobulin excretion. In contrast, abnormal N-acetyl-β-D-glucos-aminidase and γ-glutamyl transpeptidase excretion were both significantly improved in diabetic patients without overt renal dysfunction. However, in non-diabetic patients and diabetic patients with renal insufficiency, there were no changes in urinary enzyme excretion.

5. These results suggest that there is reversible tubular damage in the early stages of diabetic nephropathy. Measurement of urinary excretion of N-acetyl-β-D-glucosaminidase and γ-glutamyl transpeptidase may be especially useful in the detection of this tubular dysfunction.
Derivation of Urinary Dopamine from Plasma Dihydroxyphenylalanine in Humans
Authors: Wolfovitz Efrat , Grossman Ehud , Folio Carol J. , Keiser Harry R. , Kopin Irwin J. , Goldstein David S.
Published: August 2015

1. Dihydroxyphenylalanine is the precursor of all endogenous catecholamines. In laboratory animals, renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounts for most of dopamine in urine. Dopamine is natriuretic, and in rats, dietary salt loading increases renal dihydroxyphenylalanine uptake by increasing the rate of entry (spillover) of dihydroxyphenylalanine into arterial plasma. In experimental animals and in humans, dietary salt loading increases urinary excretion of dihydroxyphenylalanine and dopamine. The present study examined in humans the extent to which circulating dihydroxyphenylalanine is the source of urinary dopamine and of the dopamine metabolite dihydroxyphenylacetic acid, and whether, as in animals, dietary salt loading affects dihydroxyphenylalanine spillover.

2. L-Dihydroxyphenylalanine (0.33 μg min−1 kg−1) was infused intravenously for 300 min after 7 days of a low-salt (mean 41 mmol/day) or a high-salt (mean 341 mmol/day) diet in 12 healthy subjects. Concentrations of dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid were measured in urine and in antecubital venous plasma. Infusion of L-dihydroxyphenylalanine produced a steady-state mean dihydroxyphenylalanine level about 10 times the endogenous level. About 30% of infused dihydroxyphenylalanine estimated to be delivered to the kidneys via the arterial plasma was excreted as dopamine, and about 30% was excreted as dihydroxyphenylacetic acid.

3. Dietary salt loading increased urinary excretion rates of dihydroxyphenylalanine [from 0.08 ± (SEM) 0.01 to 0.14 ± 0.03 nmol/min, t = 2.80, P <0.02] and dopamine (from 1.03 ± 0.19 to 1.30 ± 0.28 nmol/min, t = 2.35, P <0.05), whereas dihydroxyphenylalanine spillover appeared to be unchanged.

4. Renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounted for virtually all the urinary excretion of endogenous dopamine, but for only a minor portion of the excreted endogenous dihydroxyphenylacetic acid.

5. We conclude that in humans: (1) circulating dihydroxyphenylalanine is the main source of urinary dopamine but only a minor source of urinary dihydroxyphenylacetic acid; and (2) increased spillover of endogenous dihydroxyphenylalanine does not account for the increased excretion of these compounds during salt loading.
Simvastatin and Intracellular pH Regulation by the Na+/H+ Antiport of Sv40-Virus-Transformed Human Mrc5 Fibroblasts
Authors: Davies J. E. , Ng L. L.
Published: August 2015

1. Inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase by simvastatin leads to inhibition of both cell growth and Na+/H+ antiport activity. The effect of simvastatin on intracellular pH and Na+/H+ antiport activity was therefore studied on an adherent cell line, the SV40-virus-transformed MRC5 human fibroblast.

2. Simvastatin led to a dose-dependent decrease in intracellular pH, attributed to a reduction in Na+/H+ exchange, together with a rounding of cell shape. Mevalonate (1 mmol/l) prevented these effects of simvastatin, and when added after inhibition of the antiport by simvastatin, reversed these changes within 1–2 h.

3. The phenomenon of mevalonate reversal of anti-port inhibition by simvastatin was not sensitive to cycloheximide, indicating its post-translational nature. This was also consistent with the short period of incubation with mevalonate leading to reversal of antiport inhibition (1-2h). These changes in intracellular pH regulation were not due to alterations in cell cholesterol content.

4. A variety of inhibitors of post-translational processes, such as N-linked glycosylation (tunicamycin), phosphorylation (staurosporine), isoprenylation (farnesol, limonene), and of pertussis-toxin-sensitive G-proteins or calmodulin (W7), had no effect on the reversal by mevalonate of simvastatin-induced changes in Na+/H+ antiport activity.

5. N-Ethylmaleimide (50 μmol/l for 5 min) prevented mevalonate reversing the effects of simvastatin, suggesting the importance of thiol groups in the phenomenon of reversal of the inhibition of Na+/H+ antiport activity by simvastatin. Furthermore, concurrent incubation of simvastatin-treated cells with dithiothreitol (1 mmol/l) and N-ethylmaleimide restored the ability of mevalonate to reverse the inhibitory effects of simvastatin on Na+H+ antiport activity.
Effect of Tri-Iodothyronine Administration on Skeletal Muscle Intracellular Ph in the Rat
Authors: Thompson C. H. , Anderson Y. , Jagasia D. H. , Radda G. K. , Rajagopalan B.
Published: August 2015

1. Male Wistar rats were injected with tri-iodothyronine intraperitoneally for either 3 or 5 days.

2. Using 31P nuclear magnetic resonance spectroscopy, skeletal muscle intracellular bioenergetics of the leg were studied at rest and during sciatic nerve stimulation.

3. Tri-iodothyronine caused intracellular alkalinization of the cell, implying that administration of tri-iodothyronine induces an alteration in the set point for the sodium/proton antiport, the chief controller of intracellular pH.

4. During stimulation, there was less acidification of the skeletal muscle cell in the tri-iodothyronine-injected rats, implying either increased intrinsic buffering capacity of the muscle or increased proton efflux possibly due to increased activity of the sodium/proton antiport.

5. Effective proton efflux from the skeletal muscle cell may be sensitive to circulating levels of tri-iodothyronine.
Dose-Response Effects of Adrenergic and Cholinergic Stimulation on Atrial Natriuretic Peptide Secretion from Beating Isolated Guinea-Pig Atria
Authors: Speake P. F. , Pirie S. C. , Kibble J. D. , Muneer A. , Taylor D. , Birring S. , Green R.
Published: August 2015

1. The possible role of autonomic neurotransmitters in atrial natriuretic peptide secretion was investigated using spontaneously beating guinea-pig atria in vitro. Dose responses were determined for adrenaline, noradrenaline and acetylcholine and the selective α- and β-adrenoceptor agonists phenylephrine and isoprenaline, respectively. Adrenoceptor effects were further studied using the selective α- and β-adrenoceptor antagonists prazosin and propranolol, respectively, in conjunction with maximal adrenaline challenge. Results for rate and force of contraction and atrial natriuretic peptide secretion are expressed as a ratio (mean ± SEM) of a 15 min treatment period (stage 2) to a corresponding pretreatment period (stage 1).

2. Adrenaline and noradrenaline caused dose-dependent increases in the rate and force of contraction and in atrial natriuretic peptide secretion with a peak secretory response at 2 × 10−6 mol/l of 1.54 ± 0.08 (P <0.01) and 1.34 ± 0.08 (P <0.01) for adrenaline and noradrenaline, respectively. Acetylcholine decreased the rate and force of contraction, and ANP secretion was reduced to 0.47 ± 0.06 at 3 × 10−5 mol/l (P <0.01). Isoprenaline increased the rate and force of contraction and atrial natriuretic peptide secretion with a peak secretory response of 152 ± 0.22 at 2 × 10−6 mol/l (P <0.01). Phenylephrine increased the force but had no effect on the rate of contraction, and stimulated atrial natriuretic peptide secretion to 1.13 ± 0.09 at 2 × 10−5 mol/l (P <0.05). After both α- and β-adrenoceptor blockade, adrenaline was still able to significantly stimulate atrial natriuretic peptide secretion and positive inotropy. There was no chronotropic effect of adrenaline in the presence of propranolol. Simultaneous α- and β-adrenoceptor blockade inhibited all the effects of adrenaline.

3. A significant correlation was observed between the absolute change in rate of contraction and the absolute change in atrial natriuretic peptide secretion upon stimulation with each of the drugs (r = 0.63, P < 0.001). A similar relationship between developed tension and atrial natriuretic peptide secretion could not be demonstrated.

4. In conclusion, secretion of atrial natriuretic peptide from guinea-pig atria was stimulated by adrenergic and inhibited by cholinergic agonists. The adrenergic response was mediated by both α- and β-adrenoceptor stimulation. The observed changes in the rate of contraction showed a significant correlation with atrial natriuretic peptide secretion.
Mitogenic Events Induced by Vasopressin in Aortic Fibroblasts from Spontaneously Hypertensive Rats
Authors: Zhu Ding Liang , Herembert Thierry , Marche Pierre
Published: August 2015

1. To further explore the mechanisms of arterial growth, we investigated the signalling pathways through which arginine-vasopressin acts as a mitogen in cultured adventitial aortic fibroblasts of the spontaneously hypertensive rat, and we examined the mechanisms involved in the hyperresponsiveness to arginine-vasopressin of fibroblasts from spontaneously hypertensive rats compared with fibroblasts from Wistar-Kyoto rats.

2. Arginine-vasopressin-induced [3H]thymidine incorporation was used to determine the peptide mitogenicity. Arginine-vasopressin-triggered hydrolysis of phosphoinositides by phospholipase C was evaluated by measuring [3H]inositol phosphate formation. The role of protein kinase C and protein tyrosine kinases in arginine-vasopressin mitogenicity was assessed by stimulating the cells with arginine-vasopressin in the presence of 12-O-tetradecanoylphorbol 13-acetate and tyrphostin (a tyrosine kinase inhibitor), respectively.

3. Arginine-vasopressin-induced DNA synthesis was completely abolished in confluent cells, whereas [3H]inositol phosphate formation was only reduced. The presence of 12-O-tetradecanoylphorbol 13-acetate markedly decreased arginine-vasopressin-induced [3H]thymidine incorporation in fibroblasts from spontaneously hypertensive rats and was without effect in fibroblasts from Wistar-Kyoto rats. Tyrphostin abolished arginine-vasopressin-induced [3H]thymidine incorporation in a dose-dependent manner and did not affect the formation of inositol phosphates.

4. These results indicate that phospholipase C activation is not sufficient for arginine-vasopressin-induced mitogenesis. They also suggest that (i) tyrosine kinase activation is a necessary step in the transduction of the arginine-vasopressin mitogenic signal, and (ii) protein kinase C participates in the increased mitogenic potency of arginine-vasopressin in spontaneously hypertensive rats.
Venous Blood Arterialization and Parameters from the Minimal Models of Glucose Disappearance and Post-Hepatic Insulin Delivery
Authors: Godsland I. F. , Felton C. , Wynn V.
Published: August 2015

1. Modelling analysis of intravenous glucose tolerance test glucose and insulin concentrations can provide measures of insulin sensitivity and metabolism from a single straightforward procedure. However, little is known of the effects of blood arterialization on model-derived parameters.

2. Intravenous glucose tolerance tests were carried out on 18 subjects, with measurement of glucose and insulin concentrations in simultaneously sampled non-arterialized and arterialized blood. Blood oxygen saturation, partial pressure of CO2 and pH were measured on both non-arterialized and arterialized blood during the intravenous glucose tolerance test. Using the minimal models of glucose disappearance and post-hepatic insulin delivery, measures of insulin sensitivity, glucose-dependent glucose disposal, firstand second-phase post-hepatic insulin responsiveness to glucose and plasma insulin elimination rate were derived from intravenous glucose tolerance test glucose and insulin concentrations in both arterialized and non-arterialized blood.

3. During the intravenous glucose tolerance test mean blood oxygen saturation was 6.7% higher, partial pressure of CO2 was 0.3 kPa lower and pH was 0.015 higher in arterialized than non-arterialized blood. Mean parameter values did not differ when derived from measurements made on non-arterialized and arterialized blood. Model-derived parameters were not related to the degree of arterialization, although there was some consistent variation with sampling site for parameters of glucose-dependent glucose disposal (Sg), first-phase post-hepatic insulin responsiveness (φ1) and insulin elimination (ni).

4. Measurements made on non-arterialized blood are suitable for analyses employing the minimal models of glucose disappearance and post-hepatic insulin delivery. Imprecision in some parameters may be diminished by adherence to a single sampling site.
Atrial Natriuretic Peptide in the Pericardial Fluid of Patients with Heart Disease
Authors: Amano Jun , Suzuki Akio , Sunamori Makoto , Shichiri Masayoshi , Marumo Fumiaki
Published: August 2015

1. The pericardial fluid of 20 open heart surgery patients with acquired heart disease was analysed for atrial natriuretic peptide by radioimmunoassay.

2. The concentration of atrial natriuretic peptide in the pericardial fluid was significantly higher than in the corresponding plasma (316.8 ±50.0 versus 121.7 ± 29.1 pg/ml; P <0.01) and was higher in patients with congestive heart failure than in those without heart failure (469.3 ±78.6 versus 181.8 ± 26.7 pg/ml; P <0.001). Pericardial and plasma atrial natriuretic peptide concentrations showed a significant positive correlation. Pericardial fluid and plasma samples were fractionated using both reverse-phase high-performance liquid chromatography and gel permeation chromatography. Each fraction was assayed for atrial natriuretic peptide by radioimmunoassay, revealing the presence of β-atrial natriuretic peptide as well as α- and γ-atrial natriuretic peptide.

3. The pericardial fluid concentration of cyclic GMP, the intracellular second messenger for atrial natriuretic peptide, was significantly higher in patients with congestive heart failure than in patients without heart failure.
Modulation of the Anabolic Effect of Synthetic Human Parathyroid Hormone Fragment-(1-34) in the Bone of Growing Rats by Variations in the Dosage Regimen
Authors: Riond Jean-Luc
Published: August 2015

1. The influence of the time of the day of the administration of synthetic human parathyroid hormone fragment-(1-34) [hPTH-(1-34)] on its anabolic effect in bone was investigated in 23 60-day-old female Wistar rats. Rats were randomly assigned to the groups vehicle control morning, hPTH-(1-34)-treated morning, vehicle control afternoon and hPTH-(1-34)-treated afternoon, and once daily received a subcutaneous injection of 8 μg of hPTH-(1-34)/100 g body weight for 11 days. The increase in net intestinal calcium absorption and the increase in calcium balance were not influenced by the time of day of hPTH-(1-34) treatment. Four days after cessation of treatment, the net intestinal calcium absorption and calcium balance in hPTH-(1-34)-treated rats were not different from those of the control rats.

2. Modulation of the anabolic effect by variation of the hPTH-(1-34) dosage regimen was investigated in 43 60-day-old female Wistar rats. Rats were randomly assigned to the groups vehicle control, environmental control, 8 μg of hPTH-(1-34)/100 g body weight every 3 days for 24 days, 8 μg of hPTH-(1-34)/100g body weight every 2 days for 16 days, 8 μg of hPTH-(1-34)/100 g body weight every day for 8 days, 4 μg of hPTH-(1-34)/100 g body weight twice a day for 8 days and 2.7 μg of hPTH-(1-34)/100 g body weight three times a day for 8 days. In all cases, the total dose of hPTH-(1-34) received was 64 μg/100g body weight. Net intestinal calcium absorption and calcium balance increased significantly in the groups that received hPTH-(1-34) once a day, twice a day and three times a day. In relation with increased frequency of dosing, a significant linear trend existed for the increase in net intestinal calcium absorption and calcium balance. The hPTH-(1-34)-induced increase in total tibia calcium, total vertebrae calcium, tibia dry weight and vertebrae dry weight also tended to be more pronounced with more frequent dosing, although the trend was not significant.

3. Thus, smaller intervals between doses of hPTH-(1-34) enhance the anabolic response in bone despite the smaller doses. This effect may be secondary to 1,25-dihydroxyvitamin D3-induced increased intestinal calcium absorption, decreased 1,25-dihydroxyvitamin D3-induced bone resorption, up-regularion of osteoblast receptors for parathyroid hormone, or a combination of these three factors.
A Possible Role for Protein Kinase C in the Regulatory Differences between Intra-Abdominal and Subcutaneous Human Adipose Tissue
Authors: Vikman Hanna-Leena , Kaartinen Johanna M. , Tuominen Raimo K. , Ohisalo Jorma J.
Published: August 2015

1. The adenosine A1-receptor agonist N6-(phenylisopropyl)adenosine inhibited lioplysis in a dose-dependent manner in human adipocytes. The effect is mediated by the inhibitory guanine-nucleotide-binding protein(s) that can be phosphory-lated and thereby inactivated by protein kinase C.

2. Stimulation of protein kinase C by 12-O-tetradecanoyl-phorbol-13-acetate attenuated the inhibitory effect of the adenosine agonist.

3. Omental fat cells are less sensitive to adenosine than subcutaneous cells, although the stimulatory arm of cyclase regulation appears normal. Protein kinase C activity was measured in the soluble and particulate fractions of human omental and subcutaneous adipose tissue. Omental adipose tissue had a twofold higher membrane-bound and a threefold higher soluble protein kinase C activity.

4. It is therefore possible that the differences in regulation between the two sites are caused by different C kinase activities, causing variable phosphorylation of the inhibitory guanine-nucleotide-binding protein(s).
Responses of Tissue Protein Synthesis to Nutrient Intake in Rats Exposed to Interleukin-1β Or Turpentine
Authors: Ballmer Peter E. , McNurlan Margaret A. , Grant Ian , Garlick Peter J.
Published: August 2015

1. The influence of an acute-phase reaction on the ability of protein synthesis rates in liver and three different muscles (gastrocnemius, soleus and heart) to respond to a short intravenous infusion of nutrients (glucose plus amino acids) was investigated during experimental inflammation induced by injection of human recombinant interleukin-1β or turpentine in young male rats.

2. Interleukin-1β induced a consistent increase of 3°C in body temperature between 3 and 5 h after injection, whereas turpentine induced a delayed fever, peaking by 13 h.

3. Interleukin-1β and turpentine stimulated fractional rates of protein synthesis in liver. The synthesis rate was inhibited by interleukin-1β in gastrocnemius and soleus muscle, but an elevation was seen in heart muscle. In this study there was no significant response of muscle to turpentine injection.

4. Two hours of parenteral nutrition increased fractional synthesis rates in all tissues when compared with Ringer's lactate. Somewhat larger responses to feeding were observed as a result of either interleukin-1β or turpentine injection in all tissues, but these improvements were not significant.

5. We conclude that the response of protein synthesis rates in liver and skeletal muscle to parenteral nutrition is not inhibited, and may be somewhat enhanced, during acute inflammatory conditions in the growing rat.
Effects of Acid Loading on Serum Amino Acid Profiles and Muscle Composition in Normal Fed Rats
Authors: Cupisti A. , Baker F. , Brown J. , Lock C. , Bevington A. , Harris K. P. G. , Walls J.
Published: August 2015

1. Impaired body growth, loss of lean body mass and negative nitrogen balance are common findings in chronic renal failure. Enhanced endogenous protein catabolism in skeletal muscle induced by co-existent metabolic acidosis seems to be an important aetio-logical factor.

2. In uraemic patients abnormalities in blood amino acid profiles are present after a protein meal, suggesting impaired metabolism of ingested proteins.

3. This study demonstrates that acidosis induces changes in arterial amino acid profiles in fed non-uraemk rats. These included increased levels of threonine, histidine, proline, serine and glycine, and decreased levels of tryptophan. These changes are similar to those found in uraemic patients after a protein meal, suggesting a pathogenic role of acidosis in the impairment of exogenous protein metabolism.

4. Intracellular amino acid levels in the muscle tissue partly reflect the changes in the extracellular level.

5. Acidotic animals had a decreased body weight gain and a reduced alkali-soluble protein/DNA ratio in muscle cells compared with controls.

6. In conclusion, the results show that acidosis per se modifies the circulating amino acid profile in fed rats, resulting in a pattern similar to the post-prandial amino acid changes described in uraemic patients. These abnormalities occur together with impaired growth of skeletal muscle cells.
Changes in Renal Function in Acute Experimental Pancreatitis in Rats: A Therapeutic Role for Somatostatin
Authors: González-Rubio M. , García-Escribano C. , Díez-Marqués M. L. , Arribas I. , Martínez-Onsurbe P. , Rodríguez-Puyol M. , Rodríguez-Puyol D.
Published: August 2015

1. The present study was designed to determine the changes in renal function in two models of experimental pancreatitis in rats, in an attempt to assess the possible pathogenic role of reactive oxygen species and to elucidate a possible therapeutic role for somatostatin.

2. Mild pancreatitis was induced by low blockade of the biliary duct and severe pancreatitis was evoked by retrograde infusion of bile salts. Renal function was studied by clearance techniques in rats with pancreatitis, treated or not treated with somatostatin. Plasma and glomerular malonyldialdehyde levels were measured by the thiobarbituric acid method.

3. Renal function did not change in rats with low blockade of the biliary duct, but animals receiving a retrograde infusion of bile salts showed a significant decrease in glomerular filtration rate and renal plasma flow with respect to sham-operated animals.

4. Plasma malonyldialdehyde levels increased significantly in rats treated with bile salts with respect to control animals, whereas no changes were detected in glomerular malonyldialdehyde levels. Thus, the renal dysfunction does not seem to be related to an increased production of reactive oxygen metabolites at the glomerular level.

5. Somatostatin infusion significantly improved renal function in rats with severe pancreatitis (retrograde infusion of bile salts) by increasing glomerular filtration rate, renal plasma flow and filtration fraction. These results support a possible therapeutic role for somatostatin in the renal dysfunction associated with the severe forms of pancreatitis.
Brisk Walking and Serum Lipoprotein Variables in Formerly Sedentary Men Aged 42–59 Years
Authors: Stensel D. J. , Hardman A. E. , Brooke-Wavell K. , Vallance D. , Jones P. R. M. , Norgan N. G. , Winder A. F.
Published: August 2015

1. The purpose of this study was to examine the influence of brisk walking on serum lipoprotein variables.

2. Seventy-two apparently healthy but physically inactive men (aged 42–59 years) were recruited. These men were normotensive non-smokers without a history of dyslipidaemia. Subjects were randomly allocated on a 2 to 1 basis into either a walking group (n = 48) or a control group (n = 24). Walkers followed a self-monitored programme of brisk walking for 1 year, whereas control subjects maintained their habitual lifestyle.

3. Treadmill walking tests were conducted to examine changes in fitness. Concentrations of serum lipids and lipoproteins were determined in fasting subjects. The amount of body fat was measured by body density. Circumferences at the waist and hip and skinfold thicknesses were used to determine the distribution of body fat. Dietary intakes were assessed by weighed food inventories.

4. Seven subjects (six walkers and one control subject) dropped out during the study. Walkers did an average of 28 (SEM 1.4; n = 42) min of brisk walking/day. This improved endurance fitness but did not influence serum concentrations of total cholesterol, high-density lipoprotein cholesterol, triacylglycerol, apolipoprotein A-1, apolipoprotein B or lipoprotein (a). Neither body mass nor the amount of body fat changed, relative to control subjects.

5. These data suggest that brisk walking does not modify lipoprotein metabolism in normolipidaemic middle-aged men.
Effects of Haemodialysis and Continuous Ambulatory Peritoneal Dialysis on Abnormalities of Ion Transport in vivo in Patients with Chronic Renal Failure
Authors: Brearley Christopher J. , Aronson Jeffrey K. , Boon Nicholas A. , Raine Anthony E. G.
Published: August 2015

1. We have studied Na+/K+ pump activity in vivo in three groups of subjects: patients with chronic renal failure not receiving maintenance dialysis, patients being treated by either haemodialysis or continuous ambulatory peritoneal dialysis, and matched control subjects.

2. To do this we have measured the changes in plasma and intraerythrocytic rubidium concentrations after an oral load of rubidium chloride, having previously shown that changes in the disposition of rubidium measured in this way reflect changes in the activity of the Na+/K+ pump in vivo.

3. Erythrocyte rubidium uptake was significantly reduced both in ten patients with chronic renal failure not receiving maintenance dialysis and in 12 patients being treated by haemodialysis, when compared with 31 healthy control subjects. In contrast, erythrocyte rubidium uptake was not altered in 13 patients treated by continuous ambulatory peritoneal dialysis. There was also a significantly reduced rate constant for erythrocyte rubidium uptake in patients with undialysed chronic renal failure (0.66 h−1) and in those treated by haemodialysis (0.78 h−1), whereas in patients treated by continuous ambulatory peritoneal dialysis the rate constant for erythrocyte rubidium uptake was not significantly different from control values (1.36h−1 and 1.41 h−1, respectively).

4. These findings are consistent with a reversal of the inhibition of erythrocyte Na+/K+ pump activity in vivo found in chronic renal failure by continuous ambulatory peritoneal dialysis, but not by haemodialysis. This difference may be due to the failure of haemodialysis to clear a circulating inhibitor of Na+, K+-ATPase or to the rapid re-accumulation of such an inhibitor after haemodialysis. Alternatively, it could be due to a dialysable inhibitor of potassium efflux, with a secondary reduction in the activity of the Na+/K+ pump.

5. Neither continuous ambulatory peritoneal dialysis nor haemodialysis reversed the abnormal disposition of rubidium in the plasma found in undialysed patients. This suggests that the putative inhibitor which accumulates in chronic renal failure does not affect cation transport in all tissues of the body, and that abnormalities of cation transport in chronic renal failure may be due to more than one mechanism.
Glucose Turnover in Pregnant Women with Acute Malaria
Authors: Davis T. M. E. , Suputtamongkol Y. , Spencer J. L. , Wilson S. G. , Mekhton S. , Croft K. D. , White N. J.
Published: August 2015

1. Hypoglycaemia is a serious complication of falciparum malaria, especially in pregnant patients. To investigate malaria-associated changes in glucose metabolism in pregnancy, steady-state [6,6-2H2] glucose turnover and clearance were measured in 10 women (eight with uncomplicated falciparum malaria and two with vivax malaria at 16–30 weeks gestation) before treatment, after intravenous quinine infusion (patients with falciparum malaria) and in convalescence.

2. Admission basal plasma glucose concentrations were higher than those in convalescence [median (range); 4.8 (3.6-7.0) versus 4.0 (3.6-4.6) mmol/l, P = 0.02], and there was a significant fall during initial quinine treatment in patients with falciparum malaria [5.0 (4.3-7.6) to 3.6 (3.2-5.4) mmol/l, P <0.01]. Basal plasma insulin levels were comparable at presentation and follow-up (P = 0.35) and rose an average of only 2 m-units/l during quinine infusion (P <0.05). Pretreatment glucose turnover rates [3.37 (2.57-4.16) mgmin−1 kg−1] were comparable with those found in a previously reported study of non-pregnant severely ill patients [3.22 (2.12-4.82) mg min−1 kg−1, n = 11] and correlated significantly with the admission parasitaemia (P <0.025). In the eight patients with falciparum malaria, there was a significant fall in turnover during intravenous quinine infusion [3.42 (238-4.16) to 2.66 [1.94-3.94) mgmin−1 kg−1] whereas clearance did not change significantly. In convalescence, turnover values showed a wide scatter, although the highest values (3.34-4.33 mgmin−1 kg−1) were in patients studied within 4 days of presentation (two patients) or with pre-eclampsia (one patient); values for glucose clearance were consistently higher than those at presentation (P = 0.004).

3. Given the simultaneous plasma glucose and insulin concentrations, these results suggest that the combination of pregnancy and severe malaria may result in greater initial glucose requirements than in severely ill but non-pregnant patients, that there is a largely insulin-independent reduction in glucose production and utilization during quinine therapy which may partly reflect attenuated parasite glycolysis, and that early convalescence in pregnant women may be associated with higher glucose utilization than that in non-pregnant patients.
Contractile Dysfunction in the Diabetic-Rat Heart is An Intrinsic Abnormality of the Cardiac Myocyte
Authors: Okayama Hideki , Hamada Mareomi , Hiwada Kunio
Published: August 2015

1. In order to clarify whether the myocardial dysfunction observed in diabetic-rat hearts is an intrinsic property of the myocytes or not, we investigated cardiac function and myocyte contractile function in diabetic rats 5 weeks after the injection of streptozotocin.

2. Maximal and minimal dP/dt and time constant of isovolumic pressure fall were measured using a micromanometer in diabetic and age-matched control rats.

3. Isolated myocytes were enzymically obtained from each rat heart and were stimulated at 1 Hz (37°C) in a buffer containing 1.5 mmol/l Ca2+. The images of myocyte contractions were recorded by a video system. Normalized maximal velocity of shortening (maximal velocity of cell shortening/resting cell length; s−1), normalized maximal velocity of relengthening (maximal velocity of cell relengthening/resting cell length; s−1) and extent of shortening [(twitch amplitude/resting cell length) × 100;%] were analysed by a digitalized computer as contractile functions of the myocyte.

4. The maximal and minimal dP/dt in diabetic rats (7876, 5341 mmHg/s) were significantly lower than those in control rats (9349, 7876 mmHg/s). The time constant of isovolumic pressure fall in diabetic rats (12.7 ms) was significantly greater than that in control rats (8.6 ms). Moreover, the normalized maximal velocity of shortening, normalized maximal velocity of relengthening and extent of shortening in myocytes from diabetic rats (1.40 s−1, 1.38 s−1, 9.5%) were significantly lower than those in myocytes from control rats (1.64 s−1, 1.60 s−1, 11.8%).

5. These results suggest that contractile impairment in this diabetic-rat heart model is mainly due to an intrinsic abnormality of the cardiac myocytes.