bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Ingested Steak and Infused Leucine on Forelimb Metabolism in Man and the Fate of the Carbon Skeletons and Amino Groups of Branched-Chain Amino Acids
Authors: Elia Marinos , Livesey Geoffrey
Published: August 2015

1. The effects of ingested grilled beef steak (250 g raw weight of lean meat) and infusion of leucine (3.8 g) on human forelimb metabolism were studied by monitoring the concentrations of various metabolites in arterial (A) and venous (V) blood of four overnight fasted and rested men.

2. The mean basal A—V for branched-chain 2-oxo acid (BCOA) was small (−3.6 μmol/l). After ingestion of steak or administration of leucine there were large positive increases in the A—V for branched-chain amino acid (BCAA) but increase in the negative A—V for BCOA was relatively small.

3. Within 2 h of ingestion of steak, BCAA accounted for approx. 50% of those amino acids with a positive A—V and glutamine for up to 75% of those with a negative A—V; the negative A—V for alanine decreased to 10% of its basal value. Infusion of leucine produced a large positive A—V for leucine by forelimb, a doubling in the negative A—V for glutamine and a rise in the blood glutamine concentration; the negative A—V for alanine was virtually unchanged and the blood alanine concentration showed a late significant decrease.

4. After ingestion of steak there was a two- to three-fold rise in the arterial insulin concentration, little change in the positive A—V for glucose and a decreased negative A—V for ‘glycolytic products’ (alanine + lactate + pyruvate), suggesting increased utilization of glucose carbon. Infusion of leucine doubled the arterial insulin concentration; the A—V for glucose decreased, that for lactate, pyruvate and alanine remained unchanged, suggesting decreased utilization of glucose carbon.

5. Circulating BCOA was distributed almost entirely in the plasma space.

6. in a variety of clinical conditions (insulin-dependent diabetes, cirrhosis, muscular dystrophy and starvation), the basal plasma concentrations of BCOA correlated well with those of BCAA (r = 0.989). Infusion of leucine increased the plasma BCAA/BCOA ratio to the same extent (about 40%) in each clinical condition despite considerable variations in the rate of leucine clearance.

7. The observations indicate that both ingested steak and infused leucine produce important changes in the selection of respiratory fuels by the human forelimb, that BCOA is preferentially oxidized rather than released from human limb tissues, and that glutamine, not alanine, is the major amino group carrier leaving the forelimb both after a protein meal and after leucine administration. Changes in cellular uptake or transamination of leucine appear not to be responsible for the varied rates of leucine clearance in a variety of clinical conditions.
Aminophylline and Fatigue of Adductor Pollicis in Man
Authors: Wiles C. M. , Moxham J. , Newham D. , Edwards R. H. T.
Published: August 2015

1. The effect of intravenous aminophylline on the contractility of adductor pollicis has been studied in three subjects both in the fresh state and following the induction of muscle fatigue.

2. Aminophylline had no influence on the frequency—force relationship and relaxation rate of adductor pollicis in the fresh state.

3. Fatigue resulted in a selective depression of the force response to low and moderate frequencies of stimulation and a slight effect on maximum force production 10 and 35 min afterwards.

4. Aminophylline given prior to, during and/or after fatigue did not influence this selective low-frequency fatigue at 10 or 35 min.

5. Aminophylline at the concentrations obtained has no significant effect on muscle contractility or fatiguability in man.
Urinary Prostaglandin E2 and Kallikrein Excretion in Glucocrticoid Hypertension in Rats
Authors: Handa Michiko , Kondo Kazuoki , Suzuki Hiromichi , Saruta Takao
Published: August 2015

1. Oral administration of dexamethasone (about 2.5 × 10-7 mol/day) caused hypertension in rats. The blood pressure rose from 108 ± 6 (mean ± sd) to 156 ± 17 mmHg on the seventh day. The urine volume and urinary excretion of sodium were increased. The plasma renin activity and plasma aldosterone were unchanged. However, the urinary excretions of prostaglandin E2 (UPGE2V) and kallikrein (Ukall.V) were markedly decreased throughout the experiment.

2. With concurrent administration of captopril, the elevation of blood pressure was partially prevented. in this group of rats, the plasma renin activity was elevated and the reductions in UPGE2V and Ukall.V were partially prevented.

3. Based on these results, it is suggested that suppression of the kallikrein—kinin and prostaglandin systems, in addition to involvement of the renin-angiotensin system, is one of the factors contributing to the hypertensive action of dexamethasone.
Abnormalities of Calcium Metabolism in Essential Hypertension
Authors: Strazzullo P. , Nunziata V. , Cirillo M. , Giannattasio R. , Ferrara L. A. , Mattioli P. L. , Mancini M.
Published: August 2015

1. Calcium metabolism has been investigated in patients with essential hypertension and normal renal function to evaluate the renal calcium handling and the reported increase in renal calcium loss.

2. In 55 hypertensive and 55 sex- and age-matched healthy normotensive subjects creatinine clearance, serum total and ionized calcium, plasma parathyroid hormone and 24 h urinary excretion of calcium, sodium and cAMP were measured. In a subgroup of 20 hypertensive patients and 20 controls the fasting calcium excretion rate was also measured.

3. Both 24 h and fasting calcium excretion rates were higher in the hypertensive group; so also were plasma parathyroid hormone and urinary cAMP. Serum total and ionized calcium levels were not different in the two groups.

4. After intravenous calcium infusion (15 mg 3 h−1 kg−1) in seven hypertensive patients and controls, the hypertensive patients excreted more calcium at all serum calcium concentrations.

5. These results support the hypothesis of primary renal calcium leak in essential hypertension. Enhanced urinary calcium excretion rate may cause compensatory parathyroid overactivity.
The Effects of Cardioselective and Non-Selective β-Adrenoceptor Blockade on the Hypokalaemic and Cardiovascular Responses to Adrenomedullary Hormones in Man
Authors: Struthers A. D. , Reid J. L. , Whitesmith R. , Rodger J. C.
Published: August 2015

1. Adrenaline was infused intravenously in nine normal volunteers to plasma concentrations similar to those found after myocardial infarction. This study was undertaken on three occasions after 5 days' treatment with placebo or the β-adrenoceptor antagonists, atenolol or timolol.

2. Adrenaline increased the systolic pressure by 11 mmHg, decreased the diastolic pressure by 14 mmHg, and increased the heart rate by 7 beats/min. These changes were prevented by atenolol. However, after timolol the diastolic pressure rose (+19 mmHg) and heart rate fell (− 8 beats/min).

3. Adrenaline caused the corrected QT interval (QTc) to lengthen (0.36 ± 0.02 s to 0.41 ± 0.06 s). No significant changes were found in the QTc when subjects were pretreated with atenolol or timolol.

4. The serum potassium fell from 4.06 to 3.22 mmol/l after adrenaline. Serum potassium fell to a lesser extent to 3.67 mmol/l after atenolol and actually increased to 4.25 mmol/l after timolol. Adrenaline-mediated hypokalaemia appears to result from the stimulation of a β2-adrenoceptor linked to membrane Na+/K+-ATPase causing potassium influx.
Effects of Indomethacin on the Guinea-Pig Pulmonary Response to Intravenous Leukotrienes C4 and D4
Authors: Leitch A. G. , Austen K. F. , Corey E. J. , Drazen J. M.
Published: August 2015

1. We measured pulmonary conductance (GL), dynamic compliance (Cdyn.), and arterial pressure in chloralose-urethane anaesthetized guinea pigs for 30 min after intravenous infusion of either leukotriene (LT) C4 (1 μg/kg) or LTD4(0.5 μg/kg) to control or indomethacin-pretreated (30 mg/kg) animals.

2. LT infusion to control animals caused decrements in GL, which were maximal at 30 s and persisted for 7.5 min (LTD4) and 15 min (LTC4), decrements in Cdyn., which were maximal at 30 s and persisted for 30 min, and hypotension.

3. Indomethacin treatment before LT infusion significantly altered the changes in GL by reducing the early (< 1 min) response and potentiating the later (3-5 min) response, significantly reduced the fall in Cdyn. at all time points, resulting in a change in the GL/Cdyn. ratio to 1.0 and prolonged the hypotensive response.

4. We conclude that cyclo-oxygenase products are responsible for the early (< 1 min) pulmonary response to LT infusion and modulate the later (3-5 min) response but do not cause hypotension. With cyclo-oxygenase inhibition, the significant. primary activity of LT is possibly less preferentially directed to contractile tissues associated with small airways.
Thermic Response to Isoenergetic Protein, Carbohydrate or Fat Meals in Lean and Obese Subjects
Authors: Nair K. S. , Halliday D. , Garrow J. S.
Published: August 2015

1. The thermic response of five lean and five obese subjects was measured by indirect calorimetry before, and for 157.5 min after a meal of protein, carbohydrate or fat, each of which provided 1.25 MJ. The change in plasma glucose, insulin and (in the case of the carbohydrate meal) the rate of exogenous glucose oxidation was also measured.

2. There was no significant difference between the lean and obese groups in the magnitude of the thermic response to any of the three meals. In both weight groups the response was largest and most prolonged after the protein meal (P < 0.01).

3. The obese group showed a higher concentration of fasting plasma insulin (P < 0.01) and a larger increase in plasma glucose (P < 0.05) after the carbohydrate meal, but there was no significant difference in the oxidation of exogenous glucose when compared with the lean group.

4. Previous studies on dietary-induced thermogenesis in lean and obese subjects have given conflicting results. In general reports of decreased thermogenesis in obese subjects are characterized by either (a) high pre-meal metabolic rates in the obese group, especially in diabetic subjects, or (b) a group classified as ‘normal’ who have been selected for their high thermogenic capacity.
Peritubular Capillaries of the Renal Cortex in Experimental Diabetes Mellitus in the Rat
Authors: Pinter G. G. , Stork John E. , Wilson P. David , Fajer Abram B.
Published: August 2015

1. Microangiopathy affects the peritubular capillaries in experimental diabetes. Five to six months after streptozotocin administration to induce experimental diabetes in rats, a progressive increase of lymph flow and of the entry of albumin from the renal peritubular capillaries into the interstitium was seen.

2. Under these conditions, owing to the alteration of peritubular physical forces, the uptake of tubular reabsorbate into the capillaries can be impaired with potentially severe consequences in diabetic nephropathy.
Effect of Dietary Protein Restriction on the Development of Renal Failure after Subtotal Nephrectomy in Rats
Authors: El-Nahas A. M. , Paraskevakou H. , Zoob S. , Rees A. J. , Evans D. J.
Published: August 2015

1. We have examined the effect of a low protein diet on the development of glomerular sclerosis and progressive renal failure after subtotal nephrectomies in rats.

2. Two groups of male Sprague-Dawley rats were studied after five-sixths nephrectomy; group 1 were maintained on a normal diet (13.5 g day−1 kg−1 body weight) and group 2 were fed with a low protein diet (6 g day−1 kg−1 body weight).

3. Rats maintained on a low protein diet survived for longer, and had significantly less glomerular sclerosis and significantly greater glomerular filtration rates when the experiment ended after 7 months.

4. We conclude that dietary protein influences favourably the development of glomerular scarring and renal failure after subtotal nephrectomy in rats.
The Effect of Vitamin D and Its Metabolites on Fracture Repair in Chicks
Authors: Dekel S. , Salama R. , Edelstein S.
Published: August 2015

1. One-day-old chicks were depleted of vitamin D. At 3 weeks their right tibiae, and those of a control group given vitamin D3, were fractured and pinned. After fracture the controls were kept on vitamin D3. Another group was left vitamin D-deficient. The remaining depleted chicks, divided into four groups, were given vitamin D3, 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or a combination of 24,25(OH)2D3 and 1,25(OH)2D3.

2. The callus obtained after 9 and 14 days was subjected to torsional stress. The callus of chicks given vitamin D continuously showed the greatest resistance, whereas that of vitamin D-deficient chicks showed the smallest resistance. Repletion with either vitamin D3 or its metabolites increased the strength of the callus. Repletion with the combination of 24,25(OH)2D3 and 1,25(OH)2D3 produced the most marked results, in that the callus was even stronger than that of chicks replete with vitamin D3.

3. It is concluded that 24,25(OH)2D3 is essential for bone formation in addition to the known active vitamin D metabolite 1,25(OH)2D3, and the possible clinical implications of these findings are discussed.
Is Dopamine a Physiological Natriuretic Hormone in the Dog?
Authors: Cuche J. L. , Selz F. , Ruget G. , Jondeau G. , Guedon J.
Published: August 2015

1. Both plasma and urinary dopamine and noradrenaline were measured as free and sulphate conjugates, by a radioenzymatic method, before and during extracellular volume expansion (ECVE) with hypo-, iso- or hyper-tonic fluid (usually sodium chloride solution) in dogs.

2. During ECVE there was a decrease in plasma catecholamine concentration. For all cases except noradrenaline, this is probably due to a dilution phenomenon since when results were expressed as pg/mg of protein, ECVE had no effect. This change in noradrenaline accounted for the increase in the dopamine/noradrenaline ratio.

3. As expected, there was an increase in the urinary excretion of dopamine during ECVE with both iso- and hyper-tonic fluid. This increase was not observed in the group of dogs given hypotonic fluid, although the increase of fractional excretion of sodium was of a similar order of magnitude.

4. The increase in the urinary excretion of dopamine was apparently not affected by an increase in plasma sodium concentration and/or osmolality.

5. The demonstrated dissociation between sodium and dopamine in urine does not support a physiological role for dopamine in renal handling of sodium during ECVE, and raises the question of its specificity.
General and Regional Haemodynamic Effects of Intravenous Ergotamine in Man
Authors: Tfelt-Hansen P. , Kanstrup I.-L. , Christensen N. J. , Winkler K.
Published: August 2015

1. The effect of intravenous ergotamine on general (blood pressure and cardiac output) and regional (splanchnic, renal and muscular) haemodynamics was studied immediately and 3 h after administration in seven male volunteers. Also plasma catecholamines were determined.

2. An increase in blood pressure with a peak just after administration was observed. The cardiac output was unchanged and the pressor effect of ergotamine was due to an increase in total peripheral resistance.

3. Plasma noradrenaline decreased 65% at the peak of the pressor effect whereas plasma adrenaline was unchanged.

4. Hepatic blood flow decreased 34% just after ergotamine administration and was normal after 3 h. Renal blood flow decreased by 29 and 19%. Calf blood flow was unchanged. These results suggest that different vascular beds in man react differently to ergotamine.
Effects of Free Radical Scavengers on Renal Circulation after Ischaemia in the Rabbit
Authors: Hansson R. , Jonsson O. , Lundstam S. , Pettersson S. , Scherstén T. , Waldenström J.
Published: August 2015

1. The intrarenal erythrocyte distribution, total renal blood flow and renal vascular resistance were studied before and during recirculation after 60 min of warm ischaemia in three groups of rabbits. One group was pretreated with superoxide dismutase, another with catalase and the third group was not pretreated at all.

2. In non-pretreated ischaemic kidneys there was a significant trapping of labelled erythrocytes in the outer stripe of the medulla. This trapping was not seen in non-ischaemic control kidneys and was completely prevented by pretreatment with either superoxide dismutase or catalase.

3. In non-pretreated ischaemic kidneys there was a transient increase in total renal blood flow during the first 5 min of recirculation, after which it returned to preischaemic values. After pretreatment with catalase the postischaemic increase in blood flow was more pronounced but again the blood flow returned to preischaemic values within 30 min. Pretreatment with superoxide dismutase resulted in a rapid postischaemic increase in blood flow which remained high throughout the 30 min period studied.

4. The renal vascular resistance decreased initially during recirculation after ischaemia in both pretreated and non-pretreated kidneys. In the latter it returned to pre-ischaemic values within 10 min whereas a slower increase was observed after catalase pretreatment. After pretreatment with superoxide dismutase the resistance remained low during the 30 min recorded.
Sequential Studies of Oxalate Dynamics in Primary Hyperoxaluria
Authors: Watts R. W. E. , Veall N. , Purkiss P.
Published: August 2015

1. We have measured the total plasma clearance, renal clearance and equilibrium distribution volume of [14C]oxalate, and the urinary oxalate excretion rate and plasma oxalate levels at approximately 6 month intervals for up to 2.5 years in five patients with primary hyperoxaluria. The renal clearance and distribution volumes of [99mTc]DTPA (diethylenetriaminepenta-acetate) were measured simultaneously to provide estimates of glomerular filtration rate (GFR) and extracellular fluid volume (ECF). The same measurements were made on each of five normal volunteers.

2. Clearances and distribution volumes were measured with a modified single injection technique.

3. The oxalate clearance was two to three times the simultaneously measured GFR in the patients and control subjects. The renal clearance of oxalate was less than the total plasma clearance in the patients. The oxalate distribution volume was approximately 1.5 times the ECF in both the patients and controls. Only small changes were observed over a 2.5 years period in these particular patients.

4. The plasma oxalate concentration was derived from the urinary oxalate excretion rate and the plasma [14C]oxalate clearance. It was raised in the patients. The oxalate removal rate was derived from the total plasma clearance and the plasma oxalate concentration.
Influence of Age on Pulmonary Haemodynamics at Rest and during Supine Exercise
Authors: Ehrsam Rolf E. , Perruchoud André , Oberholzer Martin , Burkart Felix , Herzog Heinrich
Published: August 2015

1. To determine the effects of age on the pulmonary circulation at rest and on exercise we analysed the results of right heart catheterization studies performed in 125 asymptomatic subjects aged 14-68 years, who were healthy or had indispositions which did not impair cardiac or pulmonary function.

2. Age accounted for less than 10% of total variation in resting values of right atrial, pulmonary artery and wedge pressures, and of cardiac output.

3. The pulmonary artery-wedge pressure gradient and flow resistance at rest significantly increased with age.

4. On exercise there were significant increases with age in right atrial, pulmonary artery and wedge pressures, pulmonary to wedge pressure gradient and flow resistance, but cardiac output was not influenced by age.

5. Pulmonary circulation variables at rest are mainly influenced by sex and size, but during exercise significant effects of age are apparent.
The Comparative Blood Clearance Kinetics of Modified Radiolabelled Erythrocytes
Authors: Peters A. M. , Walport M. J. , Elkon K. B. , Reavy H. J. , Ferjencik P. P. , Lavender J. P. , Hughes G. R. V.
Published: August 2015

1. The rate of clearance from blood of 111In-labelled heat damaged autologous erythrocytes (HD-RBC) has been compared with that of simultaneously injected autologous 99mTc-labelled erythrocytes (IgG-RBC) coated with a Rhesus anti-D antibody. In 17 studies, the number of antibody molecules coating the erythrocytes was 9000 (high coating) and in nine studies the number was 5000 (low coating).

2. On gamma camera imaging, IgG-RBC uptake, at both levels of coating, could be visualized only in the spleen. HD-RBC were predominantly taken up by the spleen, although slight 111In activity was visible in the liver.

3. The blood clearance of IgG-RBC was mono-exponential, whereas that of HD-RBC was bi-exponential. The reciprocal of the t1/2 (the time taken for the 3 min value to fall by 50%) of the HD-RBC clearance correlated rather poorly with the rate constant of the simultaneous IgG-RBC clearance (r = 0.47, P > 0.05 at high coating; r = 0.75, P < 0.05 at low coating). The rate constant of the second exponential of the HD-RBC clearance showed a correlation with the rate constant of IgG-RBC clearance that was closer than the reciprocal of the t1/2 of HD-RBC clearance (r = 0.89, P < 0.001 at high coating; r = 0.76, P < 0.05 at low coating) but significantly closer only at high coating.

4. Splenic blood flow, measured using indium labelled platelets in ten subjects, correlated closely with the initial slope of HD-RBC clearance (r = 0.93, P<0.001).

5. By using splenic blood flow based either on platelets or on the initial slope of the HD-RBC clearance, an estimate was made of splenic IgG-RBC extraction ratio. The normal extraction ratio at high coating was about 50% and at low coating about 30%. Some patients with systemic lupus erythematosus and rheumatoid arthritis appeared to have abnormally low extraction ratios.

6. It was concluded that HD-RBC and IgG-RBC are not interchangeable as markers of splenic reticuloendothelial function; HD-RBC clearance is mainly dependent on splenic blood flow whereas IgG-RBC clearance is dependent both on splenic blood flow and splenic macrophage function. The simultaneous use of the two markers allows therefore an estimate of the splenic IgG-RBC extraction ratio, which potentially is a more specific index of splenic reticuloendothelial function than the clearance rate of either marker used alone.
Glycogen Content and Activities of Key Glycolytic Enzymes in Muscle Biopsies from Control Subjects and Patients with Chronic Alcoholic Skeletal Myopathy
Authors: Martin F. C. , Levi A. J. , Slavin G. , Peters T. J.
Published: August 2015

1. The capacity for glycolysis in muscle biopsies obtained from long-term heavy alcohol drinking patients has been compared with tissue from control subjects by assay in vitro of the total activities of glycogen phosphorylase, phosphofructokinase and fructose 1,6-bisphosphatase, key regulatory enzymes in the anaerobic glycolytic pathway.

2. Biopsies from 13 of 22 patients had type II fibre atrophy, and the activities of all three enzymes were reduced in these biopsies, when expressed in terms of DNA content, the most striking reduction being in phosphofructokinase activity.

3. The amount of glycogen in the tissue correlated closely with these enzyme activities and was slightly lower in the most atrophic tissue, when expressed in terms of DNA content.

4. The activities of acid and neutral α-glucosidases were similar in biopsies from control subjects and patients with various severities of alcohol myopathy.

5. The reduced activities are consistent with a reduced proportion of type II fibre muscle mass in these patients, and suggest that there may be a reduced capacity for glycolysis with resultant reduced lactate production. Whether the changes in enzyme activities are primary to the selective atrophy remains to be established.
Fatty Acid Oxidation in Mitochondria from Needle Biopsy Samples of Human Skeletal Muscle
Authors: Gohil K. , Jones D. A. , Edwards R. H. T.
Published: August 2015

1. Activities for the oxidation of palmitoyl-carnitine, of palmitoyl-CoA and of carnitine palmitoyltransferase were measured in mitochondria prepared from needle biopsy samples of human skeletal muscle. Results are presented for nine normal subjects and 18 patients in whom there was evidence of mitochondrial abnormality.

2. Palmitoylcarnitine and palmitoyl-CoA oxidation were measured spectrophotometrically by following the reduction of added cytochrome c in the presence of cyanide.

3. Because of large variations in the activities between subjects it was essential to express the three activities per unit of cytochrome c oxidase activity to demonstrate unambiguous specific alterations in the activities.

4. In most of the patients the order of the three activities was similar to that in the normal subjects. However, in five cases the activity for palmitoylcarnitine oxidation was less than 4% of the mean normal value. In two of these patients, the low activity could be accounted for by very low (<10% normal) activity of carnitine palmitoyltransferase (CPT). In another two patients the activity of CPT was normal but that of palmitoyl-CoA dehydrogenase (a measure of β-oxidation) was very low.
Hypercalcaemia of Malignancy: Evidence for a Non-Parathyroid Humoral Agent with An Effect on Renal Tubular Handling of Calcium
Authors: Ralston S. H. , Fogelman I. , Gardner M. D. , Dryburgh F. J. , Cowan R. A. , Boyle I. T.
Published: August 2015

1. The renal handling of calcium was examined in 31 patients with hypercalcaemia of malignancy. Results were compared with those from patients with primary hyperparathyroidism, and normal controls rendered hypercalcaemic by calcium infusion.

2. On relating the urinary calcium excretion indices to serum calcium values, inappropriately low rates of urinary calcium excretion were generally found in patients with malignancy associated hypercalcaemia. Further, the pattern of urinary calcium excretion in these subjects was similar to that found in patients with primary hyperparathyroidism.

3. These observations suggest that, in many solid tumours, the development of hypercalcaemia may be attributable to a humoral mediator with a parathyroid hormone-like effect on renal tubular calcium reabsorption.

4. The relatively frequent occurrence of hypercalcaemia in malignant disease thus may be partially explained by the presence of this humoral agent, which may impair the renal excretion of an increase in filtered calcium load, whether due to bone metastases, or humorally mediated osteolysis.
Effect of Molecular Charge on the Induction of Proteinuria and Glomerular Ultrastructural Damage in Hyperalbuminaemic Female Wistar Rats
Authors: Lawrence Gillian M. , Brewer D. B.
Published: August 2015

1. Intraperitoneal injection of anionic carbamylated bovine albumin derivatives induced glomerular epithelial cell foot process loss and increased urinary protein excretion, the severity of which rose with the dose administered.

2. The effects induced at a given albumin dose were significantly lower than those previously measured after the administration of normal bovine albumin.

3. The amount of epithelial cell foot process loss induced after the injection of carbamylated bovine albumin derivatives correlated well with the level of induced proteinuria but, at a given level of proteinuria, the amount of foot process was lower in these rats compared with those given normal bovine albumin.

4. The results obtained are consistent with the interpretation that the more anionic carbamylated bovine albumin derivatives were not only filtered less readily at the glomerulus than their less negatively charged counterparts but were also reabsorbed to a lesser extent by the tubular epithelium.
Effect of High Sodium Intake on Tissue Distribution of Endogenous Digitalis-Like Material in the Rat
Authors: Castan̂eda-Hernandez G. , Godfraind T.
Published: August 2015

1. The effect of a high sodium intake on the endogenous digitalis-like activity of several tissues was determined, after extraction, by digoxin radioimmunoassay in rats.

2. The high sodium intake increased the digitalis-like activity in serum but not in adrenals, brain or heart.
The Dilator Response to K+ Is Reduced in the Forearm Resistance Vessels of Men with Primary Hypertension
Authors: Phillips R. J. W. , Robinson B. F.
Published: August 2015

1. The dilator response to local infusion of K+ has been assessed in the forearm resistance vessels of 17 men with primary hypertension and 11 controls, by using a standard plethysmographic method.

2. The response to infusion of K+ at 0.1 mmol/min was smaller in the patients with hypertension than in the normal controls (P<0.03).

3. The results are consistent with the view that the activity of the sodium pump is depressed in the resistance vessels of patients with hypertension, but they yield no evidence as to whether or not this abnormality contributes to the elevation of the peripheral resistance.
Investigations on the Na+, K+-pump in Erythrocytes of Patients with Renal Hypertension
Authors: Brod J. , Schaeffer J. , Hengstenberg J. H. , Kleinschmidt T. G.
Published: August 2015

1. The ouabain-sensitive 42K+ flux from an artificial medium into erythrocytes was measured in 29 control subjects, 66 patients with chronic parenchymatous renal disease and in 32 subjects with primary hypertension.

2. The ouabain-sensitive 42K+ influx was reduced in subjects with chronic renal disease by about 20%, even when they were normotensive. The reduction in these patients was greater than that in patients with essential hypertension.

3. The changes in 42K+ influx and Na+ content with a decrease in the 42K+ influx/Na+ content ratio suggest an inhibition of the Na+ pump in the patients with chronic renal disease.

4. The inhibition of the Na+ pump may be secondary to the hypervolaemia which we suggest is the initial event leading to renal hypertension.
Serial Blood Water Estimations and in-Line Blood Viscometry: The Continuous Measurement of Blood Volume during Dialysis Procedures
Authors: Greenwood R. N. , Aldridge C. , Cattell W. R.
Published: August 2015

1. It has been shown in vitro that serial measurements of blood water during ultrafiltration accurately reflect changing blood volume.

2. It has been shown that minute changes in blood hydration produce detectable changes in blood viscosity.

3. An ‘in-line’ capillary viscometer has been constructed which can be placed in parallel with an extracorporeal circuit to give a continuous semi-quantitative measure of blood viscosity during ultrafiltration or haemodialysis. By making serial measurements of blood water each ‘viscometer curve’ can be corrected to permit calculation of blood volume provided that the starting blood volume is known.

4. Blood volume changes of less than 1% can be detected in vitro and provided that blood volume changes solely as a result of the removal or influx of water it can be measured continuously to within an accuracy of 4% for volume changes up to 30% irrespective of starting packed cell volume or blood water.
Cardiac sensitivity to isoprenaline, lymphocyte β-adrenoceptors and age
Authors: Fitzgerald D. , Doyle V. , Kelly J. G. , O'Malley K.
Published: August 2015

1. The heart rate response to isoprenaline in 11 subjects aged 19–46 years was compared with lymphocyte β-adrenoceptor numbers and lymphocyte cyclic AMP responsiveness.

2. The dose of isoprenaline required to increase heart rate by 25 beats/min (CD25) increased as a function of age (r 0.79; P < 0.01). Lymphocyte receptor numbers also correlated directly with age (r 0.61; P<0.05), but there was no true correlation between CD25 and lymphocyte receptor numbers.

3. Baseline and maximum lymphocyte cyclic AMP concentrations in response to isoprenaline stimulation in vitro were unrelated to age, CD25 or receptor numbers.

4. This study confirms previous findings of a reduced responsiveness with age and a rise in receptor numbers in young and middle-aged adults. However, the decline in the heart response to isoprenaline was unrelated to any measurable change in j3-adrenoceptor concentration or responses, at least in the isolated lymphocyte.
Cell loss from human, canine and guinea-pig gastric mucosa measured by DNA radioimmunoassay
Authors: Hurst B. C. , Rees W. D. W. , Garner A.
Published: August 2015

1. A DNA radioimmunoassay, sensitive in the range 25–1000 ng, has been developed to measure gastric mucosal cell loss. Validity of the assay was based on antibody specificity, absence of interference from gastric contents, parallel tracer displacement by dilutions of gastric and standard DNA, and crossover with colorimetric assay.

2. With this assay, gastric DNA shedding was examined in two animal species and man. In the guinea-pig stomach, DNA loss was 20–100 pg/h and in the canine Pavlov pouch, 260–580pg/h. In the canine Pavlov pouch stimulation of acid secretion by histamine and exposure to exogenous acid increased DNA output. In the normal human stomach DNA loss was 544 k 175 pg/h and in duodenal ulcer patients, 649 k 225 pg/li.

3. DNA radioimmunoassay provides a sensitive and reproducible measure of cell exfoliation from the stomach and may be a useful tool for studying aspects of gastric mucosal defence.
Plexogenic Pulmonary Hypertension of Unknown Origin. What's New?
Authors: Lockhart Alain , Reeves John T.
Published: August 2015

Introduction: Pulmonary hypertension of unknown origin, also called primary pulmonary hypertension (i.e. there is no associated heart or lung disease), comprises three different pathological entities: (i) pulmonary veno-occlusive disease, (ii) recurrent thromboembolic or thrombotic pulmonary disease and (iii) plexogenic pulmonary hypertension (PPH) [1, 2]. The last-named is characterized by predominant involvement of small pulmonary arteries which has three distinctive characteristics: (i) concentric ‘onion-like’ intimal fibrosis, (ii) fibrinoid necrosis of the wall of some arteries occasionally associated with an organized or organizing thrombus, and (iii) dilated side-branches whose wall is often reduced to a single elastic lamina and is lined interiorly by cellular proliferation showing a ‘plexiform’ arrangement. This review is concerned with primary PPH and drug-induced PPH [3] as opposed to PPH complicating post-tricuspid cardiac shunts, although the actual sequence of events leading to remodelling of pulmonary vessels is better known in the latter than in the former. Since a recent exhaustive review is available [3], we shall concentrate on the role of vasodilatator treatment in PPH and the present understanding of cause(s) of PPH.
The Contribution of Reflex Inhibition to Arthrogenous Muscle Weakness
Authors: Stokes Maria , Young Archie
Published: August 2015

‘Arthrogenous muscle weakness’ is weakness of muscles acting about an injured or inflamed joint. The weakness may be due to loss of muscle or to inability to activate the muscle (Fig. 1). Weakness of the thigh muscles, and of the quadriceps in particular, is a common and important consequence of knee trauma, surgery or arthritis. Muscle weakness contributes significantly to disability and probably also renders the joint vulnerable to further damage (Fig. 1). This review starts with a brief discussion of the contribution of atrophy to weakness. It concentrates, however, on inhibition of quadriceps activation and suggests some therapeutic implications. It does not deal with the reduced oxidative capacity and increased fatiguability of disused muscle since, although important, these have not been part of our programme of work.
Plasma Clearance, Tissue Distribution and Catabolism of Cationized Albumins with Increasing Isoelectric Points in the Rat
Authors: Bergmann P. , Kacenelenbogen R. , Vizet A.
Published: August 2015

1. The infusion of cationic substances produces acute renal failure and proteinuria, and an experimental disease very similar to disseminated coagulopathy. The purpose of this work was to investigate further, in the rat, the plasma disappearance rate, the tissue distribution and the catabolism of albumins with modified isoelectric points.

2. Human serum albumin was cationized with hexanediamine and labelled with 125I or 131I.

3. During 10–180 min after their intravenous injection into the rat, these modified 125I-labelled albumins were cleared from the plasma at a rate which increased with their isoelectric point.

4. At 1 and 3 h after the injection of highly cationic proteins (isoelectric point higher than 9.5) the tissue protein bound 125I concentration was greatest (∼3.5% of the injected activity/g) in the spleen and liver. A significant amount of the basic proteins was found in the kidney and in the lung (0.75–1% /g). Their concentration was much lower in other tissues.

5. The whole body radioactivity was significantly lower 24 h after the injection of 131I-labelled cationized albumins than after similarly labelled native albumin. However, expressed as a percentage of the retention at 24 h, the body radioactivity at later times was higher for cationic than for native albumin.

6. We conclude that cationized albumins are cleared from the plasma, mainly by the reticuloendothelial system, at a rate directly related to their isoelectric point. The cationized albumins are catabolized very rapidly initially, but a fraction of the injected protein remains in the body for a longer time than native albumin.
The Biliary Excretion of Sulphated and Non-Sulphated Bile Acids and Bilirubin in Patients with External Bile Drainage
Authors: Dooley James S. , Bartholomew Carl , Summerfield John A. , Billing Barbara H.
Published: August 2015

1. The biliary excretion of total bilirubin and bile acids, and the fate of tracer doses of radioactive sulphated and non-sulphated bile acids, were studied in patients with percutaneous transhepatic bile drainage.

2. Non-sulphated bile acids were excreted in bile early after biliary decompression, and the serum total 3α-hydroxy bile acid concentrations fell rapidly to normal. Biliary bilirubin excretion was both less than and delayed compared with that of bile acids, and the serum bilirubin concentration fell more slowly.

3. The serum disappearance of [3H]chenodeoxycholate-3-sulphate was slower than that of [14C]glycocholate in all patients with bile drainage, the difference being more marked in the jaundiced patients.

4. The radioactive sulphated bile acids were recovered predominantly in the urine of the jaundiced patients. In contrast [14C]glycocholate was excreted almost exclusively in bile. In an anicteric patient, radioactive sulphated bile acid disappeared from the serum more quickly, and biliary recovery exceeded that in the urine.

5. The studies demonstrate the differences in handling of total bilirubin, and sulphated and non-sulphated bile acids in man after the relief of bile duct obstruction. The biliary excretion of radioactive labelled sulphated bile acids is low for at least 1 week after biliary drainage, but later becomes the predominant route for excretion in the anicteric patient.
Nocturnal Foot Blood Flow in Patients with Arterial Insufficiency
Authors: Jelnes R. , Tønnesen K. H.
Published: August 2015

1. Twenty-four hour continuous recording of xenon (133Xe) wash-out from the forefoot was performed on patients with normal circulations (n = 10) and on patients with different degrees of arterial insufficiency (n = 36).

2. During day hours the calculated subcutaneous blood flow in the forefoot was on average the same in patients with normal circulations and in patients with different degrees of arterial insufficiency (mean: 2.0 ± 0.8 ml min−1 100 g−1).

3. During sleep the blood flow nearly doubled in patients with normal circulations; no systematic change was seen in patients with intermittent claudication. In patients with severe ischaemia, i.e. having rest pain, the blood flow decreased by approximately 50%.

4. The changes in local blood flow may be due to changes in local sympathetic tone and to changes in local perfusion pressure.
Short-Term Studies on the Use of Glycerol as An Osmotic Agent in Continuous Ambulatory Peritoneal Dialysis (CAPD)
Authors: Heaton A. , Ward M. K. , Johnston D. G. , Nicholson D. V. , Alberti K. G. M. M. , Kerr D. N. S.
Published: August 2015

1. The use of glycerol as an osmotic agent in two different concentrations (92 mmol/l and 272 mmol/l) in peritoneal dialysis fluid was investigated over 3 days in six patients on continuous ambulatory peritoneal dialysis and compared with two concentrations of glucose (76 mmol/l and 215 mmol/l) in the same patients.

2. The calorific value of the absorbed osmotic agent was lower, by 19% with isotonic and 22% with hypertonic solutions, when glycerol was used in place of glucose. However, glycerol provided significantly lower total ultrafiltration than glucose at each concentration, despite a higher initial osmotic pressure of the glycerol-based solutions. Thus, the higher concentration of glycerol required to provide equal ultrafiltration may offset any calorific advantage.

3. Equilibration of creatinine and urea was slower and creatinine clearance lower with glycerol. Solutions containing glycerol were initially less acid (pH 6.5) than those containing glucose (pH 5.1).

4. Blood glycerol levels, which were in the physiological range with glucose as the osmotic agent, reached a peak 80-fold greater at 4.3 ± 0.8 mmol/l during dialysis with fluid containing glycerol at 272 mmol/l and eightfold higher at 0.42 ± 0.09 mmol/l with glycerol at 92 mmol/l. There was no evidence of haemolysis or other toxic effect despite these levels.

5. The rise in blood glucose and insulin noted during the use of glucose-based solutions was not found with glycerol. Circulating levels of lactate, pyruvate, alanine, non-esterified fatty acids and the ketone bodies were similar with the two agents.

6. Although these short-term studies have shown no conclusive advantage of glycerol over glucose, long-term effects of glycerol, particularly on circulating lipid levels, will determine its future role as an osmotic agent in continuous ambulatory peritoneal dialysis.
Supersensitivity of Benzodiazepine Receptors in Hepatic Encephalopathy Due to Fulminant Hepatic Failure in the Rat: Reversal by a Benzodiazepine Antagonist
Authors: Baraldi M. , Zeneroli M. L. , Ventura E. , Penne A. , Pinelli G. , Ricci P. , Santi M.
Published: August 2015

1. Benzodiazepine receptors were studied in rats with hepatic encephalopathy due to fulminant hepatic failure induced by galactosamine. [3H]-Diazepam binding studies on brain synaptic membranes of rats with mild and severe encephalopathy show a significant increase in the number of receptors in both stages of coma.

2. [3H]Diazepam binding to synaptic membrane preparations from rats in the mild or severe stage of encephalopathy hyper-responded to the stimulatory effect of γ-aminobutyric acid (GABA) applied in vitro at doses which for control rat preparations were in a subthreshold range. The effect of GABA was shown to be specific, since it was blocked by bicuculline methiodide. The sensitivity of benzodiazepine receptors in hepatic encephalopathy to nanomolar concentrations of GABA, which induced a significant increase in their affinity, seems to indicate a functional supersensitivity of benzodiazepine receptors in vivo in both mild and severe stages of encephalopathy.

3. The phenomena described may be attributed to a partial degeneration of nerve terminals in hepatic encephalopathy, leading to a supersensitivity of benzodiazepine receptors, which parallels the previously described denervation supersensitivity of GABA receptors present in this animal model of fulminant hepatic failure. These findings may account for the brain hypersensitivity to sedatives administered to patients with liver diseases.

4. The administration in vivo of a benzodiazepine antagonist, 2-phenylpyrazolo [4,3-c]-quinolin-3(5H)-one, counteracted the hypersensitivity of benzodiazepine receptors in the mild stage of encephalopathy. In fact, electrophysiological studies with visually evoked potential recordings in rats in the mild stage of encephalopathy 30-60 min after the administration of the drug showed a recovery of the wave pattern, and this electrophysiological finding was substantiated by the demonstration that both the number and the affinity of benzodiazepine receptors were strongly reduced.
The effect of Low-Dose Dopamine Infusion on Anterior Pituitary Hormone Secretion in Normal Female Subjects
Authors: Connell J. M. C. , Ball S. G. , Inglis G. C. , Beastall G. H. , Davies D. L.
Published: August 2015

1. The effect of low-dose dopamine infusion on anterior pituitary hormone secretion in a group of seven healthy female subjects is reported. Subjects were infused with NaCl solution (154 mmol/l) (control) or dopamine (0.01 and 0.1 μg min−1 kg−1 for 120 min at each rate) on separate days in the early follicular phase of consecutive menstrual cycles.

2. Serum prolactin decreased during infusion of dopamine at 0.01 μg min−1 kg−1 but a similar fall was found in the control group.

3. When the rate of dopamine infusion was increased to 0.1 μg min−1 kg−1 a further substantial decrease in prolactin concentration occurred, whereas prolactin in the control group showed no change. At the end of the period of dopamine infusion at 0.1 μg min−1 kg−1 serum prolactin remained significantly (P<0.025) lower than in the control group (85 ± 12 vs 180 ± 21 m-units/l).

4. No change in thyrotrophin (TSH), growth hormone (GH) or luteinizing hormone (LH) was seen during either rate of dopamine infusion compared with control.

5. While dopamine infusion at 0.1 μg min−1 kg−1 caused significant inhibition of prolactin secretion in normal female subjects, other pituitary hormone secretion was not affected: it is suggested that under the conditions of this study dopamine in hypophysial portal blood is not of primary importance in the control of basal TSH, GH and LH release.
The rate of Purine Synthesis de nova in Blood Mononuclear Cells in vitro from Patients with Familial Hyperuricaemic Nephropathy
Authors: Macdermot Kay D. , Allsop Jennifer , Watts R. W. E.
Published: August 2015

1. We have measured the rate of purine synthesis de novo in blood mononuclear cells in vitro and the activities of the purine salvage enzymes [hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8), adenine phosphoribosyltransferase (APRT; EC 2.4.2.7)] and ribosephosphate pyrophosphokinase (PP-ribose-P synthetase;EC 2.7.6.1)] and the concentration of phosphoribosylpyrophosphate (PP-ribose-P) in the erythrocytes of affected family members.

2. These subjects belong to families where hyperuricaemia and renal failure occur together early in life, and the genetic transmission follows an autosomal dominant mode of inheritance. We term this syndrome, familial hyperuricaemic nephropathy.

3. No significant differences were detected in either the rates of purine synthesis de novo in vitro between the index patients and the control subjects with respect to the enzyme activities or the PP-ribose-P concentrations. Two groups of controls were used, healthy individuals and patients with a comparable degree of renal failure due to non-immune complex renal disease.

4. Mononuclear cells from patients with Lesch-Nyhan syndrome (congenital HPRT deficiency) showed the expected acceleration of purine synthesis de novo in vitro.

5. The accelerated purine synthesis de novo in vitro associated with phytohaemagglutinin-induced lymphocyte transformation was detectable by the method used.

6. We conclude that familial hyperuricaemic nephropathy is not due to a metabolic lesion which causes accelerated purine synthesis de novo. This suggests that the primary abnormality may be a failure of the renal tubular net excretion of urate.