bluuebunny/crossref_metadata_2025 huggingface dataset:
No Functional Difference of the Two Iron-Binding Sites of Human Transferrin in Vitro
Authors: Van Der Heul C. , Kroos M. J. , Van Noort W. L. , Van Eijk H. G.
Published: August 2015

1. According to the Fletcher-Huehns hypothesis there exists a functional difference between the two iron-binding sites of transferrin.

2. The aim of the study presented was to evaluate this hypothesis in a homogeneous system, with human bone marrow cells and pure human monoferric transferrins A and B.

3. For this reason normal human bone marrow cells were incubated with human monoferric transferrin. The monoferric transferrins A and B were obtained by selective labelling at different pH of apotransferrin followed by preparative isoelectric focusing in granulated gels. The uptake of iron by the cell suspensions from monoferric transferrins A and B was equal.

4. In a heterogeneous but more active system for the removal of iron from human transferrin in vitro the two human monoferric transferrins did not show any significant functional differences.

5. No support for the Fletcher-Huehns hypothesis could be obtained.
Cytosine Arabinoside Deamination in Human Leukaemic Myeloblasts and Resistance to Cytosine Arabinoside Therapy
Authors: Harris A. L. , Grahame-Smith D. G. , Potter C. G. , Bunch C.
Published: August 2015

1. The conversion of cytosine arabinoside into its active metabolite cytosine arabinoside triphosphate, and catabolism by deamination to uracil arabinoside, was measured in intact marrow myeloblasts from patients with acute myeloid leukaemia. The ratio of uracil arabinoside/cytosine arabinoside triphosphate ranged from 0.32 to 19.11.

2. The effect of tetrahydrouridine, an inhibitor of cytosine arabinoside deamination, on cytosine arabinoside triphosphate production was studied. The greatest increase of cytosine arabinoside triphosphate production caused by addition of tetrahydrouridine was 27%.

3. The increase in cytosine arabinoside triphosphate production was not related to the ratio of uracil arabinoside/cytosine arabinoside triphosphate or to the deaminase activity per 106 cells. It was proportional to the percentage change of cytosine arabinoside in the incubation medium.

4. The sensitivity of DNA synthesis to inhibition by cytosine arabinoside was measured in myeloblasts from 11 patients. Addition of tetrahydrouridine did not increase the sensitivity of the marrow to cytosine arabinoside.

5. Cytosine arabinoside deamination is unlikely to be an important mechanism of resistance in myeloblasts in vivo, although it may produce apparent resistance in vitro.
Hepatic Organelle Pathology in Primary Biliary Cirrhosis and the Response to Low-Dose D-Penicillamine Therapy
Authors: Scott J. , Jenkins W. , Smith G. P. , Peters T. J.
Published: August 2015

1. Analytical subcellular fractionation in combination with enzymic microanalysis has been used to investigate the hepatic organelle pathology of primary biliary cirrhosis. Activities of plasma membrane and lysosomal enzymes in hepatic needle biopsies were increased, but marker enzymes for other organelles were normal.

2. Seven patients were treated with a low dose of penicillamine, 250 mg daily, over a 3–6 month period. The initially raised serum alkaline phosphatase and IgM levels were significantly reduced. In four patients with markedly elevated hepatic copper there was a small decrease, but urinary copper excretion was unaltered. Hepatic organelle pathology was significantly improved.

3. No serious side-effects were noted and it is suggested that a controlled trial of low-dose D-penicillamine therapy is indicated in patients with primary biliary cirrhosis.
Intra-Erythrocyte Sodium and (Na+,K+-Activated)-ATPase Concentration and Urinary Aldosterone Excretion in Spontaneously Hypertensive Rats
Authors: Berglund G. , Sigström L. , Lundin S. , Karlberg B. E. , Herlitz H.
Published: August 2015

1. Intra-erythrocyte sodium, potassium, ATP and (Na+,K+-activated)-ATPase concentrations and urinary aldosterone excretion were compared in 3-month-old spontaneously hypertensive rats (n = 11) and normotensive Wistar-Kyoto control rats (n = 11).

2. Spontaneously hypertensive rats exhibited significantly higher intra-erythrocyte sodium concentration (5.5 ± 1.3 vs 4.0 ± 1.1 mmol/l of erythrocytes, P < 0.01). No significant difference was found in intra-erythrocyte potassium, ATP or (Na+,K+-activated)-ATPase concentration.

3. Mean urinary aldosterone excretion was significantly lower in spontaneously hypertensive rats (66.3 ± 6.5 pmol/24 h) than in Wistar-Kyoto rats (90.5 ± 10.6 pmol/24 h, P < 0.01). No significant relationship between urinary aldosterone and intra-erythrocyte sodium concentration was found in spontaneously hypertensive or Wistar-Kyoto rats or in the pooled group.

4. These results are thus consistent with previous findings of an increased intracellular sodium concentration in spontaneously hypertensive rats, but do not support the hypothesis that aldosterone is a dominant regulator of intracellular sodium concentration.
The Relationship between Leucocyte and Muscle Zinc in Health and Disease
Authors: Jones R. B. , Keeling P. W. N. , Hilton P. J. , Thompson R. P. H.
Published: August 2015

1. A significant correlation between leucocyte and muscle zinc contents was observed in control patients and in patients with generalized diseases.

2. As muscle contains a large proportion of the whole-body zinc, it is suggested that leucocyte zinc content may be a useful indicator of tissue zinc status.
Different Distributions of Kinetically Apparent Molecular Varieties of α2-Macroglobulin in Health and in Patients with Cryptogenic Fibrosing Alveolitis
Authors: Topping R. M. , Craven A. H. , Whiting Susan , Rigden B. G. , Turner-Warwick M. , Turton C. W. G.
Published: August 2015

1. Proteinase inhibitors have been studied in whole serum by using a kinetic method that avoids potentially damaging protein separation procedures.

2. The α2-macroglobulin of an individual can be allocated unambiguously into one of seven categories according to the binding of trypsin to inhibitor in two kinetically apparent binding modes (β- and α-modes).

3. The distribution of α2-macroglobulin β:α ratios in a healthy adult population is defined, and shown to be independent of sex and age.

4. The distribution of β: α ratios in a group of patients with cryptogenic fibrosing alveolitis was found to be significantly different (P < 0.005) from the normal distribution.

5. Changes in the β: α ratio were noted in five of six patients with cryptogenic fibrosing alveolitis after treatment, but on no occasion when two healthy subjects were assessed a total of nine times.

6. The molecular interpretation and the possible importance of altered proteinase inhibition in inflammation and fibrosis are discussed.
Blood-Volume Expansion in the Rat: Natriuresis Accompanied by a Fall in Filtration Fraction
Authors: Querido D. , Isaacson L. C.
Published: August 2015

1. We have attempted to confirm the existence of a natriuretic hormone released in response to acute expansion of blood volume.

2. Isolated kidneys, perfused with whole blood at constant pressure, were incorporated within an extracorporeal circulation in recipient rats. In six control experiments urine flow rate, renal blood flow, glomerular filtration rate, filtration fraction, and the fractional excretion of filtered sodium and water were measured for periods of up to 120–140 min thereafter. The same variables were measured in a further 12 experiments in which, after 63 ± 11 min, the rats were volume expanded with equilibrated whole blood (15, 18 or 28 ml/kg body wt.).

3. On average the controls revealed no change in any of the variables measured; volume expansion was followed by increased renal blood flow and fractional excretion of filtered sodium and water, while the filtration fraction fell.

4. In both the control and volume-expansion experiments, there were 12 instances in which the fractional excretion of filtered sodium increased; in 10 of these, including those experiments in which the natriuresis was most marked, there was a closely correlated fall in filtration fraction.

5. In all the experiments changes in the fractional excretion of filtered sodium and water varied in parallel.

6. We conclude that volume expansion (a) changes the concentration of some circulating vasoactive substance(s) and (b) results in natriuresis and diuresis consequent upon a fall in filtration fraction.
Total Body-Glucose Turnover in Normal and Intra-Uterine Growth-Retarded Neonatal Piglets
Authors: Flecknell P. A. , Wootton R. , John Muriel
Published: August 2015

1. Because studies of the metabolic problems of the human intra-uterine growth-retarded neonate are limited by ethical considerations we have used the intra-uterine growth-retarded piglet as an animal model. Total body-glucose kinetics were measured in 16 intra-uterine growth-retarded and 11 normal piglets from the same litters with [3H]glucose as a tracer.

2. The intra-uterine growth-retarded animals had marginally smaller brains than their normal littermates, but substantially smaller livers. Liver weight was reduced in proportion to body weight.

3. Total body-glucose turnover rate was significantly lower (P < 0.001) in the intra-uterine growth-retarded animals in comparison with their normal littermates, but was appropriate for their smaller body and liver weights. Brain weight was only slightly reduced in the intra-uterine growth-retarded group so that glucose turnover adjusted to a common brain weight was significantly lower (P < 0.001) in these animals.

4. Total body-glucose pool size was lower in the intra-uterine growth-retarded animals (P < 0.01), but was appropriate for their body and liver weights. It was significantly reduced in relation to brain weight (P < 0.001).

5. Resting plasma glucose concentration was lower in the intra-uterine growth-retarded animals (P < 0.001). There was no relationship between concentration and turnover in either group.

6. It is suggested that the observed differences in total body-glucose turnover may be associated with profound differences in cerebral metabolism in the intra-uterine growth-retarded animals.
Liver Blood Flow and Oxygen Consumption during Metabolic Acidosis and Alkalosis in the Greyhound
Authors: Hughes R. L. , Mathie R. T. , Fitch W. , Campbell D.
Published: August 2015

1. Hepatic arterial and portal venous blood flow and hepatic oxygen consumption were measured in two groups of greyhounds anaesthetized with pentobarbitone. Flows were measured with electromagnetic flowmeters.

2. In the first group the effects of metabolic acidosis produced by the infusion of a molar solution of lactic acid were studied. In the second group the effects of metabolic alkalosis produced by the infusion of a molar solution of sodium bicarbonate were studied.

3. In the acidotic group hepatic arterial blood flow decreased from 35.2 to 9.6 ml min− 100 g− of liver whereas portal venous blood flow increased from 94.2 to 126.1 ml min− 100 g− of liver. Total liver blood flow was unchanged. Hepatic oxygen consumption increased, but not significantly, while hepatic venous oxygen content decreased significantly. Hepatic arterial resistance increased from 1.18 to 2.77 mmHg min− ml− while peripheral resistance was virtually unchanged. Portal venous pressure increased from 7.08 to 11.6 mmHg.

4. In the alkalotic group portal venous blood flow increased from 112 to 137 ml min− 100 g− of liver. Hepatic arterial blood flow increased, but not significantly. Total liver blood flow increased from 151 to 185, ml min− 100 mg− of liver. There were no significant changes in hepatic oxygen consumption.

5. It is concluded that metabolic acidosis reduces the supply of oxygen to the liver owing to the reduction in hepatic arterial blood flow and is therefore potentially harmful, whereas metabolic alkalosis probably has no biologically significant effect on liver blood flow.
Effect of Parathyroidc Hormone on Bicarbonate Secretion in the Guinea-Pig Stomach and the Amphibian Isolated Gastric Mucosa
Authors: Flemström G. , Garner A.
Published: August 2015

1. The effect of parathyroid hormone on gastric bicarbonate secretion was determined in the anaesthetized guinea pig. Subcutaneous injections of bovine parathyroid hormone (75 U.S.P units day−1 kg−) for 7 days caused a significant increase in HCO3− output. There was also a rise in K+ output and a slight elevation of H+ secretion. A similar increase in HCO3− output occurred after acute intravenous injection of the hormone (75 U.S.P. units/kg).

2. Both chronic and acute administration of parathyroid hormone caused a significant increase in serum calcium concentration and it is likely that the changes in gastric ion outputs reflect raised calcium levels. Given alone intravenous calcium (1.5 mg/kg body wt.) stimulated gastric secretion of both HCO3− and H+.

3. To determine whether parathyroid hormone had a direct action on gastric ion transport experiments were performed in the amphibian isolated mucosa. Antrum transports HCO3− spontaneously while HCO3− transport in fundus was studied after inhibition of the greater H+ secretion by the histamine H2-receptor antagonist metiamide. Parathyroid hormone at a concentration of 0.2 United States Pharmacopea (U.S.P.) unit/ml in the nutrient-side bathing solution inhibited both antral and fundic HCO3− transport. A higher concentration (2.0 units/ml) had no effect on fundic H+ secretion.

4. The inhibitory effect in vitro was greater in the antrum and parathyroid hormone may almost abolish the active component of HCO3− transport in this tissue. It is likely that any similar inhibition of gastric HCO3− secretion by parathyroid hormone in vivo is masked by the stimulatory effects of released calcium.
Analytical fractionation of human liver microsomal fractions: Localization of cholesterol and of the enzymes relevant to its metabolism
Authors: Balasubramaniam S. , Mitropoulos K. A. , Venkatesan S. , Myant N. B. , Peters T. J. , Postiglione A. , Mancini M.
Published: August 2015

1. The submicrosomal distribution of three enzymes concerned in cholesterol metabolism, and of free and esterified cholesterol, was determined in human liver by analytical isopycnic centrifugation on sucrose gradients.

2. The distribution profile and median density of acyl-CoA:cholesterol O-acyltransferase was similar to that of RNA, showing that this enzyme is confined largely to the ribosome-rich membranes of the endoplasmic reticulum. The distribution profiles and median densities of 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7α-mono-oxygenase showed that both enzymes are confined to the smooth, ribosome-poor, endoplasmic reticulum.

3. Most of the free cholesterol in the microsomal preparations was present in smooth membranes from the Golgi apparatus and in vesicles from plasma-membrane fragments. The distribution of esterified cholesterol was multimodal and extended throughout the whole gradient.
Caffeine: Its Effect on Catecholamines and Metabolism in Lean and Obese Humans
Authors: Jung R. T. , Shetty P. S. , James W. P. T. , Barrand M. A. , Callingham B. A.
Published: August 2015

1. The metabolic response of lean and obese women to caffeine was studied to see if caffeine could be used to demonstrate the subnormal thermogenesis in obesity previously shown after standard meals or intravenous infusions of noradrenaline.

2. The rise in resting metabolic rate with caffeine was similar in the lean and obese groups and β-adrenoceptor blockade did not reduce the increment in metabolic rate in either group. These responses did not, therefore, correspond with the other subnormal thermogenic responses of the constitutionally obese.

3. In a post-obese group, i.e. previously obese women who were now of normal weight, there was a reduced response of the resting metabolic rate to caffeine.

4. Monitoring plasma substrate concentrations showed that the change in oxygen uptake corresponded to changes in plasma free fatty acids, so that in adults the metabolic effects of caffeine seem to be mediated by increases in adipocyte lipolysis. This effect seems to be mainly independent of the adrenergic system.
The Effect of Combined Ischaemia and Acidosis on Lactate Uptake and Gluconeogenesis in the Perfused Rat Liver
Authors: Iles R. A. , Cohen R. D. , Baron P. G.
Published: August 2015

1. Perfused rat livers were subjected to an acid perfusate and varying degrees of ischaemia in an attempt to simulate the conditions of strenuous exercise or shock.

2. Lactate uptake and glucose output from the liver decreased during moderate ischaemia alone and more so when, in addition, the perfusate was made acidic.

3. Hepatic ATP and ADP content increased in the presence of an acid perfusate.

4. It is concluded that both ischaemia and acidosis may contribute to the diminished hepatic uptake of lactic acid in strenuous exercise and shock.
The Effect of Adrenaline on Hepatic Lactate Uptake in the Acidotic Partially Ischaemic Rat Liver
Authors: Iles R. A. , Cohen R. D. , Baron P. G. , Smith J. A. , Henderson R. M.
Published: August 2015

1. The effect of adrenaline (7 × 10−8 and 7 × 10−7 mol/l) on lactate uptake and glucose output was studied in the perfused liver of starved rats under conditions of reduced flow and acid perfusate.

2. Adrenaline largely prevented the decrease in hepatic lactate uptake which would otherwise occur owing to reduced blood flow and acidosis and may, therefore, have a protective effect in strenuous exercise and shock.
Airway and Metabolic Responsiveness to Intravenous Salbutamol in Asthma: Effect of Regular Inhaled Salbutamol
Authors: Harvey J. E. , Baldwin C. J. , Wood P. J. , Alberti K. G. M. M. , Tattersfield A. E.
Published: August 2015

1. Airway, metabolic and cyclic nucleotide responses to intravenous salbutamol were measured in five patients with mild asthma who had taken no medication in the week before the study. The studies were repeated after the patient had taken regular inhaled salbutamol for 4 weeks, in doses increasing to 2000 μg daily in week 4.

2. The pretreatment airway, metabolic and cyclic nucleotide responses to salbutamol were similar to those previously reported in normal subjects. These patients therefore did not show evidence of partial β-adrenoceptor blockade.

3. After 4 weeks' salbutamol therapy the airway response to intravenous salbutamol was unchanged.

4. The glucose, pyruvate and adenosine 3′:5′-cyclic monophosphate (cyclic AMP) responses to intravenous salbutamol were depressed after regular salbutamol administration. The dose-response curve for non-esterified fatty acids and insulin, though displaced downwards, did not indicate an impaired response to salbutamol since the shape was unchanged. There was no significant change in the lactate, glycerol and total ketone response.

5. This study confirms that tissues differ in the ease with which they develop resistance to β-adrenoceptor agonists. Asthmatic airways appear to be relatively protected from developing resistance when compared with other tissues in asthmatic patients and when compared with the airways of normal subjects.
Effect of Haemorrhage on Renin Concentration in Superficial and Deep Venous Outflows of the Cat Kidney
Authors: Jones Susan M. , Torretti J.
Published: August 2015

1. Plasma renin concentration is significantly higher in the subcapsular venous outflow, which drains the superficial cortex, than in the deep venous outflow, which drains the inner half of the cortex and medulla of the cat kidney. The purpose of these experiments was to observe whether this pattern is preserved or disrupted by a stimulus to renin release.

2. Plasma renin concentration in arterial samples and in the superficial and deep renal venous outflows was measured before and after haemorrhage which produced a 24 ± 6.7% drop in mean blood pressure in 13 cats.

3. After haemorrhage, total kidney plasma flow and glomerular filtration rate (GFR) did not change significantly. There was a rise in arterial plasma renin concentration. Venous minus arterial plasma renin concentration increased significantly in the deep venous outflow, but not in the superficial outflow.

4. The results suggest that both superficial and deep cortical venous drainage of the cat kidney should be considered when measuring renal renin release. In addition, they suggest that there may be differences in the response of superficial and deep juxtaglomerular apparatuses to haemorrhage.
Differential Toxicity and Pharmacokinetics of Sodium and Tris Salts of 5-fluorouracil in the Rat
Authors: Plumb Jane A. , Gardner M. L. G.
Published: August 2015

1. Rats injected intraperitoneally (i.p.) with the Tris salt of 5-fluorouracil (1.44 mmol/kg) showed severe toxic symptoms and a 15% mortality. No mortality and no obvious toxicity, apart from intestinal toxicity, resulted after injection of the sodium salt at equimolar dosage.

2. The plasma pharmacokinetics of the two salts of 5-fluorouracil (1.44 mmol/kg) were different after i.p. injection: higher plasma levels were achieved and were sustained for longer after the Tris salt than after the sodium salt.

3. No differences in plasma pharmacokinetics were observed after intra-arterial (i.a.) injection of the two salts of 5-fluorouracil (6.576 mmol/kg).

4. Thus there are fundamental (and potentially important) differences between the biological properties of the sodium and Tris salts of 5-fluorouracil. These cannot be explained at present.
Glycogen-Depletion Patterns with Isometric and Isokinetic Exercise in Patients after Leg Injury
Authors: Hultén B. , Renström P. , Grimby G.
Published: August 2015

1. The glycogen-depletion patterns were studied as a measure of muscle-fibre recruitment in patients after leg injuries (fractures, ligament injuries). Intermittent isometric and dynamic isokinetic knee extension were performed with 30 and 50% of the maximal isometric torque of the injured leg. In a third group isokinetic and dynamic exercise with weights were compared by using maximal effort procedures.

2. The 30% maximal voluntary contraction programme, which corresponded to 16% of maximal voluntary contraction of the non-injured leg, resulted in glycogen depletion of type I fibres, which was significant only in the isometric exercise. In the 50% maximal voluntary contraction programme (41% of maximal voluntary contraction of the non-injured leg) depletion of type II fibres dominated and was significant with isometric exercises. In the maximal effort programmes there was a significant depletion of type II fibres.

3. Subjects with a relatively large reduction in strength or a small number of type I fibres demonstrated more depletion of these fibres than other subjects.

4. In patients with moderately reduced muscle strength and muscle fibre atrophy static or dynamic exercises using at least 50% of the actual maximal voluntary contraction can thus be used to recruit and train type II fibres.
Regulation of 25-Hydroxy-Vitamin D-1α-Hydroxylase in Chick Isolated Renal Tubules: Effects of Prostaglandin E2, Frusemide and Acetylsalicylic Acid
Authors: Wark J. D. , Larkins R. G. , Eisman J. A. , Wilson K. R.
Published: August 2015

1. Isolated renal tubules were prepared from vitamin D-deficient chicks. The effects of added prostaglandin E2 (PGE2) and agents which modify prostaglandin metabolism on the metabolism of 25-hydroxy-vitamin D3 were studied.

2. Frusemide (0.1 mmol/l) raised the prostaglandin E (PGE) content of the tubule incubation medium; it significantly increased 1,25-dihydroxy-vitamin D3 [1,25-(OH)2D3] production from 25-hydroxy-vitamin D3 [25-(OH)D3] and significantly inhibited the net production of 24,25-dihydroxy-vitamin D3 [24,25-(OH)2D3].

3. Acetylsalicylic acid (aspirin; 0.1 mmol/l) decreased the PGE content of the tubule incubation medium and significantly inhibited 1,25-(OH)2D3 production.

4. In the presence of 1,25-(OH)2D3, 4 h exposure of tubules from vitamin D-deficient chicks to concentrations of PGE2 between 2.8 × 10−6 and 2.8 × 10−8 mol/l significantly enhanced 1,25-(OH)2D3 production.

5. It is concluded that, in view of the effects of modulation of endogenous prostaglandin levels by frusemide in aspirin, and the stimulatory effect of exogenous PGE2, prostaglandins should be considered potential regulators of the renal 25-hydroxy-vitamin D-1α-hydroxylase [25-(OH)D-1α-hydroxylase] enzyme.
The Influence of a Combined Oral Contraceptive Pill and Menstrual Cycle Phase on Digital Microvascular Haemodynamics
Authors: Tooke J. E. , Tindall H. , McNicol G. P.
Published: August 2015

1. Nailfold capillary pressure, digital blood flow and skin temperature have been measured on days 7, 14, 21 and 28 of the menstrual cycle in 10 women on a combined oral contraceptive pill and 10 control subjects with normal menstrual cycles.

2. Capillary pressure and digital blood flow were statistically significantly higher in the group taking an oral contraceptive pill compared with control subjects.

3. Capillary pressure values for women failed to show the same positive correlation with skin temperature previously described in normal men.

4. The results are interpreted as evidence for a powerful modulating influence of sex steroids on digital microvascular haemodynamics.
Urinary Ligandin and Glutathione-S-Transferase in Gentamicin-Induced Nephrotoxicity in the Rat
Authors: Feinfeld D. A. , Fleischner G. M. , Arias I. M.
Published: August 2015

1. Eight rats developed detectable glutathione-S-transferase activity in their urine after three daily injections of toxic doses of gentamicin.

2. Seven of the eight rats had immunodetectable ligandin in their urine at this time.

3. The level of enzyme activity correlated well with the degree of elevation of serum creatinine.

4. This confirms ligandinuria and urinary glutathione-S-transferase as markers of acute renal proximal tubular injury.
Total-Body Protein Turnover in Human Premature Neonates: Effects of Birth Weight, Intra-Uterine Nutritional Status and Diet
Authors: Pencharz P. B. , Masson M. , Desgranges F. , Papageorgiou A.
Published: August 2015

1. The effects of birth weight, intra-uterine nutritional status and protein and energy intake on whole-body protein turnover, and skeletal muscle protein breakdown were examined in 40 premature infants.

2. Total-body nitrogen flux was 26% higher in the small-for-gestational-age compared with appropriate-for-gestation-age infants; similarly, whole-body protein synthesis and breakdown were increased by 26 and 35% respectively (P < 0.01).

3. The lower-birth-weight neonates (< 1500 g) had higher rates of skeletal muscle protein breakdown; 1.23 ± 1.12 g day−1 kg−1, as compared with 0.54 ± 0.28 g for the high-birth-weight group (P < 0.05).

4. Protein intake was inversely correlated with the fraction of nitrogen flux coming from endogenous protein breakdown (P < 0.05) and with skeletal muscle protein breakdown (P < 0.05). There were no significant relationships found between energy intake and the parameters of protein metabolism.

5. On the basis of the turnover data, evidence is presented that the protein requirements for milk-protein fed premature neonates is less than 4.3 g day−1 kg−1.
Effects of a Meal on Plasma Clearance of [14C]Glycocholic Acid and Indocyanine Green in Man
Authors: Marigold J. H. , Gilmore I. T. , Thompson R. P. H.
Published: August 2015

1. The fasting plasma disappearance curve of [14C]glycocholic acid after intravenous injection was compared in nine normal subjects with that obtained 100 min after a standard liquid test meal.

2. Plasma disappearance curves of indocyanine green were determined in 13 normal subjects under the same conditions.

3. Plasma clearances were significantly increased after the meal for both [14C]glycocholic acid (median 455 ml min−1 m−2, range 376–672 increased to 704, 528–1968; P < 0.01) and indocyanine green (359, 227–473 increased to 435, 358–985; P < 0.01).

4. Median initial volume of distribution was unaltered, but in four subjects it was greatly increased after the meal, although no alteration in plasma volume, measured with Evans blue dye, was observed.

5. The increased postprandial plasma clearance of glycocholic acid is probably due to an increase in liver blood flow, and suggests that in health this part of the enterohepatic circulation of bile acids also varies with meals.
Effect of pH on Muscle Glycolysis during Exercise
Authors: Sutton J. R. , Jones N. L. , Toews C. J.
Published: August 2015

1. Five males were studied on three occasions, after oral administration of CaCO3 (control), NH4Cl (acidosis) and NaHCO3 (alkalosis), in a dose of 0.3 g/kg, taken over a 3 h period at rest. The subjects then exercised on a cycle ergometer for 20 min at 33% maximal oxygen uptake (Vo2 max.), followed by 20 min at 66% and at 95% Vo2 max. until exhaustion.

2. Endurance at 95% Vo2 max. was longest with alkalosis (5.44 ± 1.05 min), shortest with acidosis (3.13 ± 0.97 min) and intermediate in the control study (4.56 ± 1.31 min); venous blood pH at exhaustion was 7.33 ± 0.02 (mean ±1 sem), 7.13 ± 0.02 and 7.26 ± 0.02 respectively.

3. Concentrations of plasma lactate at exhaustion were 7.10 ± 0.8 mmol/l 4.0 ± 0.5 and 7.9 ± 0.9 mmol/l in the control, acidosis and alkalosis studies respectively.

4. Muscle lactate increased most from rest to exhaustion with alkalosis to 17.1 ± 2.5 μmol/g and least with acidosis to 12.2 ± 1.4 μmol/g. Muscle glycogen depletion was comparable in control and alkalosis studies.

5. The lower plasma lactate concentration during exercise in acidosis compared with control and alkalosis appears to be due to an inhibition of muscle glycolysis combined with a reduction in lactate efflux from muscle.
Water and Electrolyte Composition of Urine and Ileal Fluid and Its Relationship to Renin and Aldosterone during Dietary Sodium Deprivation in Patients with Ileostomies
Authors: Moss S. , Gordon D. , Forsling Mary L. , Peart W. S. , James V. H. T. , Roddis Shirley A.
Published: August 2015

1. The electrolyte and water composition of urine and ileal fluid was studied in six patients with ileostomies during dietary sodium deprivation and at the same time measurements were made of plasma renin activity, plasma aldosterone concentration, renal aldosterone excretion and plasma arginine vasopressin concentration.

2. In each subject there was a reduction in renal sodium excretion within 24 h of sodium deprivation. Significant rises in plasma renin activity, plasma aldosterone concentration and renal aldosterone excretion occurred by day 2 of sodium deprivation.

3. There was only modest conservation of sodium by the ileum during sodium deprivation, but ileal potassium concentration rose progressively. There were significant associations between ileal-fluid potassium concentration and plasma renin activity or renal aldosterone excretion.

4. Under the conditions of the experiment a diuresis was observed in each subject during dietary sodium deprivation. This did not appear to depend on changes in plasma arginine vasopressin concentration.
Brain Lesions in the Paraventricular Nuclei and Catecholaminergic Neurons Minimize Salt Hypertension in Dahl Salt-Sensitive Rats
Authors: Goto Atsuo , Ikeda Toshio , Tobian Louis , Iwai Junichi , Johnson Mary A.
Published: August 2015

1. The rise in blood pressure in Dahl salt-sensitive rats that received intracerebroventricular 6-hydroxydopamine was almost half that of the control rats throughout 20 weeks of high (8%) NaCl feeding.

2. The rise in bood pressure in Dahl salt-sensitive rats with bilateral complete electrolytic lesions of the paraventricular nuclei was almost half that of the control rats during 12 weeks of high (8%) NaCl feeding.

3. The bilateral complete electrolytic lesions of the suprachiasmatic nuclei enhanced the development of NaCl hypertension in Dahl salt-sensitive rats.

4. These results show that NaCl-induced hypertension in Dahl salt-sensitive rats requires the integrity of the central nervous system catecholaminergic neurones and the paraventricular nuclei for its full expression.
Increased Cutaneous Vasoreactivity to Cold in Anorexia Nervosa
Authors: Luck P. , Wakeling A.
Published: August 2015

1. Hand blood flows in healthy young men and women and in patients with anorexia nervosa were measured in a warm environment by using venous occlusion plethysmography. The mean core temperature of each of the three groups was similar, but the male control subjects and the anorexic patients had significantly higher peripheral blood flows than the female control subjects.

2. Blood flows were determined in the hand after 6 min localized cooling of it at varying temperatures. The female control subjects and the majority of the anorexic patients had blood flows which were similar for a given temperature, and lay between the higher values of the male control subjects and the low values of the remaining anorexic patients.

3. Those patients whose vascular responses to cold were exaggerated were characterized clinically by severe and persistent signs of ischaemia of the extremities during subsequent rehabilitation, unlike the majority of patients whose peripheral circulation rapidly improved.

4. Cold thermal stimuli evoked marked falls in blood flow of the contralateral (non-cooled) hand in the male and female control subjects, but these responses were attenuated or absent in the anorexic patients. An altered set-point for vasomotor thermoregulation in anorexia nervosa could explain these findings.

5. Plasma and whole-blood viscosity and erythrocyte deformability measured in a sample of the patients studied were similar to the values obtained from a sample of the control subjects.

6. It was concluded that the cutaneous vasoconstrictor responses to cold in the majority of the anorexic patients studied were quantitatively normal. The mechanism of the response, however, was different in that the vessels themselves were unusually reactive to cold. Increased cuteneous vasoreactivity to cold could contribute to the severe peripheral hypoperfusion observed in some anorexic patients.
Chemosensitivity in Patients with Diabetic Neuropathy
Authors: Homma Ikuo , Kageyama Shigeru , Nagai Takeshi , Taniguchi Ikuo , Sakai Toshio , Abé Masakazu
Published: August 2015

1. By using the rebreathing method, ventilatory responses to inhaled CO2 were studied in patients with diabetic neuropathy.

2. Their general respiratory functions including vital capacity (VC) and forced expiratory volume in 1 s (FEV1.0) were within normal ranges and ventilatory responses to CO2 in the range 5.32-5.99 kPa were not significantly different between patients and normal subjects. However, ventilation in the patients was significantly less than that in normal subjects when the alveolar partial pressure of CO2 (Paco2) was above 6.65 kPa.

3. The slope of the CO2 response curves obtained during hyperoxic rebreathing was significantly less in the patients than in the normal subjects. In the patients CO2 response curves with 15% (v/v) O2 were either the same or had lower slopes than those measured with 100% O2.

4. The results suggest that both peripheral and central chemosensitivity, including the activity of the respiratory centre, are reduced in patients with diabetic neuropathy.
Effect of a Long-Acting Octapeptide Analogue of Somatostatin on Growth Hormone and Pancreatic and Gastrointestinal Hormones in Man
Authors: Barnes A. J. , Long R. G. , Adrian T. E. , Vale W. , Brown M. R. , Rivier J. E. , Hanley J. , Ghatei M. A. , Sarson D. L. , Bloom S. R.
Published: August 2015

1. The biochemical specificity and duration of action of a single 5 mg subcutaneous dose of des-AA1,2,4,5,12,13-d-Trp8-somatostatin were evaluated in eight patients with symptomatic pancreatic endocrine tumours.

2. There was a reduction by more than 50% for at least 10 h in plasma concentrations of growth hormone, glucagon, gastrin and motilin and for 4–5 h in plasma insulin, pancreatic polypeptide, gastric inhibitory polypeptide and enteroglucagon.

3. This study shows that this octapeptide analogue of somatostatin, like somatostatin itself, lacks specificity in the hormones it suppresses. However, its prolonged duration of action against several hormones when given subcutaneously suggests that it may be of therapeutic use in a number of disease states where excessive plasma concentrations of one or more of these hormones occur.
Isoprenaline-Induced Secretion of Active and Inactive Renin in Anaesthetized Rabbits and by Kidney Cortex Slices
Authors: Richards H. K. , Noble A. R. , Munday K. A.
Published: August 2015

1. The effect of the β-adrenoceptor agonist isoprenaline on the secretion of active and inactive renin was investigated in two preparations.

2. in ten urethane-anaesthetized rabbits isoprenaline, given as a renal artery infusion, had relatively minor effects on renal sodium excretion (increased) and systemic arterial blood pressure (decreased). Urine volume, potassium excretion, creatinine clearance and serum electrolytes were all unchanged. Plasma active and inactive renin both increased immediately and returned to basal values after ceasing the isoprenaline infusion.

3. No significant changes in either plasma renin activity or renal function were observed in a group of ten control animals.

4. The magnitude of the isoprenaline-induced changes in plasma active renin was similar to that in a previous study of frusemide diuresis, but the time course was quite different. Inactive renin disappeared from plasma during frusemide diuresis.

5. Renin release by rabbit kidney cortex slices was also studied. Isoprenaline, added to the incubation medium, caused a dose-related increase in active renin secretion, but inactive renin release remained unchanged. This is in marked constrast to a previous study where reducing [Na+] increased active renin and inhibited inactive renin output.

6. These data support our previous suggestion that activation of inactive renin is regulated by a sodium-sensitive intrarenal mechanism.
Potassium Citrate Feeding Protects against Nephron Loss in Severe Sodium Chloride Hypertension in Rats
Authors: Ganguli M. , Tobian L. , Iwai J. , Johnson Mary Ann
Published: August 2015

1. Potassium citrate did not significantly increase plasma flow to the renal papilla in normotensive Dahl R rats on either low or high NaCl diets. Similarly, potassium citrate did not significantly increase papillary plasma flow in mildly hypertensive Dahl S rats on low NaCl diets. Thus potassium citrate feeding did not ordinarily alter papillary plasma flow.

2. When S rats were fed on a high (4%) NaCl diet for 24 weeks, they became severely hypertensive and developed nephrosclerosis with nephron loss. This accounted for the significant reduction in papillary plasma flow in S rats on 4% high NaCl diet with no potassium supplementation.

3. When S rats on high NaCl diet were given a supplement of KCl, they still developed severe hypertension and almost the same fall in papillary plasma flow, suggesting a similar degree of nephron loss from nephrosclerosis.

4. However, when S rats on high NaCl diet were given a supplement of potassium citrate, they still developed the same severe hypertension but, in contrast, they did not have a decrease in papillary plasma flow. This actually increased to 7% higher than in comparable S rats eating the low NaCl diet. Moreover, S rats receiving potassium citrate supplements in their high NaCl diet had a papillary plasma flow which was 34% higher than that of S rats receiving no potassium supplement in the high NaCl diet (P < 0.005) and was 19% higher than that of S rats receiving KCl supplements in the high NaCl diet (P < 0.04). This occurred even though the rats receiving potassium citrate were severely hypertensive.

5. Thus potassium citrate feeding protected against nephron loss from nephrosclerosis during severe NaCl-induced hypertension, whereas KCl feeding did not provide such protection.
Homocysteine in the Plasma of Renal Transplant Recipients: Effects of Cofactors for Methionine Metabolism
Authors: Wilcken D. E. L. , Gupta Vatsala J. , Betts A. K.
Published: August 2015

1. Homocysteine which is formed during the metabolism of methionine is readily oxidized and is measured by the amino acid analyser as cysteine—homocysteine mixed disulphide and homocystine. We measured plasma amino acid concentrations after an overnight fast in 27 stable long-term renal transplant recipients and 25 age-and sex-matched normal subjects with particular emphasis on sulphur-containing amino acids.

2. Plasma cysteine—homocysteine mixed disulphide was increased in the patients (mean 6.0 ± sd 3.2 μmol/l; normal 3.1 ± 0.9 μmol/l, P < 0.001) and homocystine was detectable in low concentration (< 1.0 μmol/l) in 24; the elevation in cysteine—homocysteine was related to serum creatinine (r = 0.60, P < 0.002). Cystine was also increased (91.6 ± 29.3 μmol/l; normal subjects 64.0 ± 16.7 μmol/l, P < 0.001), but methionine concentrations were normal.

3. When pyridoxine, folic acid and vitamin B12, cofactors for homocysteine metabolism, were administered sequentially to 11 arbitrarily selected transplant recipients cysteine—homocysteine decreased from 7.3 ± 2.1 to 4.3 ± 0.8 μmol/l (P < 0.001) and homocystine became undetectable. the response coincided with the giving of folic acid and occurred without alteration in serum creatinine and with normal serum folate and vitamin B12 concentrations.

4. in eight patients in whom pretreatment erythrocyte folate was measured, folic acid therapy reduced cysteine—homocysteine from 9.0 ± 3.1 to 5.4 ± 1.6 μmol/l over a 4 week period (P < 0.001), the largest response being in the one patient with subnormal erythrocyte folate; values were in the low-normal or normal range in the other seven.

5. We conclude that plasma homocysteine is increased in renal transplant recipients when serum creatinine is only moderately elevated and that the homocysteine concentrations are decreased by treatment with folic acid, suggesting that both reduced homocysteine excretion and relative shortages of folic acid are responsible.
Effect of Strain and Sex on the Induction of Hyperalbuminaemic Proteinuria in the Rat
Authors: Lawrence Gillian M. , Brewer D. B.
Published: August 2015

1. Male and female rats representing the four inbred strains [Wistar (albino), Sprague-Dawley (albino), DA (brown) and PVG (hooded) rats] were injected intraperitoneally with 4.5-5.5 mg of Cohn V bovine albumin day−1 g−1 body wt.

2. the levels of proteinuria and glomerular ultrastructural damage induced in response to hyperalbuminaemia varied widely with the strain and sex of rat studied, being highest in the male Wistar and lowest in the male Sprague-Dawley.

3. A survey of the relevant literature shows that these results probably explain most of the reported inconsistencies and anomalies concerning the effect of parenteral protein injection in the rat.
Role of Vagal Airway Reflexes in Control of Ventilation in Pulmonary Fibrosis
Authors: Savoy J. , Dhingra S. , Anthonisen N. R.
Published: August 2015

1. in 10 patients with pulmonary fibrosis and in seven control subjects, we measured the pressure at the mouth 0.1 s after onset of an inspiration against occluded airway (P0.1), minute ventilation (VI), breathing frequency (fr), tidal volume (VT), inspiratory duration (Tl) and calculated the mean inspiratory flow (VT/Tl) and the fraction of the breath cycle devoted to inspiration (Tl/Ttot.). in the patients measurements were made at normal arterial oxygen saturations (Sao2), before and after lignocaine airway anaesthesia.

2. Efficacy of airway anaesthesia was tested by the cough response to citric acid inhalation.

3. in pulmonary fibrosis P0.1, f1 and VT/Tl were greater than in the control subjects, VT and Tl, were smaller and Tl/Ttot. and VI were not different.

4. Effective airway anaesthesia did not modify P0.1 and breathing pattern parameters observed in pulmonary fibrosis.

5. These results suggest that airway receptors do not contribute to a major extent to the control of breathing in pulmonary fibrosis.
The Relationship between Plasma Lithium and the Renal Responsiveness to Arginine Vasopressin in Man
Authors: Penney M. D. , Hullin R. P. , Srinivasan D. P. , Morgan D. B.
Published: August 2015

1. Arginine vasopressin (AVP) was measured in morning samples of urine from 58 patients treated with lithium for unipolar or bipolar affective disorders and from 25 healthy control subjects.

2. the AVP excretion rate was increased in the patients treated with lithium and was related to the plasma lithium concentration. the increase in AVP excretion is the result of a renal resistance to AVP so that what has been observed is an effect of lithium in vivo related to its plasma level over the therapeutic range.
Mechanisms of Structural Vascular Changes in Genetic Hypertension: Analyses on Cultured Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats
Authors: Yamori Yukio , Igawa Takehiro , Kanbe Toshimi , Kihara Masahiro , Nara Yasuo , Horie Ryoichi
Published: August 2015

1. The basic mechanism underlying the structural vascular changes occurring in hypertension was studied in cultured aortic smooth muscle cells (SMC) obtained by an explant method from spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) and compared with that in normotensive Wistar—Kyoto (WKY) rats.

2. The growth rate of SMC from SHR and SHRSP at the age of 2.5–11 months was greater than that of SMC from WKY rats even after repeated passages.

3. [3H]Thymidine and [14C]leucine incorporation, and ornithine decarboxylase (ODC) activity of SMC were increased in SHR and SHRSP in comparison with WKY rats.

4. The application of isoprenaline but not noradrenaline to the culture media increased ODC activity acutely in SMC from WKY rats and this increase was blocked by propranolol.

5. These results indicate that SMC from SHR and SHRSP are more prone to proliferate than those from WKY rats and that a β-adrenergic neurohumoral mechanism accelerates SMC growth independently of blood pressure.
Increased Peripheral Release of Noradrenaline and Uptake of Adrenaline in Essential Hypertension?
Authors: Kjeldsen S. E. , Flaaten B. , Eide I. , Helgeland A. , Leren P.
Published: August 2015

1. Twenty middle-aged men with untreated sustained essential hypertension for more than 5 years and 19 comparable normotensive controls were investigated. Both groups were derived from The Oslo Study, where they had served as control hypertensive and normotensive subjects.

2. Supine venous and arterial plasma catecholamines were increased in the hypertensive subjects compared with the normotensive subjects. The mean arterial—venous difference for adrenaline in the hypertensive (0.45 ± se 0.08 nmol/l) was increased compared with the normotensive group (0.27 ± 0.03 nmol/l, P < 0.05). Similarly, the venous-arterial difference for noradrenaline was increased in the hypertensive (0.29 ± 0.13 nmol/l, P < 0.05) compared with the normotensive group (−0.07 ± 0.11 nmol/l).

3. The results are consistent with an increased release of adrenaline from the adrenal medulla and noradrenaline from the peripheral vascular beds (forearm) in essential hypertension. The increased arterial-venous difference for adrenaline in the hypertensive group also suggests an increased uptake of adrenaline in the peripheral vascular beds.
Aggression-Provoked Renin Release from An Unknown Source in Male Mice
Authors: Poulsen K. , Pedersen E. B.
Published: August 2015

1. An 800-fold increase in plasma renin occurs after aggressive behaviour in male mice without kidneys and submaxillary glands.

2. The aggression-provoked renin fulfils all the criteria so far studied for being identical with renin.

3. It is an acid proteinase which generates angiotensin I with the same Km and specific enzymatic activity as pure submaxillary renin and normal plasma renin.

4. It is immunologically identical with submaxillary renin in the direct renin assay and in crossed immunoelectrophoresis.

5. It is present in plasma as fully enzymatically active 40 000-mol. wt. renin.

6. It is not likely that it arises from an inactive precursor or binding protein in plasma, since there is no inactive renin present and the high-molecular-weight forms of renin are also present after the fighting.

7. None of many organs so far studied can account for the release.

8. Synthesis of renin de novo during fighting is not likely since it is released also after blockade in vivo of protein synthesis.

9. Origin of the renin is unknown.