bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolism of Intravenously Administered Dipeptides in Rats: Effects on Amino Acid Pools, Glucose Concentration and Insulin and Glucagon Secretion
Authors: Adibi S. A. , Krzysik B. A. , Drash A. L.
Published: August 2015

1. Studies were performed to investigate the metabolic fate of dipeptides when administered intravenously in rats. Glycyl-leucine, glycylglycine or glycylsarcosine was injected into the jugular vein. The plasma disappearance rate after the peak plasma concentrations was most rapid for glycyl-leucine and least rapid for glycylsarcosine.

2. During urine collection for 40 min, trace amounts of glycyl-leucine and glycylglycine and 13% of the injected glycylsarcosine were excreted.

3. Neither glycylglycine nor glycyl-leucine was detected in the liver, muscle, intestinal mucosa or renal cortex, but concentrations of glycine or leucine, or both, in these tissues were increased after each injection. In contrast, glycylsarcosine was recovered in all these tissues with concentrations in the renal cortex being far greater than in any other tissue, but sarcosine was found only in the renal cortex and intestinal mucosa.

4. The changes in plasma concentrations of free amino acids, glucose and glucagon, and tissue concentrations of free amino acids, were similar after the intravenous administration of glycyl-leucine and an equimolar mixture of free glycine and leucine. However, the amount of insulin secreted during the 40 min after glycyl-leucine injection was 1·6 times that produced after the injection of the corresponding amino acid mixture.

5. Results show that, within the present experimental conditions, the intravenous administration of dipeptides is as effective as that of the corresponding free amino acids in enriching the tissue pools of amino acids. It is suggested that efficient hydrolysis by cellular enzymes prohibits accumulation of intact dipeptides in body tissues.
Accentuation of Ethanol-Induced Fatty Liver by Phenobarbitone
Authors: Marsh A. R. , Fraser H. S. , Breckenridge A. , Lewis B. , Thompson G. R.
Published: August 2015

1. Four groups of rats received a liquid formula diet, given alone (control), or supplemented with either ethanol or phenobarbitone, or both together.

2. The ethanol-treated group showed a fall in plasma triglyceride and a rise in liver triglyceride, as compared with the control rats.

3. The phenobarbitone-treated group showed a marked rise in plasma triglyceride but not in liver triglyceride.

4. The group receiving both ethanol and phenobarbitone also showed a rise in plasma triglyceride, but this was accompanied by a striking increase in liver triglyceride.

5. These results suggest that ethanol and phenobarbitone each stimulate triglyceride synthesis but that in addition ethanol has an inhibitory effect on hepatic triglyceride secretion.
Human Hepatic δ-Aminolaevulinate Synthase: Requirement of an Exogenous System for Succinyl-Coenzyme a Generation to Demonstrate Increased Activity in Cirrhotic and Anticonvulsant-Treated Subjects
Authors: Bonkowsky H. L. , Pomeroy Joanne S.
Published: August 2015

1. We have studied activity of δ-aminolaevulinate synthase in needle liver biopsy specimens obtained from 12 human cirrhotic subjects, five subjects who had ingested anticonvulsants and from control subjects. Liver iron concentrations and quantitative urinary excretions of porphyrins plus their precursors were also determined.

2. In liver homogenates from subjects of each group, addition of an exogenous system for generation of succinyl-coenzyme A (CoA), including succinic thiokinase, resulted in appreciable enhancement of activity beyond that obtained without this system.

3. Mean activities for δ-aminolaevulinate synthase were not significantly different among patient groups when assayed without the exogenous succinyl-CoA-generating system, but liver homogenates from cirrhotic patients and subjects ingesting anticonvulsants had significantly higher activities than control subjects in the presence of the succinyl-CoA-generating system.

4. Although mean liver iron concentration in the cirrhotic group was slightly higher than in control subjects, and in control subjects there was some correlation between liver iron concentration and activity of δ-aminolaevulinate synthase, variations in this activity could not be accounted for solely on the basis of chronic hepatic deposition. Nor were these variations ascribable to differences among subjects in ingestion of ethanol before biopsy or severity of hepatic inflammation as judged biochemically and histologically.

5. Cirrhotic subjects excreted more uro- and copro-porphyrin than control subjects, whereas subjects ingesting anticonvulsants excreted more δ-aminolaevulinic acid and porphobilinogen than control subjects. However, these increases were small and not sufficient to account for all the increased δ-aminolaevulinic acid which potentially could have been formed by these subjects.

6. These considerations raise the possibilities that, in vivo: (a) rate of human hepatic synthesis of δ-aminolaevulinic acid is modulated by the supply of succinyl-CoA; (b) the rate of hepatic synthesis of haem is increased in cirrhotic patients and subjects ingesting anticonvulsants; (c) other important routes exist for disposition of haem precursors in these subjects, besides utilization for haem synthesis.
Plasma Calcitonin in Chronic Renal Failure: Relation to other Factors of Importance in Bivalent Ion Metabolism
Authors: Shainkin-Kestenbaum R. , Lerman R. , Reuben A. , Berlyne G. M.
Published: August 2015

1. Plasma concentrations of human calcitonin were measured in groups of patients with chronic renal failure, treated either conservatively or by haemodialysis, and compared with a normal group of persons.

2. Plasma calcitonin was statistically significantly elevated in both groups with renal failure.

3. When the data from the three groups were pooled, plasma calcitonin was found to be inversely correlated with total calcium and directly correlated with plasma creatinine.
Effect of Thyrotoxicosis on the Reflex Hypoxic Respiratory Drive
Authors: Stockley R. A. , Bishop J. M.
Published: August 2015

1. Oxygen breath tests were performed in seven patients with thyrotoxicosis. The inspired air was replaced by oxygen without their knowledge for 20 s and the fall in ventilation was recorded.

2. Ventilation fell significantly in all the patients within 40 s. The mean fall was 21·1% (se ± 1·7) below the control value.

3. β-Adrenoreceptor blockade with propranolol had little effect on this reduction in ventilation. The fall observed in five patients receiving propranolol was 19·6% (se ± 1·0).

4. After definitive treatment, which rendered the patients euthyroid, the observed reduction in ventilation after breathing oxygen was significantly less at 11·7% (se ± 1·2).

5. It is concluded that patients with thyrotoxicosis have an increased resting reflex hypoxic drive to respiration, when compared with the euthyroid state, and this is unaffected by β-adrenoreceptor blockade.
Respiratory Muscle Fatigue: A Cause of Respiratory Failure?
Authors: Macklem P. T. , Roussos C. S.
Published: August 2015

1. The question whether respiratory muscle fatigue ever causes respiratory failure is over 40 years old, but we still have no definitive answer to this question. Skeletal muscle fatigue occurs when the rate of energy consumption of themu scle is greater than the energy supplied, so that energy stores are utilized and eventually become depleted.

2. Five factors which are important in the development of muscle fatigue (a, the tension developed by the muscle; b, the maximum tension the muscle can develop; c, the energy stored within the muscle; d, the energy supplied to the muscle; e, the efficiency of the muscle). These can be affected in many diseases, so disposing to fatigue, thus respiratory muscle fatigue is likely to be a common occurrence.

3. Respiratory muscle fatigue can in principle easily be diagnosed at the bedside by application of a simple electromyographic technique used to detect fatigue in other skeletal muscles.
Arrested Bone Growth and Mineral Maturation in Sub-Totally Nephrectomized Rats
Authors: Letteri J. M. , Biltz R. M. , Ellis K. J. , Martino A. , Yasumura S. , Brook D. , Cohn S. H. , Pellegrino E. D.
Published: August 2015

1. Young, sub-totally nephrectomized rats were used to study the altered mineral metabolism of renal failure and its effects on bone growth and mineral maturation.

2. Rats killed at 4 weeks after sub-total nephrectomy demonstrated less bone growth than the age-matched control animals. These differences diminished in successive 4 week periods and were not significant at 12 weeks after operation.

3. The major differences in bone mineral composition between the uraemic rats and the control rats were: (i) lower CO23;− concentrations, and (ii) higher PO34;− and HPO24;− concentrations.

4. These differences are consistent with the view that bone mineral matures by the conversion of an acidic calcium phosphate precursor into a carbonate-containing apatite, an essential feature of this conversion being the replacement of PO34;− or HPO24;− by CO23;−. By this definition, uraemic rats at 4 weeks after operation contained more immature bone mineral than the control rats. These differences corresponded to the changes in bone weight, and were similarly unaffected at 12 weeks after operation.

5. The effects observed were transient and were reversed as renal function recovered. If renal failure is sustained, however, as in patients with end-stage renal disease, the maturation defect could become a feature of renal bone disease. Specific aetiological factors are discussed, but not identified.
Urine Electrolyte Response to 18-Hydroxy-11-Deoxycorticosterone in Normal Man
Authors: Nicholls M. G. , Fraser R. , Hay G. , Mason P. , Torsney B.
Published: August 2015

1. To assess whether the adrenal corticosteroid 18-hydroxy-11-deoxycorticosterone [18-(OH)DOC] affects urine electrolyte excretion in normal man, seven male volunteers received 120 μg (353 nmol) intravenously in 1 h. This was compared with glucose (50 g/l; control) and aldosterone (80 μg, 222 nmol) infusions in the same subjects.

2. A definite though weak antinatriuretic response to 18-(OH)DOC was observed, whereas urine potassium excretion was not altered. Aldosterone increased urine potassium excretion and reduced sodium output. Urine pH was lowered by both corticosteroids, aldosterone in general having a more marked effect. Urine volume was not altered by 18-(OH)DOC.

3. Plasma concentrations of 18-(OH)DOC and aldosterone rose approximately tenfold during their respective infusions. Compared with that of aldosterone, the metabolic clearance rate of 18-(OH)DOC was slower and its plasma half-life was longer.

4. We have been able to demonstrate that 18-(OH)DOC has a definite, albeit weak antinatriuretic action in normal man, but whether or not this corticosteroid is capable of elevating the blood pressure in man remains to be shown.
Collagen of Dupuytren's Disease
Authors: Bailey A. J. , Sims T. J. , Gabbiani G. , Bazin S. , Lelous M.
Published: August 2015

1. In contrast to collagen from the aponeurosis of normal adult subjects, the nodules, contractures and apparently unaffected aponeurosis from patients with Dupuytren's disease contained substantial amounts of type III collagen.

2. The presence of type III collagen supports the previous proposal that the initial response to injury is the synthesis of an increased proportion of this form of collagen. The increased amounts in the apparently unaffected aponeurosis indicate the disease is not strictly focal but more systemic than is usually considered.
The Effect of Adrenaline-Induced Endogenous Lipolysis upon the Mechanical and Metabolic Performance of Ischaemically Perfused Rat Hearts
Authors: Brownsey R. W. , Brunt R. V.
Published: August 2015

1. The isolated perfused non-working rat heart, subjected to low coronary flow, has been used to study the effects of myocardial ischaemia on both the mechanical and metabolic performance of the heart.

2. In this preparation, adrenaline initially increased developed tension and heart rate, followed shortly thereafter by marked deterioration in mechanical performance to levels below those observed in the control state. These latter responses occurred simultaneously with stimulation of endogenous myocardial lipolysis. The rate of release of non-esterified fatty acids was positively correlated with both the decline in developed tension and the rise in resting tension.

3. The anti-lipolytic agent nicotinic acid had no effect on the initial mechanical responses of the heart to adrenaline but prolonged the period of enhanced tension development after adrenaline and reduced the degree of later deterioration in performance, in addition to blocking lipolytic stimulation.

4. Hearts from rats fed on a diet rich in animal fat contained larger triglyceride reserves and exhibited greater rates of non-catecholamine-stimulated lipolysis than hearts from normally fed rats. During ischaemic perfusion such hearts showed a more marked rise in resting tension and decline in heart rate than hearts from normally fed animals. Such hearts also had an increased incidence of arrhythmias and a slight reduction in developed tension. The initial responses of these hearts from fat-fed rats to adrenaline were also depressed as compared with normal hearts. Hearts from fat-fed rats showed a greater tendency to deteriorate in performance after adrenaline, particularly with falling heart rates and the onset of ventricular fibrillation.

5. We suggest that these results indicate that myocardial lipolysis makes a significant contribution to the adrenaline-induced deterioration in performance seen in these ischaemically perfused rat hearts.
Changes in the Proportions of Plasma Insulin, Proinsulin and a Higher-Molecular-Weight Insulin during Pre- and Post-Operative Glucose-Infusion Tests
Authors: Mangnall D. , Giddings A. E. B. , Lafferty H. H. , Clark R. G.
Published: August 2015

1. Glucose-infusion tests were performed on patients admitted for elective upper abdominal surgery 1 day before and 1 day after operation. In addition to insulin and proinsulin, a third immunoreactive insulin species of mol. wt. 20 000–30 000 was detected in plasma from two patients. The heterogeneity of plasma immunoreactive insulin (IRI) and the need to consider the effects of all forms, including proinsulin and the high-molecular-weight species, is emphasized.

2. During preoperative glucose infusions there was an increase in the percentage of the total plasma IRI present as high-molecular-weight forms (i.e. proinsulin plus the species of mol. wt. 20 000–30 000) from 3·9% to 10·8%. On the first postoperative morning all patients showed an increase in the amounts of the heavier IRI types, which accounted for 13·9% of the total plasma IRI.

3. The changes in insulin and proinsulin are consistent with the release from the pancreas of an insulin/proinsulin mixture of constant proportions, and the longer circulating half-life of proinsulin.

4. Increases in the amounts of high-molecular-weight IRI species after surgery may have a partial role in the development of insulin resistance but are probably not a major determinant of the insulin-resistant state.
Ventilatory Responses to Exercise and to Carbon Dioxide in Mitral Stenosis before and after Valvulotomy: Causes of Tachypnoea
Authors: Reed J. W. , Ablett M. , Cotes J. E.
Published: August 2015

1. The ventilation and cardiac frequency during progressive exercise and the respiratory responses to breathing carbon dioxide have been measured in 33 female patients with mitral stenosis and in 31 control subjects. Compared with the control subjects, the patients' exercise ventilation and cardiac frequency were increased; the exercise tidal volume at standard minute volume, the vital capacity and the ventilatory response to carbon dioxide were reduced. The extent to which the standardized tidal volume was lower during exercise than during breathing carbon dioxide was correlated with the severity of the stenosis, as gauged by the increase in exercise cardiac frequency above the level predicted from anthropometric measurements.

2. Twenty patients were studied postoperatively. In the 12 who showed clinical improvement the exercise ventilation and cardiac frequency were reduced and the exercise tidal volume at a given minute ventilation was increased. The latter change occurred despite a reduction in vital capacity, which was probably a residual effect of thoractomy. There was no significant change in the response to breathing carbon dioxide. No material change in function was observed in the patients whose condition was not improved by the operation.

3. It is suggested that in mitral stenosis the tachypnoea which occurs during exercise, whilst mainly a mechanical consequence of the reduced vital, capacity, is also partly due to pulmonary congestion stimulating intrapulmonary receptors.
The Relationship of Urinary Kallikrein Activity to Renal Salt and Water Excretion
Authors: Levy S. B. , Frigon R. P. , Stone R. A.
Published: August 2015

1. We measured urinary kallikrein (kininogenin) excretion in black and white normotensive subjects during a variety of manipulations of salt and water balance.

2. A large intravenous saline load administered while the subjects were on an unrestricted sodium diet did not significantly change urinary kallikrein activity in either racial group.

3. After several days of dietary sodium restriction both racial groups increased their urinary kallikrein activity. An intravenous water load given then further increased urinary kallikrein activity. White subjects were studied for an additional 24 h period, and urinary kallikrein activity returned to pre-water load values, indicating that the excretion of a water load in sodium-depleted subjects is associated with an increase in kallikrein excretion.

4. Black subjects excreted less kallikrein in the urine than white subjects during the initial 24 h periods of unrestricted dietary sodium intake, but there were no other significant racial differences during the other experimental conditions.
Uptake by Bone of Pyrophosphate, Diphosphonates and their Technetium Derivatives
Authors: Bisaz Sylvia , Jung A. , Fleisch H.
Published: August 2015

1. The uptake of inorganic pyrophosphate (PPi) from blood to bone was investigated in the rat in vivo.

2. PPi is taken up by the bone, where it appears both as PPi and as inorganic orthophosphate (Pi). The latter is due at least partly to local hydrolysis.

3. The fraction of injected PPi taken up by bone, measured as total Pi, was in the same range as that of technetium—tin—PPi, diphosphonates, technetium—tin—ethane-1-hydroxy-1,1-diphosphonate and Pi, but lower than that of calcium.

4. The plasma half-life of PPi is in the same order of magnitude as that of technetium—tin—PPi, diphosphonates, technetium—tin—ethane-1-hydroxy-1,1-diphosphonate, Pi and calcium.

5. PPi, diphosphonates and their technetium complexes are only partly ultrafiltrable in plasma.

6. It appears that the technetium complexes behave in a similar fashion to free PPi or diphosphonate.
Metabolic and Body Temperature Changes during Exercise in Hyperthyroid Patients
Authors: Nazar K. , Chwalbińska-Moneta J. , MacHalla J. , Kaciuba-UściłKo H.
Published: August 2015

1. Body temperature, blood glucose, lactate, plasma free fatty acid and noradrenaline responses to exercise were studied in hyperthyroid patients during 30 min exercise on a bicycle ergometer at a work load producing a heart rate of approximately 135–140 beats/min. The results were compared with those obtained in healthy subjects exercising at work loads comparable in terms of oxygen uptake.

2. External auditory canal temperature at rest was 0·5°C higher in hyperthyroid patients than in control subjects but the exercise-induced increases in body temperature were similar in both groups.

3. Pre-exercise blood glucose concentration was higher in the thyrotoxic patients than in normal subjects. During exercise blood glucose decreased markedly in the patients whereas in the control subjects the exercise-induced changes in blood glucose were insignificant.

4. There was no difference between the groups in the pre-exercise blood lactate and plasma free fatty acid concentrations. Significantly greater increases in blood lactate and plasma free fatty acids were found during exercise in hyperthyroid patients than in the control subjects.

5. Resting plasma noradrenaline concentration in the hyperthyroid patients did not differ from that found in normal subjects, but the exercise-induced increases in plasma noradrenaline were greater in the patients than in the control group.

6. On the basis of heart rate, as well as of body temperature and blood lactate differences between the hyperthyroid patients and healthy control subjects, it appears that the patients exercising at similar oxygen uptake as normal subjects were under greater physiological strain.
The Occurrence of Folate-Derived Pteridines in Rat Liver
Authors: Reed Berenice , Weir D. , Scott J.
Published: August 2015

1. It has previously been shown that folate polyglutamates in the rat are catabolized almost exclusively via cleavage of the C-9—N-10 bond, resulting in the formation of pteridines and p-aminobenzoylglutamate. The latter catabolite is rapidly excreted, appearing in the urine as acetamidobenzoylglutamate and is undetectable in rat liver.

2. The pteridines catabolites on the other hand are retained to a much greater extent by the liver, forming an ever-increasing proportion of the retained radioactive tracer.

3. A possible role for these pteridines as cofactors in brain metabolism is discussed.
A New Technique for Measuring Protein Turnover in the Gut, Liver and Kidneys of Lean and Obese Mice with [3H]Glutamic Acid
Authors: Miller B. G. , Grimble R. F. , Taylor T. G.
Published: August 2015

1. We have measured the incorporation of an intraperitoneal injection of [3H]glutamate into the protein of the gut, liver and kidney of lean and obese siblings of the genetically obese mouse.

2. Recycling of the 3H was minimized by using glutamate labelled at the C-2 position. Loss of label from the amino acid pool by transamination and deamination was rapid, with a half-life of 4 h.

3. In tissue protein the amino acid showing the highest 3H radioactivity was glutamate.

4. The half-lives for protein synthesis and catabolism were calculated from the decay curves of both specific and total radioactivity of [3H]glutamate in tissue protein. No significant differences were found between kidney, liver and gut in lean and obese mice.
Effect of Chenodeoxycholic Acid on Serum and Biliary Lipids in Patients with Hyperlipoproteinaemia
Authors: Angelin B. , Einarsson K. , Leijd Barbro
Published: August 2015

1. In order to study the effects of chenodeoxycholic acid on serum and biliary lipids in hyperlipoproteinaemia, chenodeoxycholic acid was administered to seven type IIa, eight type IIb and eight type IV patients in a daily dose of 750 mg (1·9 mmol) for 3 months.

2. The serum concentrations of cholesterol and triglycerides were determined at 4-week intervals: cholesterol remained unchanged whereas triglycerides decreased 15–20%.

3. In 17 patients, biliary lipids were studied. The proportion of chenodeoxycholic acid in the bile increased to about 70%; lithocholic acid and ursodeoxycholic acid increased significantly.

4. Bile saturation with cholesterol decreased and correlated negatively with the proportion of chenodeoxycholic acid in biliary bile acids but positively with serum triglycerides.

5. It is concluded that chenodeoxycholic acid treatment in hyperlipoproteinaemia is associated with a parallel fall in serum triglycerides and biliary cholesterol and thus may prove to be a useful adjunct in hypolipidaemic treatment.
Renal Prostaglandins in Renal Hypertensive Dogs
Authors: Dighe K. K. , Smith G. W. , Ungar A. , Whelpdale P. H.
Published: August 2015

1. Hypertension produced in two-kidney Goldblatt dogs was accompanied by a transient fluid retention, reaching a maximum 4 days after clamping.

2. Prostaglandin E and F concentrations in venous blood from the intact kidney also rose transiently, showing a maximum by the fifth day.

3. The rise in prostaglandin release from the intact kidney may be related to the fluid retention.
Effect of Arterial Pressure and Inheritance on the Sodium Excretory Capacity of Normal Young Men
Authors: Wiggins R. C. , Basar I. , Slater J. D. H.
Published: August 2015

1. In normal young adult sons of normotensive parents the rate of renal sodium excretion is highly correlated with mean arterial pressure after a large intravenous isotonic fluid load. The correlation appeared to strengthen with time and was improved when the rate of sodium excretion was corrected for variations in the rate of glomerular filtration.

2. There was no such correlation in normal, age-matched sons of hypertensive parents.

3. In eight of the 20 normotensive sons of hypertensive parents studied, the rate of renal sodium excretion per unit of mean arterial pressure was significantly higher than in the sons of normotensive parents.

4. Because the sons of hypertensive parents are much more likely to become hypertensive than those of normotensive parents, we suggest that an abnormality of renal sodium handling precedes the development of demonstrable hypertension.
Lysosomal Enzymes in Human Urine: Evidence for Polymorphonuclear Leucocyte Proteinase Involvement in the Pathogenesis of Human Glomerulonephritis
Authors: Sanders E. , Coles G. A. , Davies M.
Published: August 2015

1. Lysosomal proteinase activity was assayed in human cadaver kidney, urine, granules from polymorphonuclear leucocytes of normal persons, and urine samples from 154 patients with renal disease.

2. Granules from polymorphonuclear leucocytes showed proteinase activity at acid and neutral pH, whereas cadaver kidney showed proteinase activity at acid pH only.

3. The urine from 13 patients with glomerulonephritis showed proteinase activity at both acid and neutral pH as well as increased amounts of antigenic glomerular basement membrane fragments. The properties of the urinary proteinases suggested that they had originated in polymorphonuclear leucocytes.

4. Only the urine samples containing these proteinases were capable of degrading isolated human glomerular basement membrane in vitro.

5. Clinical recovery, where it occurred, was accompanied by the disappearance of urinary proteinase activity, and reduction in glomerular basement membrane antigen excretion.
Changes in the Collagen of Synovial Membrane in Rheumatoid Arthritis and Effect of d-Penicillamine
Authors: Lovell C. R. , Nicholls A. C. , Jayson M. I. V. , Bailey A. J.
Published: August 2015

1. Normal synovial membrane contains approximately equal proportions of two genetically distinct forms of collagen, types I and III. The proportion of these two collagens is unchanged in rheumatoid synovium but in addition a small amount of basement membrane collagen is present. Tissue culture of rheumatoid synovium confirms the synthesis of both type I and III collagens.

2. In young normal synovium both type I and type III collagens are stabilized by a reducible keto cross-link, which is replaced in adult tissue by an as yet unknown non-reducible cross-link. During the proliferation of the collagen in adult rheumatoid synovium a high proportion of the keto cross-link is present. This cross-link is not susceptible to cleavage by d-penicillamine, nor does the drug have any effect on the rate of synthesis in vitro. The mode of action of d-penicillamine in rheumatoid arthritis does not appear to involve a direct effect on the synovial membrane collagen.
Renal Vasoconstriction in Glycerol-Induced Acute Renal Failure. Studies in the Isolated Perfused Rat Kidney
Authors: Hofbauer K. G. , Bauereiss K. , Konrads A. , Gross F.
Published: August 2015

1. Acute renal failure was produced in rats by the intramuscular injection of glycerol (6.1 mol/l, 10 ml/kg). Either 2 or 4–6 h later the right kidney was isolated and perfused for 1 h with an electrolyte solution containing a gelatin preparation (Haemaccel, 35 g/l) at pressures between 90 and 100 mmHg in a single-pass system.

2. In kidneys taken from rats with acute renal failure renal vascular resistance was markedly increased immediately after the start of the perfusion as compared with control kidneys taken from untreated rats. During the following 30 min of perfusion the resistance progressively decreased and, at 1 h of perfusion, was similar to that in control kidneys or only moderately elevated.

3. Despite the reduction of renal vascular resistance glomerular filtration rate was still markedly impaired after 1 h of perfusion and fractional reabsorption of sodium and water as well as the secretion of p-aminohippurate were diminished. Renal venous renin concentration and renin release were lower in kidneys taken from rats with acute renal failure than in the control experiments.

4. These results suggest that the increase in renal vascular resistance and the stimulation of renin release after injection of glycerol in vivo are the consequence of extra-rather than intra-renal mechanisms.
Analytical Subcellular Fractionation of Jejunal Biopsy Specimens: Enzyme Activities, Organelle Pathology and Response to Corticosteroids in Patients with Non-Responsive Coeliac Disease
Authors: Peters T.J. , Jones P.E. , Jenkins W.J. , Wells Gill
Published: August 2015

1. Jejunal biopsies from five patients with non-responsive coeliac disease have been subjected to analytical subcellular fractionation and enzymic microassay in order to compare the organelle pathology of this group with untreated but gluten-sensitive patients.

2. Compared with the gluten-sensitive group these non-responsive patients showed marked reduction of the endoplasmic reticulum enzymes, normal activities of lysosomal enzymes and slightly less severely reduced brush border activities.

3. It is suggested that the present biochemical studies in combination with previous clinical reports and measurements of DNA and protein synthesis by cultured mucosal biopsies delineate non-responsive coeliac disease as a distinct entity.

4. The patients were treated with oral prednisolone (20 mg daily) for between 5 and 9 weeks and the properties of the jejunal biopsies restudied.

5. Although morphologically there was only a partial restoration of the villus architecture the enzymic alterations and organelle abnormalities returned essentially to normal values.
Vasopressin Effects on Plasma Renin Activity in Male and Female Rats
Authors: Henderson I. W. , Balment R. J. , Oliver J. Ann
Published: August 2015

1. The influence of gonadal and pituitary factors on the plasma renin response to exogenous vasopressin was examined in anaesthetized rats.

2. Plasma renin activity (PRA) was measured in Brattleboro rats (with and without hypothalamic diabetes insipidus) and Long-Evans male and female rats, before and after single intravenous injection of antidiuretic hormone (ADH) or saline.

3. Control saline injections did not change PRA. ADH reduced PRA in male, but increased PRA in female rats. Rats with diabetes insipidus displayed the greatest changes and were used in subsequent experiments. Extrarenal renin activity (nephrectomized rats) gave qualitatively similar responses to ADH. Plasma renin concentration, which was also measured with PRA in intact and nephrectomized male and female rats with diabetes insipidus, increased in the females and decreased in the males after ADH.

4. Castration, 24 h before study, abolished the ADH-induced fall in PRA, and testosterone implanted before castration did not restore the response. Cyproterone acetate reversed the ADH effect in males, so that PRA then rose after ADH. Hypophysectomized male rats, with depressed basal plasma renin activities, also showed a reduced PRA after ADH.

5. Ovariectomy had little effect on the ADH-induced renin release and the response was similar at oestrus, metoestrus and dioestrus. In hypophysectomized female rats ADH reduced PRA; a male pattern of response was seen in hypophysectomized female rats.

6. In both sexes PRA responses to ADH were blunted but not abolished by β-adrenergic blockade (propranolol). α-Adrenergic blockade (phenoxybenzamine) had little influence on the male response but in females the typical increase disappeared so that ADH reduced PRA.

7. It is concluded that pituitary hormones, including gonadotrophins and gonadal factors as well as adrenal sex steroids, appear to affect significantly the interplay between antidiuretic hormone and the renin—angiotensin system.
The Respiratory Response to Inhaled Carbon Dioxide in Man after 3 Hours Exposure to 3% Carbon Dioxide
Authors: Prowse K. , Duvivier C. , Peslin R. , Sadoul P.
Published: August 2015

1. The respiratory response to inhaled 3% and 6% CO2 was measured in 10 normal subjects after a 3 h acclimatization period to 3% CO2 in an environmental chamber. Control studies were carried out after a 3 h period of breathing air in the chamber.

2. At the end of the acclimatization period studies were carried out during 20 min periods breathing 3% CO2, 6% CO2 and air.

3. At 2-min intervals during the studies measurements were made of tidal volume (Vt), breathing frequency (fR), minute ventilation (V̇e), viscous pulmonary rate of work (Ẇp) and total viscous rate of work across the lungs and apparatus (Ẇt). Blood gas tensions were measured at the end of this period.

4. After acclimatization to 3% CO2 there was a significant shift in the response curves V̇e/Pa,co2 and Ẇt/Pa,co2 such that subjects showed higher Pa,co2 values for given values of V̇e or Ẇt. There was no significant change in the slope of the response curves.

5. No correlation was found between the slope of the response curve after the control period breathing air and the degree of shift of the response curve.

6. There was no difference in respiratory pattern or in pulmonary resistance.

7. Similar results were found in two subjects studied after 24 h acclimatization to 3% CO2 but one subject also showed a significant change in the slope of the V̇e/Pa,co2 curve.
Age-Dependent Difference of Kidney Response to Temporary Ischaemia in the Rat
Authors: Kuneš J. , Čapek K. , Stejskal J. , JelíNek J.
Published: August 2015

1. The response to 60 min ischaemia was studied in male uninephrectomized 30-, 60-and 90-day-old rats in regard to changes of renal cytochrome oxidase activity and the effect on systemic arterial blood pressure. Mortality due to renal failure, changes in plasma urea concentration and in kidney morphology were used as indicators of the renal response.

2. Mortality was lowest in 30-day-old animals (13%) and highest in 60-day-old animals (77%). Renal cytochrome oxidase activity increased by 44% during the same period. The mortality decreased to 34% between the ages of 60 and 90 days without change in renal content of cytochrome oxidase; survival time after renal ischaemia was prolonged from 2 to 4 days.

3. Fifty days after renal ischaemia plasma urea concentration correlated positively with kidney weight. Both variables were increased in rats exposed to ischaemia at the ages of 60 and 90 days. The kidneys of these rats exhibited lesions. No relation was found between the degree of renal damage and blood pressure.

4. It is concluded that (a) the kidney of immature rats is more resistant to temporary ischaemia due to immaturity of renal oxidative metabolism, (b) the ability to survive ischaemic renal damage in less-resistant mature rats increases with age and (c) the postischaemic impairment of renal function does not influence systemic arterial blood pressure.
Hepatic Elimination of Renin in Man
Authors: Hesse B. , Andersen Ellen Damgaard , Ring-Larsen H.
Published: August 2015

1. Hepatic elimination of renin was measured in 10 well-compensated cardiac patients with normal liver function during a control period and during a period of reduced hepatic plasma flow, induced by physical exercise (seven patients) or intravenous infusion of lysine vasopressin (three patients).

2. Hepatic renin elimination rate (hepatic plasma flow × arterial-hepatic vein difference of plasma renin activity) was found to be linearly correlated with arterial plasma renin activity (r = 0.986, P < 0.001).

3. When hepatic plasma flow fell by 45% the hepatic extraction ratio of renin (arterial-hepatic vein plasma renin activity difference/arterial plasma renin activity) increased by 75%. Hepatic renin clearance (hepatic plasma flow × extraction ratio) remained constant.

4. The results indicate that changes in the hepatic elimination rate of renin do not contribute to changes in plasma renin activity during these events.
Tracing the Fate of Oxygen Consumed during Phagocytosis by Human Neutrophils with 15O2
Authors: Segal A. W. , Clark J. , Allison A. C.
Published: August 2015

1. The metabolism of oxygen by phagocytosing neutrophils was traced by using 15O2.

2. The isotope did not exchange with the incubation medium or cells to an appreciable extent and unmetabolized oxygen was readily eluted by gassing the cell suspension.

3. The polarographic measurements of oxygen consumption closely paralleled the recovery of metabolized 15O2.

4. Almost all the metabolized 15O2 was converted into water, both in the presence and absence of KCN, supporting the concept that the oxygen consumed by neutrophils is converted into H2O2. It is unlikely that an appreciable proportion of this oxygen is incorporated into the organic composition of the cell or of the ingested microorganism.
Haemodynamic Variables during Repeated Exercise in Chronic Lung Disease
Authors: Schrijen F. , Ježek V.
Published: August 2015

1. Pulmonary and systemic haemodynamics during repeated exercise were studied in 28 patients with chronic lung disease of various etiology, 16 of whom suffered from chronic bronchitis. They performed a moderate exercise repeated after a 20 min rest period. Ventilatory variables, blood gas tensions, cardiac output and vascular pressures (right ventricular end-diastolic, pulmonary arterial, wedge and systemic arterial) were measured at rest, during exercise and again at rest and during the same exercise.

2. Ventilation and blood gas tensions were similar during the two rest and exercise periods; there was, however, a slightly significant difference in oxygen consumption and hydrogen ion concentration between the first and the second exercise period. Pulmonary arterial and wedge pressures were lower during the second rest and exercise, right ventricular filling pressure was lower at rest, and systemic arterial pressure during the second exercise. Cardiac output and pulmonary vascular resistance were unchanged.

3. Changes in systemic arterial pressure were significantly different in a group of patients with arterial oxygen desaturation or perfusion defects, compared with those patients without such impairment.
Propranolol and the Ventilatory Response to Hypoxia and Hypercapnia in Normal Man
Authors: Patrick J. M. , Tutty Janice , Pearson S. B.
Published: August 2015

1. The effect on respiration of a single dose of propranolol has been studied in normal subjects.

2. The degree of β-adrenoreceptor blockade was assessed in terms of the impaired heart-rate response to progressive exercise and the plasma propranolol concentration.

3. No effect of propranolol was demonstrated on either the ventilatory response to rebreathing CO2 in hyperoxia, or the response to progressive isocapnic hypoxia. Simple indices of maximal expiratory flow (FEV1.0% and PEFR) were also unchanged.

4. The absence of any effect of propranolol on the chemical control of breathing in man is discussed in relation to the conflicting literature.
The Effect of Established β-Adrenoreceptor-Blocking Therapy on the Release of Cytosolic and Lysosomal Enzymes after Acute Myocardial Infarction in Man
Authors: Welman Elizabeth , Fox K. M. , Selwyn A. P. , Carroll Brenda J.
Published: August 2015

1. Serial venous blood samples were obtained from 45 patients with acute myocardial infarction. Ten of these patients were receiving β-adrenoreceptor-blocking drugs at the time of onset of chest pain and continued on these drugs during their stay in the coronary care unit. The activities of creatine kinase and its MB-isoenzyme (CK-MB) were assayed in the plasma. A lysosomal enzyme, β-N-acetylglucosaminidase, was also assayed.

2. In the 35 untreated patients it was found that creatine kinase activity was maximal at a mean time of 21.3 ± 1.3 h after the onset of chest pain, whereas in the patients receiving β-adrenoreceptor-blocking drugs peak activity of the enzyme occurred at 24.4 ± 0.7 h.

3. Peak CK-MB activity was also delayed from 18.1 ± 1.6 h in the control group to 22.4 ± 1.2 h in the treated patients.

4. The lysosomal enzyme showed a similar pattern of changes to that of CK-MB. Maximum activity in plasma occurred at 18.0 ± 1.0 h after the onset of chest pain in the control group of patients. In the treated patients peak lysosomal enzyme activity was not found until 24.2 ± 1.2 h.

5. These alterations in the time-course of plasma enzyme changes after acute myocardial infarction are consistent with the suggestion that β-receptor antagonists may delay tissue damage during myocardial ischaemia.
Hypoxanthine—Guanine Phosphoribosyltransferase Activity in Blood and Skeletal Muscles of Normal and Dystrophic Mice
Authors: Neerunjun J. S. , Allsop Jennifer , Dubowitz V.
Published: August 2015

1. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity was measured in erythrocyte haemolysates and quadriceps muscle extracts of normal and dystrophic 129 ReJ and C57 BL/6J mice with [8-14C]hypoxanthine as substrate and 5-phosphorylribose 1-pyrophosphate as a ribose 5-phosphate donor. [8-14C]Inosine monophosphate formed was separated by high-voltage electrophoresis and radioactivity was measured by liquid-scintillation counting.

2. In erythrocyte haemolysates, HGPRT activity was similar in normal and dystrophic C57 BL/6J mice but was significantly higher in dystrophic than in normal 129 ReJ mice. Elevated enzyme activity was observed only in mice that were clinically severely affected.

3. In muscle homogenates, HGPRT activity was significantly higher in dystrophic than in normal animals of both 129 ReJ and C57 BL/6J mice. Enzyme activity was not related to the severity of the disease.

4. It is suggested that changes in erythrocytes are secondary to the dystrophic process and that elevated HGPRT activity in skeletal muscle may be related to abnormal energy metabolism, possibly via the pentose monophosphate shunt.
Brain Catecholamines and Catecholamine-Synthesizing Enzymes in Renovascular Hypertension in the Rat
Authors: Petty Margaret A. , Reid John L.
Published: August 2015

1. Noradrenaline content of several rat brain stem and hypothalamic nuclei falls transiently at 72 h after initiation of renovascular hypertension (one-kidney Goldblatt model).

2. Tyrosine hydroxylase activity is significantly reduced in posterior, paraventricular and periventricular nuclei of hypothalamus at this time but returns to control value by 7 days.

3. Treatment with hydrallazine, 5 mg/kg intraperitoneally, twice daily or methoxamine, 5 mg/kg, three times daily for 3 days respectively raises and lowers the noradrenaline content of brain nuclei, suggesting that short-term changes in noradrenaline may be secondary to afferent baroreceptor input.

4. At later times after the development of renovascular hypertension (7 and 28 days) activity of phenylethanolamine-N-methyl transferase is increased in the nucleus of the solitary tract and the locus coeruleus.

5. Brain catecholamines may participate both early in the development and later in the maintenance of renovascular hypertension.
Renal Release of Active and Inactive Renin in Essential and Renovascular Hypertension
Authors: Derkx F. H. M. , Verhoeven R. P. , Wenting G. J. , in 't Veld A. J. Man , Schalekamp M. A. D. H.
Published: August 2015

1. Active and acid-activable inactive renin were measured in renal venous and arterial plasma of 18 patients with essential hypertension (EHT) and 19 patients with renovascular hypertension (RVHT). In seven patients with EHT and in 11 patients with RVHT measurements were made before and 25–35 min after an intravenous injection of 300 mg of diazoxide.

2. Under basal conditions the renal vein to artery ratios for active and inactive renin in EHT ranged from 0·71 to 1·96 and from 0·68 to 1·44 respectively. In 14 patients with RVHT the renal vein to artery ratio for active renin on the affected side was above the range found in EHT and in six of them the renal vein to artery ratio for inactive renin was also elevated.

3. The diazoxide-induced release of active renin from kidneys, which had a stenotic artery but were not seriously contracted, was associated with a fall of the renal vein to artery ratio for inactive renin to a value below 1·00.

4. The results indicate that changes in the release of active and inactive renin do not always run in parallel. The findings are compatible with the hypothesis that circulating inactive renin can be activated in the kidney.
Renin Secretion by the Human Kidney
Authors: Birkenhäger W. H. , De Leeuw P. W. , Falke H. E. , Van Soest G. A. W.
Published: August 2015

1. 20 subjects with uncomplicated essential hypertension were studied, 10 of whom were on propranolol treatment. Several blood samples for determination of total and active renin were drawn simultaneously from the renal artery and vein after angiographic studies.

2. In all patients renal blood flow was measured by Hippuran-clearance at the time of blood sampling. Intrarenal blood flow was assessed by xenon-washout.

3. The results indicate that under basal conditions renin is secreted mainly in the active form, although secretion of inactive renin does occur. During propranolol treatment there is a tendency for secretion of active renin to be reduced.
Effects of Prostaglandin E2 and Prostaglandin F2α Upon Urinary Kallikrein Excretion in Rats
Authors: Croxatto H. R. , Arriagada R. , Rojas M. , Roblero J. , Rosas R.
Published: August 2015

1. In normally hydrated rats prostaglandin F2α (PGF2α) in doses of 5 μg/100 g body weight given subcutaneously every 2 h (three times) induced a significant increase in urinary kallikrein activity, and in sodium, potassium and water excretion for 8 h after the first injection. In moderately hyperhydrated rats loaded 2·5% of body wt. with 0·5% NaCl solution, PGF2α produced similar changes in kallikrein activity and electrolyte excretion.

2. In normally hydrated rats prostaglandin E2 (PGE2) in the same conditions and doses as in 1 had no effect on kallikrein activity, showing a tendency to decrease potassium and water excretion.

3. PGE2 in doses of 5, 12·5 and 25 μg/100 g body wt. in overhydrated rats given 2·5% and 0·5% NaCl and 5% of tap water/100 g body wt. 1 h later, significantly increased kallikrein activity in the urine collected for 120 min after the injections. A significant decrease in potassium and water excretion was observed with the highest dose.

4. PGF2α, had no effect on kallikrein activity in overhydrated rats, but an increase in sodium and a decrease in potassium excretion was seen at the highest dose.

5. The different actions of PGE2 and PGF2α may be part of a regulatory mechanism associated with the kallikrein—kinin system which contributes maintainance of extracellular fluid homeostasis.
Evidence for an Unidentified, Adrenocorticotrophic Hormone-Dependent Mineralocorticoid Maintaining Hypertension in Young Women with Hypoaldosteronism
Authors: Hoefnagels W. H. L. , Drayer J. I. M. , Hofman J. A. , Smals A. G. H. , Benraad TH. J. , Kloppenborg P. W. C.
Published: August 2015

1. Pronounced hypoaldosteronism was found in five young women with low-renin hypertension and characteristic features of the mineralocorticoid hypertensive syndrome.

2. There was no overproduction of the mineralocorticoids 11-deoxycorticosterone and 18-OH-11-deoxycorticosterone.

3. Dexamethasone restored blood pressure to normal, decreased body weight, increased plasma potassium, and increased plasma renin activity and aldosterone excretion in all patients.

4. The data suggest overproduction of an unknown adrenocorticotrophic hormone-dependent mineralocorticoid maintaining hypertension in these patients.