bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Nephrectomy and Enterectomy on Plasma Clearance of Intravenously Administered Dipeptides in Rats
Authors: Adibi S. A. , Krzysik B. A.
Published: August 2015

1. Sham-operated and bilaterally nephrectomized rats were injected intravenously with glycyl-l-leucine, glycylglycine and glycylsarcosine, and the concentrations of these dipeptides in plasma and muscle, liver, renal cortex (in the sham-operated rats) and intestinal mucosa at various intervals were determined.

2. Initially the plasma concentrations of glycyl-leucine and glycylglycine were higher in nephrectomized than in control rats but later the concentrations were similar in both groups of rats. The disappearance of these two dipeptides from plasma was almost complete within 20 min, and their plasma half-lives were not changed remarkably by nephrectomy. In contrast, nephrectomy markedly impaired disappearance of glycylsarcosine from plasma and prolonged its half-life from 7·6 min to 52·0 min.

3. Glycyl-leucine and glycylglycine were not detected in tissues of control rats injected with these dipeptides, but glycylsarcosine was recovered from all four tissues examined. Nephrectomy resulted in greater accumulations of glycylsarcosine in tissues and the appearance of glycylglycine in the remaining three tissues and glycyl-leucine in muscle.

4. Enterectomy did not have a remarkable effect on plasma half-life of glycylglycine but it allowed recovery of this dipeptide from renal cortex, liver and muscle.

5. It is concluded that kidneys and small intestine are involved in the disposition of circulating dipeptides, but in their absence other tissues may assume a greater role in this regard. However, renal clearance appears to be an important route for the disposition of dipeptides which are poorly hydrolysed by body tissues.
Amino Acid Concentrations in Portal Venous Plasma during Absorption from the Small Intestine of the Guinea Pig of an Amino Acid Mixture Simulating Casein and a Partial Enzymic Hydrolysate of Casein
Authors: Sleisenger M. H. , Pelling D. , Burston D. , Matthews D. M.
Published: August 2015

1. The characteristics of absorption of individual amino acids from amino acid mixtures simulating casein and from enzymic hydrolysates of casein containing oligopeptides as well as free amino acids are known to be different. The differences, which are attributable to mucosal uptake of small peptides, involve more rapid absorption from the enzymic hydrolysates of certain amino acids which are relatively slowly absorbed from the amino acid mixtures. This could lead to more effective utilization of amino acids from the enzymic hydrolysates than from the amino acid mixtures.

2. To obtain further information bearing on this hypothesis, we have used a recently developed technique for portal cannulation in the guinea pig to make a preliminary investigation of amino acid concentrations in the portal venous plasma at intervals after the infusion into the duodenum of equivalent amounts of (a) an amino acid mixture simulating casein and (b) a partial enzymic (papain followed by kidney peptidases) hydrolysate of casein, the two preparations being infused in separate experiments.

3. For some amino acids, such as leucine, isoleucine, valine, phenylalanine and lysine, the curves after the enzymic hydrolysate were fairly similar to the corresponding curves after the amino acid mixture, though usually slightly lower. With other amino acids, the curves after the enzymic hydrolysate were very much lower than the corresponding curves after the amino acid mixture. With serine, glutamine, proline and glycine this discrepancy was particularly great.

4. The results cannot yet be fully explained, but their main features are explicable by the hypothesis that the lower amino acid concentrations in portal plasma after the enzymic hydrolysate are the result of entry of amino acids into the portal blood in peptide form, in which they would not be detectable by the analytical technique employed, and possibly also of more rapid clearance of amino acids from the blood during absorption of this preparation.
Plasma Glucose, Non-Esterified Fatty Acids and Amino Acids in Huntington's Chorea
Authors: Phillipson O. T. , Bird E. D.
Published: August 2015

1. The metabolic responses to an oral glucose tolerance test (100 g) and an intravenous insulin provocation test (0·1 i.u./kg) were studied in nine control subjects and nine patients with Huntington's chorea.

2. Plasma glucose responses to these stimuli were identical in both groups.

3. High fasting concentrations of non-esterified fatty acid (NEFA) were recorded in the choreic patients when compared with control subjects. This difference was maintained under hypoglycaemic conditions. However, during hyperglycaemia the differences in NEFA concentrations between the groups was abolished.

4. Total plasma tryptophan concentrations were equal in the two groups. Free plasma tryptophan, however, was markedly reduced in the choreic group, and this appeared to be a result of a disturbed relationship between free tryptophan and NEFA concentrations. The abnormalities in free tryptophan values were sensitive to plasma glucose concentrations, as hyperglycaemic conditions markedly reduced the differences between the choreic and control group.

5. Patients with Huntington's chorea showed reduced fasting plasma concentrations of leucine, isoleucine and valine.
The Urinary Excretion of Catecholamines and Their Derivatives in Primary Hypertension in Man
Authors: Bing R. F. , Harlow J. , Smith A. J. , Townshend M. M.
Published: August 2015

1. The 24 h urinary excretion of adrenaline, noradrenaline, normetadrenaline, metadrenaline and vanilloylmandelic acid has been compared in 17 male normotensive subjects and 25 age-matched male hypertensive patients studied under similar in-patient conditions.

2. 24 h urinary metadrenaline was significantly lower in the hypertensive patients. With this exception, no significant differences were found between the two groups when the total 24 h excretion of free catecholamines and their metabolites was analysed.

3. Diurnal variation in free catecholamine excretion was found in both normotensive and hypertensive subjects. There was no corresponding variation in metabolite excretion.

4. No correlation could be established between systolic or diastolic blood pressure and the amounts of the catecholamines or their metabolites in the urine of either group.

5. The results are considered in the light of recent work demonstrating high plasma catecholamine concentrations in hypertension. They lend no support to the concept that excessive circulating catecholamines are responsible for the elevated blood pressure in essential hypertension.
The Binding of Plasma Proteins to Human Placental Cell Membranes
Authors: Balfour A. H. , Jones E. A.
Published: August 2015

1. To investigate the relative degree to which human IgG and other plasma proteins bind to cell membranes of the full-term human placenta, suspensions of membranes mixed with radio-iodinated proteins were incubated at pH 6·5 and subjected to Sepharose 2B column chromatography. The amount of labelled protein associated with membrane protein in membrane-containing fractions of the eluate was then determined.

2. Binding of IgG and each of the four subclasses of IgG was appreciable. Binding of IgG was markedly reduced if membranes were incubated at pH 8·0 rather than 6·5. Binding of labelled IgG was inhibited by excess of unlabelled IgG but not by excess of unlabelled albumin. Placental membranes bound much more IgG than did erythrocyte membranes.

3. Binding of insulin was relatively greater than that of IgG, whereas binding of IgE, IgM, IgA, albumin, transferrin and polyvinylpyrrolidone was much less than that of IgG and each of its subclasses.

4. The relative binding of IgG and fragments of the IgG molecule was, in decreasing order of magnitude: light chains, IgG, Fc, heavy chains and F(ab′)2.

5. The results are consistent with Brambell's hypothesis for the mechanism of the transmission of passive immunity from mother to young. In particular the data are consistent with the existence of a limited number of IgG specific receptors on the microvillus membrane of the syncytial trophoblast. Such receptors could protect IgG molecules from degradation during their transplacental transport. The submolecular region of the IgG molecule involved in specific membrane binding appears to be common to all four subclasses and to include the Fc region.
Haemodynamic Characteristics of Low-Renin Hypertension
Authors: Schalekamp M. A. D. H. , Birkenhäger W. H. , Zaal G. A. , Kolsters G.
Published: August 2015

1. Intra-arterial pressure, cardiac output, renal blood flow and glomerular filtration rate were measured in 19 patients with low-renin hypertension and in 30 patients with normal-renin hypertension.

2. Cardiac output and renal blood flow were significantly lower in low-renin hypertension. Total peripheral and renal vascular resistance were markedly higher in this group.

3. Plasma renin concentration correlated inversely with both total peripheral and renal vascular resistance as well as with age. Multiple regression analysis indicated that part of the relationship between renin and haemodynamic variables did not depend on age. Furthermore, plasma renin concentration did not decrease with age in a group of 40 normotensive control subjects of similar age to the hypertensive patients.

4. The results provide further confirmation that renin decreases as hypertension progresses.
Catabolic rate of α1-antitrypsin of Pi type M and Z in man
Authors: Laurell C.-B. , Nosslin B. , Jeppsson J.-O.
Published: August 2015

1. Human α1-antitrypsin was isolated from three Pi M and two Pi Z subjects without alteration of its microheterogeneity. The purified proteins were labelled with either 125I or 131I by a lactoperoxidase method.

2. The disappearance rate of two types of α1-antitrypsin were studied after simultaneous injection of labelled M-protein and Z-protein into Pi M subjects.

3. The ratio of extra vascular to plasma pools of α1-antitrypsin ranged between 1·2 and 1·6 with no difference between M- and Z-protein. The mean fractional catabolic rates of M-protein and Z-protein were respectively 0·26 and 0·40 per day.

4. The difference in catabolic rate of Z- and of M-protein is too small to explain why the α1-antitrypsin content of the blood in Pi ZZ subjects is only 15% of that normally found in Pi MM subjects. The low α1-antitrypsin in Pi ZZ subjects appears mainly to be due to a low rate of biosynthesis.
Porphyrins in Erythrocytes and Blood Plasma: Preliminary Studies with Qualitative Thin-Layer Chromatography
Authors: With T. K.
Published: August 2015

1. A simple chromatographic method for the study of porphyrins in erythrocytes and blood plasma, requiring little technician time, is described. The findings in adults and neonates are presented as well as those from severely ill patients.

2. The regular occurrence of uro-, copro- and proto-porphyrin in erythrocytes is demonstrable as well as sporadic occurrence of tri-, penta-, hexa- and hepta-carboxylic porphyrin. The method gives, however, irregular values for protoporphyrin, which seems to occur in a more labile form in some subjects than in others; this is especially the case in erythropoietic protoporphyria.

3. In blood plasma, uroporphyrin occurs regularly, and coproporphyrin less regularly. Protoporphyrin and penta- to hepta-carboxylic porphyrin are found only occasionally.
Bone Necrosis and Urinary Hydroxyproline Excretion in Rabbits
Authors: Weatherley C. R. , Dale G. , McGurk J. , Walder D. N.
Published: August 2015

1. Aseptic necrosis of bone is a serious chronic complication of deep-sea diving and compressed-air work.

2. The changes to the bone which occur in this condition take time to develop to the stage where they cause the radiographic signs of bone necrosis, and consequently there is a delay of some months between the causal incident and the first diagnosis by radiography.

3. As a possible method for the earlier detection of bone necrosis the 24 h urinary excretion of hydroxyproline was measured over a period before and after experimental production of bone necrosis in rabbits by the intra-arterial injection of glass microspheres.

4. Total hydroxyproline excretion rose significantly within a few days of the injection in those rabbits in which there was later shown to be histological evidence of bone necrosis. This rise occurred long before there was any radiographic change.

5. It is suggested that measurement of urinary hydroxyproline might be used to give an early indication of bone necrosis in man.
Enzyme Activities of Cells of Different Types Isolated from Livers of Normal and Cholestatic Rats
Authors: Wootton A. M. , Neale G. , Moss D. W.
Published: August 2015

1. The distribution of three membrane-bound enzymes, alkaline phosphatase, 5′-nucleotidase and γ-glutamyl transferase, has been examined in rat liver fractionated into parenchymal cells, a Kupffer cell fraction and a biliary tract fraction by perfusion with collagenase solution.

2. In control rat livers the highest enzyme concentrations were found in Kupffer cell preparations. The fraction enriched with biliary tract cells showed concentrations two- to fourfold those in isolated parenchymal cells.

3. At 24 h after ligation of the bile duct there was a fourfold increase in the alkaline phosphatase activity in parenchymal cells and a 2·5-fold increase of the same enzyme in the biliary tract fraction. The concentration of alkaline phosphatase in Kupffer cells remained unchanged.

4. 5′-Nucleotidase and γ-glutamyl transferase concentrations tended to decrease after bile-duct ligation for 24 h, the most marked changes being found in Kupffer cells.

5. After bile-duct ligation for 7 days the overall activities of hepatic alkaline phosphatase and γ-glutamyl transferase increased fourfold and there was a small rise in 5′-nucleotidase. For alkaline phosphatase and γ-glutamyl transferase the changes were found primarily in parenchymal cells and in the biliary tract fraction. There was a small rise in the activity of 5′-nucleotidase in parenchymal cells and a fall in activity in Kupffer cells.

6. These data show marked differences in the distribution and behaviour of three enzymes which are often used as alternatives in the assessment of patients with liver disease.
Regulation of Cardiac Output during 2,4-Dinitrophenol-Induced Tissue Hypermetabolism in the Dog
Authors: Liang C. , Hood W. B.
Published: August 2015

1. Cardiac output increased in proportion to oxygen consumption in intact chloralose-anaesthetized dogs after four successive intravenous infusions of 2,4-dinitrophenol (11 μmol/kg; 2 mg/kg).

2. Splenectomy abolished the increase in cardiac output after the first three doses of 2,4-dinitrophenol. β-Adrenoreceptor blockade by practolol, on the other hand, did not prevent the cardiac output rise after the first 2,4-dinitrophenol infusion, but further increases by 2,4-dinitrophenol infusion were abolished. When splenectomy and β-adrenoreceptor blockade were combined, cardiac output did not increase significantly after all four doses of 2,4-dinitrophenol.

3. Cardiac output and mean systemic arterial blood pressure increased when the splenic venous blood collected after 2,4-dinitrophenol infusion was infused intraportally.

4. In a vascularly isolated, but normally innervated, lower half-body cross-perfusion preparation, cardiac output and mean systemic arterial blood pressure increased in the upper half-body when tissue hypermetabolism was produced in the cross-perfused area by 2,4-dinitrophenol. Neither pulmonary artery wedge pressure nor heart rate changed significantly.

5. This circulatory stimulation, after regional 2,4-dinitrophenol infusion, was abolished or was prevented from occurring by splenectomy.

6. It appears that the normal cardiac output response to tissue hypermetabolism requires both an intact spleen and normally functioning β-adrenoreceptors.
Analytical Subcellular Fractionation of Guinea-Pig Myocardium
Authors: Bloomfield F. J. , Wells G. , Welman E. , Peters T. J.
Published: August 2015

1. Homogenates of guinea-pig left ventricle were fractionated by differential pelleting and by centrifugation on continuous sucrose density gradients.

2. The principal subcellular organelles of myocardium, characterized by their marker enzyme content, were resolved by density gradient centrifugation in a small-volume zonal rotor. The equilibrium densities (p) of the principal organelles are (with marker enzymes in parentheses): sarcolemma, 1·12 (5′-nucleotidase); lysosomes, 1·16 (N-acetyl-β-glucosaminidase); mitochondria, 1·17 (cytochrome oxidase); peroxisomes, 1·18 (catalase); cytosol (lactate dehydrogenase).

3. The subcellular distribution of various adenosine triphosphatase activities and previously unassigned enzymes was determined. Leucyl-β-naphthylamidase and γ-glutamyl transpeptidase showed both cytosol and sarcolemma components. Ca2+-dependent adenosine triphosphatase showed dual localization to the mitochondria and to the sarcolemma.
Independence of Ethacrynic Acid-Induced Renal Hydrogen Ion Excretion of Sodium-Volume Depletion in Man
Authors: Györy A. Z. , Lissner Dianne
Published: August 2015

1. Neither the mechanism nor the therapeutic implications of the ability of ethacrynic acid to stimulate renal H+ secretion has been fully explored. Acute studies were carried out in six normal volunteer subjects to determine whether or not the stimulation of H+ excretion depended upon sodium chloride or volume depletion.

2. Depletion was either not corrected, or corrected by one of the following: oral water alone or sodium chloride solution (either 153 mmol/l or 513 mmol/l) intravenously to give zero or slightly positive balances of water, sodium chloride or both at all times. Urine was collected at 2 h intervals before and for 8 h after 100 mg of ethacrynic acid. Electrolytes, pH, total acid, osmolality and true creatinine were measured in each urine specimen and in the serum during the control period and 5·5 h after ethacrynic acid.

3. In all 14 experiments in six subjects, urinary pH was reduced to a mean value 4·78 ± se 0·08 within 2–8 h after ethacrynic acid irrespective of replacement therapy, indicating that the sodium chloride and volume depletions produced by ethacrynic acid were not essential to its effect on urinary pH.

4. Urinary pH correlated inversely (r = −0·81) with the logarithm of the difference between rejected chloride and sodium per unit of rejected chloride, suggesting that the discrepancy between anion-cation reabsorption was intimately linked to generation of H+ gradients, possibly by reducing chloride transport.

5. Three of the subjects were given amiloride (20 mg) with ethacrynic acid: both the pH reduction and the chloride/sodium differentials were abolished, probably by reduction of tubular sodium reabsorption. A specific but opposite effect of both agents on tubular H+ transport cannot be excluded.
The Role of Inhibitors and other Factors in the Pathogenesis of Recurrent Calcium-Containing Renal Stones
Authors: Baumann J. M. , Bisaz S. , Felix R. , Fleisch H. , Ganz U. , Russell R. G. G.
Published: August 2015

1. In order to assess the relative importance of possible pathogenetic factors in the formation of calcium-containing renal stones, a group of 18 patients (12 men, six women) with active, recurrent stone disease were compared with 16 age-matched control subjects (10 men, six women) given an identical diet.

2. Fifteen (83%) of the patients showed at least one, eight (44%) showed two, and one (6%) patient showed three abnormalities that might predispose to stone formation.

3. Increased urinary calcium excretion was the most common abnormality (11 patients, 61%), particularly in the women (83%).

4. A diminished excretion of inhibitors of crystal formation of calcium phosphate was the next most common abnormality, which occurred in eight patients (44%), all of whom were men. It was largely attributable to a diminished excretion of inorganic pyrophosphate (PPi). The PPi/orthophosphate ratios were also lower in the stone-formers. Significant differences in residual inhibitory activity after enzymatic removal of PPi between control subjects and stone-formers could not be found in 24 h urine samples but were present during certain times of the day. Pyrophosphate showed a higher inhibitory activity in urine than in control solutions, this enhancement being absent in stone-formers.

5. Nine (50%) of the patients, but only one of the control subjects, produced crystal aggregates greater than 50 μm in diameter after an oral load of oxalate.
Potentiation of Pressor Effects of Noradrenaline and Potassium Ions in the Rat Mesenteric Arteries by Physiological Concentrations of Angiotensin II: Effects of Prostaglandin E2 and Cortisol
Authors: Kondo K. , Manku M. S. , Horrobin D. F. , Boucher R. , Genest J.
Published: August 2015

1. In the perfused rat mesenteric vascular bed, the effects of angiotensin II, cortisol and prostaglandin E2 on the vascular responses to noradrenaline or potassium chloride were studied.

2. Angiotensin II in subpressor concentrations potentiated the vasoconstrictor response to noradrenaline and potassium chloride. This effect of angiotensin II was inhibited in the presence of indomethacin and prostaglandin E2.

3. Cortisol in physiological concentrations inhibited the potentiating effect of angiotensin II.

4. Prostaglandin E2 enhanced the vasoconstrictor response to noradrenaline. This effect was not abolished by cortisol.

5. These results suggest that some actions of angiotensin II and cortisol in vivo are mediated by the regulation of prostaglandin synthesis or release.
A Reappraisal of ‘Osmotic’ Evidence for Intact Peptide Absorption
Authors: Fairclough P. D. , Silk D. B. A. , Webb J. P. W. , Clark M. L. , Dawson A. M.
Published: August 2015

1. The validity of evidence for intact peptide absorption, derived from analysis of the relation of water and total solute absorption, has been tested.

2. Solute and water absorption from saline solutions of the disaccharide maltose have been studied in the normal human jejunum, using a double-lumen perfusion technique with a proximal occlusive balloon. It was expected that maltose would yield very different results from peptides, because maltose is virtually completely hydrolysed before absorption, whereas a proportion at least of some peptides is transported into the intestinal mucosal cells before hydrolysis. This expectation was not confirmed by experiment.

3. The assumption that the absorbate is always isotonic with plasma has been tested by altering the osmolality of glucose/saline solutions perfused in the jejunal lumen. This assumption was not substantiated by experiment, as when the luminal fluid was hypertonic to plasma, so was the absorbate.

4. It is suggested that our findings with peptides and saccharides could be explained by the production of a hypertonic absorbate by hydrolysis of these solutes to their monomer units. We therefore conclude that analyses of the relation of net solute and water absorption cannot be used to predict the form in which peptides enter the mucosal cells.
Influence of Deoxycholic Acid on Biliary Lipids in Man
Authors: Ahlberg J. , Angelin B. , Einarsson K. , Hellström K. , Leijd B.
Published: August 2015

1. The duodenal bile acid composition was analysed in 24 control subjects and 107 patients with various types of hyperlipoproteinaemia. A highly significant negative correlation was observed between the proportions of deoxycholic acid and cholic acid as well as between deoxycholic acid and chenodeoxycholic acid. Patients with gall-bladder disease had an increased proportion of deoxycholic acid in their bile.

2. Eight control subjects were studied before and during the ingestion of 1·9 mmol (0·75 g) of deoxycholic acid daily. In these subjects a rise in the proportion of deoxycholic acid was also accompanied by a fall in the proportion of both cholic acid and chenodeoxycholic acid in duodenal bile.

3. The biliary lipid composition and cholesterol saturation was determined before and during the administration of 1·9 mmol (0·75 g) of chenodeoxycholic acid (n = 12) or deoxycholic acid (n = 8) daily for 3–4 weeks. The cholesterol saturation was decreased during the chenodeoxycholic acid ingestion whereas no change occurred in bile saturation during deoxycholic acid administration.

4. Ingestion of chenodeoxycholic acid lowered serum triglyceride and deoxycholic acid lowered the serum cholesterol.
The Effect of Human Pregnancy on the Pulmonary Transfer Factor for Carbon Monoxide as Measured by the Single-Breath Method
Authors: Milne J. A. , Mills R. J. , Coutts J. R. T. , Macnaughton M. C. , Moran F. , Pack A. I.
Published: August 2015

1. The pulmonary transfer factor for carbon monoxide was measured by the single-breath method in 21 pregnant women with no previous history of cardiac or respiratory disease. Measurements were made at monthly intervals throughout pregnancy and once post partum.

2. The transfer factor was higher in the first trimester of pregnancy than in the non-pregnant state. There was a fall in the transfer factor during pregnancy until 26 weeks gestation, after which no further decrease was observed.

3. The changes in transfer factor were not explained by alterations in haemoglobin concentration or alveolar volume.

4. Simultaneous serial estimations of plasma 17β-oestradiol were performed in all the subjects. There was no obvious direct relation between changes in the concentration of this hormone and transfer factor measurements.
Inter-Relationships of Carbonate, Phosphate, Monohydrogen Phosphate, Calcium, Magnesium and Sodium in Uraemic Bone: Comparison of Dialysed and Non-Dialysed Patients
Authors: Pellegrino E. D. , Biltz R. M. , Letteri J. M.
Published: August 2015

1. Chemical and morphological features of uraemic bone disease were studied by comparison of bone composition in 44 patients with uraemia (12 dialysed and 32 non-dialysed) and 36 control subjects. The significant changes included decreased bone mineral carbonate associated with calcium, a concomitant increase in phosphate, and an increase in magnesium. There was also an increase in osteoid and a reduction in the specific gravity of the compact bone.

2. The most marked changes in bone composition were observed in patients with uraemia of more than 1 year's duration, who had been dialysed. Bone mineral sodium concentrations were not significantly altered in any group.

3. The changes in bone mineral composition appeared to be the result of several simultaneous and/or successive mechanisms: (i) loss of fixed base, calcium carbonate; (ii) replacement of carbonate by phosphate; (iii) the addition of immature bone mineral, which contains high concentrations of phosphate and relatively low concentrations of carbonate.

4. These observations are consistent with earlier views of the bone salt as an indefinite calcium/phosphate/carbonate complex. Variations in bone composition may arise from a reciprocal relationship between phosphate and carbonate. The bone mineral analogue that best explains these variations in bone composition is octacalcium phosphate carbonate [Ca4(PO4)2(HPO4)x(CO3)1-x,zH2O].
Circulating Inhibitor of Sodium—Potassium-Activated Adenosine Triphosphatase after Expansion of Extracellular Fluid Volume in Rats
Authors: Gonick H. C. , Kramer H. J. , Paul W. , Lu E.
Published: August 2015

1. Serum was collected from normal rats and from rats volume-expanded with isotonic sodium chloride solution.

2. The serum was fractionated by gel filtration on Sephadex G-25 and each fraction was tested for inhibitory activity against sodium—potassium-activated adenosine triphosphatase prepared from rat kidney homogenate.

3. A single low-molecular-weight fraction, eluting after the salts and after exogenously added lysine-vasopressin, had significantly greater enzyme inhibitory activity when obtained from serum of volume-expanded animals than from control serum.

4. As this fraction has been shown in previous independent studies to contain a natriuretic factor, it may be concluded that one property of this factor is the ability to inhibit sodium—potassium-activated adenosine triphosphatase.
Alterations in the Activity of Enzymes of Haem Biosynthesis in Lead Poisoning and Acute Hepatic Porphyria
Authors: Campbell B. C. , Brodie M. J. , Thompson G. G. , Meredith P. A. , Moore M. R. , Goldberg A.
Published: August 2015

1. The activities of six of the enzymes of haem biosynthesis have been assayed in peripheral blood from patients with lead poisoning, acute intermittent porphyria or hereditary coproporphyria.

2. Compared with normal subjects the lead-poisoned subjects had highly significant depression of δ-aminolaevulinate dehydratase, coproporphyrinogen oxidase and ferrochelatase.

3. Lead-poisoned subjects had highly significant elevation of δ-aminolaevulinate synthase activity.

4. δ-Aminolaevulinate synthase activity was inversely related to the haemoglobin concentration.

5. Increased δ-aminolaevulinate synthase and decreased δ-aminolaevulinate dehydratase activity are also found in acute intermittent porphyria.

6. Increased δ-aminolaevulinate synthase, normal porphobilinogen deaminase and uroporphyrinogen decarboxylase and decreased coproporphyrinogen oxidase are found in both lead poisoning and hereditary Coproporphyria.

7. These enzyme changes explain the recognized patterns of porphyrins and porphyrin precursors in blood and urine in these conditions.
Leg Blood Flow and Central Circulation at Various Blood Volumes: A Peroperative Study of Nine Patients with Varicose Veins
Authors: Brismar B. , Cronestrand R. , Jorfeldt L. , Juhlin-Dannfelt A.
Published: August 2015

1. In a group of nine middle-aged patients undergoing varicose vein surgery, cardiac output, right atrial, pulmonary arterial and capillary pressures, and leg blood flow were measured after induction of general anaesthesia but before operation, and also during operation before and after blood substitution.

2. Under anaesthesia, the mean preoperative blood flows in the superficial and common femoral arteries were 160 ml/min and 280 ml/min respectively. These flows are comparable with those obtained in other studies under similar conditions but lower than values obtained in conscious subjects. During the operation the leg blood flow decreased by 24%. As cardiac output remained unchanged, the fractional leg blood flow fell. After transfusion of 900 ml of blood the leg blood flow doubled.

3. It is concluded that anaesthesia, surgical trauma and variations in blood volume greatly influence the leg blood flow and that an adequate substitution of operative blood loss is of utmost importance to achieve an optimum peripheral circulation.
Effect of 30% Oxygen on Local Matching of Perfusion and Ventilation in Chronic Airways Obstruction
Authors: Eiser Noemi M. , Jones Hazel A. , Hughes J. M. B.
Published: August 2015

1. Sixteen patients with chronic bronchitis and airways obstruction were given radioactive nitrogen (13N) by intravenous injection and by inhalation, while breathing air and after 10–20 min breathing 30% oxygen. The clearance of 13N from four zones of each patient's whole lung field was monitored.

2. The 13N clearance of each region in these patients with chronic bronchitis was much slower than in normal subjects. Oxygen breathing produced a significant delay in the clearance of intravenously administered 13N in 23 zones in 10 patients but no systematic change in clearance after inhaled 13N.

3. With inhalation of 30% oxygen there was no significant change in the mean minute ventilation, tidal volume or arterial Pco2.

4. The results suggest that local hypoxic vasoconstriction is present in some patients on breathing air and that this is relieved by 30% oxygen, resulting in a diversion of local blood flow from well-ventilated to more poorly ventilated areas. The fall in V̇A/Q̇ on 30% oxygen is insufficient to increase arterial Pco2.
Effect of α-Methyldopa on the Pulmonary Vascular Changes Induced by Chronic Hypoxia in Rats
Authors: Suggett A. J. , Herget J.
Published: August 2015

1. Groups of young rats were kept in a hypoxic chamber or in air as control animals for 28 days.

2. Hypoxic and control animals were treated with either α-methyl-3,4-dihydroxyphenylalanine (α-methyldopa) or distilled water.

3. α-Methyldopa significantly reduced the increase in pulmonary artery pressure and right ventricular hypertrophy induced by chronic hypoxia and partially prevented the histological changes in the small pulmonary vessels.
Decreased Plasma Renin Activity and Renin Release in Rats with Phaeochromocytoma
Authors: Fray J. C. S. , Mayer P. V. H.
Published: August 2015

1. We have examined the response of renin to chronic low and high sodium chloride intake in rats with transplanted phaeochromocytoma.

2. Phaeochromocytoma suppressed the usual elevated plasma renin activity observed during sodium deprivation.

3. Studies in isolated perfused kidneys indicated that sodium-deprived phaeochromocytoma rats released substantially less renin than sodium-deprived control rats despite an almost identical renal renin content in both sets of animals. In addition, low perfusion pressure (50 mmHg) failed to stimulate renin release in kidneys from these phaeochromocytoma rats.

4. Additional experiments demonstrated that chronic sodium chloride loading suppressed plasma renin activity, renin content and renin release in both phaeochromocytoma and control rats. Both sodium-loaded phaeochromocytoma and sodium-loaded control rats were unresponsive to low perfusion pressure.

5. We conclude that noradrenaline-secreting phaeochromocytoma impairs the response of plasma renin activity in the rat by inhibiting renin release. We also conclude that chronic sodium chloride loading has a similar effect, but the mechanisms remain to be determined.
Protein Turnover, Synthesis and Breakdown before and after Recovery from Protein-Energy Malnutrition
Authors: Golden M. H. N. , Waterlow J. C. , Picou D.
Published: August 2015

1. Rates of total protein turnover, synthesis and breakdown were measured in five children before and after recovery from severe protein-energy malnutrition and while receiving 0·6 g of protein and 397 kJ day−1 kg−1.

2. These rates were calculated after giving doses of [15N]glycine every 2 h along with the feeds and measuring the rate of excretion of [15N]urea in urine.

3. Malnourished children had significantly lower rates of protein turnover, synthesis and breakdown than after they had recovered.

4. During recovery from protein-energy malnutrition, two children on a daily intake of 1·2 g of protein and 605 J/kg body weight, had rates of protein turnover, synthesis and breakdown that were twice as great as those found on admission and higher than after recovery.

5. On the study diet the malnourished children maintained their weight while the recovered children lost weight; the apparent nitrogen balance was more positive in the malnourished children.

6. In recovered children, the rate of protein synthesis was unchanged over a wide range of protein intake, whereas the rate of protein breakdown appeared to rise with a reduction in protein intake.
Effects of Analgesics and Related Compounds on Renal Metabolism in Rats
Authors: Tange J. D. , Ross B. D. , Ledingham J. G. G.
Published: August 2015

1. The metabolic effects of p-aminophenol have been compared with those of paracetamol and other analgesics in studies of rat liver and kidney in vitro.

2. p-Aminophenol injected into rats inhibited gluconeogenesis from lactate in renal cortical tubules, but not in isolated hepatocytes, and reduced kidney ATP content without affecting the ATP content of liver. Perfused kidneys from rats previously injected with p-aminophenol showed a 50% reduction of ATP content, severe inhibition of Na+ reabsorption and reduction of inulin clearance without significant inhibition of gluconeogenesis from lactate.

3. Paracetamol, p-phenetidine, phenazone and aspirin, when given intravenously to rats, had no effect on renal tubular glucose synthesis from lactate or pyruvate. Paracetamol and aspirin both slightly inhibited renal glucose synthesis from several different substrates when added directly to tubules.

4. Paracetamol (4 mmol/l) inhibited glucose synthesis from lactate and other substrates by 50% or more in isolated hepatocytes. Glucose synthesis from lactate was inhibited 30% by concentrations of paracetamol as low as 0–5 mmol/l.

5. These results indicate that p-aminophenol is a potent inhibitor of proximal tubular function, with its main site of action the inhibition of ATP synthesis and energy production, and they confirm the primary hepatotoxic effect of paracetamol.
Abnormalities in Enzymes Involved in Catecholamine Synthesis and Catabolism in Phaeochromocytoma
Authors: Jarrott B. , Louis W. J.
Published: August 2015

1. The activities of the enzymes involved in catecholamine synthesis, tyrosine hydroxylase, aromatic amino acid decarboxylase and dopamine β-hydroxylase, were markedly enhanced in homogenates of phaeochromocytoma compared with human adrenal medulla homogenates measured under optimum substrate concentrations.

2. It was demonstrated in fresh tumour slices that the rate of formation of dopamine (3,4-dihydroxyphenethylamine) from tyrosine was much slower than the rate of formation of dopamine from dopa (3,4-dihydroxyphenylalanine) (suggesting that tyrosine hydroxylase was the rate-limiting enzyme in noradrenaline synthesis in phaeochromocytoma) and that the tyrosine hydroxylation step was still susceptible to end-product inhibition by catecholamines.

3. It is suggested that catecholamine overproduction in phaeochromocytoma is due to the increased activities of catecholamine synthetic enzymes rather than to an insensitivity of tyrosine hydroxylase to end-product inhibition.

4. The activities of the enzymes involved in catecholamine catabolism, monoamine oxidase and perhaps catecholamine O-methyltransferase, were reduced in phaeochromocytoma. This finding provides a biochemical basis for the previous published observations of nonexocytotic release of catecholamines in these tumours. Thus excess amounts of newly synthesized noradrenaline which cannot be stored in the filled catecholamine storage vesicles may not be degraded owing to the reduced monoamine oxidase activity and could diffuse from the phaeochromocytoma into the circulation.
Subcellular Localization of Enterokinase in Human Duodenal Mucosa
Authors: Lobley R. W. , Franks Ruth , Holmes R.
Published: August 2015

1. Specimens of human duodenal mucosa were obtained at duodenotomy. Superficial mucosal scrapings were homogenized in isotonic sucrose solution and fractionated by differential centrifugation. The distribution of organelles among the subcellular fractions was monitored by assay of suitable marker enzymes.

2. Enterokinase was recovered predominantly in the nuclear + brush-border fraction and 80% of the total activity was found to be particulate; approximately 20% of the enzyme was present in the soluble fraction, compared with 1% of the brush-border markers sucrase and alkaline phosphatase.

3. The brush-border-containing fraction was subfractionated by treatment with hypertonic Tris followed by differential and density gradient centrifugation. Enterokinase was distributed among the subfractions in parallel with brush-border markers and was concentrated in a subfraction which was highly enriched in microvillous membranes.

4. It was concluded that enterokinase is localized primarily to the microvillous membrane of the epithelial cell brush border in man, but that in addition a proportion of the enzyme may be present in a soluble or easily released form in the duodenal mucosa.
Role of Cyclic AMP in the Natriuresis of Extracellular Fluid Volume Expansion in the Dog
Authors: Friedler R. M. , Descoeudres C. , Kurokawa K. , Kreusser W.-J. , Massry S. G.
Published: August 2015

1. The effect of extracellular volume expansion (ECVE) on renal production of cyclic AMP was evaluated in 19 thyroparathyroidectomized dogs. ECVE was produced by the infusion of Ringer bicarbonate solution at a rate of 2 ml min−1 kg−1 body weight; cyclic AMP was measured in plasma obtained from the aorta and renal vein and in the urine.

2. During the natriuresis of ECVE urinary excretion of cyclic AMP, the clearance of cyclic AMP, net nephrogenous cyclic AMP added both to urine and to the renal vein and hence total nephrogenous cyclic AMP increased significantly.

3. This rise in net production of cyclic AMP and a significant natriuresis by the kidney persisted for 60–90 min after discontinuation of active ECVE and return of renal plasma flow to normal.

4. The results support the notion that an increase in the production of cyclic AMP by the kidney may play a role in the natriuresis of ECVE.
The Renin-Aldosterone System in Exaggerated Natriuresis of Essential Hypertension
Authors: Pedersen E. B. , Kornerup H. J.
Published: August 2015

1. The effect of intravenous loading with 500 ml of sodium chloride solution (50 g/l) on plasma renin concentration, plasma aldosterone concentration, urinary sodium excretion and mean blood pressure was studied in 15 young patients with mild essential hypertension and 10 healthy normotensive control subjects.

2. Plasma renin concentration and plasma aldosterone concentration were suppressed to the same degree during loading in both the hypertensive and normotensive groups. Urinary sodium excretion was significantly higher in the hypertensive patients than in the normotensive subjects. Mean blood pressure increased slightly in both groups.

3. Plasma renin concentration and plasma aldosterone concentration were significantly correlated in both groups before sodium loading. The increase in urinary sodium excretion was significantly correlated to the suppression of plasma aldosterone concentration in the hypertensive, but not in the normotensive, group. No correlation was found between changes in urinary sodium excretion and changes in plasma renin concentration or mean blood pressure.

4. The results indicate that the suppressibility of the renin—aldosterone system by hyperosmotic sodium chloride solution is normal in young patients with mild essential hypertension. It is suggested that the changes in plasma aldosterone concentration induced by sodium loading might be involved in the regulation of exaggerated natriuresis in essential hypertension.
Increase in Serum Ionized Calcium during Exercise
Authors: Nielsen S. Pors , Christiansen T. Falch , Hartling O. , Trap-Jensen J.
Published: August 2015

1. Normal subjects showed an average increase in serum ionized calcium (Ca2+) concentration of 0·11 mmol/l in peripheral venous blood 10 min after onset of bicycle exercise at 70% of maximum aerobic capacity. The corresponding mean rise in serum total calcium concentration was 0·21 mmol/l.

2. The change in serum Ca2+ as result of acidification was studied in 20 normal subjects by carbon dioxide equilibration in vitro followed by measurement of serum Ca2+. The log serum Ca2+ was inversely proportional to serum pH.

3. The Δlog serum Ca2+/ΔpH in vitro was similar to the Δlog serum Caa+/ΔpH in vivo during exercise, this ratio, however, being somewhat greater during the first minute of exercise.

4. Serum Ca2+ returned to normal values about 20 min after stopping exercise as the pH returned to normal, but the fall immediately after stopping exercise was more pronounced than that due to the change in pH, as predicted from the studies in vitro.

5. Blood lactate concentration rose from 0·86 to 8·41 mmol/l after 10 min exercise, but the rise in blood lactate during exercise was slower than the rise in serum Ca2+. Also the fall during the recovery period was delayed compared with the fall in serum Ca2+.

6. It is suggested that the rise in serum Ca2+ during severe muscular exercise might be important for the physiological adaptations during work, and for bone metabolism.
Pulmonary Blood Volume in Chronic Bronchitis
Authors: Raffestin B. , Valette H. , Hebert J. L. , Duhaze P. , Lockhart A.
Published: August 2015

1. Pulmonary blood volume was measured in 39 patients with severe chronic bronchitis, of whom 29 had recently recovered from an acute exacerbation. Pa,o2 was below 10·3 kPa in all but five patients, Pa,co2 was above 5·6 kPa in 26 cases, and pulmonary artery mean pressure was above 20 mmHg in 29 cases. Pulmonary blood volume was measured with the double-injection—single-sampling technique using Indocyanine Green and pulmonary wedge injection.

2. Pulmonary blood volume in the 39 patients was significantly lower (343 ± 95 ml) than in a group of 16 normal subjects (469 ± 117 ml) studied previously by the same method. There was no correlation between pulmonary blood volume and driving pressure across the pulmonary circulation, or between pulmonary blood volume and Pa,o2.

3. Breathing 26–29% oxygen in 19 patients caused no significant changes in either pulmonary blood volume or pulmonary vascular resistance. Therefore the reduced pulmonary blood volume could not be attributed to hypoxic pulmonary vasoconstriction.

4. The finding of a diminished pulmonary blood volume in chronic bronchitis is best explained by a loss of pulmonary vessels. Pulmonary blood volume was not correlated with total lung capacity nor with the residual volume/total lung capacity ratio, nor was it significantly higher in the 16 patients with normal total lung capacity (352 ± 73 ml) than in the 23 patients with a total lung capacity greater than 110% of normal (331 ± 110 ml). There was therefore no correlation between the amount of emphysema and the reduction in pulmonary blood volume.
Intracellular Free Amino Acids in Muscle Tissue of Patients with Chronic Uraemia: Effect of Peritoneal Dialysis and Infusion of Essential Amino Acids
Authors: Bergström J. , Fürst P. , Norée L.-O. , Vinnars E.
Published: August 2015

1. Free amino acids were determined in the plasma and in the muscle tissue of 14 patients with chronic uraemia; eight were not on dialysis and six were having regular peritoneal dialysis. The concentration of each amino acid in muscle water was calculated with the chloride method.

2. In both groups of patients there were low intracellular concentrations of threonine, valine, tyrosine and carnosine, and high glycine/valine and phenylalanine/tyrosine ratios. Both groups of patients had increased amounts of 1- and 3-methylhistidine in plasma and in muscle water.

3. The non-dialysed patients had low intracellular concentrations of lysine, and the dialysed patients had high intracellular concentrations of lysine, isoleucine, leucine and of some of the non-essential amino acids.

4. After peritoneal dialysis for 22 h, the plasma concentration of several amino acids decreased but the intracellular concentrations of most amino acids did not change significantly.

5. Intravenous administration of essential amino acids and histidine during the last 4 h of dialysis increased in muscle the total free amino acids, the ratio of essential to non-essential amino acids and the valine and phenylalanine concentrations.

6. The results demonstrated that the plasma and muscle concentrations of several amino acids are grossly abnormal in chronic uraemia. Non-dialysed and dialysed patients exhibit important differences, especially in the intracellular amino acid patterns. Infusion of essential amino acids may result in enhancement of protein synthesis.