bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Conjugated and Unconjugated Bile Acids on Water and Electrolyte Absorption in the Human Jejunum
Authors: Russell R. I. , Allan J. G. , Gerskowitch V. P. , Cochran K. M.
Published: August 2015

1. The effect of conjugated and unconjugated bile acids in various concentrations on the absorption of water, sodium and chloride in the proximal jejunum in man has been studied using a perfusion system incorporating a proximal occluding balloon.

2. Unconjugated cholic acid and its glycine and taurine conjugates had no significant effect on water and electrolyte absorption. Unconjugated deoxycholic acid significantly inhibited water and electrolyte absorption at 3 mm concentration and net secretion occurred at concentrations of 5 mm, 7 mm and 10 mm. Similar results were found when taurodeoxycholic and glycodeoxycholic acid solutions were used. A greater effect was noted when higher concentrations of bile acids were used.

3. Unconjugated chenodeoxycholic acid caused net water and electrolyte secretion at 3 mm concentration and this effect became more marked with higher bile acid concentrations. Inhibition of absorption also occurred with taurochenodeoxycholic acid in a concentration of 3 mm and net secretion occurred at a concentration of 10 mm.

4. The results show that dihydroxy bile acids, conjugated or unconjugated, inhibit water and electrolyte absorption in the proximal jejunum in low concentration and cause net secretion in high concentration.
Circadian Variation in Plasma Iron Concentration and Reticuloendothelial Iron Release in the Rat
Authors: Lynch S. R. , Simon Monica , Bothwell T. H. , Charlton R. W.
Published: August 2015

1. As in man, the plasma iron concentration in rats exhibits a circadian variation, with an early morning peak and an evening trough.

2. The release into the plasma of iron liberated from haemoglobin within the reticuloendothelial cells of the liver and spleen was studied by injecting heat-damaged erythrocytes containing 59Fe-labelled haemoglobin.

3. The percentage of 59Fe released was lower in the morning than in the evening.

4. These observations suggest that a circadian variation in reticuloendothelial cell behaviour influences the plasma iron concentration.
Some Aspects of Pulmonary Function after Rapid Saline Infusion in Healthy Subjects
Authors: Collins J. V. , Cochrane G. M. , Davis Jane , Benatar S. R. , Clark T. J. H.
Published: August 2015

1. Rapid intravenous (i.v.) infusions of saline were administered to five healthy male volunteers. Measurements were made of static and dynamic lung volumes, ‘closing volume’ and pulmonary compliance before and after infusion; all measurements were made in the seated upright position.

2. Following a 1 litre infusion small decreases occurred in static and dynamic lung volumes in all studies and were associated in each case with an increase in ‘closing volume’. ‘Closing volume’ returned to normal within 1 h of the infusion.

3. After 2 litre infusions more marked decreases in all lung volumes occurred and were associated with variable changes in ‘closing volume’. The pattern of change varied between individual subjects and this is thought to reflect differences in localization within the lungs of the effects of the saline load in different subjects.

4. After 2 litre infusions static compliance was decreased in all subjects during the first 10–15 min. Changes in dynamic compliance showed marked individual variation.
Hepatic Synthesis of Transcobalamin II in the Rat
Authors: England J. M. , Tavill A. S. , Chanarin I.
Published: August 2015

1. Perfusion of the isolated rat liver was accompanied by a rising level of transcobalamin II in the perfusate. There was no change in the concentration of transcobalamin I over the 5 h perfusion period.

2. When [G-14C]leucine was added to the perfusate a 14C-labelled protein appeared in the same position as transcobalamin II on column chromatography.

3. It was concluded that transcobalamin II is synthesized by rat liver.
Influence of Albumin on the Extravascular Distribution of Unconjugated Bilirubin
Authors: Bloomer J. R. , Berk P. D. , Vergalla J. , Berlin N. I.
Published: August 2015

1. [3H]Bilirubin and 131I-labelled albumin were given simultaneously to six healthy adults by intravenous route and the amounts in the plasma were measured for several days. Multicompartmental analysis of the data showed that the rate of movement of [3H]bilirubin from the plasma into the extrahepatic extravascular space was 29·7 ± 7·3% (mean ± SEM) of the plasma pool/h, whereas the rate of movement of 131I-labelled albumin from plasma into the extravascular space was only 7·2 ± 1·0% of the plasma pool/h.

2. [14C]Bilirubin was found to equilibrate throughout the body of a child with the Crigler-Najjar syndrome within 24 h of intravenous administration, whereas 131I-labelled albumin required 4–5 days in human subjects.

3. Multicompartmental analysis of the plasma data in the six healthy adults indicated that the mass of material in the extrahepatic extravascular space relative to that in plasma was greater for unconjugated bilirubin than for albumin.

4. Studies of the tissue distribution of unconjugated bilirubin in homozygous Gunn rats demonstrated that the organs which comprise the rapidly exchanging extravascular albumin pool (liver, kidney and intestine) accumulated unconjugated bilirubin in excess of their albumin content, whereas lesser amounts of unconjugated bilirubin were accumulated in the tissues which make up the slowly exchanging extravascular albumin pool (muscle, fat and skin).

5. These findings indicate that unconjugated bilirubin moves more rapidly between plasma and extrahepatic extravascular sites than can be accounted for by transport bound to albumin. They also indicate that extravascular binding of unconjugated bilirubin includes tissue sites, as well as extravascular albumin.
Relationship between Plasma Cortisol and Peak Expiratory Flow Rate in Exercise-Induced Asthma and the Effect of Sodium Cromoglycate
Authors: Jaffe P. , König P. , Ijaduola O. , Walker S. , Godfrey S.
Published: August 2015

1. The changes in peak expiratory flow rate (PEF) and plasma cortisol were studied in relation to a 6 min period of treadmill running in six normal and eighteen asthmatic subjects. Of the asthmatics patients, five were not receiving treatment with steroids, six were receiving low doses of steroids (under 7·5 mg of prednisone daily) and seven were receiving high doses of steroids (over 7·5 mg of prednisone daily) at the time of study.

2. All subjects were studied twice within 1 week at similar times of day, once after premedication with sodium cromoglycate (SCG) and once after a placebo.

3. Resting PEF and plasma cortisol did not differ between placebo and SCG tests.

4. No change in PEF occurred as a result of exercise in the control subjects. The asthmatic patients developed post-exercise bronchoconstriction which was partly prevented by SCG but was not affected by steroids.

5. Plasma cortisol rose after exercise in the asthmatic subjects but not in the control subjects. The rise may have been related to the stress of exercise-induced asthma. SCG had no significant effect on plasma cortisol after exercise.
Turnover of Cholesteryl Esters in Plasma Low-Density and High-Density Lipoproteins in Familial Hyperbetalipoproteinaemia
Authors: Myant N. B. , Balasubramaniam S. , Moutafis C. D. , Mancini M. , Slack Joan
Published: August 2015

1. The turnover of cholesteryl esters in plasma high-density (HDL) and low-density (LDL) lipoproteins was measured in patients with familial hyperbetalipoproteinaemia in the homozygous and heterozygous forms and in control subjects.

2. The fractional rates of turnover of HDL and LDL cholesteryl esters were significantly lower in the patients than in the control subjects, but there was no significant difference between the absolute rates of turnover (expressed in mg h−1 kg body wt.−1) in the patients and controls.
Relationships between Ion and Water Movement in the Human Jejunum, Ileum and Colon during Perfusion with Bile Acids
Authors: Wingate D. L. , Krag E. , Mekhjian H. S. , Phillips S. F.
Published: August 2015

1. Perfusion of the human jejunum with low concentrations of glycine-conjugated bile acids in physiological solutions induced net fluid flow that varied between absorption and secretion, with only slight variation of the luminal osmotic and ionic milieu.

2. Transmucosal net flux rates for water and the principal ions were calculated. Regression analysis of the flux data was consistent with the concept of a ‘net transported fluid’ which was iso-osmotic with respect to the lumen, with a superimposed fixed net anion exchange unaffected by the rate or direction of bulk flow.

3. Recalculation of earlier data from comparable studies of the human colon showed similar relationships consistent with varying iso-osmotic bulk flow and fixed ion exchange, the latter differing from that found in the proximal bowel.

4. Studies were performed also in the human ileum. Variable iso-osmotic bulk flow was again encountered, but ion exchange was of a lower magnitude than in the jejunum or colon. Qualitatively, ion exchange in the ileum was intermediate between the jejunum and colon.

5. These analyses suggest that transmucosal bulk flow and ion exchange may be quantitatively and spatially independent processes. They provide support for the hypothesis that bulk flow may be intercellular (and hence extracellular), while ion exchange may take place across the luminal face of the mucosal cell.

6. Secretory agents, such as the dihydroxy bile acids, provide a useful means of analysing solute-solvent flow relationships in greatly differing bulk flow conditions with relatively stable physicochemical parameters.
Plasma Porphyrin Concentrations in Porphyria Cutanea Tarda
Authors: Moore M. R. , Thompson G. G. , Allen B. R. , Hunter J. A. A. , Parker Sheena
Published: August 2015

1. Plasma porphyrin concentrations in twelve patients with porphyria cutanea tarda (symptomatica) were compared with twenty normal controls.

2. The concentrations in porphyria cutanea tarda were significantly elevated.
The Mechanism of the Entry of Dye into Neutrophils in the Nitroblue Tetrazolium (NBT) Test
Authors: Segal A. W. , Levi A. J.
Published: August 2015

1. Washed buffy-coat preparations of human blood suspended in different media were exposed to the Nitroblue Tetrazolium (NBT) and the mechanism of entry of the dye into neutrophil polymorphonuclear leucocytes was investigated.

2. Stimulation of neutrophils with endotoxin and the presence of heparin and/or fibrinogen in the suspending medium were necessary for dye reduction.

3. NBT complexed with and precipitated heparin and/or fibrinogen from solution. The percentage of cells reducing the dye and the degree of precipitation of fibrinogen and heparin depended on the concentration of dye; the critical concentration of NBT necessary for each effect was the same.

4. Electron microscopy of stimulated neutrophils revealed the presence of amorphous material, which was probably complexed NBT, outside the cell, in the process of endocytosis and within membrane-bound vacuoles within the cytoplasm.

5. Neither complement nor immunoglobulins were obligatory for dye reduction in this system.

6. It is suggested that NBT only enters neutrophils in quantities visible by light microscopy, after stimulation which produces phagocytosis of a macromolecular complex of the dye and heparin and/or fibrinogen.
Intestinal Absorption of Dipeptides Containing Glycine, Phenylalanine, Proline, β-Alanine or Histidine in the Rat
Authors: Boullin D. J. , Crampton R. F. , Heading Christine E. , Pelling D.
Published: August 2015

1. The intestinal absorption of carnosine, glycylglycine, glycyl-d-phenylalanine, glycyl-l-phenylalanine, glycyl-l-proline and l-prolylglycine were investigated after intraluminal injection of dipeptide into anaesthetized rats.

2. With all six dipeptides, the intact substance was detected by ion-exchange chromatography in blood samples taken from the superior mesenteric vein.

3. The rate of hydrolysis of the dipeptides in tissue homogenates was measured in vitro.

4. The relative rates of hydrolysis varied by a factor of 300; there was an apparent inverse relationship between rate of hydrolysis and detection of intact peptide.

5. Peptide absorption was accompanied by increases in venous concentrations of the component amino acids, which appeared in proportions appropriate to the view that peptide absorption preceded hydrolysis.

6. It is suggested that slowly hydrolysed dipeptides may pass intact through the intestine wall under physiological conditions.
Spironolactone and Amiloride in the Treatment of Low Renin Hyperaldosteronism and Related Syndromes
Authors: Kremer D. , Beevers D. G. , Brown J. J. , Davies D. L. , Ferriss J. B. , Fraser R. , Lever A. F. , Robertson J. I. S.
Published: August 2015

1. Prolonged treatment with spironolactone in low-renin hyperaldosteronism invariably corrects plasma electrolyte abnormalities and usually lowers blood pressure.

2. Total exchangeable sodium, total body water, extracellular fluid and plasma volumes are reduced; total exchangeable and total body potassium, plasma renin and angiotensin II concentrations are increased.

3. Spironolactone is similarly effective in patients with apparently isolated deoxycorticosterone (DOC) excess; also in suspected mineralocorticoid excess not associated with elevation of aldosterone or DOC.

4. Studies of amiloride reveal similar effectiveness to spironolactone in low-renin hyperaldosteronism and in suspected mineralocorticoid excess.
The Formation of Deoxycholic Acid and Chenodeoxycholic Acid in Man
Authors: Einarsson Kurt , Hellström Kjell
Published: August 2015

1. The turnover of deoxycholic acid and chenodeoxycholic acid was studied in six normolipaemic patients after oral administration of trace amounts of isotopically labelled compounds.

2. The mean values for half-life, pool size and turnover of deoxycholic acid were 3·0 days, 663 mg and 171 mg/day respectively. The corresponding values recorded for chenodeoxycholic acid were 2·8 days, 781 mg and 207 mg/day.

3. A comparison of the turnover rates of deoxycholic acid and cholic acid in three subjects indicated that 25–61% of the cholic acid was converted into deoxycholic acid.

4. Only trace amounts of radioactivity were recovered in the trihydroxycholanic acid fraction of duodenal bile after the administration of [14C]deoxycholic acid or [3H]chenodeoxycholic acid.
Competitive Protein-Binding Assay for 25-Hydroxycholecalciferol
Authors: Edelstein S. , Charman M. , Lawson D. E. M. , Kodicek E.
Published: August 2015

1. A competitive protein-binding assay for plasma 25-hydroxycholecalciferol was developed, using Sephadex LH-20 columns for the isolation of the sterol and a partially purified protein from rat serum as the binding protein.

2. The mean plasma 25-hydroxycholecalciferol in eighteen male and female normal volunteers was 38 ± SD 14 pmol/ml (15–2 ± 5–6 ng/ml).

3. Levels of 25-hydroxycholecalciferol in plasma of four male volunteers maintained for 2 months on a diet supplemented with 26·1 nmol (10 μg) of cholecalciferol a day were found to be significantly higher.

4. High correlation was established between plasma 25-hydroxycholecalciferol values obtained by the competitive protein-binding assay and values obtained by bioassay.
Lithium Accumulation in Bone after Oral Administration in Rat and in Man
Authors: Birch N. J.
Published: August 2015

1. The concentration of lithium in bone was determined after various periods of lithium administration in rats of differing ages and also after discontinuation. Lithium content was determined in human bone of three lithium-treated and two control subjects.

2. There was an inverse relationship between age at commencement of treatment and the final bone lithium content. This suggests that lithium is incorporated into the mineral of rapidly growing bone.

3. The loss of lithium from bone after discontinuation of medication indicates that one fraction is lost rapidly, and a large fraction remains and is lost very slowly.

4. Analysis of human bone from three subjects after lithium discontinuation shows that concentrations exist similar to those of rat bone. Control human bone had a lithium concentration which was similar to that of control rat bone.
A Comparative Study of the Distribution of Soluble and Particulate Glycyl-l-Leucine Hydrolase in the Small Intestine
Authors: Das Manjusri , Radhakrishnan A. N.
Published: August 2015

1. A comparative study has been made of glycyl-l-leucine hydrolase activity in the soluble and particulate fractions of intestinal mucosa from monkey, guinea-pig, rabbit and rat. The specific activity of the soluble enzyme is very high in monkey and guinea-pig, and lower in rabbit and rat. The particulate enzymes from all the four species show low specific activities and form 1–10% of the total activity.

2. The pH optima in all cases lie in the range 7·6–7·8. The Km values of the substrate were similar for both soluble and particulate enzyme from monkey and guinea-pig, but in the rabbit and rat the Km value with the particulate enzyme was higher than with the soluble enzyme.

3. The particulate enzyme activity in all cases was the highest in the distal regions of the intestine, whereas the soluble enzyme showed maximal activity in the proximal and middle regions.
Sodium and Potassium Transport Rates in Normal Human Leucocytes in Hypo-Osmolal Extracellular Fluid
Authors: Hilton P. J. , Patrick J.
Published: August 2015

1. Sodium and potassium transport rates were studied in normal human leucocytes exposed to iso-osmolal and hypo-osmolal extracellular fluid.

2. Hypo-osmolality of the extracellular fluid led to an increase in sodium influx and a decrease in potassium influx expressed as mmol h−1 kg−1 cell dry weight. The fall in potassium influx was smaller than the rise in sodium influx and was confined to the ouabain-insensitive portion of the flux.

3. The rate constants for sodium and potassium efflux did not differ significantly between the iso-osmolal and hypo-osmolal media.
The Interference of Human IGG with the Double-Antibody Radioimmunoassay of Thyrotrophic Hormone and its Clinical Significance
Authors: Chapman C. , Hutton W. N. , Hayter C. J.
Published: August 2015

1. High values for plasma thyrotrophic hormone, which did not correlate with other parameters of thyroid function, were found in patients with abnormally high plasma immunoglobulin concentrations.

2. Results indicate that human IgG interferes with the post-precipitation double-antibody radioimmunoassay of thyrotrophic hormone. It is possible that this interference occurs with similar radioimmunoassays of other substances.
Effects of Ethacrynic Acid and Frusemide on Urinary Phosphate in the Dog
Authors: Duarte C. G.
Published: August 2015

1. The renal excretion of phosphate was studied in dogs under control conditions and during infusion of ethacrynic acid or frusemide at different levels of filtered load.

2. Both of these diuretic compounds significantly enhanced the fractional excretion of phosphate at normal and moderately decreased filtered loads, and a good correlation between fractional excretions of sodium and phosphate could then be demonstrated.

3. When the blood flow to the left kidney was decreased by constricting the aorta below the right and above the left renal arteries, fractional excretion of phosphate decreased below control levels in the left kidney although that of sodium remained above pre-diuresis values.

4. The phosphaturic effect of ethacrynic acid and frusemide might be the result of a proximal site of action. The reversal of the phosphaturia by aortic constriction might have been caused by enhanced proximal reabsorption of phosphate and minimal delivery of this ion to the more distal sites of diuretic action.
The Contrasting Effects on Bone Histology of Vitamin D and of Calcium Carbonate in the Osteomalacia of Chronic Renal Failure
Authors: Eastwood J. B. , Bordier P. J. , Clarkson E. M. , Chot S. Tun , De Wardener H. E.
Published: August 2015

1. The histological appearances of cancellous bone from the ilium have been quantified in thirteen patients with osteomalacia due to chronic renal failure.

2. There was an excess of osteoid tissue and a reduction in the extent of the calcification front in that osteoid lamella lying next to calcified bone.

3. Administration of calcium compounds orally produced an increase of punctate calcification within the osteoid, but there was no change in the extent of the calcification front.

4. Administration of vitamin D produced a marked rise in the extent of the calcification front but no increase of punctate calcification within the osteoid.

5. This rise in the extent of the calcification front was not dependent on a rise in plasma calcium × plasma phosphorus product.

6. It is concluded that vitamin D has a direct action on the bone in patients with the osteomalacia of chronic renal failure.
Variation in Glomerular Sialic Acid Content in Diabetes and as the Result of Ageing
Authors: De Bats A. , Gordon A. H. , Rhodes E. L.
Published: August 2015

1. The glomerular sialic acid content of kidneys from diabetic subjects, aged subjects and healthy young individuals was determined.

2. Similar mean sialic acid contents were found in the glomeruli of elderly diabetic subjects, and in age- and sex-matched non-diabetic subjects.

3. Higher mean sialic acid content was found in glomeruli from healthy, young non-diabetic subjects.

4. These results, in conjunction with other reported work, indicate that low sialic acid content may result from both diabetic and age changes in the glomeruli.
Pyloric Reflux: A Modification of the Two-Component Hypothesis of Gastric Secretion
Authors: Hobsley M.
Published: August 2015

1. Gastric juice was obtained during continuous maximal stimulation with histamine diphosphate, 0.13 μmol h−1 kg−1 (0.04 mg h−1 kg−1) intravenously, in thirty-four control subjects, twenty-eight patients with duodenal ulcer, and eighteen with gastric ulcer. After correction for pyloric losses, the average rate of outputs of water, and of H+, Na+, K+ and Cl− were determined.

2. The results were analysed in terms of the two-component theory of gastric secretion. The acid components in control subjects and duodenal ulcer patients were similar in composition, but that in gastric ulcer patients was by comparison hypotonic and less acid and contained more sodium ions.

3. Calculation of the volume and composition of the alkaline component gave reasonable results in the control and duodenal ulcer groups, but impossible results in the gastric ulcer group. The gastric juice of gastric ulcer patients could not be described in terms of classical two-component theory.

4. In all three groups, volume correlated quite well with Cl− output alone, less well with H+ output, poorly with K+ output, and not at all with Na+ output. However, when volume was expressed as a function of the outputs of Cl− and one other ion, K+ performed poorly, H+ well, and Na+ best of all.

5. Some features suggest that reflux of alkaline liquid from the duodenum is a better explanation of these results than back-diffusion of H+ in exchange for Na+ between the lumen and wall of the stomach.

6. If the refluxing liquid is assumed to be isotonic, its composition can be calculated. Hence, the volume of reflux in a sample of gastric juice can be deduced. Reflux appeared to be more important in the gastric ulcer patients than in the other two groups.
Effects of a Sustained Muscular Contraction on Human Intraocular Pressure
Authors: Marcus D. F. , Edelhauser H. F. , Maksud M. G. , Wiley R. L.
Published: August 2015

1. Normal subjects performed fatiguing static hand-grip contraction at tensions of 20% and 55% of their maximum voluntary contraction (MVC). Intraocular pressure (IOP) was measured by applanation tonometry before, during and after the isometric exercise. Forearm blood samples were taken from the antecubital vein in both the exercised and non-exercised arm before and 2 min post-exercise for measurement of plasma lactate, osmolality, Pv,o2, Pv,co2 and pH.

2. During hand grip the heart rate and blood pressure increased significantly, whereas the IOP remained unchanged from control in both the 20% and 55% MVC experiments.

3. In the recovery period heart rate and blood pressure returned to control values within 3 min and the IOP decreased significantly from control in both the 20% and 55% MVC experiments.

4. When an occlusion cuff was inflated on the exercising arm just before release of the 55% MVC grip, the decreased IOP could be delayed until the cuff was released.

5. Post-exercise blood samples showed elevated lactate concentrations and Pv,o2 and decreased pH in the exercised arm; however, the values remained unchanged in the non-exercised arm. The decreased IOP after exercise may be related to an increased blood lactate concentration.
Changes in the Fatty Acid Composition of Plasma Lipoproteins during Administration of Intralipid to a Patient with Essential Fatty Acid Deficiency
Authors: Thompson G. R. , Heath J. , Press M.
Published: August 2015

1. The fatty acid composition of the cholesterol esters, triglycerides and lecithin components of the major plasma lipoprotein classes was determined before and after the intravenous infusion of a linoleate preparation into a patient with essential fatty acid deficiency.

2. Marked differences developed between the fatty acid composition of the cholesterol esters of very-low-density lipoprotein (VLDL) on the one hand and of low- and high-density lipoproteins (LDL and HDL) on the other hand.

3. The data suggest that the infused linoleate was selectively incorporated into LDL and HDL cholesterol esters by the action of plasma lecithin-cholesterol acyltransferase, after prior incorporation into lipoprotein lecithin. In contrast, there was no rise in the linoleate content of VLDL cholesterol esters, which probably originated in either the liver or the small intestine.

4. These findings support the concept that plasma cholesterol esters are heterogeneous.
The Effect of Prolonged Ethanol Treatment on the Sodium-Plus-Potassium-Ion-Stimulated Adenosine Triphosphatase Content of Cultured Human and Mouse Cells
Authors: Lindsay R.
Published: August 2015

1. HeLa cells from human cervix and L cells from mouse fibroblasts were cultured in the presence and absence of ethanol.

2. Ethanol produced an increase in the sodium-plus-potassium-ion-stimulated adenosine triphosphatase (Na-ATPase).

3. This effect was inhibited by cycloheximide.

4. Ethanol did not change the Na-ATPase content of mouse L cells.
Vitamin D Metabolism and Parathyroid Function in Man
Authors: Mawer E. Barbara , Backhouse Joan , Hill L. F. , Lumb G. A. , De Silva Priyadarshini , Taylor Carol M. , Stanbury S. W.
Published: August 2015

1. The metabolism of an intravenous pulse dose of double-isotope-labelled cholecalciferol has been studied in control subjects with widely differing states of vitamin D nutrition and in patients with primary disorders of parathyroid function.

2. The formation of labelled 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and labelled 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] has been related to the prevailing concentrations in serum of 25-hydroxycholecalciferol [25-(OH)D3], immunoreactive parathyroid hormonel, calcium and orthophosphate (Pi).

3. In control subjects with relative vitamin D deficiency [serum 25-(OH)D3 <2.5 nmol/l (10 ng/ml)], serum labelled 1,25-(OH)2D3 was related inversely to the serum 25-(OH)D3 and serum calcium, and directly to serum immunoreactive parathyroid hormone. No formation of 1,25-(OH)2D3 was detectable in vitamin D-replete individuals, who appeared to form labelled 24,25-(OH)2D3 preferentially.

4. No control subject produced significant amounts of both labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously.

5. All subjects with primary hyperparathyroidism produced significant amounts of labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously; the renal turnover of 25-(OH)D3 was apparently greater than in nutritionally matched controls. Serum labelled 1,25-(OH)2D3 in this disease was not correlated with serum 25-(OH)D3, immuno-reactive parathyroid hormone, calcium or Pi. Production of labelled 24,25-(OH)2D3 was inappropriately high for the prevailing nutritional state.

6. The indirectly estimated molar concentration of 1,25-(OH)2D3 showed only a fourfold variation in control subjects (45-180 pmol/l), compatible with its having a regulated hormonal function.

7. The data suggest that the production of 1,25-(OH)2D3 from a pulse dose of cholecalciferol is normally regulated, directly or indirectly, by the parathyroid hormone.
Autoregulation of Renal Blood Flow in Dogs at Normal Body Temperature and at 27°C
Authors: Chapman B. J. , Withey W. R. , Munday K. A.
Published: August 2015

1. Dogs cooled to 27°C were compared with control dogs maintained at 38°C. The mean arterial blood pressure, renal blood flow and glomerular filtration rate were lower in the hypothermic animals.

2. The relation between mean arterial blood pressure and renal blood flow was investigated. Autoregulation of renal blood flow occurred in the kidneys of normothermic and hypothermic animals. Thus the reduction in renal blood flow during hypothermia is not due simply to the fall in mean arterial blood pressure.

3. Similarities between recordings of renal blood flow obtained at 38°C and 27°C suggest that its autoregulation occurs by the same mechanism at the two temperatures.

4. Autoregulation of renal blood flow occurred in hypothermic kidneys in the presence of a cold-induced vasoconstriction. The observed responses to cold and to alterations in mean arterial blood pressure may take place in different areas of the renal vasculature.
Effects of Beta-Adrenergic Receptor Blockade on the Renal Vascular Response to a Low Sodium Diet in the Rabbit
Authors: Warren D. J. , Ledingham J. G. G.
Published: August 2015

1. The effect of propranolol on total and regional renal blood flow was measured in conscious rabbits after 6 days on normal or low sodium diets.

2. Propranolol inhibited the fall in total superficial cortical renal blood flow which occurred in response to the low sodium diet but did not influence renal blood flow in rabbits on a normal sodium diet.

3. Reduction and redistribution of renal blood flow in response to a low sodium diet appears to be mediated by a beta-receptor mechanism and may be a consequence of intrarenal release of renin.
Anti-Hypertensive Adrenergic-Blocking Agents: Effects on Sodium Balance, the Renin-Angiotensin System and Haemodynamics
Authors: Safar M. E. , Weiss Y. A. , Corvol P. L. , Menard J. E. , London G. M. , Milliez P. L.
Published: August 2015

1. The changes in plasma volume, haemodynamic variables, plasma renin activity and plasma aldosterone were studied in forty-one hypertensive patients after administration of adrenergic-blocking agents. Four drugs were used: alpha-methyldopa (fourteen patients), guanethidine (ten patients), clonidine (nine patients) and reserpine (eight patients). Drugs were administered orally during 7 days' hospitalization on a normal sodium diet (110 mmol/day).

2. The four drugs had similar effects: a significant decrease in blood pressure, a significant increase in plasma volume and no change in stroke volume.

3. With alpha-methyldopa and guanethidine, heart rate, plasma renin activity and plasma aldosterone were unchanged.

4. With reserpine and clonidine, heart rate and plasma renin activity were significantly decreased, whereas plasma aldosterone did not change significantly.

5. This study suggests that the decrease in plasma renin activity was related to the lowering of the heart rate rather than to sodium retention and that adrenergic-blocking agents can impair the normal relationship between stroke index and plasma volume, between plasma volume and plasma renin activity, and between plasma renin activity and plasma aldosterone.
Prazosin in the Treatment of Hypertension
Authors: Fernandes M. , Smith I. Sanford , Weder A. , Kim K. E. , Gould Anne B. , Busby Patricia , Swartz C. , Onesti G.
Published: August 2015

1. Prazosin decreases blood pressure in normotensive, renal hypertensive and spontaneous hypertensive rats. The effect is greatest in the last-named.

2. In spontaneously hypertensive rats the decrease in pressure is associated with a decrease in heart rate.

3. In hypertensive patients prazosin decreases blood pressure by decreasing total peripheral resistance with minor effects on cardiac output.

4. Prazosin is effective in the long-term therapy of hypertensive patients, alone and in combination with a diuretic. The effect on blood pressure is the same in the supine and standing position.
Carotid Baroceptor Re-Setting in the Hypertensive Dog
Authors: Sleight P. , Robinson J. L. , Brooks D. E. , Rees P. M.
Published: August 2015

1. The behaviour of forty-four single carotid baroreceptor fibres from nine dogs with normal blood pressure was contrasted with that of forty-seven single fibres from nine dogs with renal (nephrectomy-clip) hypertension.

2. It was found that in response to a square-wave pressure step, the mean steady-state threshold pressure was 99.23 mmHg for the normotensive dogs and 12913 mmHg for the hypertensive dogs.

3. The degree of re-setting appeared to correlate with the duration of the hypertension but was not seen until an animal had been hypertensive for more than 4 days.

4. In one animal, hypertensive for 7 weeks but whose blood pressure returned towards normal after removal of the clip, the receptor characteristics were normal.

5. No change in the gain of the receptor sensitivity was seen.

6. Light-microscopy and electron miscroscopy of the opposite (non-perfused) carotid sinus revealed no differences in the fibre morphology or density between the hypertensive and normotensive animals (a random sampling, four normal and six hypertensive).
Localization of Central Noradrenergic Mechanisms in Cardiovascular Regulation in Rats
Authors: Boudier H. Struyker , Smeets G. , Brouwer G. , Van Rossum J.
Published: August 2015

1. Various drugs were injected stereotactically into the brain of anaesthetized rats.

2. Noradrenaline injected into the area of the nucleus of the tractus solitarius in the lower brain stem or into the far anterior hypothalamus/pre-optic region induced a fall in blood pressure and in heart rate related to the administered dose.

3. When injected into the anterior hypothalamus/pre-optic region, clonidine and alpha-methyl-noradrenaline induced a long-lasting decrease in blood pressure and heart rate.
Dopa, Catecholamines and Their Metabolites in Essential Hypertension
Authors: Januszewicz W. , Wocial B.
Published: August 2015

1. Urinary excretion of dopa, catecholamines and their metabolites (vanillylmandelic acid, methoxycatecholamines, 3-methoxy-4-hydroxyphenylglycol and homovanillic acid) were studied in eighty patients with essential hypertension and in twenty-five healthy control subjects.

2. Increased urinary excretion of catecholamines, dopa and catecholamine metabolites was found in a proportion of cases.

3. The relationship between urinary excretion of catecholamine metabolites and the excretion of dopa and noradrenaline was studied.

4. In view of the suggested significance of 3-methoxy-4-hydroxyphenylglycol as an index of brain catecholamine metabolism, particular attention was paid to urinary excretion of this metabolite in the subjects under study.
Adrenergic Responses to Sustained Handgrip in Patients with Juvenile-Onset-Type Diabetes Mellitus
Authors: Nazar K. , Tatoń J. , Chwalbińska-Moneta J. , Brzezińska Z.
Published: August 2015

1. The response of plasma noradrenaline, arterial blood pressure and heart rate to sustained handgrip at 30% of maximal voluntary contraction was studied in patients with long-term juvenile-onset-type diabetes mellitus and healthy subjects of comparable age.

2. There was no significant difference between the intensity and duration of handgrip in diabetic patients and healthy subjects.

3. Sustained handgrip produced an increase in plasma concentration of noradrenaline both in diabetic and healthy subjects but the response in the diabetic subjects was significantly less.

4. The increase in systolic blood pressure during handgrip was significantly greater in diabetic subjects than in normal subjects. The increases in diastolic and mean blood pressure did not differ significantly.

5. The increase in heart rate during handgrip was greater in healthy subjects than in diabetic subjects. The response was smaller in diabetic patients with retinopathy than in the patients without retinopathy.

6. The sustained handgrip test may be useful for the diagnosis of abnormal sympathetic nervous system and haemodynamic responsiveness in diabetic patients.
Changes in the Renal and Extrarenal Handling of Phosphate Induced by Disodium Etidronate (EHDP) in Man
Authors: Walton R. J. , Russell R. G. G. , Smith R.
Published: August 2015

1. The diphosphonate, disodium etidronate (disodium ethane-1-hydroxy-1,1-diphosphonate; EHDP), is known to increase plasma inorganic phosphate in man. The present study examines the mechanism of this effect.

2. When EHDP was given by mouth at a dose of 80 μmol (20 mg) kg−1 day−1, plasma phosphate was significantly increased 24 h after the first dose but did not reach its maximum value for 2–3 weeks. When the drug was stopped, plasma phosphate returned to pretreatment values within 3 weeks.

3. Urinary excretion rate of phosphate was not greatly changed during treatment with EHDP despite the large increase in plasma phosphate, suggesting an alteration in renal handling. This was examined directly by infusing phosphate and inulin in six patients off and on EHDP.

4. EHDP had no effect on glomerular filtration rate (GFR) but produced a large increase in the maximum rate of renal tubular reabsorption of phosphate (Tm,P). The ratio Tm,P/GFR increased from a mean value of 1.15 mmol/l to 2.10 mmol/l on EHDP. This increase accounted for the hyperphosphataemia.

5. The same amount of phosphate infused at the same rate produced a greater rise in plasma phosphate when patients were on EHDP than when they were not, indicating a reduced net rate of entry of phosphate into tissues other than kidney.

6. Fasting total plasma calcium concentration and urine calcium excretion rate were not significantly altered by EHDP but the ability of infused phosphate to decrease plasma calcium was diminished.

7. It is suggested that EHDP alters phosphate transport in kidney and other tissues by a mechanism which is probably independent of the known hormonal influences on phosphate metabolism.
Effect of Liver Failure on the Response of Ventilation and Cerebral Circulation to Carbon Dioxide in Man and in the Goat
Authors: Stanley N. N. , Salisbury B. G. , McHenry L. C. , Cherniack N. S.
Published: August 2015

1. The acid-base state of arterial blood and cerebrospinal fluid, and the ventilatory response to CO2, were measured in twelve patients with liver disease. The CO2 response was also measured in eight goats before and after the experimental production of liver failure. Arterial Pco2 and pH, cerebral blood flow and the cerebral metabolic rate for oxygen were also measured in four of the goats while they breathed air and various CO2-enriched gas mixtures.

2. Liver failure was accompanied by a respiratory alkalosis in both the patients and in the goats. Decreased Pco2 and increased pH occurred in the cerebrospinal fluid and in the arterial blood of the patients.

3. The slope of the ventilatory response to CO2 was reduced when liver failure was severe, in patients and goats alike. In addition there was a reduction in the extrapolated Pco2 at zero ventilation, even when liver failure was mild.

4. Cerebral blood flow and metabolic rate were consistently reduced in the goats during liver failure. There was also less cerebral vasodilatation and a greater reduction in cerebral metabolism during experimental hypercapnia when these animals were in liver failure.

5. The decreases in the ventilatory and cerebral circulatory responsiveness to CO2 indicate that the brain is less well defended against hypercapnia in liver failure, and these changes are especially unfavourable as cerebral function deteriorates when the Pco2 is increased.
Effect of Proportional Reduction of Sodium Intake on the Adaptive Increase in Glomerular Filtration Rate/Nephron and Potassium and Phosphate Excretion in Chronic Renal Failure in the Rat
Authors: Espinel C. H.
Published: August 2015

1. The influence of dietary sodium intake on the glomerular filtration rate (GFR/nephron) and potassium and phosphate excretion was examined at three stages of progressive chronic renal failure produced in rats by sequential partial nephrectomies.

2. The adaptive increased sodium excretion per nephron in the control group receiving a constant sodium intake did not occur in the experimental group that had a gradual reduction of dietary sodium in direct proportion to the fall in GFR.

3. Despite the difference in sodium excretion, the increase in GFR/nephron, the daily variation in the amount of potassium and phosphate excreted, the increase in potassium and phosphate excretion per unit nephron, and the plasma potassium and phosphate concentrations were the same in the two groups.

4. The concept of ‘autonomous adaptation’ in chronic renal failure is presented.
Increased Plasma Calcitonin in Early Acute Renal Failure
Authors: Ardaillou R. , Beaufils M. , Nivez Marie-Paule , Isaac R. , Mayaud C. , Sraer J.-D.
Published: August 2015

1. High plasma immunoreactive calcitonin concentrations were observed in ten of eleven patients with acute renal failure, particularly in the oliguric phase.

2. Immunoreactive calcitonin decreased progressively with time, independently of recovery of renal function.

3. Radioimmunoassay curves obtained with serial dilutions of plasma from these patients were parallel to or superimposed upon those obtained with calcitonin standards.
A Common Mechanism for Transport of Di- and Tri-Peptides by Hamster Jejunum in Vitro
Authors: Addison Jill M. , Burston D. , Dalrymple Judith A. , Matthews D. M. , Payne J. W. , Sleisenger M. H. , Wilkinson S.
Published: August 2015

1. This paper describes the results of a survey of the effects of peptides and amino acids on uptake by rings of everted hamster jejunum in vitro of glycylsarcosylsarcosine, a tripeptide which is taken up by an active mechanism but is very resistant to hydrolysis, appearing intact in the rings. The results of a small number of similar experiments with β-alanylglycylglycine, another tripeptide which is taken up with very little hydrolysis, are also described.

2. Uptake of the two tripeptides was inhibited by other di- and tri-peptides, but not by free amino acids. The results suggest that dipeptides and tri-peptides share a common uptake mechanism. The tetrapeptide glycylsarcosylsarcosylsarcosine did not inhibit uptake of glycylsarcosylsarcosine, and appears to be unable to utilize the uptake mechanism.

3. The results add to information about the influence of molecular structure on intestinal uptake of peptides by the system used by glycylsarcosylsarcosine, which is shared by a wide range of other di- and tri-peptides. In conjunction with previous results, they suggest that substitution of the N-terminal amino or C-terminal carboxyl groups reduces affinity for transport, that the presence of a β-amino acid residue in a peptide is tolerated by the transport system, and that the presence of a d-amino acid residue reduces affinity for transport. Some peptides containing or made up of basic or acidic amino acid residues appear to have a low affinity for the transport system used by glycylsarcosylsarcosine.

4. Of two biologically active peptides, one, cephalexin, a peptide antibiotic, inhibited uptake of glycylsarcosylsarcosine and is probably transported by the same system. The other, prolylleucylglycineamide, which has the action of a hypothalamic regulatory factor, did not, and its structural features may make it unsuitable for carrier-mediated transport by the small intestine.
The Direct Effect of Calcium on the Hyperparathyroidism of Chronic Renal Failure
Authors: Kaye M.
Published: August 2015

1. The direct effect of calcium on the hyperparathyroidism of chronic renal failure was studied in rats with induced chronic renal failure, who were fed on a diet low in phosphate and who received supplemental phosphate by injection. They were given a normal (0·8%), or low (0·1%) or high (1·7%) calcium diet.

2. The animals on the low calcium diet had larger parathyroids and more severe bone disease at the end of 4 weeks, indicating the importance of calcium intake in directly influencing the degree of hyperparathyroidism.

3. Increasing the calcium content of the diet from 0·8% to 1·7% produced no additional benefits.
Hepatic Glutathione Depletion and Impaired Bromosulphthalein Clearance Early after Paracetamol Overdose in Man and the Rat
Authors: Davis M. , Ideo G. , Harrison N. G. , Williams R.
Published: August 2015

1. Plasma clearance of bromosulphthalein was impaired in patients within 8 h, and in rats within 2 h, of paracetamol overdose, before biochemical signs of liver damage had appeared.

2. Paracetamol and bromosulphthalein competed for uptake into the liver and excretion into the bile. Impaired hepatic uptake of bromosulphthalein could also be demonstrated in man at doses of the drug within the therapeutic range.

3. In patients studied a smaller proportion of bromosulphthalein was retained in the plasma as the glutathione conjugate after an overdose than after therapeutic doses. This effect could be reproduced in the rat and shown to be due to depletion of hepatic glutathione and to impairment in the activity of the enzyme glutathione-S-aryl transferase.

4. These studies provide further evidence that depletion of hepatic glutathione occurs after paracetamol overdose in man, as in the experimental animal, allowing the subsequent accumulation and binding of a toxic metabolite of the drug within liver cells. Impaired enzymic conjugation of the toxic metabolite with hepatic reduced glutathione may also be important in this situation.
Systolic Blood Pressure Variation during the First 6 Days of Life
Authors: De Swiet M. , Fancourt R. , Peto J.
Published: August 2015

1. Systolic blood pressure was measured by a Doppler ultrasound technique in twenty normal babies on 6 successive days after the day of delivery. In three babies blood pressure was recorded every 15 min for 24 h.

2. Systolic blood pressure during the first 6 days of life was 95 (sem = 2) mmHg.

3. Systolic blood pressure increased on average by 2 mmHg/day, but increased most between the second and third days of life.

4. Systolic blood pressure was 11 mmHg higher when awake than when the babies were asleep.

5. There was marked within-baby variation in the systolic blood pressure of neonates, which could not be accounted for by age or recognizable changes in level of consciousness.
Plasma Uric Acid Concentration Related to the Urinary Excretion of Aldosterone and of Electrolytes in Normal Subjects
Authors: Ramsay L. E. , Auty R. M. , Horth C. E. , Levine D. , Shelton J. R. , Branch R. A.
Published: August 2015

1. The relations between the concentration of plasma uric acid and urinary excretion of aldosterone, sodium and potassium, were studied in ten healthy males on a diet containing 160 mmol of sodium and 90 mmol of potassium per day.

2. Plasma uric acid correlated positively with aldosterone excretion and this correlation was statistically independent of sodium and potassium excretion.

3. Plasma uric acid correlated positively with potassium excretion and negatively with the urinary sodium/potassium ratio. There was no significant simple correlation with sodium excretion but the partial correlation of plasma uric acid and sodium excretion was negative and significant when excretion of aldosterone and potassium were held constant.