bluuebunny/crossref_metadata_2025 huggingface dataset:
An Investigation into the Pathogenesis of Hypertension in Acromegaly
Authors: Snow M. H. , Piercy D. A. , Robson Valerie , Wilkinson R.
Published: August 2015

1. In 29 patients with acromegaly, plasma renin activity and growth hormone were measured during fasting and recumbency on free diet. Exchangeable sodium was measured in all cases and expressed as a percentage of the expected value on the basis of lean body mass.

2. Twenty-two control subjects without evidence of cardiovascular, renal or endocrine disease were studied in the same way.

3. There was a significant increase in exchangeable sodium and suppression of plasma renin activity in the acromegalic patients in comparison with control subjects.

4. There was a significant positive correlation between exchangeable sodium and plasma growth hormone.

5. Hypertensive acromegalic patients (diastolic blood pressure ≥ 100 mmHg) tend to have a lower (although not significantly so) exchangeable sodium than normotensive subjects.

6. We conclude that (a) suppression of plasma renin activity in acromegaly can be explained by sodium retention, (b) hypersecretion of growth hormone is probably responsible for the increased exchangeable sodium, and (c) sodium overload cannot be directly related to blood pressure but may contribute to the increased occurrence of hypertension in acromegaly.
Measurement of Mouth Occlusion Pressure as an Index of Respiratory Centre Output in Man
Authors: Burki N. K. , Mitchell L. K. , Chaudhary B. A. , Zechman F. W.
Published: August 2015

1. Simultaneous measurements of mouth pressure at the end of the first 0·1 s of inspiratory occlusion (P0·1) at functional residual capacity and the maximum rate of rise of this pressure (dP/dt max.) were made repeatedly in five normal subjects during resting respiration; the coefficient of variation of dP/dt max. was 36·2%, compared with 50·6% for P0·1.

2. During both isocapnic hypoxia and hyperoxic hypercapnia in five normal subjects there was a close correlation between ventilation (V̇E) and both P0·1 and dP/dt max., and between end-tidal Pco2 or Po2 and P0·1 and dP/dt max.; during both procedures there was a close correlation between P0·1 and dP/dt max.

3. The time at which dP/dt max. occurred (Tmax.) was not correlated with changes of dP/dt max. in either procedure. Tmax. was greater than 0·12 s in most studies.

4. The regression coefficients of P0·1 and dP/dt max. on V̇E were significantly different in hypoxia as compared with hypercapnia in four out of the five subjects; on repeated hypercapnic stimulation in two out of three subjects these regression coefficients again varied significantly. Changes in lung volume or inspiratory volume-timing relationship were not responsible for these differences. These results suggest that mouth occlusion pressure, as reflected by P0·1 or dP/dt max., is a complex variable, reflecting the motor output of the respiratory centre, but also affected by random variations in the measurements and probably by changes in lung volume.
Effects of Phenylalanine Analogues on Renal Tubular Reabsorption of Amino Acids in the Rat
Authors: Owens C. W. I.
Published: August 2015

1. A method is described for the serial determination of renal tubular reabsorption of amino acids in the ethanol-anaesthetized rat. It utilizes intravenous radio-labelled inulins, automated amino acid analysis and forced diuresis.

2. Intravenous loading with phenylalanine and infusion of phenylalanine analogues in this preparation decrease reabsorption of endogenous amino acids in accordance with existing concepts of amino acid transport.

3. Maximal tubular reabsorption (Tmax.) could not be demonstrated for phenylalanine at plasma concentrations below 9 mmol/l.

4. Infusion of phenylalanine analogues into phenylalanine-loaded (‘phenylketonuric’) rats did not specifically inhibit tubular reabsorption of phenylalanine and it is unlikely that any of the substances tested have a potential therapeutic use in man.

5. p-Guanidino derivatives of phenylalanine, in contrast to p-amino derivatives, appear to cause a dose-related basic aminoaciduria.

6. Consideration of urinary flow rates and sodium excretion suggests that the ethanol anaesthesia does not modify amino acid reabsorption through effects on sodium transport or antidiuretic hormone.
Excretion of Active Metabolites of Vitamin D in Urine and Bile of the Adult Rat
Authors: Larsson S.-E. , Lorentzon R.
Published: August 2015

1. One-year-old male rats were injected intravenously with 200 pmol of 25-hydroxy[26(27)-methyl-3H]cholecalciferol per 100 g body weight and the presence of this metabolite of vitamin D, as well as other metabolites, produced during the following 8 h was examined in serum, urine and bile.

2. The chromatography data indicated an excretion of 25-hydroxycholecalciferol both in bile and urine and, in urine, also of 1,25-dihydroxycholecalciferol. In bile, fractions of labelled substances were also obtained which, according to their elution positions, might represent cholecalciferol and conjugated metabolites.

3. The excretion of active metabolites of vitamin D in normal urine might be elevated in chronic renal failure and, in conjunction with a reduced synthesis, contribute to the occurrence of renal osteodystrophy.
Effect of Acute Hypoxaemia on Plasma Arginine Vasopressin in Conscious Man
Authors: Baylis P. H. , Stockley R. A. , Heath D. A.
Published: August 2015

1. Acute hypoxaemia has been reported to stimulate vasopressin release in animals.

2. Hypoxaemia induced by breathing 9·3% oxygen for 15–20 min failed to produce a rise in plasma arginine vasopressin concentration in six out of eight healthy human subjects. The two subjects who developed an increase in plasma arginine vasopressin concentration had a significant rise in serum cortisol.

3. Breathing 100% nitrogen until impairment of consciousness caused no rise in plasma arginine vasopressin concentration.
Regulation of Gluconeogenesis and Ketogenesis during Rest and Exercise in Diabetic Subjects and Normal Men
Authors: Sestoft L. , Trap-Jensen J. , Lyngsøe J. , Clausen J. P. , Holst J. J. , Nielsen S. L. , Rehfeld J. F. , De Muckadell O. Schaffalitzky
Published: August 2015

1. The splanchnic—hepatic metabolism of glucose, lactate, pyruvate, alanine, glycerol, non-esterified fatty acids (NEFA), ketone bodies and oxygen were investigated in five normal men and six juvenile diabetic subjects at rest and during exercise after an overnight fast.

2. A linear relationship was found between load (arterial concentration multiplied by hepatic blood flow) and splanchnic—hepatic uptake of lactate, pyruvate, glycerol and NEFA. The uptake of alanine was highly sensitive to load, but was also regulated by the concentration of hepatic venous glucagon. The uptake of pyruvate was high in exercising diabetic subjects, who had a high lactate/pyruvate concentration ratio in hepatic venous blood.

3. The rate of uptake of the total measured gluconeogenic precursors was significantly higher in the diabetic group at a given load.

4. The rate of ketogenesis was linearly related to the NEFA load in both groups; however, the rate of ketogenesis was twofold at a given load in the diabetic group. The highest rates of ketogenesis were found coincident with the highest concentrations of glucagon in hepatic venous blood.

5. The observed antiketogenic effect of exercise was due to a decreased load of NEFA, mainly caused by a decrease in the hepatic blood flow.
The Carriers of Native Vitamin B12 in Normal Human Serum
Authors: Hall C. A.
Published: August 2015

1. After fractionation of the vitamin B12-binding proteins of ten normal sera the components containing transcobalamin II and R-type binders of vitamin B12 respectively were studied for endogenous vitamin B12 content by two distinct systems of vitamin B12 assay.

2. The measurements of total serum vitamin B12 by either bioassay with Euglena gracilis or a radioisotope dilution assay agreed closely.

3. The native vitamin B12 carried by transcobalamin II was higher as measured by bioassay than by isotope dilution assay.

4. The presence of the transcobalamin II fraction of human serum altered the key reaction between the binding reagent of the isotope dilution assay, so that this assay failed to measure vitamin B12 quantitatively.

5. Probably, the mean fraction of plasma vitamin B12 carried by transcobalamin II is in the range 20–30%.
Effect of Isometric Hand-Grip Exercise on the Carotid Sinus Baroreceptor Reflex in Man
Authors: Mancia G. , Iannos J. , Jamieson G. G. , Lawrence R. H. , Sharman P. R. , Ludbrook J.
Published: August 2015

1. The changes in R—R heart interval that result from step-increase and step-decrease in carotid sinus transmural pressure induced by a variable-pressure neck chamber were measured in seven normal men. Observations were made at rest, and during isometric hand-grip exercise at 24%, 44% and 64% of maximal voluntary contraction.

2. The response of heart interval to increase in carotid sinus transmural pressure was progressively and markedly diminished according to the strength of hand-grip. This effect was fully developed from the moment of onset of the exertion.

3. The response of heart interval to decrease in carotid sinus transmural pressure was much less consistently affected by hand-grip exercise.
Skeletal Blood Flow in Paget's Disease of Bone and its Response to Calcitonin Therapy
Authors: Wootton R. , Reeve J. , Spellacy E. , Tellez-Yudilevich M.
Published: August 2015

1. Blood flow to the skeleton was measured by the 18F clearance method of Wootton, Reeve & Veall (1976) in 24 patients with untreated Paget's disease. In every patient but one, resting skeletal blood flow was increased. There was a significant positive correlation between skeletal blood flow and serum alkaline phosphatase and between skeletal blood flow and urinary total hydroxyproline excretion.

2. Fourteen patients were re-studied after they had received short-term (7 days or less) or long-term (7 weeks or more) calcitonin. Skeletal blood flow, alkaline phosphatase and urinary hydroxyproline excretion fell towards normal in every case. There was some evidence from the short-term studies that calcitonin produced a more rapid fall in skeletal blood flow than in alkaline phosphatase.

3. Glomerular filtration rate appeared to increase transiently in response to calcitonin.
Hepatic Metabolism of Aminopyrine in Patients with Chronic Renal Failure
Authors: Scherrer S. , Haldimann B. , Küpfer A. , Reubi F. , Bircher J.
Published: August 2015

1. To evaluate potential alterations in hepatic metabolism of drugs occurring in patients with renal insufficiency the fate of aminopyrine was studied in 17 patients with chronic renal failure and in 27 normal subjects.

2. Although patients with chronic renal failure exhibited large variations, their aminopyrine plasma disappearance times (mean 0·62 ± sd 0·24 h−1) were significantly higher than those found in normal subjects (0·30 ± 0·07 h−1, P < 0·002).

3. 14CO2 derived from [dimethylamine-14C]aminopyrine disappeared from breath more rapidly in patients with chronic renal failure and a history of analgesic abuse (0·40 ± 0·04 h−1) than in control subjects (0·22 ± 0·03 h−1, P < 0·01) and in other patients with chronic renal failure (0·24 ± 0·04 h−1).

4. Dialysis treatment and serum creatinine concentrations were not correlated with the rates of aminopyrine metabolism. Two additional patients, however, with combined renal and hepatic disease, exhibited markedly slowed rates of aminopyrine demethylation.

5. Although chronic renal failure by itself might not alter microsomal drug metabolism it is concluded that, in patients with a history of abuse of phenacetin-containing analgesics, marked acceleration in aminopyrine N-demethylation may be observed.
Influence of Indomethacin on the Systemic and Pulmonary Vascular Resistance in Man
Authors: Wennmalm Å.
Published: August 2015

1. Indomethacin, an inhibitor of the cyclo-oxygenase system that converts arachidonic acid into prostaglandins and related substances, was infused intravenously in 12 healthy volunteer subjects.

2. Systemic systolic and diastolic blood pressures and heart rate were recorded in all subjects, and in most of them also the systemic arteriovenous oxygen difference, the total oxygen uptake and the pulmonary arterial and wedge pressures.

3. The infusion of indomethacin was followed by a decreased cardiac output (from 7·3 ± 0·3 to 6·3 ± 0·3 litres/min) and an increased mean systemic blood pressure (from 92 ± 1 to 102 ± 1 mmHg), indicating an elevation of the total systemic vascular resistance (from 98 ± 4 to 124 ± 5 kPa)l−1 s) by indomethacin. The ventilation and the pulmonary vascular resistance did not change after the infusion of indomethacin.

4. The results suggest that products formed by the cyclo-oxygenase system at rest exert a relaxing effect in certain parts of the systemic vascular bed, thereby lowering the systemic vascular resistance.
Concurrent Estimation of Total Body and Exchangeable Body Sodium in Hypertension
Authors: Boddy K. , Brown J. J. , Davies D. L. , Elliott A. , Harvey I. , Haywood J. K. , Holloway I. , Lever A. F. , Robertson J. I. S. , Williams E. D.
Published: August 2015

1. Total-body neutron-activation analysis in vivo was carried out in 11 hypertensive subjects to measure simultaneously the total body content of sodium, chlorine, calcium, phosphorus and nitrogen.

2. There was a highly significant correlation between total body sodium measured by activation analysis and total exchangeable sodium measured by a standard isotope-dilution technique (r = 0·92, P < 0·001). Exchangeable sodium averaged 80·3% of total body sodium.

3. The measured values of chlorine, calcium, phosphorus and nitrogen were similar to those for healthy subjects reported by others.

4. Activation analysis in vivo appears promising as an additional tool for investigating sodium metabolism in hypertension, as it is the only method available for determining the total body content of this element. The radiation dose (1 rem) is sufficiently low to permit repeated measurements in the same subject.
Subcellular Distribution of Hydrolase Activities for Glycine and Leucine Homopeptides in Human Jejunum
Authors: Nicholson J. A. , Peters T. J.
Published: August 2015

1. The subcellular distribution of peptidase activities in the normal human jejunum against glycine and leucine homopeptides has been investigated with an analytical fractionation technique.

2. An 8000 g-min supernatant was prepared from homogenates of Crosby capsule biopsy specimens and subjected to isopycnic centrifugation in a Beaufay automatic zonal rotor.

3. The distribution of subcellular organelles in the gradient was established by measurement of organelle-specific marker enzymes.

4. A sensitive fluorimetric assay for glycine peptidase was developed and used for the localization of peptidase activity with peptides composed of from two to five glycine residues as substrates.

5. Glycine peptidase activity was located in the cytosol and in the brush-border membrane but the distribution of activity varied markedly with the chain-length of substrate; the longer the peptide the greater the proportion of activity associated with the brush border. Leucine peptidase showed a similar variation in cytosol—brush border distributions.

6. The results are consistent with concepts that suggest absorption and intracellular hydrolysis of small peptides and brush-border digestion of larger peptides.
Effects of Ileal and Caecal Resection on the Colon of the Rat
Authors: Scarpello J. H. B. , Cary B. A. , Sladen G. E.
Published: August 2015

1. Rats were subjected to resection of either the distal 50 cm of small bowel, the caecum or a combined ileocaecal operation. The effects on stool production and growth were observed over the following 8 weeks. Subsequently measurements were made at various levels in the remaining gut of intestinal weight, mucosal thickness, mucosal adenosine 3′:5′-phosphate (cyclic AMP) concentration and the water and bile acid content of luminal material.

2. Rapid adaptation, in terms of growth and the production of formed stools, was seen after ile-ectomy or caecectomy. This was slower and less complete after ileocaecectomy. Changes in water content indicated that colonic absorption of water was normal after ile-ectomy but impaired after ileocaecectomy.

3. After ile-ectomy there was growth of the caecum but not colon, whereas after ileocaecectomy there was growth of the remaining colon.

4. The intraluminal bile acid concentration in the small-gut remnant was markedly decreased at 2 weeks with little further change at 8 weeks after ileal resection. The colonic intraluminal bile acid concentration was only modestly increased after ile-ectomy or ileocaecectomy.

5. When studied by a perfusion technique in vivo, deoxycholate (2·5 mmol/l) in intact rats induced a net secretion of water into the colon; by contrast the colon of 8 week ile-ectomized rats absorbed water, although this was at a reduced rate compared with control rats. Deoxycholate increased mucosal cyclic AMP concentrations in the intact rats but not in the ile-ectomized rats.

6. Sodium ricinoleate (5·0 mmol/l) inhibited colonic water absorption and when mixed with deoxycholate (2·5 mmol/l) the effect on water transport was summatory. However, ricinoleate either alone or with deoxycholate did not alter mucosal cyclic AMP concentrations.

7. These results demonstrate that the colon can absorb water effectively after ile-ectomy in spite of being exposed to increased concentrations of luminal bile acids. This may result in part from an altered mucosal response to secretagogues. If so this represents a form of functional adaptation by the colon to ileal resection.
Tidal Pressure/Volume and Flow/Volume Respiratory Loop Patterns in Human Neonates
Authors: Milner A. D. , Saunders R. A. , Hopkin I. E.
Published: August 2015

1. Tidal pressure/volume and flow/volume respiratory loops were constructed from records obtained during 98 studies on 48 neonates of various ages and gestations. Records were obtained with a total body plethysmograph and an oesophageal balloon. Total pulmonary resistance was computed at five separate levels in the breathing cycle and results were expressed graphically as tidal resistance profiles by plotting total pulmonary resistance against percentage tidal volume above functional residual capacity.

2. Values obtained for standard pulmonary mechanical measurements and thoracic gas volume were similar to those of other workers. In addition six distinctive resistance profile patterns were found and related to different breathing patterns.

3. The technique appeared to be particularly useful in identifying air trapping and also demonstrated that total pulmonary resistance is open to misinterpretation when measured only at the mid-tidal-volume level, as is the present convention.
The Mechanism of Renomedullary Antihypertensive Action: Haemodynamic Studies in Hydronephrotic Rats with One-Kidney Renal-Clip Hypertension
Authors: Sušić D. , Sparks J. C. , MacHado E. A. , Kentera D.
Published: August 2015

1. The protective action of the renal medulla was studied in one-kidney renal-clip hypertension in rats with unilateral hereditary hydronephrosis and almost complete atrophy of the medulla of the affected kidney.

2. Rats were unilaterally nephrectomized. The first group had a normal kidney remaining, and the animals from the second and third groups were left with a hydronephrotic kidney and received renomedullary and renocortical autotransplants respectively. Two weeks later all rats were made hypertensive by placing a silver clip (0·2 mm) on the renal artery.

3. From the fourth day after clipping until the end of the experiment blood pressure was found to be significantly (P < 0·01) lower in rats with medullary transplants than in the other groups. No differences in renal excretory function, plasma volume and plasma renin activity were found between the groups either before or during development of hypertension (5 and 21 days after clipping). Early in the course of hypertension (5 days) cardiac output was significantly (P < 0·05) lower in the rats with medullary transplants than in the other groups, although an increase in plasma volume was noted in all three groups. At that time no difference in total peripheral resistance was found between the groups.

4. The results are consistent with the hypothesis that the renomedullary antihypertensive substance(s) mitigates hypertension by preventing a hypertensive haemodynamic response to sodium/volume overload.
Excretion of Conjugated Bilirubin in the Isolated Perfused Rat Kidney
Authors: Gollan J. L. , Dallinger K. J. C. , Billing Barbara H.
Published: August 2015

1. Renal mechanisms of conjugated bilirubin excretion have been studied in isolated rat kidneys perfused with a protein-free dextran medium, containing conjugated bilirubin isolated from human bile.

2. In nine perfused kidneys with a low glomerular filtration rate (GFR) (<0·5 ml/min) and depressed tubular function, there was a significant linear correlation between conjugated bilirubin clearance and GFR (r = 0·97).

3. In contrast, nine kidneys with a normal GFR (> 0·8 ml/min) and good tubular function exhibited substantial tubular reabsorption of filtered conjugated bilirubin (mean 74%). Reabsorption was proportional to the filtered conjugated bilirubin load and a tubular transport maximum was not observed even at high concentrations (144 μmol/l).

4. The fractional reabsorption of bilirubin was unchanged by the addition of sodium aminohippurate to the medium. Perfusion with an albumin medium (10 g/l) resulted in a tenfold reduction in conjugated bilirubin clearance.

5. These observations indicate that non-protein-bound conjugated bilirubin is freely filtered by the glomeruli and then largely reabsorbed in the tubules. Evidence of tubular secretion was not obtained.

6. Chromatographic separation of bilirubin conjugates showed that the proportion of di- to monoconjugates in the urine was greater than in the perfusate. Whether this indicated further conjugation by the kidney of the monoconjugates or differential clearance of the conjugates was not established.
Thyroid Function and Blood Pressure in Two New Strains of Spontaneously Hypertensive and Normotensive Rats
Authors: Vincent M. , Bornet H. , Berthezene F. , Dupont J. , Sassard J.
Published: August 2015

1. The influence of thyroid function on the development of hypertension was studied in strains of spontaneously hypertensive (SH) and normotensive rats.

2. Surgical thyroidectomy decreased systolic blood pressure more markedly in SH rats than in normotensive rats. The effects of oral administration of 5 and 100 μg of thyroxine 24 h—1 100 g—1 were studied in the thyroidectomized animals. In the two strains the blood pressure returned to control levels only after administration of the larger dose.

3. The evolution of body weight, total plasma tri-iodothyronine (T3) and tetraiodothyronine (T4) concentrations were followed as a function of age in SH rats and normotensive rats from 5 to 21 weeks. At each age, SH rats showed significantly larger body weight and decreased T4 concentrations. Plasma T3 in SH rats was lower than in normotensive rats until 15 weeks of age, after which the difference was not significant. At 11 weeks, plasma free T3 and T4 concentrations were slightly lower in SH rats than in normotensive rats.

4. The more marked hypotensive effects of surgical thyroidectomy in SH rats cannot be related to increased thyroid function.
Effect of Hyperosmolar Stimuli and Coeliac Disease on the Permeability of the Human Gastrointestinal Tract
Authors: Wheeler P. G. , Menzies I. S. , Creamer B.
Published: August 2015

1. Oral loads have been used to assess the permeability of the human gastrointestinal tract, with lactulose (mol. wt. 342), raffinose (mol. wt. 504), stachyose (mol. wt. 666) and a fluoresceinlabelled dextran (mol. wt. 3000) as marker substances. Timed urinary recovery of these substances, which are not metabolized, was measured by quantitative paper chromatography and direct fluorimetry, and the results were used as an indication of passive intestinal permeability.

2. Results in healthy adults showed that permeability to these markers was dependent on molecular size, even after correction for aqueous diffusion differences, such that a profile of restricted permeability could be described for this range of markers. Interpretation in terms of conventional pore theory suggested the presence of more than one population of pores.

3. Ingestion of solutions made hyperosmotic by inclusion of glycerol resulted in a large increase in permeability, in a pattern that suggested an increase in either the size or frequency of a range of smaller pores.

4. A similar increase in permeability and alteration in the profile of restriction was found in patients with coeliac disease.

5. The possible location of such pores in the gastrointestinal mucosa is discussed in relation to the cell membrane, the intercellular junction, and the sites of cell exfoliation.
Saline-Induced Natriuresis in the Dog without Prior Exposure of the Kidney to the Physical Effects of Expansion of the Extracellular Fluid Compartment
Authors: Klemmer P. J. , De Los Santos C. , Blythe W. B.
Published: August 2015

1. Experiments were carried out in dogs in which renal perfusion pressure was reduced 40 min before beginning expansion of the extracellular fluid space by 10% with isotonic sodium chloride solution. Sodium excretion increased up to 590% of control values in spite of the fact that the filtered load of sodium was below that of the control period and circulating mineralocorticoids were not suppressed.

2. The findings indicate that, in the dog, prior exposure of the kidney to the volume-expanded state is not a prerequisite for natriuresis to occur.
Control of Enzymatically Inactive Renin in man under Various Pathological Conditions: Implications for the Interpretation of Renin Measurements in Peripheral and Renal Venous Plasma
Authors: Derkx F. H. M. , Wenting G. J. , Veld A. J. Man In 'T , Verhoeven R. P. , Schalekamp M. A. D. H.
Published: August 2015

1. Human plasma contains two types of renin: one is active in its native form (active renin), the other has renin-like activity after exposure to low pH (inactive renin). Reactions of acid-activated plasma renin and kidney renin with either homologous or heterologous substrate showed identical Km values.

2. Peripheral venous values for active and inactive renin in essential hypertension (n = 22), renovascular hypertension (n = 14), primary aldosteronism (n = 12), adrenal insufficiency (n = 6) and control subjects (n = 13) were directly correlated. But the percentage of renin that was active varied widely.

3. After bilateral nephrectomy in 12 patients both active and inactive plasma renin fell, but did not completely disappear. Estimates of half-life in two patients were 30–80 min for active renin and 150–165 min for inactive renin.

4. Renal vein to peripheral vein ratios of active and inactive renin in ten patients with essential hypertension (19 determinations) ranged from 0·96 to 1·60 and from 0·68 to 1·44 respectively with mean values (±sem) of 1·21 ± 0·04 and 1·06 ± 0·05.

5. The renal vein to peripheral vein ratio of active renin on the affected side in 13 out of 17 patients with renovascular hypertension was above the range found in essential hypertension. Six of them also had an elevated ratio of inactive renin on that side, which indicated renal release of this form of renin into the circulation. But, in contrast to the renal vein to peripheral vein ratio of active renin, the mean value of the ratio of inactive renin on the affected side was not significantly higher than on the contralateral side. The results suggest a renal mechanism not only for controlling the total quantity of circulating renin but also for modulating its degree of activation.
Effect of Saralasin and Serum in Myohaemoglobinuric Acute Renal Failure of Rats
Authors: Bauereiss K. , Hofbauer K. G. , Konrads A. , Gross F.
Published: August 2015

1. In rats deprived of food and water for 24 h acute renal failure was produced by the intramuscular injection of glycerol. Eight hours later plasma urea concentration had increased threefold despite a small rise in urine volume. Plasma concentrations of renin and renin substrate were elevated.

2. When saralasin, a competitive antagonist of angiotensin II, was infused for 8 h after glycerol injection, urine volume and plasma urea were similar to values in rats that had received an infusion of saline.

3. Administration of rat serum (4·5 ml h−1 kg−1) for 4 h suppressed plasma renin concentrations, but plasma urea increased to the same extent as in rats without serum.

4. When saralasin and serum were infused at the same time, urine volume, urine osmolality and solute excretion increased and the rise of plasma urea was diminished.

5. Saralasin has a protective effect against glycerol-induced acute renal failure only when volume is replaced concomitantly.
Purine Metabolism and Immunodeficiency: Urinary Purine Excretion as a Diagnostic Screening Test in Adenosine Deaminase and Purine Nucleoside Phosphorylase Deficiency
Authors: Simmonds H. Anne , Sahota A. , Potter Catherine F. , Cameron J. S.
Published: August 2015

1. We have compared urinary purine excretion by two different methods in three separate paediatric disorders of purine metabolism: purine nucleoside phosphorylase deficiency, adenosine deaminase deficiency and adenine phosphoribosyltransferase deficiency.

2. The abnormal purines identified in each case were specific for the defect and directly related to it: adenine in adenine phophoribosyltransferase deficiency; the abnormal nucleosides inosine, guanosine and their corresponding deoxyribosides in purine nucleoside phosphorylase deficiency; deoxyadenosine in adenosine deaminase deficiency, the latter having previously been identified erroneously as adenine after degradation in the acidic conditions used.

3. Deoxyriboside excretion was specific for the two defects associated with immunodeficiency; adenine for adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadenine urolithiasis. The results obtained by a quantitative method were reflected in a simple rapid qualitative technique, isotachophoresis of the urine.

4. Purine overexcretion (principally inosine) was evident only in purine nucleoside phosphorylase deficiency, which emphasizes the importance of hypoxanthine salvage for the overall control of purine production in man. In none of these disorders was any inhibition of pyrimidine biosynthesis as reflected by oroticaciduria noted. Orotic acid excretion was within normal limits in all cases.

5. From these results it is suggested that the associated immunodeficiency in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency relates directly to the intracellular accumulation of 2′-deoxyribosides and not indirectly to an inhibitory effect on pyrimidine metabolism.
Effect of Blood Transfusion on the Carbon Monoxide Transfer Factor of the Lung in Man
Authors: Clark Elizabeth H. , Woods R. L. , Hughes J. M. B.
Published: August 2015

1. Ten studies were performed on nine patients with haematological disorders but with normal lungs, who required intermittent blood transfusions. The transfer factor for carbon monoxide and uptake of carbon monoxide per unit lung volume (KCO) were measured with the single breath technique before and at various intervals after transfusion.

2. The mean haemoglobin concentration increased from 7·7 to 11·1 g/dl.

3. The TLCO increased according to a formula based on the Roughton & Forster (1957) diffusion equations, TLCO (standardized) = TLCO (observed). (10·2 + Hb)/1·7 Hb, where haemoglobin (Hb) is expressed as g/dl.

4. The correlation between measured and predicted values was slightly better if changes in alveolar volume were taken into account, by using the KCO value.
The Nature of Inactive Renin in Human Plasma and Amniotic Fluid
Authors: Shulkes A. A. , Gibson R. R. , Skinner S. L.
Published: August 2015

1. The properties of inactive and active renin in human plasma and amniotic fluid were studied chromatographically. Activation was achieved at pH 3.3 with and without added pepsin.

2. Acid activation of renin was time- and temperature-dependent but was inhibited by dilution of the sample. The dilution effect was corrected by adding pepsin. Such characteristics indicate that activation at low pH is catalysed by intrinsic enzymes.

3. Separation and/or dilution of the activating enzyme during ion-exchange chromatography concealed the eluted position of inactive renin and reduced the amount recovered. Only after full activation of the eluted renin was achieved with added pepsin was a distinct peak of inactive renin exposed.

4. At pH 7.5 inactive renin carried a lower negative charge than the active enzyme. This charge difference was lost after activation.

5. No molecular-weight differences between active, inactive renin or the International Renin Standard were detected by gel filtration. No renin of larger molecular weight was present.

6. These findings will be helpful in purification studies of human inactive renin.
Catecholamines in Peripheral Venous Plasma in Patients on Chronic Haemodialysis
Authors: McGrath B. P. , Ledingham J. G. G. , Benedict C. R.
Published: August 2015

1. Concentrations of noradrenaline and adrenaline from peripheral venous plasma were measured after 60 min of supine rest in 55 patients on chronic haemodialysis (including six anephric patients) and in 18 normal subjects. In the patients, plasma catecholamine measurements were related to concurrent measurements of blood pressure, pulse rate, plasma renin activity, plasma angiotension II, blood volume and sulphate space.

2. Mean resting peripheral venous plasma noradrenaline concentration was higher by almost twofold, but mean resting plasma adrenaline concentration was lower, in the 49 non-nephrectomized patients than in the normal subjects. In the six anephric patients, resting peripheral venous plasma noradrenaline concentrations were similar to those of normal subjects.

3. Mean resting plasma noradrenaline concentrations in peripheral venous blood were similar in normotensive and hypertensive non-nephrectomized patients; mean plasma adrenaline concentration was higher in the hypertensive patients. A positive correlation was found between plasma adrenaline and plasma renin activity but not between plasma noradrenaline and plasma renin activity.

4. Resting concentrations of both catecholamines were positively correlated with resting pulse rate and inversely related to blood volume.

5. After renal transplantation resting peripheral venous plasma noradrenaline concentrations were normal in eight patients in whom high values had been recorded whilst on chronic haemodialysis.

6. In response to 40° of head-up tilt, plasma noradrenaline increased significantly in six non-nephrectomized patients, whether sodium replete or depleted, and the changes observed in both these states were similar to those of 14 normal subjects studied on a normal diet.

7. Diastolic blood pressure increased on standing in the majority (41/55) of patients: in only four patients was there a fall in diastolic pressure of more than 5 mmHg in the erect position and in two of these blood volumes were low.

8. The cause of increased peripheral plasma noradrenaline concentrations in haemodialysis patients is uncertain.
Impaired Skeletal Muscle Vasomotor Response to Infused Noradrenaline in Baboons with Obstructive Jaundice
Authors: Bomzon L. , Wilton P. B. , McCalden T. A.
Published: August 2015

1. We have measured muscle blood flow by a 133Xe clearance technique, and its response to noradrenaline in baboons before and 2 weeks after ligation of the bile ducts when they were jaundiced.

2. In the normal baboons, the response to noradrenaline was a dose-dependent decrease in muscle blood flow.

3. Bile-duct ligation caused no significant alteration in skeletal muscle blood flow but the response to noradrenaline in the jaundiced baboons was significantly attenuated. This effect was not observed in four sham-operated baboons.
Revised Standards for Normal Resting Dead-Space Volume and Venous Admixture in Men and Women
Authors: Harris E. A. , Seelye Eve R. , Whitlock R.M.L.
Published: August 2015

1. Data have been combined from three previous series to provide revised standards for the prediction of physiological dead-space volume (VD), arterial oxygen tension (Pa,o2), alveolar-to-arterial oxygen-tension difference (Pa,o2 - Pa,o2) and venous admixture fraction (Q̇va/Q̇t) in the sitting position.

2. These standards, based on measurements in 96 healthy men and women aged from 20 to 74 years, largely confirm conclusions drawn from the first series of 48 subjects.

3. VD is best predicted on age, height, tidal volume and the reciprocal of respiratory frequency. Pa,o2, (Pa,o2 - Pa,o2) and Q̇va/Q̇t are adequately predicted on age alone.
Metabolism of Intact and Desialylated α1-Antitrypsin
Authors: Jones E. A. , Vergalla J. , Steer C. J. , Bradley-Moore P. R. , Vierling J. M.
Published: August 2015

1. To study the metabolism of α1-antitrypsin in man, radioiodinated purified α1-antitrypsin of protease inhibitor type MM was injected intravenously into seven normal volunteer subjects of protease inhibitor type MM and plasma and urine radioactivity data were analysed. The purified glycoprotein inhibited trypsin and exhibited micro-heterogeneity characteristic of α1-antitrypsin on acid starch-gel electrophoresis.

2. The intravascular mass was 116 ± 16.1 mg/kg (mean ± sem); extravascular/intravascular pool ratio was 1.07 ± 0.067; the fractional catabolic rate was 33.3 ± 1.37% of the intravascular pool/day; half-life was 4.6 ± 0.21 days; synthetic rate was 33.8 ± 6.3 mg day−1 kg−1.

3. The data indicated that the serum concentration of α1-antitrypsin varies independently of its fractional catabolic rate and that it is catabolized in, or in close relationship to, the intravascular compartment.

4. Plasma curves of protein-bound radioactivity were also defined after the intravenous administration of 131I-labelled desialylated α1-antitrypsin to two additional subjects. The fractional plasma disappearance rates were approximately 150 times as great as those for the intact protein. The rapid disappearance of 131I-labelled desialylated α1-antitrypsin from plasma coincided with an equally rapid uptake of radioactivity by the liver.

5. The results are compatible with the existence of receptor sites for desialylated glycoproteins in the surface membrane of human hepatocytes and emphasize that the catabolism of α1-antitrypsin can be influenced by the structure of its carbohydrate moiety.
Peptide Excretion in Experimental Fanconi Syndrome in the Rat
Authors: Asatoor A. M. , Bending M. R. , Milne M. D.
Published: August 2015

1. A study has been made of urinary peptide output in rats before and after production of a Fanconi syndrome induced by a single injection of sodium maleate. There was an unequivocal increase of urinary peptides on the first and second days after the injection, without any detectable change in the concentration of plasma peptides.

2. Similar results were obtained in osteolathyritic rats in which skeletal lesions had been produced by ingestion of β-aminopropionitrile.

3. The fractional amino acid content of urinary peptides after maleate and β-aminopropionitrile is shown to be significantly different from that in control animals.

4. Evidence is presented that the increased output of peptides is mainly due to increased renal clearance similar to that previously described for amino acids, glucose and several electrolytes in this type of experimental Fanconi syndrome.
Intestinal Cholecalciferol Absorption in the Elderly and in Younger Adults
Authors: Barragry J. M. , France M. W. , Corless D. , Gupta S. P. , Switala S. , Boucher B. J. , Cohen R. D.
Published: August 2015

1. A method for assessing cholecalciferol absorption in man is described.

2. The intestinal absorption of [3H]cholecalciferol was studied in 20 female geriatric patients, most of whom were vitamin D-depleted.

3. The plasma [3H]cholecalciferol response after oral ingestion was significantly lower than that of a group of younger female subjects.

4. The plasma response of labelled polar metabolites of cholecalciferol was also lower in the geriatric than in the younger group, suggesting that increased removal of label by conversion into more polar metabolites could not account for the reduced plasma [3H]cholecalciferol response.

5. There was no evidence that alteration in gastrointestinal motility could account for the different rate of appearance of the labelled vitamin in the plasma in the two groups.

6. It is suggested that there is a defect in intestinal absorption of cholecalciferol in the elderly.
Post-Mortem Migration of Bone-Seeking Radionuclides in the Rat and Rabbit and its Effect on Estimates of Bone Uptake
Authors: Tothill P. , MaCpherson J. N.
Published: August 2015

1. The continued uptake of 18F, 85Sr and 47Ca by bone after death has been studied in rats and rabbits after aortic injection followed by quick killing, a period of recirculation of tracer before death, and perfusion of the carcase. In each case an approximately linear increase of bone radioactivity was observed during a period of 1 h at about the same rate. The proportionate increase depended on the initial concentration of bone-seeking nuclide, ranging from a factor of 1.5 to 4.5. Boiling the carcase did not increase the migration rate.

2. Delay between death and dissection may therefore lead to spuriously high bone concentrations of these radionuclides, leading to overestimates of bone uptake, extraction ratio or bone blood flow.
Abnormalities of Renal Transport of Sodium o-[131I]Iodohippurate (Hippuran) in Essential Hypertension
Authors: Reeve J. , Crawley J. C. W. , Goldberg A. D. , Kennard Cherry , Kenny D. , Smith I. K.
Published: August 2015

1. Renal function has been studied in 312 hypertensive patients by quantitative renography with sodium o-[131I]iodohippurate (131I-labelled Hippuran) and estimation of overall effective renal plasma flow. In 59% of the patients the results were normal.

2. Severe hypertension was associated not only with reduced effective renal plasma flow but also a characteristic abnormality of Hippuran transport in 10% of the patients in which there was a wider than normal variation in transit times of Hippuran through the kidney, which may reflect non-uniformity of reabsorption of filtrate by different groups of nephrons.

3. Plasma renin activity was higher in a group of 14 patients with multimodal transit time spectra than in a matched hypertensive control group, with very substantial overlap between the two groups.

4. The renographic abnormality was usually reversed by treatment.
Effect of Unconjugated and Conjugated Phenol and Uraemia on the Synthesis of Adenosine 3′:5′-Cyclic Monophosphate in Rat Brain Homogenates
Authors: Turner G. A. , Wardle E. N.
Published: August 2015

1. The effects of phenol and phenyl glucuronide on the responses of normal rat brain adenyl cyclase to noradrenaline and dopamine have been investigated. Neurotransmitter responses have also been examined in brains from uraemic and normal rats.

2. A depressive effect of phenol on the adenosine 3′: 5′-cyclic monophosphate response of the neostriatum to dopamine was shown to be completely abolished if the toxin was present in the conjugated form; the response of the cortex to noradrenaline was stimulated by the presence of phenyl glucuronide, even though the unconjugated form had no effect.

3. The uraemic state in the rat also resulted in a depression of the neostriatum response to dopamine, yet an enhancement of the cortical response to noradrenaline.

4. The action of phenols on the brain is relevant to hepatic and uraemic coma.
The Distribution of Cardiac Output in the Anaesthetized Spontaneously Hypertensive Rat
Authors: Hiley C. R. , Yates M. S.
Published: August 2015

1. Radioactive 15 μm and 50 μm diameter microspheres were used to determine cardiac output, its regional distribution and tissue blood flow in adult normotensive Wistar and Okamoto spontaneously hypertensive rats.

2. Cardiac output in the spontaneously hypertensive rats was the same as in Wistar normotensive rats, but its distribution in the hypertensive rats appeared to differ: there was a significant increase in the proportion of microspheres trapped in the liver whereas fewer were found in the gastrointestinal tract. This indicates that a greater fraction of the cardiac output passes along the hepatic artery and less through the splanchnic bed.

3. Blood flow in skin and skeletal muscle in spontaneously hypertensive rats was approximately 50% of that in Wistar normotensive rats.
Pressure-Independent Hypertrophy of Veins and Pulmonary Arteries of Spontaneously Hypertensive Rats. Characterization of Function, Structural and Histochemical Changes
Authors: Greenberg Stan , Palmer Eugene C. , Wilborn Walter M.
Published: August 2015

1. Portal veins, vena cavae and pulmonary arteries from spontaneously hypertensive (SH) rats were found to undergo medial smooth-muscle hypertrophy when compared with corresponding blood vessels from age- and sex-matched Wister—Kyoto (WKy) normotensive rats. There was an increase in the density of the mucopolysaccharide and glycoprotein staining in veins, pulmonary arteries vena venorum and ventricular myocardium of SH rats.

2. Electron-microscopic examination of the blood vessels and myocardium of SH rats suggested enhanced protein synthesis and hypertrophy both in the smooth muscle and endothelial cells. Central venous, portal venous and right ventricular pressures were measured in SH rats and were not elevated when compared with corresponding values for WKy rats. Veins and pulmonary arteries from SH rats developed more tension when challenged with vasoconstrictor stimuli than corresponding vessels obtained from WKy rats.

3. Veins and pulmonary arteries obtained from SH rats demonstrated a greater uptake of [14C]glycosamine than corresponding blood vessels from WKy rats.

4. These findings demonstrate the existence of pressure-independent hypertrophy of smooth muscle in blood vessels obtained from SH rats, associated with an increase in glycoprotein synthesis and an enhanced contractile activity of the muscle. The data suggest that the enhanced contractility of blood vessels from SH rats reflects the enhanced muscle mass. It may represent an aberrant humoral or cellular mechanism which results in the hypertension.