bluuebunny/crossref_metadata_2025 huggingface dataset:
The Acute Effects of Respiratory and Metabolic Acidosis on Renal Function in the Dog
Authors: Farber M. O. , Szwed J. J. , Dowell A. R. , Strawbridge R. A.
Published: August 2015

1. Effective renal plasma flow, glomerular filtration rate and cardiac output were measured in osmotically loaded dogs before and during comparable acute respiratory and metabolic acidosis.

2. Urine output increased in control dogs and in animals with metabolic acidosis, but declined with respiratory acidosis. Effective renal plasma flow and glomerular filtration rate declined with respiratory and metabolic acidosis.

3. When respiratory acidosis was buffered with sodium bicarbonate, urine volume increased and glomerular filtration rate and effective renal plasma flow were unchanged; with trihydroxymethylaminomethane, urine volume increased but glomerular filtration rate and effective renal plasma flow fell.

4. When metabolic acidosis was buffered with sodium bicarbonate, urine volume increased; with trihydroxymethylaminomethane, urine volume increased but glomerular filtration rate fell. Cardiac output declined only during metabolic acidosis, both buffered and unbuffered.

5. These studies demonstrate that, even with osmotic loading: (1) respiratory acidosis causes a decrease in glomerular filtration rate, effective renal plasma flow and urine volume; (2) metabolic acidosis depresses glomerular filtration rate and effective renal plasma flow but does not change urine volume even though cardiac output falls; (3) sodium bicarbonate is more effective than trihydroxymethylaminomethane in preserving renal function during respiratory and metabolic acidosis.
Cell Size and Glucose Oxidation Rate in Adipose Tissue from Non-Diabetic and Diabetic Obese Human Subjects
Authors: Harrison L. C. , King-Roach A. P.
Published: August 2015

1. The rate of oxidation of [1-14C]glucose to 14CO2 was examined in subcutaneous adipose tissue from fifteen obese non-diabetic subjects and from eleven obese maturity-onset diabetic patients. Production of 14CO2, measured in the basal state and in the presence of insulin, was significantly correlated with mean cell size in both the non-diabetic and the diabetic subjects, independent of age, relative weight and fasting plasma insulin concentration.

2. Comparison of the regressions of glucose oxidation rates on mean cell size indicated: (i) that insulin produced a significant increase in activity over the basal value in both groups, and (ii) that basal and insulin-stimulated activity were both significantly lower in diabetic than in non-diabetic adipose tissue.
Changes in the Carotid Body and the Ventilatory Response to Hypoxia in Chronically Hypoxic Rats
Authors: Barer Gwenda R. , Edwards C. W. , Jolly Angela I.
Published: August 2015

1. Young rats were kept in a hypoxic chamber for 2–11 weeks and compared with littermate control animals.

2. The carotid bodies of the hypoxic rats enlarged, resembling those of men and animals living at high altitude.

3. Permanent blunting of the ventilatory response to hypoxia did not occur. Immediately on removal from the chamber, the rats, lightly anaesthetized, showed a smaller increase in ventilation during hypoxia than did control animals but this difference disappeared after 3 days' recovery in normoxia.
Branched-Chain Amino Acids, Nitrogen Excretion and Injury in Man
Authors: Wedge J. H. , De Campos R. , Kerr A. , Smith R. , Farrell Rose , Ilic Vera , Williamson D. H.
Published: August 2015

1. Venous blood concentrations of the branched-chain amino acids, valine, leucine and isoleucine, and urinary nitrogen excretion have been measured in sixteen adult males, from 2 h to 7 days after injury, and in four adults after elective skin grafts.

2. In the injured group the concentrations of these amino acids rose significantly 24 h after injury and had doubled at 4 days and remained high; in contrast the skin-graft patients showed no significant change.

3. In those injured patients with initial hyperketonaemia, defined as more than 0·2 mmol/l, the increase in concentrations of branched-chain amino acids at the fourth and seventh days after injury was significantly less than in those with normoketonaemia, and was accompanied by lower urinary nitrogen excretion throughout the whole period.

4. It is suggested that the changes in the concentration of branched-chain amino acids after injury indicate decreased uptake by muscle or excessive release due to an imbalance between protein synthesis and protein catabolism in this tissue.
The Effect of Anaesthesia of the Airway in Dog and Man: A Study of Respiratory Reflexes, Sensations and Lung Mechanics
Authors: Cross Brenda A. , Guz A. , Jain S. K. , Archer Sietske , Stevens J. , Reynolds Felicity
Published: August 2015

1. The effect of breathing an anaesthetic aerosol of 5% bupivacaine hydrochloride has been assessed in dog and man.

2. In the dog, the cough reflex was abolished and the Hering—Breuer inflation reflex severely impaired or abolished; breathing became slower and deeper; no pathological changes were found in the lungs of these dogs.

3. In man, no untoward effects resulted from a 10 min period of aerosol inhalation; there were no systematic effects on airway resistance or lung volumes and the cough reflex in response to either tactile or chemical (citric acid aerosol) stimulation was invariably abolished. The Hering—Breuer inflation reflex was impaired, but this was not associated with any change in resting ventilation. The V̇E/CO2 response was enhanced after aerosol anaesthesia; subjects felt an exaggerated dyspnoea. The aerosol anaesthesia abolished the afferent pathway of a reflexly elicited bronchoconstriction in one subject. There was no effect on the ability to hold the breath, or on the quality of the associated sensation.

4. Control aerosols of sodium chloride solution or phosphate buffer produced no effects. Control experiments with intravenous infusions of bupivacaine proved that none of the effects could have been produced by systemic effects of the absorbed anaesthetic.

5. Plasma concentrations of bupivacaine in man did not exceed a recognized toxic level. The experiments demonstrate a safe reversible anaesthesia of the airways in man lasting for a period of 10–20 min.
Studies of Amino Acid and Protein Metabolism in Normal Man with l-[U-14C]Tyrosine
Authors: James W. P. T. , Garlick P. J. , Sender P. M. , Waterlow J. C.
Published: August 2015

1. Six men were infused intravenously for 10 h with a tracer amount of l-[U-14C]tyrosine while on a standardized food intake.

2. Measurements of plasma l-[14C]-tyrosine specific radioactivity and the excretion rate of 14CO2 were made at frequent intervals and showed plateau labelling of plasma and expired carbon dioxide within 6–8 h. The tyrosine flux was calculated from the specific radioactivity in plasma at plateau value.

3. The excretion rate of 14CO2, corrected for retention of label within the bicarbonate pool, showed that oxidation accounted for 20% of the tyrosine flux. Urinary excretion of label was negligible.

4. Rates of protein synthesis were calculated from the flux of tyrosine after subtracting the proportion oxidized. Although the mean rate of synthesis was consistent with other measurements of protein turnover, the individual values ranged from 284 to 387 g/day. The variation was not reduced by relating turnover to body weight, lean body mass or energy expenditure.

5. Estimating the rates of protein breakdown from the tyrosine flux involved some assumptions about pathways of phenylalanine metabolism. The use of a labelled essential amino acid would therefore give more accurate values for short-term measurements of whole body protein turnover.
The Transport of Endogenous Vitamin B12 in Normal Human Serum
Authors: England J. M. , Down Margaret C. , Wise Irene J. , Linnell J. C.
Published: August 2015

1. Serum from normal subjects has been chromatographed on Sephadex G-200 columns and the fractions containing transcobalamins 0, I and II have been identified.

2. The fractions corresponding to transcobalamin I contained, on average, 90% of the endogenous vitamin B12. Only 3% was attached to transcobalamin 0, and 7% was bound to transcobalamin II.
The Sodium-Retaining Effect of Renal Nerve Activity in the Cat: Role of Angiotensin Formation
Authors: Johns E. J. , Lewis Barbara A. , Singer Bertha
Published: August 2015

1. The effect of low-frequency stimulation of the renal nerves on renal function and renin release has been investigated. The experiments were performed in unilaterally nephrectomized, anaesthetized cats in which the nerves to the remaining kidney were sectioned.

2. When stimulation frequency was adjusted to reduce renal blood flow by approximately 15% for 15 min, glomerular filtration rate was hardly affected. The ratio sodium clearance/glomerular filtration rate was significantly reduced and plasma renin activity was significantly increased.

3. When the renal nerves were similarly stimulated in the presence of the β-adrenergic receptor blocking agent, propranolol, the glomerular filtration rate was significantly reduced and the rise in plasma renin activity was significantly inhibited. The reduction of sodium clearance/glomerular filtration rate was as great as in the control animals.

4. The results are consistent with the view that the maintenance of glomerular filtration rate, during renal nerve stimulation which reduced renal blood flow, may be mediated by the local generation of angiotensin. The results also suggest that angiotensin does not play an important role in the sodium retention associated with increased renal nerve activity.
The Absorption of Sugars from the Human Buccal Cavity
Authors: Manning A. S. , Evered D. F.
Published: August 2015

1. Certain sugars were transported across the buccal mucosa by a carrier-mediated mechanism.

2. The metabolic loss of sugars from the mouth in a 5 min test period was negligible.

3. The buccal mucosal transport process was stereospecific for d-glucose and l-arabinose.

4. The absorption of d-glucose, galactose and 3-O-methyl-d-glucose was at least partly dependent on the presence of sodium ions in the luminal fluid.

5. The transport of d-glucose was inhibited by galactose and 3-O-methyl-d-glucose, suggesting at least one common carrier system.
Density-Dependence of Maximal Expiratory Flow Rates before and after Bronchodilators in Patients with Obstructive Airways Disease
Authors: Wellman J. J. , McFadden E. R. , Ingram R. H.
Published: August 2015

1. Gas-density-dependence of maximal expiratory flow rates (V̇max), defined as the ratio of V̇max while breathing helium/oxygen (80:20) to V̇max. while breathing air at the same lung volume, was examined in relation to other measurements of airways obstruction in patients with obstructive airways disease before and after administration of bronchodilators.

2. Seventeen patients showed a 45% or greater increase in specific conductance(sGaw) after bronchodilator therapy (group A) and thirteen patients demonstrated a lesser response (group B).

3. Before the administration of bronchodilators, the degree of obstruction in the two groups was not different as measured by lung volumes, sGaw, forced expiratory volume in 1 s, and flow rates high in the vital capacity; yet the maximal mid-expiratory flow rate and the degree of density-dependence were significantly lower in group B.

4. After bronchodilators, both groups of patients showed significant improvements in sGaw flow rates and lung volumes. However, group A patients showed a significant increase in density-dependence whereas group B patients did not.

5. Increased density-dependence after bronchodilators in the group A patients was associated with an increase in the computed resistance of the upstream segment with air and a decrease in resistance with helium/oxygen. These changes could be explained by a more mouthward movement of equal pressure points, and therefore a further increase in the relative contribution of the larger density-dependent airways to limitation of flow.

6. The fact that density-dependence was not altered after bronchodilators in the group B patients suggests that the site of limitation of flow did not change appreciably. The shift in the pressure—flow curve for the upstream airways was such that the computed resistance of these airways fell. Thus it appears that the airways comprising the upstream segment were dilated.
Effect of Age on Oxygen-Binding in Normal Human Subjects
Authors: Tweeddale P. M. , Leggett R. J. E. , Flenley D. C.
Published: August 2015

1. Oxygen-binding, plasma and intra-erythrocytic pH, and haemoglobin, 2,3-diphosphoglycerate and inorganic phosphate concentrations were measured in sixty-two healthy non-smokers aged between 18 and 89 years.

2. P50 (oxygen tension at 50% oxygen saturation) expressed at plasma pH 7·40 and Pco2 5·33 kPa showed a positive correlation with age.

3. This correlation of P50 with age was closer when P50 was expressed at a constant intra-erythrocytic pH 7·20. On average P50 at intra-erythrocytic pH 7·20 increased from 3·59 kPa at 20 years to 3·96 kPa at 90 years of age.

4. 2,3-Diphosphoglycerate, inorganic phosphate, haemoglobin and mean corpuscular haemoglobin concentrations did not correlate with P50 or with age.
Relationship of Epicardial ST Segment Elevation to the Plasma Free Fatty Acid/Albumin Ratio during Coronary Occlusion in Dogs
Authors: Miller N. E. , Mjøs O. D. , Oliver M. F.
Published: August 2015

1. Intravenous infusions of lipid-free albumin were used to lower the arterial non-esterified fatty acids (NEFA)/albumin ratio during coronary occlusion in dogs.

2. Reduction of the NEFA/albumin ratio was accompanied by proportionate reductions in myocardial uptake of NEFA and the degree of ST segment elevation in epicardial electrocardiographic recordings from the ischaemic zone. Aortic pressure and heart rate were unchanged.

3. Infusions of control albumin preparations had no effect on the NEFA/albumin ratio or ST segment elevation.

4. These observations support the proposition that the disturbance of cellular function during myocardial ischaemia is influenced by the degree of saturation of albumin-binding sites with NEFA and by their availability.
Potassium Transport across the Distal Colon in Man
Authors: Salas-Coll C. A. , Kermode J. C. , Edmonds C. J.
Published: August 2015

1. The mechanism of potassium transport across human distal colon was investigated in twenty-two individuals without evidence of bowel disease, by using a dialysis method in conjunction with measurements of the transepithelial potential difference (p.d.).

2. Whether potassium was absorbed or secreted depended on its initial concentration in the lumen. The potassium net flux was approximately zero when the luminal potassium concentration was between 30 and 50 mmol/l.

3. Potassium secretion rate was little affected by sodium absorption rate, or by the luminal sodium concentration or by the osmolality of the luminal solution.

4. Potassium secretion rate was increased by partial substitution of other cations for sodium, in the descending order Li > NH4 > Rb > Na. Potassium concentration increased on average to over 80 mmol/l when lithium was in the lumen.

5. The observed transepithelial p.d. was inadequate to account for the intraluminal potassium concentrations attained, the discrepancy being most marked when ammonium or lithium was in the lumen. It is suggested that some potassium is secreted by the epithelial cells and this component of the total potassium flux into the lumen is increased when rubidium, ammonium or lithium is substituted for sodium.
Blood Flow through the Calf during Recovery from Fractures of the Lower Limb
Authors: Imms F. J. , Lorde D. A. , Prestidge S. P. , Thornton Christine
Published: August 2015

1. Venous occlusion plethysmography has been used to measure the blood flow in the calves of nineteen patients with fractures of the lower limb and in six normal control subjects.

2. The resting blood flows were significantly higher in the injured legs than in uninjured legs, irrespective of the site of injury. Flows in the uninjured limbs were similar to those of the control subjects.

3. During reactive hyperaemia after 10 min arterial occlusion, the increase of flows in both legs of the patients was significantly lower than in the control subjects. Because of the increased resting flow, the maximal flow in the injured leg was similar to that in the control subjects, whereas the maximal flow in the uninjured leg was significantly lower than in the control group.

4. The changes in resting flow cannot be accounted for by a change in the proportions of tissues in the limb but they may be explained by an increase of the flow through muscle secondary to a relative increase in the mass of slow to fast muscle fibres.
The Arteriolar Lesions of Steroid Hypertension in Rats
Authors: Goldby F. S.
Published: August 2015

1. The arteriolar lesions of rats with deoxycorticosterone (DOCA)—salt hypertension have been studied by colloidal carbon injection and light- and electron-microscopy.

2. Colloidal carbon particles enter the media of arterioles to form focal deposits when hypertension develops.

3. The focal lesions are similar to those seen after angiotensin infusion or renal artery constriction. They are characterized by endothelial damage and plasma deposition in the media.

4. Heavy deposition of carbon in the glomeruli of DOCA-treated animals was found to be caused by increased mesangial uptake and not by hypertensive vascular damage.

5. Angiotensin II concentrations fell during the development of hypertension and vascular lesions. The renin—angiotensin system was not implicated in the development of vascular damage in this form of hypertension.
Skin Collagen in Idiopathic Adolescent Scoliosis and Marfan's Syndrome
Authors: Francis M. J. O. , Sanderson M. C. , Smith R.
Published: August 2015

1. Skin collagen from fifteen patients with idiopathic adolescent scoliosis, three with congenital scoliosis, and fourteen patients with various degrees of Marfan's syndrome has been examined.

2. The stability of a polymeric collagen fraction, extracted from the skin of these patients, to depolymerization, has been compared with that from thirty-one matched control subjects.

3. The mean polymeric collagen stability was significantly reduced (P < 0·01) in the group of fifteen patients with idiopathic adolescent scoliosis. The individual reductions in stability were greater in the younger patients and no reduction was found in two patients aged 19 years who had a mature skeleton.

4. The mean stability of polymeric skin collagen from the group of patients with Marfan's syndrome was not significantly abnormal, although there were individual low values.

5. Polymeric collagen of low stability was present in individual patients from each clinical group. Instability of collagen (from whatever cause) at a time of rapid growth may contribute to the high incidence of scoliosis in adolescent girls. In boys, adolescent scoliosis is less common and the maximum growth rate occurs at a time when collagen stability is less reduced.
Effect of Acupuncture on Bronchial Asthma
Authors: Yu D. Y. C. , Lee S. P.
Published: August 2015

1. Needle acupuncture was performed at three sites in twenty patients in a clinical attack of bronchial asthma.

2. In all patients the symptoms of bronchoconstriction improved during the attacks when the correct site was stimulated, and in five patients wheezing was abolished.

3. Stimulation at the correct site produced a significant increase in the mean FEV1·0 (58%) and FVC (29%) but not in maximal mid-expiratory flow rate (MMFR; 76%), when compared with the findings before acupuncture, along with a significant fall in the Pa,co2 and an insignificant fall in Pa,o2. A mild tachycardia was also observed.

4. After acupuncture a greater improvement in FEV1·0, FVC and MMFR was produced by inhalation of isoprenaline.

5. No significant changes in FEV1·0, FVC, MMFR, pulse rate or arterial blood gas tensions occurred after acupuncture at control sites.

6. In four of the patients during clinical remission acupuncture was performed before and after histamine aerosol challenge, but there was no effect on either the severity or the duration of the histamine-induced bronchoconstriction.

7. It is concluded that acupuncture probably reduced the reflex component of the bronchoconstriction, but failed to influence direct smooth muscle constriction caused by histamine.
A Simple Method for the Differential Measurement of 125I and 3H by Liquid-Scintillation Spectrometry
Authors: Shand J. H. , Noble R. C.
Published: August 2015

1. A method is described for the differential radioactivity counting of 125I and 3H in a liquid-scintillation spectrometer without a separate gamma counter.

2. The sample was contained in a polyethylene miniature vial placed centrally in a standard 20 ml glass scintillation vial containing a tin-loaded scintillant.

3. A direct measure of the 125I radioactivity at an efficiency of 30% was then obtained by radioactivity counting in the pre-set 3H window of a scintillation spectrometer. No counts for 3H radioactivity were registered at this stage because of the barrier to the passage of the low-energy β-particles provided by the wall of the polyethylene vial.

4. After mixing the sample and scintillant both 125I and 3H were detected at efficiencies of 73 % and 29% respectively. Subtraction of the 125I contribution from the combined radioactivity count rate then gave the net 3H count.
Analytical Subcellular Fractionation of Jejunal Biopsy Specimens: Methodology and Characterization of the Organelles in Normal Tissue
Authors: Peters T. J.
Published: August 2015

1. Portions of closed jejunal biopsies were gently homogenized in isotonic sucrose or sorbitol and centrifuged at 800 g for 10 min to prepare a cell extract.

2. The extract was fractionated in a single-step procedure by isopycnic centrifugation on a continuous sucrose or sorbitol density gradient with the Beaufay automatic zonal rotor.

3. The subcellular organelles were located in the density gradient by assay of marker enzymes and previously unassigned enzymes were localized to particular organelles.

4. The following organelles were characterized by their modal equilibrium densities in sucrose density gradients: brush borders (1·21), peroxisomes (1·18), mitochondria (1·16), endoplasmic reticulum (1·16), basal—lateral membranes (1·12). At least three distinct populations of lysosomes with different modal densities and enzyme content were demonstrated.

5. This analytical fraction technique can be used to study the subcellular pathology of human jejunum.
Renin Release from Isolated Rat Glomeruli
Authors: Holdsworth S. , McLean A. , Morris B. J. , Dax E. , Johnston C. I.
Published: August 2015

1. By the use of a mechanical graded sieving technique a high yield of isolated glomeruli has been obtained from rat kidney.

2. Microscopy and renin assay have shown the presence of renin-containing juxtaglomerular cells attached to these glomeruli.

3. The viability of isolated glomeruli has been confirmed by the ability of the cells to survive and divide in tissue culture and by their exclusion of vital dyes.

4. In superfusion after washout of extracellular renin, the glomeruli actively release constant amounts of renin over 3 h in direct proportion to the number superfused.

5. Decreasing sodium concentration from 140 to 110 mol/l with constant osmolarity of 305 mosmol/l stimulated renin release by a direct effect on juxtaglomerular cells.

6. Catecholamines stimulated renin release in vitro in proportion to the potency of their action on β-adrenoreceptors.

7. The system of superfusion of isolated glomeruli provides a technique for studying the influence of mediators leading to renin release acting directly on juxtaglomerular cells, independent of pressure change, tubular sodium, the sympathetic nervous system and circulating hormones.
Effects of Carotid Occlusion and Clonidine on Renin Secretion in Anaesthetized Dogs
Authors: Reid I. A. , Jones A.
Published: August 2015

1. Sympathetic reflexes were activated by carotid occlusion in anaesthetized dogs in which changes in renal perfusion pressure were prevented. This produced a prompt and reversible increase in plasma renin activity.

2. Administration of clonidine decreased plasma renin activity, arterial pressure and heart rate and blocked the renin secretory and blood pressure responses to carotid occlusion.

3. These results support the hypothesis that the suppression of renin secretion by clonidine is a consequence of the decrease in sympathetic activity produced by this drug.
Evidence of Altered Permeability of the Erythrocyte Membrane for Sodium and Potassium ions in Spontaneously Hypertensive Rats
Authors: Postnov YU. V. , Orlov S. N. , Gulak P. V. , Shevchenko A. S.
Published: August 2015

1. Erythrocyte membrane permeability to sodium and potassium ions was studied in 8–10 weeks spontaneously hypertensive rats (SHR, Kyoto/Wistar strain), normotensive Wistar and Sprague—Dawley rats.

2. The rate of 22Na efflux from the erythrocytes and the rate constant of Na/Na exchange were considerably greater in SHR than in normotensive Wistar and Sprague—Dawley rats. This difference remained the same in rats adrenalectomized 7 days before the experiment. The maximum difference in the constants was found when the sodium—potassium pump was blocked by ouabain.

3. The accumulation of 42K in the erythrocytes of SHR (the sodium—potassium pump being blocked) took place at a considerably slower rate, and the K+ wash-out into a potassium-free medium was faster than that in the normotensive Wistar and Sprague—Dawley rats.

4. These results indicate a higher permeability of the erythrocyte membrane of SHR for Na+ and K+, compared with normotensive Wistar and Sprague—Dawley strains. It is suggested that this may reflect a more widespread cell-membrane defect, which could serve as a general cause for activating the mechanisms maintaining high blood pressure.
Selective Hypoaldosteronism: A Study of Steroid Biosynthetic Pathways under Adrenocorticotrophin and Angiotensin II Infusion
Authors: Lebel M. , Grose J. H.
Published: August 2015

1. The functional integrity of the adrenal cortex has been tested in a case of selective hypoaldosteronism by adrenocorticotrophin (ACTH) and angiotensin II (AII) infusion.

2. During ACTH infusion a normal functioning zona fasciculata was indicated by the impressive increase of the ACTH-dependent plasma steroids; the aldosterone response was moderate.

3. During AII infusion the plasma aldosterone response was blunted with an unexpected dose-dependent increase in pregnenolone, resulting in abnormal decreasing progesterone/pregnenolone ratios during the infusion, suggesting a slow-down in the conversion of pregnenolone into progesterone.

4. This defect, a probable consequence of chronic renin deficiency on the zona glomerulosa, could be a contributing factor to the hypoaldosteronism.
Peripheral and Central Catecholaminergic Neurons in Genetic and Experimental Hypertension in Rats
Authors: Grobecker H. , Saavedra J. M. , Roizen M. F. , Weise V. , Kopin I. J. , Axelrod J.
Published: August 2015

1. Activity of peripheral and central catecholaminergic neurons was studied in spontaneously hypertensive rats (SHR) and deoxycorticosterone (DOCA)—salt hypertensive rats.

2. In young SHR (4 weeks) the plasma values of both noradrenaline and dopamine-β-hydroxylase activity were increased compared with those of normotensive rats of the Wistar/Kyoto strain. Total catecholamines (mostly adrenaline) were not significantly different.

3. In the adrenal glands of 2-weeks-old and 4-weeks-old SHR activities of tyrosine hydroxylase, dopamine-β-hydroxylase, phenylethanolamine-N-methyl transferase were decreased, compared to Wistar/Kyoto rats.

4. The adrenaline-forming enzyme was elevated in the A1 and A2 regions of the brain stem of 4-weeks-old SHR and in the A1 region of adult DOCA—salt hypertensive rats.

5. In the adrenal glands of adult DOCA—salt hypertensive rats tyrosine hydroxylase activity was increased.

6. These results implicate peripheral noradrenaline-containing neurons and central adrenaline-containing neurons in the development of genetic and experimental hypertension in rats.
Increase of Total Body Potassium and Decrease of Exchangeable Sodium after Long-Term Treatment with a β-Receptor-Blocking Agent (Prindolol) in Essential Hypertension
Authors: Brecht H. M. , Werner E. , Schoeppe W.
Published: August 2015

1. The effect of long-term treatment with prindolol on blood pressure, total body potassium (Kt), exchangeable sodium (Nae) and plasma renin activity was investigated in twelve patients with essential hypertension.

2. Systolic and diastolic pressures were significantly reduced from 164/112 to 127/90 mmHg under basal conditions.

3. Before treatment Na. in patients with essential hypertension was significantly higher than in normotensive individuals. After an average of 16 weeks on prindolol Nae in patients with essential hypertension was significantly decreased, despite an average increase in body weight of 2 kg in the patients.

4. In contrast to the decrease in Nae, Kt was found to be significantly increased after long-term treatment with prindolol. Kt values of patients before and after prindolol, however, did not differ significantly from the corresponding sex- and age-dependent normal values.

5. Plasma renin activity was slightly diminished under basal and orthostatic conditions; the stimulatory effect of orthostasis was not abolished but reduced by prindolol.

6. It is suggested that the changes in sodium balance contribute to the anti-hypertensive effect of prindolol in patients with essential hypertension.
A Within-Patient Comparison of Bethanidine, Methyldopa and Propranolol in the Treatment of Hypertension
Authors: Prichard B. N. C. , Boakes A. J. , Graham B. R.
Published: August 2015

1. A within-patient comparison showed that bethanidine, methyldopa and propranolol produced similar control of the blood pressure.

2. Unlike bethanidine, propranolol did not produce postural and exercise hypotension; methyldopa was intermediate in effect.

3. Overall side effects were of a similar incidence though there were differences in incidence of particular side effects.
A Comparison of the Effects of Chlorothiazide and of Metolazone in the Treatment of Hypertension
Authors: Hua A. S. P. , Kincaid-Smith Priscilla
Published: August 2015

1. A cross-over study was done in twenty patients with hypertension to compare the effects of chlorothiazide (0·5 g twice daily) and metolazone (5 mg daily) in combination with other anti-hypertensive agents.

2. Compared with absence of diuretic therapy, chlorothiazide and metolazone both produced significantly lower blood pressures.

3. Blood pressures on metolazone tended to be lower than on chlorothiazide but this difference was not statistically significant.

4. Both diuretics significantly lowered serum potassium concentrations and total body potassium to a similar degree, but the serum potassium did not fall below the normal range in any patient and no potassium supplements were needed. No electrocardiographic changes suggestive of hypokalaemia were noted.

5. Small but significant increases in serum bicarbonate, calcium, urea and uric acid were observed with both diuretics.

6. Patient acceptance was excellent and no adverse effects were encountered.
Natriuresis in Rats Acutely Depleted of Chloride
Authors: Luke R. G. , Khanh B. T. , Schmidt R. D. , Galla J. H.
Published: August 2015

1. Acute chloride depletion, without sodium depletion, was produced in rats by a single exchange peritoneal dialysis against sodium bicarbonate solution. Blood volume was restored after dialysis by infusion of salt-free albumin, and exogenous deoxycorticosterone and antidiuretic hormone were given.

2. Clearance studies in the period (3 h) after dialysis revealed no difference in the glomerular filtration rate or in the filtered sodium load between experimental and control rats but urinary sodium concentrations and absolute and fractional sodium excretion were significantly higher in the chloride-depleted group.

3. There was also a significant kaliuresis, increased urinary flow rate and diminished free water reabsorption. Urinary bicarbonate excretion increased to a variable degree but the major rise in anion excretion was ‘unmeasured’ (Na+ + K+ — [Cl− +HCO3− +PO43-]).

4. It is postulated that chloride depletion imposes limitations on sodium reabsorption in the ascending limb of the loop of Henle.
Effect of Propranolol on Blood Pressure and Renin in Renal Hypertension in the Rat
Authors: Fernandes M. , Onesti G. , Fiorentini R. , Gould A. B. , Kim K. E. , Swartz C.
Published: August 2015

1. Propranolol was administered to groups of mature rats before and during the development of renal hypertension induced by ligation of the aorta between the renal arteries.

2. At a dose 10 μmol (3 mg) of propranolol/kg, administered by intraperitoneal injection, the onset and severity of hypertension were not affected, although plasma renin concentration was significantly lower than in the untreated hypertensive rats in the first 5 days after the operation.

3. With 200 μmol (60 mg) of propranolol/kg, administered in the drinking water, peak blood pressure 5 days after aortic ligation was lower than in the untreated control rats, but plasma renin concentration was no lower than with the smaller dose.

4. The development of severe hypertension despite reduction in plasma renin concentration on the low dose of propranolol suggests the participation of renal vasopressor factors other than renin in this model.

5. A higher dose of propranolol reduced the rise in plasma concentration to an equal extent but the rise of blood pressure at 5 days was also reduced, which supports this concept.
A Study of the Contractility, Biochemistry and Morphology of an Isolated Preparation of Human Skeletal Muscle
Authors: Moulds R. F. W. , Young A. , Jones D. A. , Edwards R. H. T.
Published: August 2015

1. A new method of studying isolated human skeletal muscle has been evaluated. This involves the incubation and electrical stimulation of strips of muscle, obtained at surgical biopsy, that are tied at the cut ends of the fibre bundles.

2. Morphological examination showed that the fibres were sealed off at the cut ends. Damage appeared to be restricted to the areas immediately adjacent to the ties.

3. Contractile properties were well maintained for several hours and measurements of tissue metabolites showed that muscle contents of the high-energy phosphate compounds were well preserved.

4. The isolated preparations were found to have the same contractile properties as human quadriceps femoris studied in vivo by the methods described in the preceding paper.

5. Correlation was found between the relaxation speed of the isolated preparations and their fibre-type composition histochemically determined.

6. It is concluded that this technique is a valid addition to the present methods of studying the physiology and pharmacology of human skeletal muscle.
Muscle-Protein Catabolism after Injury in Man, as Measured by Urinary Excretion of 3-Methylhistidine
Authors: Williamson D. H. , Farrell Rose , Kerr Alison , Smith R.
Published: August 2015

1. Urinary excretion of 3-methylhistidine, an index of the rate of muscle breakdown, has been measured during the first 7 days in patients after elective surgery or accidental injury.

2. There was no major difference between the mean daily excretion after skin grafting or total hip replacement, or in injured patients who were hyperketonaemic for the first 24 h after admission.

3. The group of injured patients who did not develop hyperketonaemia had a mean urinary 3-methylhistidine excretion which was twice that of the other groups.

4. It is concluded that increased breakdown of muscle protein makes a major contribution to the greater urinary nitrogen excretion in the normoketonaemic group of injured patients.
Effects of Clonidine on Biochemical Indices of Sympathetic Function and Plasma Renin Activity in Normotensive Man
Authors: Wing L. M. H. , Reid J. L. , Hamilton C. A. , Sever P. , Davies D. S. , Dollery C. T.
Published: August 2015

1. A single oral dose of clonidine hydrochloride (300 μg) lowered systolic blood pressure by 20 ± 2 mmHg and diastolic blood pressure by 15 ± 2 mmHg in seven healthy normotensive subjects.

2. Resting supine plasma noradrenaline concentration fell from 2·42 ± 0·47 nmol/l before dosing to a minimum of 0·59 ± 0·18 nmol/l at 6 h. The value subsequently rose and was not significantly different from that before the dose at 12 h. There was a significant reduction in urinary free catecholamine excretion in the first 12 h after dosing.

3. Resting supine plasma renin activity before dosing was 0·95 ± 0·16 pmol of angiotensin I h−1 ml−1 of plasma and rose significantly after clonidine to 3·50 ± 0·39 pmol of angiotensin I h−1 ml−1 of plasma at 6 h. By 12 h plasma renin activity had returned to control values.

4. When the same subjects were studied on a control, drug-free, day under the same conditions, there was no significant change in blood pressure or plasma noradrenaline. Although plasma renin activity rose during this control day, it was significantly lower than after clonidine.

5. In normotensive subjects single doses of clonidine lower blood pressure and are associated with a reduction of sympathetic nervous activity. Delayed elevation of plasma renin activity may be secondary to the fall in blood pressure. There is no evidence for an overshoot of sympathetic activity after a single dose of clonidine.
A Slow Component of Iodine Turnover in Athyreotic Individuals
Authors: Smith T. , Edmonds C. J.
Published: August 2015

1. Whole-body retention and plasma values of 131I after a test dose were measured for up to 32 days in patients previously rendered athyreotic by surgery and 131I treatment for thyroid carcinoma, and who were without detectable functioning tissue at the time of study.

2. About 99·8% of the administered 131I was rapidly excreted, consistent with renal iodide excretion. The remainder (about 0·2%) was eliminated slowly, with mean half-life 15 days; we call this the slow-turnover component.

3. By the sixth day after the 131I dose, very little [131I]iodide remained in the plasma. The average protein-bound 131I was only 0·0035% of dose/l, with mean half-life 14·1 days; 90% was non-extractable in butanol. Labelled albumin accounted for about 80% of the non-extractable fraction.

4. The distribution space estimated from the slow-turnover component and protein-bound 131I was 34 1, indicating that most of the slow-turnover component is extravascular.

5. Stable potassium iodide administration, starting 2 days after giving 131I, had no observable effect on the variables measured.

6. Impairment of renal function delayed [131I]iodide excretion and increased both slow-turnover component and plasma protein-bound 131I.

7. A simple model describing iodine kinetics in athyreotic individuals is suggested. It predicts that the slow-turnover component contains only about 4 μg of iodine and, since this is distributed widely in body tissues, it is unlikely to be of biological significance.
The Crystalline Salts of Calcium Bilirubinate in Human Gallstones
Authors: Sutor D. June , Wilkie Lynette I.
Published: August 2015

1. The acid, neutral and ‘intermediate’ salts of calcium bilirubinate have been synthesized.

2. All are crystalline, and the intermediate salt which has 1½ molecules of bilirubin per calcium atom probably has a crystal structure containing molecules of both acid and neutral salts.

3. The acid or intermediate salts have been found in 14 out of 70 gallstones analysed recently by X-ray diffraction.
Muscle Metabolism during Exercise in Hemiparetic Patients
Authors: Landin S. , Hagenfeldt L. , Saltin B. , Wahren J.
Published: August 2015

1. A group of eight male patients with moderate hemiparesis was studied at rest and during 40 min of exercise on four occasions. Both two-leg and one-leg exercise were performed and each leg was studied separately. Arterial concentrations and leg exchange of carbohydrate substrates and free fatty acids were examined. In addition, the concentrations of intramuscular metabolites for each leg were measured at rest and immediately after exercise.

2. In two-leg exercise, oxygen uptake for the paretic leg was significantly lower than for the non-paretic leg at rest (55%) as well as during exercise (40%). Glucose uptake by the paretic leg was smaller (25–50%) and there was no measurable net leg exchange for lactate. Recordings of pedal pressure indicated that the paretic leg did considerably less work than the non-paretic leg throughout the exercise period. The rate of uptake of oleic acid was lower for the paretic leg (50%) in the resting state but similar for the two legs during exercise. The recovery of 14CO2 from [14C]oleic acid during exercise was significantly reduced for the paretic leg.

3. During one-leg exercise, oxygen and glucose uptakes by the working leg were similar for the paretic and non-paretic leg but lactate release was significantly greater for the paretic leg during exercise (30–45%).

4. The concentrations of ATP and creatine phosphate in the basal state were similar for the two legs. ATP and creatine phosphate fell significantly in the two legs during both the two-leg and the one-leg exercise period. The most marked decrease in ATP was noted for the paretic leg during one-leg exercise. The pattern of glycogen depletion during one-leg exercise for the paretic leg indicated primarily activation of the type II fibres. In contrast, the depletion pattern for the non-paretic leg suggested mainly recruitment of type I fibres.

5. The results indicate that, during exercise, paretic muscle shows a reduced blood flow, an augmented lactate production and a diminished capacity to oxidize free fatty acids. These metabolic derangements may be referrable to an augmented number and increased activation of type II muscle fibres as well as to alterations in the structure of muscle mitochondria. In addition, the present study indicates that one-leg exercise should be preferred to two-leg exercise when studying leg muscle circulation and metabolism in hemiparetic patients.
Total Protein Synthesis in Elderly People: A Comparison of Results with [15N]glycine and [14C]leucine
Authors: Golden M. H. N. , Waterlow J. C.
Published: August 2015

1. Total body protein turnover was studied in six elderly patients.

2. During the study they were fed by continuous infusion of a liquid formula through a nasogastric tube. l-[1-14C]Leucine and [15N]glycine were infused at a constant rate for 30 h. The labelled glycine was infused into the intragastric line; the labelled leucine was given either by this route or intravenously.

3. The specific radioactivity of free leucine in plasma and the rate of output of 14CO2 in expired air both reached a plateau at 10 h, and remained constant until the end of the infusion at 30 h.

4. The 15N abundance in urinary urea and total N was very similar. In neither was a plateau reached by 30 h but in four out of the six patients the abundance in urinary NH4+ had attained a plateau by the end of the infusion.

5. Flux rates and rates of protein synthesis were calculated in four ways: (A) from the specific radioactivity of plasma leucine at plateau; (B) from the proportion of dose excreted as 14CO2 at plateau; (C) from the final rates of 15N excretion in urea or total urinary N; (D) from the final or plateau rates of 15N excretion in urinary NH4+.

6. On average, the estimates of synthesis rate obtained by methods B and C agreed closely; those given by methods A and D were lower. Methods A, B and D ranked the individual patients in almost identical order.

7. The comparison of methods makes it possible to examine the validity of the assumptions on which the different methods depend. Method B is probably theoretically the most satisfactory and, of the methods used in this work, probably gives the best estimate of the absolute turnover rate. The other methods can be used for comparative purposes.

8. The results suggest that the rate of protein turnover is reduced in the elderly, compared with younger subjects.
Two Methods for Determination of Renin Secretion Rates in Rats
Authors: Iaina A. , Nakash I. , Reisin E. , Spivack B. , Eliahou H. E.
Published: August 2015

1. Renin secretion rates in normal rats were determined with two different methods: (a) the product of renal plasma flow as measured by sodium p-aminohippurate and the difference between renal and peripheral vein renin activity; (b) the product of this latter difference and the renal plasma flow as calculated from the clearance and extraction of inulin.

2. The renin secretion rates, as calculated by these two methods, were not significantly different (P > 0·1) and were found to be highly correlated (r = 0·943; P < 0·001).
Detection of Na+ and K+ in the Rat Adrenal Cortex with the Electron Microprobe
Authors: Decorzant C. , Riondel A. M. , Philippe M.-J. , Bertrand J. , Vallotton M. B.
Published: August 2015

1. In order to demonstrate whether modification of aldosterone secretion is mediated by parallel changes of K+ in the adrenal zona glomerulosa, the total (intracellular + extracellular) Na+ and K+ content of the rat adrenal cortex was determined with the electron microprobe.

2. Groups of rats were submitted to one of the following dietary regimens: standard, low Na+, high K+ or high Na+.

3. Distribution of Na+ and K+ across the zona glomerulosa and zona fasciculata was compared. Standards of known electrolyte concentration were also analysed.

4. The [Na+] was found to be greater in the zona glomerulosa than in the zona fasciculata but K+ was distributed evenly in both zones. This was independent of dietary regimen.

5. Aldosterone production, assessed by plasma aldosterone concentrations, could not be correlated with zona glomerulosa K+ content.
Intracellular pH and Bicarbonate Concentration as Determined in Biopsy Samples from the Quadriceps Muscle of Man at Rest
Authors: Sahlin K. , Alvestrand A. , Bergström J. , Hultman E.
Published: August 2015

1. A method for measuring intracellular pH and bicarbonate concentration of human muscle is described.

2. Muscle biopsies from the quadriceps muscle of 13 healthy subjects at rest were analysed for acid-labile carbon dioxide and volume of extra- and intra-cellular water. Extracellular water volume was estimated from the chloride content and intracellular water volume from the potassium content, or alternatively derived from the sample weight.

3. The measured total carbon dioxide content in muscle was 9·84 ± 1·39 mmol/kg.

4. Assuming a normal membrane potential (88 mV) and Pco2 of muscle equal to venous blood, calculated intracellular pH was 7·00 ± 0·06 and intracellular bicarbonate concentration was 10·2 ± 1·2 mmol/l of water.
Effect of Inhibition of Prostaglandin Synthesis on the Natriuresis Induced by Saline Infusion in Man
Authors: Mountokalakis Th. , Karambasis Th. , Mayopoulousymvoulidou D. , Merikas G.
Published: August 2015

1. The effect of oral administration of an inhibitor of prostaglandin synthetase, indomethacin, on the natriuresis induced by the infusion of sodium chloride (saline) was studied in 11 healthy volunteers.

2. The administration of indomethacin did not alter sodium excretion before saline infusion, but it resulted in a significant increase of the natriuresis after saline infusion. This increase was not accompanied by any change in post-infusion urine flow rate or free water reabsorption.

3. It is suggested that intrarenal prostaglandins might suppress the natriuretic effect of saline infusion, probably by increasing sodium reabsorption in the distal nephron.