bluuebunny/crossref_metadata_2025 huggingface dataset:
Sodium Homeostasis in Patients with Autonomic Failure
Authors: Wilcox C. S. , Aminoff M. J. , Slater J. D. H.
Published: August 2015

1. The renal excretion of sodium by five patients with autonomic failure (Shy—Drager syndrome) was compared with a matched control group who had normal autonomic reflexes (Parkinson's disease). For 8 or 9 days the daily sodium intake was reduced to 17 mmol, and for 5 subsequent days it was increased to 189 mmol.

2. The sodium excretion of the patients with autonomic failure was not significantly reduced during 7 days of restricted intake whereas that of the control group fell rapidly to values comparable with their sodium intake. Patients with autonomic failure had a larger fall in body body weight than the control subjects.

3. Both lying and standing values of mean blood pressure fell during salt restriction in the patients with autonomic failure, but not in the control subjects.

4. Values of plasma renin activity (PRA) were significantly depressed in patients with autonomic failure. However, PRA rose to values similar to those of control subjects while standing during the period of restricted sodium intake. At this time the patients with autonomic failure had a large orthostatic fall in blood pressure and creatinine clearance.

5. Aldosterone secretion rates were measured in three patients with autonomic failure at both levels of sodium intake and were considerably lower than the rates found in the control group.

6. A mineralocorticoid drug (9α-fludrocortisone; 2 mg/day), given on the last 2 days of restricted sodium intake, failed to correct fully the negative sodium balance of the patients with autonomic failure, since an excessive sodium excretion persisted during the period of recumbency at night.

7. These results demonstrate a severe defect in renal salt conservation in certain patients with autonomic failure. They suggest that the defect may not be entirely due to deficient secretion of mineralocorticoid hormones.
Mechanisms of the Uricosuric Effect of the Diuretic Tienilic Acid (Ticrynafen) in Man
Authors: Lau K. , Stote R. M. , Goldberg M. , Agus Z. S.
Published: August 2015

1. We have studied the effects of the diuretic tienilic acid (Ticrynafen) upon renal tubular transport of urate, in 11 healthy volunteers on a constant dietary intake.

2. Daily administration of tienilic acid for 10 days to six subjects reduced the mean body weight from 67·1 ± 4·7 kg to 64·5 ± 4·7 kg and a reversible fall in serum urate from a mean value of 0·34 ± 0·04 to 0·16 ± 0·01 mmol/l. Fractional urate excretion in the six subjects on the first day of therapy was 30·3 ± 5·6% and then fell to reach a new steady-state mean value of 17·4 ± 2·0%.

3. To evaluate the mechanism of the uricosuria, studies were performed during acute sustained water diuresis in five subjects to assess the effects of tienilic acid, pyrazinamide, probenecid and their combinations.

4. Fractional urate excretion increased markedly with tienilic acid from 11·2 ± 1·3% to 47·5 ± 5·7%. Pyrazinamide, 24·4 mmol (3 g) orally, decreased urate excretion to 5·1 ± 0·7% and markedly blunted the uricosuric effects but not the natriuresis of tienilic acid. Probenecid increased urate excretion to 26 ± 6·0 % and when given with tienilic acid increased urate excretion to 66·4 ± 2·6%. Addition of pyrazinamide to this combination decreased urate excretion to 19·6 ± 4·0%, which was greater than the effect with pyrazinamide alone.

5. We suggest that tienilic acid increased urate excretion by inhibiting reabsorption of both filtered and secreted urate. We have used our results to construct semi-quantitative estimates of the various components of urate transport in man.
Vitamin D Metabolism in Adult Rats at Low and Normal Calcium Intake and the Effect of Cadmium Exposure
Authors: Lorentzon R. , Larsson S.-E.
Published: August 2015

1. Chromatography measurements indicated that adult rats converted 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol at a lower rate than that reported earlier for young animals. In serum, less-polar metabolites were found which probably represented vitamin D esters and vitamin D3.

2. A low dietary intake of calcium resulted in an evident increase in the fraction corresponding to 1,25-dihydroxycholecalciferol in the kidneys and also in the intestinal mucosa and serum.

3. Inclusion of 0·67 mmol of cadmium/l of drinking water at a low dietary intake of calcium resulted in an increased accumulation of both cadmium and zinc in the kidneys and liver compared with values at a normal dietary calcium intake.

4. At a normal dietary calcium intake, cadmium exposure caused inhibited production of 1,25-dihydroxycholecalciferol by the kidneys and an increased accumulation of 24,25-dihydroxycholecalciferol, vitamin D3 and vitamin D esters in the serum.

5. The inhibitory effect of cadmium on the renal conversion of 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol was almost completely counteracted by a simultaneous low dietary calcium intake. Cadmium-exposed, calcium-deficient animals also showed a maintained accumulation of 1,25-dihydroxycholecalciferol in the intestinal mucosa.
Excretion of Salt and Water by Patients with Sickle-Cell Anaemia: Effect of a Diuretic and Solute Diuresis
Authors: Forrester T. E. , Alleyne G. A. O.
Published: August 2015

1. Patients with sickle-cell anaemia were unable to increase free water reabsorption (TcH2O) in response to intravenous hypertonic sodium chloride solution.

2. Ethacrynic acid caused a brisk natriuresis in patients with sickle-cell anaemia but fractional sodium excretion was lower in these patients.

3. These findings could be explained by abnormal function of the loop of Henle.
Anaemia, Iron Deficiency and Exercise: Extended Studies in Human Subjects
Authors: Charlton R. W. , Derman D. , Skikne B. , Torrance J. D. , Lynch S. R. , Sayers M. H. , Zwi S. , Goldman H. I. , Van As A. , Margo G. , Schneider J. T. , Bothwell T. H.
Published: August 2015

1. Ventilation and cardiac frequency were measured during repeated treadmill exercise in three healthy subjects over 36 weeks, before, during and after iron-deficiency anaemia was produced and after iron treatment. The haemoglobin and 2,3-diphosphoglycerate concentrations and the oxygen-binding (P50) were measured.

2. There was an inverse relationship between the haemoglobin concentrations and the 2,3-diphosphoglycerate concentrations and the P50 values.

3. The mean cardiac frequencies during the fourth to tenth minutes of exercise showed a negative correlation with the haemoglobin concentrations in all three subjects, and the mean minute ventilations in two of them.
Oxygen Transport in Children on Maintenance Haemodialysis
Authors: Bursaux E. , Broyer M. , Poyart C. , Bohn B. , Jean G.
Published: August 2015

1. Adaptive mechanisms of oxygen transport by blood have been studied in severely anaemic young patients on maintenance haemodialysis, in conditions of hyperphosphataemia (P1 ≥ 2·2 mmol/l) or normophosphataemia.

2. In hyperphosphataemia whole-blood affinity for oxygen was slightly decreased, as measured by an increase in P50 (the partial pressure of oxygen necessary to half saturate haemoglobin). 2,3-Diphosphoglycerate was increased by 10% (P < 0·10) whereas P1, total erythrocyte phosphate and ATP were increased by 100%, 47% and 36% respectively, compared with control values.

3. After correction of hyperphosphataemia a small but significant decrease in P50 and 2,3-diphosphoglycerate, to normal values, was observed whereas the other variables, although significantly lowered, remained above control values.

4. In these severely anaemic and hyperphosphataemic patients P50 and 2,3-diphosphoglycerate are only slightly increased. ATP synthesis appears to be favoured over that of 2,3-diphosphoglycerate. This is possibly due to alterations in the erythrocyte membrane elicited by bi-weekly extracorporeal circulation. Adequate oxygen transport can be achieved only through a drastic increase in blood flow. Correction of hyperphosphataemia adds further to the abnormality. It is concluded that this condition could induce a long-term myocardial fatigue, which might be prevented with occasional small blood transfusions.
The Measurement of Calcium Absorption and Absorption Rate with an External Arm Radioactivity Counter
Authors: Smart R. C. , Holdsworth C. D.
Published: August 2015

1. A large-volume scintillation counter was used to measure calcium absorption from the ratio of forearm uptake of 47Ca after oral 47CaCl2 (administered with milk) to forearm uptake after intravenously administered 47CaCl2.

2. In some subjects serial measurements of both forearm uptake of 47Ca and blood 47Ca radioactivity were also recorded, and by using deconvolution both total calcium absorption and calcium absorption rate were determined.

3. The forearm ratio determination of 47Ca absorption correlated well with that obtained by deconvolution of either serial blood 47Ca or forearm 47Ca measurements provided that the forearm radioactivity measurements were made at least 8 h after the administrations of 47CaCl2.

4. Although the two deconvolution techniques gave similar estimates of total calcium absorption there were discrepancies between their measurements of calcium absorption rate. These discrepancies were reduced but not eliminated by the use of additional lead shielding around the Armac counter.
Bone Blood Flow and Age in the Rat
Authors: MacPherson J. N. , Tothill P.
Published: August 2015

1. The proportion of the cardiac output delivered to the skeleton and individual bones has been determined in rats of differing ages and weights with radioactive microspheres.

2. There was a decrease in the blood flow to the tibia—fibula, jaw, femur, pelvis, humerus, radius and ulna, and scapula with increase in age and weight of rats, but no change was seen in blood flow to the ribs, spine, skull or whole skeleton.

3. The proportion of the cardiac output delivered to the whole skeleton was approximately 3%.

4. The derived values for skeletal blood flow agree well with estimates by other authors using the technique of bone uptake and blood clearance of 45Ca.
Comparative Effects of Oestrogen and a Progestogen on Bone Loss in Postmenopausal Women
Authors: Lindsay R. , Hart D. M. , Purdie D. , Ferguson M. M. , Clark A. S. , Kraszewski A.
Published: August 2015

1. The value of progestogen therapy in the prevention of postmenopausal bone loss was assessed in 30 women, by a preliminary randomized controlled trial of gestronol or mestranol, in comparison with a placebo.

2. When the skeletal response was measured by photon absorptiometry, bone mineral loss was prevented by both the oestrogen and the progestogen.

3. We confirm that mestranol significantly reduced the urinary output of hydroxyproline-containing peptide, but this did not occur during gestronol therapy, suggesting that progestogen has a different action on bone, perhaps stimulating bone formation.
Lipolytic Activities in Post-Heparin Plasma in Man Measured with Different Substrate Emulsions
Authors: Vessby B. , Boberg J. , Lithell H.
Published: August 2015

1. Post-heparin lipolytic activity in man has been studied by using a triglyceride substrate emulsion containing different emulsifiers.

2. The lipolytic activity measured was profoundly influenced by the type of emulsifier used in the substrate. Substrates stabilized by synthetic emulsifiers give higher lipolytic activity than Intralipid, which contains egg phospholipids as emulsifiers. This difference was solely explained by higher salt-resistant lipase activities found with emulsions containing synthetic emulsifiers. The salt-inhibited lipase activity, which has properties as a lipoprotein lipase, was not influenced by the type of emulsifier.

3. When used under specified conditions Intralipid seems to be virtually specific for extrahepatic post-heparin lipolytic activity.
Renin, Blood Volume and Response to Saralasin in Patients on Chronic Haemodialysis: Evidence against Volume- and Renin-‘Dependent’ Hypertension
Authors: McGrath B. P. , Ledingham J. G. G.
Published: August 2015

1. No significant relationship was found between blood pressure and blood volume, sulphate space or plasma angiotensin II concentration in 59 non-nephrectomized haemodialysis patients, of whom 42 were hypertensive. Supine mean blood pressure was only weakly correlated with plasma renin activity and the correlation was not improved when blood pressure was related to expressions combining renin and volume.

2. Changes in supine mean blood pressure during saralasin infusion were related to pre-infusion plasma renin activity (P < 0·001) or plasma angiotensin II (P < 0·02) but also to blood volume (P < 0·001) or sulphate space (P < 0·001). A fall of more than 10% in mean blood pressure during saralasin infusion was observed in only 12 patients (one normotensive), in five of whom there was evidence of volume depletion.

3. Thirteen patients (nine hypertensive) were studied at two levels of dietary sodium: 100 mmol/day and < 20 mmol/day. Supine mean blood pressure in hypertensive patients was lower during the period of higher salt intake despite increased volumes.

4. Hypertension in haemodialysis patients cannot be adequately explained by abnormalities either in volume homeostasis and/or in the renin—angiotensin system.
The Causation of Splenomegaly in Schistosomiasis in Mice
Authors: Mahmoud Adel A. F. , Woodruff A. W.
Published: August 2015

1. Mice were infected with fertile bisexual Schistosoma mansoni and compared with similar animals infected with unisexual worms or sterile bisexual worms.

2. A significant increase in splenic weight occurred in all infected animals.

3. Administration of well-tolerated doses of 6-mercaptopurine abolished the increase in relative splenic weight in animals infected with ordinary S. mansoni.

4. In splenectomized uninfected mice leucocytosis but no other haematological changes developed.

5. In splenectomized mice lower values for packed cell volume were observed 8 weeks after, but not 12 weeks after, infection with S. mansoni.

6. Slight prolongation of the life-span of erythrocytes occurred in splenectomized infected mice.

7. It is concluded that anaemia in schistosomiasis depends to a significant extent on immunity developed to adult schistosomal worms and can develop in the absence of schistosomal ova.

8. The anaemia resulting from such an immune response may be suppressed by administration of 6-mercaptopurine.

9. Such anaemia occurs even in splenectomized mice; thus hypersplenism is not necessary for its development although splenectomy slightly prolongs the erythrocyte life-span.
Circadian Rhythmicity of Delayed Hypersensitivity to Oxazolone in the Rat
Authors: Pownall R. , Knapp M. S.
Published: August 2015

1. A marked circadian rhythm was detected in the ear swelling of rats immunized and then challenged with oxazolone.

2. The peak response observed at 10.00 hours was over eight times the minimum at 16.00 hours.

3. As related tests are used frequently in man greater attention to clock time is necessary in clinical immunology.
Effects of Diuretics on Renal Glucose Transport in the Dog
Authors: Wen S.-F. , Boynar J. W. , Stoll R. W.
Published: August 2015

1. In order to study the relationship between sodium and glucose transport along the nephron, clearance and micropuncture experiments were performed in 16 dogs before and after administration of diuretics with different sites of action.

2. Administration of acetazolamide, 20 mg (90 μmol)/kg, in nine dogs significantly reduced proximal tubular reabsorption of sodium and glucose and slightly increased ‘distal’ delivery of glucose. Since no glycosuria developed despite significant natriuresis, the increased ‘distal’ load of glucose must have been reabsorbed.

3. The possible site of this ‘distal’ glucose reabsorption was further studied in seven dogs which had received extracellular volume expansion to 10% of body weight and acetazolamide, 10 mg (45 μmol)/kg, to suppress proximal tubule reabsorption. When frusemide, 10 mg (30 μmol)/kg, was added, fractional glucose excretion increased from 0·3 to 2% in the absence of additional proximal tubular effect. However, the frusemide effect on ‘distal’ glucose transport was far smaller than that on sodium since fractional sodium excretion reached 40%.

4. Our results indicate a good correlation between sodium and glucose transport in the proximal tubule since both are inhibited by acetazolamide. Administration of large doses of frusemide leads to a modest glycosuria, probably by inhibition of glucose reabsorption in the loop of Henle. However, frusemide effect on the proximal tubule of deep nephrons cannot be completely excluded. The large discrepancy in the magnitude of natriuresis and glycosuria suggests dissociation of ‘distal’ sodium and glucose transport. Alternative explanations for the frusemide-induced glycosuria are also discussed.
Biochemical and Clinical Effects of Ethane-1-Hydroxy-1,1-Diphosphonate in Calcium Nephrolithiasis
Authors: Baumann J. M. , Bisza S. , Fleisch H. , Wacker M.
Published: August 2015

1. The short- and longer-term effects of ethane-1-hydroxy-1,1-diphosphonate (EHDP), an inhibitor of crystal growth and potential preventive agent against urinary tract stones in man, have been studied.

2. Measurement of urinary excretion of EHDP was used to define the best dosage regimen. When 4·4 mmol of EHDP was given daily in four divided doses the urinary concentration of EHDP achieved was high enough (10−5 mol/l) to inhibit the crystallization of calcium crystals throughout the day.

3. Nine patients with recurrent calcium stones were given this dose of EHDP daily for 12 months and seven were then studied for a further 12 months under placebo. During treatment with EHDP, inhibitory activity in urine towards precipitation of calcium phosphate was restored from low values to greatly above normal. This could be accounted for by the inhibitory effect of EHDP itself, coupled with an increase in urinary inorganic pyrophosphate. After stopping EHDP the excretion of EHDP rapidly fell to undetectable levels but the excretion of pyrophosphate remained elevated throughout the 12 months of placebo treatment. EHDP also induced a rise in plasma phosphate and an increase in the urinary excretion of oxalic acid and uric acid, but these changes were all fully reversible when EHDP was stopped.

4. The average rate of stone formation per patient per year decreased from 2·4 to 0·2 during treatment with EHDP and remained low during the following 24 months. However, the dose needed for this effect is known to affect bone turnover and mineralization.
Effect of Zinc on Leucocyte Sodium Transport In Vitro
Authors: Patrick J. , Michael J. , Golden M. N. , Golden B. E. , Hilton P. J.
Published: August 2015

1. In a preparation of human leucocytes maintained in tissue culture fluid, increasing the extracellular zinc concentration leads to a significant increase in both ouabain-sensitive sodium efflux and in sodium influx.

2. Cell water and sodium content do not alter significantly with increasing extracellular zinc concentration.

3. A small increase in the ouabain-insensitive sodium efflux can be demonstrated when the external zinc concentration is raised from 0·75 μmol/l to 90 μmol/l.
Natriuretic Effect of Propranolol on Dogs with Chronic Bile-Duct Ligation
Authors: Winaver J. , Chaimovitz C. , Better O. S.
Published: August 2015

1. Chronic ligation of the bile duct in dogs is associated with salt retention and a blunted natriuretic response to extracellular volume expansion. The mechanism of this phenomenon has not been clarified.

2. We have examined the influence of chronic β-adrenergic blockade on sodium excretion in dogs with bile-duct ligation during extracellular hypotonic volume expansion.

3. Urinary excretion of sodium and fractional excretion of sodium rose significantly after 5 days of oral dl-propranolol administration to dogs with bile-duct ligation.

4. The antinatriuresis after bile-duct ligation was not followed by a significant alteration in the mean peripheral plasma renin activity as compared with control values.

5. It is suggested that propranolol can partially reverse the antinatriuresis of chronic bile-duct ligation, and that this is mediated by an extrarenal effect of the β-adrenergic blockade.
Central and Peripheral Fatigue in Sustained Maximum Voluntary Contractions of Human Quadriceps Muscle
Authors: Bigland-Ritchie B. , Jones D. A. , Hosking G. P. , Edwards R. H. T.
Published: August 2015

1. The fatigue of force that occurs during the first 60 s of a maximum voluntary contraction of the human quadriceps has been examined by comparing the voluntary force with that obtained by brief tetanic stimulation at 50 Hz in nine healthy subjects. In three subjects the voluntary force declined in parallel with the tetanic force whereas in the remainder it fell more rapidly, suggesting that central fatigue was present.

2. For those subjects who showed little or no central fatigue, surface electromyograph (EMG) activity remained approximately constant while the force declined by about 60%. In the others, EMG activity and force declined in parallel but when an extra effort was made the subjects could briefly increase their force and this was accompanied by a proportionately greater increase in EMG activity (generally up to the original value).

3. It is concluded that in sustained maximum voluntary contractions of the quadriceps (a) central fatigue may account for an appreciable proportion of the force loss, (b) surface EMG recordings provide no evidence that neuromuscular junction failure is the limiting factor determining the loss of force in this muscle.
Blood Alcohol and Impairment of Judgment
Authors: Pohl J.E.F.
Published: August 2015

1. The cerebral depressant effect of 30 ml of aqueous ethanol diluted to 25% and administered orally to 16 volunteer subjects was compared with a control group of 15 volunteer subjects.

2. The two parallel forms of the Watson-Glaser Critical Thinking Appraisal tests were employed as a measure of cerebral function.

3. The control group showed a small but statistically insignificant improvement on retesting with Watson-Glaser test form ZM after preliminary administration of form YM.

4. The relationship between the blood alcohol time curve and the alcohol effect was analysed for each individual subject, each subject being used as his own control.

5. The main peak cerebral depressant effect was substantial and occurred on average 25.5 min before the attainment of the peak blood alcohol concentration.

6. There was no significant correlation between blood alcohol concentration and contemporaneous cerebral impairment (r = −0.01).

7. There was a highly significant correlation (r = 0.60) between the effect upon cerebral function and the gradient of the blood alcohol curve at that time.
Definition of a Conjugation Dysfunction in Gilbert's Syndrome: Studies of the Handling of Bilirubin Loads and of the Pattern of Bilirubin Conjugates Secreted in Bile
Authors: Goresky C. A. , Gordon Ellen R. , Shaffer E. A. , Paré P. , Carassavas D. , Aronoff A.
Published: August 2015

1. Intravenous doses of bilirubin (3.4 μmol/kg) were given to normal subjects and patients with Gilbert's syndrome. Both groups displayed an identical initial disappearance of a substantial proportion of the bilirubin but, late in time, the Gilbert's patients exhibited reduced clearance with a sustained elevation of the plasma bilirubin and no reflux into the plasma space of conjugated bilirubin. Increasing the dose in normal subjects (by factors of 3 and 6) failed to reproduce the response found in the Gilbert's patients.

2. In the bile-containing duodenal aspirates of Gilbert's patients the average proportion of bilirubin found as bilirubin diglucuronide was 68% (normal 88%) and of bilirubin monoglucuronide, 23% (normal 7%). Both differences were significant at the P < 0.001 level. In the Gilbert's patients restriction of caloric intake to 1569 kJ/day for 2 days characteristically raised the serum bilirubin with no modification of the biliary pigment pattern; phenobarbital (180 mg/day for 2 weeks) decreased the plasma bilirubin to the normal range with, concomitantly, a reversion of the biliary pigment pattern towards normal.

3. We conclude that there is no hepatic uptake defect in Gilbert's syndrome but that there is decreased activity in the conjugation process underlying the addition of the second glucuronic acid moiety to bilirubin, to form bilirubin diglucuronide.
Exchange of Metabolites in the Leg of Exercising Juvenile Diabetic Subjects
Authors: Lyngsøe J. , Clausen J. P. , Trap-Jensen J. , Sestoft L. , de Muckadell O. Schaffalitzky , Holst J. J. , Nielsen S. L. , Rehfeld J. F.
Published: August 2015

1. Exchange of metabolic substrates was studied across the leg at rest and during a bicycle exercise demanding 50% of the maximal oxygen uptake in seven patients with juvenile diabetes and six control subjects. The leg blood flow and the femoral arterial and venous substrate concentrations were measured in the fasting state and, in the diabetic subjects, 24 h after the last administration of insulin.

2. At rest a close correlation was seen in the control subjects between the leg glucose uptake and the arterial insulin concentration. The diabetic subjects, including three patients in whom it could be shown that the insulin concentrations were extremely low, had a resting glucose uptake in the same order of magnitude as the control subjects. The glucose uptake was inversely related to the arterial concentrations of non-esterified fatty acids in both groups.

3. During exercise the glucose uptake increased in both patients and control subjects, but the increase was not related to arterial concentrations of insulin or non-esterified fatty acids.

4. The release of lactate, pyruvate, alanine and glycerol from the leg was not different in diabetic and control subjects neither at rest nor during exercise.

5. The ketonaemia was increased in the diabetic subjects, but the uptake of total ketone bodies was not different in the two groups. No increase in the uptake of total ketone bodies in control and diabetic subjects was found during exercise. The leg uptake of acetoacetate was a function of the substrate load and tended to be higher in diabetic subjects during exercise, when no net uptake of β-hydroxybutyrate was found.

6. The above results suggest that the glucose uptake in human skeletal muscle at rest depends on the concentration of insulin and possibly also of non-esterified fatty acids in arterial blood. In contrast the glucose uptake during exercise is not related to the concentration of insulin or non-esterified fatty acids, which may explain why no differences in this aspect are seen between the leg metabolism of diabetic and normal subjects.
Biphasic Changes in Thymus Structure during Evolving Renal Hypertension
Authors: Chatelain R. E. , Ferrario C. M.
Published: August 2015

1. Structural changes in the thymus during the evolution of experimental renal hypertension were investigated to determine their possible role in the genesis of hypertensive vascular disease.

2. The thymus, adrenal glands and the progression of hypertensive vascular lesions were investigated in rats during the first 30 days after occlusion of the aorta between the two renal arteries.

3. Hypertension was initially accompanied by marked atrophy of the thymus, most pronounced 9 days after operation. During this time, the adrenal glands doubled in size and the heart became enlarged.

4. After 21 days the thymus regenerated and became hypertrophic. Histological features of hyperactivity accompanied by infiltration of plasma cells were evident, while the adrenal glands remained enlarged.

5. The observed structural changes of the regenerated thymus in the presence of sustained adrenal hypertrophy indicate that the thymus may contribute to the production of hypertensive vascular disease.
Analytical Subcellular Fractionation Studies on Enterocytes from the Jejunum and Ileum of the Rat and Some Properties of Brush-Border Alkaline Phosphatase
Authors: Batt R. M. , Peters T. J.
Published: August 2015

1. Enterocytes, isolated from the proximal jejunum and distal ileum of the rat, were homogenized and their organelles separated by isopycnic centrifugation on continuous sucrose density gradients. The distributions of marker enzymes for the principal organelles, RNA and protein were determined in the sucrose gradients and related to the activities per enterocyte.

2. In the jejunum the modal equilibrium densities of the various organelles were: brush borders (1.20), lysosomes (1.20), peroxisomes (1.19), mitochondria (1.17) and basal-lateral membranes (1.13). These values were not significantly different in the ileum. The activities of brush-border enzymes, soluble and mitochondrial malate dehydrogenase, soluble and membrane-associated lactate dehydrogenase and particulate protein content, however, were greater in the jejunal than the ileal enterocytes.

3. Detergent exposed latent alkaline phosphatase activity in jejunal enterocytes and indicated that this enzyme is present not only in the brush border but also in the basal-lateral membrane and soluble fractions of the cell.

4. Isolated jejunal brush-border preparations showed latent activities of both alkaline phosphatase and γ-glutamyltransferase whereas the activities of α-glucosidase and leucyl-β-naphthylamidase were not affected by detergent. Mechanical disruption of these preparations suggested the presence of two forms of alkaline phosphatase in the brush border and provides a technique to assess membrane fragility.
Role of Persistent Vascular Renin after Bilateral Nephrectomy in Goldblatt-Two Kidney Hypertension
Authors: Thurston H. , Hurst B. C. , Bing R. F. , Swales J. D.
Published: August 2015

1. Aortic homogenate contains renin-like activity which on incubation generates angiotensin I over a wide pH range.

2. Rat aortic renin measured at an incubation pH of 6·5 rose and fell in parallel to plasma renin with salt depletion and salt-loading respectively. Renin measured at an incubation pH of 5·3 showed little relationship with plasma renin.

3. Aortic renin (pH 6·5) was elevated in Goldblatt-two kidney hypertension and slowly fell for 24 h after bilateral nephrectomy whereas the fall in plasma renin was complete by the first hour. Aortic renin (pH 5·3) was also high, but did not fall after bilateral nephrectomy.

4. Aortic renin (pH 6·5) is probably derived from plasma renin whereas renin measured at pH 5·3 is probably a tissue renin.

5. The prolonged half-life of aortic renin (pH 6·5) explains the observation that the renin—angiotensin system appears to be active in maintaining blood pressure for several hours after bilateral nephrectomy whereas the decline in plasma renin is rapid and does not continue significantly beyond 1 h.
Bile Secretion and Bile Composition in the Freely Moving, Unanaesthetized Rat with a Permanent Biliary Drainage: Influence of Food Intake on Bile Flow
Authors: Vonk R. J. , van Doorn A. B. D. , Strubbe J. H.
Published: August 2015

1. In freely moving, unanaesthetized rats bile flow was measured continuously over the whole day-night cycle. Bile composition was analysed and the influence of food intake on bile flow was investigated.

2. In both sexes a distinct circadian variation of bile production was observed. The mean night-time production was 50% higher than the day-time value for female rats and 38% for male rats. In the morning when the light was switched on, a sharp decrease in secretion rate was prominent and bile flow gradually increased in the afternoon.

3. The pattern of food intake was positively correlated with the pattern of bile secretion. During fasting only the general level of bile flow decreased, but the circadian variation persisted. Refeeding again increased the mean level of bile flow.

4. The chenodeoxycholate/cholate ratio in these rats with permanent bile fistulae was higher than in rats with ‘acute’ bile fistulae and changed during the day-night cycle. The ratio decreased from 1.01 at 05.00 hours to a minimum of 0.41 at 15.00 hours.

5. During the day-night cycle the sodium, potassium, calcium and cholesterol concentrations were relatively constant. The total bile salt concentration was only slightly changed, so that both the bile salt-dependent fraction and the bile salt-independent fraction were subject to about the same circadian variations.
The Relationship between Blood Pressure and Aortic Collagen Metabolism in Renal Hypertensive Rats
Authors: Foidart J. M. , Rorive G. L. , Nusgens B. V. , Lapiere C. M.
Published: August 2015

1. Biosynthesis and deposition of collagen, as well as DNA and total proteins, are increased in aortae of rats after 1, 3 and 6 weeks of hypertension.

2. The maximal increase in the rate of synthesis of collagen is observed within one week of hypertension when the stress to the arterial wall is maximal.

3. Reserpine administration prevents hypertension and inhibits the increase of collagen metabolism.

4. At any time of evolution of the hypertension, a linear positive correlation is found between the collagen content in the aorta and the level of blood pressure.

5. These data suggest that synthesis of matrix components by the arterial smooth-muscle cells is controlled by variation in the blood pressure level and is not a direct consequence of circulating humoral factors liberated by the ischaemic kidney.
Biliary Excretion of Dibromosulphthalein in the Freely Moving Unanaesthetized Rat: Circadian Variation and Effects of Deprivation of Food and Pentobarbital Anaesthesia
Authors: Vonk R. J. , Scholtens E. , Strubbe J. H.
Published: August 2015

1. In unanaesthetized, freely moving rats, which displayed a circadian rhythm in bile flow, hepatic transport of dibromosulphthalein was investigated at midnight when bile flow was high and at noon when bile flow was lower. The influence of pentobarbital anaesthesia and starvation on hepatic transport of dibromosulphthalein was also studied. The influence of bile salts on the hepatic transport process was investigated by interruption of the enterohepatic circulation.

2. Maximal biliary transport of dibromosulphthalein was subject to circadian variations: the biliary transport maximum at night was 25% higher than at noon, although maximal biliary concentration was not significantly altered. The distribution volume was increased by 21% during the night, but the primary hepatic clearance constant was not changed.

3. Pentobarbital anaesthesia decreased the maximal biliary concentration and the maximal biliary excretion rate of dibromosulphthalein, but the primary hepatic clearance constant was not changed.

4. Starvation for 48 h changed the primary hepatic clearance constant as well as the biliary excretion of dibromosulphthalein.

5. Interruption of the enterohepatic circulation of bile did not change the primary hepatic clearance constant of dibromosulphthalein, but decreased biliary excretion of the drug.

6. This study clearly indicates that time of the day, feeding conditions, the use of anaesthetics and interruption of the enterohepatic circulation of bile are important determinants in biliary excretion of cholephilic dyes.
Analytical Subcellular Fractionation Studies on Different Cell Types Isolated from Normal Rat Liver
Authors: Selden Clare , Wootton A. M. , Moss D. W. , Peters T. J.
Published: August 2015

1. Parenchymal, Kupffer and biliary tract cells were isolated from normal rat liver by perfusion with collagenase solution.

2. The specific activities (munits of enzyme activity/mg of protein) of marker enzymes for the principal subcellular organelles were determined in the isolated cell homogenates and compared with whole liver homogenates.

3. The cells were disrupted and the extracts subjected to analytical subcellular fractionation by sucrose-density-gradient centrifugation. Lysosomal integrity was determined by assaying latent β-N-acetylglucosaminidase in the extracts.

4. Similar subcellular distributions were found for lysosomal, endoplasmic reticulum and plasma membrane marker enzymes in the whole liver and in parenchymal and biliary tract cells. In Kupffer cells, the proportion of these enzymes in the cytosol was significantly increased compared with the other fractions. In addition the equilibrium densities of the various organelles in these cells were lower than those from parenchymal cells.
Comparison of Cardiac Output Determined by a Carbon Dioxide-Rebreathing and Direct Fick Method at Rest and during Exercise
Authors: Reybrouck T. , Amery A. , Billiet L. , Fagard R. , Stijns H.
Published: August 2015

1. To study the validity of a CO2-rebreathing method at rest and during graded exercise, cardiac output was measured simultaneously on 59 occasions in 16 subjects with normal pulmonary function with the CO2-rebreathing method and the direct Fick method for oxygen. The correlation coefficient between the results of both methods was significantly higher during exercise than at rest.

2. No systematic difference was shown between (a-v̄)CO2 content difference determined on whole blood and end-tidal gas, which justified the exclusion of a correction factor for blood to alveolar gas Pco2 gradients.

3. In the calculation of cardiac output by the direct Fick method for CO2 and by CO2 rebreathing, a standard CO2 dissociation curve was preferred to a synthetic CO2 dissociation curve, constructed by allowance for changes in haemoglobin concentration, pH and oxygen saturation. The latter curve tended to increase values for cardiac output and induced a large dispersion around the line of identity, when compared with simultaneous cardiac output estimates by the direct Fick method for oxygen.
The Nature of Hepatic Cytochrome P-450 Induced in Hexachlorobenzene-Fed Rats
Authors: Blekkenhorst G. H. , Eales L. , Pimstone N. R.
Published: August 2015

1. The effect of feeding with a diet containing 0.2% (w/w) hexachlorobenzene on hepatic and urinary porphyrins and hepatic cytochrome P-450 was studied at various time intervals in female Wistar rats.

2. Hexachlorobenzene administration for 45 days resulted in the development of porphyria in rats, which biochemically closely resembles symptomatic porphyria in humans, with elevation of urinary uroporphyrin excretion, hepatic uroporphyrin content, and hepatic cytochrome P-450 content, in addition to appearance of porphyrins of the isocoproporphyrin (P1) series in the faeces.

3. Spectral studies of the induced hepatic cytochrome P-450 at 45 days with carbon monoxide and ethyl isocyanide as ligands indicated the presence of a greater admixture of a haemoprotein distinct from cytochrome P-450.

4. Study in vitro of the kinetics of two reactions, namely aminopyrine N-demethylation and 3,4-benzpyrene hydroxylation, catalysed by the hepatic microsomal cytochrome P-450-dependent enzyme system, suggested that hexachlorobenzene induced a form of cytochrome P-450 with different catalytic properties from those of forms induced by either phenobarbital or 3-methylcholanthrene.
The Physical Properties of Human Pulmonary Arteries and Veins
Authors: Banks J. , Booth F. V. McL. , MacKay E. H. , Rajagopalan B. , De J. Lee G.
Published: August 2015

1. We have studied the extensibility of circumferential strips of main pulmonary artery and large pulmonary veins obtained at post mortem from patients of all ages, dying from conditions other than heart and lung disease.

2. The vessel strips were submitted to increasing loads in a tension balance. The pulmonary arteries were found to be readily extensible. This extensibility became less with increasing age. The pulmonary veins were virtually inextensible at all ages.

3. It is postulated that the large extraparenchymal pulmonary veins have a capacitative role in supplying blood from the lungs to the left atrium. This may be accomplished by their collapsible nature, as they have little capability of distension.
The Retention of Lung Secretions during the Night in Normal Subjects
Authors: Bateman J. R. M. , Pavia D. , Clarke S. W.
Published: August 2015

1. Mucociliary clearance has been measured over a 6 h period by using the radioaerosol technique in seven normal male subjects lying supine, both during the day when awake, and during the night when asleep.

2. The percentage of radioaerosol cleared during the night, when asleep, was significantly less than during the day when awake (P < 0.02).

3. A comparison of radioaerosol clearance before and after the time of onset of sleep demonstrates that reduced clearance occurred during sleep, indicating that this is probably a sleep-related phenomenon and not merely a result of diurnal variation.

4. This finding has important implications for patients with chronic bronchitis or asthma, in whom early morning cough or wheeze may be a predominant feature.
The Role of Prostaglandins in the Pathogenesis of Hypertension
Authors: Markov C. M.
Published: August 2015

1. Biosynthesis of PGE2 from [14C]arachidonic acid has been found to be lower and PGF2α higher in the renal medulla of spontaneously hypertensive (SH) rats than in normal Wistar (NW) rats.

2. Biosynthesis of prostacyclin (PGF1α) from [14C]arachidonic acid was decreased in lungs, aorta and heart of SH rats.

3. Metabolism of [3H]PGF1α was decreased in renal cortex and lungs and PGE2 increased in SH rats in comparison with NW rats. Thus the lungs of SH rats let more PGF and less PGE enter the systemic circulation.

4. Emotional stress decreased the metabolism of [3H]PGF1α in lungs of SH and NW rats, the effect being less in SH rats.
The Natural History of Hypertension in Turkeys
Authors: Pagnan A. , Pessina A. C. , Thiene G. , Dal Palù C.
Published: August 2015

1. Variables involved in the genesis of hypertension in male broad-breasted white turkeys include social environment, obesity and high salt intake.

2. The hypertension is characterized by low plasma renin activity and, with increasing age, normal to high plasma aldosterone.

3. Medionecrosis of the abdominal aorta is a common pathological finding.

4. The absence of atherosclerotic plaques is probably related to the high concentrations of alpha-lipoproteins.
Results of a National Therapeutic Trial Conducted in 10 000 Hypertensive Patients by 2000 General Practitioners
Authors: Jouve A. , Goldet L. , Mathieu M.
Published: August 2015

1. 10 294 hypertensive patients were treated and followed by 2200 general practitioners under the supervision of 130 cardiologists and nephrologists.

2. The treatment groups, randomly allocated, were designated to use three distinct antihypertensive drugs, administered alone, and combined two-by-two.

3. Some 75% of patients had a supine diastolic blood pressure of less than 95 mmHg after 4 months treatment.

4. A total of 12% of patients had dropped out by 4 months from entry; no clear relationship was established between side effects and drop out.
The Role of Intrarenal Vasoactive Substances in the Pathogenesis of Essential Hypertension
Authors: Abe K. , Yasujima M. , Irokawa N. , Seino M. , Chiba S. , Sakurai Y. , Sato M. , Imai Y. , Saito K. , Ito T. , Haruyama T. , Otsuka Y. , Yoshinaga K.
Published: August 2015

To investigate the role of renal vasoactive substances in the pathogenesis of essential hypertension, urinary prostaglandin E excretion, urinary kallikrein excretion, plasma renin activity, plasma aldosterone concentration and urinary Na excretion were measured in normal subjects and patients with essential hypertension after stimulation of the renin—angiotensin—aldosterone system by the intravenous injection of frusemide or a low Na diet; after the inhibition of renin—angiotensin—aldosterone by an angiotensin II antagonist and after the inhibition of renal prostaglandin E synthesis by indomethacin. The urinary excretions of prostaglandin E and kallikrein, plasma renin activity and plasma aldosterone concentration increased after frusemide administration. The urinary excretion of kallikrein increased after frusemide or a low Na diet but decreased after the angiotensin II antagonist and indomethacin during Na depletion. Changes in urinary kallikrein excretion paralleled those in the renin—angiotensin—aldosterone system after various stimuli. The urinary excretion of prostaglandin E increased after frusemide. However, a dissociation between the urinary excretions of prostaglandin E and kallikrein was found during the low Na diet: the former decreased and the latter increased. The urinary excretion of prostaglandin E was closely related to urinary Na output after various stimuli. Basal levels of urinary prostaglandin E and kallikrein excretion were lower in essential hypertension than in normal subjects. The release of renal prostaglandin E and kallikrein after frusemide was also suppressed in essential hypertension compared with that in normal subjects. The data indicate that renal kallikrein—kinin and renin—angiotensin—aldosterone may interact in a dynamic fashion to maintain blood pressure, that renal prostaglandin E may be involved in renal Na handling and that the suppression of renal kallikrein—kinin and prostaglandin E in essential hypertension may be an etiological factor in essential hypertension.
Muscle–Nerve Sympathetic Activity in Man. Relationship to Blood Pressure in Resting Normo- and Hyper-Tensive Subjects
Authors: Sundlöf G. , Wallin B. G.
Published: August 2015

1. Simultaneous recordings of multi-unit muscle nerve sympathetic activity and arterial blood pressure were made in 29 subjects, 17 healthy and 12 hypertensive. The neural activity, quantified by counting the number of pulse-synchronous sympathetic bursts in the mean voltage neurogram (burst incidence), was plotted against blood pressure. The effect of spontaneous temporary blood pressure fluctuations was studied by correlating different pressure parameters of individual heart beats to the occurrence of a sympathetic burst.

2. Between subjects there were marked differences in burst incidence but no correlation was found to interindividual differences in blood pressure level.

3. When for each heart beat the occurrence of a burst was correlated to different pressure parameters there was a close negative correlation to diastolic, a low correlation to systolic, and an intermediate negative correlation to mean blood pressure.

4. In a given subject, when comparing heart beats with the same diastolic pressure, the occurrence and the amplitudes of the sympathetic bursts were higher during falling than during rising pressure. This directional dependence of the muscle—nerve sympathetic activity was slightly more pronounced in the hypertensive group, but this was considered secondary to the hypertension.

5. The findings of an intimate correlation with dynamic variations in blood pressure and the absence of correlation to the static blood pressure suggest that the sympathetic outflow to skeletal muscle is of importance for buffering acute blood pressure changes but has little influence on the long-term blood pressure.
Metabolism of p-aminobenzoic Acid in the Perfused Livers of Chronically Uraemic Rats
Authors: Howie M. B. , Bourke E.
Published: August 2015

1. Chronic renal failure was induced in rats by surgical removal of thirteen-sixteenths of renal tissue.

2. The metabolism of p-amino[14C]benzoic acid was studied in the isolated perfused livers of control and chronically uraemic rats. There was a slower rate of clearance and decreased overall metabolism of the compounds in the uraemic rats.

3. Conjugation of p-amino[14C]benzoic acid with glycine and the formation of p-aminobenzoic acid glucuronide were both significantly decreased in the uraemic rats, but there was a significant increase in acetylation of both p-aminobenzoic acid and its glycine conjugate.