bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Glucocorticoid Deficiency on Renal Medullary Cyclic Adenosine Monophosphate of Rats
Authors: Kurokawa K. , Aznar E. , Descoeudres C. , Zulueta Anicia , Massry S. G.
Published: August 2015

1. The effects of adrenalectomy on the adenylate cyclase—adenosine 3′:5′-cyclic monophosphate (cyclic AMP) system of rat renal medulla were examined to evaluate the mechanism of the impaired water diuresis in glucocorticoid deficiency.

2. Concentrations of cyclic AMP in medullary tubules from adrenalectomized rats were significantly higher than in the tubules from control animals both in the presence and absence of antidiuretic hormone.

3. This abnormality was corrected by the treatment in vivo of the adrenalectomized rats with dexamethasone, but addition of this drug to the incubation medium did not abolish the differences in cyclic AMP between tubules from adrenalectomized and normal rats.

4. The activity of adenylate cyclase or cyclic AMP phosphodiesterase in vitro was not affected by adrenalectomy.

5. In glucocorticoid deficiency, the concentration of cyclic AMP in medullary tubules is increased both with and without antidiuretic hormone. This abnormality may render medullary tubules more permeable to water and may underlie the impaired water diuresis in glucocorticoid deficiency.
Factors Related to Potassium Transport in Chronic Stable Renal Disease in Man
Authors: Kahn T. , Kaji D. M. , Nicolis G. , Krakoff L. R. , Stein R. M.
Published: August 2015

1. The inter-relationships between plasma aldosterone, plasma renin activity, potassium excretion and plasma potassium were evaluated in subjects with normal and decreased glomerular filtration rate.

2. In seven studies of healthy control subjects and 12 studies of patients with renal disease, daily urine collections, plasma aldosterone and plasma renin activity were measured on a free diet for 5–10 days and subsequently during the addition of 50 mmol of potassium chloride daily for 5 days. Plasma aldosterone was also measured in 22 hospital patients with normal glomerular filtration rate and 24 patients with reduced glomerular filtration rate.

3. Plasma aldosterone was similar in base-line conditions in patients with or without renal disease and increased similarly during the administration of potassium chloride, suggesting that potassium excretion in patients with reduced glomerular filtration rate probably does not depend primarily upon increased aldosterone.

4. Plasma renin activity increased similarly in control subjects and patients with renal disease during the administration of 50 mmol of potassium chloride/day, but plasma renin activity did not increase when 100 mmol of potassium chloride/day was given to control subjects.

5. With the administration of 50 mmol of potassium chloride/day mean daily potassium excretion increased similarly in control subjects and patients with renal disease but plasma potassium increased significantly (4·7 to 5·4 mmol/l) only in patients with renal disease, suggesting that their uptake of potassium into cells was impaired.
Renin Release from Renin Granules in the Dog
Authors: Funakawa S. , Higashio T. , Yamamoto K.
Published: August 2015

1. Renin release from isolated dog renin granules was limited to within 20% of the total renin during incubation at 37°C in isotonic medium and did not depend on the external concentration of renin.

2. Although the renin granules were osmotically and mechanically fragile, they were quite stable at 0°C in isotonic medium.

3. The bulk of renin activity appeared in the supernatant when the granules were ruptured by osmotic lysis. About 8% of the total renin still remained in the membrane fraction of the granules after treatment by freezing and thawing.

4. Therefore stored renin in the granules can be described as comprising three components: a readily released soluble form; a soluble but hard-to-release form; a membrane-bound form.
Gastric Ulcers with and without Associated Duodenal Ulcer Have Different Pathophysiology
Authors: Lam S. K. , Lai C. L.
Published: August 2015

1. Maximal acid output after pentagastrin stimulation, and fasting and postprandial serum gastrin concentrations were determined in 25 normal subjects, 30 patients with corpus gastric ulcers, 10 patients with prepyloric ulcers and 30 patients with both duodenal and gastric ulcers.

2. Corpus ulcers and prepyloric ulcers formed one distinct group. Maximal acid output was abnormally low in the corpus ulcer patients and no different from normal in prepyloric ulcer patients, whereas fasting serum gastrin and postprandial integrated gastrin response was abnormally high in the former and no different from the normal in the latter. Furthermore, as in the normal subjects, a significant negative correlation between maximal acid output expressed in mmol h−1 kg−1 body weight and postprandial integrated gastrin response was observed in the corpus and prepyloric ulcer patients taken as a group.

3. In complete contrast patients with both duodenal and gastric ulcers, in whom postprandial integrated gastrin response was statistically highest amongst the three types of gastric ulcers, had a significantly positive correlation between maximal acid output and the integrated gastrin response.

4. These findings suggest the operation of different pathophysiological mechanisms in gastric ulcers with and without associated duodenal ulcers.
Galactose and Hepatic Metabolism in Malnutrition and Sepsis in Man
Authors: Royle G. , Kettlewell M. G. W. , Ilic Vera , Williamson D. H.
Published: August 2015

1. Hepatic carbohydrate metabolism was studied by an intravenous galactose test in control patients, malnourished non-septic patients, patients with prolonged severe sepsis and patients after recovery from sepsis.

2. Blood galactose half-life was not significantly increased in the septic group despite abnormal liver-function tests, whereas it was approximately doubled in the malnourished patients.

3. The rise in blood glucose after galactose injection was less in both the septic and malnourished groups, as compared with that in the control subjects.

4. Fasting blood glucose, lactate and pyruvate concentrations were similar in all groups, whereas blood ketone bodies were increased in the malnourished and septic groups, and blood alanine was decreased only in the septic group.

5. The changes in hepatic metabolism and function were reversible on recovery from sepsis.

6. It is suggested that alterations in hepatic blood flow and the metabolic fate of galactose within the liver may explain the changes in the metabolic response to galactose observed in malnourished or septic patients.
Excretion of Urea by the Foetal Guinea Pig
Authors: Horn Jane
Published: August 2015

1. The placental transfer of urea was studied by perfusing the guinea-pig foetal placenta in situ with dextran solutions containing various amounts of urea, and radioactively labelled urea.

2. Transfer of urea was linearly related to the difference in concentration between the maternal and the foetal sides of the placenta, but transfer in both directions across the placenta was equal when the concentration of urea in the perfusing fluid was 2.5–3.5 mmol/l less than the maternal arterial value. This suggested that urea may be transferred against a concentration gradient.

3. Foetal plasma urea concentrations were found to be 0.5 mmol/l less than the maternal, suggesting that active transfer from the foetal circulation to the maternal can occur. However, because of the close relationship between foetal and maternal plasma urea (r = 0.96), it is concluded that the major control of foetal urea concentrations is by diffusion of urea between maternal and foetal extracellular fluids.
Effect of a Surgically Created Side-to-Side Arteriovenous Fistula on Heat Elimination from the Human Hand and Forearm: Evidence for a Critical Role of Venous Resistance in Determining Fistular Flow
Authors: Wallace W. F. M. , Jamison J. P.
Published: August 2015

1. In eight patients with a unilateral fistula between the radial artery and a nearby superficial vein, heat elimination from both hand and forearm, as measured by calorimetry, was always substantially greater on the side of the fistula (mean excess from hand-plus-forearm 889 J/min).

2. Fistular blood flow measured by hand-plus-forearm plethysmography in these patients averaged 431 ml/min. Correlation between fistular blood flow and heat elimination was poor (r = 0.70, P < 0.06), probably because heat elimination due to the fistula takes place mainly from veins, whose pattern varies from patient to patient.

3. Approximately half of the total increased heat elimination due to the fistula is from the hand. Occlusion of the circulation to the hand caused fistular flow rate to be reduced by about half. This suggests that the main resistance to fistular flow is venous, proximal veins offering a similar resistance to distal veins.

4. The obligatory heat loss due to the fistula is unlikely to embarrass temperature regulation, except in severe cold stress.
Assessment of Early and Delayed Responses in Vitamin B12 Absorption during Antibiotic Therapy in Tropical Malabsorption
Authors: Tomkins A. M. , Smith T. , Wright S. G.
Published: August 2015

1. Vitamin B12 absorption was measured in 18 patients with tropical malabsorption.

2. Absorption was particularly impaired in patients with severe mucosal lesions.

3. Sequential measurements with 57Co- and 58Co-labelled vitamin B12 were made before and 48 h after the start of tetracycline therapy. A rapid improvement (on average 22% increase in absorption) occurred in four of six patients with marked mucosal lesions. Further improvement occurred in four of five patients measured after 4 weeks' tetracycline, including the two who failed to improve initially.

4. These rapid changes in vitamin B12 absorption after antibiotics occur too early to be due to mucosal recovery and suggest that bacterial metabolism is an important factor in the malabsorption in these patients.
The Absence of 24,25-Dihydroxycholecalciferol in Anephric Patients
Authors: Taylor Carol M. , Mawer E. Barbara , Wallace Jayne E. , St John Judy , Cochran M. , Russell R. G. G. , Kanis J. A.
Published: August 2015

1. In subjects with normal renal function there was a strong positive correlation between serum concentrations of 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol, as measured by competitive protein-binding assay.

2. The 24,25-dihydroxycholecalciferol concentration was about 7% of the prevailing 25-hydroxycholecalciferol concentration.

3. In contrast, sera from anephric patients contained very low or undetectable amounts of 24,25-dihydroxycholecalciferol even after the serum 25-hydroxycholecalciferol concentrations in these patients had been elevated by oral administration of 25-hydroxycholecalciferol.

4. In a further group of anephric patients, all having normal serum 25-hydroxycholecalciferol concentrations, no radioactively labelled 24,25-dihydroxycholecalciferol was formed from an injected pulse dose of [3H,14C]cholecalciferol.

5. These results indicate that in man the kidney is the major site of 24-hydroxylation of 25-hydroxycholecalciferol.
Relationship of Basal Plasma Noradrenaline to Blood Pressure, Age, Sex, Plasma Renin Activity and Plasma Volume in Essential Hypertension
Authors: Chobanian A. V. , Gavras H. , Melby J. C. , Gavras Irene , Jick H.
Published: August 2015

1. The relationship of basal plasma noradrenaline to blood pressure, age, sex, urinary sodium excretion, and plasma volume has been examined in 117 untreated ambulatory patients with essential hypertension.

2. No significant correlations between basal plasma noradrenaline and either age or sex were apparent in the total group of essential hypertensive patients. In addition, no significant correlations were observed between plasma noradrenaline and 24 h urinary sodium excretion.

3. Basal plasma noradrenaline concentration was significantly higher in high renin essential hypertensive subjects compared with those with normal or low plasma renin activity.

4. Plasma noradrenaline was reduced significantly in relatively young patients with low renin essential hypertension, but appeared to be normal in other low renin subjects.

5. Basal plasma noradrenaline correlated significantly with blood pressure in patients with normal or low renin essential hypertension but the relationships were only significant in male patients.

6. No significant relationship between basal plasma noradrenaline and either blood pressure or plasma volume could be demonstrated in this population of essential hypertensive patients.
Hypertension and Brain Catecholamine Distribution in the Hebrew University Sabra, H and N Rats
Authors: Zamir N. , Gutman Y. , Ben-Ishay D.
Published: August 2015

1. The concentration of catecholamines was measured in several brain areas of the Hebrew University Sabra rat (SB rat), and in two substrains selected for their respective sensitivity (H) or immunity (N) to hypertension.

2. Hypertension was induced in SB rats by DOCA—salt, renal artery constriction and NaCl 1·7% drinking. The noradrenaline content was consistently elevated in the medulla oblongata of hypertensive animals. In other brain areas the rise in noradrenaline varied in the different types of hypertension.

3. Administration of DOCA—salt to H and N rats, while causing marked hypertension in the former, had no effect on noradrenaline in either strain.

4. Untreated, normotensive N rats had in the medulla oblongata, significantly higher concentrations of noradrenaline than did H rats.

5. Differences in brain noradrenaline may explain the inherited susceptibility or resistance to hypertension in H and N rats.
Purification of Human Renal Renin
Authors: Slater Eve E. , Cohn Robert C. , Dzau Victor J. , Haber Edgar
Published: August 2015

1. Human renal renin has been purified 200 000-fold from cadaver kidney cortex by a method which employs affinity chromatography on aminohexyl pepstatin.

2. The product of this purification has a specific activity of 400 Goldblatt units/mg when compared with Haas human renin standard.

3. This product appears as a single band on sodium dodecyl sulphate gel and polyacrylamide-disc gel electrophoresis. Renin enzymatic activity was recovered after elution from a polyacrylamide-disc gel run at pH 7·8.

4. Yield with this method was 1%.
Definitive Evidence for Renin in Rat Brain by Affinity Chromatographic Separation from Protease
Authors: Inagami Tadashi , Yokosawa Hideyoshi , Hirose Shigehisa
Published: August 2015

1. Angiotensin I-generating activity of rat brain extract was separated into two components by affinity chromatography on a casein—Sepharose gel column.

2. The component without affinity to the gel was identified as true renin on the basis of its sensitivity to anti-renin antibody and the lack of protease activity.

3. The second renin-like component with affinity to the gel was a protease insensitive to the anti-renin antibody. Its renin-like activity examined with sheep substrate was pronounced compared with the rate of angiotensin I generation from the rat substrate.

4. It was concluded that rat brain contains true renin, which can be detected by the use of rat substrate but can be masked when examined with sheep substrate.
Is High-Molecular-Weight-Renin Binding of Renin to the Protease Inhibitors and Lipoproteins?
Authors: Poulsen K. , Nielsen A. H. , Lykkegaard S. , Malling C. , Krøll J. , Jensenius J.
Published: August 2015

1. Two high-molecular-weight forms of renin (molecular weights 800 000 and 70 000) are present in mouse plasma.

2. The 800 000 form could be activated and converted into the fully active 40 000 form, by acid or limited proteolysis. The 70 000 form was activated without change in molecular weight.

3. In addition to its enzymic activity, renin was measured by a direct radioimmunoassay, which revealed that the current acid treatment of plasma did not activate all the renin present.

4. Renin is stored as fully active 40 000 renin, with a specific enzymic reactivity of 0·4 × 10−3 GU ng−1, in the submaxillary gland of mice.

5. Pure 125I-labelled 40 000 submaxillary renin did not bind to plasma proteins. However, by changing the tertiary structure of renin, it was bound to some of the plasma protease inhibitors; α2-macroglobulin, inter-α-trypsin inhibitor and α2-antithrombin. It was also bound to α1- and β1-lipoprotein, albumin and an unidentified plasma protein. No binding was seen to more than 50 other studied plasma proteins.
An Endogenous Protease Activating Plasma Inactive Renin
Authors: Leckie B. J.
Published: August 2015

1. The protease inhibitors Trasylol and soya-bean trypsin inhibitor prevented the activation of plasma inactive renin by acid.

2. N-Ethylmaleimide inhibited acid-activation to some extent but o-phenanthroline had no effect.

3. Acid-activation of the inactive renin in human plasma is mediated by a serine protease.
Cryoactivation of Plasma Renin
Authors: Hara A. , Matsunaga M. , Yamamoto J. , Morimoto K. , Nagai H. , Kanatsu K. , Pak C. H. , Ogino K. , Kawai C.
Published: August 2015

1. The mechanism of increased renin activity after human plasma had been kept at −5°C for 4 days (cryoactivation) was investigated.

2. The increase in renin activity of human plasma by cryoactivation was closely correlated to the increase obtained by incubation with trypsin (r = 0·88, P < 0·001, n = 10).

3. An inhibitor of thiol enzyme, N-ethylmaleimide did not inhibit cryoactivation.

4. Soyabean trypsin inhibitor and di-isopropylfluorophosphate (DFP) inhibited cryoactivation, suggesting that the cryoactivation may be due to the action of a trypsin-like serine enzyme.

5. In an experiment in the rat haemorrhagic shock caused parallel increments of renin activity in non-cryoactivated and cryoactivated plasma, the renin activity being about two times higher in the latter. No significant differences were found in the concentrations of renin and renin substrate between the non-cryoactivated and cryoactivated plasma samples.

6. The results may indicate that a destruction of an inhibitor of the renin—renin substrate reaction is responsible for the increase of renin activity after exposure of rat plasma to low temperature. A trypsin-like enzyme in plasma might have destroyed the inhibitor during this procedure.
Acid-Activated Renin Responses to Hydrochlorothiazide, Propranolol and Indomethacin
Authors: McKenzie J. K. , Reisin E.
Published: August 2015

1. Six essential hypertensive patients (five with low renin) were treated in successive weeks with placebo; hydrochlorothiazide 100 mg (382 μmol)/day; hydrochlorothiazide and 50 mmol of sodium/day diet; hydrochlorothiazide, 50 mmol of sodium diet and propranolol 160 mg (544 μmol)/day; and hydrochlorothiazide, 50 mmol of sodium and indomethacin 100 mg (287 μmol)/day.

2. Although blood pressure remained unchanged and serum potassium fell on diuretic with or without low salt, there was a marked increase of active renin and a lesser increase of inactive renin, resulting in an increased proportion of active to total renin.

3. Propranolol decreased both active and inactive renin, but not significantly.

4. Indomethacin produced a marked suppression of active renin, a smaller reduction in inactive renin, and a reduction of the ratio of active to total renin almost to placebo values.

5. Blood pressure rose to control values on indomethacin despite the fall in renin whereas it fell with propranolol with little change in renin.

6. Serum aldosterone rose with stimulation but remained elevated despite effective renin suppression with indomethacin and continuing reduced serum potassium concentration.
Implications of Prostacyclin Generation for Modulation of Vascular Tone
Authors: Dusting G. J. , Moncada S. , Mullane K. M. , Vane J. R.
Published: August 2015

1. The biotransformation of arachidonic acid and prostacyclin in the circulation was studied in anaesthetized dogs, using the blood-bathed organ technique.

2. In passage through the lungs, arachidonate (50–800 μg kg−1 min−1) was transformed into prostacyclin. No thromboxane A2 or prostaglandin E2 could be detected in arterial blood.

3. In dogs treated with indomethacin (5 mg/kg), intravenous infusions of arachidonate had no cardiovascular effects and no prostacyclin was produced. Therefore, the vasodilator effects of arachidonate in vivo may be attributable to prostacyclin formation.

4. Prostacyclin, unlike prostaglandin E2, is not inactivated by passage across the lungs, and only about 50% disappears in one passage through peripheral vascular beds.

5. Thus prostacyclin released from the lungs could function as a circulating vasodilator and contribute to the regulation of blood vessel tone and blood pressure.
Endogenous Prostaglandin Synthesis Inhibitor in the Renal Cortex. Effects on Production of Prostacyclin by Renal Blood Vessels
Authors: Terragno Norberto A. , Terragno Alicia , Early Judith A. , Roberts Mary A. , McGiff John C.
Published: August 2015

1. The capacity of various tissues of the porcine kidney to convert [1-14C]arachidonic acid into radiolabelled prostaglandins was studied.

2. Only after removal from the cortical matrix, were renal blood vessels able to convert arachidonic acid into prostaglandins (primarily prostacyclin). In contrast, convoluted tubules showed a low capacity to metabolize arachidonic acid.

3. The failure to demonstrate prostaglandin synthesis by renal cortical slices is related to the presence of an inhibitor of cyclo-oxygenase. Thus, the addition of renal cortical incubate to isolated vascular tissues and ram seminal vesicles inhibited their ability to synthesize prostaglandins.

4. Slices of renal medulla metabolized arachidonic acid primarily to prostaglandin F2α; lesser amounts of prostaglandin E2 and prostacyclin were generated.

5. The large capacity of the renal vasculature to generate prostacyclin is consistent with an important role for this prostaglandin in regulation of renin release and renal haemodynamics.
Intrarenal Control of Urine Concentration by Angiotensin II
Authors: Imbs J. L. , Schmidt M. , Schwartz J.
Published: August 2015

1. The intrarenal role of angiotensin II in the recovery of urinary concentration after frusemide was examined in anaesthetized dogs by the intrarenal infusion of angiotensin II antagonists.

2. Renin secretion and renal inner medullary blood flow (tissue clearance of intraparenchymatously injected 133Xenon) were simultaneously measured before and 3 h after frusemide injection.

3. Intrarenal angiotensin II blockade delayed the recovery of urinary osmolality after frusemide.

4. An inverse relationship was found between renin secretion and renal inner medullary blood flow.
The Role of Vasopressin in Blood Pressure Control and in Experimental Hypertension
Authors: Pullan P. T. , Johnston C. I. , Anderson W. P. , Korner P. I.
Published: August 2015

1. The role of vasopressin in blood pressure control and in the pathogenesis of one-kidney Goldblatt hypertension in the conscious dog was investigated.

2. Infusion of synthetic arginine vasopressin to elevate plasma levels approximately five-fold caused bradycardia in normal dogs and increase in mean arterial blood pressure in dogs with pharmacological autonomic blockade.

3. A similar degree of elevation of plasma vasopressin concentration was observed after mild non-hypotensive haemorrhage.

4. Renal artery constriction in unilaterally-nephrectomized dogs caused a rise in plasma renin activity and only a doubling of plasma vasopressin concentration, but a marked rise in mean arterial blood pressure.

5. Vasopressin may play a role in normal cardiovascular homeostatic responses, but its role in the pathogenesis of this form of hypertension is unlikely to be significant.
Pharmacokinetics of Intravenous and Oral Pindolol in Hypertensive Patients with Chronic Renal Failure
Authors: Safar M. E. , Chau N. Ph. , Levenson J. A. , Simon A. Ch. , Weiss Y. A.
Published: August 2015

1. The pharmacokinetics of intravenous and oral pindolol were determined in 24 hypertensive patients with normal or impaired renal function.

2. In patients with normal renal function, the total clearance of the drug was the sum of both the renal and non-renal clearances in equal parts. The non-renal clearance was found to equal the hepatic clearance directly measured from the hepatic extraction ratio and hepatic blood flow.

3. Compared with patients with normal renal function, patients with chronic renal failure exhibited (i) unchanged transfer rate constants and distribution volumes, (ii) decreased total body clearance with decreased renal clearance and unchanged non-renal clearance.

4. Analysis of data obtained after oral administration of the drug by the Loo—Riegelman method showed that the pindolol absorption kinetic was non-linear. Compared with patients with normal renal function, patients with chronic renal failure exhibited (i) a significantly decreased fraction of dose effectively absorbed, (ii) an increased initial rate of absorption. The initial rate of absorption was inversely correlated with creatinine clearance.

5. The study provided evidence that in patients with renal insufficiency, (i) no increase in the metabolism of the drug accompanied the decrease in renal function, and (ii) decreased bio-availability was associated with a reduced fraction of the dose effectively absorbed and an increased rate of absorption.
Maximal Discrimination of Renovascular from Essential Hypertension by the Saralasin Test
Authors: Maxwell M. H. , Varady P. , Zawada E. T. , Burkhalter J.-F. , Waks U. , Marks L.
Published: August 2015

1. Thirty-four patients with essential hypertension and 37 with proven renovascular hypertension were tested with saralasin after frusemide-induced diuresis.

2. Variables used for analysis were: pre-saralasin plasma renin activity (PRA), post-saralasin PRA, and ratios of systolic and diastolic blood pressures (saralasin blood pressure/control blood pressure).

3. Stepwise linear discriminant analysis demonstrated that the most significant variables were diastolic ratio, systolic ratio, and post-saralasin PRA.

4. Minimal misclassification (14·1%) was achieved by combining diastolic ratio, baseline supine PRA and post-saralasin PRA; but using post-saralasin PRA alone resulted in misclassification of only 15·5% (7 essential hypertension and 4 renovascular hypertension).

5. Thus, PRA increased disproportionately after saralasin in renin-dependent renovascular hypertension because of the fall in blood pressure and/or interruption of the short, negative angiotensin II feedback loop.

6. It is concluded that the rise in PRA after the combined stimuli of volume depletion and saralasin is more sensitive than the fall in blood pressure in discriminating between essential hypertension and renovascular hypertension, although minimal misclassification is achieved by analysing baseline PRA, diastolic ratio and post-saralasin PRA simultaneously.
Treatment of Mild Hypertension
Authors: Morgan T. , Adam W. , Gillies A. , Carney S.
Published: August 2015

1. A total of 206 patients, elderly males with hypertension (diastolic blood pressure 95–110 mmHg) were followed for periods varying from 1 to 5 years, 107 patients with diastolic blood pressure <95 mmHg were followed over the same period, and 101 patients with diastolic blood pressure ≥110 mmHg were also followed.

2. The mortality of each group and the effect of therapy for hypertension on mortality has been compared.

3. The incidence of myocardial infarct in the group treated with thiazide diuretics is greater than in the other groups.

4. It would appear unlikely that therapy will improve the prognosis in elderly people with mild hypertension.
Increased Ratio between Serum β- and α-Lipoproteins during Diuretic Therapy: An Adverse Effect?
Authors: Glück Z. , Baumgartner G. , Weidmann P. , Peheim E. , Bachmann C. , Mordasini R. , Flammer J. , Keusch G.
Published: August 2015

1. The effect of diuretic therapy on serum lipids and lipoprotein fractions was evaluated in 16 normal or labile hypertensive subjects who received in cross-over fashion chlorthalidone, frusemide or mefruside, each for 4 weeks (group A); and in 13 patients with essential hypertension treated with chlorthalidone for 6 weeks (group B).

2. All three diuretics significantly increased the ratio between serum β- and α-lipoprotein fractions. This was due to an increase of the serum β-lipoprotein fraction while the α-lipoprotein fraction was not changed significantly (group A) or decreased (group B). Serum cholesterol or triglycerides tended to be increased, but mean changes were often not significant.

3. The observed alterations in serum lipoproteins are consistent with the possibility of an increased risk for coronary heart disease which could offset partly the beneficial effects of a lowered blood pressure in diuretic-treated patients with hypertension.
Effects of Prazosin on Blood Pressure and Plasma Renin Activity in Man
Authors: Rosenthal J. , Jaeger H. , Arlart I.
Published: August 2015

1. The effects of oral administration of 4·5 mg of prazosin/day on blood pressure and on plasma renin activity were assessed in patients with essential hypertension and in healthy normotensive volunteer subjects.

2. Mean blood pressure in the hypertensive group fell significantly within 2 weeks of treatment, whereas heart rate was little affected. None of the parameters measured in the normotensive subjects during treatment with prazosin revealed significant changes.

3. Sub-classification of the hypertensive patients into low-, normal- and high-renin categories revealed significant decreases of renin in all six patients with high renin- and in four out of 12 patients with normal renin- but not in the two patients with low renin-essential hypertension.

4. The results indicate that prazosin exerts its hypotensive action and suppresses plasma renin activity particularly in patients with high renin-essential hypertension. These may be considered to have increased sympathetic drive.

5. Conceivably, the blood pressure-lowering effect of prazosin is effected by peripheral vasodilatation and also by a decreased venous return to the heart.
The Hypertension Register of the North Karelia Project
Authors: Nissinen A. , Tuomilehto J. , Puska P.
Published: August 2015

1. One major subprogramme of the North Karelia Project was the hypertension programme which aimed at lowering of the high blood pressure among the whole population, and especially among middle-aged men. The hypertension programme consisted of intervention integrated with the existing health care structure of the county of North Karelia.

2. The hypertension register, which was the major tool of the programme, aimed to maintain patients in treatment and to get information about the development of the programme. Registration of hypertensive subjects was continuous between 1972 and 1977 and registered patients had annual follow-up examinations.

3. After 5 years of the programme, there were approximately 17 000 registered patients which is 9·7% of the total population.

4. Proportion of drop-outs at the annual follow-up examinations was less than 10%. 83% of the registered hypertensive subjects were under drug treatment after 3 years intervention. The percentage of normotensive subjects increased significantly year by year.

5. Preliminary results from the stroke register of the North Karelia Project indicate that the incidence of stroke decreased as hypertension control was improved.
Familial Hypertension and Hormonal Profile, Renal Haemodynamics and Body Fluids of Young Normotensive Subjects
Authors: Bianchi G. , Picotti G. B. , Bracchi G. , Cusi D. , Gatti M. , Lupi G. P. , Ferrari P. , Barlassina C. , Colombo G. , Gori D.
Published: August 2015

1. Almost all the factors that may cause a rise in blood pressure are, in turn, influenced by the increase in blood pressure per se. Thus any primary involvement of one or more of these factors in the pathogenesis of essential hypertension must be evaluated before or during the development of hypertension.

2. Young normotensive subjects both of whose parents are hypertensive have a much higher probability of developing hypertension than those whose parents are both normotensive.

3. The following measurements were made in 56 subjects of the first group (both parents hypertensive) and 35 of the second group (both parents normotensive), matched for age, sex and body surface area: renal plasma flow and glomerular filtration rate, using p-aminohippurate and inulin clearance; 24 h urinary excretion of aldosterone, protein and electrolytes; plasma renin activity; plasma volume. Plasma catecholamines and cardiac index were also measured in 26 subjects of the first group and 25 subjects of the second group using a radioenzymic method and echocardiography.

4. All these factors were similar in the two groups except that renal plasma flow was higher in the first group (767·2 ± 30 versus 650·7 ± 17 ml/min, P < 0·01). Plasma renin activity tended to be lower in subjects with a higher renal plasma flow, but there was no significant negative correlation between the two factors.

5. The possibility that the higher renal plasma flow in subjects with a high probability of developing hypertension is a compensatory mechanism for a primary intrarenal defect is discussed.
Are Racial Differences in Essential Hypertension Due to Different Pathogenetic Mechanisms?
Authors: Sever P. S. , Peart W. S. , Meade T. W. , Davies I. B. , Gordon D. , Tunbridge R. D. G.
Published: August 2015

1. Plasma noradrenaline concentration and plasma renin activity were measured in a control, British, urban population (n = 115) in which blacks were matched for age and sex with whites.

2. Similar measurements were made in subjects with essential hypertension (77 white and 23 black), and 48 healthy normotensive white civil servants.

3. In controls blood pressure was significantly higher in blacks; it correlated with age in both races and with pulse rate in blacks. There were no significant racial differences in plasma noradrenaline which was positively correlated with age in both blacks and whites. Mean plasma renin activity was 55% lower in blacks, and this difference was not related to urinary sodium excretion.

4. In hypertensive subjects plasma noradrenaline positively correlated with age in blacks. This relationship was not found in whites in whom 20% of young hypertensive subjects (<45 years) had significantly raised plasma noradrenaline. Plasma renin activity was again significantly lower in blacks. In white hypertensives plasma noradrenaline and renin activity were significantly correlated.

5. There may be racial differences in the pathogenesis of essential hypertension.
Kinetics of Mucosal Influx of Glycylsarcosine, Glycine and Leucine into Hamster Jejunum and Ileum in Vitro
Authors: Schedl H. P. , Burston D. , Taylor E. , Matthews D. M.
Published: August 2015

1. This paper describes an investigation of the kinetics of influx of the dipeptide glycylsarcosine and the amino acids glycine and l-leucine into rings of everted hamster small intestine in vitro, in proximal and distal small intestine (jejunum and ileum). Results were expressed per unit wet weight of intestine.

2. At all concentrations studied (0·1–100 mmol/l), influx of glycylsarcosine was more rapid in the jejunum than in the ileum. In contrast, at all concentrations studied, influx of glycine and leucine was more rapid in the ileum than the jejunum.

3. Estimates of the simple diffusion component in total influx were made. This component became increasingly large as the substrate concentration was raised. After correction for simple diffusion, transport of all three substrates conformed to Michaelis-Menten kinetics in both jejunum and ileum. Values for simple diffusion, apparent Kt and Vmax. are reported.

4. Possibly physiological implications of the results are discussed, and it is pointed out that under experimental conditions similar to our own, simple diffusion is too large a component in total influx to be ignored.
Arterial Wall Renin and Renal Venous Renin in the Hypertensive Rat
Authors: Garst Josephine B. , Koletsky S. , Wisenbaugh P. E. , Hadady Magdalena , Matthews D.
Published: August 2015

1. Infusion of sufficient renin to raise the blood pressure of normal rats to hypertensive levels resulted in increased renin in the arterial wall.

2. Arterial wall renin and renal venous renin were normal in younger spontaneously hypertensive rats, but in older spontaneously hypertensive rats arterial wall renin was significantly increased and renal venous renin was significantly decreased.

3. Arterial wall renin in rats with either acute or chronic two-kidney Goldblatt renal hypertension was significantly increased, whereas circulatory renin was elevated in the former, but depressed in the latter.

4. Arterial wall renin may play a role in the maintenance of acute and chronic renal hypertension and also perhaps of spontaneous hypertension of long duration in older rats.
Binding of Human Serum Ferritin to Concanavalin A
Authors: Worwood M. , Cragg S. J. , Wagstaff M. , Jacobs A.
Published: August 2015

1. A high proportion of the ferritin in normal serum binds to concanavalin A. Binding is prevented by the addition of α-d-methylglucoside to the reaction mixture.

2. Ferritin in extracts of normal heart, liver and spleen or serum ferritin from patients with massive hepatic necrosis does not bind to concanavalin A.

3. Isoelectric focusing of preparations of serum ferritin from patients with primary haemochromatosis shows that the ferritin fraction binding to concanavalin A consists, predominantly, of the more acidic isoferritins.

4. These findings suggest that carbohydrate residues may be added to ferritin during its secretion into the plasma. Glycosylation may account for the heterogeneity of serum ferritin on isoelectric focusing.

5. Direct release of intracellular ferritin from damaged tissue may be indicated by an increase in the proportion of circulating ferritin which does not bind to concanavalin A. Such an increase has been found in sera from patients with iron overload.
Structural and Functional Alterations in the Mucosa of Self-Filling Intestinal Blind Loops in Rats
Authors: Menge H. , Köhn R. , Dietermann K.-H. , Lorenz-Meyer H. , Riecken E. O. , Robinson J. W. L.
Published: August 2015

1. Self-filling blind loops of jejunum were constructed in three groups of rats; in the first, blind loops were created without further manipulation; in the second the bile was diverted permanently into the lower ileum below the blind loop, whereas in a third neomycin was added to the drinking water throughout the experiment. Two weeks after the creation of the blind loops, they were used for structural and functional studies.

2. Morphometric and microdissection techniques demonstrated that the surface area of the individual villi of the mucosa of ‘ordinary’ blind loops had increased fourfold in comparison with corresponding control jejunum, whereas the increase was only twofold in rats with bile diversion or in the series treated with neomycin. There were proportional increases in crypt length and mitotic activity of the crypts in all three series, which suggest that the alterations in the mucosa were due to hyperplasia in both villus and crypt compartments.

3. Sucrase, succinate dehydrogenase, alkaline phosphatase and non-specific esterase activities, determined biochemically or histochemically, were reduced in the mucosae of all blind loops, though the changes were most pronounced in the ‘ordinary’ blind loops. The accumulation of l-phenylalanine by mucosal slices in vitro was depressed, although the decrease was less marked in the series treated with neomycin.

4. These results suggest that both bacteria and deconjugated bile acids play a role in the development of the hyperplastic changes of the blind-loop mucosa, but that another factor might also be involved: as a possible candidate, stasis of the intestinal contents was considered.

5. To test this hypothesis, loops of rat colon were transposed into the jejunum. Above the transposed loop, the jejunal mucosa developed hyperplasia of both villus and crypt compartments, with a reduction in its ability to accumulate l-phenylalanine. It is argued that these changes, probably caused by stasis of the intestinal contents, are triggered off by the dilatation of the gut, which may also be implicated in the mucosal alterations in blind loops.
Carbohydrate-Containing Materials in Urine from Normal and Diabetic Subjects
Authors: Clamp J. R. , Hartog M. , Shelley J. H.
Published: August 2015

1. Abnormalities in glycoprotein metabolism are believed to play a role in diabetic microangiopathy. We have therefore measured the urinary excretion of carbohydrate-containing materials in normal and diabetic subjects.

2. Diabetic subjects were found to excrete excessive quantities of such material, which may parallel the increases observed in plasma and structural glycoproteins found in previous studies.

3. Systemic administration of a synthetic derivative of vasicine, which is known to affect mucus glycoprotein, was shown to restore these elevated urinary concentrations seen in diabetic subjects to values close to normal, but this drug had no significant effect on urinary concentrations of such materials in normal subjects.
Diuretics, Hepatic and Thoracic Duct Lymph Flows in the Dog
Authors: Szwed J. J. , Maxwell D. R.
Published: August 2015

1. Simultaneous thoracic duct and hepatic lymph flows were measured in 29 mongrel dogs before and after the intravenous administration of mannitol, ethacrynic acid, frusemide and chlorothiazide in separate experiments.

2. Thoracic duct lymph flow increased significantly after each diuretic agent was administered.

3. Hepatic lymph flow increased only after ethacrynic acid and mannitol administration. Frusemide and chlorothiazide did not alter hepatic lymph flow.

4. These data show that increases in thoracic duct lymph flow after ethacrynic acid and mannitol arise partly from the liver, as well as from other organs.
Plasma Renin Activity in Diabetes Mellitus
Authors: Burden A. C. , Thurston H.
Published: August 2015

1. The plasma renin activity (PRA) was measured in 76 diabetic patients who were attending an outpatients clinic. Of these patients 16 had untreated hypertension and 28 had diabetic complications, which ranged from microaneurysms to renal failure and blindness.

2. Compared with age- and sex-matched normotensive control subjects, both normotensive and hypertensive diabetic patients had significantly higher PRA (P < 0·001).

3. Hypertensive diabetic patients also showed a higher PRA than matched hypertensive control subjects (P < 0·005). There were no significant differences between diabetic patients with hypertension or complications compared with those without these features.

4. Although this elevation of PRA could be due to a change in another component of the renin—angiotensin system, hypersecretion of renin is the most likely explanation.
Sites of Clearance of Leucocyte Pyrogen in the Rabbit
Authors: Townsend Yvonne , Cranston W. I.
Published: August 2015

1. The dose—response curve for sustained infusions of leucocyte pyrogen has been demonstrated, and an optimum dose indicated for leucocyte pyrogen clearance experiments.

2. The lungs, liver and small bowel are not significantly involved in removal of leucocyte pyrogen from the circulation in conscious rabbits.

3. A single circulation through one kidney removes up to half of the infused dose of leucocyte pyrogen.
Ammoniagenesis by the Isolated Perfused Rat Kidney: The Critical Role of Urinary Acidification
Authors: Tannen R. L. , Ross B. D.
Published: August 2015

1. The effect of metabolic acidosis simulated in vitro on ammoniagenesis was investigated by using the isolated kidney of the rat perfused with an albumin Krebs—Henseleit medium containing glutamine and glucose.

2. Addition of HCl to a perfusate of normal bicarbonate concentration resulted in a prompt increase in urine flow rate, decrease in fractional sodium reabsorption and decrease in urine pH.

3. A minimum urine pH as low as 5·15 was achieved, with an average value of 5·92, indicating that this preparation has the capacity to acidify normally.

4. In contrast with studies in vitro with other preparations, with the functional perfused kidney a diminution in perfusate bicarbonate concentration resulted in a prompt increase in ammonia production, which was strikingly correlated with the decrease in urine pH.

5. The increase in ammonia production was diminished in studies carried out with a non-urinating kidney, in comparison with those that exhibited significant urine acidification.

6. These data suggest that a decrease in urine pH with trapping of ammonia in the urine may be a critical stimulus for increased ammonia production in acute metabolic acidosis.
Carbohydrate Moieties of Glycoproteins in Human Hepatic and Gall-Bladder Bile, Gall-Bladder Mucosa and Gall Stones
Authors: Lee S. P. , Lim T. H. , Scott A. J.
Published: August 2015

1. The soluble glycoproteins of human bile, gall-bladder mucosa and gall stones have been extracted and hydrolysed, and the monosaccharides analysed by gas-liquid chromatography.

2. Human biliary glycoproteins contained 55–75% of carbohydrate, the major monosaccharide components being galactose, fucose and N-acetylglucosamine, accounting for 70–85% of all the monosaccharides. Mannose, glucose, N-acetylgalactosamine and N-acetylneuraminic acid (sialic acid) were also present. N-Acetylneuraminic acid was present in large amounts in the gall-bladder mucosa and bile of one ulcerated and markedly inflamed gall bladder.

3. The proportion of monosaccharides in soluble glycoproteins of mucosa and bile were not different in samples from subjects with or without gall stones.

4. Gall stones were analysed for cholesterol, calcium and bilirubin and classified as ‘cholesterol stones’ (7/10) and ‘pigment stones’ (3/10). Both cholesterol and pigment stones contain a variable amount of glycoprotein. The pattern of carbohydrate constituents was similar to that present in the gall-bladder mucosa and bile in the same subject. There was also no major difference between the pattern found in ‘cholesterol’ and ‘pigment’ stones.

5. Evidence and argument are presented suggesting that some glycoprotein is secreted by the gall bladder and incorporated into gall stones. This calls for further work upon the influence of these carbohydrate-rich macromolecules on cholesterol solubilization in mixed micelles.