bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II Blockade before and after Marked Sodium Depletion in Patients with Hypertension
Authors: Van Hoogdalem P. , Donker A. J. M. , Leenen F. H. H.
Published: August 2015

1. Angiotensin II blockade before and after marked sodium depletion in patients with hypertension [unilateral renovascular (eight), bilateral renovascular (four) and essential (four)] was performed by intravenous administration of the angiotensin II antagonist Sar1-Ala8-angiotensin II (saralasin).

2. On normal sodium intake, saralasin decreased mean blood pressure by 8 mmHg in the unilateral renovascular group, by 6 mmHg in the bilateral renovascular group and increased it by 3 mmHg in the essential hypertensive group. After sodium depletion saralasin decreased mean blood pressure by 33 mmHg, 35 mmHg and 18 mmHg respectively. The saralasin-induced decrease in blood pressure significantly correlated with the log of the initial plasma renin activity.

3. Saralasin infusion decreased effective renal plasma flow (ERPF) in all three hypertension subgroups, both on normal sodium intake and after sodium depletion. Glomerular filtration rate decreased in direct relation to the hypotensive effect of saralasin but ERPF showed this relationship only after sodium depletion. On normal sodium intake saralasin increased filtration fraction by 17%, but decreased it by 7% after sodium depletion.

4. It is concluded that the hypotensive action of saralasin closely correlates with the value of circulating plasma renin activity, apparently independent of the aetiology of the hypertension. The decrease in ERPF during saralasin infusion in the patients on normal sodium intake seems mainly related to the agonistic activity of saralasin, but that after sodium depletion to the hypotensive effect of saralasin.
Intensive Iron-Chelation Therapy with Desferrioxamine in Iron-Loading Anaemias
Authors: Pippard M. J. , Callender S. T. , Weatherall D. J.
Published: August 2015

1. Urinary iron excretion after desferrioxamine has been examined in nine patients with different iron-loading anaemias. Particular attention has been paid to individual variation in response and the kinetics of iron removal in order to determine the most efficient and convenient method of administration.

2. Twelve-hour subcutaneous infusions of desferrioxamine were comparable with intravenous infusions and gave a mean value of 62% more iron excretion than similar intramuscular bolus doses (range 20–125%).

3. Increasing doses as 12 h subcutaneous infusions produced a linear increase in iron excretion, which was followed by a tendency to reach a plateau. Iron excretion varied greatly between patients, was not related solely to age or estimated iron load, and in most cases was increased by ascorbic acid saturation.

4. Maximum iron-excretion rates were achieved after 3–6 h and then maintained throughout an infusion. With bolus injections excretion rates declined rapidly after the first 6 h, during which approximately 60% of the total iron excretion occurred.

5. The dose and method of administration should be ‘tailor-made’ for each patient. Overnight 12 h subcutaneous infusions can be both as effective as similar doses given over 24 h and a practical way of achieving substantial negative iron balance.

6. Since children receiving regular blood transfusions for congenital anaemias such as thalassaemia usually die at the end of the second decade, this approach to iron chelation offers the possibility of alleviating what have hitherto been fatal iron-loading states.
Characterization of Immunoreactive Angiotensin in Canine Cerebrospinal Fluid as Des-Asp1-Angiotensin II
Authors: Hutchinson J. S. , Csicsmann J. , Korner P. I. , Johnston C. I.
Published: August 2015

1. Immunoreactive angiotensin II was measured in cerebrospinal fluid of four normal dogs.

2. The migration of this immunoreactive angiotensin II on polyacrylamide-slab gel electrophoresis was identical with the migration of the heptapeptide, Des-Asp1-angiotensin II, in each case.

3. The biological activity of the material from canine cerebrospinal fluid in a pressor bioassay was similar to that of Des-Asp1-angiotensin II.

4. The pressor activity of the canine material was abolished by treating the pressor bioassay rat with a competitive antagonistic analogue, Sar1-Ala8-angiotensin II.

5. The results suggest that the biologically active immunoreactive angiotensin II present in normal canine cerebrospinal fluid is composed mainly of the heptapeptide fragment of angiotensin II, Des-Asp1-angiotensin II.
Metabolism in Vitro of 25-Hydroxycholecalciferol in Chicks Fed on Phosphorus-Deficient Diets
Authors: Swaminathan R. , Sommerville Barbara A. , Care A. D.
Published: August 2015

1. Three groups of 10-days-old chicks were fed on one of three diets having phosphorus contents of 0·08 mol/kg, 0·14 mol/kg or 0·21 mol/kg. Ten days later duodenal calcium absorption by the ligated loop technique in vivo, and plasma calcium and phosphorus concentrations, were measured. In addition the metabolism in vitro of 25-hydroxycholecalciferol [25-(OH)D3] by kidney homogenates was studied.

2. In the low phosphorus group (0·08 mol/kg) calcium absorption and the activity of 25-(OH)D3-1-hydroxylase were significantly higher than those of the high phosphorus group (0·21 mol/kg). However, in the medium phosphorus group (0·14 mol/kg), calcium absorption was significantly higher although the activity of 25-(OH)D3-1-hydroxylase was not significantly higher when compared with the high phosphorus group (0·21 mol/kg).

3. It is concluded that in phosphorus deprivation, unlike in calcium deprivation, a diet very low in phosphorus is required to stimulate the renal 25-(OH)D3-1-hydroxylase activity.
Muscle Electrolytes and Fluid Compartments in Six Children with Bartter's Syndrome
Authors: Delaporte Christine , Stulzaft J. , Loirat C. , Broyer M.
Published: August 2015

1. Muscle electrolyte (Na, K, Cl, P) concentrations and fluid compartments of six children with Bartter's syndrome were compared with those of 17 control children. From four of the patients biopsies were taken twice, before and after treatment with potassium chloride and spironolactone. Muscle electrolytes were determined by neutron activation in tissue sampled by needle biopsy. Results were expressed in relation to fat-free dry solids. Trapped extracellular fluid was calculated from the chloride space, a normal resting membrane potential being assumed.

2. In hypokalaemic patients total muscle potassium (Km) (33·0 ± 2·1 sem) was below the normal range (43·8 ± 0·7 mmol/100 g of fat-free dry solids) in all cases. When plasma potassium was corrected, total muscle potassium returned to normal. There was a significant correlation between plasma potassium concentration and total muscle potassium (r = 0·87; P < 0·01). Total muscle sodium (Nam) was increased: 18·7 ± 2·9 mmol/100 g in hypokalaemic patients (11·3 ± 0·6 mmol/100 g of fat-free dry solids in control subjects). A negative relationship was found between Km and Nam (r = —0·85; P < 0·01). With treatment, intracellular potassium concentration remained low (142·0 mmol/l of intracellular water; control, 163·0 ± 2·4 mmol/l) despite normokalaemia and normal total muscle potassium. Muscle phosphorus (32·1 ± 1·8 mmol/100 g) was higher than in control subjects (28·1 ± 0·4 mmol/100 g of fat-free dry solids).

3. These data suggest that sodium replaces potassium in muscle of patients with Bartter's syndrome. The low intracellular potassium concentration in the binephrectomized sister of one child and in all treated children suggests that there are generalized anomalies in the handling of cations in Bartter's syndrome.
Parathyroid Hormone-like Biological Activity in Urine
Authors: Wolf N. Nijs-De , De Nutte N. , Brauman H. , Corvilain J.
Published: August 2015

1. The parathyroid hormone-like biological activity of concentrated urine was measured by the increase of plasma calcium concentration after intravenous injection of the sample into chickens.

2. Urine was tested in hypoparathyroid patients, normal volunteer subjects, primary hyperparathyroid patients before and after surgery and patients with secondary hyperparathyroidism.

3. In primary and secondary hyperparathyroidism the biological activity was significantly higher than in urine from normal subjects, which was in turn significantly higher than the activity in the urine of hypoparathyroid patients. This bioactivity diminished after surgical removal of a hyperparathyroid adenoma.

4. Decreased activity after trypsinization indicated the peptidic nature of the hypercalcaemic substance.
Effect of Streptozotocin-Diabetes on the Local and General Responses to Injury in the Rat
Authors: Elebute E. A. , Little R. A.
Published: August 2015

1. The effects of streptozotocin-diabetes on the local and general responses to a 4 h period of bilateral hind-limb ischaemia in the rat have been investigated. The rats were injured 48 h after the intravenous injection of the streptozotocin.

2. Less fluid was lost from the circulation into the injured limbs after injury in the diabetic rats and this was directly related to the severity of the diabetes, but could not be explained by dehydration. However, when the diabetic and non-diabetic injured rats were considered together there was a significant negative correlation between either plasma osmolality or plasma glucose concentration and water content in the injured hind limb.

3. The relationship between plasma glucose concentration and plasma osmolality was changed by injury such that, particularly in the injured diabetic rats, plasma osmolality at a given glucose concentration was higher than that predicted from the relationship between these variables in the uninjured rat.
Role of Endotoxin in Glycerol-Induced Renal Failure in the Rat
Authors: Nolan J. P. , Venuto R. C. , Goldmann Gwendolyn S.
Published: August 2015

1. A relationship between bacterial endotoxin absorbed from the gut and acute renal failure has been postulated. Experiments employing either the endotoxin-tolerant state or the enhancement of endotoxin injury were undertaken to test this relationship in rats.

2. Endotoxin tolerance was induced by the administration of increasing doses of Escherichia coli 026 lipopolysaccharide. The severity of renal injury was assessed at various times after glycerol administration in endotoxin-tolerant and control animals. At 48 h, endotoxin-tolerant rats had higher urine volume and creatinine clearance than the non-tolerant control animals. In rats studied 72 h after glycerol, functional and anatomical assessment showed the endotoxin-tolerant rats to have lower serum urea concentrations and also less renal histological injury than the non-tolerant, control animals.

3. Lead acetate, which potentiates endotoxin injury, or diluent alone was administered to rats after glycerol. At 2, 3 and 10 days later there was a twofold increase in mortality in the lead acetate-treated animals.

4. A small dose of endotoxin (0·1 mg) was shown to be innocuous in control rats. Also, all rats given glycerol alone were alive 24 h later. In contrast, administration of the same dose of endotoxin simultaneously with glycerol resulted in an 80% mortality at 24 h.

5. These studies demonstrate enhancement of glycerol-induced renal injury by endotoxin and support a possible role for endotoxin in this model of acute renal failure.
Characterization of β-Adrenergic Receptor Linked to Adenylate Cyclase in a Human Cancer Cell Line (COLO 16)
Authors: Martin T. J. , Nahorski S. R. , Hunt N. H. , Dawborn J. K. , Loomes R. S. , Underwood J. C. E.
Published: August 2015

1. A human cancer cell line (COLO 16) derived originally from an epidermal squamous cell carcinoma was found to possess adenylate cyclase responsiveness to β-adrenergic agonists.

2. The adenylate cyclase response was characterized with respect to activation constants (KA) for various β-adrenergic agonists and inhibition constants (Ki) for antagonists.

3. Intact cells responded with dose-dependent increases in production of cyclic adenosine 3′:5′-monophosphate.

4. Properties of the β-adrenergic receptor were evaluated by using the specific binding of [3H]propranolol to cell membranes. Specific binding was saturable, with KD 5.79 nmol/l and binding sites 0.68 pmol/mg of protein.

5. Competition for binding to cell membranes was shown by β-adrenergic agonists and antagonists and was stereospecific. There was close agreement between the affinity of these various agents on adenylate cyclase and receptor binding.

6. It is likely that the β-adrenergic receptor-linked adenylate cyclase in COLO 16 cells represents persistence in a cancer cell line of a receptor present normally in epidermal cells.
Catabolic Rate of α1-Antitrypsin of Pi Types S, and MMalton and of Asialylated M-Protein in Man
Authors: Jeppsson J.-O. , Laurell C.-B. , Nosslin B. , Cox D. W.
Published: August 2015

1. Human α1-antitrypsin was isolated with preserved microheterogeneity from subjects of Pi types M, S and MMalton. The M-protein was partially (20%) and completely desialylated. The proteins were labelled with either 125I or 131I.

2. The disappearance rate of these α1-antitrypsins was studied after simultaneous injection of the two types of labelled protein into Pi M subjects. The fractional catabolic rates of S- and MMalton-protein were 0.36 and 0.34 day−1 respectively compared with 0.28 day−1 for M-protein. The ratio of extravascular to plasma pools was 1.4 for S-protein and 1.6 for MMalton-protein. The 20% desialylated M-protein showed an increase of about 100% in its fractional catabolic rate. The disappearance rate of completely desialylated α1-antitrypsin was extremely rapid.

3. The slightly higher fractional catabolic rate of S- than of M-protein can only partly explain the 40% lower plasma concentration in subjects of Pi type S. Similarly the slight increase in catabolic rate of Pi MMalton-protein is too small to explain why the α1-antitrypsin content of the blood in Pi MMalton subjects is only 15% of that normally found. A low hepatic secretion seems to be the major cause of the low α1-antitrypsin concentration found in subjects of types Pi S and MMalton, as in Pi type Z.
Urinary Dopamine in Man and Rat: Effects of Inorganic Salts on Dopamine Excretion
Authors: Ball S. G. , Oats N. S. , Lee M. R.
Published: August 2015

1. Plasma and urine free dopamine (3,4-dihydroxyphenethylamine) were measured in six normal male volunteer subjects and the urinary clearance of dopamine was calculated for each subject.

2. The excretion rates for free dopamine in man were greater than could be explained by simple renal clearance. It was concluded that free dopamine must, therefore, be formed in the kidney.

3. Changes in urinary dopamine excretion were studied in four groups of rats initially maintained on a low sodium diet and then given equimolar dietary supplements of NaCl, NaHCO3, KCl or NH4Cl, to study the specificity of the previously observed increase in dopamine excretion after increased dietary NaCl.

4. The mean dopamine excretion increased significantly in rats given NaCl, KCl and NH4Cl, whereas dopamine excretion decreased in those given NaHCO3.

5. The failure of dopamine excretion to rise in response to loading with NaHCO3 was unexpected, and argues against a simple effect of volume expansion by the sodium ion. The increase in dopamine excretion with KCl and NH4Cl showed that this response was not specific to the sodium ion.
Effects of the β-Receptor Antagonists Propranolol, Oxprenolol and Labetalol on Human Vascular Smooth-Muscle Contraction
Authors: Moulds R. F. W. , Jauernig R. A. , Hobson J. D. , Shaw J.
Published: August 2015

1. Spiral strips of human digital arteries have been studied in vitro to investigate whether dl-propranolol, d-propranolol, oxprenolol and labetalol have peripheral vascular effects in man.

2. Labetalol was a potent inhibitor of contractile responses to noradrenaline, but had less effect on responses to 5-hydroxytryptamine and barium chloride.

3. dl-and d-propranolol were equally effective inhibitors of responses to barium chloride. They were only weak antagonists of noradrenaline responses, but stronger, non-competitive antagonists of 5-hydroxytryptamine responses.

4. Oxprenolol was only a weak inhibitor of the responses to both noradrenaline and 5-hydroxytryptamine and had little effect on responses to barium chloride.

5. It is concluded that labetalol has specific α-adrenoreceptor-blocking properties, which are probably relevant to its therapeutic action in man. Propranolol has non-specific inhibitory effects on vascular smooth muscle, which might contribute to its hypotensive activity at high concentrations, but oxprenolol has only slight peripheral effects that are probably therapeutically insignificant.
Analytical Subcellular Fractionation of Jejunal Biopsy Specimens: Enzyme Activities, Organelle Pathology and Response to Gluten Withdrawal in Patients with Coeliac Disease
Authors: Peters T. J. , Jones P. E. , Wells G.
Published: August 2015

1. Portions of jejunal biopsy specimens from patients with coeliac disease were homogenized in isotonic sucrose solution and subjected to analytical subcellular fractionation by sucrose-density-gradient centrifugation.

2. The activities and distribution of marker enzymes for the principal subcellular organelles were determined by highly sensitive enzymic micro-assays employing fluorigenic and radiolabelled substrates.

3. In untreated coeliac disease the brush border showed decreased activities of five marker enzymes, which were reduced to up to one-eighth of control values. On sucrose density gradients the distinct brush-border peak at density 1.21 was replaced by a broad peak at density 1.16.

4. Two out of three lysosomal enzymes showed increased activities and there was evidence of enhanced fragility of both lysosomes and peroxisomes.

5. There were reduced activities of both mitochondrial and cytosol malate dehydrogenase, with increased activities of cytosol lactate dehydrogenase.

6. The endoplasmic reticulum and basal-lateral membranes were relatively unaffected except that the equilibrium densities were slightly increased and decreased respectively.

7. The patients were treated by gluten withdrawal and subsequent biopsies examined as above. Biopsies from patients treated for 2–4 weeks and who had not yet achieved a morphological improvement showed a partial return to normal of the pathological organelles.

8. Treated patients with partial villus atrophy showed progressively improved enzyme activities and a partial reappearance of the brush-border peak on the sucrose density gradients.

9. Patients whose intestinal mucosa had returned to morphological normality after prolonged gluten withdrawal showed a persistent defect in the brush-border enzyme activities. This was particularly striking for β-glucosidase, which was persistently deficient from the brush-border although approximately one-third of the total activity of this enzyme is normally found in this organelle.

10. The properties and enzyme activities of lysosomes, peroxisomes, endoplasmic reticulum, mitochondria and cytosol were essentially normal in the biopsies from fully treated patients.
Effects of Chronic Renal Insufficiency and Metabolic Acidosis on Glutamine Metabolism in Man
Authors: Tizianello A. , De Ferrari G. , Garibotto G. , Gurreri G.
Published: August 2015

1. Arterial concentration and arterial-venous differences of glutamine across the kidney, forearm, hepato—splanchnic bed and brain were measured in patients with chronic renal insufficiency and in patients with normally functioning kidneys before and during chronic ammonium chloride acidosis.

2. In chronic renal insufficiency and in chronic metabolic acidosis there is a rise in glutamine release from the muscle and a suppression of glutamine uptake by the hepato—splanchnic bed and the brain.

3. In chronic renal insufficiency arterial glutamine concentration is significantly increased in comparison with subjects with normal renal function and either normal acid-base balance or chronic metabolic acidosis.

4. In patients with chronic renal insufficiency the kidney extracts negligible amounts of glutamine, which cannot account for the renal ammonia production measured in the same patients.
The Formation of Tri-Iodothyronine and Reverse Triiodothyronine from Thyroxine in Isolated Rat Renal Tubules
Authors: Heyma P. , Larkins R. G. , Stockigt J. R. , Campbell D. G.
Published: August 2015

1. Conversion of thyroxine into triiodothyronine and reverse tri-iodothyronine in intact cells was studied with isolated renal tubules prepared by collagenase digestion.

2. Conversion of thyroxine into triiodothyronine and reverse tri-iodothyronine increased progressively for at least 90 min.

3. Studies of tri-iodothyronine production from increasing amounts of thyroxine revealed that the thyroxine to tri-iodothyronine conversion is saturable.

4. Iodide and carbimazole had no effect on the thyroxine to tri-iodothyronine conversion.

5. 6-Propyl-2-thiouracil had a direct noncompetitive inhibitory effect on the conversion of thyroxine into tri-iodothyronine with a 75% inhibition of the conversion at a propylthiouracil concentration within the therapeutic range in vivo. Propylthiouracil also inhibited the net formation of reverse tri-iodothyronine from thyroxine at a similar propylthiouracil concentration, as well as inhibiting the subsequent degradation of reverse triiodothyronine.
Differences in Reflex Control of Arterial Pressure and Renin Release during Head-Up Tilting in the Cat
Authors: Stella A. , Dampney R. A. L. , Golin R. , Zanchetti A.
Published: August 2015

1. Anaesthetized cats were subjected to two 10 min trials of head-up tilting spaced 30 min. Arterial pressure, heart rate, blood flow to an innervated kidney and to the contralateral denervated one, and renin release from both kidneys were measured.

2. The same haemodynamic changes and comparable increases in renin release from innervated kidneys occurred during both episodes of tilting when cats were subjected to sham cervical vagotomy between the two tilting trials.

3. Bilateral cervical vagotomy, performed after the first episode of head-up tilting, did not affect the haemodynamic response to the change in posture, but significantly and markedly reduced the increase in renin release from the innervated kidney.

4. After sino-aortic denervation a marked and sustained arterial hypotension occurred during tilting, and the postural increase in renin release from the innervated kidney was even greater.

5. In no condition, even during the marked fall in blood pressure in sino-aortic denervated cats, did head-up tilting increase renin release from the denervated kidney.

6. It is concluded that maintenance of arterial pressure during tilting is mainly due to sino-aortic reflexes, whereas vagal reflexes are mostly responsible for the postural increase in renin release.
Antihypertensive Activity of Metyrosine in Spontaneously Hypertensive Rats and its Enhancement by Carbidopa
Authors: Scriabine A. , Ludden C. T. , Sweet C. S. , Porter C. C. , Ulm E. H. , Stone C. A. , Watkins C. J. , Wurtman R. J. , Cronin B. L.
Published: August 2015

1. Metyrosine (l-α-methyl-p-tyrosine, Demser), an inhibitor of tyrosine hydroxylase, has moderate antihypertensive activity in spontaneously hypertensive rats (20–40 mmHg fall in mean arterial pressure) at 20–80 mg/kg intraperitoneally or 80 mg/kg orally. The maximal effect is reached at 4 h after treatment and the duration of action exceeds 12 h.

2. A peripheral inhibitor of amino acid decarboxylase, carbidopa ([—]-l-α-hydrazino-3,4-dihydroxy-α-methylbenzenepropanoic acid monohydrate), (25 mg/kg intraperitoneally) has little or no antihypertensive activity alone but if administered 5 min before metyrosine, it greatly enhances the antihypertensive potency of metyrosine. The relative potency of metyrosine + carbidopa (both intraperitoneally), as compared with metyrosine alone, was 74 with 95% confidence limits of 31 and 142.

3. In another series of experiments, the antihypertensive activity of metyrosine (80 mg/kg orally) was enhanced and prolonged by carbidopa, (25 mg/kg intraperitoneally). This effect was independent of the interval between administration of the two drugs (5 or 45 min).

4. Metyrosine (20 mg/kg intraperitoneally), reduced brain and heart noradrenaline concentrations in spontaneously hypertensive rats as determined 6 h after treatment. Carbidopa (25 mg/kg intraperitoneally) slightly enhanced the noradrenaline-depleting effect of metyrosine in the whole brain but not in the heart.

5. After metyrosine or carbidopa + metyrosine, low concentrations of α-methyldopamine were found in the brain of spontaneously hypertensive rats. Methyldopa at the same dose (20 mg/kg intraperitoneally) produced a 10 times greater increase in α-methyldopamine concentrations.

6. The inhibition by carbidopa of noradrenaline synthesis in sympathetic nerve endings in the heart and in peripheral blood vessels may be at least partially responsible for the carbidopa-induced enhancement of the antihypertensive action of metyrosine.
Antihypertensive Therapy in Patients above Age 60 Years (Fourth Interim Report of the European Working Party on High Blood Pressure in Elderly: EWPHE)
Authors: Amery A. , Berthaux P. , Birkenhäger W. , Boel A. , Brixko P. , Bulpitt C. , Clement D. , De Padua F. , Deruyttere M. , De Schaepdryver A. , Dollery C. , Fagard R. , Forette F. , Forte J. , Henry J. F. , Hellemans J. , Koistinen A. , Laaser U. , Lund-Johansen P. , MacFarlane J. , Miguel P. , Mutsers A. , Nissinen A. , Ohm O. T. , Pelemans W. , Suchett-Kaye A. I. , Tuomilehto J. , Willems J. , Willemse P.
Published: August 2015

1. A total of 450 hypertensive patients above the age of 60 years have entered the double-blind multicentre trial of the European Working Party on High blood pressure in Elderly (EWPHE). After stratification and randomization half were treated with one capsule daily containing 25 mg of hydrochlorothiazide and 50 mg of triamterene and half were given placebo. In those receiving active treatment, if blood pressure control was not adequate they were given a second capsule and if necessary up to 2 g of methyldopa/day.

2. No significant differences between the groups were present before randomization. A significant blood pressure difference of 25/10 mmHg was obtained between the groups and maintained during 4 years of follow-up. No major disturbances in serum potassium or serum sodium were noted with the present drug combination.

3. During the initial phase an increase in serum creatinine and serum uric acid was noted in the actively treated group, which was maintained during the later years. This increase in serum creatinine in the actively treated group was related (P = 0·003 and r = −0·247) to the decrease in sitting systolic blood pressure. Changes in serum uric acid were (r = 0·3 and P = 0·003) correlated with the changes in serum creatinine both in the placebo and in the actively treated group, but independent of the change in creatinine; the serum uric acid was on average 1 mg higher in the actively treated than in the placebo group.

4. Fasting blood glucose did not change significantly in the placebo-treated group but in the active treatment group the rise was statistically significant.

5. A favourable influence on prognosis by active treatment can be expected on the basis of the blood pressure reduction and in the absence of major electrolytes disturbances. However, the balance between this decreased risk and the increased risk produced by the rise in blood glucose and the other treatment effects remains to be determined. Therefore the trial continues and more patients are being admitted.
Relationship between the Hypotensive and Renin-Stimulating Actions of Diuretic Therapy in Hypertensive Patients
Authors: Leonetti G. , Terzoli Laura , Sala Carla , Bianchini C. , Sernesi Laura , Zanchetti A.
Published: August 2015

1. The pressor role of renin stimulated by chronic diuretic therapy has been assessed in 31 patients with essential hypertension by infusing the angiotensin II antagonist, saralasin, immediately before and at the end of 2 weeks' treatment with the diuretic, chlorthalidone.

2. Under diuretic therapy the change in blood pressure caused by saralasin was found to be correlated to plasma renin activity values, in such a way that small pressor responses were again observed in patients whose renin was mildly stimulated by the diuretic, whereas a marked depressor response occurred in patients whose renin was markedly increased.

3. On the other hand, the hypotensive effect of chlorthalidone was correlated to values of plasma renin activity under diuretic therapy in an opposite direction: indeed little or no decrease and sometimes an increase in blood pressure were observed in patients with marked renin activation by diuretic therapy.

4. It is concluded that stimulation of renin release by chronic diuretic therapy can be considered a factor limiting the hypotensive activity of diuretic drugs.
Blood Pressure Control: The Effect of Facilitated Access to Treatment
Authors: Alderman M. H. , Miller Kathryn F.
Published: August 2015

1. Effectiveness of hypertension care has been compared in patients treated at a Union health centre and at their place of work.

2. Patient adherence and blood pressure control is not affected by the place of treatment.

3. A systematic approach to treatment can be successful in a large population group.
Niacin Depletion in Parkinsonian Patients Treated with L-dopa, Benserazide and Carbidopa
Authors: Bender D. A. , Earl C. J. , Lees A. J.
Published: August 2015

1. Benserazide and carbidopa, decarboxylase inhibitors used in the treatment of Parkinson's disease, have been shown to inhibit the enzyme kynurenine hydrolase in rat and mouse liver. This results in reduced synthesis of nicotinamide coenzymes from tryptophan, and hence an increased reliance on dietary niacin.

2. Pellagra might be expected as a result of this inhibition of endogenous synthesis of nicotinamide nucleotides, but has not been reported in patients treated with either drug.

3. The urinary excretion of N1-methylnicotinamide, a product of nicotinamide nucleotide metabolism, is considerably reduced in patients treated with dopa alone or in combination with an inhibitor of peripheral dopa decarboxylase, to as low as 40% of the control value. This means that many of these patients could be classified as ‘at risk’ of niacin deficiency, even if not frankly deficient.

4. Patients treated with dopa plus a decarboxylase inhibitor, but not those treated with dopa alone, also show a reduced excretion of xanthurenic acid, and an increased excretion of kynurenine, as would be expected after inhibition of the kynurenine pathway, and possibly indicative of marginal vitamin B6 deficiency.
Myopathy in Bone Loss of Ageing: Improvement by Treatment with 1α-hydroxycholecalciferol and Calcium
Authors: Sørensen O. H. , Lund BI. , Saltin B. , Lund BJ. , Andersen R. B. , Hjorth L. , Melsen F. , Mosekilde L.
Published: August 2015

1. Eleven patients with the bone loss of ageing were treated with the vitamin D analogue 1α-hydroxycholecalciferol and calcium for 3–6 months.

2. Muscle biopsies were taken from the vastus lateralis before and after the treatment and the activity of several enzymes was measured. Succinate dehydrogenase and total phosphorylase activities, which are a measure of the oxidative capacity, were low and increased significantly with the treatment. The lactate dehydrogenase activity, which can be taken as a measure of the anaerobic metabolism, was normal and did not change with treatment. The phosphagen stores, ATP and creatine phosphate were low and increased to normal with treatment.

3. Histochemical classification of the fibre composition revealed that the treatment induced an increase in the relative number of fast-twitch a (FTa or type II A) fibres accompanied by a reduction of the fast-twitch b (FTb or type II B) fibres. The cross-sectional area of the FTa fibres also increased with the treatment.

4. The present findings indicate that treatment with the active vitamin D analogue, 1α-hydroxycholecalciferol, and calcium improves the myopathy associated with the bone loss of ageing.
Central and Peripheral Circulation in Relation to Muscle-Fibre Composition in Normo- and Hyper-Tensive Man
Authors: Juhlin-Dannfelt A. , Frisk-Holmberg M. , Karlsson J. , Tesch P.
Published: August 2015

1. Fibre composition in the vastus lateralis muscle, and blood pressure, were determined in age-matched normotensive (n = 22) subjects and previously untreated patients (n = 19) with essential hypertension.

2. In all subjects the muscle fibres were classified, as fast-twitch (FT) and slow-twitch (ST), and blood pressure was recorded. Eleven patients and seven of the normotensive subjects participated in an extended haemodynamic study with intraarterial pressure measurements and determinations of leg blood flow.

3. In both normo- and hyper-tensive subjects, ambulant and intra-arterial blood pressure and leg vascular resistance were negatively correlated to the percentage of ST fibres; no significant correlation was found to total leg blood flow.

4. The findings show that muscles with a high proportion of FT fibres have a higher resistance than muscles rich in ST fibres and suggest that the type of fibre in skeletal muscle might be of importance for the development of the hypertensive disease.
Action of Angiotensin I Converting Enzyme Inhibitor on the Control of Renal Function in the Cat
Authors: Johns E. J.
Published: August 2015

1. The renal responses to low level renal nerve stimulation and reduction in renal perfusion pressure within the autoregulatory range were measured before and after blockade of converting enzyme activity. Experiments were carried out using the unilaterally nephrectomized cat with the nerves of the remaining kidney acutely sectioned.

2. Renal nerves were stimulated to cause a 14% fall in blood flow for 15 min. Glomerular filtration rate was unchanged but sodium excretion and the ratio of sodium clearance to glomerular filtration rate fell significantly.

3. Renal nerve stimulation after blockade of converting enzyme activity was associated with a significant fall in glomerular filtration rate. The reductions in sodium excretion and in the ratio of sodium clearance to glomerular filtration rate were as large as in the absence of the blocking drug.

4. Reduction in renal perfusion pressure was associated with autoregulation of both renal blood flow and glomerular filtration rate but with large falls in sodium excretion and the ratio of sodium clearance to glomerular filtration rate.

5. After blockade of converting enzyme activity blood flow was still autoregulated in response to similar perfusion pressure reduction and glomerular filtration rate fell significantly. The ratio of sodium clearance to glomerular filtration rate, and sodium excretion, were reduced to the same extent as in the absence of the drug.

6. This information suggests that regulation of glomerular filtration rate associated with nerve stimulation or pressure reduction may be mediated by the intrarenal formation of angiotensin II, possibly acting at the efferent arteriole. They also indicate that angiotensin II is probably not involved in causing the increased sodium reabsorption.
Changes in Cholesterol Metabolism with Dietary Cholesterol in Children with Familial Hypercholesterolaemia
Authors: Martin Gillian M. , Nestel P.
Published: August 2015

1. Possible defects in cholesterol metabolism were sought in children with familial hypercholesterolaemia.

2. In nine affected children (eight heterozygotes and one homozygote) and in five healthy children, cholesterol synthesis and bile acid synthesis were determined from the excretion of steroids in the faeces during a low cholesterol diet. Cholesterol synthesis of 10·1 ± 4·4 mg day−1 kg−1 in the hypercholesterolaemic children was similar to that in these and other normal children. Mean bile acid synthesis of 4·0 ± 2·1 mg day−1 kg−1 also resembled normal values though three severely affected heterozygotes excreted substantially less.

3. The response to 4 weeks' additional 450 mg of dietary cholesterol/day led to variable changes in the plasma cholesterol and in the sterol balance. On average the affected children showed a rise in plasma cholesterol which resembled that in healthy subjects. The sterol balance fell in most, suggesting a reduction in cholesterol synthesis, which is the normal response to dietary cholesterol.

4. The response to dietary cholesterol was therefore at least qualitatively similar in the hypercholesterolaemic children to that reported in healthy subjects.
Effect of Phenobarbitone on Plasma Apolipoprotein B and Plasma High-Density-Lipoprotein Cholesterol in Normal Subjects
Authors: Durrington P. N.
Published: August 2015

1. Further observations from an earlier study in which phenobarbitone in a dose of 180 mg daily was administered to ten normal men and women for 3 weeks are reported. There was a significant increase in plasma high-denity-lipoprotein (HDL) cholesterol concentration and in the concentration of both total plasma and low-density-lipoprotein (LDL) apolipoprotein B.

2. There was no change in the ratios of the cholesterol: apolipoprotein B and triglyceride: apolipoprotein B in LDL.

3. There was no significant change in plasma very-low-density-lipoprotein (VLDL) apolipoprotein B concentration and the proportion of lipid and apolipoprotein B in VLDL remained unchanged.

4. There was no change in the ratio of HDL:LDL cholesterol concentrations.
Fractured Neck of Femur in the Elderly: An Attempt to Identify Patients at Risk
Authors: Wootton R. , Brereton P. J. , Clark M. B. , Hesp R. , Hodkinson H. M. , Klenerman L. , Reeve J. , Slavin G. , Tellez-Yudilevich M.
Published: August 2015

1. During a 15-month period, 110 elderly patients admitted with fractured neck of femur were studied in comparison with 72 elderly control patients undergoing elective surgery admitted over the same period to the same orthopaedic wards.

2. A striking finding was the marked similarity of all variables measured in the fracture and control groups. The principal differences between the two populations were that the fracture patients had a lower mean forearm bone mineral content, and that their serum concentrations of albumin, globulin and phosphate were reduced.

3. Neither measurements of radioisotopic calcium absorption, nor those of the serum concentrations of calcium, 25-hydroxy-vitamin D3 nor alkaline phosphatase provided satisfactory discrimination between the groups.

4. Several indices were devised, based on linear combinations of the test results obtained, in an attempt to predict the liability to future fractures of patients being considered for prophylactic therapy with oestrogens or other drugs. However, further work is required to define an index of improved predictive power and to evaluate it prospectively.
Effect of Decrease in Bicarbonate Concentration on Metabolism of the Isolated Perfused Rat Kidney
Authors: Ross B. D. , Tannen R. L.
Published: August 2015

1. An isolated perfused rat kidney preparation which responds to acidification of the perfusion medium with the production of an acid urine and increased ammonia production was used to study the metabolic regulation of ammonia production from glutamine.

2. An inhibitor of gluconeogenesis at phosphoenolpyruvate carboxykinase(GTP), mercaptopicolinate, completely prevented the increase in ammoniagenesis, without preventing acidification of the urine.

3. Acidification of the perfusion medium from pH 7·4 to 7·0 reduced the renal concentrations of malate and 2-oxoglutarate.

4. Malate concentration was restored by inhibition of phosphoenolpyruvate carboxykinase(GTP), but 2-oxoglutarate content remained low. This indicates that accelerated gluconeogenesis in acute acidosis cannot be the explanation for the fall in 2-oxoglutarate concentration.

5. The fall in 2-oxoglutarate content is taken to indicate an important fall in tissue pH or in the redox ratio (NAD+/NADH) or both during acute metabolic acidosis.

6. From these studies with lowered bicarbonate two separate stimuli to ammoniagenesis in acute metabolic acidosis are postulated: urinary trapping of ammonia and increased disposal of glutamine carbon atoms via the pathway of glucose synthesis.
Effects of β-Adrenoreceptor Antagonists on Sino-Aortic Baroreflex Sensitivity and Blood Pressure in Hypertensive Man
Authors: Watson R. D. S. , Stallard T. J. , Littler W. A.
Published: August 2015

1. Sensitivity of the sino-aortic baroreflex was investigated before and after acute (23 patients) and chronic (23 patients) β-adrenoreceptor antagonism in patients with essential hypertension.

2. Sensitivity was inversely related to age (r = −0·60) and systolic blood pressure (r = −0·46); a positive relationship was noted between sensitivity and initial pulse intervals (r = 0·40).

3. Sensitivity increased significantly in patients less than 40 years of age after chronic treatment. No change occurred after acute treatment or in older patients treated chronically.

4. The fall in ambulatory intra-arterial blood pressure after chronic treatment was unrelated to alteration of baroreflex sensitivity.
Effect of Age on Hypertensive Stimuli and the Development of Hypertension in Brattleboro Rats
Authors: Dlouhá H. , Křeček J. , Zicha J.
Published: August 2015

1. In rats with inherited diabetes insipidus, unilateral nephrectomy plus drinking of 0·6% NaCl solution (saline) did not influence blood pressure in adult rats. However, when these factors applied before puberty, they produced hypertension.

2. We therefore analysed whether saline administration before puberty or unilateral nephrectomy before puberty was more important for this hypertensive response.

3. Saline drinking was found to be necessary for the response because hypertension was elicited by unilateral nephrectomy in adult rats only if saline consumption began before puberty.
Peptiduria in Experimental Fanconi Syndrome in Rats
Authors: Asatoor A. M. , Bending M. R. , Milne M. D.
Published: August 2015

1. The plasma concentrations and urinary output of proline and hydroxyproline contained in peptides were measured in normal rats and in rats with Fanconi syndrome produced by injection of sodium maleate. All animals received a prior injection of 10 mg of the dipeptide l-prolyl-l-hydroxyproline to increase plasma and urinary peptide content. There was a significant increase of urinary output of the two imino acids contained in peptides and a fall in their plasma concentrations.

2. It is concluded that increased output of peptides derived from collagen degradation in the experimental Fanconi syndrome in rats is at least in part due to diminished tubular reabsorption of these compounds from the glomerular filtrate. The results are claimed to be relevant to the increased output of urinary peptides in the Fanconi syndrome in man.
The Role of Dietary Lipid in the Regulation of Unconjugated Hyperbilirubinaemia in Gunn Rats
Authors: Gollan J. L. , Hole D. R. , Billing Barbara H.
Published: August 2015

1. The purpose of this study was to characterize the mechanisms of diet-induced hyperbilirubinaemia in Gunn rats with emphasis on the role of lipids, and to examine their relationship with regard to fasting hyperbilirubinaemia.

2. A lipid-free normocaloric diet produced a threefold increase in plasma bilirubin concentration (baseline 109.4 μmol/l), which was maximal by 10 days and thereafter remained constant. The level of hyperbilirubinaemia attained was not influenced by fasting or phenobarbitone, and returned to baseline concentration within 10 days of resuming a normal diet.

3. Determination of hepatic bilirubin showed that the magnitude of the hepatic bilirubin pool was increased by the lipid-free diet but was unchanged by fasting. Hepatic ligandin concentrations were comparable in fasted Gunn rats and those fed normal or lipid-free diets, although total hepatic ligandin was reduced in the fasted animals.

4. The hyperbilirubinaemic effect of the lipid-free diet was largely reversed by the inclusion of 10% lipid in the diet and was affected to a lesser extent by 5% lipid. Similar reductions in plasma bilirubin concentration were observed with a variety of other lipids (10%), regardless of their fatty acid chain length or degree of saturation.

5. In fasting animals a direct correlation was observed between plasma bilirubin and free fatty acid concentrations and insulin levels were greatly depressed, whereas in those fed on the lipid-free diet no significant changes were evident in plasma concentrations of free fatty acids or insulin.

6. Plasma bilirubin concentration was unrelated to alterations in plasma triglycerides produced by the administration of clofibrate. However, an unexplained decrease in plasma bilirubin (40%) without a significant change in triglycerides was noted when clofibrate was added to the lipid-free diet.

7. Analysis of kinetic data obtained from [14C]bilirubin clearance studies revealed that hyperbilirubinaemia associated with the lipid-free diet reflected a marked reduction (60%) in plasma clearance with no change in bilirubin turnover. This was accompanied by a relative redistribution of bilirubin from the extravascular pool to the plasma pool.

8. Although these studies indicate that fasting and the withdrawal of dietary lipid have some similar effects on bilirubin metabolism, it seems likely that different mechanisms are responsible for the hyperbilirubinaemia.
A Micropuncture Study of Proximal Tubular Function after Acute Hydrochlorothiazide Administration to Brattleboro Rats with Diabetes Insipidus
Authors: Walter S. J. , Laycock J. F. , Shirley D. G.
Published: August 2015

1. Renal function in anaesthetized Brattleboro rats with hereditary hypothalamic diabetes insipidus was studied with micropuncture techniques before, and 1–3 h after, a single injection of hydrochlorothiazide.

2. In rats given hydrochlorothiazide and kept in sodium and water balance, total glomerular filtration rate and superficial nephron filtration rate were similar to values in control animals, whereas fractional fluid reabsorption in the proximal tubule (as evidenced by tubular fluid/plasma inulin concentration ratios) was slightly, but significantly, reduced. This suggests that hydrochlorothiazide may have a small direct inhibitory effect on proximal tubular reabsorption.

3. When rats were given hydrochlorothiazide and the resultant extra urinary sodium losses were not replaced, there was a marked antidiuresis. In these animals total glomerular filtration rate was reduced by 23% and superficial nephron filtration rate by 27% when compared with values in control rats. Fractional proximal tubular fluid reabsorption increased significantly whereas absolute proximal fluid reabsorption was unaffected.

4. It is concluded that the reduction in body sodium which follows acute hydrochlorothiazide administration over-rides any inhibitory effect of the drug on proximal tubular reabsorption, and leads instead to an increase in fractional fluid reabsorption at this site. This effect, combined with the fall in glomerular filtration rate, results in a greatly reduced delivery of fluid to the more distal nephron segments, and is probably largely responsible for the observed antidiuresis.
Study of the Oligosaccharide Units from Mucus Glycoproteins of Meconium from Normal Infants and from Cases of Cystic Fibrosis with Meconium Ileus
Authors: Clamp J. R. , Gough M.
Published: August 2015

1. The mucus glycoproteins in meconium from normal infants and from infants having cystic fibrosis with meconium ileus have been studied.

2. Whereas normal meconium contained about 50% protein-bound carbohydrate, the meconium from cystic fibrosis contained only about 10%.

3. Glycopolypeptides were prepared from the mucus glycoproteins. The oligosaccharide units from this material were released and fractionated. The fractions ranged widely in size and composition.

4. The fractions from cystic fibrosis specimens had a significantly higher content of fucose than those from normal specimens.