bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.