bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of indomethacin on urine concentration and dilution in the rat
Authors: Ray C. , Carney S. L. , Gillies A. H. B. 
Published: August 2015

1. The precise role of prostaglandins in modulating urine concentration and dilution is unclear. Evidence in vitro has recently cast doubt on the accepted theory that renal prostaglandins inhibit the hydro-osmotic effect of vasopressin.
2. Urine clearance studies were performed on indomethacin treated (prostaglandin deficient) and control anaesthetized water diuretic rats both before and during the addition of vasopressin in maximal (10 m-units) and supramaximal (100 m-units) concentrations.
3. Before the addition of vasopressin, indomethacin treatment inhibited the excretion of a water load by 48.7%. The mean papillary sodium concentration was also greater in this group of rats.
4. Vasopressin (10 m-units) increased the urine osmolality in control and indomethacin treated rats; however, the mean urine osmolality was greater in the indomethacin group (1521 ± 103 compared with 1120 ± 98 mosmol/kg; P &lt; 0.01), as was the papillary sodium concentration. A tenfold increase in vasopressin depressed the papillary sodium concentration to a level similar to that in the control group and produced a marked natriuresis. Consequently, the mean urine osmolalities and urine flows were similar in control and indomethacin treated rats.
5. These experiments suggest that a major function of renal prostaglandins is to increase the ability of the kidney to excrete a water load. Renal prostaglandins do not interfere with the vasopressin induced increase in distal nephron water permeability.
A family with mild hereditary xerocytosis showing high membrane cation permeability at low temperatures
Authors: Stewart G. W. , Ellory J. C. 
Published: August 2015

1. Radioisotopic cation transport studies are described in a family whose erythrocytes had previously been found to show an abnormal net efflux of potassium when cooled to room temperature. This net efflux effect, which was inherited as an autosomal dominant trait, was associated with a few target cells on the blood film and a mild compensated haemolytic state.
2. Measurements of intracellular electrolyte concentrations, cell water and of Na+ and K+ transport rates across the membrane at 37°C were consistent with a diagnosis of mild hereditary xerocytosis.
3. Studies of cation transport in the temperature range 20–37°C revealed that the fluxes attributable to the Na+-K+ pump showed a temperature dependence comparable with that in normal cells, but that the ouabain plus loop-diuretic insensitive fluxes of K+, which probably represent the ‘passive diffusional leak’ to K+, were less sensitive to temperature than normal over the range 20–37°C. These findings were held to account for the net efflux effect previously reported.
A circadian rhythm of proteinuria in patients with a nephrotic syndrome
Authors: Koopman M. G. , Krediet R. T. , Zuyderhoudt F. J. M. , De Moor E. A. M. , Arisz L. 
Published: August 2015

1. Circadian variations in proteinuria were studied in 17 patients with different types of glomerulopathies. During 3–4 successive days urine was collected over periods of 3 h under standardized conditions.
2. Thirteen of the 17 patients showed a circadian rhythm of their proteinuria with a maximum excretion in daytime around 16.00 hours and a minimum excretion at night around 03.00 hours.
3. In the majority of patients the urinary excretory rhythms of albumin, transferrin and immunoglobulin G were ‘in phase’ with each other and with the circadian rhythm of total protein excretion.
4. Nine patients had a larger degree of rhythmicity for immunoglobulin G than for transferrin excretion. In eight of them a circadian rhythm of the selectivity index of proteinuria was seen with the lowest index at night.
5. No relation was observed between the circadian rhythm of proteinuria and the type of glomerulopathy.
The porphyrogenic effects of calcium channel blocking drugs
Authors: Schoenfeld N. , Aelion J. , Beigel Y. , Epstein O. , Atsmon A. 
Published: August 2015

1. Treatment of monolayers of chick embryo hepatocytes with the calcium channel blocking drugs nifedipine and verapamil resulted in a decrease in the activity of uroporphyrinogen decarboxylase, an increase in the activity of δ-aminolaevulinate synthase and accumulation of porphyrins with uroporphyrin and heptacarboxylic porphyrin predominating.
2. Diltiazem, another calcium channel blocking drug, did not affect uroporphyrinogen decarboxylase activity and had a slight effect only on the accumulation of porphyrins.
3. Experiments with nifedipine and verapamil in the presence of various concentrations of calcium indicate that the porphyrogenic effect is apparently not related to blocking of calcium channels.
The calmodulin content of the epidermis in psoriasis
Authors: Mac Neil S. , Tucker W. F. G. , Dawson R. A. , Bleehen S. S. , Tomlinson S. 
Published: August 2015

1. The calmodulin content of epidermis was determined by assay of biologically active and radioimmunoassayable calmodulin in epidermal biopsy samples of 16 normal control subjects and 36 patients with psoriasis.
2. Calmodulin levels in the involved epidermis of patients with psoriasis were significantly greater than in epidermis of control subjects, with both methods of calmodulin measurement. Levels of calmodulin in the uninvolved epidermis were also elevated but to a lesser degree, achieving statistical significance only when measured by radioimmunoassay. However, the degree of correlation between the two measurements of calmodulin was poor for the patient samples, suggesting that each may measure a different form of calmodulin.
3. The specificity of the elevated calmodulin in psoriatic epidermis was investigated by measuring calmodulin in another unrelated tissue. Calmodulin activity in circulating peripheral blood lymphocytes of seven patients with psoriasis was similar to that found in the lymphocytes of ten normal volunteers.
4. The relationship between calmodulin and the hyperproliferative state of the psoriatic epidermis was investigated. No significant increase in calmodulin activity was found after mitogen stimulation of lymphocyte proliferation or after Sellotape-stripping of the epidermis by a protocol which has been shown to cause hyperproliferation of the epidermis.
5. Elevated calmodulin in psoriatic epidermis therefore appears to be a localized phenomenon of the disease and does not appear to be a consequence of the hyperproliferative state of the epidermis.
Effects of an intravenous saline load on erythrocyte sodium transport in normal human subjects
Authors: Boero Roberto , Quarello Francesco , Guarena Cesare , Rosati Clelia , Piccoli Giuseppe 
Published: August 2015

1. The effects of a 2 litre intravenous infusion of saline (0.9% NaCl solution) over 3 h on erythrocyte transmembrane sodium transport were studied in 12 normal human subjects.
2. After saline infusion a significant (P &lt; 0.01) reduction of both outward Na+, K+ pump- and Na+, K+ cotransport-mediated Na+ effluxes was observed. The Na+, Li+ countertransport rate and the passive Na+ permeability did not change.
3. The incubation of the subjects' erythrocytes, obtained on a separate occasion, with their own plasma taken after the saline infusion, induced an inhibition of both Na+, K+ pump and Na+, K+ cotransport outward sodium fluxes. The percentage decrease after incubation was closely correlated with the percentage reduction induced by the saline infusion in vivo (r = 0.93 for the pump and r = 0.96 for cotransport; P &lt; 0.01).
4. These data suggest that extracellular fluid volume expansion affects the release of circulating factors modulating sodium transport by the Na+, K+ pump and by Na+, K+ cotransport.
Short-term effects of β-adrenoceptor blocking drugs with and without cardioselectivity and intrinsic sympathomimetic activity on lipoprotein metabolism in hypertriglyceridaemic patients and in normal men
Authors: Durrington P. N. , Brownlee W. C. , Large D. M. 
Published: August 2015

1. In six patients with hypertriglyceridaemia presenting whilst receiving treatment with β-adrenoreceptor blocking drugs (mean serum triglycerides 31.2 mmol/l) the half-life (t1/2) of an intravenously administered triglyceride emulsion was 32.8 ± 7.9 min (mean ± sem) on β-blocker and 22.8 ± 4.8 min after stopping β-blocker treatment.
2. In three of these patients subsequent administration of a β-blocker with intrinsic sympathomimetic activity had no effect on t1/2.
3. In a cross-over trial of placebo, atenolol (β1-blocker), propranolol (β1- and β2-blocker) and pindolol (β1- and β2-blocker with intrinsic sympathomimetic activity) in 11 normal men t1/2 was 11.8±0.9, 12.6±1.1, 14.3±1.7 and 12.4±1.1 min respectively. None of the apparent differences achieved statistical significance, but in two men marked increases in t1/2 occurred on propranolol.
4. The concentrations of serum triglycerides and very low density lipoprotein cholesterol in the normal men were, however, increased by β-blockade, most markedly by pindolol.
5. Serum high density lipoprotein (HDL) cholesterol concentration decreased in normal men on β-blockers, most clearly on atenolol and propranolol. This decrease was due to a reduction in cholesterol in the HDL2 subfraction.
6. No statistically significant effects on serum low density lipoprotein cholesterol or apolipoprotein B concentrations occurred in the normal men.
7. The doses of atenolol and propranolol used in this study were equipotent as judged by the heart rate response to exercise.
Partial characterization of abnormal salivary proteins associated with rheumatoid arthritis
Authors: Mairs Robert J. , Beeley Josie A. 
Published: August 2015

1. Isoelectric focusing of parotid saliva from 33 patients with rheumatoid arthritis but without clinical evidence of salivary gland involvement revealed multiple abnormal proteins of pI 3.95–4.25 in all cases, whereas only two out of 16 samples from normal healthy individuals exhibited any similar bands.
2. Although rheumatoid factors of abnormally low isoelectric point and restricted heterogeneity were detected in this pI region in five of the diseased samples, these could not account for all of the bands even in these cases. The abnormal proteins did not otherwise cross-react with antisera to immunoglobulin (Ig) G, IgA or albumin.
3. Analysis of rheumatoid arthritis parotid saliva by a method involving adsorption of rheumatoid factors to immobilized rabbit immunoglobulin revealed the presence of salivary rheumatoid factors (in seven patients) of all the major immunoglobulin classes, including secretory-IgA in two patients.
4. Although these abnormal proteins are as yet uncharacterized, their presence could form the basis of a non-invasive procedure in the diagnosis of salivary gland and connective tissue disorders.
Iron uptake and ferritin synthesis in human erythroblasts
Authors: Hodgetts J. , Hoy T. G. , Jacobs A. 
Published: August 2015

1. The erythroblasts from four normal bone marrows were enriched by using an anti-myeloid monoclonal antibody (TG-1), and a polyclonal antibody against mononuclear cells to effect complement mediated lysis of unwanted cells.
2. The erythroblasts were cultured for 2h in medium containing [59Fe]transferrin and [3H]-leucine, then fractionated on Percoll gradients according to their density.
3. Whole cell iron uptake by early erythroblasts was greater than in the dense late erythroblasts. In all marrows, iron uptake into ferritin was highest in fractions containing the earliest erythroblasts and decreased with increasing erythroblast maturity. In three of the four marrows this paralleled the pattern of ferritin synthesis.
4. It seems likely that apoferritin is synthesized in response to the amount of iron taken into the cell and this iron is incorporated within the protein shell to form ferritin.
Age-related differences in granulocyte Chemotaxis and degranulation
Authors: McLaughlin B. , O'Malley K. , Cotter T. G. 
Published: August 2015

1. In the present study we have demonstrated that human peripheral blood granulocytes from elderly subjects exhibit reduced chemotaxis and degranulation in response to stimulation with fMet-Leu-Phe.
2. Cyclic AMP levels in non-stimulated cells were not significantly different (mean ± sem): 4.8 ± 0.6 and 3.9 ± 0.4 pmol/107 cells for young and elderly respectively. Stimulation with fMet-Leu-Phe (5 × 10−7 mol/l) for 30 s induced the production of cyclic AMP: 8.4 ± 0.5 and 6.7 ± 0.3 pmol/107 cells for young and elderly.
3. These findings, together with those previously published by us, suggest that cyclic AMP production and cellular functions which this molecule participates in are reduced in cells from elderly individuals.
Inhibition by omeprazole of adrenocortical response to ACTH: Clinical studies and experiments on bovine adrenal cortex in vitro
Authors: Howden C. W. , Kenyon C. J. , Beastall G. H. , Reid J. L. 
Published: August 2015

1. Omeprazole, a substituted benzimidazole, is a potent inhibitor of gastric acid secretion which is currently being evaluated in patients with peptic ulcer and Zollinger-Ellison syndrome.
2. Drugs which possess an imidazole nucleus have previously been shown to inhibit cortisol release from the adrenal cortex, secondary to inhibition of mitochondrial cytochrome P-450 dependent hydroxylation reactions.
3. In a double-blind placebo-controlled crossover study in healthy male volunteers, omeprazole (60 mg daily for 7 days) did not alter basal cortisol levels. The peak cortisol response to ACTH stimulation was significantly reduced. Cortisol levels 60 min after ACTH were 824 ± 27 nmol/l on omeprazole (mean ± sem), and 929 ± 35 on placebo (P &lt; 0.005).
4. In vitro, omeprazole caused a concentration-dependent inhibition of ACTH-stimulated cortisol release from isolated bovine adrenal cells (ED50 = 20 μg/ml). This was associated with a decrease in deoxycortisol synthesis. Therefore, unlike some other imidazole-containing drugs, the inhibitory effects of omeprazole are not entirely due to steroid 11 β-hydroxylase inhibition.
5. Substantial inhibition occurred at omeprazole concentrations which are higher than plasma levels normally achieved in clinical use. However, impairment of adrenocortical function may occur in patients on long-term high dose omeprazole treatment for Zollinger-Ellison syndrome.
The influence of streptozotocin-induced diabetes mellitus on fluid and electrolyte handling in rats
Authors: Hebden R. A. , Gardiner S. M. , Bennett T. , MacDonald I. A. 
Published: August 2015

1. Intakes and urine outputs of fluid and electrolytes were measured daily in rats before, and for 3 weeks after, induction of diabetes by intraperitoneal injection of streptozotocin (STZ; 60 mg/kg); control animals received saline.
2. Water intakes and urine outputs were increased on and after the first day after injection with STZ; after a transient period of negative water balance, fluid intakes and urine outputs increased in parallel.
3. Food intake was reduced for the first 3 days after injection of STZ but thereafter there was a steady increase. On the final experimental day, the food intake of the diabetic group was 60% greater than that of the control group.
4. Urinary electrolyte excretion was increased after injection of STZ; at the end of the experiment, the increase in urinary sodium excretion was similar to the increase in intake but the increase in urinary potassium excretion was less.
5. On day 21 after injection of STZ plasma sodium concentration and packed cell volume were significantly reduced in the diabetic group but plasma potassium concentration was not.
6. There was a difference between the measured osmolality and the calculated osmolarity of the plasma of the diabetic animals which was not seen in the controls. This difference was not due to pseudohyponatraemia, but was probably due to the presence of unidentified solutes, since there was a significant gap between the urinary osmolal and osmolar excretion in the diabetic animals that was not present in the control animals.
Tissue specific modulation of β-adrenoceptor number in rats with chronic hypoxia with an attenuated response to down-regulation by salbutamol
Authors: Winter R. J. D. , Dickinson K. E. J. , Rudd R. M. , Sever P. S. 
Published: August 2015

1. The number of β-adrenoceptors and their affinity for the radioligand 125I-labelled cyanopindolol (125I-CYP) were measured in crude membrane preparations of left ventricle, spleen and lung from Wistar rats exposed to 28 days continuous hypoxia.
2. β-Adrenoceptor density in the left ventricle was not significantly altered after exposure to chronic hypoxia (binding site maxima, Bmax: normoxic control 36 sem 5, hypoxic 24.8 sem 2 fmol/mg of protein). There was no change in β-adrenoceptor number in the spleen in response to chronic hypoxia (Bmax: normoxic control 76 sem 19 fmol/mg of protein, hypoxic 80 sem 15 fmol/mg of protein).
3. Chronic hypoxia resulted in a significant increase in β-adrenoceptor number in lung tissue (binding site maxima, Bmax.: normoxic control 406 (sem 31) fmol/mg of protein; hypoxic 535 (sem 30) fmol/mg of protein, P &lt; 0.01 without change in the dissociation constant (KD) of the radioligand.
4. β-Adrenoceptor subtypes in lung homogenates were studied by establishing displacement curves for 125I-CYP by ICI 118551 (a selective β2-antagonist). A significant difference was seen in the proportion of β1-/β2-adrenoceptor subtypes after hypoxia (normoxic control 66 sem 2.5%, hypoxic 79 sem 2.4% β2-adrenoceptors, P &lt; 0.01).
5. α1-Adrenoceptor number in lung membranes was measured with 125I-labelled 2-[β-(4-hydroxyphenyl)ethylaminomethyl]tetralone (125I-HEAT). No difference was seen in the number of α1-receptors in normoxia and in chronic hypoxia [Bmax.: normoxic control 48 (sem 3), hypoxic 48 (sem 5) fmol/mg of protein].
6. Treatment with salbutamol (2.5 mg/kg twice daily subcutaneously) did not reduce the number of β-adrenceptors in lung either during normoxia or in hypoxia. In spleen β-adrenoceptor number was decreased by 80% after chronic salbutamol treatment of rats in normoxia [Bmax.: normoxic control 76 (sem 19) fmol/mg of protein, treated 14 (sem 7) fmol/mg of protein, P &lt; 0.01]. After treatment during hypoxia, however, there was no significant reduction in β-adrenoceptor number in spleen [Bmax.: hypoxic control 80 (sem 15) fmol/mg of protein, treated 77 (sem 13) fmol/mg of protein].
7. These data suggest that there is a tissue specific modulation in β-adrenoceptor numbers in response to chronic hypoxia and that their capacity for down-regulation is reduced.
Haemodynamic effects of vasopressin in man are related to posture
Authors: Simpson H. C. R. , Zubillaga J. E. , Collier J. G. , Bennett E. D. , Ang V. T. Y. , Mehta N. , Jenkins J. S. 
Published: August 2015

1. Ten healthy volunteers received intravenous infusions of arginine vasopressin (AVP) at 0.1 m-unit min−1 kg−1 and 5% d-glucose on separate days. AVP caused a small fall in forearm blood flow and small rises in mean arterial pressure and systemic vascular resistance. Cardiac output was unaffected.
2. When subjects were tilted to 50° the fall in forearm blood flow was much greater, mean fall being 44.8% with AVP compared with 18.2% with d-glucose. Cardiac output also fell significantly more with AVP, and diastolic pressure, mean arterial pressure and systemic vascular resistance rose significantly more on tilting during AVP infusion than with d-glucose.
3. Six of the same volunteers were given sequential infusions of ‘low dose’ (0.0125 m-unit min−1 kg−1) and ‘high dose’ (0.3 m-unit min−1 kg−1) AVP on a third occasion. Tilting still produced a mean fall in forearm blood flow of 41.2% during low dose infusion, despite a mean plasma AVP level of only 1.9 pg/ml, which is well within the physiological range. When the AVP concentration was increased 24-fold to the high dose, forearm blood flow fell only a further 8.8%. The low dose infusion was also associated with a marked fall in cardiac output on tilting and a rise in systemic vascular resistance.
4. We conclude that AVP has profound haemodynamic effects in man at physiological concentrations. Although these effects are modest in the supine position, they become marked on tilting, suggesting a possible role for AVP in the postural control of blood pressure.
Age-dependent blood pressure response to increased salt intake in rats influenced by a transient renal ischaemia
Authors: Kuneš J. , Jelínek J. , Zicha J. 
Published: August 2015

1. The influence of renal dysfunction (induced by ischaemic injury) on the development of salt hypertension was studied in rats which were exposed to 60 min of renal ischaemia when either immature or adult. Saline-drinking age-matched animals served as controls. The blood pressure, plasma urea concentration, extracellular fluid volume (ECFV) and renal mass were measured 21 and 50 days after renal ischaemia.
2. Increments of plasma urea concentration and ECFV were considered to be indicators of renal dysfunction. Increased renal mass was used as an estimate of the degree of renal injury.
3. In adult rats, both plasma urea concentration and ECFV were increased 3 weeks after renal ischaemia. This correlated with a pronounced increase of renal mass. A similar relation of renal mass to ECFV was still present 50 days after renal ischaemia.
4. In rats treated when immature the increment of plasma urea concentration was much smaller and ECFV did not differ significantly from the control volumes.
5. A mild salt hypertension developed only in those rats which were treated when immature. On the other hand, the blood pressure tended to decrease in animals treated when adult.
6. It is concluded that mild renal dysfunction facilitates the development of salt hypertension in immature rats. This is in contrast with the reversed effects of extensive renal dysfunction in adult animals.
7. It is suggested that the age of animals is more important for the induction of salt hypertension than the degree of renal dysfunction.
Activation of human muscle pyruvate dehydrogenase with activity and immobilization
Authors: Ward G. R. , Macdougall J. D. , Sutton J. R. , Toews C. J. , Jones N. L. 
Published: August 2015

1. The activity of pyruvate dehydrogenase (PDH) was measured in samples of triceps muscle obtained in 15 males, before and after immobilization for 5 weeks and 5 months of strength training carried out in random order with cross-over of treatment.
2. Although the total PDH activity was unchanged at 300 nmol min−1 g−1, the proportion in the active form increased after strength training (62 ± 10.1%) and decreased after immobilization (12 ± 2.3%) compared with control (36 ± 3.4%).
3. In six subjects measurements were repeated after 10 min maximal exercise (arm ergometer). The proportion of PDH in the active form increased least after immobilization (to 52 ± 13.6%), compared with control (95 ± 11.7%) and post-training (98 ± 6.6%).
4. After exercise muscle glycogen fell to the greatest extent and lactate rose the least in the post-training state, with opposite findings post-immobilization, suggesting that PDH activation contributes to the control of lactate formation in muscle during heavy exercise, and that the effects of training and immobilization are mediated at least in part through changes in the activation of this regulatory enzyme.