bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurogenic hyperacute ascites in mice
Authors: Nelson David P. , Robin Eugene D. , Wong Ronald J. , Morin Mark E. , Bensch Klaus G. , Murphy Brian J. , Theodore James
Published: August 2015

1. Four groups of mice were subjected to controlled fatal head trauma and then evaluated for the presence of ascites (neurogenic hyperacute ascites, NHA). The animals died virtually instantaneously and without evidence of maintained pain or suffering. The volume of ascites was determined in one group of animals. Two of the traumatized groups were pretreated, one with the β-blocker propranolol and the other with the α-blocker phentolamine. A fifth, non-traumatized, group which was killed with ether inhalation served as a control group. Two more groups of non-traumatized mice were administered either the α-adrenergic agonist methoxamine hydrochloride or the β-agonist isoethrane mesylate before killing by ether inhalation, and then evaluated for ascites.

2. Transudative ascitic fluid was found in 87–100% of untreated traumatized mice and in no control animals. Pretreatment with phentolamine had no effect on the prevalence of ascites. Pretreatment with propranolol produced a significant decrease in the prevalence of ascites compared with trauma alone (P < 0.001). Isoethrane (β-agonist) administration caused ascites in 100% of the treated animals. Methoxamine (α-agonist) administration did not cause ascites.

3. A previously undescribed consequence of acute brain trauma is described (NHA) which appears to be mediated by β-sympathetic activity of central origin. NHA is inhibited by β-blockade and can be simulated with β-agonist administration.
Parathyroidectomy, cardiovascular reactivity and calcium distribution in aorta and heart of spontaneously hypertensive rats
Authors: Schleiffer R. , Pernot F. , Gairard A.
Published: August 2015

1. In order to elucidate the mechanisms by which parathyroidectomy (PTX), performed in young spontaneously hypertensive rats (SHR), delays the development and attenuates the level of hypertension, we studied, in vivo, cardiovascular reactivity (CVR, blood pressure response to bolus noradrenaline administration), aortic calcium distribution and cardiac calcium content in SHR with or without parathyroid glands.

2. PTX was performed in 6-week-old animals and experiments were done in pretreated anaesthetized animals 2 and 22 weeks after surgery. A significantly decreased CVR was observed 22 weeks after PTX in SHR-PTX as compared with controls.

3. These data are not specific for hypertensive animals since similar data are also obtained on nor-motensive Wistar rats treated in an identical fashion. In addition, after PTX in SHR and Wistar rats myocardial (auricle and ventricle) calcium content was more rapidly reduced (after 2 weeks) than aortic membrane-bound and cellular calcium fractions.

4. The present studies established that PTX decreases CVR and alters calcium content and distribution in the cardiovascular systems of rats from hypertensive and normotensive strains. Furthermore, the results confirm a requirement for the parathyroid glands in the pathogenesis of spontaneous hypertension in SHR and for the normal CVR.
The effects of posture on the metabolic and ventilatory response to low level steady state exercise
Authors: Weissman Charles , Askanazi Jeffrey , Rosenbaum S. H. , Hyman Allen I. , Milic-Emili J. , Kinney John M.
Published: August 2015

1. Low level exercise is frequently used to assess cardiac and pulmonary function. This study examines the differences in both metabolic and respiratory patterns between the sitting and supine position.

2. Six normal male subjects were studied in both positions during four levels of exercise (12.5, 25, 37.5 and 50 W). Oxygen consumption (Vo2), carbon dioxide production (Vco2) and minute ventilation (Ve2) were greater when sitting as were the ventilatory equivalents to O2 (Ve2/ Vo2) and CO2 (Ve2/ Vco2).

3. Respiration was compared at equivalent workloads; the greater minute ventilation observed during sitting was due to greater tidal volumes (Vt) and mean inspiratory flows (Vt/Vi,). Expiratory time (Te) was longer and inspiratory duration shorter under most conditions when sitting.

4. When breathing patterns were compared at similar degrees of minute ventilation, Vt, Te and Vt/Ti were greater when sitting, while respiratory frequency (fr) was slower.
The differential effect of arginine vasopressin on skin blood flow in man
Authors: Wiles P. G. , Grant P. J. , Davies J. A.
Published: August 2015

1. Physiological elevation of plasma vasopressin in man results in a small reduction in skeletal muscle blood flow but the action on skin blood flow has not been reported.

2. We have studied eight male subjects during infusion of arginine vasopressin (AVP) at 2 units/h for 90 min. Plasma levels of AVP, measured by radioimmunoassay, rose to 68.5 (7.0) pg/ml, mean (sem). Forearm and finger blood flow was measured with an electronic plethysmograph, hand interdigital skin-fold blood flow with a laser-Doppler blood flow meter and facial temperature with a thermocouple.

3. All subjects developed marked facial pallor during infusion of AVP, facial temperature falling from 34.2 (0.2) to 32.7 (0.1)°C (P < 0.001) then rising to 33.7 (0.1)°C (P < 0.01) after AVP was stopped. Hand interdigital skin-fold blood flow also fell from 2.6 (0.02) to 2.3 (0.02) V (P < 0.001) and rose sharply to 3.6 (0.2) V (P < 0.001) on stopping the infusion. There were small changes in forearm and finger blood flow: both rose, from 6.3 (0.1) to 6.9 (0.1) (P < 0.001) and 46.1 (1.0) to 54.3 (0.7) ml min−1 100 ml−1 (P < 0.001) respectively. Neither fell when AVP was stopped. Heart rate remained unchanged throughout.

4. These results indicate that high physiological levels of AVP, comparable with those attained during physical stress, produced a fall in blood flow in the face and interdigital skin-fold of the hand consistent with a fall in nutritional blood flow to skin. Blood flow to skeletal muscle, however, remained little changed whereas that through arteriovenous anastomoses in skin of the finger rose.

5. We conclude that AVP has a selective vasoactive effect in skin, constricting nutritional blood vessels and venules while promoting an increase in arteriovenous shunting of blood.
Changing effects on erythrocyte sodium and potassium during the development of chronic renal failure with anaemia in rats
Authors: Thomas T. H. , Mason C. , Illingworth K. M.
Published: August 2015

1. Rats were studied 7 days and 17 days after the onset of renal failure which was induced by a surgical technique.

2. Plasma urea, creatinine (PCr) and potassium had increased after 7 days; plasma potassium increased much more after 17 days but PCr was slightly lower.

3. Renal failure caused resetting of erythropoietic control to a lower level of packed cell volume (PCV). After 7 days renal failure some rats had a low PCV, whereas others still had a normal PCV apparently due to slower erythrocyte destruction of pre-renal failure cells.

4. After 7 days renal failure, rats with a normal PCV had an increased erythrocyte membrane leak to potassium that resulted in a low erythrocyte potassium [K+]RBC. This was accompanied by an increase in active sodium pump units [increased ouabain sensitive sodium flux (Fo) and its rate constant (ko)] that caused erythrocyte sodium ([Na+]RBC) to fall. The increased active pump units retarded the fall in [K+]RBC and may have extended the life of the normal erythrocytes in the renal failure environment.

5. The PCV was below normal in all rats after 17 days renal failure. [K+]RBC was increased and since ko was normal there appeared to be compensation to produce erythrocytes with reduced membrane leak to potassium with longer standing renal failure.

6. PCr was only related to PCV after 17 days renal failure and not in the earlier phase of erythrocyte destruction. The changes in erythrocyte membrane permeability were very significantly related to PCV after 17 days.
Effects of intra-arterial arginine-vasopressin infusions on peripheral blood flows in conscious dogs
Authors: Liard Jean-Francois
Published: August 2015

1. We reported in an earlier study that intravenous infusions of arginine-vasopressin (AVP), 220 pg min−1 kg−1 for 1 h, substantially reduced blood flow to the skin, skeletal muscle, pancreas, colon, small intestine, abdominal fat and myocardium [1] in conscious dogs. In the present study, we infused AVP directly into the artery supplying these organs and tissues in order to determine the relative contribution of local versus systemic mechanisms in the vascular resistance changes previously observed.

2. Regional blood flows were measured with radioactive microspheres in conscious, chronically instrumented dogs before and during intra-arterial infusions of AVP administered into the left axillary artery (n = 6), the left coronary artery (n = 6), and the cranial mesenteric artery (n = 6). The infusion rates were calculated to increase local, target organ plasma concentrations of AVP to the levels reached in our previous study while minimizing systemic changes.

3. Left axillary AVP artery infusion significantly reduced skin and compact bone blood flow, but had no effect on skeletal muscle blood flow. Intra-coronary AVP infusion had no effect on myocardial blood flow nor on cardiac output. Intramesenteric AVP infusion had no effect on blood flow to the colon, small intestine and abdominal fat, but significantly reduced blood flow to those areas of the pancreas which received blood from the cannulated artery.

4. Measurements in a limited number of dogs indicated that the local axillary and mesenteric venous levels of AVP were similar when the hormone was infused systemically at a rate of 220 pg min−1 kg−1 or intra-arterially at a lower rate.

5. These findings suggest that the increase in resistance measured in the skeletal muscle, small intestine, colon and abdominal fat after systemic administration of small amounts of AVP results in large part from indirect mechanisms. Direct vasoconstrictor effects of AVP at these plasma concentrations appear limited to the skin, the pancreas and the compact bones.
Prostacyclin in the circulation of patients with vascular disorders undergoing surgery
Authors: Ritter J. M. , Hamilton G. , Barrow S. E. , Heavey D. J. , Hickling N. E. , Taylor K. M. , Hobbs K. E. F. , Dollery C. T.
Published: August 2015

1. The object of this study was to investigate clinical conditions in which increased production of prostacyclin (PGI2) has been reported. 6-Oxo-prostaglandin F1α (6-oxo-PGF1α) is the stable hydrolysis product of PGI2 and was measured in plasma from patients undergoing hepatic or cardiac surgery and in unoperated patients with vascular and hepatic disease, using gas chromatography/mass spectrometry.

2. Blood obtained simultaneously from portal and peripheral veins, during emergency surgery for bleeding oesophageal varices in six patients with cirrhosis of the liver, contained very high concentrations of 6-oxo-PGF1α (range 99–11485 pg/ml of plasma). 6-Oxo-PGF1α was higher in portal than in peripheral blood in five out of six patients.

3. Six unoperated patients with cirrhosis and oesophageal varices which were not bleeding all had normal peripheral plasma concentrations of 6-oxo-PGF1α < 2 pg/ml (normal up to 5 pg/ml).

4. Seventeen patients with severe vascular disease had normal basal plasma 6-oxo-PGF1α concentrations (< 2 pg/ml).

5. Eighteen subjects with atheromatous coronary artery disease underwent aorta–coronary artery grafting, and plasma concentrations of 6-oxo-PGF,α were markedly elevated during surgery (range 55–1207 pg/ml).

6. We conclude that surgery stimulates PGI2 production substantially, and argue that the function of PGI2 may be to limit intravascular extension of thrombus from sites of haemostasis. Inappropriate PGI2 synthesis may contribute to the massive haemorrhage characteristic of oesophageal variceal bleeding.
Plasma atrial natriuretic peptide: Its relationship to changes in sodium intake, plasma renin activity and aldosterone in man
Authors: Sagnella Giuseppe A. , Markandu Nirmala D. , Shore Angela C. , Forsling Mary L. , MacGregor Graham A.
Published: August 2015

1. Plasma levels of immunoreactive atrial natriuretic peptide (IrANP), plasma renin activity, aldosterone and vasopressin were measured in 11 normotensive subjects on a low (10 mmol/day), a normal (150 mmol/day) and a high (350 mmol/day) sodium intake.

2. Plasma levels of IrANP increased significantly with increasing dietary sodium intake with levels (means ± sd) of 3.9 ± 2.1 pg/ml on the fifth day of the low sodium diet, 6.1 ± 3.4 pg/ml on the fifth day of the normal sodium diet and 11.4 ± 4.6 pg/ml on the fifth day of the high sodium diet.

3. Plasma renin activity and aldosterone decreased significantly with increasing sodium intake whereas plasma vasopressin was highest on the high sodium intake.

4. These results suggest that the atrial peptides may be a new and important component in the overall control of sodium and water balance during increased sodium intake.
The role of RT1 antigen differences in semi-allogeneic rat pregnancy
Authors: Power D. A. , Cunningham C. , Catto G. R. D.
Published: August 2015

1. The immunological mechanisms involved in sustaining normal semi-allogeneic pregnancies and in the enhancement of organ allografts were investigated in inbred rats.

2. The antigenic targets for alloantibodies formed after leucocyte transfusions and multiple allogeneic pregnancies were defined by the EA rosette inhibition (EAI) assay in several congenic and recombinant inbred rat strains.

3. Alloantibodies produced by leucocyte immunization (conventionally induced antisera) were directed only to RT1-encoded (major histocompatibility complex, MHC) antigens. Both RT1A (class I MHC) and either RT1B, D (class II MHC) or RT1C (Qa-like) antigens were targets for these alloantibodies; responses to the latter three antigens could not be separated with available congenic recombinant inbred rat strains.

4. Alloantibodies produced as a consequence of multiple semi-allogeneic pregnancies (pregnancy-induced antisera) were directed only to RT1A antigens.

5. Allogeneic pregnancies in which the paternal strain differed from the maternal strain only at the RT1A gene locus produced suppression of a subsequent maternal immune response.
Studies in vivo and in vitro of terbutaline-induced β-adrenoceptor desensitization in healthy subjects
Authors: Martinsson Arne , Larsson Kjell , Hjemdahl Paul
Published: August 2015

1. β-Adrenoceptor function was studied in eight healthy subjects before, during and 24 and 72 h after cessation of 2 weeks continuous oral treatment with the β2-adrenoceptor agonist terbutaline (sustained release, 7.5 mg twice daily). In vivo, blood pressure, heart rate, plasma noradrenaline and plasma cyclic AMP responses to isoprenaline (0.01, 0.02 and 0.05 μg min−1 kg−1 intravenously) were related to the plasma concentrations of isoprenaline. For comparison, β2-adrenoceptor function was evaluated in lymphocytes in vitro by studies of isoprenaline-induced accumulation of cyclic AMP and radioligand binding studies using 125I-iodohydroxybenzylpindolol.

2. In vivo, the β2-mediated plasma cyclic AMP response to isoprenaline was markedly attenuated during terbutaline treatment and was still reduced by 38% (P < 0.05) 72h. after discontinuation of treatment. The blood pressure and heart rate responses to isoprenaline were unaffected by treatment. Isoprenaline-induced elevations of plasma noradrenaline concentrations were markedly reduced during terbutaline treatment. This indicates an attenuation of isoprenaline-induced increases in sympathetic nerve function and could explain why no attenuation of the isoprenaline-induced vasodilatation was observed. Thus, plasma cyclic AMP seems to be a better marker than diastolic blood pressure when evaluating β2-adrenoceptor responsiveness in vivo in man, since it is not influenced by counter-regulatory increases in sympathetic nerve activity and/or noradrenaline overflow from sympathetic nerves.

3. In lymphocytes, the isoprenaline-stimulated cyclic AMP accumulation was reduced by 75% and the β-adrenoceptor binding sites were reduced by 40% 12 h after dosing. Also the lymphocyte β2-adrenoceptors recovered slowly after withdrawal of treatment. Normal responsiveness was not restored within 72 h after the last dose of terbutaline.

4. Thus, we obtained evidence in vivo and in vitro showing a markedly attenuated β2-adrenoceptor function, which persisted at least 72 h after discontinuation of terbutaline treatment. The slow rate of resensitization of β2-adrenoceptors after withdrawal may have practical implications in the treatment of, for example, asthma, since a state of ‘physiological β2-adrenoceptor blockade’ seems to be produced by β2-agonist treatment.
δ-Aminolaevulinic acid in plasma, cerebrospinal fluid, saliva and erythrocytes: Studies in normal, uraemic and porphyric subjects
Authors: Gorchein A. , Webber R.
Published: August 2015

1. ô-Aminolaevulinic acid (ALA) was determined by g.l.c. with electron-capture detection. Normal plasma level was 92 nmol/l (sd = 39, n = 89, range 24–270 nmol/l).

2. ALA was undetectable in 35 of 53 samples of normal cerebrospinal fluid (limit of assay 2 nmol/l). The mean of the other 18 samples was 19 nmol/l (sd = 10, range 6–36 nmol/l).

3. Salivary ALA was generally only 10–30% of the plasma level in normal and porphyric subjects.

4. Erythrocytes of normal and porphyric subjects contained no detectable ALA and were impermeable to its entry.

5. ALA clearance correlated closely with that of creatinine, consistent with it being excreted by glomerular filtration with limited tubular reabsorption.

6. In chronic renal failure, serum ALA was elevated to a maximum of three to four times the normal, but its urinary excretion was reduced, in keeping with lessened production.

7. In two cases of acute intermittent porphyria with overwhelming neuropathy the maximum plasma levels of ALA were 9 and 12 μmol/l. Haematin infusion decreased the ALA levels but without obvious clinical benefit. Limited neurological recovery occurred without major reduction in plasma levels of ALA.

8. One subject's attack was precipitated by pregnancy. The neonate was apparently normal, despite high levels of ALA in maternal plasma throughout gestation and a high level of ALA in the cord blood.

9. The observations described here do not support the view that ALA may be directly neurotoxic.
Decreased distensibility of resistance vessels of the skin in type 1 (insulin-dependent) diabetic patients with microangiopathy
Authors: Kastrup J. , Nørgaard T. , Parving H.-H. , Lassen N. A.
Published: August 2015

1. The distensibility of the resistance vessels of the skin at the dorsum of the foot was determined in 11 long-term type 1 (insulin-dependent) diabetic patients with nephropathy and retinopathy, nine short-term type 1 diabetic patients without clinical microangiopathy and in nine healthy non-diabetic subjects.

2. Blood flow was measured by the local 133Xexenon washout technique in a vascular bed locally paralysed by the injection of histamine. Blood flow was measured before, during and after a 40 mmHg increase of the vascular transmural pressure, induced by head-up tilt.

3. The mean increase in blood flow during headup tilt was only 24% in diabetic subjects with and 48% in diabetic patients without clinical microangiopathy, compared with 79% in normal non-diabetic subjects (P < 0.0005 and P < 0.05, respectively).

4. An inverse correlation between microvascular distensibility and degree of hyalinosis of the terminal arterioles in biopsies from the skin was demonstrated (r = − 0.57, P < 0.001).

5. Our results suggest that terminal arteriolar hyalinosis reduces the microvascular distensibility and probably increases the minimal vascular resistance, thereby impeding hyperaemic responses.
The effect of sodium taurocholate on proximal tubular reabsorption in the rat kidney
Authors: Better O. S. , Guckian V. , Giebisch G. , Green R.
Published: August 2015

1. Microperfusion of tubules in situ was used to study the direct effect of sodium taurocholate on reabsorption of fluid by the proximal tubule of the rat.

2. Sodium taurocholate (0.1 mmol/l) in the tubular perfusate reduced proximal tubular fluid reabsorption by approximately 30%.

3. Thus, the proximal tubule appears to be a major site at which bile salts cause a natriuresis in the rat, and possibly in obstructive jaundice in man.
Relationship between the renin–aldosterone system and atrial natriuretic polypeptide in rats
Authors: Hirata Yasunobu , Ishii Masao , Sugimoto Tokuichiro , Hiroaki Matsuoka , Ishimitsu Toshihiko , Atarashi Keiichiro , Sugimoto Tsuneaki , Miyata Atsuro , Kangawa Kenji , Matsuo Hisayuki
Published: August 2015

1. In order to examine the relationship between the renin–aldosterone system and atrial natriuretic polypeptide (ANP), we investigated the effects of α-human atrial natriuretic polypeptide (α-hANP) on the plasma concentrations of renin (PRC) and aldosterone (PAC), as well as the effects of captopril pretreatment on the natriuresis and blood pressure reduction induced by α-hANP in rats.

2. Although α-hANP infused into conscious rats at 0.67 μg min−1 kg−1 markedly increased the urinary excretion of sodium and decreased mean arterial pressure, its infusion did not change PRC; however, it significantly lowered PAC. Frusemide infusion at 20.8 μg min−1 kg−1 induced natriuresis comparable with that of α-hANP and it elevated both PRC and PAC, but mean arterial pressure was not altered.

3. Pretreatment of rats with captopril did not have any significant influence on the acute natriuretic and hypotensive effects of α-hANP.

4. Although the inhibitory effect of ANP on the renin-aldosterone system may be involved in the chronic modulation of body fluid volume and blood pressure, this effect does not seem to be directly involved in the acute natriuretic and hypotensive effects of the peptide.
Dissociation between circulating concentrations of immunoreactive growth hormone releasing factor and growth hormone in normal human subjects
Authors: Sopwith A. M. , Penny Elizabeth S. , Lytras N. , Besser G. M. , Rees Lesley H.
Published: August 2015

1. Using a highly specific radioimmunoassay we have measured immunoreactive human growth hormone releasing factor (ir-hGRF) concentrations in the peripheral circulation of a total of 12 normal subjects.

2. Neither insulin-induced hypoglycaemia, intravenous arginine nor oral carbohydrate caused any change in venous plasma ir-hGRF concentrations, despite the expected stimulation and suppression respectively of growth hormone secretion.

3. Growth hormone secretion was not increased by oral fat or protein but each of these two foods stimulated ir-hGRF concentrations two- to fourfold.

4. Spontaneous pulses of growth hormone secretion on control days were unaccompanied by any increase in plasma ir-hGRF.

5. The dissociation between peripheral circulating ir-hGRF and growth hormone responses demonstrated under different circumstances suggests that an important source of human growth hormone releasing factor lies outside the hypothalamus and that secretion from this source is unconnected with the normal control of pituitary growth hormone secretion.
Effect of partial ornithine carbamoyltransferase deficiency on urea synthesis and related biochemical events
Authors: Kay J. D. S. , Oberholzer V. G. , Seakins J. W. T. , Hjelm M.
Published: August 2015

1. The biochemical response to an intravenous alanine load of 0.25 g/kg was studied in nine adult female relatives of children with ornithine carbamoyltransferase deficiency. Six were classified as affected by partial deficiency and three as unaffected.

2. The plasma ammonium concentration showed no change after the alanine load in the unaffected group, but marked increases occurred in all but one of the affected group. The maximum rate of urea synthesis after the alanine load was decreased by 37% (P = 0.02) and delayed by 43% (P = 0.02) in the affected group.

3. In the affected group a low rate of urea synthesis was associated with high urinary orotate excretion, high maximum plasma ammonium concentration and delay in the time taken to reach the maximum rate of urea synthesis (Kendall concordance W = 0.55, P < 0.05).

4. The effects of a higher dose of alanine and of oral protein were compared. The alanine load of 0.25 g of alanine/kg body weight was shown to provide an adequate stimulus to urea synthesis with a more rapid return of ammonium concentration to the pre-load level than with the protein load.

5. The implication of these results in determining the distribution of flux control of urea synthesis, the discrepancy between them and predicted results and the necessary modifications to quantitative simulations are discussed.
Effects of a high K+/low Na+ diet on blood pressure in young spontaneously hypertensive rats
Authors: Sugden A. Louise , Straw James A. , Bean Barbara L.
Published: August 2015

1. Blood pressure was measured after treatment with a high K+, a low Na+ and a combined high K+/low Na+ diet in young spontaneously hypertensive rats (SHR).

2. A high K+ diet reduced blood pressure by approximately 10 mmHg during the development of hypertension. This decrease was accompanied by a significant increase in water intake and urine volume and a significant decrease in plasma renin activity (PRA).

3. A low Na+ diet also decreased blood pressure significantly, but, in contrast to the high K+ diet, water intake and urine volume significantly decreased and PRA increased.

4. When both diets were given together, the antihypertensive effects of both were eliminated. Thus while an increase in dietary K+ and a decrease in dietary Na+ are both effective antihypertensive regimens in SHR, the mechanism of action of each appears to be different and may be antagonistic in these animals.
Extrarenal synthesis of 1,25-dihydroxyvitamin D: Sensitivity to glucocorticoid treatment
Authors: Adami Silvano , Graziani G. , Tartarotti D. , Cappelli R. , Casati S. , Cantaluppi A. , Braga V. , Cascio V. Lo
Published: August 2015

1. The response of circulating 1,25-dihydroxyvitamin D [l,25-(OH)2D] to challenge with vitamin D treatment both before and after 7–10 days of prednisone therapy (25 mg/day) was investigated in five anephric subjects, six patients with chronic renal failure (CRF), two patients with vitamin D intoxication and four patients with hypoparathyroidism.

2. In anephric subjects serum 25-hydroxyvitamin D [25-(OH)D] rose from 58 ± 48 (sd) to 377±221 (sd) nmol/l after administration of 150 μg of 25-(OH)D3 for 1 month. Serum l,25-(OH)2D, which was barely detectable in only two out of five patients under basal conditions, rose to 30 ± 21 pmol/l after 2 weeks of therapy with 25-(OH)D3, but fell to 10 ± 5 pmol/l during prednisone treatment.

3. In CRF patients circulating l,25-(OH)2D rose from 37 ± 24 to 58 ± 24 pmol/l during 25-(OH)D3 therapy, but fell to 41 ± 31 pmol/l during prednisone treatment. In two patients with rheumatoid arthritis, hypercalcaemia due to vitamin D intoxication was associated with raised levels of 1,25-(OH)2D (288 and 317 pmol/l). Administration of prednisore resulted in suppression of l,25-(OH)2D levels (132 and 96 pmol/l respectively) and reduction of serum calcium to within the normal range.

4. In the hypoparathyroid patients prednisone therapy did not affect circulating 25-(OH)D levels but serum l,25-(OH)2D fell from 192 ± 42 to 117 ± 23 pmol/l and serum calcium from 2.41 ± 0.21 to 2.20 ± 0.05 mmol/l.

5. These findings indicate that a steroid sensitive extrarenal production of l,25-(OH)2D may occur in all subjects with a threshold serum concentration of the precursor 25-(OH)D.
A randomized controlled trial of the effect of dietary fibre on blood pressure
Authors: Margetts Barrie M. , Beilin Lawrence J. , Vandongen Robert , Armstrong Bruce K.
Published: August 2015

1. Eighty-eight healthy omnivores with normal blood pressure participated in a randomized, controlled, cross-over trial of the effect on blood pressure of increasing dietary fibre intake. Subjects were randomly allocated to a control group eating a low fibre diet throughout, or to one of two experimental groups eating a high fibre diet for one of two 6-week experimental periods. Changes in body weight, other dietary constituents and lifestyle factors were avoided as far as possible.

2. Twenty-four hour diet records showed a substantial increase in dietary fibre when subjects were on the high fibre diet.

3. There was no consistent effect of change in dietary fibre intake on group mean systoloic or diastolic blood pressures. Adjusting blood pressures for changes in other dietary components, plasma lipids, electrolytes, body weight and other lifestyle variables did not alter this result.

4. These findings do not support the hypothesis that the blood pressure lowering effect of a vegetarian diet is solely due to an increase in fibre intake.
The effect of prostaglandin E1 upon the pressor and hormonal response to exogenous angiotensin II in human pregnancy
Authors: Pipkin F. Broughton , Morrison R. , O'Brien P. M. S.
Published: August 2015

1. The effect of prostaglandin E1 (PGE1) on the pressor and hormonal response to angiotensin (ANG) II has been studied in 22 women in second trimester pregnancy. Three-point dose–response curves were initially determined for all women. Eleven then received an infusion of PGE1 while the remainder received an infusion of normal saline as controls. The dose–response curves to ANG II were re-studied after a period of stabilization.

2. Although assignation to treatment group was random, differences were found in age and basal blood pressure between the control group and those given PGE1. The pressor data from the PGE1 group were thus split by age for analysis.

3. The administration of ANG II alone was associated with significant (P<0.001 at all doses) pressor effects without accompanying bradycardia. Plasma renin concentration (PRC) was suppressed (P<0.001). Plasma aldosterone concentration rose (P<0.001), the magnitude of the rise being directly associated with the plasma ANG II concentrations achieved (P<0.05).

4. The infusion of PGE, had no significant effect on basal blood pressure, but evoked a sustained tachycardia in both age groups (P<0.001). Basal hormone concentrations were unchanged.

5. The pressor response to ANG II was blunted in the presence of PGE1, in both age groups, the overall effect being greatest when the initial response had been large (P<0.05). Measured plasma concentrations of ANG II were lower under these circumstances (P<0.02). PRC fell (P<0.05 for both groups) and plasma aldosterone concentrations rose (P<0.005 for the treated and P<0.001 for the control groups), but the magnitude of these changes did not differ significantly in the two groups.

6. These data support the hypothesis of a for the vasodilator prostaglandins in minimizing the potential pressor effects of the raised ANG II concentrations seen in pregnancy.
Amiloride inhibits the rise of urinary kallikrein excretion induced by frusemide administration in the rat
Authors: Obika L. F. O. , MARIN-GREZ M.
Published: August 2015

1. The effect of amiloride administration on the urinary kallikrein response to the injection or continuous infusion of frusemide in normal Sprague–Dawley rats was investigated.

2. Injections of frusemide induced repeatedly an increase in urinary kallikrein excretion. This effect was suppressed by amiloride. Amiloride also blocked the response to mannitol injection. A continuous infusion of frusemide lasting 100 min also induced an increase in urinary kallikrein excretion which persisted throughout the experiment. This response was completely blocked by the injection of amiloride.

3. Urinary kallikrein excretion was directly and positively related to urine volume and urinary sodium excretion before and after amiloride injection. The regression lines had markedly decreased slopes after amiloride administration. The urinary kallikrein excretion was also positively related to the urine volume and urinary sodium excretion when frusemide was continuously infused. However, these relationships were abolished after amiloride injection.

4. In both the injection and the infusion experiments, there was a direct relationship of urinary kallikrein excretion to urinary potassium excretion. Although this relationship persisted after amiloride injection, the regression line was shifted to the left.

5. The suppression of the kallikrein stimulating effect of frusemide by the sodium channel blocker amiloride indicates that distal tubule sodium re-absorption is the triggering factor in urinary kallikrein excretion. The study suggests that the mechanism involved in the release of kallikrein by the distal tubular cells is linked to the renal mechanism affected by amiloride.
The effects of four β-adrenoceptor antagonists during modest exercise on plasma ammonia and heart rate
Authors: Hall P. E. , Smith S. R. , Kendall M. J.
Published: August 2015

1. Plasma ammonia and heart rate were measured in normal volunteers before, during and after an exercise test following administration of placebo, propranolol, pindolol, metoprolol and nadolol.

2. Small changes in plasma ammonia occurred during exercise after placebo. However, all four β-adrenoceptor antagonists produced considerably greater rises. This effect was most marked after propranolol with the response to pindolol, metoprolol and nadolol being similar and intermediate between placebo and propranolol.

3. Resting heart rate was reduced by all the β-adrenoceptor antagonists except pindolol. Exercise induced changes in heart rate were significantly reduced to a similar degree by all the β-adrenoceptor antagonists.
Multiple forms of immunoreactive renin in human adrenocortical tumour tissue from patients with primary aldosteronism
Authors: Mizuno Kenji , Ojima Motoko , Hashimoto Shigeatsu , Tani Makio , Niimura Susumu , Kunii Nobuyasu , Yabe Ryuji , Watari Hiroaki , Inagami Tadashi , Fukuchi Soitsu
Published: August 2015

1. There is increasing evidence which suggests that the adrenal gland contains the renin–angiotensin cycle. The localization of renin has been reported to be mainly in the zona glomerulosa rather than the fasciculata medullary portion. In the present study we have investigated extracts from aldosteronomas (n = 3), which are believed to derive from the zona glomerulosa cells. In addition, we have attempted to characterize the biochemical properties of the adrenal renin.

2. Sizable quantities of renin-like activity (32.0 ± 7.7 ng of angiotensin I generated h−1 mg−1 of protein, mean ± SEM) were detected in the extracts. This renin-like activity was inhibited by anti-renin antibody raised against pure renin (mean, 95% of the total renin-like activity), indicating that it was not due to the non-specific action of proteases such as cathepsin D.

3. The optimum pH of the tissue renin-like enzyme was 6.0 for rat plasma substrate. Differences were found, however, in the molecular mass (36000, 37000, 44000 and 48000), binding to concanavalin A and isoelectric points (4.40, 4.68 and 5.00).

4. These results confirm the existence of specific renin in aldosteronoma. Renin microheterogeneity could be evidence for local production of the enzyme.
The effect of insulin-induced hypoglycaemia on gastrointestinal motility in man
Authors: Fellows I. W. , Evans D. F. , Bennett T. , Macdonald I. A. , Clark A. G. , Bloom S. R.
Published: August 2015

1. The effect of insulin-induced hypoglycaemia on gastro-jejunal motility was studied in five, healthy, male subjects using tethered, pressure sensitive, radiotelemetry capsules.

2. Thirty minutes after the intravenous injection of soluble insulin (0.15 unit/kg body weight), a significant reduction in blood glucose concentration (control: 5.26 ± 0.19 sem mmol/l; insulin: 1.48 ± 0.44 mmol/l; P < 0.001) was associated with a rise in heart rate (mean peak rise 29 ± 8 beats/min, P < 0.05), systolic arterial blood pressure (mean peak rise 28 ± 4 mmHg, P < 0.01) and plasma pancreatic polypeptide concentration (control: 20 ± 7 pmol/l; insulin: 287 ± 66 pmol/l; P < 0.01). These events coincided with a short period of jejunal motor activity, which was not associated with gastric motor activity nor with raised plasma motilin concentrations.

3. During the control study, there were no changes in blood glucose concentration, heart rate, arterial blood pressure or plasma pancreatic polypeptide concentrations, and there was no jejunal motor activity.

4. The interval between successive gastric migrating motor complexes (MMC) was not significantly different in the insulin and control studies (control: median interval 110 min, range 108–148 min; insulin: median interval 124 min, range 115–125 min), suggesting that the fasting gastro-jejunal MMC and jejunal motor activity arose independently.

5. Insulin-induced hypoglycaemia is accompanied by jejunal motor activity, which may underlie the abdominal symptoms associated with hypoglycaemia.
The influence of oral alkali citrate on intestinal calcium absorption in healthy man
Authors: Rüumenapf G. , Schwille P. O.
Published: August 2015

1. The influence of citrate on intestinal calcium absorption (CaA) was studied in eight healthy males.

2. On separate occasions, either a load containing 5 mmol of calcium chloride and 21 mmol of citrate in the form of sodium potassium citrate or a citrate-free vehicle load corrected for pH and cations was ingested. CaA was measured over 3 h with a 47Ca–85Sr double tracer method.

3. After citrate administration, 10 min fractional CaA decreased significantly from 30 to 110 min post-load, and 3 h cumulative CaA dropped to 54.6 ± (sem)6.1% of the total dose as opposed to 76.3 ± 4.5% after vehicle administration (P < 0.002). Citrate administration raised serum and urinary citrate, but had little effect on blood acid–base status. After both loads, urinary specific activity of 47Ca significantly correlated with 3 h cumulative CaA, while citrate administration decreased urinary calcium excretion only slightly as compared with vehicle.

4. The results suggest that, in man, higher doses of oral citrate inhibit CaA, probably by way of intraluminal complexation of calcium by citrate.

5. The finding might help explain the fall in urinary calcium excretion observed in patients treated with alkali citrate for recurrent calcium urolithiasis.
Permeability of the rat small intestine to carbohydrate probe molecules
Authors: Hamilton I. , Rothwell J. , Archer D. , Axon A. T. R.
Published: August 2015

1. Absorption of carbohydrate probe molecules from ligated loops of rat small intestine was studied. Absorption was determined by measuring recovery of molecules in the urine, corrected for incomplete recovery after intravenous injection, and was examined for correlation with several parameters of molecular dimension.

2. Absorption depended on molecular volume rather than relative molecular mass, molecular radius or molecular area.

3. Molecules with a molecular volume below 225 × 10−3 nm3 were absorbed to a greater extent than larger molecules, and absorption was affected critically by molecular volume, small changes in volume producing considerable variation in absorption.

4. Absorption of larger molecules was not affected by changes in volume within the range 362 × 10−3–1128 × 10−3 nm3.

5. These findings support the concept that there are at least two aqueous diffusion pathways across the intestinal mucosa, small molecules diffusing through a small channel of finite dimension, compatible with a transcellular aqueous pore, whilst large molecules diffuse through a less frequent pathway of considerably larger dimensions.
Measurement of secretion in nasal lavage
Authors: Bisgaard Hans , Krogsgaard Ole W. , Mygind Niels
Published: August 2015

1. The amount of admixture in nasal lavage fluids was determined by addition of 99mTc labelled albumin, providing a correction factor for measurements of cellular material and humoral substances in nasal lavage return as well as a quantitative measure of nasal secretions.

2. Albumin was chosen as marker molecule, since only negligible amounts were absorbed or adsorbed to the mucosa during the nasal lavage.

3. Labelling of the albumin with 99mTc ensured an accuracy of measurements only limited by the precision of the weighing. The isotope allowed for the determination of the amount of admixed secretion to be carried out on the whole sample of lavage fluid, thereby avoiding the necessity of complete admixture between marker and lavage fluid which would be pertinent to marker molecules measured chemically. The radiation from a nasal lavage is minimal and the procedure is fully acceptable for repeated use in humans.

4. The nasal lavage technique adopted allowed the return of 99.2% (median value) of the instilled volume. The area irrigated was visualized on a gamma-camera, and was demonstrated to cover an area larger than the area reached by challenge from a pumpspray, i.e. a large part of the nose, yet not the oropharynx.

5. A dose related increase in nasal secretion harvested by the nasal lavage in 10 persons challenged with histamine chloride could be demonstrated by this technique.

6. It is concluded that the use of 99mTc-albumin in a nasal washing provides a safe, simple and quick method for determination of the admixed nasal secretion with a remarkable degree of accuracy. The method is therefore suggested to improve determinations of admixture in nasal lavage fluid.
Erythrocyte cation fluxes during the menstrual cycle in normal female subjects
Authors: Monaghan J. C. , Willcocks D. A. , Sinosich M. J. , Stokes G. S.
Published: August 2015

1. Studies of erythrocyte cation transport mechanisms in vitro were performed on eight normotensive, premenopausal female subjects at the mid-points of the follicular and luteal phases of their menstrual cycles. Concurrent plasma concentrations of 17β-oestradiol, progesterone, aldosterone and renin activity were measured.

2. Ouabain-resistant, frusemide-resistant rubidium influx (an index of passive potassium diffusion) was significantly lower in the luteal than the follicular phase.

3. In further studies in four of the eight subjects, the mean rate constant of the rubidium influx measurement was also lower in the luteal than in the follicular phase.

4. There were no changes in Na+-K+ co-transport, sodium pump activity or intracellular cation concentrations throughout the cycle.

5. There was a tenfold fall in the mean plasma 17β-oestradiol/progesterone ratio, as well as increases in plasma aldosterone concentration and renin activity between the mid-follicular and mid-luteal phases.

6. We conclude that changes in plasma oestrogen/progesterone ratio during the menstrual cycle may be associated with alterations in passive potassium diffusion.
Enhanced diurnal variation of blood pressure in the renal hypertensive rat: effect of angiotensin II suppression
Authors: Wallace E. C. H. , Balmforth A. J. , Morton J. J.
Published: August 2015

1. Chronic two-kidney, one-clip hypertensive rats were infused with captopril for 5 days and the daily variability of blood pressure compared with that for both hypertensive rats infused with glucose and normotensive animals.

2. Blood pressure was measured continuously using a computer data collecting system.

3. Normotensive animals showed a stable level of arterial pressure throughout each 24 h period with troughs occurring when they slept during the daytime.

4. Hypertensive animals given glucose had an enhanced diurnal rhythm of blood pressure compared with normotensive rats, with peaks occurring during periods of activity at night as well as troughs when they slept during the day.

5. Hypertensive rats given captopril retained this enhanced pressure variability, in spite of the fact that blood pressure was significantly lower and angiotensin II was suppressed.

6. These results suggest that angiotensin II is not involved in the increased blood pressure variability of renal hypertension and that some other irreversible mechanism is responsible.
Loop-acting diuretics do not bind to Tamm–Horsfall urinary glycoprotein
Authors: Brunisholz M. C. , Lynn K. L. , Hunt J. S.
Published: August 2015

1. Binding between the radiolabeled loop-acting diuretics ([14C]frusemide, [14C]ethacrynic acid and [3H]bumetanide) and human Tamm–Horsfall glycoprotein or human serum albumin in vitro was evaluated by equilibrium dialysis.

2. The diuretic action and binding to urinary Tamm–Horsfall glycoprotein of the radiolabeled diuretics in vivo, after intravenous administration, were examined in rabbits.

3. In vitro, all three radiolabeled diuretics bound strongly to human serum albumin, but not to Tamm–Horsfall glycoprotein.

4. Radiolabeled frusemide and bumetanide, but not ethacrynic acid, caused a diuresis in rabbits, but no binding between the drugs and Tamm–Horsfall glycoprotein was seen in vivo.

5. Binding to Tamm–Horsfall glycoprotein does not appear to be an important mechanism in the action of loop diuretics.
Detection of Hypercapnia by Normal Subjects
Authors: Schwartzstein R. M. , Hive K. La , Pope A. , Steinbrook R. A. , Leith D. E. , Weiss J. W. , Fencl V. , Weinberger S. E.
Published: August 2015

1. To investigate whether changes in Paco2 can be detected independently of the CO2-induced changes in pulmonary ventilation, we tested five normal subjects for the ability to distinguish different levels of end-tidal Pco2 (PETco2) while holding minute ventilation constant.

2. Helped by a visual feedback system, the subjects maintained a constant ventilation targeted at a level that was higher than that dictated by the chemical drive at PETco2 = 50 mmHg (6.7 kPa). End-tidal Pco2 was held at 40 mmHg (5.3 kPa) during the first 2 min of each test trial ('control period'); then, for 4 min ('test period'), PETco2 was either elevated to 50 mmHg or kept at 40 mmHg. Twelve runs were performed by each subject.

3. In 24 out of the total 30 trials (80%) in which PETco2 was raised during the test period to 50 mmHg, the subjects detected the changes. There was one false positive result (3%), when PETco2 kept at 40 mmHg during the test period was reported as different from control. In four out of the five subjects the ability to detect the change in PETco2 from 40 to 50 mmHg was statistically significant.

4. We conclude that increases in PETco2 can be detected independently of changes in the absolute level of ventilation.
Changes in plasma renin, insulin, aldosterone and arginine vasopressin during plasmapheresis
Authors: Rainfray MUriel , Pruszczynski Wojciech , Bussel Annette , Ardaillou Raymond
Published: August 2015

1. Nineteen patients with a spectrum of immunologically related disorders were studied before and immediately after plasmapheresis for changes in plasma aldosterone, insulin and arginine vasopressin (AVP). Renin was also measured in 11 of these patients by direct radioimmunoassay. 125% of the initial plasma volume was replaced, which corresponded to a predicted removal of 72% for any plasma constituent.

2. The intial, final (experimental) and final (predicted) concentrations (means ± sem) were 337 ± 50, 185 ± 23 and 100 ± 16 pg/ml respectively for renin, 465 ± 86, 146 ± 38 and 124 ± 22 pmol/l respectively for aldosterone, 218 ± 35, 69 ± 11 and 63 ± 11 pmol/l respectively for insulin, 7.2 ± 1.9, 6.1 ± 0.5 and 1.8 ± 0.2 pmol/l respectively for AVP. The predicted final concentration was calculated from the initial concentration and the fraction of plasma volume exchanged. The experimental final concentration was lower than the initial concentration for renin, aldosterone and insulin (P < 0.001) but not for AVP. The predicted final concentration was lower than the experimental final concentration for AVP and renin (P < 0.001) but not for aldosterone and insulin. Plasma volume, osmolality, glucose, sodium and potassium concentrations did not change significantly.

3. The concentrations of renin, aldosterone, insulin and AVP in the removed plasma were 84 ± 17 pg/ml, 179 ± 36, 98 ± 15 and 4.8 ± 0.7 pmol/l respectively. The amount subtracted expressed as percentage of the total amount present in plasma was markedly greater for AVP than for the three other plasma constituents.

4. These results demonstrate that the response of the releasing cells to the fall in the plasma concentration of their secretory product does not follow the same kinetics for all substances. There is probably for AVP a fast releasing pool stimulated by a negative feedback.