bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal and extra-renal levels of renin mRNA in experimental hypertension
Authors: Samani Nilesh J. , Brammar William J. , Swales John D. 
Published: August 2015

1. Using a ribonuclease-protection assay, renin mRNA levels were compared in the kidneys, livers, brains, hearts and adrenal glands of two-kidney, one-clip Goldblatt hypertensive rats with those of age-matched control rats at 4 weeks (‘early’) and 20 weeks (‘chronic’) after clipping, and in the kidneys and adrenal glands of rats treated for 3 weeks with deoxycorticosterone and salt (deoxycorticosterone-salt hypertension) with those of control rats.
2. While marked changes were observed in kidney renin mRNA levels in all three experimental groups compared with their respective controls, in most of the extrarenal tissue studied minimal, if any, difference was seen in renin mRNA levels between the hypertensive and control rats.
3. The findings suggest that in these extra-renal tissues renin gene expression is differently regulated from that in the kidney, and particularly that it is not profoundly affected by changes in the level of circulating angiotensin II.
4. An increase in renin mRNA was observed in the adrenal glands of the ‘chronic’ Goldblatt rats, which may be of relevance to the maintenance of hypertension in this model.
Doxepin therapy for postprandial symptomatic hypoglycaemic patients: neurochemical, hormonal and metabolic disturbances
Authors: Lechin Fuad , van der Dijs Bertha , Lechin Alex , Lechin Marcel , Coll-García Eduardo , Jara Héctor , Cabrera Alejandra , Jiménez Vladimir , Gómez Francisco , Tovar Duilia , Rada Isaís , Arocha Luis 
Published: August 2015

1. Three oral glucose tolerance tests were performed in each of 32 symptomatic postprandial hypoglycaemic patients (before placebo, before doxepin therapy and after doxepin therapy). Plasma neurotransmitters were determined in parallel with assays of plasma insulin and glucose levels.
2. Three different types of patients were distinguished. Type I showed a low noradrenaline/adrenaline ratio, high dopamine levels and low platelet 5-hydroxytryptamine (serotonin) levels during basal periods. After a glucose load, late peaks of dopamine and free 5-hydroxytryptamine, which coincided with the symptoms but not with the nadir of plasma glucose, were observed. Type II showed a low basal plasma noradrenaline/adrenaline ratio. After a glucose load, progressive increases in adrenaline and decreases in glucose were seen. Adrenergic symptoms coincided with the nadir of glucose. Although type III patients showed hyperinsulinaemia after a glucose load similar to the other types of patient, they did not show hyperglycaemia, but rather exhibited a sustained and progressive reduction in plasma glucose. These patients were characterized by a high basal plasma noradrenaline/adrenaline ratio, high basal plasma levels of 4-hydroxy-3-methoxyphenylethyleneglycol and high basal levels of platelet 5-hydroxytryptamine, all of which increased after a glucose load. Systolic and diastolic blood pressure decreases paralleled reductions in heart rate and glucose. The nadir of plasma glucose occurred simultaneously with the appearance of symptoms (weakness, heartburn, oppressive chest pain, tension headache, abdominal cramps, dizziness, etc.). Therapy with doxepin led to disappearance of the symptoms within 3–4 weeks. Normalization of all other disordered variables (cardiovascular, metabolic and neurochemical, and the clonidine test) paralleled the disappearance of the symptoms.
3. Symptoms varied in the three types of patients and we conclude that they are related to hypoglycaemia-induced disorders of plasma neurotransmitters, rather than to hypoglycaemia per se. We postulate that an uncoping stress situation (type I and II patients) and depression (type III patients) underlie the physiopathological mechanisms.
Differential stimulation by oxygen-free-radical-altered immunoglobulin G of the production of superoxide and hydrogen peroxide by human polymorphonuclear leucocytes
Authors: Kleinveld H. A. , Sluiter W. , Boonman A. M. C. , Swaak A. J. G. , Hack C. E. , Koster J. F. 
Published: August 2015

1. The effect of free-radical-altered IgG (monomer and polymer u.v.-irradiated IgG), compared with that of native and heat-aggregated IgG, on the production rate of superoxide anion and hydrogen peroxide by granulocytes (polymorphonuclear leucocytes) from normal blood and granulocytes obtained from the blood and synovial fluid of patients with rheumatoid arthritis was studied.
2. Similar rates of superoxide production by granulocytes from normal blood at rest and in the presence of any form of IgG were found. In contrast, the rate of hydrogen peroxide production could be stimulated in a dose-dependent fashion by monomer or polymer u.v.-irradiated IgG.
3. The stimulatory effect of free-radical-altered IgG on the rate of hydrogen peroxide production did not occur in the presence of 2-deoxyglucose, which deprives the NADPH:O2 oxidoreductase of its substrate NADPH by inhibition of glycolysis and the pentose phosphate pathway. This points to a stimulatory effect on the direct divalent reduction of oxygen without intermediate superoxide production by this enzyme complex.
4. Granulocytes obtained from the blood and synovial fluid of patients with rheumatoid arthritis reacted differently to polymer u.v.-irradiated IgG. In the presence of this stimulus the rate of release of both superoxide and hydrogen peroxide was increased. Furthermore, these granulocytes synthesized superoxide and hydrogen peroxide at a higher rate than did granulocytes from normal blood in the presence of serum-treated zymosan but not in the presence of phorbol myristate acetate.
5. Taken together, these results indicate that the rate of superoxide and hydrogen peroxide production by the granulocyte NADPH:O2 oxidoreductase depends on the pathological condition of the donor and the type of stimulus used.
Urinary excretion of nitrogenous and non-nitrogenous compounds in the chronic ethanol-fed rat
Authors: Preedy Victor R. , Hammond Barry , Iles Richard A. , Davies SiâN E. C. , Gandy Joan D. , Chalmers Ronald A. , Peters Timothy J. 
Published: August 2015

1. The metabolic consequences of chronic ethanol feeding was investigated by assay of urinary metabolites. Male Wistar rats were fed a liquid diet containing 35% of total energy as ethanol or isovolumetric, isocaloric and isonitrogenous amounts of the same diet in which ethanol was substituted by isocaloric glucose (controls).
2. At 6 weeks the entire skeletal muscle mass was reduced by approximately 20%. The urinary excretion of nitrogen, urea and uric acid increased by between 23 and 128%. Urinary creatinine excretion was not significantly altered.
3. Urinary excretion of magnesium was significantly increased by 43%. Urinary excretion of sodium, potassium, calcium and phosphate was increased slightly (i.e. 5–22%), but this change was not statistically significant.
4. Proton n.m.r. spectroscopic analysis showed that ethanol feeding reduced the urinary excretion of citrate and 2-oxoglutarate (by approximately 50%), suggesting decreased citric acid cycle activity. There was an increased excretion of alanine (44%), but excretion of succinate and acetate was not significantly altered. Ethanol in the urine of ethanol-fed rats comprised approximately 2% of total ethanol intake and less than 1% of total energy intake.
5. Lactose was detectable in urine of ethanol-fed rats, but not in control rats, reflecting the reported decreased intestinal lactase activity and increased gut permeability in alcoholics. Urinary galactose excretion decreased by 41%, but relatively large increases in lactate excretion (50%) did not achieve statistical significance.
6. It was concluded that chronic ethanol feeding causes disturbances in whole-body nitrogen homoeostasis and alterations in intermediary metabolism.
Evidence for altered Na+/H+ antiport activity in cultured skeletal muscle cells and vascular smooth muscle cells from the spontaneously hypertensive rat
Authors: Davies J. E. , Ng L. L. , Ameen M. , Syme P. D. , Aronson J. K. 
Published: August 2015

1. Intracellular pH and Na+/H+ antiport activity were determined by a fluorimetric method in cultured skeletal muscle cells (myoblasts) and aortic vascular smooth muscle cells from spontaneously hypertensive and normotensive Wistar-Kyoto rats.
2. The intracellular pH was significantly more alkaline at three different extracellular pH values in both myoblasts and vascular smooth muscle cells from the spontaneously hypertensive rats than in those from the normotensive control rats.
3. A kinetic analysis of the Na+/H+ antiport activity in these cells showed that the raised activity in the spontaneously hypertensive rats was due to an increased maximal transport capacity in vascular smooth muscle cells and to an increase in the affinity of the antiport for internal H+ in the myoblasts.
4. When the extracellular pH was reduced in the skeletal muscle cells of both types of rat, the intracellular pH fell. However, in vascular smooth muscle cells, a reduction in the extracellular pH was not associated with a fall in the intracellular pH. This resistance of the intracellular pH to changes in the extracellular pH differentiates vascular smooth muscle cells from other cells that have been studied in this way.
Effects of acute insulin-induced hypoglycaemia on haemostasis, fibrinolysis and haemorheology in insulin-dependent diabetic patients and control subjects
Authors: Fisher B. M. , Quin J. D. , Rumley A. , Lennie S. E. , Small M. , MacCuish A. C. , Lowe G. D. O. 
Published: August 2015

1. The effects of acute hypoglycaemia on haemostasis, fibrinolysis, blood viscosity and erythrocyte aggregation were examined after acute insulin-induced hypoglycaemia in six normal male subjects and in six male patients with poorly controlled insulin-dependent diabetes. In the control subjects hypoglycaemia caused a significant increase in the concentration of von Willebrand factor, with no change in the concentrations of fibrinogen and cross-linked fibrin degradation products. Fibrinolysis was enhanced, as indicated by significant increases in tissue plasminogen activator concentration and the fibrin plate lysis area, with a fall in plasminogen-activator inhibitor activity, suggesting complex formation. Whole-blood and plasma viscosity increased significantly after hypoglycaemia, but there was no significant change in erythrocyte aggregation tendency.
2. In diabetic patients the increase in the concentration of von Willebrand factor was significantly greater than in the control group (analysis of variance, P &lt; 0.02). The basal concentration of tissue plasminogen activator was reduced at 3.7 ± 0.7 mg/l (mean ± sem) in the diabetic group compared with 8.5 ± 1.3 mg/l in the control group (Student's t-test, P &lt; 0.01), but thereafter the increase in response to hypoglycaemia was similar. The changes in the other variables were not significantly different from the changes in the control group.
3. During acute hypoglycaemia in poorly controlled diabetic patients there is promotion of haemostasis with a greater increase in the concentration of von Willebrand factor, which, in association with the increase in viscosity, might reduce perfusion in diabetic microangiopathy, leading to aggravation of the microvascular complications of diabetes.
Energy expenditure and substrate metabolism measured by 24 h whole-body calorimetry in patients receiving cyclic and continuous total parenteral nutrition
Authors: Pullicino E. , Goldberg G. R. , Elia M. 
Published: August 2015

1. Twenty-four hour energy expenditure and its components, i.e. ‘basal metabolic rate', activity energy expenditure and diet-induced thermogenesis were measured, using continuous whole-body indirect calorimetry, in patients receiving total parenteral nutrition while in remission from Crohn's disease (weight 51.9 ± 9.9 kg, body mass index 19.2 ± 2.0 kg/m2).
2. Total parenteral nutrition was infused continuously over 24 h in four subjects and cyclically, between 22.00 and 10.00 hours, in eight subjects. Twenty-four hour energy expenditure (6.83 ± 1.10 MJ/24 h) was lower than total energy intake (10.09 ± 1.63 MJ/24 h), resulting in a positive energy balance (3.26 ± 1.42 MJ) in all subjects. Repeated measurements of resting energy expenditure in the continuously fed subjects (5.82 ± 1.11 MJ/24 h) did not change significantly at different times of day (coefficient of variation 2.2–6.6%). In contrast, in cyclically fed subjects, resting energy expenditure was 24.2 ± 9.0% higher towards the end of the 12 h feeding period than the ‘basal metabolic rate', which was measured just before the start of the feeding period.
3. Diet-induced thermogenesis, calculated as the increment in resting energy expenditure above ‘basal metabolic rate’ over the 24 h period (adjusted for the reduction in energy expenditure during sleep), was found to be 0.60 ± 0.29 MJ or 6.1 ± 3.1% of the energy intake.
4. The energy cost of activity (activity energy expenditure) in the continuously fed patients, calculated as the difference between 24 h energy expenditure and the integrated 24 h measurements of resting energy expenditure, was 0.88 ± 0.53 MJ, i.e. 12.9 ± 5.9% of the 24 h energy expenditure.
5. The non-protein nonglycerol respiratory quotient exceeded 1.0 for varying periods of time (0.5–17 h) in 11 subjects, indicating net lipogenesis from carbohydrate.
6. The results demonstrate favourable rates of deposition, during intravenous feeding, of both energy and nitrogen over a 24 h period in patients recovering from an episode of Crohn's disease. The efficacy of these commonly used total parenteral nutrition regimens in these patients is related to three features that are absent in normal healthy individuals, namely a low basal metabolic rate, a low activity-related energy expenditure and prolonged periods of lipogenesis from carbohydrate.
Increased symptoms of hypoglycaemia in the standing position in insulin-dependent diabetes mellitus
Authors: Hirsch Irl B. , Heller Simon R. , Cryer Philip E. 
Published: August 2015

1. To test the hypothesis that patients with insulin-dependent diabetes mellitus perceive the symptoms of hypoglycaemia to a greater extent when they are in the standing position than when they are in the lying position, we assessed symptoms of hypoglycaemia, as well as heart rate and plasma noradrenaline and adrenaline concentrations, in both positions during hyperinsulinaemic glucose clamps on three occasions in seven patients.
2. Plasma glucose concentrations were clamped at 5.0 mmol/l (90 mg/dl) and 5.0 mmol/l on one occasion, at 5.0 mmol/l and 3.9 mmol/l (70 mg/dl) on another occasion, and at 5.0 mmol/l and 2.8 mmol/l (50 mg/dl) on yet another occasion.
3. During euglycaemia there was no effect of position on the symptom panels used to assess the symptomatic response to hypoglycaemia. However, at the plasma glucose concentration of 2.8 mmol/l, total (P&lt; 0.003) and neurogenic (P&lt; 0.005), but not neuroglycopenic, hypoglycaemic symptom scores were higher with the patients in the standing than in the lying position. Increments in total hypoglycaemic symptom scores, over those during the corresponding euglycaemic phase, were 5 ± 2 in the lying position and 11 ± 2 in the standing position (means ± sem, P &lt; 0.01).
4. Thus patients with insulin-dependent diabetes mellitus perceive symptoms of hypoglycaemia to a greater extent when they are in the standing position than when they are in the lying position because of enhanced neurogenic symptoms.
Measurement of tumour protein synthesis in vivo in human colorectal and breast cancer and its variability in separate biopsies from the same tumour
Authors: Heys S. D. , Park K. G. M. , McNurlan M. A. , Calder A. G. , Buchan V. , Blessing K. , Eremin O. , Garlick P. J. 
Published: August 2015

1. A method is described for measuring the rates of protein synthesis in vivo in human colorectal and breast tumours by the intravenous injection of l-[1-13C]leucine as a ‘flooding dose'.
2. The incorporation of isotope into colorectal tumour protein was measured in six patients, whose tumours were biopsied after the injection. Fractional rates of protein synthesis were calculated from the enrichment of leucine in protein and the average free leucine enrichment in plasma. The range of rates obtained was 17.2–33.9%/day, with a mean rate (± sem) of 22.5 ± 2.6%/day.
3. Tumour protein synthesis rates were also measured in 15 patients with breast cancer. The range of rates obtained was 5.3–15.9%/day, with a mean rate (± sem) of 10.3 ± 0.8%/day. These rates are significantly lower than those obtained with colorectal tumours (P &lt; 0.001).
4. In 9 of the breast cancer patients, protein synthesis was measured in multiple random biopsies taken from the same tumour. The mean (± sem) difference between the highest and lowest rates in biopsies from the same tumour was only 1.1 ± 0.3%/day. Only 13% of the variation in protein synthesis between separate tumours could be explained by sampling error because of variation within the tumour itself, the remainder being genuine variation between individual tumours.
Na+,K+-ATPase activity and hormones in single nephron segments from nephrotic rats
Authors: Vogt B. , Favre H. 
Published: August 2015

1. In the nephrotic syndrome the kidneys retain salt and water, which leads to oedema formation. The site of this sodium retention has been localized in the cortical collecting tubule by micropuncture studies. Whether or not this phenomenon is an intrinsic renal problem or is the consequence of changes in hormonal activities is still a matter of discussion.
2. Using the model of puromycin aminonucleoside-induced nephrotic syndrome in the rat, we measured Na+,K+-ATPase activity in nephron segments from control and nephrotic rats and investigated the regulatory role of aldosterone and endogenous-ouabain-displacing factor.
3. Nephrotic animals had a twofold increase in Na+,K+-ATPase activity in the cortical collecting tubule only (control versus nephrotic: 1065 ± 68 versus 2081 ± 274 pmol h−1 mm−1, P = 0.036), which was not modified by adrenalectomy and was independent of the kidney content of endogenous ouabain-displacing factor. Na+,K+-ATPase activity in the cortical collecting tubule correlated with the sodium balance in both control and nephrotic rats.
4. The data are consistent with the view that sodium retention in this model of the nephrotic syndrome is a primary event, i.e. an increase in sodium transport throughout the cortical collecting tubule expressed as a twofold increase in Na+,K+-ATPase activity which is no longer under hormonal regulation (aldosterone and endogenous ouabain-displacing factor).
Twenty-four hour intragastric acidity and plasma gastrin concentration profiles in female and male subjects
Authors: Prewett E. J. , Smith J. T. L. , Nwokolo C. U. , Sawyerr A. M. , Pounder R. E. 
Published: August 2015

1. Simultaneous 24 h intragastric acidity and plasma gastrin concentration profiles were determined in 35 healthy young women and 96 healthy young men.
2. The females had a consistently lower median hourly intragastric acidity, and a higher median hourly plasma gastrin concentration, throughout the 24 h.
3. The 24 h integrated intragastric acidity was significantly lower in the female group (females, 485 mmol · h · l−1; males, 842 mmol · h · l−1; P &lt; 0.001). The 24 h integrated plasma gastrin concentration was significantly higher in the female group (females, 407 pmol · h · l−1; males, 185 pmol · h · l−1; P &lt; 0.001).
Haemodynamic responses to psychosocial stress during the menstrual cycle
Authors: Manhem Karin , Jern Christina , Pilhall Martin , Shanks Guy , Jern Sverker 
Published: August 2015

1. The haemodynamic effects of hormonal changes during the menstrual cycle were examined in 11 normotensive women (age 20–46 years). The subjects were studied on days 2–8 (follicular phase) and days 18–26 (luteal phase) in a randomized order. A standardized mental stress test and a 24 h recording of ambulatory blood pressure and heart rate were performed.
2. Pre-stress resting levels of heart rate and blood pressure were similar during the two phases of the menstrual cycle.
3. During mental stress, the heart rate response was significantly greater during the luteal phase than during the follicular phase (14.7 versus 9.7 beats/min; P &lt; 0.05).
4. Blood pressure, plasma catecholamine concentrations and subjective stress experience increased significantly in response to stress, without any significant differences between the two phases.
5. During 24 h ambulatory monitoring, higher levels of systolic blood pressure and heart rate were observed in the luteal phase than in the follicular phase (P &lt; 0.005 and P &lt; 0.0001, respectively).
6. These data indicate that cyclic variations in female sex hormones not only affect systolic blood pressure and heart rate, but also alter the haemodynamic responses to psychosocial stress.
Intracellular pH in rat resistance arteries during the development of experimental hypertension
Authors: Izzard Ashley S. , MacIver David H. , Cragoe Edward J. , Heagerty Anthony M. 
Published: August 2015

1. In order to examine the effects of experimental hypertension on intracellular pH in mesenteric resistance arteries, intracellular pH was measured in mesenteric resistance arteries from rats with coarctation 72 h, 9 days and 28 days after the aorta was partially constricted between the origins of the renal arteries. Carotid arterial pressure was significantly raised at all time points.
2. Second-order mesenteric resistance arteries were mounted in a myograph and were loaded with the acetoxymethyl ester of the pH-sensitive dye 2′,7′-bis(carboxyethyl)-5,6-carboxyfluorescein. Morphological measurements demonstrated that arteries from rats with coarctation had an increased media volume at 9 days and at 28 days compared with vessels from sham-operated control animals, but this was only statistically significant at 28 days.
3. Resting intracellular pH was not significantly different at any time point in arteries from rats with coarctation compared with control animals, although there was a rise in intracellular pH in both groups of rats between 72 h and 9 days. The application of 4,4-di-isothiocyanatostilbene-2,2′-disulphonic acid produced a fall in intracellular pH which was significantly greater in the sham-operated rats at 9 days; this difference was not found at 28 days. Blockade of Na+/H+ exchange with 60 μmol/l ethylisopropylamiloride led to a similar fall in intracellular pH in both groups of rats at 9 days but a significantly greater fall in intracellular pH in arteries of rats with coarctation at 28 days. Activation with noradrenaline (10 μmol/l) induced acid changes in intracellular pH that were similar in both groups of rats.
4. It is concluded that induction of coarctation of the aorta was associated with the development of significant growth in mesenteric resistance arteries, but that this structural change was not associated with an intracellular pH that was significantly different from that seen in sham-operated control rats at any time. Increased regulation of intracellular pH by Na+/H+ exchange was observed only at 28 days, after medial growth had occurred, which argues against a fundamental role of this exchange system as a mediator of cell growth.