bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Acidosis is a Potent Stimulus for Cellular Inorganic Phosphate Generation in Uraemia
Authors: Bevington Alan , Brough Dennis , Baker Frease E. , Hattersley Jane , Walls John 
Published: August 2015

1. During metabolic acidosis, significant fluxes of inorganic phosphate (Pi) may occur from cellular to extracellular fluid. In this study Pi was measured in erythrocytes of uraemic patients before and after haemodialysis and was related to their plasma pH (acidosis), plasma Pi (hyperphosphataemia) and cellular organic phosphate concentrations.
2. Before dialysis, the ratio of cellular to extracellular Pi concentration correlated inversely with plasma pH, increasing 2.5-fold as pH fell from 7.4 to 7.2.
3. An increase in cellular Pi similar to that seen in the patients was observed within 90 min of adding acid to normal erythrocytes in vitro.
4. The total Pi content of the cell suspension increased 25% on decreasing plasma pH from 7.4 to 7.2, largely as a result of generation of Pi from 2,3-bisphosphoglycerate in the cells. This was accompanied by net efflux of Pi into plasma.
5. In addition, the increase in the steady-state cellular Pi concentration on adding a constant extracellular Pi load was 50% greater at pH 7.2 than at 7.4, implying that alterations in the regulation of the transmembrane Pi gradient also contribute to the rise in cellular Pi observed at low pH.
6. At normal plasma Pi concentration (1 mM), glycolytic flux (lactate production) was inhibited by 20% when pH was lowered from 7.4 to 7.2. However, this inhibition was blocked when cellular Pi was increased by adding Pi to the plasma in vitro.
7. Metabolic acidosis is therefore a potent stimulus for Pi generation in erythrocytes, and this Pi may serve to stimulate glycolysis which is normally inhibited by low pH.
Comparison of Intraperitoneal and Subcutaneous Insulin Administration on Insulin Sensitivity and Serum Lipids in Type I Diabetic Patients on Continuous Ambulatory Peritoneal Dialysis Treatment
Authors: Lahtela Jorma T. , Mustonen Jukka , Pasternack Amos 
Published: August 2015

1. The metabolic effects of intraperitoneal and subcutaneous insulin delivery were compared in a crossover manner in six C-peptide-negative diabetic patients with end-stage renal disease on continuous ambulatory peritoneal dialysis. Each treatment period lasted at least 3 months. Hyperinsulinaemic euglycaemic clamp was performed and glucose turnover assessed using [3-3H]glucose as a tracer.
2. During intraperitoneal delivery the daily insulin dose was 2.4 times higher than during subcutaneous administration and glycaemic control was significantly better (HbA1c 7.63% ± 0.46% and 9.52% ± 0.51% during intraperitoneal and subcutaneous insulin respectively, P &lt; 0.01). The number of hypoglycaemic episodes was lower during intraperitoneal insulin than during subcutaneous therapy.
3. Intraperitoneal insulin resulted in an enhanced glucose disposal rate (P &lt; 0.01) and reduced fasting hepatic glucose production (P &lt; 0.01). High-density lipoprotein-cholesterol decreased and the ratio of low-density lipoprotein/high-density lipoprotein-cholesterol increased significantly (P &lt; 0.05) during intraperitoneal insulin delivery.
4. The results suggest that intraperitoneal insulin, while resulting in better glycaemic control and improved insulin sensitivity than subcutaneous insulin, increases serum triacylglycerol and total cholesterol and reduces high-density lipoprotein-cholesterol, possibly via a direct effect on the liver.
Is Voluntary Control of Breathing Impaired in Patients with Chronic Obstructive Pulmonary Disease?
Authors: Cohen Eytan , Murphy Kevin , Adams Lewis , Guz Abraham , Benchetrit Gila 
Published: August 2015

1. To assess whether voluntary control of breathing is impaired in patients with chronic obstructive pulmonary disease, a group of such patients performed a tracking task, requiring volitional control of respiratory muscles.
2. Eight patients (mean age 60 years; mean ratio of forced expiratory volume in 1 s to forced vital capacity = 31%) took part in the study. Five of the seven patients in whom blood gas measurements were made were mildly hypoxaemic (Pao2 = 53–71 mmHg), and one of these was hypercapnic (Paco2 = 55 mmHg). Each subject performed a compensatory ventilatory tracking task using a tracking system which comprised a fixed target displayed on a monitor screen and a cursor moving in a line bisecting the target. The position of the cursor was perturbed by a forcing function and patients were required to keep the cursor on the target by breathing in and out of a spirometer.
3. To allow for any non-specific deficiency in motor control, patients performed a similar manual tracking task, using their dominant arm to move a joystick. As a control group, 11 healthy subjects (mean age 58 years; mean ratio of forced expiratory volume in 1 s to forced vital capacity = 77%) underwent an identical experimental protocol.
4. Motor control performances were measured in terms of the error between the target position and the subject's positioning of the cursor. Indices of performance were the root mean square of the error and the averages of the zero errors (i.e. end expiration/arm movement towards the trunk) and the peak errors (i.e. end inspiration/arm movement from the trunk).
5. For manual tracking, patients with chronic obstructive pulmonary disease, were not significantly different from control subjects in terms of mean root mean square (69.3 versus 60.9), mean zero error (93.8 versus 72.2) or mean peak error (99.5 versus 82.7). For ventilatory tracking, mean root mean square was significantly higher in patients (83.4 versus 65.9). This was due to a significantly higher mean zero error (101.4 versus 66.1); mean peak error was not significantly different (68.3 versus 82.1). Comparison of flows achieved during ventilatory tracking with those possible during a maximal forced expiratory manoeuvre in the patients suggested that poor expiratory control in this group could be explained by their degree of airflow limitation rather than a deficiency in motor control per se.
6. These results provide no evidence that patients with chronic obstructive pulmonary disease have any impairment in their voluntary motor control of breathing.
Human Skeletal Muscle Protein: Effect of Malnutrition, Elective Surgery and Total Parenteral Nutrition
Authors: Petersson Benny , Hultman Eric , Andersson Kerstin , Wernerman Jan 
Published: August 2015

1. The concentration of alkali-soluble protein, DNA and RNA in percutaneous muscle biopsy specimens was analysed. Tissue alkali-soluble protein/DNA ratio is a measure of muscle protein concentration, while tissue RNA/DNA ratio may reflect the capacity for protein synthesis.
2. Patients with weight loss due to cancer (n = 6) were compared with metabolically healthy patients before elective surgery (n = 7). Alkali-soluble protein/DNA and RNA/DNA ratios in the weight loss group were 248 (14) g/g and 1.3 (0.1) g/g respectively as compared with 404 (13) g/g and 2.1 (0.1) g/g in otherwise healthy patients. All of the alkali-soluble protein/DNA ratios and 5/6 of the RNA/DNA ratios in the weight loss group were below the 95% confidence interval for the healthy control subjects.
3. Patients undergoing elective open cholecystectomy (n = 7) were studied preoperatively and on days 3, 10, 20 and 30 post-operatively. The alkali-soluble protein/DNA ratio remained unchanged on postoperative day 3 but decreased by 8.7% (P &lt; 0.01), 9.6% (P &lt; 0.05) and 20.4% (P &lt; 0.01) on days 10, 20 and 30 respectively in patients eating at will after the operation. No significant post-operative changes in alkali-soluble protein/DNA ratio were seen in patients given post-operative total parenteral nutrition with (n = 9) or without (n = 7) glycyl-glutamine supplementation for 3 days after surgery.
4. In conclusion, patients with weight loss due to malignant disease have a low muscle protein concentration. Elective surgery of medium magnitude results in a decrease in muscle protein lasting for more than 30 days. This is in contrast to patients receiving post-operative total parenteral nutrition, in whom no significant reduction in muscle protein was noted following surgery regardless of whether or not the total parenteral nutrition was supplemented with glutamine.
Adriamycin-Related Hypertension in Pregnant Rats: Response to a Thromboxane Receptor Antagonist
Authors: Rathaus Mauro , Podjarny Eduardo , Pomeranz Avishalom , Green Janice , Bernheim Jacques 
Published: August 2015

1. In previous works we have described the development of hypertension and aggravation of proteinuria in rats who became pregnant after the administration of Adriamycin. This was associated with an increase in the glomerular thromboxane B2—prostaglandin E2 ratio.
2. To assess the pathogenetic role of thromboxane in this model, female Wistar rats were mated 2 weeks after receiving Adriamycin (3.5 mg/kg intravenously). Rats were then treated with the thromboxane-receptor antagonist daltroban, 60 mg day−1 kg−1 orally, beginning on day 11 of pregnancy. Systolic blood pressure, proteinuria and the urinary excretion of thromboxane B2, 6-keto-prostaglandin F1α and prostaglandin E2 were measured serially before mating, and on days 14 and 21 of pregnancy. The results were compared with those in Adriamycin-(treated) pregnant rats not treated with daltroban, Adriamycin-treated virgin rats and normal virgin or pregnant rats either treated or untreated with daltroban.
3. In daltroban-treated pregnant and virgin rats treated with Adriamycin, systolic blood pressure remained normal, whereas it increased significantly (P &lt; 0.05) in untreated animals. On day 14, blood pressure was higher in non-daltroban-treated Adriamycin-treated pregnant rats than in non-daltroban-treated Adriamycin-treated virgin rats. Treatment had no effect on blood pressure in normal virgin or pregnant rats. Proteinuria was higher in pregnant rats treated with Adriamycin than in Adriamycin-treated virgin rats, but it was not reduced by daltroban. Urinary thromboxane B2 tended to increase in Adriamycin-treated virgin rats and was significantly higher than in the other groups at the period corresponding to end-pregnancy, whereas in Adriamycin-treated pregnant rats thromboxane B2 was not significantly increased. Daltroban did not change the urinary excretion of thromboxane B2, whereas urinary 6-keto-prostaglandin F1α increased significantly.
4. We conclude that elevation of blood pressure after Adriamycin in rats is mediated by thromboxane B2/endoperoxide receptors. This suggests a further analogy, in this model, with one of the pathogenetic mechanisms of pregnancy-related hypertension.
Effects of Exercise and Nitrates on Blood Flow in Internal Mammary Artery to Coronary Artery Grafts: A Non-Invasive Study
Authors: Mauric Andrea , Samani Nilesh J. , de Bono David P. 
Published: August 2015

1. The aim of the present study was to investigate the effects of exercise and of sublingual glyceryl trinitrate on the pattern of blood flow, as studied by Doppler ultrasound, in internal mammary artery grafts performed to relieve severe stenosis of the left anterior descending coronary artery. The accessibility of the graft to transcutaneous ultrasound examination allows the effects of exercise and nitrate administration on coronary blood flow to be studied non-invasively.
2. Angina-free patients with left internal mammary to left anterior descending coronary artery grafts were studied using transcutaneous duplex ultrasound at rest, after leg exercise and after sublingual administration of 0.5 mg or 1 mg of glyceryl trinitrate.
3. Resting graft blood flow showed a biphasic pattern, with forward flow in both systole and diastole. Exercise caused an increase in time-averaged velocity of graft blood flow from 17.3 (3.3) to 24.0 (7.2) cm/s (P = 0.001), and of calculated volume flow from 44.7 (3.08) to 59.8 (5.89) ml/min (P = 0.002). Diastolic peak velocity increased from 36.1 (9.9) cm/s to 46.8 (16.2) cm/s (P = 0.04), while peak systolic velocity was unchanged. Nitrate administration caused a fall in systolic and diastolic blood pressure and an increase in heart rate; graft flow was maintained [time-averaged velocity 18.3 (6.2) cm/s before and 16.7 (5.7) cm/s after 500 μg of glyceryl trinitrate], but systole was shortened and the proportion of blood flow in diastole increased [systolic/diastolic flow ratio 0.558 (0.139) before and 0.374 (0.156) after 500 μg of glyceryl trinitrate, P = 0.01].
4. Doppler ultrasound examination of internal mammary artery to coronary artery grafts is one of the few ways in which physiological changes in coronary flow can be assessed non-invasively in human subjects. Exercise-induced increases in graft flow involve both increased graft distension in systole and increased run-off in diastole — the elasticity of internal mammary artery grafts may be important in sustaining an exercise-induced increase in graft flow. Limitations of the technique include the difficulty of accurately measuring graft diameter, the possibility of flow through persisting connections between the graft and chest wall vessels and competing flow from the native circulation.
Down-Regulation of Vasopressin VlA Receptor mRNA in Diabetes Mellitus in the Rat
Authors: Phillips Paddy A. , Risvanis John , Hutchins Anne-Marie , Burrell Louise M. , MacGregor Duncan , Gundlach Andrew L , Johnston Colin I. 
Published: August 2015

1. To investigate the mechanism of hepatic V1a vasopressin receptor down-regulation in streptozotocin-induced diabetes mellitus in the rat, we measured hepatic V1a receptor mRNA by in situ hybridization histochemistry using oligonucleotide probes to the V1a receptor and Northern blotting.
2. Diabetes mellitus caused hyperglycaemia, hyperosmolality and increased plasma vasopressin concentrations (P &lt; 0.01). Hepatoycte V1a receptor mRNA was reduced by 76% in diabetic rats (P &lt; 0.01) and by 53% in insulin-treated diabetic rats (P &lt; 0.01) versus control rats, in parallel with reduced V1a radioligand binding and vasopressin-stimulated inositol phosphates production. There was a similar decrease in hepatic V1a/18S mRNA density ratio in the diabetic and diabetic + insulin groups (both P &lt; 0.05 versus control).
3. These findings suggest that altered V1a mRNA transcription is responsible for the reduced hepatic V1a receptor density in diabetes mellitus.
Renal Handling of Lithium and the Effects of Mannitol and Arginine Vasopressin in man
Authors: Noormohamed Faruq H. , Lant Ariel F. 
Published: August 2015

1. A study has been undertaken in six healthy male subjects to clarify whether post-proximal segments of the nephron contribute to the renal handling of lithium under conditions of maximal forced osmotic load diuresis and arginine vasopressin-induced antidiuresis. Increments in the fractional clearance of free water, as a measure of effect at the proximal tubule, were positively correlated with incremental changes in flow rate, factored for glomerular filtration rate (mean r = 0.80 ± 0.12, P &lt; 0.001), and fractional excretion of lithium (mean r = 0.84 ± 0.06, P &lt; 0.001). Changes in flow rate and fractional excretion of lithium were also closely correlated with one another (mean r = 0.81 ± 0.06, P &lt; 0.001), and the mean slope of these regression lines was not significantly different from unity (1.18; 95% confidence interval 0.76–1.59). These results show that, under conditions of maximal hydration, mannitol-induced changes in proximal tubular function were closely correlated with induced changes in the fractional excretion of lithium.
2. Infusion of arginine vasopressin alone (0.5 m-units/min) caused a marked reduction in both fractional clearance of free water (10.7% ± 1.2% to −1.2% ± 0.2%, P &lt; 0.001) and flow rate factored for glomerular filtration rate (14.0 ± 1.5 to 0.8 ± 0.2%; P &lt; 0.001) while the fractional excretion of lithium showed only a small non-significant decrease (25.3% ± 2.0% to 23.3% ± 2.2%). A similar dissociation was noted between fluid and lithium excretion when arginine vasopressin was superimposed on mannitol infusion with reductions in the fractional clearance of free water (12.7% ± 1.0% to −0.9% ± 0.7%, P &lt; 0.001) and flow rate (18.6% ± 1.5% to 5.7% ± 1.0%; P &lt; 0.001), while the fractional excretion of lithium showed a significant increase (28.4% ± 1.7% to 33.1% ± 2.4%; P &lt; 0.05). The lack of correlation between fluid and lithium excretion, in the presence of arginine vasopressin with or without mannitol, indicates that the late distal tubule and collecting duct have little or no significant capacity to reabsorb lithium.
3. These findings, taken as a whole, strengthen the view that renal tubular handling of lithium is primarily a proximal event.
Longitudinal Studies of Platelet Cyclic AMP during Healthy Pregnancy and Pregnancies at Risk of Pre-Eclampsia
Authors: Horn E. H. , Cooper J. A. , Hardy E. , Heptinstall S. , Rubin P. C. 
Published: August 2015

1. Platelet behaviour in vitro in relation to cyclic AMP was studied longitudinally during pregnancy and in the same women when they were not pregnant. Subjects comprised a group of healthy primigravidae and a group of women deemed at risk of pre-eclampsia, on the basis of a previous history of the condition.
2. There was a progressive decline during pregnancy in sensitivity of platelets to inhibition of the arachidonic acid-induced release reaction by agents which act via cyclic AMP. This effect was maximum at 36 weeks' gestation.
3. Basal platelet cyclic AMP levels, and those in the presence of a phosphodiesterase inhibitor, did not change throughout the period of the study.
4. By contrast, platelet cyclic AMP accumulation in response to a variety of adenylate cyclase stimulators was reduced from early pregnancy, throughout the gestational period, compared with post-natally. This effect was noted when platelets were incubated with prostaglandins acting via different surface receptors or with forskolin and was most marked on co-incubation with a phosphodiesterase inhibitor.
5. Compared with healthy women, platelets from women with a previous history of pre-eclampsia tended to accumulate less cyclic AMP in response to adenylate cyclase stimulators. This was the case both during pregnancy and post-natally. Further investigation of adenylate cyclase activity in platelets in relation to pre-eclampsia is required.
Insensitivity of the HEring—Breüer Reflex to Spontaneous Changes in Metabolic Rate in the Infant
Authors: Mortola Jacopo P. , Saiki Chikako , Fox Gordon 
Published: August 2015

1. In infants, metabolic rate is highly variable. We investigated whether the strength of the vagal ventilatory inhibitory reflex was modified by the spontaneous changes in metabolic rate.
2. In 20 2-day-old infants, we measured the intensity of the Hering—Breüer expiratory-promoting reflex (inhibition of breathing during maintained lung inflation), the inspired and expired O2 and minute ventilation (V̇E), from which oxygen consumption (V̇o2) was calculated. The measurements were performed twice, a few hours apart [6 ± 1 h SEM)].
3. On average, V̇o2 differed by 39 ± 7% between the two measurements, with no correlation with the time of the day (morning/afternoon) or the time interval from a meal. V̇E was also significantly higher (19 ± 6%) when V̇o2 was higher, because of a larger tidal volume. The Hering—Breüer reflex (quantified as the apnoea time during lung inflation, either the absolute value or normalized by the airway pressure or lung volume) did not differ significantly between the two tests (&lt;5% difference, P &gt; 0.05), and did not correlate with the changes in V̇o2 or V̇E.
4. We conclude that, in the infant, pulmonary vagal inhibition is not sensitive to changes in metabolic drive, presumably because of the low ventilatory chemosensitivity of the newborn.
Biliary Excretion of Chylomicron Remnant Cholesterol in the Rat: Responses to the Expansion of Their Plasma Pool and Promoting Role of Stimulated Bile-Acid Synthesis
Authors: Carrella Massimino , Csillaghy Annalisa , de Mercato Renato , D'Arienzo Agesilao 
Published: August 2015

1. Chylomicron remnants, the intermediate intestinal lipoproteins carrying the bulk of dietary cholesterol, are actively taken up and degraded in the hepatocytes, releasing cholesterol which can be excreted in bile. To study this pathway, a mass of remnants, leading to a consistent rise in hepatic cholesterol, was administered as an intravenous bolus in rats with chronic bile fistula equilibrated by water, electrolyte and taurocholate infusions, and changes in biliary lipids and bile acids were evaluated for up to 24 h in comparison with baseline.
2. A mean 16% increase in the net output of bile acids was observed at each time interval after lipoprotein injection, accounting for a 24 h cumulative excretion of approximately one-third of the administered cholesterol mass. These changes did not reach statistical significance however. The cholesterol output and concentrations of all biliary lipids did not vary either. Without taurocholate replacement, remnants injection was followed by a 15–20% decrease in bile acid and bile lipid secretion, presumably due to an insufficient hepatic bile-acid flux.
3. When [3H]cholesterol-labelled remnants were administered at the same mass in the chronic equilibrated bile fistula model, 21% of injected radioactivity was excreted in 24 h, distributing mostly in acidic rather than neutral sterols (20.02 ± 1.85 compared with 1.07 ± 0.04), with an acidic to neutral sterol mean ratio of 16.
4. To exclude interfering effects from the administered cholesterol mass and chronic bile fistula, 3H-labelled remnants were also studied as a cholesterol trace injected in rats with acute bile fistula. In this case, however, 24 h total sterol radioactivity only reached approximately 10% of that injected, and partitioned relatively less in acidic (6.84 ± 0.59) than in neutral (3.15 ± 0.39) sterols, with an acidic to neutral sterol mean ratio of 2.
5. The study suggests that remnant cholesterol reaches bile mainly in the form of bile acids, by a steady slow-rate process which is magnified under conditions of stimulated bile-acid synthesis.