bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atrial natriuretic peptide-induced relaxation of pre-constricted isolated rat perfused lungs: A comparison in control and hypoxia-adapted animals
Authors: Stewart A. G. , Thompson J. S. , Rogers T. K. , Morice A. H. 
Published: August 2015

1. To further understand the vasodilator actions of atrial natriuretic peptide and its role in hypoxic pulmonary hypertension, we studied the effects of atrial natriuretic peptide in the isolated perfused rat lung during normoxic ventilation and after elevation of pulmonary artery pressure by either hypoxic ventilation or infusion of prostaglandin F2α. Control animals were compared with littermates that had become adapted to a 10% O2 environment for 3 weeks. Atrial natriuretic peptide was compared with atriopeptin I and atriopeptin III in order to study its structure-activity relationship.
2. Five experiments, each involving six control and six chronically hypoxic rats, were performed. During normoxic ventilation, atrial natriuretic peptide (30 ng-3 μg) produced a dose-dependent reduction in pulmonary artery pressure in chronically hypoxic rats, but had no action in the control animals.
3. Atrial natriuretic peptide dose-dependently abolished hypoxic pulmonary vasoconstriction to a greater extent in chronically hypoxic rats (EC50 98 ng) than in control rats (EC50 298 ng; P &lt; 0.001). Bolus atrial natriuretic peptide (100 ng) produced a plasma concentration of 22.6 pmol/l at 1 min, which is within the pathophysiological range. Initial plasma atrial natriuretic peptide levels were 9.4 pmol/l in control animals and 27.4 pmol/l in chronically hypoxic rats.
4. Chronically hypoxic rats were more sensitive to atriopeptin I, atriopeptin III and atrial natriuretic peptide than were the control rats (P &lt; 0.05). Atrial natriuretic peptide and atriopeptin III were equipotent and were 10 times more potent than atriopeptide I in both groups (P &lt; 0.001).
5. Although atrial natriuretic peptide lowered pulmonary artery pressure in isolated perfused lungs pre-constricted with prostaglandin F2α (5 μg/min), there was no difference between the control and chronically hypoxic groups, and the EC50 296 ng in the chronically hypoxic rats was significantly (P &lt; 0.001) less than that seen in the chronically hypoxic despite similar levels of induced constriction by the two stimuli.
6. A set dose of atrial natriuretic peptide produced the same percentage reduction in hypoxic pulmonary vasoconstriction despite differing levels of pre-constriction produced by ventilating with 7%, 5%, 3% or 0% O2. There was no change in the arterial partial pressure of O2 or the alveolar-arterial gradient after injection of atrial natriuretic peptide, suggesting that its effects are not due to a reduction in pulmonary oedema.
7. Atrial natriuretic peptide relaxes pre-constricted pulmonary arteries in the isolated perfused rat lung in a dose-dependent manner within the pathophysiological range. The greater action of atrial natriuretic peptide in chronic hypoxia could be due to its action at the new sites of hypoxic pulmonary vasoconstriction, the newly muscularized alveolar arteries which develop during adaptation to hypoxia.
Effect of glutamine-enriched total parenteral nutrition on septic rats
Authors: Ardawi M. Salleh M. 
Published: August 2015

1. The effect of total parenteral nutrition with or without glutamine enrichment was studied in septic rats after 4 days of treatment.
2. Septic rats treated with glutamine-enriched total parenteral nutrition survived sepsis significantly better than other TPN-treated septic rats: the cumulative percentage of deaths over 4 days in septic rats treated with glutamine-enriched total parenteral nutrition was 25% compared with 55% in septic rats given total parenteral nutrition without glutamine and 70% in septic rats given glucose.
3. Glutamine-enriched total parenteral nutrition resulted in improved nitrogen balance in septic rats: the cumulative nitrogen balance over the 4 days of treatment was the least negative as compared with other groups of septic rats.
4. The rate of loss of intracellular glutamine in skeletal muscle was markedly decreased (P &lt; 0.001) in response to glutamine-enriched total parenteral nutrition in septic rats.
5. The rate of protein synthesis was increased (21.2%) and the rate of protein degradation was decreased (35.5%) in response to glutamine-enriched total parenteral nutrition in septic rats.
6. It is concluded that the administration of glutamine-enriched total parenteral nutrition is beneficial to septic rats and possibly to septic patients.
Effect of insulin-induced hypoglycaemia on antral, pyloric and duodenal motility in fasting subjects
Authors: Fraser R. , Fuller J. , Horowitz M. , Dent J. 
Published: August 2015

1. Hyperglycaemia alters gastric motility and delays gastric emptying. By contrast, there is little information regarding the effect of sub-normal blood glucose concentrations on gastric and, in particular, pyloric motility, although limited data suggest that hypoglycaemia is associated with accelerated gastric emptying despite an apparently increased basal pyloric pressure.
2. To determine the effects of hypoglycaemia on pyloric motility, we compared the effects of an intravenous injection of insulin (0.15 units/kg) with those of a placebo injection of saline in eight healthy human volunteers during phase I of the interdigestive migrating motor complex.
3. All subjects developed profound hypoglycaemia (mean blood glucose concentration 1.6 mmol/l compared with 4.0 mmol/l in the control group).
4. There was no significant difference in the number of antral (9 versus 7, P = 0.34), pyloric (3 versus 0, P = 0.31) or duodenal (21 versus 13, P = 0.42) pressure waves or in the basal pyloric pressure (0.3 mmHg versus 0.1 mmHg, P = 0.37) in the 45 min after insulin injection (hypoglycaemia) when compared with the 45 min after saline injection (euglycaemia). In both the euglycaemic and hypoglycaemic studies there was a time-dependent increase in the numbers of antral and duodenal waves consistent with the expected changes in the interdigestive migrating motor complex.
5. These results indicate that insulin-induced hypoglycaemia has no significant effect on pyloric motility during phase I of the interdigestive migrating motor complex.
Additive antiproteinuric effect of angiotensin-converting enzyme inhibition and non-steroidal anti-inflammatory drug therapy: A clue to the mechanism of action
Authors: Heeg Jan E. , de Jong Paul E. , de Zeeuw Dick 
Published: August 2015

1. Both the angiotensin-converting enzyme inhibitor, lisinopril, and the non-steroidal anti-inflammatory drug, indomethacin, lower urinary protein excretion in renal disease and improve the selectivity of the residual proteinuria. Despite the clearly different renal haemodynamic profiles of the two drugs, we hypothesize that the antiproteinuric effect has a final common pathway that is a reduction in glomerular filtration pressure.
2. We studied the effects of lisinopril and indomethacin, separately and in combination, on urinary protein excretion, selectivity of proteinuria and renal haemodynamics in nine non-diabetic patients with overt proteinuria.
3. Urinary protein excretion was 5.4 ± 2.5 g/24 h in the control period. Lisinopril monotherapy lowered urinary protein excretion by 53 ± 26%. During indomethacin treatment urinary protein excretion was reduced by 63 ± 24%. After adding indomethacin to lisinopril, urinary protein excretion fell by a further 58 ± 23%, resulting in a 79 ± 17% decrease during combined therapy.
4. Although both lisinopril and indomethacin monotherapy appeared to result in an improvement in glomerular protein permselectivity, no further improvement was seen during the combination therapy.
5. The changes in proteinuria were associated with changes in glomerular filtration rate, which showed a pronounced fall with combination therapy. The renal haemodynamic profiles during the different therapies suggest a post-glomerular vasodilatation by lisinopril and a pre-glomerular vasoconstriction by indomethacin, and the combination of both during the combined treatment.
6. These data suggest a synchronous afterload and preload reduction of glomerular filtration pressure as the cause of the additive effect of the combination of angiotensin-converting enzyme inhibition and non-steroidal anti-inflammatory drug therapy in lowering glomerular filtration rate and proteinuria.
Evidence for heterogeneity of glycosylation of human renin obtained by using lectins
Authors: Hosoi Masayuki , Kim Shokei , Yamamoto Kenjiro 
Published: August 2015

1. In this study, the carbohydrate structure of pure human renin was examined by using various lectins.
2. Pure renin could be separated into three forms by concanavalin A chromatography, a concanavalin A-unbound form, a loosely bound form and a tightly bound form, termed renins A, B and C, respectively. Renins A, B and C accounted for 3, 13 and 84%, respectively, of the purified renin. These forms were all present in individual human plasma and the relative proportions in plasma were 27 ± 3, 33 ± 4 and 39 ± 5% (means ± sem) for renins A, B and C, respectively (n = 5).
3. Each form, electroblotted on to the nitrocellulose sheet after gel electrophoresis, was incubated with five peroxidase-labelled lectins, lentil lectin, erythroagglutinating phytohaemagglutinin, wheat-germ agglutinin, Ricinus communis agglutinin and peanut agglutinin. The protein was stained with 4-chloro-l-naphthol.
4. The staining pattern obtained with these lectins was significantly different among the three forms of human renin, confirming that they have different carbohydrate structures. Furthermore, the positive staining of human renin with erythroagglutinating phytohaemagglutinin, wheat-germ agglutinin and Ricinus communis agglutinin was in contrast with the lack of binding of rat renin to these lectins.
5. These results indicate the renal secretion of differently glycosylated multiple forms of human renin. The carbohydrate structure of human renin appears to differ from that of rat renin.
Chloride influx in human leucocytes: A triple-isotope technique for the assessment of chloride transporters
Authors: Hogg M. , Ng L. L. , Davies J. E. 
Published: August 2015

1. A novel triple-isotope method using 3H2O, [14C]-sucrose and 36Cl− for measuring initial Cl− uptake rates in human leucocytes that had been preincubated in 10% (v/v) autologous serum is described.
2. There was a marked dependence of Cl− influx on intracellular pH, the flux at an intracellular pH of 7.20 being about 11.2% of that at an intracellular pH of 7.56.
3. This Cl− influx was inhibited by 4,4-di-isothiocyanatostilbene-2,2-disulphonic acid in a dose-dependent manner. Half-maximal inhibition by 4,4-diisothiocyanatostilbene-2,2-disulphonic acid at an internal pH of 7.56 in the presence or absence of HCO−3 was 0.30 or 0.35 mmol/l, respectively.
4. Depletion of intracellular Cl− resulted in a 70.7% decrease in Cl− influx, whereas depletion of cellular ATP led to a 37.7% decrease in Cl− influx.
5. The phorbol ester 12-O-tetradecanoyl phorbol acetate at a concentration of 0.1 μmol/l reduced Cl− influx, especially the 4,4-di-isothiocyanatostilbene-2,2-disulphonic acid-sensitive component. This effect was independent of intracellular pH changes or Na+/H+ anti-port activity.
Mediators of the direct effects of amino acids on the rat kidney
Authors: El Sayed A. A. , Haylor J. , El Nahas A. M. 
Published: August 2015

1. The response of the isolated rat kidney to a mixed amino acid solution was examined in the presence of three renal autacoid inhibitors, indomethacin (a cyclo-oxygenase inhibitor), sulpiride (a dopamine antagonist) and l-nitroarginine methyl ester (an inhibitor of nitric oxide synthesis).
2. Increasing the concentration of the mixed amino acid solution perfusing the kidney from 2 to 8 mmol/l (n = 6) produced a sustained increase in renal perfusate flow (P &lt; 0.01) and reversed the time-dependent fall in [14C]inulin clearance (P &lt; 0.01) demonstrated in kidneys perfused with 2 mmol/l mixed amino acids alone. A significant increase in the fractional sodium reabsorption and decrease in the fractional albumin excretion was also observed.
3. Indomethacin (10−4 mol/l, n = 6) produced partial (50%) inhibition of the effect of mixed amino acids on [14C]inulin clearance, but did not influence their ability to increase renal perfusate flow.
4. Sulpiride (0.7 μmol min−1 kg−1, n = 6) produced partial inhibition of the effect of mixed amino acids on both [14C]inulin clearance and renal perfusate flow by 60% and 50%, respectively. Sulpiride also entirely inhibited the reduction in fractional albumin excretion.
5. l-Nitroarginine methyl ester (10−4 mol/l, n = 6) completely inhibited the effect of mixed amino acids on [14C]inulin clearance, but did not inhibit the increase in renal perfusate flow, even though the basal vascular resistance was markedly enhanced. l-Nitroarginine methyl ester also inhibited the increase in fractional sodium reabsorption produced by the mixed amino acids.
6. It is concluded that prostaglandins, dopamine and nitric oxide may all have a role to play in the direct effect of mixed amino acids on renal function. This does not, however, preclude further modification by additional stimuli generated in vivo.
Effect of angiotensin-converting enzyme inhibitors on glomerular eicosanoid production in normotensive and spontaneously hypertensive rats
Authors: Harding P. , Stonier C. , Aber G. M. 
Published: August 2015

1. This study was designed to examine the production of certain eicosanoids (prostaglandin E2), prostacyclin (as 6-keto-prostaglandin F1α) and thromboxane A2 (as thromboxane B2) by glomeruli isolated from normotensive Wistar-Kyoto and spontaneously hypertensive rats both before and after the administration of one of three angiotensin-converting enzyme inhibitors, captopril, enalapril or fosinopril, for 10 days.
2. Measurements of glomerular eicosanoid production were made under basal conditions and in the presence of excess exogenous arachidonic acid.
3. The production of prostaglandin E2, 6-keto-prostaglandin F1α and thromboxane B2 was greater by glomeruli from untreated spontaneous hypertensive rats (prostaglandin E2 2.24 ± 0.41, 6-keto-prostaglandin F1α 1.20 ± 0.13 and thromboxane B2 2.75 ± 0.43 ng 10 min−1 mg−1 of protein) than by those from Wistar-Kyoto rats (prostaglandin E2 1.41 ± 0.28, 6-keto-prostaglandin F1α 0.98 ± 0.11 and thromboxane B2 1.29 ± 0.24 ng 10 min−1 mg −1 of protein) under basal conditions. However, these differences only achieved statistical significance for thromboxane B2 (P &lt; 0.01). Similar strain-related differences were noted in the presence of arachidonic acid.
4. The ratio of glomerular (prostaglandin E2 + prostacyclin)/thromboxane A2 production was significantly lower in spontaneously hypertensive rats than in their normotensive counterparts under basal conditions with values of 1.3 ± 0.18 and 2.2 ± 0.20, respectively (P &lt; 0.01).
5. Angiotensin-converting enzyme inhibitors induced significant changes in the glomerular production of some eicosanoids, which differed both between strains and with the nature of the inhibitor.
6. All three angiotensin-converting enzyme inhibitors increased the ratio of glomerular (prostaglandin E2 + prostacyclin)/thromboxane A2 production in both strains of rat. This only achieved statistical significance in Wistar-Kyoto rats after treatment with enalapril (from 2.2 ± 0.20 to 5.3 ± 0.83, P &lt; 0.01) and fosinopril (from 2.2 ± 0.20 to 7.9 ± 1.68, P &lt; 0.01), and in spontaneously hypertensive rats after treatment with fosinopril (from 1.3 ± 0.18 to 4.2 ± 0.50, P &lt; 0.005).
7. None of the angiotensin-converting enzyme inhibitors induced any change in the systolic blood pressure of Wistar-Kyoto rats, whereas captopril, enalapril and fosinopril induced significant and comparable reductions in that of spontaneously hypertensive rats from mean pretreatment values of 167.8 ± 3.2, 164.7 ± 2.5 and 175.2 ± 4.0 mmHg to 150.3 ± 2.7, 141.0 ± 2.2 and 154.0 ± 3.4 mmHg, respectively (P &lt; 0.0005).
8. The effects of angiotensin-converting enzyme inhibitors on eicosanoid production by glomeruli from Wistar-Kyoto rats and spontaneously hypertensive rats appear to be unrelated to changes in systemic blood pressure or to the presence of a thiol group.
Glutamine and alanine metabolism in lungs of septic rats
Authors: Ardawi M. Salleh M. 
Published: August 2015

1. The metabolism of glutamine and alanine in the lung was studied in rats made septic by a caecal ligation and puncture technique.
2. The blood glucose concentration was not significantly different in septic rats, but blood pyruvate, lactate, glutamine and alanine concentrations were markedly increased as compared with sham-operated rats. Conversely, blood ketone body and plasma cholesterol concentrations were significantly decreased in septic rats. Both plasma insulin and plasma glucagon concentrations were markedly elevated in response to sepsis. Sepsis resulted in a negative nitrogen balance.
3. Sepsis increased the rates of production of glutamine (52.5%, P &lt;0.001), alanine (38.9%, P &lt;0.001) and glutamate (48.6%, P &lt;0.001) by lung slices incubated in vitro.
4. Sepsis increased lung blood flow by 27.6% (P &lt;0.05). Blood flow and arteriovenous concentration difference measurement across the lung of septic rats showed an increase in the net exchange rates of glutamine (142.5%, P &lt;0.001), alanine (129.4%, P &lt;0.001), glutamate (100.9%, P &lt;0.001) and ammonia (138.0%, P &lt;0.001) as compared with sham-operated control rats.
5. Sepsis produced significant decreases in the lung concentrations of glutamine (36.8%), glutamate (20.8%), 2-oxoglutarate (64.8%) and AMP (18.3%). The lung concentrations of alanine (95.9%), ammonia (67.7%) and pyruvate (89.7%) were increased.
6. The maximal activities of glutamine synthetase (20.4%, P &lt;0.05), phosphate-dependent glutaminase (18.9%, P &lt;0.05) and alanine aminotransferase (25.5%, P &lt;0.05) were increased, but there was no marked change in that of glutamate dehydrogenase, in the lungs of septic rats.
7. It is concluded that there are enhanced rates of production of glutamine and alanine from lungs of septic rats (both in vitro and in vivo). This may be due to changes in efflux and/or increased intracellular biosynthesis of both glutamine and alanine; these suggestions are discussed.
Variability in the measurement of nebulized aerosol deposition in man
Authors: Thomas S. H. L. , O'Doherty M. J. , Page C. J. , Nunan T. O. 
Published: August 2015

1. This study was performed to determine the variability of two different scintigraphic methods of measuring pulmonary aerosol deposition, and to examine nebulizer particle size and drug output as potential sources of this variability.
2. A radioaerosol was produced from a 3 ml solution of 99mTc-labelled colloidal human serum albumin (0.05 mg, 37 MBq) using a standard jet nebulizer and air compressor. This was inhaled on three separate occasions by nine healthy male subjects. On one of these occasions, a further inhalation was performed to assess immediate repeatability using increased 99mTc activity (92 MBq).
3. Intrapulmonary aerosol deposition was measured with a γ-camera and was corrected for tissue attenuation and geometric distribution by using two different methods.
4. Estimated mean pulmonary deposition was 4.3% of the nebulizer dose using a lung phantom correction method, and 6.1% using a tissue attenuation method. For these two methods respectively variability between subjects (coefficient of variation) was 54 and 47%. For both methods, within-subject variability (coefficient of variation) was 37% between occasions and 23% within occasions.
5. The particle-size output of several nebulizers was highly reproducible (coefficient of variation &lt; 4%), but the nebulizer mass and radionuclide output of two nebulizers was more variable (coefficient of variation 5–19%), and appeared to be an important contributor to the variability in pulmonary aerosol deposition.
6. The data presented here for pulmonary deposition, used with appropriate power statistics formulae, can be used to estimate the sample sizes required for comparative studies of lung aerosol deposition.
Oxidation-resistant variants of recombinant anti-leucoprotease are better inhibitors of human-neutrophil-elastase-induced emphysema in hamsters than natural recombinant antileucoprotease
Authors: Rudolphus A. , Heinzel-Wieland R. , Vincent V. A. M. M. , Saunders D. , Steffens G. J. , Dijkman J. H. , Kramps J. A. 
Published: August 2015

1. Antileucoprotease, being sensitive to oxidative inactivation, can be produced by recombinant techniques. Via site-directed mutagenesis, two mutants of recombinant antileucoprotease were produced in which one or more of the oxidation-sensitive methionine residues were replaced by leucine: in rALP242, methionine-73 was replaced by leucine, and in rALP231, leucine was substituted for four methionine residues. In vitro, native antileucoprotease and the recombinant antileucoprotease preparations have similar inhibitory characteristics towards human neutrophil elastase. We hypothesized that replacement of methionine residues in the antileucoprotease molecule would result in a reduced oxidation sensitivity of the mutants.
2. After incubation of recombinant antileucoprotease and its mutants with increasing dosages of cis-platinum(II)diammine dichloride, we observed that native antileucoprotease and recombinant antileucoprotease were inactivated by this reagent to the same extent. Compared with this, rALP242 was less inactivated, whereas the inhibitory capacity of rALP231 was not influenced by cis-platinum(II)diammine dichloride at all.
3. After incubation of recombinant antileucoprotease, rALP242 and rALP231 with triggered polymorphonuclear leucocytes, which are thought to produce an excess of oxidants, we measured residual inhibitory activities towards human neutrophil elastase of 10%, 55% and 87%, respectively.
4. In vivo, the inhibitory effects of intratracheally administered rALP242 and rALP231 towards human-neutrophil-elastase-induced emphysema were significantly greater than that of recombinant antileucoprotease. There were no significant differences between the mutants. With respect to secretory cell metaplasia and haemorrhage, rALP231 tended to be a better inhibitor than recombinant antileucoprotease and rALP242.
5. We conclude that the recombinant antileucoprotease mutants are less sensitive to oxidation and consequently inhibit human-neutrophil-elastase-induced emphysema to a greater extent than recombinant antileucoprotease.
Effects of alcohol intake on plasma fatty acids assessed independently of diet and smoking habits
Authors: Burke V. , Croft K. D. , Puddey I. B. , Cox K. L. , Beilin L. J. , Vandongen R. 
Published: August 2015

1. This study was designed to determine prospectively whether changing alcohol consumption influenced the proportion of plasma linoleic acid independently of diet or smoking habits, and to evaluate changes in the plasma linoleic acid concentration as a potential marker of changes in alcohol consumption.
2. Fasting plasma fatty acid profiles were investigated in 72 male drinkers who were randomly assigned to drink low-alcohol beer or to maintain their usual drinking habits for a period of 4 weeks.
3. At entry to the study, a higher alcohol intake was associated with lower proportions of plasma linoleic acid, arachidonic acid and dihomolinolenic acid and higher proportions of plasma palmitoleic acid, independently of changes in body mass index. Smoking habits were unchanged and there were no major changes in diet during the period of the intervention.
4. Because the plasma palmitoleic acid concentration has been suggested as a possible marker of ‘at risk’ drinking, we investigated plasma fatty acid concentrations as indicators of alcohol intake. The plasma palmitoleic acid concentration was not a useful discriminator. Indices determined using logistic regression and combining plasma apolipoprotein A-II and linoleic acid concentrations gave better discrimination than either variable alone.