bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restoration by Corticosteroids of the Hyperaldosteronism in Hyponatraemic Rats with Panhypopituitarism
Authors: Decaux G. , Crenier L. , Namias B. , Gervy C. , Soupart A. 
Published: August 2015

1. In the syndrome of inappropriate secretion of antidiuretic hormone, hyponatraemia is associated with a normal bicarbonate concentration despite dilution. This normal bicarbonate concentration is related to the development of a hyperaldosteronism, which is attributed to a direct stimulation of the zona glomerulosa by the hyponatraemic state. Some workers have suggested that, to develop this hyperaldosteronism requires the presence of a pituitary factor. To determine whether the pituitary gland plays a role in this hyponatraemia-induced hyperaldosteronism, water intoxication was performed for 24 h in normal and in panhypopituitaric rats.
2. In normal rats, hyponatraemia (108 mmol/l), induced by the administration of 1-desamino-8-D-arginine vasopressin and 2.5% D-glucose-0.45% NaCl by gavage (15% body weight) was associated with a mild increase in bicarbonate concentration, and blood acid-base equilibrium showed a mixed metabolic and respiratory alkalosis (pH 7.57, partial pressure of CO2 29 mmHg, base excess + 5.5 mmol/l), and aldosterone concentration was increased 3-fold as compared with the control value. When hyponatraemia (110 mmol/l) was induced in a similar manner in panhypopituitaric rats, we observed a very low aldosterone concentration (&lt; 50 pg/ml) and a compensated respiratory alkalosis (pH 7.45, partial pressure of CO2 30 mmHg, base excess −2.6 mmol/l). The restoration of a hyperaldosteronaemic state in this group of rats was related essentially to corticosteroid intake.
3. These data suggest that corticosteroids play a critical role in the development of hyponatraemia-related hyperaldosteronism, a phenomenon not necessarily dependent on a pituitary factor.
Fatty Acid Synthesis by Rat Liver after Chronic Ethanol Feeding with a Low-Fat Diet
Authors: Simpson K. J. , Venkatesan S. , Peters T. J. 
Published: August 2015

1. Chronic alcohol feeding with a low-fat diet (4.4% total calories) produced a two- to three-fold increase in hepatic triacylglycerol and esterified cholesterol compared with pair-fed low-fat diet controls. Plasma lipids were similar in both groups.
2. Hepatic fatty acid synthesis rates measured in vivo with 3H2O were significantly lower in the alcohol-fed animals than in controls. Activities of hepatic fatty acid synthase (EC 2.3.1.85) and acetyl-CoA carboxylase (EC 6.4.1.2) were reduced in the alcohol-fed rats.
3. These results indicate that enhanced hepatic fatty acid synthesis does not occur in rats fed alcohol and a low-fat diet for 4 weeks, and is thus not implicated in the pathogenesis of alcohol-induced fatty liver.
Model for Whole Body Production of Tumour Necrosis Factor-α in Experimental Endotoxaemia in Healthy Subjects
Authors: Koopmans R. , Hoek F. J. , van Deventer S. J. H. , van der Poll T. 
Published: August 2015

1. Tumour necrosis factor-α is considered an important mediator in the pathophysiology of several diseases. Although much information is available about the serum concentrations of this cytokine in these illnesses, little is known about the production of tumour necrosis factor-α in disease in vivo.
2. In the present study we aimed to estimate the extent and the kinetics of whole body tumour necrosis factor-α synthesis in experimental endotoxaemia in six healthy humans. For this purpose we first examined the pharmacokinetic behaviour of an intravenously injected bolus of recombinant human tumour necrosis factor-α (50 μg/m2) in another group of six normal subjects. We then calculated the total amount of tumour necrosis factor-α produced after intravenous injection of endotoxin (2 ng/kg) as the product of the systemic clearance of recombinant human tumour necrosis factor-α (9.5 ± 5.0 ml min−1 kg−1) and the area under the tumour necrosis factor-α concentration-time curves in the endotoxaemic subjects.
3. Recombinant human tumour necrosis factor-α showed evident two-compartment kinetics with an initial rapid disappearance (t1/2 5.1 ± 2.2 min) and a terminal slower elimination (t1/2 49 ± 5 min). Tumour necrosis factor-α synthesis after endotoxin varied markedly between individuals, ranging from 11.8 to 114.1 μg (52.7 ± 34.7 μg). The changes in time of the serum concentrations of tumour necrosis factor-α after administration of endotoxin could be accurately described with an adapted two-compartment open model that incorporated both rapid tumour necrosis factor-α production (74% of the total amount) and slow tumour necrosis factor-α production (26%).
4. Our results suggest that, in endotoxaemia, circulating tumour necrosis factor-α originates from two different sources, one in rapid and one in slow equilibrium with the circulation. We propose that the pharmacokinetic characteristics of intravenous recombinant human tumour necrosis factor-α may be used to estimate the production of rumour necrosis factor-α in clinical disease.
Ammonium Chloride Inhibits Pyruvate Oxidation in Rat Liver Mitochondria: A Possible Cause of Fatty Liver in Reye's Syndrome and Urea Cycle Defects
Authors: Maddaiah Vaddanahally T. , Kumbar Uday 
Published: August 2015

1. Earlier studies with liver slices showed that inhibition by NH+4 of the oxidation of palmitate to CO2 was greater than total oxidation, whereas salicylate exerted a stronger inhibitory effect on the latter. We have now investigated the effects of NH4Cl and salicylate on ADP-induced O2 consumption by mitochondria (State 3 rate) respiring on pyruvate, and oxidation of [1-14C]- and [2-14C]-pyruvate to14CO2.
2. The rate of State 3 respiration was inhibited and plateaued at 45% with 10 mmol/l NH4Cl.
3. Oxidation of [1-14C]pyruvate was not significantly affected by either NH4Cl or salicylate. Oxidation of [2-14C]pyruvate was strongly inhibited and plateaued at 70% with 1 mmol/1 NH4Cl (IC50 = 0.125 mmol/1). ADP (1 mmol/l) increased the rate of decarboxylation of [2-14C] pyruvate but the extent of NH4Cl inhibition was not affected. Salicylate had a slight activating effect in the absence or presence of NH4Cl.
4. These results indicate that NH4Cl inhibits the oxidative metabolism of acetyl-CoA in the tricarboxylic acid cycle. Therefore, inhibition of fatty acid oxidation to acetyl-CoA as well as its further oxidative metabolism occurring under hyperammonaemia (&gt;0.1 mmol-1.49 mmol/l in Reye's syndrome patients) may be one of the causes of fatty acidaemia.
5. The cumulative inhibitory effects of NH+4 and fatty acyl derivatives on mitochondrial oxidative metabolism and production of ATP, as well as the uncoupling effects of salicylate, may contribute to some of the pathophysiology observed in patients with Reye's syndrome, and enzyme defects of the urea cycle.
Renal Impairment Associated with the Pre-Operative Administration of Recombinant Interleukin-2
Authors: Deehan D. J. , Heys S. D. , Broom J. , Eremin O. , Whiting P. H. 
Published: August 2015

1. The T-cell-derived cytokine interleukin-2 may be used to reverse the immune suppression associated with major surgery. However, both major surgical procedures and recombinant interleukin-2 therapy are known to induce renal dysfunction.
2. Eighteen patients were randomized to receive either recombinant interleukin-2 (18 × 106 i.u./day) or placebo, given subcutaneously for 3 days before undergoing curative colorectal cancer surgery. Indices of renal function were determined pre-operatively and for 21 days after surgery.
3. Pre-operative recombinant interleukin-2 was found to significantly increase, compared with placebo controls, N-acetyl-β-D-glucosaminidase [peak levels 28 (SEM 2) versus 11 (SEM 3) i.u./mmol of Cr] and γ-glutamyltransferase [peak levels 5.3 (SEM 0.6) versus 2.4 (SEM 0.2) i.u./mmol/l] and decrease urinary fractional excretion of sodium [peak difference 0.32 (SEM 0.06) versus 0.76 (SEM 0.08)] (all P &lt; 0.05). Significantly increased urinary excretions of creatinine, N-acetyl-β-D-glucosaminidase and γ-glutamyltransferase were also identified after surgery. All variables returned to pretreatment limits by the seventh day post-operatively, except N-acetyl-β-D-glucosaminidase, which was still significantly elevated 21 days after surgery. No differences in the serum concentrations of sodium, creatinine or urea were observed before or after surgery in either group.
4. Recombinant interleukin-2, when given in the preoperative period, was associated with significant renal dysfunction. However, routine monitoring of serum indices (i.e. sodium, urea, creatinine and albumin) failed to detect such renal damage. These results suggest that, with the use of recombinant interleukin-2 to enhance natural cytotoxicity in the peri-operative period, such therapy may potentiate the renal impairment occurring after surgery.
Glomerular Filtration Rate and Segmental Tubular Function in the Early Phase after Transplantation/Uninephrectomy in Recipients and Their Living-Related Kidney Donors
Authors: Kamper Anne-Lise , Holstein-Rathlou Niels-Henrik , Strandgaard Svend , Leyssac Paul Peter , Munck Ole 
Published: August 2015

1. Glomerular filtration rate and sequential tubular function were investigated in 18 adult renal transplant recipients and in their matched, adult living-related kidney donors before and 5 days after transplantation/uninephrectomy. At day 54, 13 donors and 11 recipients were re-investigated. Sixteen of these constituted eight matched pairs. This reduction in the study population was caused by the application of two withdrawal criteria.
2. In the recipients glomerular filtration rate was unchanged at day 5 and had increased to 61 ml/min at day 54 (P &lt; 0.05). In the donors glomerular filtration rate had increased to 59 ml/min by day 5 (P &lt; 0.01) and was unchanged at day 54.
3. In the recipients lithium clearance was unchanged at day 5 and had increased to 23 ml/min at day 54 (P &lt; 0.01). In the donors the lithium clearance had increased by day 5 (P &lt; 0.01).
4. In the recipients the absolute proximal fluid reabsorption rate was about 36 ml/min throughout the study period. In the donors the absolute proximal fluid reabsorption rate had increased to 42 ml/min by day 5 (P &lt; 0.05) and increased further to 44 ml/min by day 54 (P &lt; 0.01).
5. In the recipients sodium clearance increased from 0.54 ml/min to 2.10 ml/min at day 54 (P &lt; 0.01). In the donors it increased from 0.64 ml/min to 0.99 ml/min at day 54 (P &lt; 0.05).
6. Donor-recipient comparison showed that at day 54 there was no significant difference with regard to glomerular filtration rate, lithium clearance, absolute and fractional proximal fluid reabsorption rate and absolute distal sodium reabsorption rate. The sodium clearance was higher and the fractional distal sodium reabsorption rate was lower in the recipients.
7. In conclusion, the difference in function between donors and recipients at day 5 can probably be explained by the damaging effect of many inevitable factors on the graft. Fifty-four days after transplantation the function of the graft could not be distinguished from that of the remaining kidney. This suggests that the ideal homograft possesses a normal potential for compensatory hypertrophy once the effects of the initial post-operative ischaemia and toxic factors have subsided.
Lack of Importance in Humans of the Slow Component of the Response of Force to an Increase in Cardiac Muscle Length
Authors: Noble Mark I. M. , Drake-Holland Angela J. 
Published: August 2015

1. An increase in length in isolated animal muscles causes an immediate increase in contractile force, which is followed by a slower further progressive increase: the slow component. However, the pressure-volume concept, used in characterizing left ventricular function, is dependent on a constant relationship between pressure and volume.
2. We therefore examined the possible occurrence of the slow inotropic component of the response to cardiac muscle stretch in man at cardiac catheterization.
3. Human subjects undergoing left heart catheterization for clinical indications were studied. The development of the slow component was studied by measurement of rate of rise in left ventricular developed pressure and the time course after an increase in end-diastolic volume.
4. No evidence for any slow component was elicited.
5. It is concluded that the slow component of force (or pressure) increase after an increase in cardiac muscle length (or volume) does not have a role in the human heart in situ.
Plasma Kinins Increase after Angiotensin-Converting Enzyme Inhibition in Human Subjects
Authors: Pellacani Andrea , Brunner Hans R. , Nussberger Jürg 
Published: August 2015

1. In patients treated with angiotensin-converting enzyme inhibitors, kinin-related effects have been postulated repeatedly, but information on changes in plasma kinin levels in these patients is sparse. Difficulties in the measurement of plasma kinins account for this, at least in part.
2. The main purpose of the present study was to investigate, in normal human subjects, the effect of the angiotensin-converting enzyme inhibitor quinapril on plasma kinins.
3. High-affinity antisera (Kd &lt;10−11 mol/l) of C-terminal specificity were raised in rabbits for radioimmunoassay of immunoreactive kinins activating the bradykinin B2-receptor, and three different liquid-and solid-phase extraction methods for plasma kinins were evaluated. Ethanol and subsequent petroleum ether extraction of 5–40 fmol of bradykinin added to plasma yielded recoveries of 39 ± 16% (mean ± SD); normal kinin levels in human plasma were 18.6 ± 3.3 pmol/l (mean ± SEM). Solid-phase extraction on urea-equilibrated phenylsilylsilica produced recoveries of 89 ± 5% and normal values of 36.4 ± 18 pmol/l. Finally, with an assay based on ethanol extraction alone, recoveries of 100 ± 16% and normal values of 16.8 ± 5.8 pmol/l were obtained, with a detection limit of 1.5 fmol/ml of plasma. Blanks were below the detection limit. Serial dilution of plasma extracts (n = 4) provided linear kinin concentrations (r = 0.99). For two different plasma pools, coefficients of variation for within-assay precision were 16.7% and 21.7%, respectively. Between-assay coefficients of variation were 12.8% and 17.4%.
4. After an oral quinapril dose of 20 mg, we found, in nine healthy men, an increase in plasma kinin levels from 16.1 ± 1.9 pmol/1 (mean ± SEM) to 22.4 ± 2.8, 23.9 ± 23, 29.1 ± 4.7 (P &lt; 0.05) and 203 ± 4.2 pmol/1 at 2, 4, 8 and 24 h after drug intake, respectively.
5. Thus, in normal subjects treated with angiotensin-converting enzyme inhibitor plasma levels of B2-receptor stimulating kinins increase.
Reflex Sympathetic Dystrophy: Result of Autonomic Denervation?
Authors: Kurvers H. A. J. M. , Jacobs M. J. H. M. , Beuk R. J. , Van den Wildenberg F. A. J. M. , Kitslaar P. J. E. H. M. , Slaaf D. W. , Reneman R. S. 
Published: August 2015

1. To investigate the nature of sympathetic dysfunction in the pathogenesis of reflex sympathetic dystrophy, the microcirculatory vasoconstrictive responses to dependency were investigated in the skin of the hand of 76 reflex sympathetic dystrophy patients with unilateral disease by means of laser Doppler flowmetry (in perfusion units) and capillary microscopy. The patients were divided into three stages according to their perception of skin temperature (stage I in the case of a stationary warmth sensation, stage II in the case of an intermittent warmth and cold sensation, and stage III in the case of a stationary cold sensation). The vasoconstrictive responses were induced by lowering of the affected hand.
2. As compared to controls, the mainly sympathetically mediated vasoconstrictive response at thermoregulatory level of the skin microcirculation, as measured by laser Doppler flowmetry, was attenuated at stage I (1.82 versus 1.41, P &lt; 0.05), stage II (1.82 versus 1.09, P &lt; 0.0001) and stage III (1.82 versus 1.14, P &lt; 0.01), suggesting the involvement of sympathetic denervation at all stages of the reflex sympathetic dystrophy syndrome. This sympathetic denervation may also account for the observed increase in thermoregulatory skin blood flow at stage I as compared to controls (152 versus 81, P &lt; 0.01).
3. Since sympathetic denervation has been reported to cause increased sensitivity of vascular structures to catecholamines, the decrease in thermoregulatory skin blood flow at stages II (54 versus 81, P &lt; 0.05) and III (31 versus 81, P &lt; 0.05), both as compared to controls, may result from hypersensitivity to catecholamines of skin microvessels.
4. The sympathetically independent vasoconstrictive response at the nutritive level of skin microcirculation, as measured by capillary microscopy, was impaired only at stage III as compared to controls (1.04 versus 2.06, P &lt; 0.05). This divergence in microvascular reactivity upon dependency of the nutritive and thermoregulatory subsystems also supports the hypothesis of sympathetic dysfunction.
5. The disturbed vasoconstrictive responses to dependency may give rise to raised capillary pressures, contributing to the formation of oedema.
6. These findings suggest that sympathetic denervation and consequent hypersensitivity to catecholamines play an important role in the pathophysiology of reflex sympathetic dystrophy.
Plasma Atrial and Brain Natriuretic Peptides in Mitral Stenosis Treated by Valvulotomy
Authors: Tharaux Pierre-Louis , Dussaule Jean-Claude , Hubert-Brierre Jérôme , Vahanian Alec , Acar Jean , Ardaillou Raymond 
Published: August 2015

1. In order to appreciate the effect of changes in left atrial pressure on plasma brain natriuretic peptide, 20 patients with mitral stenosis treated by percutaneous valvulotomy were studied 10 min before and 15 min after the first balloon inflation. They were also studied 24 h before and 48 h after the valvulotomy. At these times the effect of postural changes on brain natriuretic peptide secretion was examined. A group of 10 control subjects was also studied under basal conditions. In each case, plasma atrial natriuretic peptide was measured in parallel with plasma brain natriuretic peptide.
2. Similarly to plasma atrial natriuretic peptide, plasma brain natriuretic peptide was elevated in patients with mitral stenosis (32 ± 2.9 and 32 ± 2.8 pg/ml in the upright and supine position respectively versus 13.5 ± 0.5 and 13.8 ± 1.8 pg/ml in controls; P &lt; 0.01). Changing from standing to lying did not modify plasma brain natriuretic peptide, whereas it produced an increase in plasma atrial natriuretic peptide in controls (13.3 ± 1.6 versus 24.8 ± 5.2 pg/ml; P &lt; 0.01) and in patients 48 h after valvulotomy (52.5 ± 4.6 versus 66.9 ± 6.6 pg/ml; P &lt; 0.01). Plasma brain natriuretic peptide also fell at this time (18.8 ± 1.1 and 19.1 ± 1.1 pg/ml in the upright and supine position respectively; P &lt; 0.01) similarly to plasma atrial natriuretic peptide and cyclic GMP (P &lt; 0.01). The acute left atrial mean pressure variation was significantly correlated with the parallel change in plasma atrial natriuretic peptide (P &lt; 0.001) but not in plasma brain natriuretic peptide. Plasma brain natriuretic peptide measured 24 h before and 48 h after valvulotomy was not correlated with plasma cyclic GMP, contrary to plasma atrial natriuretic peptide (P &lt; 0.001).
3. The results of the present study indicate that plasma brain natriuretic peptide depends on long-term but not on acute changes in left atrial pressure. This difference from atrial natriuretic peptide may result from both its preferential ventricular site of synthesis and its longer biological half-life.
Site of Action of Platelet-Activating Factor within the Mucosa of Rabbit Distal Colon
Authors: Travis S. P. L. , Crotty B. , Jewell D. P. 
Published: August 2015

1. To determine how platelet-activating factor stimulates colonic anion secretion and increases epithelial permeability, epithelial sheets of rabbit distal colon excluding the submucosal neural plexus were mounted in Ussing chambers. The influence of specific inhibitors and 50 nmol/l platelet-activating factor on short-circuit current and transepithelial resistance was then investigated.
2. Pretreatment with 1 μmol/l indomethacin or 1 μmol/l doxantrazole abolished the biphasic stimulation of the short-circuit current and decrease in transepithelial resistance induced by platelet-activating factor. Addition of 10 μmol/l mepyramine attenuated the early phase and completely inhibited the late phase. Pretreatment with 1 μmol/l ranitidine, 0.1 μmol/l tetrodotoxin, 0.1 μmol/l ritanserin or a 5-lipoxygenase inhibitor (1 μmol/l MK886) had no effect.
3. To assess the influence of platelet-activating factor on epithelial function isolated from lamina propria elements, monolayers were cultured from a human colonic epithelial cell line (T-84).
4. The short-circuit current across monolayers mounted in Ussing chambers stimulated by 10 μmol/l ionomycin could be inhibited by pretreatment with ouabain or frusemide, consistent with the capacity for chloride secretion. Addition of platelet-activating factor (up to 500 nmol/l) had no effect on short-circuit current or transepithelial resistance. Receptor expression was examined with [3H]platelet-activating factor in isolated T-84 and HT-29 cells and found to be absent.
5. The influence of physiological concentrations of platelet-activating factor on colonic epithelial anion secretion and increased permeability in rabbit distal colon is indirect and consistent with mediation by prostaglandins released from mucosal mast cells. Other mediators, including histamine acting through H1 but not H2 receptors, may have a role. 5-Lipoxygenase metabolites or 5-HT2 receptors appear not to be involved and, contrary to previous reports, the influence of platelet-activating factor on colonic epithelial function is independent of the submucosal neural plexus.
Contractile Properties of the Quadriceps Muscle in Growth Hormone-Deficient Hypopituitary Adults
Authors: Rutherford Olga M. , Beshyah Salem A. , Schott Jonathan , Watkins Yvonne , Johnston Desmond G. 
Published: August 2015

1. Growth hormone-deficient hypopituitary adults often complain of weakness and fatigue. The cause of the fatigue is unknown but could be an increased proportion of fast, fatiguable, type 2 fibres in the muscle. The aim of this study was to examine the contractile properties of the quadriceps muscle in a group of these patients compared with healthy controls. Changes in these properties were also examined in a small subset of the patients following growth hormone replacement.
2. Isometric strength, half-relaxation time from a twitch (t1/2) and the force—frequency relationship were measured using electrically evoked contractions in 14 growth hormone-deficient patients and 14 age- and sex-matched controls. Six patients were restudied following 6–24 month's replacement therapy with growth hormone (daily dose 0.04 ± 0.01 i.u./kg).
3. The growth hormone-deficient patients had a significantly lower t1/2 than the controls (46.1 ± 6.1 ms versus 56.1 ± 10.5 ms respectively; P = 0.0072; mean ± SD). The 10/100% ratio was also significantly lower in growth-hormone-deficient patients (38.6 ± 9.9% versus 52.3 ± 8.0%; P = 0.0005), as was muscle strength (349 ± 99 N versus 493 ± 215 N; P = 0.036). Following growth hormone replacement, muscle strength increased significantly (P &lt; 0.05). The 10/100% ratio also increased towards control values, but this change was not significant.
4. These results demonstrate that the relaxation times of the quadriceps are significantly shorter and that the force—frequency relationship shifted to the right in growth hormone-deficient patients, which is consistent with a greater proportion of type 2 fibres within the muscle. Preliminary data on a small group suggest that replacement with growth hormone results in a change in these properties towards that of controls.