bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between insulin's haemodynamic effects and insulin‐mediated glucose uptake
Authors: Ter Maaten  , Voorburg  , De Vries  , Ter Wee  , Donker  , Gans  
Published: March 2003

BackgroundInsulin resistance and hyperinsulinaemia are associated with hypertension. The relationship between insulin's metabolic and haemodynamic actions has not been fully elucidated however.MethodsWe investigated, using the euglycaemic clamp technique, the relationship between insulin‐mediated glucose uptake and insulin‐induced changes in leg blood flow and cardiac index in 13 healthy subjects. As insulin's effects on blood flow are time dependent, studies were performed during a 4‐h insulin (50 mU kg−1 h−1) infusion period.ResultsMean arterial pressure during insulin infusion increased (82.9 ± 6.7 to 89.8 ± 7.7 mmHg; P < 0.001), whereas heart rate was unaltered. Leg blood flow gradually increased from 1.09 ± 0.57 to 1.47 ± 0.67 mL min−1 dL−1 during the second hour, and to 1.65 ± 0.68 mL min−1 dL−1 during the fourth hour of the clamp (P = 0.01). Stroke volume index increased from 56.5 ± 13.3 to 63.7 ± 16.3 mL m−2 (P = 0.004) and cardiac index from 3.42 ± 1.02 to 3.73 ± 1.05 L min−1 m−2 (P = 0.04). The insulin‐mediated glucose disposal and the increases in leg blood flow were not correlated during the second hour (r = 0.21, P = 0.51) but showed a strong correlation during the fourth hour of the clamp (r = 0.88, P < 0.001). Insulin‐mediated glucose disposal was not correlated with the increases in cardiac index.ConclusionThus, insulin‐mediated muscle blood flow may be an important contributor to glucose uptake during sustained exogenous hyperinsulinaemia aiming at physiological insulin levels.
Effects of endotracheal intubation on airway neuropeptide content, arterial oxygenation and lung volumes in anaesthetized rats
Authors: Högman  , Reber  , Hua  , Dueck  , Yaksh  
Published: March 2003

BackgroundGeneral anaesthesia affects lung volume and pulmonary gas exchange. What role is played by mechanical stimulation by the endotracheal tube?MethodsWe investigated the effects of intubation on arterial oxygenation and lung volume in rats.ResultsEndotracheal intubation caused an increase in PA–a
O2 and volume of trapped gas in the lung. This was accompanied by a reduction in neuropeptides and calcitonin gene‐related peptide (CGRP) in trachea, bronchi and lung, and in vasoactive intestinal peptide (VIP) in the trachea. The increase in PA–a
O2 and volume of trapped gas due to intubation was not altered in the animals given capsaicin, in which neuropeptide levels were reduced.ConclusionsThese data suggest that the decrease in CGRP and VIP content in the airway tissues may be one of the consequences, but not the cause, of impaired gas exchange by endotracheal intubation. The increase in volume of trapped gas in the lung is apparently not mediated by activation of capsaicin‐sensitive sensory nerves.
Influence of plasma phytanic acid levels in Refsum's disease on the behaviour of the erythrocyte membrane sodium–lithium countertransporter
Authors: Wierzbicki  , Hardman  , Lumb  , Sankaralingam  , Morrish  , Patel  , Sidey  , Gibberd  
Published: March 2003

BackgroundAbnormal behaviour of the erythrocyte membrane sodium–lithium countertransporter (SLC) is associated with plasma triglyceride concentrations. Refsum's disease is characterized by progressive neurological dysfunction and accumulation of phytanic acid, an isoprenoid fatty acid, in fat‐containing tissues.MethodsThis study explored the effects of plasma phytanic acid on SLC kinetics in nine Caucasian patients with Refsum's disease and in age‐ and sex‐matched Caucasian control subjects.ResultsA dose‐dependent association was seen between countertransporter maximal velocity and phytanic acid content of low‐density lipoprotein (LDL)‐cholesterol (r = −0.61, r = −0.65 respectively; P = 0.05, P = 0.04) and high‐density lipoprotein (HDL)‐cholesterol (r = − 0.81, − 0.82 respectively; P = 0.005, P = 0.003). No significant association was seen with the sodium affinity of the transporter (r = − 0.44, P = 0.20, for LDL; and − 0.43, P = 0.21, for high‐density lipoprotein).ConclusionThese findings suggest that phytanic acid may alter the behaviour of the sodium–lithium countertransporter.
Expression of tenascin is related to angiogenesis in pre‐eclampsia
Authors: Ribatti  , Loverro  , Vacca  , Greco  , Roncali  , Selvaggi  
Published: March 2003

MethodsTen samples of decidua basalis from pre‐eclamptic women and 10 from healthy primigravid women subjected to caesarean section (control tissues) were investigated immunohistochemically for changes in angiogenesis and expression of tenascin, an extracellular matrix protein thought to modulate angiogenesis. In addition, pre‐eclamptic and control samples were grafted onto the chick embryo chorioallantoic membrane (CAM) to study their possible angiogenic activity in vivo.ResultsAlthough the microvessel area was low in control samples, it increased significantly in the pre‐eclamptic decidua. In parallel, the area covered by tenascin staining underwent a significant expansion that was highly correlated with the microvessel area. Angiogenic activity was assessed both macroscopically and microscopically on histological sections 4 days after grafting. In contrast to control samples, pre‐eclamptic decidua induced an intense capillary growth, and numerous capillaries converging towards the implant and forming a spoke‐wheel pattern were evident. Histological examination using a planimetric point‐count method showed that microvessel counts in the CAM area under and around the pre‐eclamptic implants were significantly higher than those of control samples. Again, the extracellular matrix of nearby microvessels was strongly immunoreactive with tenascin.ConclusionIt is suggested that, unlike normal decidua, pre‐eclamptic decidua displays an intense, autonomous angiogenic activity, probably mediated by tenascin in addition to its own angiogenic factors.
Sodium selenite and N‐acetylcysteine in antiretroviral‐naive HIV‐1‐infected patients: a randomized, controlled pilot study
Authors: Look  , Rockstroh  , Rao  , Barton  , Lemoch  , Kaiser  , Kupfer  , Sudhop  , Spengler  , Sauerbruch  
Published: March 2003

BackgroundThe aim of this work was to study the effects of combined oral administration of N‐acetylcysteine (NAC) and sodium selenite (Se) on plasma glutathione (GSH), lymphocyte subpopulations and viral load in asymptomatic human immunodeficiency virus (HIV)‐infected patients.MethodsWe used a prospective, randomized and controlled therapy trial with partial cross‐over. Twenty‐four antiretroviral‐naive HIV‐infected outpatients at Centers for Disease Control (CDC) '93 stages I and II were randomized to receive the antioxidant combination NAC 600 mg t.i.d. and Se 500 μg per day for either 24 weeks (group A, n = 13) or from the end of week 12 (group B, n = 11) until the end of week 24. Thus, group B served as untreated control during the first 12 weeks.ResultsThere was (a) a trend towards an increase in the percentage of CD4+ lymphocytes after 6 weeks (P = 0.08); (b) an increase in the CD4/CD8 ratio after 6 and 12 weeks (P = 0.02 and P = 0.04 respectively); and (c) a decrease in the absolute CD8/CD38 count and percentage of lymphocytes after 6 weeks (P = 0.002 and P = 0.033 respectively) and 12 weeks (P = 0.033, P = 0.1 respectively) in group A compared with the control period of group B. The effects observed in group A were, however, not paralleled to the same extent by group B after crossing‐over to treatment after 12 weeks. In addition, erythrocyte glutathione peroxidase (GSH‐Px) activity and GSH, glutathionedisulphide (GSSG) concentrations and the reduced/total GSH ratio were not affected by the treatment. Serum selenium levels increased significantly (P < 0.001) upon treatment. Viral load was not altered.ConclusionsThe changes in lymphocyte subsets after NAC/Se treatment were not comparable to those after standard antiretroviral drug therapy. This, however, does not preclude per se possible benefits of antioxidant supplementation in HIV disease.
Hepatocellular defence against acidosis is preserved after cold storage
Authors: Helbling  , Renner  
Published: March 2003

BackgroundPrimary non‐function of liver allografts is related to preservation time, during which hypoxia leads to intracellular accumulation of acid. Preservation‐induced failure of hepatocellular pH regulation may play a role in the pathogenesis of primary graft non‐function.MethodsUsing cultured/suspended rat hepatocytes and fluorimetric determination of intracellular pH, we determined whether preservation in University of Wisconsin solution (4°C) impairs hepatocellular defence mechanisms against acidosis.ResultsIn non‐preserved, 24‐h‐preserved and 48‐h‐preserved hepatocytes acidified to pH 6.7–6.8, initial Na+/H+ antiport‐mediated H+ fluxes averaged 12 ± 5, 9 ± 5 and 12 ± 5 nmol μL−1 min−1 and initial Na+/HCO3− symport‐mediated HCO3− fluxes 7 ± 2, 7 ± 3 and 6 ± 2 nmol μL−1 min respectively (P = NS). Preservation did not affect the inverse relationship between Na+/H+ antiport activity and intracellular pH. Thus, hepatocellular defence against intracellular acidosis is maintained during up to 48 h in University of Wisconsin solution.ConclusionAltered pHi homeostasis is unlikely to play a role in the pathogenesis of primary non‐function of liver allografts.
Tamm–Horsfall protein isolated from urine of pregnant and non‐pregnant women has similar oligosaccharides
Authors: Olczak  , Kubicz  , Kokot  , Duława  
Published: March 2003

BackgroundDifferences in the immunosuppressive activity of Tamm–Horsfall protein and uromodulin claimed by many investigators are controversial. They have been ascribed to variations in the carbohydrate moiety.MethodsWe isolated urinary glycoproteins from 18 non‐pregnant (THP) and 12 pregnant (UM) women using the same method (adsorption on diatomaceous earth) and performed comparative studies including monocarbohydrate analysis and tests of reactivity with lectins, cytokines and serum proteins.ResultsNo significant differences in monocarbohydrate content or in the reactivity with specific lectins were found between the native urinary glycoproteins or between their proteolytic products. Also, in Sda+ and Sda− donors monitored throughout pregnancy and after delivery, no time‐dependent differences in the sugar moiety were observed. We found that THP/UM from Sda+ donors reacted more strongly with PHA‐L than THP/UM from Sda− donors, providing further evidence for carbohydrate variations between Sda+ and Sda− determinants. No differences between THP and UM in terms of their reactivity with recombitant human interleukin (rhIL) 1α, recombinant human tumour necrosis factor (rhTNF) α and some serum proteins were found, indicating similar biological activity.ConclusionThe results of our carbohydrate analysis together with previous data on amino acid analysis indicate that Tamm–Horsfall protein and uromodulin are identical or very similar glycoproteins.
Time course of immunological markers in patients with the systemic inflammatory response syndrome: evaluation of sCD14, sVCAM‐1, sELAM‐1, MIP‐1α and TGF‐β2
Authors: Stoiser  , Knapp  , Thalhammer  , Locker  , Kofler  , Hollenstein  , Staudinger  , Wilfing  , Frass  , Burgmann  
Published: March 2003

BackgroundThe systemic inflammatory response syndrome (SIRS) is viewed as a system‐wide inflammatory response. Up until now, no parameter has been available for predicting the development of septic shock. In the present study, we evaluated the usefulness of serum levels of CD14, vascular cell adhesion molecule‐1 (VCAM‐1), endothelial leucocyte adhesion molecule‐1 (ELAM‐1), macrophage inflammatory protein (MIP) 1α and transforming growth factor β2 (TGF‐β2) as early markers of outcome in patients with SIRS.MethodsA group of 28 SIRS patients (13 survivors/15 non‐survivors) was compared with a healthy control group and with patients with local inflammation. Blood samples were analysed on days 0, 4 and 7. Proinflammatory parameters such as sCD14, sVCAM‐1, sELAM‐1, MIP‐1α and anti‐inflammatory parameters such as TGF‐β2 were determined using enzyme‐linked immunosorbent assay (ELISA).ResultsAt the beginning, all evaluated proinflammatory immunological parameters with the exception of sVCAM‐1 were significantly increased in patients with SIRS compared with the healthy control group. However, no significant difference could be observed for all immunological parameters comparing survivors and non‐survivors, with the exception of interleukin (IL) 6 at day 7.ConclusionAll evaluated proinflammatory parameters were increased in patients with SIRS during the course of the disease. However, the parameters have no correlation with outcome and prognosis of SIRS patients.
Haemodynamic effects of 8‐day octreotide and prazosin administration in portal hypertensive rats
Authors: Lin  , Wu  , Huang  , Hou  , Lee  , Hong  
Published: March 2003

BackgroundOctreotide and prazosin are both effective portal hypotensive drugs in the control or prevention of variceal bleeding. The present study was undertaken to investigate the haemodynamic effects of octreotide and prazosin, alone or in combination, in portal hypertensive rats.MethodsPortal hypertension was induced by partial portal vein ligation. Portal hypertensive rats were allocated into one of the four groups — vehicle group (saline, 0.5 mL 12 h−1), octreotide group (30 μg kg−1 12 h−1), prazosin group (0.4 mg kg−1 12 h−1), and octreotide (30 μg kg−1 12 h−1) plus prazosin (0.4 mg kg−1 12 h−1) group — with eight rats in each group. Prazosin or saline was administered by gavage, whereas octreotide was administered by subcutaneous injection. The drug was given on the day of ligation and continued for 8 consecutive days. Systemic as well as splanchnic haemodynamic parameters were measured thereafter.ResultsPortal vein‐ligated rats exhibited typical hyperdynamic state compared with sham‐operated rats. The portal venous pressure, portal tributary blood flow and cardiac index were significantly reduced by treatment of octreotide, prazosin or octreotide plus prazosin in portal hypertensive rats. Hyperdynamic parameters of systemic, renal and portal territory vascular resistances, and renal as well as hepatic arterial blood flow were ameliorated by treatment of octreotide or octreotide plus prazosin in portal hypertensive rats. Overall, octreotide treatment exerted more beneficial haemodynamic effects than prazosin treatment. The combination of octreotide and prazosin exerted better haemodynamic effects in cardiac index but worse effects in systemic as well as portal territory vascular resistance than octreotide treatment alone.
Effects of digoxin and digitoxin on circadian blood pressure profile in healthy volunteers
Authors: Grossmann  , Jamieson  , Kirch  
Published: March 2003

BackgroundThe aim of the study was to investigate the potential effects of chronic digoxin or digitoxin treatment on circadian blood pressure profile in normotensive subjects.MethodsIn two randomized double‐blind, placebo‐controlled cross‐over protocols, 22 healthy normotensive subjects were enrolled, 12 subjects in either study. After adequate loading doses, digoxin 0.25 mg twice daily or digitoxin 0.1 mg daily was given for a total of 10 days. Automatic 24‐h ambulatory blood pressure measurements were carried out at days 4 and 10 of either glycoside or placebo.ResultsDigoxin treatment significantly decreased heart rate (HR) and diastolic blood pressure (DBP) during the overnight sleeping phase of day 10 compared with placebo (HR, 4 beats min−1; DBP, 8 mmHg; P < 0.05). Digitoxin treatment significantly decreased heart rate and diastolic blood pressure during the overnight sleeping phase of day 4 (HR, 8 beats min−1; DBP, 7 mmHg) and day 10 (HR, 7 beats min−1; DBP, 5 mmHg) compared with placebo (P < 0.05). Neither digoxin nor digitoxin significantly affected systolic blood pressure.ConclusionsBoth digoxin and digitoxin, within therapeutic steady‐state plasma concentrations, reduce diastolic blood pressure and heart rate during overnight sleep, presumably because of increased parasympathetic activity or decreased sympathetic activity.
Increased risk for endogenous hypertriglyceridaemia is associated with an apolipoprotein C3 haplotype specified by the SstI polymorphism
Authors: Hoffer  , Sijbrands  , De Man  , Havekes  , Smelt  , Frants  
Published: March 2003

BackgroundHypertriglyceridaemia is a common metabolic disorder frequently found in patients with coronary heart disease. Numerous studies have revealed an association between the SstI polymorphism in the APOC3 gene and increased plasma apoC3 and triglyceride levels. In addition, two different variants within the promoter region have been recently suggested to be the mutations of the APOC3 gene leading to hypertriglyceridaemia.MethodsIn the present study, we have applied haplotype analysis to investigate whether these promoter polymorphisms are involved in the lipid disorders of patients with distinct types of hypertriglyceridaemia: combined hyperlipidaemia (CHL), familial dysbetalipoproteinaemia (FD) and endogenous hypertriglyceridaemia (HTG).ResultsThe −482 and −455 polymorphisms were significantly more frequent in FD patients (P = 0.017) and endogenous HTG patients (P < 0.0001) than in CHL patients and a control group. The SstI polymorphism was only significantly more frequent in HTG patients (P < 0.0001). However, we did not find differences in frequencies for these polymorphisms in the APOC3 gene between CHL patients and a control group. Haplotype analysis indicates that the SstI polymorphism arose on the allele containing both promoter polymorphisms.ConclusionThe haplotype containing the SstI polymorphism is found five times more frequently among HTG patients (OR 5.28, 95% CI 1.65–16.90), which strongly suggests it is associated with an increased risk for severe hypertriglyceridaemia.
Endothelin‐1 receptor antagonism does not influence myocardial function in hypertensive dogs
Authors: Massart  , Hodeige  , Van Mechelen  , Heyndrickx  , Donckier  
Published: March 2003

BackgroundAs endothelin‐1 exerts positive inotropic effects, the present study evaluated whether the hypotensive effects of the endothelin‐1 receptor antagonist bosentan were partially related to a decrease in myocardial performance.MethodsIn group I, eight anaesthetized open‐chest dogs with perinephritic hypertension received four cumulative doses of bosentan (B1–B4). In group II, eight animals received the same doses of bosentan after autonomic blockade. Indices of heart function were derived from the pressure–length loops obtained during vena cava occlusion.ResultsIn group I, bosentan decreased left ventricular systolic pressure (LVSP) and mean aortic pressure (MAP) dose dependently, reaching 21% and 23% respectively at B4 (LVSP from 190 ± 8 to 150 ± 5 mmHg, P < 0.001; MAP from 167 ± 7 to 128 ± 5 mmHg, P < 0.001). These effects were only related to peripheral vasodilatation, without depression of myocardial contractility, as systemic vascular resistance dropped (from 670 ± 83 to 446 ± 53 mmHg mL−1 min−1 × 104; P < 0.05), and the end‐systolic pressure–length relationship (ESPLR) remained unchanged (4.0 ± 0.4 vs. 4.3 ± 0.7 mmHg mm−1 kg−1). Concomitantly with pressure decline, heart rate tended to increase in this group (from 150 ± 4 to 156 ± 6 beats min−1). When autonomic system was blocked (group II), administration of bosentan induced similar hypotensive effects as in group I (26% and 28% reduction in LVSP and MAP respectively, P < 0.001) whereas ESPLR did not change (3.0 ± 0.9 vs. 3.1 ± 0.5mmHg−1 mm kg−1 ). Under these sympathetically blocked conditions, heart rate significantly fell after bosentan infusion (from 120 ± 4 to 110 ± 6 beats min−1, P < 0.001).ConclusionsWithout influencing heart function, bosentan is an efficient and safe therapy that opens up new therapeutic perspectives in human essential hypertension.
Acute hyperglycaemia causes severe disturbances of mesenteric microcirculation in an in vivo rat model
Authors: Schäffler  , Arndt  , Schölmerich  , Palitzsch  
Published: March 2003

BackgroundChronic hyperglycaemia in diabetes is suggested to be a major cause of diabetic angiopathy. Up until now, the effects of acutely induced hyperglycaemia in non‐diabetic subjects as well as hyperglycaemic effects in early diabetes, on mesenteric microcirculation and leucocyte endothelial cell interaction have not been investigated extensively.MethodsThe aim of this study was to examine rat mesenteric microcirculatory parameters such as leucocyte adhesion, leucocyte emigration, venular shear rate and leucocyte rolling velocity using a new rat model both with continuous venous glucose infusion and with continuous arterial measurement of blood glucose concentration while observing mesenteric microcirculation with in vivo capillary microscopy in the non‐diabetic and diabetic state.ResultsIn normal non‐diabetic rats, acute elevation of glucose concentration resulted in a highly significant, rapid and step‐by‐ step enhancement of adhesion and emigration in a dose dependent manner. Leucocyte rolling velocity was reduced with rising glucose levels. Venular shear rate showed a similar reduction at all hyperglycaemic levels. In streptozotocin‐induced diabetes, adhesion and emigration were significantly enhanced while shear rate and leucocyte rolling velocity were severely reduced, resembling the effects of glucose infusion experiments. Longer duration of diabetes resulted in a further enhancement of leucocyte adhesion and reduction of leucocyte rolling velocity while emigration and shear rate were not influenced by a longer period of diabetes manifestation.ConclusionExperiments using different mannitol concentrations revealed that most of the observed glucose effects can be mimicked by mannitol and are therefore — at least in part — due to changes in osmolarity by yet unknown mechanisms.
Effects of spiroglumide, a gastrin receptor antagonist, on acid secretion in humans
Authors: Beltinger J. , Hildebrand P. , Drewe J. , Christ A. , Hlobil K. , Ritz M. , D'Amato M. , Rovati L. , Beglinger C. 
Published: March 2003

BackgroundA gastrin receptor antagonist, CR2194 (spiroglumide), was used to explore the physiological role of gastrin in regulating gastric acid secretion in humans.Materials and methodsThe effect of CR2194 on inhibition of gastrin‐stimulated acid output was evaluated in a four‐period crossover study. Each subject received intravenous doses of 1, 2.5 or 7.5 mg kg−1 h−1 CR2194 or saline (control) followed by graded increasing doses of gastrin (6.4–800 pmol kg−1 h−1). Secondly, the effect of CR2194 on meal‐stimulated intragastric acidity was evaluated by infusing either saline (control) or CR2194 (7.5 mg kg−1 h−1) before and after food ingestion.ResultsAcid secretion was dose‐dependently inhibited by CR2194. With CR2194, acidity was significantly reduced in the pre‐meal and post‐prandial period (P < 0.01 and 0.002 respectively), and the integrated gastrin response was augmented to 8.0 ± 1.4 ng mL−1 240 min compared with 1.5 ± 0.8 ng mL−1 240 min in the control experiment (P < 0.01). Finally, acid secretion in response to sham feeding was significantly reduced: 15.9 ± 0.9 mmol 90 min−1 in the control experiment compared with 2.8 ± 0.9 mmol 90 min−1 during CR2194 infusion (P < 0.05).ConclusionGastrin receptor blockade with CR2194 alters gastric acid secretion in response to food ingestion or to sham feeding. The results support a physiological role for gastrin in regulating acid secretion in humans.