bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dipyridamole and dilazep suppress oxygen radicals in puromycin aminonucleoside nephrosis rats
Authors: Nakamura  , Kojima  , Arai  , Shirai  , Usutani  , Akimoto  , Masaoka  , Nagase  , Yamamoto  
Published: March 2003

BackgroundReactive oxygen species (ROS) are involved in the pathophysiology of puromycin aminonucleoside (PAN) nephrosis. To elucidate further the role of radicals in PAN nephrosis and the to determine the particular radical species scavenged by dipyridamole (DPM) and dilazep (DZ), we applied chemiluminescence and electron spin resonance (ESR) techniques.MethodsChemiluminescence of glomeruli, which were isolated on day 7 from rats injected with 100 mg kg−1 PAN, was measured with or without scavengers. The inhibitory effects of DPM and DZ on hydroxyl radical adduct formation in the Fenton's reaction were evaluated using ESR.ResultsChemiluminescence was greater in glomeruli from rats with PAN nephrosis than in the the glomeruli of control rats. This increase was suppressed by superoxide dismutase, catalase, dimethylthiourea and also by DPM and DZ. ESR indicated that DPM and DZ inhibited hydroxyl radical adduct formation with a second‐order rate constant of 2.9 × 1010 and 1.6 × 1010 (mol L−1 s−1) respectively, similar to that of dimethylthiourea.ConclusionDPM and DZ scavenge hydroxyl radicals, thereby alleviating PAN nephrosis.
Sudden infant death syndrome and nitrogen metabolism: further development of a hypothesis
Authors: Wiklund  , George  , Nord  , Ronquist  , Saldeen  
Published: March 2003

BackgroundA hypothesis suggesting an inducible inability of the enteric bacteria to metabolize urea in infants, resulting in metabolic alkalosis and subsequent respiratory insufficiency, has been proposed as the cause of sudden infant death syndrome (SIDS).MethodsMicrobiological cultivation and determination of faecal urease activity and faecal urea content were carried out in 30 cases of unexpected infant deaths out of which 22 were considered to be due to SIDS and eight from other causes. The concentration of nitric oxide (NO) in sealed test tubes was determined after incubation of faeces in normal saline.ResultsThe SIDS subjects differed significantly from the control cases in two respects: they had low or no sigmoid faecal urease activity and an unmetabolized sigmoid faecal urea content, whereas the control subjects had normal faecal urease activity and none, or very little, remaining faecal urea. The NO concentration in faeces was correlated with the faecal content of urea in the SIDS cases.ConclusionThe present findings lend support to the hypothesis of an insufficient metabolism of enteric urea in infants with SIDS.
Aspirin inhibits inducible nitric oxide synthase expression and tumour necrosis factor‐α release by cultured smooth muscle cells
Authors: Sánchez de Miguel L. , De Frutos T. , González‐Fernández F. , Del Pozo V. , Lahoz C. , Jiménez A. , Rico L. , García R. , Aceituno E. , Millás I. , Gómez J. , Farré J. , Casado S. , López‐Farré A. 
Published: March 2003

BackgroundInflammatory related cardiovascular disease, i.e. cardiac allograft rejection, myocarditis, septic shock, are accompanied by cytokine production, which stimulates the expression of inducible nitric oxide (iNOS).Materials and methodsThe aim of the present study was to examine whether anti‐inflammatory doses of acetylsalicylic acid (aspirin) could regulate iNOS protein expression in bovine vascular smooth muscle cells (BVSMCs) in culture.ResultsInterleukin 1β (IL‐1β, 0.03 U mL−1) induced nitric oxide release by BVSMCs. Aspirin inhibited nitric oxide release from IL‐1β‐stimulated BVSMCs in a dose‐dependent manner. In addition, aspirin significantly inhibited iNOS protein expression in BVSMCs and reduced the translocation of the nuclear factor‐κB (NF‐κB). Furthermore, aspirin and the blockade of NO generation by BVSMCs reduced the production of tumour necrosis factor α (TNF‐α) by these cells.ConclusionHigh doses of aspirin inhibited iNOS protein expression in BVSMCs and decreased NF‐κB mobilization. The inhibition of iNOS expression by aspirin was further associated with a reduced ability of BVSMCs to produce TNF‐α. This study could provide new mechanisms of action for aspirin in the treatment of the inflammation‐related cardiovascular diseases.
Determination of heparin‐induced IgG antibody in heparin‐induced thrombocytopenia type II
Authors: Wang  , Huhle  , Malsch  , Hoffmann  , Song  , Harenberg  
Published: March 2003

BackgroundHeparin‐induced thrombocytopenia is a relatively uncommon but severe side‐effect of heparin therapy. Heparin‐induced IgG antibody has been elucidated to be the main isotype and the most pathogenic antibody in the pathophysiology. As affected patients are at high risk of developing thrombotic events, confirmation of the clinical diagnosis and avoidance of heparin re‐exposure are important and desirable.Materials and methodsIn the present study, heparin‐induced IgG was measured by the binding of neoantigens, which were prepared by incubating FITC‐heparin with platelet factor 4 present in normal serum. The cross‐reactivities of heparin‐induced IgG with low‐molecular‐weight heparin and danaparoid were analysed by competitive binding.ResultsA total of 81 clinically suspected heparin‐induced thrombocytopenia type II patients were analysed. Thirty‐seven of 38 heparin‐induced thrombocytopenia type II patients, in whom thromboembolism was confirmed by objective methods, had elevated relative fluorescence intensity ratios (patient normal control) and 36 had positive heparin‐induced platelet activation results. The prevalence of heparin‐induced IgG in heparin‐induced thrombocytopenia type II patients was 97.4%. Positive heparin‐induced IgG results were: 0/319 healthy volunteers, 0/38 other thrombo‐cytopenia and 2/56 heparin/low‐molecular‐weight heparin‐receiving patients without thrombocytopenia, 2/41 hyperbilirubinaemic patients and 2/50 hyperlipidaemic patients. A small amount of cross‐reaction assays showed similar results as obtained in heparin‐induced platelet activation.ConclusionOur results suggest that a very high frequency of heparin‐induced IgG in heparin‐induced thrombocytopenia type II patients can be detected using a novel antigen assay. The rapid determination of pathogenic heparin‐induced IgG may be a useful tool for the rapid diagnosis of heparin‐induced thrombocytopenia type II that could facilitate further management of the patients.
Serum zinc, copper, insulin and lipids in Alzheimer's disease epsilon 4 apolipoprotein E allele carriers*
Authors: González  , Martín  , Cacho  , Breñas  , Arroyo  , García‐Berrocal  , Navajo  , González‐Buitrago  
Published: March 2003

BackgroundCopper (Cu) and zinc (Zn) have been implicated in the development of Alzheimer's disease (AD) and, in this regard, Cu and Zn serum concentrations have been analysed but with inconclusive results. Serum insulin, glucose and cholesterol concentrations have been related to the apolipoprotein E genotype in non‐AD populations.DesignIn this study, we have analysed the relationship between serum Cu, Zn, insulin, glucose and lipid parameters (cholesterol, triglycerides, apoA and apoB apolipoproteins) in AD and AD epsilon 4 apolipoprotein E carriers by multivariate analysis using logistic regression, including the variables that showed a significance of P < 0.05 in the bivariate analysis.ResultsThe results obtained show that epsilon 4 apoE allele is an independent AD risk factor (OR = 6.67, 95% CI = 2.59–17.16). In AD epsilon 4 apoE allele carriers, we found significantly higher Zn, Cu and insulin serum concentrations. Non‐demented control subjects with at least one epsilon 4 apoE allele had the lowest serum insulin concentrations. There was no significant association between epsilon 4 apolipoprotein E allele and lipid parameters in the sample studied.ConclusionsIn AD we have found a significant association between higher serum Zn, Cu and insulin concentrations and the presence of an epsilon 4 apoE allele, but only greater serum Zn concentration appears to be an independent risk factor associated with the development of AD.
Echocardiographic features of primary, secondary and familial amyloidosis
Authors: Moyssakis I. , Triposkiadis F. , Rallidis L. , Hawkins P. , Kyriakidis M. , Nihoyannopoulos P. 
Published: March 2003

BackgroundCurrently recognized types of amyloidosis include primary, familial and secondary, each of which may affect the heart. There may be differences in the heart response to the deposition of amyloid fibrils in these three forms of the disease.Materials and methodsOver a period of 10 years (1985–95), 28 consecutive patients with primary, 11 with secondary and 17 with familial amyloidosis were studied at the Departments of Cardiology of Laiko and Hammersmith Hospitals. The diagnosis of amyloidosis was confirmed by biopsies of subcutaneous fat, rectum, kidney, bone marrow, gum or sural nerve. Diagnosis of cardiac involvement was based on typical electrocardiographic and echocardiographic findings.ResultsThe left ventricular fractional shortening (%) was reduced in primary compared with familial or secondary amyloidosis (29.8 ± 10.2 vs. 36.2 ± 6.5 vs. 36 ± 5.9, P < 0.05). The transmitral flow velocity pattern was compatible with abnormal relaxation in most patients in the three groups [primary 16 (57%), familial 11 (64.7%), secondary 6 (54.5%), P = NS]. Right ventricular systolic dysfunction (right ventricular dP/dt < 220 mmHg s−1 or tricuspid annulus systolic excursion < 10 mm) was present in 8 (28.6%), 2 (11.8%) and 0 patients. Patients with primary amyloidosis were followed up for 15 ± 6 months. There were 12 deaths, and repeat echocardiography in the survivors revealed a significant deterioration of left ventricular systolic function (fractional shortening = 23.6% ± 8.8%, P < 0.05 vs. baseline).ConclusionPrimary amyloidosis is characterized by more severe cardiac involvement than the familial or secondary amyloidosis and has an ominous course.
Insulin decreases plasma cholesteryl ester transfer but not cholesterol esterification in healthy subjects as well as in normotriglyceridaemic patients with type 2 diabetes
Authors: Dullaart  , Riemens  , Scheek  , Van Tol  
Published: March 2003

BackgroundPlasma cholesterol esterification (EST) and subsequent cholesteryl ester transfer (CET) from high‐density lipoproteins (HDLs) towards apolipoprotein (apo) B‐containing lipoproteins are key steps in HDL metabolism.Materials and methodsThe effects of exogenous hyperinsulinaemia on plasma CET and EST, measured with isotope methods, were evaluated in 10 male normotriglyceridaemic (plasma triglycerides <2.0 mmol L−1) patients with type 2 diabetes and 10 individually matched healthy subjects during a two‐step hyperinsulinaemic euglycaemic clamp over 6–7 h.ResultsNo between‐group differences in baseline plasma lipid parameters were observed, but the HDL cholesteryl ester content was lower (P < 0.02) and the HDL triglyceride content was higher (P < 0.05) in diabetic patients. Baseline CET and EST were similar in the groups. In both groups, hyperinsulinaemia decreased plasma triglycerides (P < 0.01) and the HDL triglyceride content (P < 0.01) compared with saline infusion in healthy subjects, whereas the HDL cholesteryl ester content increased (P < 0.05 vs. saline infusion) in diabetic patients. CET was similarly decreased by hyperinsulinaemia in both groups (P < 0.01 vs. saline infusion). In contrast, the change in EST in either group was not different from that during saline administration. In the combined group, baseline CET was positively correlated with plasma triglycerides (Rs = 0.68, P < 0.01). The HDL cholesteryl ester content was negatively (Rs = −0.48, P < 0.05) and the HDL triglyceride content was positively (Rs = 0.64, P < 0.01) correlated with CET.ConclusionInsulin infusion decreases plasma CET in conjunction with a fall in triglycerides but does not decrease cholesterol esterification in healthy and type 2 diabetic subjects, indicating that acute hyperinsulinaemia has a different effect on these processes involved in HDL metabolism. Despite unaltered fasting plasma CET, HDL core lipid composition was abnormal in diabetic patients, suggesting that additional mechanisms may contribute to changes in HDL metabolism in diabetes mellitus.
High dose insulin does not increase glucose transfer across the blood–brain barrier in humans: a re‐evaluation
Authors: Knudsen  , Hasselbalch  , Hertz  , Paulson  
Published: March 2003

BackgroundThis study re‐evaluates previously published data on blood–brain barrier transfer coefficients in humans exposed to high insulin levels.DesignIn this study of seven volunteers, global blood–brain barrier permeability to glucose and phenylalanine was measured by means of the intracarotid double‐indicator method before, during, and after an insulin‐glucose clamp. Data were reanalyzed by means of a mathematical model that takes capillary heterogeneity and labelled glucose backflux from the brain into account.ResultsThe permeability‐surface area product (PS) for glucose transport from the blood into the brain, PS1, was 0.145 (0.102–0.211) (median and quartiles), 0.146 (0.113–0.259), and 0.157 (0.133–0.181) ml g−1 min−1 before, during, and after insulin challenge, respectively. In six of the subjects, PS for transport from brain to blood over the brain glucose distribution volume, PS2/Ve decreased under hyperinsulinemia, from a baseline value of 6.56 (3.0–14.9) to 3.86 (1.41–5.32), and restored to a value of 3.8 (2.8–12.1) min−1 after insulin challenge. This decrease in PS2/Ve is probably due to an increase in the brain glucose distribution volume induced by an insulin induced increased intracellular glucose uptake during the experiment. For phenylalanine (n = 5), PS1 was unchanged before, during, and after insulin challenge. In hyperinsulinemia, PS3/Ve for phenylalanine decreased in all subjects.ConclusionWe conclude that acutely elevated high plasma insulin levels in humans does not alter the brain uptake of glucose or phenylalanine from the blood. It seems, however, that high plasma insulin levels induce an increase in the movement of d‐glucose and
l‐phenylalanine from the brain interstitial fluid into the intracellular compartment.
Acute methylprednisolone administration induces a transient alteration of glucose tolerance and pyruvate dehydrogenase in humans
Authors: Pellacani  , Fornengo  , Bruno  , Ceruti  , Mioletti  , Curto  , Rinaudo  , Pagano  , Cavallo‐Perin  
Published: March 2003

BackgroundGlucocorticoid administration induces alteration of glucose tolerance, and impairment of glucose oxidation may contribute to glucocorticoid‐induced derangement of glucose metabolism. We investigated glucose tolerance following methylprednisolone administration in humans. In the same model, we evaluated pyruvate dehydrogenase (PDH), the rate limiting enzyme of glucose oxidation, in peripheral blood mononuclear cells.Materials and methodsMethylprednisolone (2 × 40 mg, iv, one dose every 12 h) was administered to six healthy volunteers. Glucose tolerance was evaluated through an oral glucose tolerance test (oGTT, 75 g glucose) at least a week before and after drug administration (2 and 24 h post‐drug). To assess modifications of lipid metabolism circulating free fatty acids (FFA) and glycerol were measured, during fasting and oGTT. The active form of PDH (PDHa) was evaluated in peripheral blood mononuclear cells, both as ex vivo activity and as in vitro response to insulin (30pmol l−1).ResultsMethylprednisolone induced an alteration of glucose tolerance 2 h after its administration. Such alteration was completely reversed at 24 h. Alteration of glucose tolerance was accompanied by decreased ex vivo PDHa activity. PDH responsiveness to insulin in vitro was also impaired. Circulating FFA were unmodified, but decreased glycerol levels suggested a slight inhibition of lipolysis.ConclusionsAcute methylprednisolone administration in humans induced a transient decrease of glucose tolerance 2 h after drug administration, accompanied by hyperinsulinaemia, inhibition of ex vivo PDH activity and its response to insulin in vitro. These alterations were completely abolished at 24 h, suggesting that methylprednisolone can be safely administered acutely. Furthermore, methylprednisolone induced only minor modifications of circulating FFA and glycerol, indicating minimal impact on lipid metabolism.
Creatine corrects muscle 31P spectrum in gyrate atrophy with hyperornithinaemia
Authors: Heinänen  , Näntö‐Salonen  , Komu  , Erkintalo  , Alanen  , Heinonen  , Pulkki  , Nikoskelainen  , Sipilä  , Simell  
Published: March 2003

BackgroundEye fundus destruction and type II muscle fiber atrophy in gyrate atrophy of the choroid and retina with hyperornithinaemia (GA) may be mediated by elevated ornithine concentrations which strongly inhibit creatine biosynthesis. This results in deficiency of creatine phosphate (PCr), a key intracellular energy source, as we have demonstrated in skeletal muscle of the patients by 31P magnetic resonance spectroscopy (31P MRS).Materials and methodsPossible correction of the relative PCr deficiency by long‐term daily exogenous supplementation of creatine or its precursors was investigated in four GA patients receiving creatine and in five patients treated with guanidinoacetic acid‐methionine combination. The relative PCr concentration, expressed as PCr/Pi (Pi; inorganic phosphate) or as PCr/ATP ratios, was compared with the values of untreated GA patients, and matched healthy volunteers.ResultsMuscle PCr/Pi ratios (mean ± SD) of the untreated and creatine supplemented GA patients and controls were 4.9 ± 1.4, 7.9 ± 0.4 and 8.4 ± 1.3. Guanidinoacetate‐methionine combination was similarly effective (respective PCr/Pi ratios: 4.9 ± 0.7, 6.3 ± 1.1 and 10.7 ± 2.8).ConclusionSupplementation with creatine or creatine precursors almost normalised low muscle PCr/Pi ratios of patients with GA.
The p22 phox polymorphism C242T is not associated with CHD risk in Asian Indians and Chinese
Authors: Saha  , Sanghera  , Kamboh  
Published: March 2003

BackgroundOxygen free radicals such as superoxide anion have been implicated in the pathogenesis of atherosclerosis and coronary heart disease (CHD). The nonglycosylated 22 kDa α‐subunit of the NADH/NADPH oxidase (p22 phox) of the vasculature acts as the final electron transporter in the generation of superoxide anion. Recently, a common polymorphism (C242T) at codon 72 in the p22 phox gene has been reported to be associated with CHD risk.Study designWe examined the role of the C242T polymorphism with the risk of CHD in a biracial sample of Asian Indians and Chinese from Singapore. The sample comprised angiographically confirmed CHD patients (126 Asian Indians and 151 Chinese) and age‐ and sex‐matched healthy control subjects (154 Asian Indians and 167 Chinese).ResultsThe frequency of the T allele was significantly higher in Asian Indian control subjects than in Chinese control subjects (0.38 vs. 0.09; P < 0.0001). However, there was no difference in the frequency of this allele between case patients and control subjects either in Chinese (0.10 vs. 0.09) or Asian Indians (0.38 vs. 0.40). This polymorphism was also not associated with plasma lipid and apolipoprotein levels in any group.ConclusionsThe p22 phox codon 72 polymorphism is not associated with the risk of CHD in the present samples of Asian Indians and Chinese.
Influence of physical exercise on polyamine synthesis in the rat skeletal muscle
Authors: Turchanowa  , Rogozkin  , Milovic  , Feldkoren  , Caspary  , Stein  
Published: March 2003

BackgroundPhysical exercise and testosterone administration result in a series of adaptive anabolic phenomena in the skeletal muscle. The role of polyamines in these processes has been poorly explored.DesignWe measured the activities of polyamine‐synthesising enzymes, ornithine decarboxylase (ODC) and S‐adenosylmethionine decarboxylase (SAMDC) and polyamine content in skeletal muscle of male rats exposed to endurance or resistance exercise, or a single testosterone treatment. Soleus muscle (consisting mainly of slow‐twitching oxidative fibres—STO) and extensor digitorum longus (mainly fast‐twitching glycolytic muscle fibres—FTG) were analysed for polyamine content by HPLC, and ODC and SAMDC activity.ResultsBoth endurance and resistance exercise induced a threefold increase in endogenous testosterone production. Two hours after exercise, ODC was increased in STO fibres, returning to baseline after 24 h; in FTG fibres the increase was less prominent. An increase in SAMDC activity occurred in a more sustained manner, with its peak 8 h after exercise. Polyamines were subsequently accumulated in both skeletal muscle fibres, with a rise in putrescine concentration after 2 h, and a fall corresponding to conversion of putrescine to spermidine and spermine by SAMDC. Single dose of 17α‐methyltestosterone resulted in a similar increase in polyamine‐synthesising enzyme activities and polyamine concentrations in the skeletal muscle.ConclusionPolyamine accumulation in the skeletal muscle after physical exercise is likely to occur secondary to testosterone production. Polyamines are apparently involved in the oxidative, but not in glycolytic processes related to muscle adaptation to exercise.
Effectiveness of recombinant erythropoietin and iron sucrose vs. iron therapy only, in patients with postpartum anaemia and blunted erythropoiesis
Authors: Breymann  , Richter  , Hüttner  , Huch  , Huch  
Published: March 2003

BackgroundTo compare efficacy between recombinant human erythropoietin (rhEPO) plus parenteral iron vs. iron alone (parenteral vs. oral) in postpartum anaemia.MethodsSixty patients (haemoglobin 8.6 ± 1.1 g dL−1) were randomized to rhEPO plus intravenous (i.v.) iron sucrose (group 1), rhEPO placebo plus i.v. iron sucrose (group 2), or oral iron alone (group 3), daily for 4 days beginning 48–72 h postpartum. Erythropoiesis and iron status were assessed before, and on 4, 7 and 14 days after, starting therapy.ResultsOn day 7 the group 1 haematocrit increase was 7.7 ± 3.1% vs. 5.3 ± 1.9% (group 2, P < 0.01) and 4.4 ± 3.2% (group 3, P < 0.01), and on day 14, 11.3 ± 2.9% vs. 9.2 ± 3.4% (group 2, P < 0.05) and 8 ± 2.8% (group 3, P < 0.01). The odds of achieving a target haematocrit > 32% on day 7 and > 35% on day 14 were higher on rhEPO (1.5–2.7) than on either iron regimen alone. Group 1 reticulocyte counts were also higher on days 4 (P < 0.05 vs. oral iron) and 7 (P < 0.01 vs. oral and parenteral iron).ConclusionAll three regimens were effective in postpartum anaemia, but the haematocrit and reticulocyte responses to rhEPO plus parenteral iron were significantly greater than to iron alone. Benefit was greatest in the blunted erythropoiesis subgroup with elevated post‐Caesarean section C‐reactive protein levels.