bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zinc salts precipitate unconjugated bilirubin in vitro and inhibit enterohepatic cycling of bilirubin in hamsters
Authors: Méndez‐Sánchez N. , Roldán‐Valadez E. , Flores M. A. , Cárdenas‐Vázquez R. , Uribe M. 
Published: March 2003

Background We have evidence for enterohepatic cycling of bilirubin experimentally and in vivo in humans. This study was designed to investigate whether Zn salts might inhibit such cycling of bilirubin.Materials and methods Micellar bile salt solutions with unconjugated bilirubin were prepared, appropriate concentrations of Zn salts were added, and unconjugated bilirubin precipitation was measured. Hamsters and Wistar rats were fed a chow diet or a chow diet enriched with 1% ZnSO4, and bilirubin secretion rates were monitored.Results Unconjugated bilirubin was precipitated maximally (90%) after a 10‐min incubation with 5 mM Zn salts in the pH range of 6·8–9·0. In control hamsters, total bilirubin secretion rates into bile were 36·0 ± 2·8 nmol h−1 100g −1 body weight, whereas they were 25·0 ± 3·3 nmol h−1 100 −1g in the ZnSO4 group (P < 0·05).Conclusions Zn salts that flocculate at physiological pH adsorb unconjugated bilirubin almost completely from unsaturated micellar BS solutions. In addition, Zn salts administered orally suppress biliary bilirubin secretion rates in hamsters. These findings suggest that the administration of Zn salts may inhibit the enterohepatic cycling of unconjugated bilirubin in humans who are predisposed to pigment gallstone formation due to diet, disease or drugs.
Incidence and geographical distribution of sudden infant death syndrome in relation to content of nitrate in drinking water and groundwater levels
Authors: George M. , Wiklund L. , Aastrup M. , Pousette J. , Thunholm B. , Saldeen T. , Wernroth L. , Zarén B. , Holmberg L. 
Published: March 2003

Background Previous studies indicate that the enteral bacterial urease is inhibited in victims of sudden infant death syndrome (SIDS). One possible inhibitor of this bacterial activity is nitrate. If ambient pollution by nitrate is involved in the etiology of SIDS only a fraction of the nitrate concentration not infrequently found in drinking water would be enough for this inhibition.Methods Occurrence of SIDS (n = 636) in Sweden during the period 1990 through 1996 were analysed regarding geographical and seasonal distribution in relation to the nitrate concentration in drinking water and changes in the groundwater level.Results Both the birth rate and the incidence of SIDS decreased during the study period. One quarter of the municipalities constituting 11% of the population had no cases, the maximum incidence being 6·5 per 1000 live births. Seasonality: The northernmost parts of the country had its highest incidence when the rest of the country had its lowest incidence, and the occurrence of individual deaths was associated with the recharge of groundwater which increases its nitrate content. The local incidence of SIDS was correlated (rs = 0·34–0·87) to maximally recorded concentrations of nitrate in drinking water.Conclusions The seasonal distribution of SIDS was widely different from the south to the north of the country and seems to be associated with differences in the groundwater level changes subsequent to precipitation, frost penetration, and melting of snow. Use of drinking water with high peak concentrations or great variations in nitrate concentration was correlated to the incidence of SIDS.
Glutathione in blood of patients with Friedreich's ataxia
Authors: Piemonte F. , Pastore A. , Tozzi G. , Tagliacozzi D. , Santorelli F. M. , Carrozzo R. , Casali C. , Damiano M. , Federici G. , Bertini E. 
Published: March 2003

Oxidative stress and mitochondrial dysfunction have long been considered to play a role in Friedreich's ataxia, a neurodegenerative disease due to a GAA expansion in a gene coding for a mitochondrial protein (frataxin), implicated in the regulation of iron metabolism. Since glutathione is an important antioxidant whose role has been recently proposed in the pathogenesis of some neurodegenerative diseases, we investigated glutathione metabolism in the blood of 14 patients with Friedreich's ataxia by measuring total, free and protein‐bound glutathione concentrations.Blood samples were obtained from 14 unrelated patients with Friedreich's ataxia (nine males, five females) and 20 age‐matched healthy controls (10 males, 10 females). Total and free glutathione concentrations were determined by reverse‐phase liquid chromatography with fluorescence detection; the glutathionyl‐haemoglobin separation from healthy and pathological subjects was obtained by electrospray ionization–mass spectrometry.We consistently found a reduction of free glutathione levels (0·55 ± 0·06 nmol mg−1 haemoglobin, vs. 8·4 ± 1·79 nmol mg−1 haemoglobin, P < 0·001) in the blood of patients with Friedreich's ataxia, a total glutathione concentration comparable to the controls (15 ± 2·6 nmol mg−1 haemoglobin, vs. 15·4 ± 1·4 nmol mg−1 haemoglobin), and a significant increase of glutathione bound to haemoglobin (15 ± 1·5 vs. 8 ± 1·8%, P < 0·05) in erythrocytes.Our findings give evidence of an impairment in vivo of glutathione homeostasis in Friedreich's ataxia, suggesting a relevant role of free radical cytotoxicity in the pathophysiology of the disease; this study may also prove useful in the search for an oxidative stress marker in neurodegeneration.
Alcohol consumption alters insulin secretion and cardiac autonomic activity
Authors: Flanagan D. E. H. , Pratt E. , Murphy J. , Vaile J. C. , Petley G. W. , Godsland I. F. , Kerr D. 
Published: March 2003

AbstractBackground Alcohol may have a cardioprotective effect. One possible mechanism is by modifying insulin resistance/secretion. The aims of this study were: (i) to examine the effect of short‐term alcohol consumption on the metabolic control of glucose tolerance; (ii) to study the influence of short‐term alcohol consumption on cardiac autonomic activity using spectral analysis of heart rate variability.Methods Twenty‐one healthy subjects, in a randomized crossover design, either received three units of ethanol daily for 1 week or abstained from ethanol. The control of glucose tolerance was assessed using the intravenous glucose tolerance test with minimal modelling.Results There was no difference in fasting glucose, fasting insulin or insulin sensitivity between the two groups. Alcohol showed a lower insulin first phase insulin response (no alcohol 659·0 ± 394·1 SD, alcohol 535·2 ± 309·1) pmol L−1 min−1, P = 0·027). There was no difference in heart rate or blood pressure but a significant difference in the ratio of high to low frequency spectral power of heart rate variability; (no alcohol 4·55 ± 3·78, alcohol 8·16 ± 6·77, P = 0·033). This suggests decreased sympathetic and/or increased vagal modulation of heart rate in the alcohol group.Conclusion The finding of no difference in insulin sensitivity between the two groups contrasts with, but does not entirely contradict, the results of previous epidemiological studies – perhaps suggesting that longer term changes such as liver enzyme induction may be important. The difference in insulin secretion questions the validity of previous studies of the influence of alcohol on insulin sensitivity, where insulin levels were used as a surrogate for insulin resistance.
Can a determination of tartrate‐resistant acid phosphatase predict postmenopausal loss of bone mass?
Authors: Rico H. , Arribas I. , Villa L. F. , Casanova F. J. , Hernández E. R. , Cortés‐Prieto J. 
Published: March 2003

AbstractBackground  A study was carried out over a 24‐month interval to determine if an initial measurement of serum tartrate‐resistant acid phosphatase would be predictive of bone mass loss quantified by dual‐energy X‐ray absorptiometry, as total bone mineral content and total bone mineral content corrected for weight.Design  Sixty‐two women were studied (at onset: mean age 59·7 ± 8·9 years, 10·8 ± 8·8 years since menopause; at conclusion: mean age 61·9 ± 8·8 and 13·0 ± 8·7 since menopause).Results  A paired Wilcoxon test showed a small, but significant, increase in weight (P < 0·05) and decrease in height (P < 0·05). Total bone mineral content and total bone mineral content corrected for weight decreased (P < 0·005 and 0·0001, respectively). Serum tartrate‐resistant acid phosphatase increased (P < 0·005). Single‐regression analysis showed that the per cent bone mass loss observed between the first and second body bone mineral content measurements correlated negatively with the first serum tartrate‐resistant acid phosphatase determination (r = −0·62, P < 0·0001). Changes in tartrate‐resistant acid phosphatase correlated negatively with changes in total bone mineral content (r = −0·79, P < 0·0001). In a multiple regression analysis of per cent change in bone mass against initially important variables such as age, years since menopause, weight, and tartrate‐resistant acid phosphatase, only tartrate‐resistant acid phosphatase was significant (P < 0·0001). The sensitivity and specifity of tartrate‐resistant acid phosphatase for evaluating bone loss were 86% and 78%, respectively, and the area under the curve was of 0·83 (95% CI 0·71–0·95).Conclusion  These results show that a simple measurement of serum tartrate‐resistant acid phosphatase can help to predict the potential rate of bone mass loss in women.
Hyperhomocysteinemia and impaired vasomotor function in type 2 diabetes mellitus
Authors: Tan K. C. B. , Karmin O. , Chow W.‐S. , Ai V. H. G. , Siow Y. L. , Lam K. S. L. 
Published: March 2003

AbstractBackground Hyperhomocysteinemia has been shown to adversely affect vascular function. The aim of this study was to determine whether hyperhomocysteinemia was independently associated with changes in endothelium‐dependent and ‐independent vasomotor functions in patients with type 2 diabetes mellitus.Materials and methods Fasting homocysteine (tHcy) was measured in 123 patients with type 2 diabetes and in 61 nondiabetic controls. Endothelium‐dependent and ‐independent vasodilation was measured using high‐resolution vascular ultrasound.Results Plasma tHcy concentration was increased in the diabetic patients (11·1 ± 3·7 µmol L−1 vs. 9·8 ± 2·9, P < 0·05). The prevalence of hyperhomocysteinemia (defined as tHcy > 15 µmol L−1) was higher in the diabetic patients (P < 0·05). Within group comparisons showed that both the abnormalities in endothelium‐dependent and ‐independent vasodilation were significantly more severe in diabetic patients with tHcy 10–15 (P < 0·05) and tHcy > 15 µmol L−1 (P < 0·05) than in those patients with tHcy < 10 µmol L−1. When compared with nondiabetic controls matched for tHcy levels, impairment of endothelium‐dependent and ‐independent vasodilation were already evident, even in patients with normal tHcy levels (P < 0·01). Despite significant univariate relationships between tHcy and endothelium‐dependent (r = −0·24, P < 0·01) and ‐independent vasodilation (r = −0·33, P < 0·01) in patients with diabetes, only the relationship between tHcy and endothelium‐independent vasodilation remained significant after adjusting for other cardiovascular risk factors in multiple regression analysis.Conclusions Impairment of endothelium‐dependent and ‐independent vasodilation was already present in diabetic patients with normal tHcy levels, and these abnormalities became more severe with increasing tHcy levels. Only the association between tHcy and endothelium‐independent vasodilation was free of other cardiovascular risk factors.
Biological effects of secretory phospholipase A2 group IIA on lipoproteins and in atherogenesis
Authors: Jaross Werner , Eckey Rolf , Menschikowski Mario 
Published: March 2003

AbstractSecretory phospholipase A2 group IIA(sPLA2 IIA) can be produced and secreted by various cell types either constitutionally or as an acute‐phase reactant upon stimulation by proinflammatory cytokines. The enzyme prefers phosphatidylethanolamine and phosphatidylserine as substrates. One important biological function may be the hydrolytic destruction of bacterial membranes. It has been demonstrated, however, that sPLA2 can also hydrolyse the phospholipid monolayers of high density lipoprotein (HDL) and low density lipoprotein (LDL) in vitro. Secretory phospholipase A2‐modified LDL show increased affinity to glycosaminoglycans and proteoglycans, a tendency to aggregate, and an enhanced ability to deliver cholesterol to cells. Incubation of cultured macrophages with PLA2‐treated LDL and HDL is associated with increased intracellular lipid accumulation, resulting in the formation of foam cells. Elevated sPLA2(IIA) activity in blood serum leads to an increased clearance of serum cholesterol. Secretory phospholipase A2(IIA) can also be detected in the intima, adventitia and media of the atherosclerotic wall not only in developed lesions but also in very early stages of atherosclerosis. The presence of DNA of Chlamydia pneumoniae, herpes simplex virus, and cytomegalovirus was found to be associated with sPLA2(IIA) expression and other signs of local inflammation. Thus, sPLA2(IIA) appears to be one important link between the lipid and the inflammation hypothesis of atherosclerosis.
Gastric emptying in myotonic dystrophy
Authors: Rönnblom A. , Andersson S. , Hellström P. M. , Danielsson Å. 
Published: March 2003

AbstractBackgroundGastrointestinal symptoms are common and important for the quality of life in patients with myotonic dystrophy (MD). Gastric emptying was studied in patients with MD who suffered from symptoms suggesting slow gastric emptying and the effect of prokinetic treatment was evaluated.MethodsGastric emptying was studied in 10 patients with MD who were suffering from nausea, early satiety, bloating, regurgitation, vomiting, or abdominal pain using a99Tc‐labelled test meal, and was compared with gastric emptying in a group of healthy controls. The patients were subsequently treated with erythromycin and their gastrointestinal symptoms were recorded and the gastric emptying test was repeated.ResultsPatients with MD had a significantly longer gastric lag phase (46·1 ± 4·3 vs. 31·9 ± 4·0 min,P = 0·03), a slower emptying phase (7·1 ± 0·9 vs. 10·2 ± 0·9 kJ min−1,P = 0·02) and a longer half‐emptying time,T50(141·7 ± 10·5 vs. 98·6 ± 8·7 min,P = 0·01) than a matched control group. Erythromycin did not stimulate the gastric emptying rate. The effect on gastrointestinal symptoms was modest, except for a reduction of diarrhoea.ConclusionsPatients with MD suffering from nausea, vomiting and early satiety, displayed a slow gastric emptying. Treatment with erythromycin had only moderate effect on gastric emptying or gastric symptoms, but reduced diarrhoea in a majority of the patients.
The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase‐2 negative colon cancer cells
Authors: Yu H.‐G. , Huang J.‐A. , Yang Y.‐N. , Huang H. , Luo H.‐S. , Yu J.‐P. , Meier J. J. , Schrader H. , Bastian A. , Schmidt W. E. , Schmitz F. 
Published: March 2003

SummaryBackground Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti‐inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase‐2 (COX‐2) negative colorectal cancer cell lines.Materials and Methods After treatment with various concentrations of ASA, cell proliferation was measured in the human colon cancer cell line SW480. Apoptotic cells were identified by transmission electron microscopy, acridine orange staining, and flow cytometry. The invasive potential of SW480 cells was detected using an in vitro invasion assay. The production of carcinoembryonic antigen was measured by microparticle enzyme immunoassay. Expression of Bcl2, Bax, CD44v6, and nm23 were evaluated by immunocytochemistry.Results ASA significantly inhibited the proliferation of SW480 cells and stimulated apoptosis. Production of carcinoembryonic antigen and the invasive potential of SW480 cells were also inhibited by ASA. After treatment with ASA, down‐regulation of Bcl2 and CD44v6 expression and up‐regulation of nm23 expression were observed in SW480 cells. No obvious effect of ASA was found on Bax expression.Conclusion Our findings reveal that ASA inhibits the proliferation and promotes apoptosis in the human colon cancer cell line SW480. Down‐regulation of Bcl2 expression might represent a potential mechanism by which ASA induces apoptosis in this COX‐2 negative colon cancer cell line. Our results also suggest that ASA decreases the invasive potential of these colon cancer cells. Decreased CEA content and CD44v6 expression and elevated nm23 expression may contribute to the effect of ASA on invasive potential of SW480 colon cancer cells.
Association between increased levels of IL‐2 and IL‐15 and outcome in patients with early acute respiratory distress syndrome
Authors: Agouridakis P. , Kyriakou D. , Alexandrakis M. G. , Perisinakis K. , Karkavitsas N. , Bouros D. 
Published: March 2003

AbstractBackground Acute respiratory distress syndrome remains a serious, often fatal, condition, despite progress in modern critical care treatment. Cytokines play an important role in the pathogenesis of the syndrome, although their role in the evolution and outcome has not been clearly elucidated. We explored whether the measurement of serum and bronchoalveolar lavage IL‐2 and IL‐15 at the time of hospital admission can predict the outcome of this syndrome.Methods Serum and bronchoalveolar lavage levels of IL‐2 and IL‐15 were measured in eight patients with ARDS (group A) and 26 patients on high risk for ARDS development who never developed ARDS (group B) from samples obtained at the time of admission.Results Serum IL‐2 (P > 0·05) and IL‐15 (P < 0·05) levels were higher in group A than in group B. Serum levels of both cytokines were higher in patients who did not survive in both of the groups A and B compared to those who survived (P < 0·05, and P < 0·0001, respectively). The only significant change in BALF was the higher level of IL‐15 in surviving group A patients (P < 0·05) when compared with the non survivors of the same group. For a serum cut‐off level of 173 pg mL−1 for IL‐2 and 250 pg mL−1 for IL‐15, they exhibited a very high positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for survival (100% in all). A positive correlation was found between serum levels of both cytokines and APACHE II score (IL‐2, r = 0·61, and IL‐15, r = 0·62, respectively, and P < 0·0001 for both).Conclusion Determination of serum IL‐2 and IL‐15 levels may be a valuable and simple aid to improve identification of patients with ARDS or at risk for ARDS who are at high risk of subsequent mortality.
Ferric saccharate induces oxygen radical stress and endothelial dysfunction in vivo
Authors: Rooyakkers T. M. , Stroes E. S. G. , Kooistra M. P. , Van Faassen E. E. , Hider R. C. , Rabelink T. J. , Marx J. J. M. 
Published: March 2003

AbstractBackground  Intravenous iron supplementation is used widely in haemodialysis patients. However, nontransferrin‐bound iron (NTBI), which increases after intravenous supplementation of ferric saccharate, has been suggested to act as a catalytic agent in oxygen radical formation in vitro and may thus contribute to endothelial impairment in vivo.Materials and methods  In 20 healthy volunteers the effect of 100 mg ferric saccharate infusion was investigated. Vascular ultrasound was used to assess endothelium‐dependent vasodilatation at baseline, and 10 and 240 min after ferric saccharate infusion. Whole blood was collected to measure NTBI and in vivo radical formation was assessed by electron spin resonance. A time‐control study was performed using saline infusion.Results  Infusion of ferric saccharate induces a greater than fourfold increase in NTBI, as well as a transient, significant (P < 0·01) reduction of flow‐mediated dilatation 10 min after infusion of ferric saccharate, when compared with saline. The generation of superoxide in whole blood increased significantly 10 and 240 min after infusion of ferric saccharate by, respectively, 70 and 53%.Conclusions  Iron infusion at a currently used therapeutic dose for intravenous iron supplementation leads to increased oxygen radical stress and acute endothelial dysfunction.
Nature of nontransferrin‐bound iron
Authors: Hider R. C. 
Published: March 2003

AbstractNontransferrin‐bound iron is now recognized to exist by many workers. It is present in the serum of patients suffering from a wide range of disease states and may be induced by certain therapeutic treatments. The chemical nature of this iron pool is unknown but almost certainly it is a multicomponent pool including a considerable proportion of protein‐bound iron. Methods are required to separate and quantify these different components. The biological properties of the individual isoforms need to be established; it is possible that some forms are relatively nontoxic, while others are highly toxic. This paper reviews what is known about the nature of nontransferrin‐bound iron and describes the methods currently available to quantify this important serum component.
Human immunodeficiency virus type 1 replication inhibition by the bidentate iron chelators CP502 and CP511 is caused by proliferation inhibition and the onset of apoptosis
Authors: Georgiou N. A. , Van Der Bruggen T. , Oudshoorn M. , Hider R. C. , Marx J. J. M. , Van Asbeck B. S. 
Published: March 2003

AbstractBackgroundThe iron chelators deferoxamine (DF) and deferiprone (CP20) have been shown to inhibit human immunodeficiency virus type 1 (HIV‐1) replication in human peripheral blood lymphocytes (PBL). The orally active bidentate chelators CP502 and CP511, which also belong to the 3‐hydroxypyridin‐4‐one family, but with higher affinities for iron than CP20, were monitored for their antiviral properties by checking for p24 antigen production and nuclear factor (NF)‐κB activation, and their ability to induce apoptosis.Materials and methods Human PBLs were isolated from HIV‐1 seronegative donors and subsequently infected with HIV‐1Ba‐L for 2 h. After 5 days’ incubation, HIV‐1 replication was monitored by p24 antigen production. Cellular proliferation as well as caspase‐3 activity were monitored in uninfected cells after a period of 5 days and after 1 day infection, respectively. NF‐κB activity was also monitored by electromobility shift assays (EMSA) performed on nuclear extracts of Jurkat cells treated with the different chelators for 4 h.Results CP502 and CP511 decrease HIV‐1 replication by decreasing cellular proliferation in a similar manner to DF and CP20. CP511 seemed to be more potent than either CP502 or CP20. Due to the reduction in cellular proliferation, there was an increase in caspase‐3 activity after 24 h incubation. NF‐κB activity was not affected by any of the chelators.Conclusions Iron chelators with high affinities for iron, which are under development for the treatment of iron overload, could contribute to the reduction of HIV‐1 replication in infected patients by cellular proliferation inhibition rather than by a direct antiviral action.
Dinucleotide repeat polymorphisms within the Flt‐1 gene in minimal change nephropathy
Authors: Parry R. G. , Gillespie K. M. , Clark A. G. B. , Mathieson P. W. 
Published: March 2003

AbstractDysregulation of Flt‐1, a major receptor for vascular permeability factor (VPF), may provide a mechanism for the development of proteinuria in minimal change nephropathy (MCN). The gene for Flt‐1 has a polymorphic dinucleotide repeat. We have demonstrated an 88% predominance of one allele and an 80% rate of homozygosity for this polymorphism with no association with MCN.