bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exhaled nitric oxide during incremental and constant workload exercise in chronic cardiac failure
Authors: Lovell  , Stevenson  , Young  , McDowell  , McEneaney  , Riley  , Nicholls  
Published: March 2003

BackgroundNitric oxide (NO) is present in exhaled breath and produced by the pulmonary vascular endothelium as a potent vasodilator. Exercise is normally associated with pulmonary vasodilatation and a decrease in pulmonary vascular resistance to accommodate the increase in cardiac output. If production of NO is impaired in patients with chronic congestive cardiac failure (CCF), this might contribute to their exercise intolerance.Patients and methodsWe quantified NO production (V˙ NO) in 12 patients with chronic stable CCF and 12 controls, at rest and during incremental cardiopulmonary exercise on a treadmill, and at a later date during constant workload exercise.ResultsPatients had reduced V˙ NO compared with controls during incremental exercise [381 (180) vs. 777 (275) nL min−1; mean (SD); P < 0.0001] but at constant workload V˙ NO was similar between the two groups [353 (124) vs. 389 (189) nL min−1; P = 0.25]. Plasma levels of nitrate, the stable end‐product of NO production, were significantly higher in patients [resting value 46.1 (21.6) vs. 23.0 (10.0) μM; P = 0.004] and were not influenced by exercise.ConclusionImpaired NO‐mediated pulmonary vasodilatation does not appear to contribute to exercise limitation in CCF. Alternatively, the lower NO production observed during maximal exercise in the patient group compared with controls may reflect a reduced incremental response of a system that is already abnormally activated in heart failure.
Effects of exogenous zinc supplementation on intestinal epithelial repair in vitro
Authors: Cario  , Jung  , Harder d'Heureuse  , Schulte  , Sturm  , Wiedenmann  , Goebell  , Dignass  
Published: March 2003

BackgroundSubstitution of zinc modulates antioxidant capabilities within the intestinal mucosa and improves intestinal wound healing in zinc‐deficient patients with inflammatory bowel diseases. The aim of this study was to characterize the modulating effects of zinc on intestinal epithelial cell function in vitro.Materials and methodsThe effects of zinc on intestinal epithelial cell morphology were assessed by phase contrast and transmission electron microscopy using the non‐transformed small intestinal epithelial cell line IEC‐6. Zinc‐induced apoptosis was assessed by DNA fragmentation analysis, lactate dehydrogluase (LDH) release and flow cytometry with propidium iodine staining. Furthermore, the effects of zinc on IEC‐6 cell proliferation were assessed using a colorimetric thiazolyl blue (MTT) assay and on IEC‐6 cell restitution using an in vitro wounding model.ResultsPhysiological concentrations of zinc (25 μm) did not significantly alter the morphological appearance of IEC‐6 cells. However, a 10‐fold higher dose of zinc (250 μm) induced epithelial cell rounding, loss of adherence and apoptotic characteristics. While physiological zinc concentrations (< 100 μm) did not induce apoptosis, supraphysiological zinc concentrations (> 100 μm) caused apoptosis. Physiological concentrations of zinc (6.25–50 μm) had no significant effect on intestinal epithelial cell proliferation. In contrast, physiological concentrations of zinc (12.5–50 μm) significantly enhanced epithelial cell restitution through a transforming growth factor‐β (TGFβ)‐independent mechanism. Simultaneous addition of TGFβ and zinc resulted in an additive stimulation of IEC‐6 cell restitution.ConclusionZinc may promote intestinal epithelial wound healing by enhancement of epithelial cell restitution, the initial step of epithelial wound healing. Zinc supplementation may improve epithelial repair; however, excessive amounts of zinc may cause tissue injury and impair epithelial wound healing.
Detrimental effects of nitric oxide inhibition on hepatic encephalopathy in rats with thioacetamide‐induced fulminant hepatic failure
Authors: Chu C.‐J. , Wang S.‐S. , Lee F.‐Y. , Chang F.‐Y. , Lin H.‐C. , Hou M.‐C. , Chan C.‐C. , Wu S.‐L. , Chen C.‐T. , Huang H.‐C. , Lee S.‐D. 
Published: March 2003

Hepatic encephalopathy is a complex neuropsychiatric syndrome seen secondary to acute liver failure, chronic parenchymal liver disease, or portal‐systemic anastomosis. Vasodilatation induced by nitric oxide (NO) may be involved in the development of hepatic coma. However, there are no comprehensive data concerning the effects of NO inhibition on the severity of hepatic encephalopathy.Male Sprague‐Dawley rats weighing 300–350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of thioacetamide (TAA, 350 mg kg−1day−1) for 3 days. Rats were divided into two groups to receive eitherNG‐nitro‐l‐arginine methyl ester (l‐NAME, 20 mg kg−1 day−1via intragastric gavage) or normal saline (N/S) from 2 days prior to TAA administration for 5 days. Severity of encephalopathy was assessed by counts of motor activity and neurobehaviour test scores. Plasma levels of endotoxin, tumour necrosis factor‐α and nitrate/nitrite were determined by the chromogenicLimulusassay, enzyme‐linked immunosorbent assay and colorimetric assay, respectively.Compared with N/S‐treated rats, the mortality rate was significantly higher in rats receivingl‐NAME (59% vs. 18%,P < 0·01). Inhibition of NO had detrimental effects on the counts of motor activities (P < 0·05) and neurobehaviour score (P < 0·01). Rats treated withl‐NAME had significantly higher plasma levels of endotoxin (26·7 ± 3·8 pg mL−1) and tumour necrosis factor‐α (29·4 ± 6·5 pg mL−1) compared with rats treated with N/S (13·2 ± 2·7 pg mL−1and 11·2 ± 2·6 pg mL−1, respectively,P < 0·01). Plasma levels of endotoxin and tumour necrosis factor‐α, but not of nitrate/nitrite, were significantly correlated with the severity of hepatic encephalopathy (P < 0·05).Chronicl‐NAME administration had detrimental effects on the severity of encephalopathy in TAA‐treated rats, suggesting a protective role of NO in the development of fulminant hepatic failure.
Increased expression of VEGF following exercise training in patients with heart failure
Authors: Gustafsson T. , Bodin K. , Sylvén C. , Gordon A. , Tyni‐Lenné R. , Jansson E. 
Published: March 2003

Background and aims During the last decades several angiogenic factors have been characterized but so far it is unknown whether local muscle exercise training increases the expression of these factors in patients with moderate heart failure. Expression of the major putative angiogenic factor vascular endothelial growth factor (VEGF) at the level of messneger RNA (mRNA) and/or protein was therefore studied before and after 8 weeks of training in patient with chronic heart failure.Methods VEGF mRNA and protein concentrations were determined in skeletal muscle biopsies before and after 8 weeks of one‐legged knee extension training in patients with chronic heart failure (New York Heart Association II–III).Results Exercise training increased the citrate synthase activity and peripheral exercise capacity by 46% and 36%, respectively, in parallel with a two‐fold increase in VEGF at both the mRNA (P = 0·03) and protein (P = 0·02) levelsConclusion The increase in VEGF gene expression in response to exercise training indicates VEGF to be one possible mediator in exercise‐induced angiogenesis and may therefore regulate an important and early step in adaptation to increased muscle activity in patient with chronic heart failure.
Sodium–lithium countertransport is increased in normoalbuminuric type 1 diabetes but is not related to other risk factors for microangiopathy
Authors: Vervoort G. , Elving L. D. , Wetzels J. F. M. , Lutterman J. A. , Smits P. , De Pont J. J. H. H. M. , Berden J. H. M. 
Published: March 2003

AbstractBackground It has been reported that sodium–lithium countertransport (Na/Li CT) activity is increased in patients with diabetes mellitus and that this increased Na/Li CT activity is associated with the development of diabetic nephropathy. It is unclear however, whether Na/Li CT is related to other pathophysiological factors in diabetic patients. We studied kinetic parameters of Na/Li CT activity together with other putative risk factors for microangiopathy in normoalbuminuric type 1 diabetic patients and matched control subjects.Subjects and methods We measured maximum velocity (Vmax) and sodium affinity (Km) of Na/Li CT in 53 diabetic patients and 45 healthy controls. Endothelial function was assessed by monitoring forearm vascular response to intrabrachial infusion of acetylcholine. Blood samples were collected for measurement of HbA1c, glucose, insulin and lipids. Blood pressure was measured intra‐arterially. Renal haemodynamics were measured by inulin/p‐aminohippurate clearance. Urinary albumin was measured by enzyme‐linked immunosorbent assay. Transcapillary escape of albumin (TERalb) was calculated by the disappearance curve of 125I‐labelled albumin.Results V
max was increased in diabetic patients (779 ± 36 µmol Li+ h−1 L−1 erythrocytes vs. 623 ± 35 in controls, P < 0·01), whereas Km was decreased (64 ± 16 mmol L−1 vs. 76 ± 27 in controls, P = 0·03). The ratio of Vmax : Km was 12·4 ± 0·6 in diabetic patients and 8·9 ± 0·9 in controls (P < 0·001). When comparing diabetic patients in the lowest and highest quartile of Vmax or Km there were no differences in blood pressure, renal haemodynamics, urinary albumin excretion, TERalb, endothelial function, HbA1c, glucose, insulin, or lipid profile.Conclusion Na/Li CT is increased in uncomplicated type 1 diabetes and characterized by an increase in Vmax and a decrease in Km. The increase in Na/Li CT is not associated with changes in endothelial function, degree of metabolic control, blood pressure or renal haemodynamics.
Serum paraoxonase activity in patients with type 1 diabetes compared to healthy controls
Authors: Mackness B. , Durrington P. N. , Boulton A. J. M. , Hine D. , Mackness M. I. 
Published: March 2003

AbstractBackground The oxidation of low‐density lipoprotein (LDL) is central to current theories on the initiation and progression of atherosclerosis. Type 1 diabetes is associated with an increase in oxidative stress, which may be responsible for the increased susceptibility to coronary heart disease seen in type 1 diabetes. High‐density lipoprotein (HDL) associated paraoxonase (PON1) can retard the oxidation of LDL.Design Paraoxonase activity, concentration and genotype were therefore investigated in 152 people with type 1 diabetes and 282 healthy controls. These parameters were also investigated in the group with type 1 diabetes in relation to the presence of diabetic complications.Results Both PON1 activity and concentration were significantly lower by 16·7% and 19·2% (both P < 0·05) in the type 1 diabetes group. These differences were independent of the PON1 coding region polymorphisms. The distribution of PON1 activity and mass were the same in both populations, i.e. for the PON1‐192 polymorphism RR > RQ > QQ and for the PON1‐55 polymorphism LL > LM > MM. There were no differences in either the PON1 polymorphisms, PON1 activity and concentration in people with type 1 diabetes in the presence or absence of micro and macro vascular complications of diabetes.Conclusions Low PON1 activity may contribute to the increased atherosclerosis found in type 1 diabetes by reducing the ability of HDL to retard LDL oxidation despite the frequently‐found increased HDL in type 1 diabetes when good glycaemic control is established.
Glucocorticoids and 11β‐hydroxysteroid dehydrogenase type 2 gene expression in the aging kidney
Authors: Audigé A. , Dick B. , Frey B. M. , Frey F. J. , Corman B. , Vogt B. 
Published: March 2003

AbstractBackground Aging is associated with increased concentrations of circulating glucocorticoids, a situation expected to induce a glucocorticoid‐mediated mineralocorticoid effect, resulting in sodium retention and hypertension unless counteracting mechanisms are operative. Conversion of glucocorticoids to inert 11β‐keto compounds by the enzyme 11β‐hydroxysteroid dehydrogenase type 2 (11β‐HSD2) is one of these mechanisms. We hypothesized therefore that 11β‐HSD2 gene expression and/or activity increase with age in male WAG/Rij rats, a strain without increased blood pressure with age or senescence‐related obesity or kidney disease.Materials and methods Corticosterone (B) concentrations in plasma and urinary excretion of corticosterone and dehydrocorticosterone (A) tetrahydro metabolites, THB + 5α‐THB + THA, were assessed by gas chromatography‐mass spectrometry (GC‐MS) in 10‐month‐old‐rats (n = 6) and in 30‐month‐old rats (n = 6). Renal 11β‐HSD2 messenger ribonucleic acid (mRNA) abundance was measured by real‐time quantitative TaqMan polymerase chain reaction and microarray assays.Results Thirty‐month‐old rats had significantly higher corticosterone concentrations in plasma and increased urinary excretion of corticosterone and dehydrocorticosterone tetrahydro metabolites. Conversion of B to A in kidney microsomes from 30‐month‐old rats was moderately but not significantly increased compared with 10‐month‐old rats. The urinary ratios of (THB + 5α‐THB)/THA and free B/A and renal 11β‐HSD2 mRNA abundance were equal in 10‐ and 30‐month‐old rats.Conclusions There is no evidence for an enhanced gene expression or activity of renal 11β‐HSD2 in these aging rats, suggesting either that endogenous 11β‐HSD2 is able to cope with the increased corticosterone concentrations characteristic of the aging process or that alternative mechanisms contribute to the maintenance of a normal sodium excretion in these animals.
Intestinal absorption and biliary secretion of ursodeoxycholic acid and its taurine conjugate
Authors: Rudolph G. , Kloeters‐Plachky P. , Sauer P. , Stiehl A. 
Published: March 2003

AbstractBackground  Ursodeoxycholic acid (UDCA) and its taurine conjugate (TUDCA) exert a protective effect in cholestatic liver diseases. A greater hepatoprotective effect of TUDCA has been suggested. Absorption appears to be a limiting factor and up to now has not been studied in man.Methods  We studied absorption and biliary bile acid secretion and composition after administration of UDCA and TUDCA in patients who had complete extrahepatic biliary obstruction caused by pancreatic carcinoma but had no intestinal or liver disease. After 5 days of intact enterohepatic circulation eight patients with a percutaneous biliary–duodenal drainage received, during two study periods, 1000 mg (1916·9 µmol; mean 29·6 µmol kg−1) TUDCA and 750 mg (1910·4 µmol; mean 29·5 µmol kg−1) UDCA in random order. Each patient served as his own control.Results  After UDCA and TUDCA administration the biliary UDCA content increased to 55·2% and 54·6% of total bile acids, respectively (not significant). Biliary secretion of cholic and chenodeoxycholic acids remained unchanged whereas that of lithocholic acid increased slightly. A total of 64·6% of the orally administered TUDCA and 55·1% of the UDCA was absorbed (not significant). After TUDCA administration, biliary UDCA was preferentially (95·4%) taurine‐conjugated whereas after UDCA administration biliary UDCA was mainly (79·8%) glycine‐conjugated.Conclusions  After oral administration of TUDCA and UDCA, no significant differences in their absorption and in biliary bile acid secretion exist. Whether biliary enrichment with taurine conjugates of UDCA instead of glycine conjugates offers advantages in the treatment of cholestatic liver disease is unclear at present.
Factor XIII a‐positive dermal dendrocytes and shear wave propagation in human skin
Authors: Hermanns‐Lê T. , Uhoda I. , Piérard‐Franchimont C. , Piérard G. E. 
Published: March 2003

AbstractBackground The in vivo interdependence between the phenotypic characteristics of dermal cells and the strain imposed on the tissue has not been studied thoroughly in humans. In particular the mechanical force modulation of Factor XIII a expression in dermal dendrocytes (DD) remains unknown.Materials and methods The present study compares the numerical density of Factor XIII a‐positive DD and the in vivo shear wave velocity in the skin. The investigation was performed in 20 men of normal weight and 20 obese men before and after entering a slimming process.Results Excess cutaneous fat places the skin under increased intrinsic tension. The resonance running time measurement (RRTM) and the DD density were significantly reduced in overweight individuals. After a short‐term but intense slimming process, the same individuals showed a trend to normalization of these two parameters without, however, reaching significance. Pooling all data yielded a significant logarithmic correlation between RRTM values and densities in Factor XIII a‐positive DD.Conclusion Factor XIII a expression in human DD may be partially regulated by the intrinsic resting tensions in the skin.
Starvation reduces allergen‐induced skin wheal responses and plasma substance P and vasoactive intestinal peptide in patients with atopic eczema/dermatitis syndrome
Authors: Kimata H. 
Published: March 2003

AbstractThe effect of starvation on allergen‐induced skin wheal responses and plasma neuropeptide levels was not previously reported. Starvation for 24 h reduces allergen‐induced skin wheal responses and plasma levels of substance P and vasoactive intestinal peptide in patients with atopic eczema/dermatitis syndrome, but not in control subjects. These results may have implications for the pathophysiology of the atopic eczema/dermatitis syndrome.
Soluble leptin receptors and serum leptin in end‐stage renal disease: relationship with inflammation and body composition
Authors: Pecoits‐Filho R. , Nordfors L. , Heimbürger O. , Lindholm B. , Anderstam B. , Marchlewska A. , Stenvinkel P. 
Published: March 2003

AbstractBackground Elevated serum leptin (S‐leptin) levels have been reported in patients with end‐stage renal disease (ESRD). Apart from the decreased glomerular filtration rate (GFR), body composition and inflammation may affect leptin levels in ESRD. Leptin circulates both free of and bound to soluble leptin receptors (sOB‐R), which are the main determinants of leptin activity and have not been described in ESRD until now.Design To analyze the association between S‐leptin, sOB‐R, and inflammation and body composition, we studied 149 (62% males) normal weight (BMI 24·7 ± 0·4 kg m−2) ESRD patients (51 ± 1 years old) shortly before the start of dialysis (GFR 7·0 ± 0·2 mL min−1). sOB‐R and plasma interleukin‐6 (IL‐6; n= 113) levels were evaluated using ELISA, S‐leptin using RIA, and body composition was assessed by X‐ray absorptiometry (n = 139). Forty‐one healthy subjects age (51 ± 1 years), BMI (23·6 ± 0·5 kg m−2) and gender‐matched (59% males) were used as controls.Results Median S‐leptin was higher in the ESRD patients (10·0 ng mL−1) compared with the controls (3·9 ng mL−1) (P < 0·001). The median sOB‐R did not differ significantly between the ESRD patients (44 U mL−1) and the controls (37 U mL−1). Thus, the sOB‐R/S‐leptin ratio was lower in the ESRD patients (9·5 ± 1·2 vs. 12·3 ± 1·8; P < 0·01) than the controls. A negative correlation was observed between S‐leptin and sOB‐R (Rho = −0·42; P < 0·0001) in the ESRD patients, a positive correlation was observed between lean body mass and the sOB‐R/S‐leptin ratio (Rho = 0·33, P = 0·0001) whereas fat mass was negatively correlated to both sOB‐R (Rho = −0·26, P = 0·002), and the sOB‐R/S‐leptin ratio (Rho = −0·62, P < 0·0001). Positive correlations were observed between IL‐6 and S‐leptin (Rho = 0·19; P < 0·05) and weak but significant body fat mass (Rho = 0·20; P < 0·05), respectively.Conclusions This study demonstrates that despite markedly elevated S‐leptin levels in the ESRD patients, sOB‐R did not differ from the controls. In view of the anorexigenic and pro‐atherogenic effects of leptin, further elucidation of the consequences of free bioactive leptin in the development of complications such as malnutrition and cardiovascular disease in ESRD patients is required.
p53 codon 72 polymorphism and susceptibility to development of human papilloma virus‐associated cervical cancer in Indian women
Authors: Nagpal J. K. , Sahni S. , Das B. R. 
Published: March 2003

AbstractBackground Infection with human papilloma virus (HPV) is an important etiological factor in the development of cervical cancer and it has been proposed that individuals homozygous for Arg/Arg at codon‐72 of p53 are seven times more susceptible to HPV‐mediated cancer. In this study, we have analyzed the genetic predisposition of the India population to HPV infection and cervical carcinogenesis.Methods We investigated 71 cases of squamous cell carcinoma of the cervix, 14 cases of low‐grade squamous intraepithelial lesions, 25 cases of high‐grade squamous intraepithelial lesions and 29 noncancer controls for presence of HPV16/18 infections by L‐1‐specific PCR assay and Southern hybridization, and its association with polymorphism at p53 codon 72.Results We observed that 69·1% (76/110) of the cervical cancer patients were HPV positive, among which the presence of HPV16, 18 and 16/18 coinfection was 40·9%, 8·2% and 13·6%, respectively. The allele frequencies of the three p53 genotypes Arg/Arg, Arg/Pro and Pro/Pro in the HPV‐positive tumour samples were 0·34, 0·57 and 0·09 in comparison with frequencies of 0·18, 0·44 and 0·38 for HPV‐negative tumours. Hence, there is a significant difference in the allelic frequency of p53 Arg/Arg in high‐risk HPV‐infected cervical carcinoma cases (0·34) and HPV‐negative carcinomas (0·18).Conclusion Our results indicate a striking over‐representation of homozygous arginine at codon 72 of p53 in HPV‐associated cervical carcinogenesis. We conclude that women with Arg/Arg homozygous allele are more prone to infection by HPV16/18, which leads to cervical carcinomas having poor prognosis.
Iron chelation and hydroxyl radical scavenging reduce the inflammatory response of endothelial cells after infection with Chlamydia pneumoniae or influenza A
Authors: Visseren F. L. J. , Verkerk M. S. A. , Van Der Bruggen T. , Marx J. J. M. , Van Asbeck B. S. , Diepersloot R. J. A. 
Published: March 2003

AbstractBackground Chronic low‐grade inflammation is associated with increased risk of vascular diseases. The source of inflammation is unknown but may well be chronic and/or repetitive infections with microorganisms. Direct infection of endothelial cells (ECs) may also be a starting point for atherogenesis by initiating endothelial procoagulant activity, increased monocyte adherence and increased cytokine production. We hypothesized that iron‐mediated intracellular hydroxyl radical formation after infection is a key event in triggering the production of interleukin‐6 (IL‐6) by ECs in vitro.Methods Cultured ECs were incubated with Fe(II) and Fe(III) or infected with Chlamydia pneumoniae or influenza A/H1N1/Taiwan/1/81 for 48 and 24 h, respectively. To determine the role of iron and reactive oxygen species, cells were coincubated with the H2O2 scavenger N‐acetyl‐l‐cysteine, with the iron chelator deferoxamine (DFO) or with the intracellular hydroxyl radical scavenger dimethylthiourea (DMTU). After the incubation periods, supernatants were harvested for IL‐6 determination.Results Incubating ECs with Fe(II) and Fe(III) resulted in increased IL‐6 production. Similarly, infection with C. pneumoniae and influenza A also induced an IL‐6 response. Coincubating ECs with DFO or DMTU blocked this response. Nuclear factor‐κB activity was increased after infection and blocked by coincubation with DFO or DMTU.Conclusion Cultured ECs respond to infection and iron incubation with increased production of IL‐6. Iron, the generation of intracellular hydroxyl radical and NF‐κB activity are essential in cellular activation, suggesting that reactive oxygen species generated in the Haber–Weiss reaction are essential in invoking an immunological response to infection by ECs.