bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased antioxidant defence in individuals infected by the human immunodeficiency virus
Authors: Treitinger  , Spada  , Verdi  , Miranda  , Oliveira  , Silveira  , Moriel  , Abdalla  
Published: March 2003

BackgroundThe oxidative stress associated with HIV infection may be important for the progression of the disease because reactive oxygen species activate the nuclear transcription factor NF‐κB, which is obligatory for HIV replication.Patients and methodsThe activities of the antioxidant enzymes superoxide dismutase (SOD, EC 1.15.1.1) and glutathione peroxidase (GPx, EC 1.11.1.9) of blood plasma and peripheral blood mononuclear cells, as well as the plasma levels of ascorbate, α‐tocopherol and β‐carotene, were measured in 75 subjects with HIV infection and in 26 controls. The HIV‐infected patients were classified according to the Walter Reed Army Institute criteria.ResultsThe extracellular SOD (EC‐SOD) of blood plasma activity was decreased in HIV‐infected patients compared to controls, while the SOD activity of mononuclear cells decreased with the HIV‐associated disease progression. GPx activities and α‐tocopherol concentration of HIV‐infected patients neither differed as compared to controls nor in relation to disease progression. Lower concentrations of ascorbate and β‐carotene were found in HIV‐infected patients than in controls. A positive correlation between CD4 lymphocyte counts and the SOD activities of plasma and mononuclear cells was found.ConclusionThese results suggest that abnormalities of antioxidant defence, mainly of SOD activity, are related to the progression of the HIV infection.
Mutation analysis of the human adipocyte‐specific apM‐1 gene
Authors: Schäffler A. , Barth N. , Palitzsch K‐D. , Drobnik W. , Schölmerich J. , Schmitz G. 
Published: March 2003

BackgroundThe aim of this study was to analyse the human adipocyte‐specific apM‐1 gene for sequence variations.MethodsSequence analysis was performed in 344 randomly chosen blood samples using a capillary sequencer.ResultsWhereas no mutations were detected in intronic regions and in 2.7 kb of the promoter, two sequence variations were found within the coding sequence of apM‐1. For both mutations, a polymerase chain reaction‐(PCR) based restriction fragment length polymorphism (RFLP) analysis was developed, which provided a rapid screening method. A conservative T → G transition at nucleotide + 45 within exon‐2 [Gly15Gly] was detected with an allelic frequency of 0.9 for the wild‐type allele and 0.1 for the mutated allele. In addition, a missense point mutation at nucleotide + 331 within exon‐3 [Tyr111His] was detected with an allelic frequency of 0.97 for the wild‐type allele and 0.03 for the mutated allele. This mutation replaces a tyrosine by an histidine within the carboxyterminal globular domain of apM‐1. Concerning the Gly15Gly polymorphism, the TT genotype was found in 275 subjects (79.9%), the TG genotype in 67 subjects (19.5%) and the GG genotype in 2 subjects (0.6%): one with maturity onset diabetes of young age (MODY‐diabetes) and one with Lipoatrophic Diabetes Syndrome (LPDS). Concerning the Tyr111His polymorphism, the TT genotype was found in 328 subjects (95.4%), the TC genotype in 15 subjects (4.3%) and the CC genotype in 1 subject (0.3%).ConclusionThe existence of two yet unknown mutations within the apM‐1 gene was demonstrated and RFLP analysis was established for rapid screening. Well defined cohorts of patients are necessary to determine the putative role of apM‐1 gene mutations in the pathogenesis of metabolic disorders.
Circulating concentrations of C‐reactive protein and total sialic acid in tobacco smokers remain unchanged following one year of validated smoking cessation
Authors: Crook M. A. , Scott D. A. , Stapleton J. A. , Palmer R. M. , Wilson R. F. , Sutherland G. 
Published: March 2003

BackgroundElevated plasma concentrations of C‐reactive protein (CRP) and total sialic acid (TSA) have been associated with increased cardiovascular risk. Additionally, levels of both CRP and TSA have been reported to be significantly elevated in smokers. However, it is not clear if the raised TSA and CRP levels noted in smokers are directly attributable to the smoking experience, or if they may be elevated due to a secondary mechanism(s), such as smoking‐induced tissue inflammation.Subjects and methodsWe measured the plasma concentration of CRP and TSA in a group of smokers at baseline and following one year of validated smoking cessation (n = 30) and in a control group of tobacco users who continued to smoke over the year (n = 30).ResultsThe baseline concentration of TSA and CRP was 67.2 mg dL−1 and 1.91 mg L−1, respectively (n = 60). No significant dose‐dependent relationship was noted between baseline CRP or TSA concentration and either plasma cotinine, expired‐air CO or daily cigarette consumption. There was no difference in the mean change in CRP level in the quitters over one year (− 0.2 mg L−1) compared to the continuing smokers (+ 0.5 mg L−1), P = 0.80, or in the change in concentration of TSA in the quitters (− 2.7 mg dL−1) compared to the continuing smokers (+ 0.4 mg dL−1), P = 0.26.ConclusionsAs the circulating concentrations of both CRP and TSA remain unchanged following one year of smoking cessation, these results would suggest that the elevated levels noted in smokers are not directly attributable to tobacco use and are more likely to be elevated due to a secondary process that is yet to be established.
Ibuprofen inhibits adhesiveness of monocytes to endothelium and reduces cellular oxidative stress in smokers and non‐smokers
Authors: Zapolska‐Downar D. , Naruszewicz M. , Zapolski‐Downar A. , Markiewski M. , Bukowska H. , Millo B. 
Published: March 2003

Cigarette smoking is a major risk factor in atherosclerosis and a useful model from which to study chronic inflammation. We compared monocyte function, lipid profiles and inflammatory markers in smokers and non‐smokers, before and after oral ibuprofen intake. The adhesion of freshly isolated monocytes to native and tumour necrosis factor α (TNFα) stimulated human umbilical vein endothelial cells (HUVEC), as well as superoxide anion (O2−) levels and hydrogen peroxide (H2O2) production in resting and phorbol myristate acetate (PMA) stimulated monocytes were determined.A group of nine smokers without any other coronary risk factor was compared with an age‐matched group of 9 non‐smokers. Tests were performed before and after a two‐week course of oral ibuprofen (600 mg day−1).In smokers before ibuprofen, monocyte adhesion to native and TNFα‐stimulated HUVEC was increased (P < 0001 and P < 0·01, respectively), and so were O2− levels in native and PMA‐stimulated monocytes (P < 0·01 and P < 0·001, respectively). Ibuprofen reduced the adhesion of monocytes to native and stimulated HUVEC (P < 0·001) and O2− generation by resting and PMA‐stimulated cells (P < 0·01) in both groups. H2O2 production by resting and PMA‐stimulated monocytes was reduced in smokers and non‐smokers (P < 0·01). Interestingly, ibuprofen increased HDL cholesterol levels in smokers (P < 0·01) and non‐smokers (P < 0·001), and reduced the level of triglycerides in smokers (P < 0·05).Oral administration of ibuprofen reduced the adhesion of monocytes to HUVEC, suppressed oxidative stress and increased HDL cholesterol levels in smokers and non‐smokers.
New mechanisms of adrenostatic compounds in a human adrenocortical cancer cell line
Authors: Fassnacht M. , Hahner S. , Beuschlein F. , Klink A. , Reincke M. , Allolio B. 
Published: March 2003

BackgroundAdrenostatic compounds are frequently used in the treatment of patients with Cushing's syndrome and act via direct inhibition of steroidogenic enzymes. However, additional mechanisms may be involved in the blockade of adrenal steroid secretion. We therefore investigated the effects of aminoglutethimide (AG), metyrapone (MTP) and etomidate (ETO) in the human NCI‐h295 adrenocortical carcinoma cell line.Materials and methodsCells were incubated with increasing doses of the adrenostatic compounds. Steroid hormone secretion (cortisol, 17‐OH‐progesterone, DHEA‐S) and cAMP synthesis were determined and Northern blot analysis and cell proliferation experiments were performed.ResultsETO was the most potent adrenostatic compound inhibiting P450c11 hydroxylase at low concentrations (IC50 15 nM), and also blocking P450 side‐chain cleavage (scc) enzyme (IC50 400 nM) at higher concentrations. The pattern of enzyme inhibition was similar for MTP with an IC50 of 3á5 μM for P450c11 and 17 μM for P450scc, while AG blocked P450scc with an IC50 of 10 μM. AG significantly suppressed the baseline ACTH‐R mRNA expression in a dose‐dependent fashion (300 μM AG: 5% ± 1%; 30 μM AG: 64% ± 1%; 3 μM AG: 108% ± 19% compared with control cells: 100% ± 11%) but increased glucocorticoid receptor mRNA. The reduced ACTH‐R mRNA was paralleled by low ACTH‐induced cAMP accumulation indicating reduced expression of ACTH‐R protein. The simultaneous incubation of hydrocortisone together with AG reversed the inhibitory effect of AG on the ACTH‐R expression. AG and ETO inhibited cell proliferation in the NCI‐h295 cells, but ETO was much more potent and showed antiproliferative effects at concentrations of 6 μM. The growth inhibition was not reversed by administration of hydrocortisone.ConclusionsOur data demonstrate that adrenostatic compounds not only act by suppression of steroidogenic enzymes but can also influence both ACTH‐R expression and cell proliferation in adrenal cells. As these effects occur in vitro at concentrations that are reached during treatment with theses drugs in patients, they are probably also of clinical relevance. Particularly the antiproliferative activity of ETO may be useful in Cushing's syndrome due to adrenocortical cancer. The interaction of steroidogenesis, ACTH‐R and glucocorticoid receptor expression as well as cell proliferation provides a new concept of the intra‐adrenal response to stress in humans.
Reduction of hepatitis C virus load by H.E.L.P.–LDL apheresis
Authors: Schettler V. , Monazahian M. , Wieland E. , Ramadori G. , Grunewald R. W. , Thomssen R. , Müller G. A. 
Published: March 2003

The association of HCV with apolipoprotein B containing lipoproteins has been observed and this led to the assumption that the LDL receptor may also serve as a candidate receptor for HCV. H.E.L.P.–LDL apheresis is suggested to be an effective and rapid tool to safely eliminate apolipoprotein B containing lipoproteins.In this pilot study, we have investigated whether H.E.L.P. treatment would reduce HCV load in five patients, all infected for more than 4 years with HCV and resistant against established anti‐HCV therapy (interferon, ribaverin). HCV–RNA was determined by RT–PCR in plasma immediately before the start of apheresis (SA) and after treatment of 2500 mL plasma (AA).H.E.L.P. apheresis led to a mean decrease of 77·3%(16th percentile 36·5%, 84th percentile 89·6%) of HCV–RNA when AA values were compared to SA values. This decline was reproducible during nine treatment procedures, but was not correlated to the decrease in LDL cholesterol.This investigation shows for the first time that HCV load can be reduced by H.E.L.P. apheresis, which is an established and approved therapy for hypercholesterolemia. Even though the efficiency of viral load reduction varied between single procedures and did not correlate to LDL removal, this extracorporeal therapy opens the possibility to treat patients with established immune modulatory and antiviral therapy in the interval between two apheresis procedures.
Inhibition of prostacyclin by indomethacin ameliorates the splanchnic hyposensitivity to glypressin in haemorrhage‐transfused common bile duct‐ligated rats
Authors: Lee F.‐Y. , Chu C.‐J. , Wang S.‐S. , 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

Prostacyclin (PGI2) is an important contributor to the mediation of hyporeactivity to vasoconstrictors and the development of hyperdynamic circulation in portal hypertensive states. Inhibition of PGI2 synthesis in haemorrhage‐transfused partially portal vein‐ligated rats could ameliorate the splanchnic hyposensitivity to glypressin, a long‐acting vasopressin analogue. This study investigated whether the hyposensitivity to glypressin also exists in rats with common bile duct ligation (BDL) and whether the inhibition of PGI2 synthesis by indomethacin could potentiate the portal‐hypotensive effect of glypressin in bleeding BDL rats.Two series of BDL rats were used. Series 1 investigated the haemodynamic effects of low dose glypressin (0·07 mg kg−1) in BDL rats with or without bleeding by catheterization. In series 2, haemodynamic parameters were measured in stable or bleeding BDL rats that were receiving intravenously high dose glypressin (0·2 mg kg−1) or indomethacin (5 mg kg−1) followed by high dose glypressin. In rats with a hypotensive haemorrhage, 4·5 mL of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin or indomethacin.Splanchnic hyposensitivity to glypressin was demonstrated in haemorrhage‐transfused BDL rats receiving high, but not low, doses of glypressin. Indomethacin infusion did not cause significant systemic and portal haemodynamic changes in bleeding BDL rats (P > 0·05). The addition of indomethacin significantly enhanced the portal‐hypotensive effects of glypressin (P < 0·05) and potentiated the increases in mean arterial pressure induced by glypressin infusion (P < 0·001) in bleeding BDL rats.Splanchnic hyposensitivity to glypressin observed in haemorrhage‐transfused BDL rats could be ameliorated by the addition of indomethacin, suggesting a role of endogenous PGI2 in its pathophysiology.
Influence of D‐ and L‐glucose on erythrocytes and blood viscosity
Authors: Bühler I. , Walter R. , Reinhart W. H. 
Published: March 2003

Background Elevated blood glucose levels are associated with substantial morbidity and mortality. The pathomechanism behind it is not well understood. The aim of the present study was to investigate the effect of glucose on blood rheology. Materials and methods Blood from healthy volunteers was incubated with various concentrations of D‐ and L‐glucose for 1 h at 37 °C. Whole blood viscosity at haematocrit 45% was measured at high and low shear rate (94·5 and 0·1 s−1). Erythrocyte shape and volume were assessed. Haemoglobin solutions were incubated with
D‐glucose for up to 96 h and the viscosity was measured. Results D‐glucose dissolved in H2O and diluted with isotonic NaCl, added to whole blood (additional D‐glucose concentrations 0–80 m
m), led to a red cell swelling and an increase in blood viscosity at low shear rate (0·1 s−1). This process was reversible upon removal of D‐glucose. L‐glucose, which is not transported into the red cell by the D‐glucose‐specific transport protein GLUT‐1, had no effect. When D‐glucose was dissolved and diluted in autologous plasma, haematocrit and viscosity remained unaffected, but L‐glucose decreased both values. Incubation of a haemoglobin solution with D‐glucose at 37 °C led to a time‐dependent increase in glycosylated haemoglobin (HbA1C) up to 8%, but left the viscosity unchanged. Conclusion Blood glucose tested in a wide range of concentrations did not affect blood viscosity and morphological or biophysical properties of erythrocytes.
Role of various tissues in apo(a) fragmentation and excretion of fragments by the kidney
Authors: Frank S. , Hrzenjak A. , Blaschitz A. , Dohr G. , Kostner G. M. 
Published: March 2003

Background Lipoprotein(a) [Lp(a)] is an atherothrombotic plasma lipoprotein with unknown function. Little is known about the catabolism of this lipoprotein, in particular the steps related to apolipoprotein(a) [apo(a)] fragmentation and excretion by the kidney.Material and methods High plasma levels (up to 9 mg dL−1) of the N‐terminal fragment of apo(a) were expressed in mice by adenovirus mediated gene transfer. Plasma of such N‐apo(a) mice was injected into acceptor mice and the fragmentation and urinary secretion of N‐apo(a) were followed by immunochemical techniques.Results Mice transduced with N‐Ad expressed apo(a)‐fragments with 3–11 kringle‐IV (KIV) repeats. Injection of N‐apo(a)‐plasma from donor mice into acceptor mice resulted in fragmentation of N‐apo(a)s with 3–11 KIVs yielding smaller peptides down to 2 KIVs. Secretion of N‐apo(a)‐fragments with 2 to maximally 6 KIVs into urine occurred as early as 2 min after injection. Immunohistochemical studies of kidney suggested filtration as a mechanism of apo(a)‐fragment excretion.When N‐apo(a) was incubated in vitro with various tissues from perfused mice, skeletal muscle and kidney followed by liver and spleen contributed to fragmentation. Tissues from unperfused organs, or the addition of normal mouse plasma, caused marked reduction in N‐apo(a) fragmentation. EDTA, and not aprotinin or leupeptin, prevented apo(a) cleavage.Conclusion Here we provide evidence that apo(a) is cleaved by metalloproteinases located on skeletal muscle, kidney and other organs. Small apo(a)‐fragments up to a size of 6 KIVs are excreted into urine, yet a major portion of apo(a) fragments is removed from circulation extrarenally.
Large rearrangements of the LDL receptor gene and lipid profile in a FH Spanish population
Authors: Chaves F. J. , Real J. T. , García‐García A. B. , Puig O. , Ordovas J. M. , Ascaso J. F. , Carmena R. , Armengod M. E. 
Published: March 2003

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the low‐density lipoprotein receptor (LDLR) gene. To date, there has not been a systematic survey of the frequency of gross mutations in the LDLR gene in the Spanish population. The objective of our study was to investigate large rearrangements in the Spanish FH population and the relation between the kind of large rearrangement and the phenotype in carrier families.Material and methods The LDLR gene was screened to detect major rearrangements in a sample of 89 probands. Southern blot, long polymerase chain reaction (PCR), reverse transcription (RT) ‐PCR and DNA sequencing were used to detect and characterize the mutations.Results Five large rearrangements were found in six probands. Two mutations were due to duplications of internal regions of the gene, whereas the rest were caused by partial deletions, which eliminated the promoter region in two cases. The internal rearrangements, two duplications and one deletion, were apparently caused by recombination between ALU sequences and the study of their mRNA indicated that the reading frame was maintained. The analysis of the lipid profile between patients with similar characteristics (age, sex, body mass index, etc.) but carrying mutations that either eliminated the promoter region or produced internal rearrangements showed significant differences (total cholesterol: 366·6 ± 81·8 vs. 304·6 ± 25·1 P = 0·023, and LDL cholesterol: 317·7 ± 65·1 vs. 249·2 ± 27·4 P = 0·003).Conclusions The frequency of large mutations in a Spanish FH sample was close to 7% and at least four of the mutations found had not been described in other populations. Mutations that eliminate the promoter region originate more severe hypercholesterolemia than defective mutations, which suggests that the absence of the promoter region and transcription of the LDLR gene is worse compensated than the synthesis of a defective LDL receptor.
Effect of nitric oxide inhibition on nasal airway resistance after nasal allergen challenge in allergic rhinitis
Authors: Maniscalco M. , Sofia M. , Carratù L. , Higenbottam T. 
Published: March 2003

Background Nitric oxide has been detected by chemiluminescence in the lumen of nasal airway, which is increased in nasal breathing in patients with seasonal rhinitis during a chronic exposure. The purpose of this study was to determinate the effect of a NO‐synthase inhibitor NGL‐arginine methyl ester (L‐NAME) on nasal airway resistance (NAR) in patients with seasonal allergic rhinitis after an acute challenge to the allergen.Methods Nitric oxide levels in the nose were measured by the chemiluminescence method in nine non‐atopic volunteers and in seven patients with seasonal rhinitis at rest and after an acute challenge with the allergen. NAR were measured by active anterior rhinomanometry.Results Basal nasal NO concentration in allergic rhinitis was 496·5 ± 151·4 parts per billion (ppb). (n = 7) and it was not significantly different from levels found in the control group: 458·4 ± 105·9 ppb (n = 9). The topical administration of L‐NAME in allergic rhinitis reduced the NO concentration (338·6 ± 99·3 ppb, P < 0·001; n = 7). In the rhinitic patients the challenge with the allergen did not modify the nasal NO levels (504·5 ± 138·5 ppb). The application of the allergen after the pretreatment with placebo caused a significant increase in NAR (from 0·32 ± 0·11 Pa s cm−3 to 1·01 ± 0·12 Pa s cm−3, P < 0·001; n = 7). Pre‐treatment with L‐NAME did not prevent the increase in NAR induced by allergen challenge (from 0·36 ± 0·15 Pa s cm−3 to 1·06 ± 0·26 Pa s cm−3).Conclusions The results indicate that nasal administration of a NOS inhibitor L‐NAME, at doses capable of decreasing nasal NO levels, has no effect on NAR and it does not prevent the NAR increase induced by an acute challenge with allergen in subjects with seasonal rhinitis.
Gemfibrozil treatment potentiates oxidative resistance of high‐density lipoprotein in hypertriglyceridemic patients
Authors: Chen M.‐F. , Wang T.‐D. , Yeh H.‐T. , Hsu H.‐C. , Lee Y.‐T. 
Published: March 2003

Background Studies suggest that both oxidized low and high density lipoprotein (LDL and HDL) play a role in the pathogenesis of atherosclerosis. Gemfibrozil is widely used and is reported to increase cholesterol of LDL and HDL in hypertriglyceridemic patients. The aim of this study was to investigate the effect of gemfibrozil treatment on the oxidative status of lipoprotein particles in Fredrickson phenotype IV hypertriglyceridemic patients.Methods Twenty‐two patients, aged 38–64 years, with fasting plasma triglyceride concentrations between 2·90 and 8·97 mmol L−1, were recruited and were given gemfibrozil 300 mg three times daily for 12 weeks. Venous blood samples were collected before gemfibrozil treatment, after 4, 8, or 12 weeks of treatment, and 4 weeks after termination of treatment, and used to analyse the plasma lipid profile, isolate lipoproteins, and analyse the chemical composition and in vitro oxidation of lipoprotein particles.Results Gemfibrozil treatment resulted in a decrease in plasma total triglyceride levels and the triglyceride content of all lipoproteins. Plasma total cholesterol levels were decreased as a result of a decrease in very low density lipoprotein (VLDL) cholesterol levels. A slight increase in LDL cholesterol levels was observed, whereas the thiobarbituric acid‐reactive substances (TBARS) of LDL were decreased and the lag and peak time of LDL to oxidation were unchanged and maximal diene production was decreased. Plasma HDL cholesterol levels, the surface‐to‐core ratio of HDL particles, and the resistance of HDL to oxidation were increased.Conclusion The decreased TBARS and diene production of LDL, increased HDL cholesterol levels, and increased resistance of HDL to oxidation may, in part, explain why gemfibrozil treatment was found to be generally beneficial in terms of protection against coronary heart disease.