bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of bile salts and aliphatic ionic surfactants on human lymphocyte proliferation
Authors: Podevin P. , Correia L. , Montet J C. , Conti F. , Chéreau C. , Calmus Y. , Poupon R. 
Published: March 2003

Background The molecular mechanisms involved in the immunosuppressive properties of bile salts are partly unknown.Methods The aim of the study was to compare the effects of bile salts to those of various compounds with a steroid structure, or straight‐chain hydrocarbons of different lengths and polar groups in the human mixed lymphocyte reaction.Results We showed a significant correlation between the effects of bile salts and a low critical micellar concentration, a high surface activity index, and the absence of conjugation. In addition to mixed lymphocyte reaction (MLR) inhibition, chenodeoxycholate (CDC) inhibit ConA‐induced IL2 production without any effect on IL2 R expression. Fusidate, a negatively charged steroid, with physical properties comparable to those of deoxycholate, had similar effects. Cetyltrimethylammonium bromide (CTAB), which exhibited a very low critical micellar concentration, inhibited mixed lymphocyte reaction in an extent comparable to cyclosporin A. In contrast, aliphatic compounds with critical micellar concentrations in the same range as bile salts but with a lower molecular area had no effect.Conclusion Amphiphilic negatively charged molecules inhibit T‐cell proliferation to an extent that is dependent upon their hydrophobicity. These results may be explained, at least in part, by a modification in the cell membrane lipid bilayer structure.
Suppression of superantigen‐induced lung injury and vasculitis by preadministration of human urinary trypsin inhibitor
Authors: Onai H. , Kudo S. 
Published: March 2003

We examined whether the lung injury produced in rats by intraperitoneal injection of the superantigen, staphylococcal enterotoxin B (SEB), could be inhibited by intravenous preadministration of human urinary trypsin inhibitor (UTI), which exhibits multipotent inhibitory effects on serine proteinases such as plasmin, chymotrypsin, or human leukocyte elastase or cathepsin G, since preliminary experiments showed the ability of UTI to bind lipopolysaccharides and bacterial toxins.For ligand blotting analysis, four kinds of toxins were run on a slab gel and the binding of UTI to the toxins was visualized by immunoblotting. Lung tissue from 26 rats was used for immunohistochemistry using a mouse antirat CD 45 mAb and an antirat macrophage mAb. Lung tissue from 31 rats was used for measurement of myeloperoxidase activity before and after intraperitoneal injection of SEB, after infusion of PBS, UTI, PBS‐SEB or UTI‐SEB combination. Ten of the 26 rats described above were used for electron microscopy. Rat sera were used for measurement of TNF‐α. Statistical analysis was performed using the Mann–Whitney U‐test.Intraperitoneal injection of SEB caused an increase in the number of punctate areas of haemorrhage on the surface of the lung with time, and histological examination revealed lung injuries with different extents, vasculitis where inflammatory cells were concentrated, and infiltration of numbers of eosinophils into the alveolar septa. However, preadministration of UTI for rats markedly attenuated lung injury and vasculitis induced by intraperitoneal injection of SEB. This revealed, from a marked reduction in the number of inflammatory cells and the extent of injury, a marked inhibition of serum TNF‐α production and reduction of myeloperoxidase content of rat lungs compared to controls.UTI may have defensive effects to infection by suppressing the early responses of stimulated cells to activated stimulus such as SEB as well as the release of stimulant‐mediated cytokines via trapping of bacterial toxins.
Anabolic effects of rhIGF‐I/IGFBP‐3 in vivo are influenced by thyroid status
Authors: Svanberg E. , Healey J. , Mascarenhas D. 
Published: March 2003

Background There are close interrelationships between hormones that regulate bone formation and protein biosynthesis. For example, growth hormone and thyroid hormones can influence plasma levels of insulin‐like growth factor‐I (IGF‐I). A patient's status regarding hormones other than IGF‐I may thus indirectly modify the efficacy of IGF‐I treatment. The aim of the current study was to determine if a statistical method could be used to identify key endocrine variables controlling an individual's response to IGF‐I treatment.Design Biochemical profiles from the somatotropic, thyroid and adrenal axes were determined on two separate occasions in two different study cohorts. Each cohort was divided into four groups: placebo, low, medium and high dose of recombinant human IGF‐I/IGF binding protein‐3 (rhIGF‐I/IGFBP‐3). The relative changes in collagen C‐terminal peptide (CICP) levels were explained as a function of the basal endocrine profile of each treated individual. This relationship was further examined in an experimental rat model, where undernourished rats were rendered hypothyroid by propylthiouracil and subsequently treated with rhIGF‐I/IGFBP‐3.Results The results of our statistical analysis in both cohorts indicated that each subject's response to rhIGF‐I/IGFBP‐3 administration was controlled in part by the individual's thyroid status prior to drug administration (r = 0·78 for both cohorts). The results from the animal study revealed that IGF‐I treatment stimulated muscle protein synthesis by 35 ± 9% (P = 0·05) in euthyroid rats but not in hypothyroid rats.Conclusion The relationship between endocrine axes is not simple. An improved understanding of the interactions between neuroendocrine systems may facilitate the design of efficient drug regimens in the treatment of diseases such as osteoporosis and muscle wasting.
Myocardial gene expression of leukaemia inhibitory factor, interleukin‐6 and glycoprotein 130 in end‐stage human heart failure
Authors: Eiken H. G. , Øie E. , Damås J. K. , Yndestad A. , Bjerkeli V. , Aass H. , Simonsen S. , Geiran O. R. , Tønnessen T. , Christensen G. , Frøland S. S. , Gullestad L. , Attramadal H. , Aukrust P. 
Published: March 2003

Background Studies in different animal models and plasma analyses in humans suggest that members of the interleukin‐6 (IL‐6) cytokine family may be involved in the pathogenesis of congestive heart failure (CHF). Accordingly, we have examined IL‐6‐related cytokines in chronic CHF in humans by analysing gene and protein expression in myocardium derived from patients with end‐stage heart failure and donor hearts.Methods Gene expression of cytokines/receptors of the IL‐6 family was documented in myocardial samples using cDNA array hybridization and RNase protection assays. Immunohistochemistry was used to detect leukaemia inhibitory factor (LIF), IL‐6 and glycoprotein 130 (gp130) in myocardial tissues.Results Myocardial gene activity was documented for the majority of IL‐6 family cytokines and their receptors. Immunohistochemical analysis localized IL‐6, LIF and their common receptor subunit gp130 to myocytes and vascular smooth muscle cells. LIF mRNA levels were enhanced in the left ventricles of CHF patients relative to the left ventricles of donor hearts (patients 4·6 ± 4·7 vs. donors 0·3 ± 0·3, P < 0·005). Myocardial IL‐6 and gp130 mRNA levels were not statistically different between patients and donors, but in contrast to LIF mRNA expression in heart explants, gp130 mRNA levels were significantly higher in left atrium compared with left ventricle in both patients and donors.Conclusions Both mRNA and proteins of gp130 and its ligands IL‐6 and LIF are expressed in both nonfailing and failing human myocardium. The elevated LIF mRNA levels in left ventricles from patients with end‐stage heart failure suggest a role for LIF in the pathogenesis of CHF.
Hypouricemia and hyperuricemia in type 2 diabetes: two different phenotypes
Authors: Bo S. , Cavallo‐Perin P. , Gentile L. , Repetti E. , Pagano G. 
Published: March 2003

Background and Design Conflicting data exist about uric acid levels in type 2 diabetes mellitus, as low levels were found in diabetic patients, while elevated serum uric acid is a feature of hyperinsulinemia and impaired glucose tolerance. The present study was addressed to evaluate the relation between uric acid and metabolic parameters, creatinine clearance and albumin excretion rate in a cohort of type 2 diabetic patients.Results Hyperuricemic patients were older and had higher values of body mass index (BMI), systolic and diastolic blood pressure, triglycerides, albumin excretion rate, C‐peptide and prevalence of hypertension, metabolic syndrome and macroalbuminuria and lower values of high‐density lipoprotein (HDL)‐cholesterol, creatinine clearance and glycated haemoglobin (HbA1c). The correlations between uric acid levels and triglycerides, BMI, systolic blood pressure, albumin excretion rate, C‐peptide, creatinine clearance, HDL‐cholesterol and HbA1c remained significant in a multiple regression analysis after adjustment for age, sex and duration of diabetes. After performing multiple logistic regression analyses, uric acid levels were independently associated with hypertension [odds ratio (OR) = 1·8; 95% confidence interval (CI) 1·6–2], after adjustment for age, sex, duration of diabetes and macroalbuminuria (OR = 1·5; 95% CI 1·1–2·0), after adjustment for age, sex, HbA1c levels, creatinine clearance, duration of diabetes and blood pressure levels and the metabolic syndrome (OR = 1·6; 95% CI 1·5–1·8), after adjustment for age, sex and creatinine clearance.Conclusions In type 2 diabetes, hyperuricemia seems to be associated with the insulin‐resistant syndrome and with early onset or increased progression to overt nephropathy, while hypouricemia is associated with worse metabolic control, hyperfiltration and a late onset or decreased progression to overt nephropathy.
N‐acetyl‐L‐cysteine exerts direct anti‐aggregating effect on human platelets
Authors: Anfossi G. , Russo I. , Massucco P. , Mattiello L. , Cavalot F. , Trovati M. 
Published: March 2003

Background N‐acetyl‐l‐cysteine, a thiol compound, has been shown to potentiate the inhibition of platelet aggregation exerted by organic nitrates and to increase the anti‐aggregating effect of l‐arginine, which promotes endogenous synthesis of nitric oxide (NO) acting as substrate of platelet constitutive nitric oxide synthase (NOS). It is not known whether this thiol can exert direct effects on platelet aggregability.Materials and methods 14 healthy male volunteers provided platelet samples to investigate whether N‐acetyl‐l‐cysteine directly influences platelet function and intraplatelet levels of 3′,5′ cyclic guanosine monophosphate (cGMP), which represents the second messenger involved in NO‐induced antiaggregation. Some experiments were repeated in the presence of NOS inhibitor NG‐monomethyl‐l‐arginine (L‐NMMA), of nitric oxide‐sensitive guanylyl cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ), of the selective cGMP phosphodiesterase inhibitor zaprinast and of calcium ionophores (A23187, ionomycin).Results N‐acetyl‐l‐cysteine at 3000–6000 µmol L−1 decreases the responses of human platelets both in platelet‐rich plasma (aggregation induced by adenosine 5‐diphosphate) and in whole blood (aggregation induced by collagen). The anti‐aggregating effect was prevented by preincubation with L‐NMMA and guanylyl cyclase inhibitor ODQ. In resting platelets, N‐acetyl‐l‐cysteine increased the levels of cGMP starting from a concentration of 3000 µmol L−1. Permeabilized platelets exhibited an increased sensitivity to the anti‐aggregating effect of N‐acetyl‐l‐cysteine. Also, cGMP phosphodiesterase inhibition or the increase in calcium availability, enhanced N‐acetyl‐l‐cysteine effects on platelets.Conclusion N‐acetyl‐l‐cysteine exerts direct anti‐aggregating effects through an increased bioavailability of platelet nitric oxide.
Mitochondrial DNA deletion associated with the reduction of adenine nucleotides in human atrium and atrial fibrillation
Authors: Tsuboi M. , Hisatome I. , Morisaki T. , Tanaka M. , Tomikura Y. , Takeda S. , Shimoyama M. , Ohtahara A. , Ogino K. , Igawa O. , Shigemasa C. , Ohgi S. , Nanba E. 
Published: March 2003

Background Structural changes in the number, size, and shape of mitochondria (mt) have been observed in the atrial muscles of patients with atrial fibrillation (AF) and of animals with rapid atrial pacing, however, it is not known whether the mitochondrial function is impaired in human atrium with AF.Materials and Methods We determined adenine nucleotides concentrations and mtDNA deletions in 26 human right atria obtained at the time of cardiac surgery, using HPLC and PCR amplification, and studied the relationship between mtDNA deletions and clinical manifestations, the haemodynamic parameters of the patients and adenine nucleotide concentrations in their atrium.Results The age and the prevalence of AF were significantly higher in the patients with a mtDNA deletion of 7·4 kb than in those without a deletion; there were no significant differences regarding haemodynamic parameters between the two groups. The concentrations of ATP, ADP, AMP and total adenine nucleotides in the right atrium were significantly lower in the patients with mtDNA deletions than the patients without a deletion. In a gender‐ and diseased‐matched population, the mtDNA deletion was still significantly associated with age and a decreased concentration of adenine nucleotides in the atrium. Using quantitative PCR analysis, the proportion of mtDNA deletion to normal mtDNA of the atrium, was estimated to be 0·3–2% in four cases.Conclusion These results suggest that the deletion of mtDNA associated with ageing or AF can lead to a bioenergetic deficiency due to an impaired ATP synthesis in the human atrium; however, no conclusion can be made whether mtDNA deletion were the result or the cause of an impaired ATP synthesis, ageing, hemodynamic deterioration, or AF.
Leucine suppresses acid‐induced protein wasting in L6 rat muscle cells
Authors: Bevington A. , Brown J. , Walls J. 
Published: March 2003

Background Metabolic acidosis induces protein wasting in skeletal muscle cells, accompanied by decreased glycolysis and compensatory increased consumption of other metabolic fuels, implying that protein wasting arises from fuel starvation and might be rectified by fuel supplements. Design To test this hypothesis, total protein and protein degradation (release of 14C‐phenylalanine) were measured in L6 skeletal muscle cells cultured in Eagle's Minimum Essential Medium at pH 7·1–7·5 for 3 days with metabolic inhibitors or metabolic fuel supplements. Results Inducing metabolic fuel starvation with inhibitors (1 mmol L−1 2‐deoxyglucose or 0·1 mmol L−1 KCN [potassium cyanide]) failed to stimulate protein degradation or net protein wasting under nonacidaemic conditions (pH 7·5). Conversely metabolic fuel supplements (1 mmol L−1 octanoate, pyruvate or alanine) failed to increase the protein content of the cultures at any pH tested, in spite of significant consumption of the fuels by the cells. Only leucine (1–3 mmol L−1) increased protein content and suppressed protein degradation in opposition to the catabolic effect of acidaemia (pH 7·1). Conclusion Leucine exerts a beneficial anabolic effect on cultured skeletal muscle cells in the face of metabolic acidaemia. The failure of other metabolic fuels to do this, and of the metabolic inhibitors to exert a catabolic effect, suggests that leucine acts as a specific modulator of protein turnover and not as a nonspecific source of carbon for oxidation as a fuel.
Homocysteine levels in patients treated with lipid apheresis: effect of a vitamin therapy
Authors: Julius U , Pietzsch J. , Gromeier S. , Schorr H. , Herrmann W. 
Published: March 2003

Background Patients treated with lipid apheresis already suffer from familial hypercholesterolemia and severe coronary heart disease: any additional risk factor is dangerous for these patients. Hyperhomocysteinemia has been recognized as an independent risk factor for atherosclerotic disease. We checked the frequency of hyperhomocysteinemia in lipid apheresis patients and measured the effect of a vitamin therapy.Materials and Methods Sixteen heterozygous patients (10 males, 6 females) were studied, who were being treated by three different apheresis procedures. Homocysteine was measured using an enzyme conversion immunoassay. Cystathionine and methylmalonic acid were assessed by gas chromatography/mass spectrometry. Serum levels of folic acid, vitamin B12, and vitamin B6 were also determined. The patients received a vitamin therapy (3 mg folate, 60 µg cyanocobalamine, 10 mg pyridoxine hydrochloride daily) for 12 weeks.Results In 9 out of 16 patients, plasma homocysteine levels were found to be elevated (> 12 µmol L−1). Cystathionine concentrations were also increased, especially in those patients with elevated homocysteine. Methylmalonic acid levels were not elevated. Serum folic acid, vitamin B6, and vitamin B12 concentrations were initially in the normal range and not correlated to plasma homocysteine. The vitamin therapy reduced the plasma homocysteine concentrations in all patients significantly by 33%. Among those patients with elevated homocysteine levels, the optimal range < 12 µmol L−1 for homocysteine was rarely reached.Conclusions In patients treated with lipid apheresis, a hyperhomocysteinemia can be frequently seen. The constellation of both elevated homocysteine and cystathionine levels points to the existence of tissue vitamin deficiencies, folate and vitamin B‐6, which were improved by vitamin supplements. Because methylmalonic acid was mostly normal, a vitamin B‐12 deficiency was not proven.
Assessment of the left ventricular diastolic reserve in essential hypertension: the acute saline load test
Authors: Triposkiadis F. , Moyssakis I. , Makris T. , Hatzizaharias A. , Hadjinikolaou L. , Kyriakidis M. 
Published: March 2003

ObjectivesThe aim of this study was to evaluate the significance of the development of a restrictive response to an acute saline load, defined as an increase in the ratio of peak early to peak late diastolic transmitral flow velocity (E/A ratio) associated with a decrease in the deceleration time, in patients with mild to moderate untreated hypertension.BackgroundRecognised abnormal patterns of transmitral diastolic flow include, from ‘best’ to ‘worst’: prolonged relaxation, pseudonormalisation, and restrictive physiology. The common denominator of these transitions is the constellation of an increase in the E/A ratio associated with a decrease in deceleration time.Patients and MethodsSixteen normal control subjects (6 males, 10 females, age 51·6 ± 6·9 years) and 24 patients with mild to moderate untreated hypertension (12 males, 12 females, age 46·8 ± 7·5 years) underwent supine blood pressure measurement with sphygmomanometry, biochemical studies, and transthoracic M‐mode, 2D, and Doppler echocardiography before and after an acute saline load (7 mL kg−1, maximum 500 mL, NaCl 0·9% within 15 min IV).ResultsThe baseline E/A ratio was lower (0·90 ± 0·14 vs. 1·04 ± 0·18; P < 0·01) and the deceleration time was longer (158·8 ± 19·4 vs. 135 ± 8·9 ms; P < 0·01) in patients with hypertension compared with normotensive controls. However, no patient with hypertension exhibited a transmitral flow velocity pattern compatible with typical prolonged relaxation. A restrictive response to the acute saline load was observed in 12 (50%) of the hypertensive and none of the control subjects. Hypertensive patients with a restrictive response to the acute saline load had a lower baseline E velocity (54·8 ± 8·7 cm s−1 vs. 66 ± 6·4 cm s−1; P = 0·003), a lower baseline E/A ratio (0·83 ± 0·13 vs. 0·97 ± 0·12; P = 0·015), and a longer deceleration time (167·5 ± 15·4 ms vs. 150 ± 19·5; P = 0·03) than hypertensive patients without such a response.ConclusionA restrictive response to an acute saline load is indicative of a limited diastolic reserve in patients with mild to moderate untreated hypertension. Further studies are required in order to evaluate the significance of such a response with regards to risk stratification and efficacy of medical treatment in this patient population.
A noninvasive method to collect nasally exhaled air condensate in humans of all ages
Authors: Griese M. , Latzin P. , Beck J. 
Published: March 2003

Background The analysis of exhaled breath condensate may provide valuable insights into inflammatory and other metabolic processes of the lungs. However, its collection by active exhalation with conventional methods is cumbersome, demands a substantial level of co‐operation with high motivation and is very difficult or impossible in children younger than about 4–6 years or in the elderly. A comfortable, noninvasive and efficient method is desirable.Design and patients For collection a high‐performance pump connected to a cold trap and nasal prongs were used. The volume of the condensate collected was assessed in 141 children of all ages and five adults. As an example for a low molecular component, H2O2 a marker of oxidative stress, was determined fluorometrically.Results On average, in healthy children from 4 weeks to 18 years of age, 84·0 (79·4, 87·3) µL min−1 of nasally exhaled air condensate were collected. The volume obtained was about 45% less in 1–6‐year‐old children, increased linearly with collection time, and averaged about 20–30% of the exhaled water vapour. The concentration of H2O2 in the healthy children was 0·49 (0·48, 0·61) μM and did not depend on age, the time of the day, family, or personal history of atopy and sex.Conclusions The method described is generally applicable, comfortable, noninvasive, safe and efficient and allows the collection of nasally exhaled air condensate for the evaluation of metabolic processes of the lungs.
ACE and angiotensinogen gene genotypes and left ventricular mass in athletes
Authors: Diet F. , Graf C. , Mahnke N. , Wassmer G. , Predel H. G. , Palma‐Hohmann I. , Rost R. , Böhm M. 
Published: March 2003

Background Genetic factors may be important in modifying heart size due to long‐term athletic training. The significance of polymorphisms of genes of the renin–angiotensin system in myocardial mass in a population of athletes participating in different disciplines is not known.Methods The angiotensin I‐converting enzyme gene insertion/deletion (I/D) polymorphism, angiotensinogen gene M235T polymorphism and angiotensin II type 1 receptor gene A1166C polymorphism were determined in 83 male Caucasian endurance athletes and associated with left ventricular mass.Results No association with left ventricular mass was found for the polymorphisms of angiotensin I‐converting enzyme gene I/D, angiotensinogen gene M235T and angiotensin II type 1 gene A1166C when studied separately. However, combined analysis of the angiotensin I‐converting enzyme gene I/D polymorphism and angiotensinogen gene M235T polymorphism genotypes suggested an association with left ventricular mass (g m−2) (P = 0·023). Athletes with the angiotensin I‐converting enzyme gene DD/angiotensinogen gene TT genotype combination had greater left ventricular mass compared with all other genotype combinations (179·8 ± 26·1 g m−2 vs. 145·2 ± 27·3 g m−2, P = 0·003).Conclusions These results suggest an association of combined angiotensin I‐converting enzyme gene I/D polymorphism genotypes, and angiotensinogen gene M235T polymorphism genotypes with left ventricular hypertrophy due to long‐term athletic training. A synergistic effect of angiotensin I‐converting enzyme gene DD genotype and angiotensinogen gene TT genotype on left ventricular mass in endurance athletes appears to occur.