bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo modifications of AcSDKP metabolism and haematopoiesis in mice treated with 5‐fluorouracil and Goralatide
Authors: Comte  , Lorgeot  , Bignon  , Volkov  , Dupuis  , Wdzieczak‐Bakala  , Praloran  
Published: March 2003

BackgroundThe tetrapeptide acetyl‐Ser‐Asp‐Lys‐Pro (AcSDKP), a physiological inhibitor of the proliferation of haematopoietic stem cells, is degraded by the angiotensin‐I‐converting enzyme (ACE). Whereas synthetic AcSDKP (Goralatide) protects normal mice from the haematological toxicity of chemotherapy, it has a lower beneficial effect in humans. This discrepancy could be dependent on Goralatide administration schedules, as well as on the endogenous concentrations of AcSDKP and ACE, which vary during chemotherapy.MethodsWe investigated the effect of one myelotoxic dose of 5‐fluorouracil (5‐FU, 200 mg kg−1) administered without or with Goralatide on blood, bone marrow (BM) and spleen AcSDKP concentrations, ACE activity, nucleated cell counts and survival of the primitive haematopoietic progenitors high proliferative potential colony‐forming cells (HPP‐CFCs).ResultsThe 5‐FU treatment dramatically decreased the BM concentrations of AcSDKP by 73% and increased the ACE activity in plasma by 50% during the period of active BM regeneration. Repeated injections of Goralatide from 24 h before to 36 h after the i.p. injection of 5‐FU spared BM HPP‐CFCs. As an injection of 10 mg of Goralatide induced a short peak of plasma AcSDKP without modifying its BM concentrations, we suggest that its protective effect on HPP‐CFCs could be mediated by its interference with other plasma molecules targeting to the BM.ConclusionBy improving our knowledge of the biology of AcSDKP in vivo during chemotherapy, our results could help to better define the therapeutic use of Goralatide.
The effects of iloprost infusion on microcirculation is independent of nitric oxide metabolites and endothelin‐1 in chronic peripheral ischaemia
Authors: Mazzone  , Cusa  , Bucci  , Vezzoli  , Ghio  , Buggia  , Regazzi  , Fossati  , Mazzucchelli  , Gritti  
Published: March 2003

BackgroundEndothelial vascular tone modulators are thought to be involved in aetiopathogenesis of systemic sclerosis (SS) and of peripheral artery occlusive disease (PAOD). Iloprost, a prostacyclin (PGI2) analogue, induces clinical benefit in patients suffering from peripheral ischaemia. This study was performed to investigate the effect of this drug on endothelial function in vivo to elucidate the role of vascular tone modulators.MethodsFourteen PAOD and 15 SS patients were treated for 24 and 10 days respectively. On the first day, before and after therapy, nitric oxide metabolites (NO2−/NO3−) and endothelin‐1 (ET‐1) plasma concentrations were detected; moreover, the endothelium‐dependent vasodilatation in response to artificial ischaemia was evaluated by means of an echo‐Doppler device.ResultsThe echo‐Doppler evaluation showed that the percentage of arterial reactive dilatation was not modified by placebo or by iloprost, and that the increase in blood velocity flow lasted for a significant longer time after drug infusion (226.79 ± 17.49 vs. 310.71 ± 36.32 s; P > 0.04). NO2−/NO3− and ET‐1 plasma concentration were higher in patients than in control subjects (P < 0.004). After 6 h of iloprost infusion, no significant modifications were detected.ConclusionThis study provides evidence that iloprost enhances the microvascular functional capacity and clinical benefit for patients. The effects of the drug seem to be independently or not directly correlated with its interactions with vascular tone modulators such as NO2−/NO3− or ET‐1.
Post‐prandial chylomicron response may be predicted by a single measurement of plasma apolipoprotein B48 in the fasting state
Authors: Smith  , Watts  , Dane‐Stewart  , Mamo  
Published: March 2003

BackgroundThe clearance of chylomicron remnants was assessed in normolipaemic, dyslipidaemic and obese male subjects by monitoring the plasma kinetics of apolipoprotein (apo) B48, retinyl palmitate and triglyceride after a lipid meal. Regression analysis of fasting plasma apo B48 with the area under the post‐prandial curves of apo B48, retinyl ester and triglyceride was carried out in order to determine whether the post‐prandial response could be predicted by the fasting concentration of this exclusive chylomicron marker.Materials and methodsFasted subjects were given an oral fat load supplemented with retinyl palmitate, and blood samples were drawn over a 10‐h period. Apolipoprotein B48 was determined by Western blotting in the plasma density fraction less than 1.063 g mL−1. Plasma retinyl palmitate and triglyceride were determined by high‐performance liquid chromatography (HPLC) and colorimetric procedures respectively. The areas under the apo B48, retinyl ester and triglyceride curves were determined by integration. Relationships between the post‐prandial response and the fasting concentration of apolipoprotein B48 were assessed using least‐squares regression analysis.ResultsWe found a strong positive relationship between the fasting plasma concentration of apo B48 and the post‐prandial kinetics of apo B48. Similarly, there was a positive relationship of fasting apo B48 with the retinyl ester area under the curve. Collectively, the data suggested that chylomicron remnant kinetics can be predicted based on the fasting level of apo B48. There was also a significant but weaker relationship of fasting apo B48 with post‐prandial triglyceride kinetics, consistent with removal of this lipid by hydrolytic mechanisms in addition to particle uptake.ConclusionThe fasting plasma concentration of apo B48 appeared to be a good surrogate marker for the degree of post‐prandial lipidaemia and may circumvent the need for oral fat challenges. Moreover, in the fasting state apo B48 concentration is a marker of chylomicron remnants, which are considered to be the proatherogenic form of these intestinally derived lipoproteins.
Distribution of diacylglycerols among plasma lipoproteins in control subjects and in patients with non‐insulin‐dependent diabetes
Authors: Lalanne F. , Pruneta V. , Bernard S. , Ponsin G. 
Published: March 2003

BackgroundDiacylglycerols (DAGs), which are well‐known components of insect lipophorins, have been recently recognized as a major glyceride of human high‐density lipoprotein (HDL). Moreover, DAGs are good substrates for hepatic lipase and for the phospholipid transfer protein (PLTP). The present work was undertaken to determine the lipoprotein concentrations of DAGs, in control subjects, in non‐insulin‐dependent diabetic (NIDD) patients and in patients with severe hypertriglyceridaemia.Materials and methodsLipoproteins were isolated from 11 control subjects, 17 diabetic patients and three hypertriglyceridaemic patients, using a combination of ultracentrifugation and precipitation. After lipid extraction, DAGs were separated by thin‐layer chromatography and quantified by a glyceride assay.ResultsDAGs were detectable in all lipoprotein fractions of the three groups of subjects. Total DAGs were correlated with total triglycerides (TGs) and even more strikingly with very low‐density lipoprotein triglycerides. Although the majority of DAG was recovered in apo B‐containing lipoproteins, the proportion of DAG with respect to TG was most elevated in HDL.ConclusionThese findings indicate that DAGs are probably formed from TG during lipolysis and that they can be transported to HDL through the action of PLTP. This raises the question whether DAG might act as an inhibitor of phospholipid transfer by competition for binding to PLTP.
Glucocorticoid receptors are down‐regulated in inflamed colonic mucosa but not in peripheral blood mononuclear cells from patients with inflammatory bowel disease
Authors: Rogler  , Meinel  , Lingauer  , Michl  , Zietz  , Gross  , Lang  , Andus  , Schölmerich  , Palitzsch  
Published: March 2003

BackgroundGrowing evidence indicates that the immune system and the hypothalamic–pituitary–adrenal system are linked by several mechanisms, for example intracellular glucocorticoid receptors (hGR). Glucocorticoids are the standard treatment of acute attacks of inflammatory bowel disease (IBD). Binding of glucocorticoids to hGR down‐regulates the transcription of inflammatory genes that can propagate IBD.Patients and methodsIBD patients were either treated with 5–60 mg of prednisolone for more than 1 week or were without glucocorticoid treatment for more than 4 weeks. hGR levels were determined from isolated cytosol of peripheral blood mononuclear cells (PBMCs) or mucosal biopsies using a radioassay with [3H]‐dexamethasone. Interleukin (IL) 6 levels were determined by enzyme‐linked immunosorbent assay (ELISA).ResultsThe systemic (PBMC) hGR levels of corticosteroid‐treated IBD patients were significantly lower than those of control subjects (59.6 ± 57.1 dpm mg−1 cytosol protein vs. 227.0 ± 90.8 dpm mg−1 cytosol protein, P = 0.007) and IBD patients not receiving glucocorticoid treatment (179.7 ± 171.3 dpm mg−1 cytosol protein, P = 0.002). Systemic hGR levels in untreated IBD patients did not differ significantly from those in control subjects. In patients with connective tissue diseases, systemic hGR levels were also found to be decreased in the absence of glucocorticoid treatment. Systemic hGR levels in patients with Crohn's disease (CD) treated with steroids (66.6 ± 61.0 dpm mg−1 cytosol protein) were not different from those in patients with ulcerative colitis (UC) (56.1 ± 51.6 dpm mg−1 cytosol protein). In contrast to these findings, mucosal hGR levels were significantly decreased in both steroid‐treated (18.0 ± 15.5) and not steroid‐treated (37.8 ± 30.5) patients compared with control subjects (125.6 ± 97.1; P = 0.00009 and P = 0.0008 respectively). IL‐6 levels in all IBD groups with and without steroids were significantly different from those in control subjects.ConclusionIn IBD there is no difference in systemic hGR levels between not steroid‐treated patients and control subjects, in spite of inflammatory activity (IL‐6). Mucosal hGR levels were decreased independently of treatment, probably leading to a decreased protection against NF‐κB action in the intestinal mucosa.
Chlamydia pneumoniae reactive T lymphocytes in the walls of abdominal aortic aneurysms
Authors: Halme S. , Juvonen T. , Laurila A. , Juvonen J. , Mosorin M. , Saikku P. , Surcel H.‐M. 
Published: March 2003

BackgroundThe presence of Chlamydia pneumoniae in the walls of abdominal aortic aneurysms (AAAs) has been demonstrated recently, but its role in the cause and/or maintenance of aortic wall inflammation is not known. In the present study, we have investigated the possible relationship between C. pneumoniae and the antigen specificity of T lymphocytes mediating inflammation in AAA tissue.Materials and methodsTissue specimens were obtained from 22 consecutive AAA patients undergoing elective surgery (mean age 67 ± 1 year). Immunohistochemical analysis of the formalin‐fixed tissue was performed using the streptavidin–biotin–peroxidase method. In vivo activated T lymphocytes were propagated from the specimens with interleukin (IL) 2, and antigen specificity of the established T‐cell lines was analysed in the presence of autologous antigen‐presenting cells using radioactive thymidine labelling.ResultsImmunohistological staining of AAA tissue showed the presence of C. pneumoniae antigen in 55% (6/11) of the samples studied. The inflammatory cell infiltrate of the AAA tissue contained 60–90% T (CD45RO) and 0–10% B (CD20) cells. When the tissue specimens were cultured without antigen in the presence of IL‐2, lymphocyte propagation was achieved in 17 out of the 22 samples. Chlamydia pneumoniae antigen was found to induce a positive proliferative response in 8 of the 17 lines.ConclusionsThe presence of C. pneumoniae specific T lymphocytes among in vivo activated cells from the AAA tissue specimens suggests that C. pneumoniae participates in the maintenance of the inflammatory response in the tissue and may thus be involved in the progression of the disease.
Muscle creatine phosphate in gyrate atrophy of the choroid and retina with hyperornithinaemia–clues to pathogenesis
Authors: Heinänen  , Näntö‐Salonen  , Komu  , Erkintalo  , Heinonen  , Pulkki  , Valtonen  , Nikoskelainen  , Alanen  , Simell  
Published: March 2003

BackgroundIn gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), inherited deficiency of ornithine‐δ‐aminotransferase leads to progressive fundus destruction and atrophy of type II skeletal muscle fibres. Because high ornithine concentrations inhibit creatine biosynthesis, the ensuing deficiency of high‐energy creatine phosphate may mediate the pathogenesis.Materials and methodsRelative concentrations of inorganic phosphate (Pi), creatine phosphate (PCr) and ATP in resting calf muscle were recorded in 23 GA patients and 33 control subjects using 31P‐magnetic resonance spectroscopy (MRS). Eight patients with autosomal recessive retinitis pigmentosa with matched control subjects constituted an additional reference group.ResultsThe PCr/Pi and PCr/ATP ratios (means ± SD) were lower for the GA patients than for healthy control subjects [4.66 ± 0.37 vs. 9.75 ± 2.17 (P < 0.0001) and 2.85 ± 0.37 vs. 3.70 ± 0.50 (P < 0.05) respectively]. In retinitis pigmentosa the respective values were 9.12 ± 2.57 and 4.25 ± 0.45. Age and stage of the disease had no effect.ConclusionMuscle 31P‐MRS spectra were markedly abnormal in all GA patients.
Lack of association between changes in plasma leptin concentration and in food intake during the menstrual cycle
Authors: Paolisso G. , Rizzo M. R. , Mazziotti G. , Rotondi M. , Tagliamonte M. R. , Varricchio G. , Carella C. , Varricchio M. 
Published: March 2003

BackgroundChanges in plasma leptin concentration and food intake occur during the menstrual cycle; because leptin regulates food intake, one could hypothesize that changes in plasma leptin concentration and in food intake are associated throughout the menstrual cycle. However, no data have ever been provided to support such a relationship. The aim of our study was to investigate, during the different phases of the menstrual cycle, (a) the changes in plasma leptin concentration and, if such changes were demonstrated, (b) the potential relationship between the changes in plasma leptin concentration and food intake.DesignThe study was designed as an observational study. The plasma leptin concentration was determined in 16 healthy, young women during different phases of the menstrual cycle. At the same time, the basal metabolic rate (BMR), respiratory quotient (RQ) and food intake (FI) were also determined.ResultsThe plasma leptin concentration increased throughout the menstrual cycle (P < 0.01 for trend) and was significantly correlated with plasma progesterone concentration (r = 0.55, P < 0.007, for follicular phase, r = 0.58, P < 0.02, for the periovulatory period and r = 0.57, P < 0.02, for the luteal phase). No significant differences in BMR and fasting RQ throughout the different phases of the menstrual cycle were found. In contrast, FI significantly declined in the periovulatory phase. No significant correlations between BMR, RQ and FI values and fasting plasma leptin concentration at all menstrual phases were found.ConclusionChanges in plasma leptin concentration and in food intake were found at different phases of the menstrual cycle. Nevertheless, no correlation among those parameters at any phase of the menstrual cycle was observed.
Integrin mediated adhesion of mononuclear cells from patients with familial hypercholesterolemia
Authors: De Bont  , Geijtenbeek  , Netea  , Smilde  , Demacker  , Figdor  , Van Der Meer  , Stalenhoef  
Published: March 2003

BackgroundLow‐density lipoproteins (LDL) can induce the adhesion of monocytes to endothelial cells. Monocytes of patients with familial hypercholesterolemia (FH) are exposed to high concentrations of LDL, and it has been reported that adhesiveness of these cells in hypercholesterolemic patients is enhanced. We investigated whether LFA‐1 or VLA‐4 mediated adhesion is altered in FH patients and whether HMG‐CoA reductase inhibitors influence this adhesion.Patients and methodsLFA‐1 and VLA‐4 mediated adhesion to ICAM‐1 and VCAM‐1 coated beads was investigated using freshly isolated monocytes and T‐lymphocytes from patients with homozygous FH, heterozygous FH (before and after cholesterol lowering treatment), and from controls. In addition, the expression of β1‐ and β2‐integrins on these cells was determined.ResultsBoth LFA‐1 and VLA‐4 mediated adhesion and integrin expression of monocytes and CD3+ cells from patients with homozygous FH and heterozygous FH was similar to that of monocytes from a control population. Treatment with HMG‐CoA reductase inhibitors did not affect the adherence to ICAM‐1 or VCAM‐1, and did not influence the expression of integrins.ConclusionsIn contrast to studies by others, we demonstrated in the present study that the actual LFA‐1 and VLA‐4 mediated adhesion of T‐lymphocytes and monocytes is not altered in patients with FH.
Hypoleptinemia in female and male elite gymnasts
Authors: Weimann  , Blum  , Witzel  , Schwidergall  , Böhles  
Published: March 2003

BackgroundElite gymnasts favour low body fat mass as the current aesthetic ideal required for complex movements in this sports discipline. Pubertal development and growth are retarded in juvenile gymnasts. Leptin, the protein product of the ob‐gene, is secreted by fat cells. Besides its role in regulation of body weight, leptin also stimulates the reproductive axis. We investigated various serum hormones including leptin, body composition and nutrition in cohorts of female and male elite gymnasts to elucidate if there is a relationship between leptin levels and delayed puberty in elite gymnasts.Materials and methodsTwenty‐two female and 18 male elite gymnasts were enrolled in this study. Pubertal stage, various hormonal levels and body composition were determined and nutritional intake was assessed. Leptin was analysed using a specific RIA.ResultsPubertal development and growth were delayed in the study group, especially in girls. The percentage of body fat was reduced as compared to a normal age‐matched population: 14.4% versus 21.9% in girls and 10.4% versus 15.1% in boys. Serum leptin levels were decreased, especially in pubertal girls, and did not show the normal developmental pattern with a steady increase in girls and a peak in boys of pubertal stage 2. In all gymnasts leptin levels correlated with the amount of fat mass (r = 0.6, P = 0.005 in girls; r = 0.44, P = 0.038 in boys). When leptin levels were transformed into standard deviation scores (SDS) it became obvious that the gymnasts, especially pubertal females, had significantly lower values than normal controls of the same sex, pubertal stage and body mass index (BMI): leptin SDS (BMI) = –1.21 and −3.99 in prepubertal and pubertal girls, − 0.94 and −0.91 in prepubertal and pubertal boys, respectively. When leptin SDS were based on % body fat instead of BMI, mean values were still significantly decreased compared to normal controls: −1.05 in girls (P < 0.001) and −0.60 in boys (P = 0.025).ConclusionsAdjustment of serum leptin levels in elite gymnasts for gender, pubertal stage and BMI or % body fat reveals inappropriately low values. The reason for this hypoleptinemia is most probably insufficient caloric intake. The data suggest that hypoleptinemia in turn causes delayed puberty and growth in this particular group of athletes.
Changes of plasma total homocysteine levels during the menstrual cycle
Authors: Tallova  , Tomandl  , Bicikova  , Hill  
Published: March 2003

BackgroundIt is known that plasma total homocysteine (tHcy) levels are lower in premenopausal and pregnant women compared with postmenopausal women. To confirm the suggestion that sex steroid hormones are nongenetic factors affecting homocysteine metabolism, we investigated the effect of natural steroid hormone levels on the fasting plasma tHcy in healthy women during the menstrual cycle.Materials and methodsFifteen premenopausal women were enrolled in this study. Plasma tHcy, estradiol, progesterone and cortisol concentrations were measured in the luteal and follicular phase. The plasma tHcy concentration was determined by high performance liquid chromatography with fluorescence detection, and the steroid hormones by RIA methods.ResultsMean homocysteine values increased from 7.8 μmol L−1 in the luteal phase to 8.9 μmol L−1 in the follicular phase (P < 0.000005, Student's paired t‐test). We also found slight negative but insignificant correlations of homocysteine levels with estradiol in both phases of the menstrual cycle. In the case of cortisol and progesterone, no significant correlations with plasma homocysteine were found.ConclusionThe study provides the first evidence of significant differences in plasma homocysteine concentration during the menstrual cycle. From our observed findings it is necessary to account for the phase of the menstrual cycle when determining homocysteine in premenopausal women.
Does jejunal feeding activate exocrine pancreatic secretion?
Authors: Vu  , Van Der Veek  , Frölich  , Souverijn  , Biemond  , Lamers  , Masclee  
Published: March 2003

BackgroundThe upper small bowel is of pivotal importance for the stimulation of exocrine pancreatic secretion in response to a meal. We hypothesize that more distal delivery of nutrients into the small intestine will result in less activation of pancreatic secretion.Materials and methodsEight healthy subjects (3 male, 5 female; age 23 ± 1 years) participated in two experiments, performed in random order. Subjects were intubated with a 4‐lumen tube. Duodenal outputs of pancreatic enzymes and bilirubin were measured by aspiration using a recovery marker. The distal opening was used for continuous administration of a mixed liquid meal and located at either the ligament of Treitz or 60 cm further distally. Gallbladder volume was measured and blood samples were drawn for determination of gastrointestinal hormones. The duration of each experiment was 4 h; with 1 h fasting and 3 h continuous administration of nutrients.ResultsDuring proximal jejunal feeding, pancreatic enzyme output increased significantly over basal levels. No significant increase over basal levels was observed during distal jejunal feeding. Bilirubin output and gallbladder contraction were significantly (P < 0.05) reduced during distal compared to proximal jejunal feeding. No significant differences were found in plasma levels of CCK, PYY and neurotensin between proximal and distal jejunal feeding.ConclusionContinuous feeding in the distal jejunum does not stimulate exocrine pancreatic secretion but maintains gallbladder contraction, although to a lesser extent. These effects are not related to hormonal changes but probably reduced activation of the enteropancreatic reflexes.