bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperglycaemia reduces gastrin‐stimulated gastric acid secretion in humans
Authors: Lam  , Masclee  , De Boer  , Lamers  
Published: March 2003

BackgroundRecent studies have pointed to the role of plasma glucose in the regulation of gastrointestinal function.MethodsWe have investigated the effect of acute hyperglycaemia on gastric acid secretion and pancreatic polypeptide (PP) release. Gastric acid output was measured under basal conditions and in response to intravenous infusion of gastrin‐17 in two doses: 5 pmol kg−1 h for 60 min and 15 pmol kg−1 h for another 60 min. Seven healthy subjects were studied during normoglycaemia and during acute hyperglycaemia at 15 mmol L−1. Acid output was measured by continuous aspiration using phenol red as recovery marker. Plasma PP levels were determined at regular intervals.ResultsGastrin infusion at 5 pmol kg−1 h significantly (P < 0.05) increased acid output both during normoglycaemia and during hyperglycaemia. Gastrin infusion at 15 pmol kg−1 h further and significantly (P < 0.05) increased the acid output during both experiments. Hyperglycaemia significantly (P < 0.05) reduced basal acid output (2.5 ± 0.9 vs. 6.3 ± 1.9 mmol h−1), low‐dose gastrin stimulated acid output (6.5 ± 1.7 vs. 13.0 ± 1.8 mmol h−1) and high‐dose gastrin stimulated acid output (11.7 ± 3.0 vs. 19.4 ± 3.0 mmol h−1) compared with normoglycaemia. Plasma PP levels were not stimulated by gastrin‐17 infusion and were significantly (P < 0.05) reduced during hyperglycaemia.Conclusions(a) Basal and gastrin‐17‐stimulated gastric acid secretion are reduced during hyperglycaemia; (b) infusion of gastrin‐17 to physiological post‐prandial levels does not affect plasma PP levels; (c) plasma PP levels are reduced during hyperglycaemia, suggesting vagal‐cholinergic inhibition of gastric acid secretion during hyperglycaemia.
Type I and type III procollagen propeptides in amniotic fluid of normal pregnancies and in a case of mild osteogenesis imperfecta
Authors: Kauppila  , Tekay  , Risteli  , Koivisto  , Risteli  
Published: March 2003

BackgroundThe propeptides derived from type I and III procollagens, PICP, PINP and PIIINP, indicate the synthesis of the corresponding collagens. Their circulating concentrations reflect the growth velocity in infants and childrenMethodsWe measured these propeptides in 145 samples of amniotic fluid of normal pregnancy. In addition, we have analysed an amniotic fluid and serum sample from a mother with osteogenesis imperfecta, and later the infant's serum sample was also collected for procollagen propeptide analysis.ResultsHigh concentrations of propeptides, 100–1000 times higher than those in adult serum, were found in early second trimester, decreasing significantly towards term, reflecting the decreased foetal growth rate. Interestingly, the amino‐terminal propeptide of type I procollagen, PINP, decreased more that the corresponding carboxy‐terminal propeptide, PICP, although both are in principle derived from the same protein. At both stages of pregnancy, the discrepant ratio of PICP to PINP indicated a molar excess of PINP. Abnormally low concentrations of PICP and PINP with normal PIIINP concentrations measured in amniotic fluid and in the serum indicated decreased synthesis of type I procollagen in a foetus/infant with mild osteogenesis imperfecta.ConclusionsOur data show a decrease in collagen synthesis with the stage of pregnancy and lower values of type I procollagen propeptides in a case of OI.
Decreased nitric oxide‐mediated natural killer cell activation in chronic fatigue syndrome
Authors: Ogawa  , Nishiura  , Yoshimura  , Horikawa  , Yoshida  , Okajima  , Matsumura  , Ishikawa  , Nakao  , Tomiyama  , Kanayama  , Kanakura  , Matsuzawa  
Published: March 2003

Background L‐Arginine (
L‐Arg), one of the essential amino acids, has been reported to have an immunomodulatory effect. The precise mechanism of the
L‐Arg‐induced natural killer (NK) cell activation remains unresolved ,and the effect of
L‐Arg on NK cells in chronic fatigue syndrome (CFS) patients has not been estimated.MethodsNK cell function was evaluated in 20 subjects with CFS and compared with that in 21 healthy individuals.ResultsIn healthy control subjects, NK activity was significantly increased after treatment with L‐Arg, an NK function enhancer, for 24 h, whereas the same treatment failed to enhance NK activity in the CFS patients. We thus focused on
L‐Arg metabolism, which involves nitric oxide (NO) production through NO synthase (NOS). The expression of inducible NO synthase (iNOS) transcripts in peripheral blood mononuclear cells was not significantly different between healthy control subjects and CFS patients. The
L‐Arg‐mediated NK cell activation was abolished by addition of NG‐monomethyl‐
L‐arginine, an inhibitor for iNOS. Furthermore, incubation with S‐nitroso‐N‐acetyl‐penicillamine, an NO donor, stimulated NK activity in healthy control subjects but not in CFS patients.ConclusionThese results demonstrate that the L‐Arg‐induced activation of NK activity is mediated by NO and that a possible dysfunction exists in the NO‐mediated NK cell activation in CFS patients.
In vitro expression of soluble and cell surface‐associated CD44 on endometrial cells from women with and without endometriosis
Authors: Prifti  , Sillem  , Arslic  , Monga  , Rehberger  , Runnebaum  
Published: March 2003

BackgroundEndometriosis is one of the most common benign gynaecological diseases, and attachment of retrogradely shed viable endometrial cells is considered to be important in its development. CD44 is a multifunctional adhesion molecule that undergoes alternative splicing, giving rise to different isoforms.MethodsThe expression of cell surface‐associated CD44 std, v4, v5, v6 and v10 variants before and after cytokine treatment was investigated in endometrial cultures derived from 10 endometriosis patients and 22 women without the disease using immunocytochemistry. The immunoreactivity of soluble CD44 std, v5 and v6 variants was measured in culture medium using an enzyme immunoassay kit.ResultsWe report on the presence of soluble CD44 in endometrial culture supernatants. In particular, circulating CD44 standard form levels were significantly higher than levels of splice variants. We also found that both epithelial and stromal cells express surface‐associated CD44 molecules in a distinct pattern and that this expression is not modulated by tumour necrosis factor (TNF)‐α or/and interleukin 1 (IL‐1) α/β. Finally, cell surface‐associated as well as soluble CD44 expression was similar in the two groups.ConclusionOur results indicate that endometrial cells can serve as a source of circulating CD44, but a direct role in the pathogenesis of endometriosis is rather improbable.
Lack of interleukin 10 regulation of antigen presentation‐associated molecules expressed on colonic epithelial cells
Authors: Bourreille  , Segain  , Raingeard de la Blétière  , Siavoshian  , Vallette  , Galmiche  , Blottière  
Published: March 2003

BackgroundColonic epithelial cells may behave as antigen‐presenting cells. Interleukin 10 (IL‐10) is known to play a major role in the intestinal immune system; however, it remains to be determined whether human intestinal epithelial cells express IL‐10 receptor, and whether this cytokine modulates their expression of antigen presentation‐associated moleculesMethodsThe binding of biotinylated IL‐10 was studied in SW 1116, HT‐29 and T84 human colonic epithelial cell lines and freshly isolated normal colonic epithelial cells. Reverse transcription‐polymerase chain reaction was also performed to detect IL‐10 receptor mRNA. The effect of IL‐10 on antigen presentation associated molecules was assessed by flow cytometry.ResultsBiotinylated IL‐10 bound to SW 1116, HT‐29, T84, and normal colonic epithelial cells. IL‐10 receptor mRNA was detected in SW 1116 and normal epithelial cells. SW 1116 and HT‐29 cells expressed MHC class I and ICAM‐1, but not CD80, and SW 1116 constitutively expressed HLA‐DR. Interferon‐γ up‐regulated HLA‐DR and ICAM‐1 expression on both cells, whereas lipopolysaccharide increased ICAM‐1 expression only on SW 1116. IL‐10 failed to modulate these antigens, even after stimulation by lipopolysaccharide or interferon‐γ. Moreover, these molecules decreased IL‐10 binding in both lines.ConclusionThe presence of IL‐10 receptor on intestinal epithelial cells suggest that IL‐10 may play a role in mucosal physiology, however its effect on the immune response remains to be determined.
Parathyroid hormone is not a key hormone in the rapid minute‐to‐minute regulation of plasma Ca2+ homeostasis in rats
Authors: Wang  , Lewin  , Olgaard  
Published: March 2003

BackgroundThe role of parathyroid hormone (PTH) in the rapid minute‐to‐minute regulation of plasma Ca2+ (p‐Ca2+) was studied in vivo in rats.Materials and methodsThe rapid calcaemic response to exogenous rat PTH1–34 (16 μg) was examined in normal rats, and the long‐term calcaemic response was examined in parathyroidectomized (PTX) rats receiving PTH1–34 for 24 h at 0.2, 0.4 and 0.8 μg h−1. Acute hypocalcaemia was induced by EGTA for 30 min, and then the rapid recovery of p‐Ca2+ was studied for 130 min in normal rats, 24 h after PTX and in PTX rats infused with exogenous rat PTH1–34. The dynamics of the rapid recovery of p‐Ca2+ was studied at two additional doses of EGTA.ResultsNo rapid calcaemic response was observed in the first 60 min after administration of PTH and no hypocalcaemia was seen for 2 h after acute PTX. This slow effect of PTH suggests that PTH might not be responsible for maintaining the stable p‐Ca2+ on a rapid minute‐to‐minute basis. EGTA induced acute hypocalcaemia in both normal and PTX rats (P < 0.01). In both groups a rapid and similar increase in p‐Ca2+ took place 10 min after discontinuing EGTA (P < 0.05). Within 60 min, p‐Ca2+ increased further, independently of the presence of PTH. Infusion of PTH to PTX rats did not affect the rapid recovery of p‐Ca2+ (P < 0.05) from EGTA induced hypocalcaemia.ConclusionPTH is not a key hormone in the rapid recovery of p‐Ca2+ after induction of hypocalcaemia, but might, however, set the long‐term levels of p‐Ca2+ maintained by mammalian organisms. The involvement of an as yet unknown factor in the rapid regulation of p‐Ca2+ is suggested.
Delayed post‐prandial lipid metabolism in subjects with intra‐abdominal visceral fat accumulation
Authors: Taira  , Hikita  , Kobayashi  , Bujo  , Takahashi  , Murano  , Morisaki  , Saito  
Published: March 2003

BackgroundIndividuals with obesity, in particular those with intra‐abdominal visceral fat accumulation, are known to have various complications, such as hyperlipidaemia, impaired glucose tolerance, hyperinsulinaemia and hypertension, leading to the development of coronary heart disease. Post‐prandial hyperlipidaemia has repeatedly been shown to be an independent risk factor for coronary heart disease. The aim of the present study was to investigate post‐prandial lipoprotein metabolism in subjects with excessive visceral fat accumulation.Materials and methodsEighty‐three patients (52 men, 31 women) [average age 48 ± 14 years; mean body mass index (BMI) 25 ± 5 kg m−2] were recruited to the study. Visceral (or subcutaneous) fat accumulation was analysed as areas of fat deposition by computerized tomography at the umbilicus level. After a 12‐h overnight fast, oral vitamin A and a fatty meal (40 g m−2 fresh cream containing 50 000 units m−2 vitamin A) were administered to these subjects. The concentration of retinyl palmitate (RP) was measured by high‐performance liquid chromatography.ResultsThe visceral fat area (V) was positively correlated with plasma triglyceride (TG) 0, 2, 4 and 6 h after fat loading and with plasma RP 0, 4 and 6 h after fat loading. The BMI did not show any correlation with plasma TG and RP at any point. The visceral fat area was positively correlated with the RP area under the curve (AUC) in the serum from the subjects [V vs. RP AUC: n = 83, r = 0.327, P = 0.013]. The BMI of the subjects did not show any correlation with the RP AUC (r = 0.021, P = 0.85).ConclusionThese results suggest that post‐prandial lipid metabolism is impaired in subjects with intra‐abdominal visceral fat accumulation, irrespective of BMI, leading to the development and progression of coronary atherosclerosis.
Energetics and function of the failing human heart with dilated or hypertrophic cardiomyopathy
Authors: Kalsi K. K. , Smolenski R. T. , Pritchard R. D. , Khaghani A. , Seymour A‐M. L. , Yacoub M. H. 
Published: March 2003

BackgroundImpaired energy metabolism in the failing human heart could be an important mechanism of functional deterioration. The purpose of this study was to assess the changes of myocardial energy metabolism in the human heart at end‐stage heart failure.Materials and methodsThe left ventricular myocardium of patients undergoing heart transplantation due to dilated (DCM, n = 14) or hypertrophic cardiomyopathy (HCM, n = 5) and non‐diseased donor heart samples (n = 4) were analysed for citrate synthase (CS), enzymes of the glycolytic pathway as well as concentrations of phosphocreatine (PCr), creatine (Cr), adenine and guanine nucleotides.ResultsTotal creatine levels (phosphocreatine + creatine) were significantly decreased (P < 0.05) in both groups of diseased hearts (3.87 ± 0.57 in DCM, 5.09 ± 1.23 in HCM compared with control 10.7 ± 3.5 μmol g−1 wet weight). There was a trend for higher guanine nucleotide content in failing hearts, but no significant differences were observed in total adenine nucleotides and total NAD content. CS was markedly reduced (P < 0.05) in both groups of diseased hearts: in the DCM to 13.8 ± 1.3 μmol min−1 g−1 wet weight, and in HCM to 11.9 ± 2.4 compared with the control 29.2 ± 2.2. Glycolytic enzymes were decreased compared with the control, and this decrease was greater in DCM than in HCM. Echocardiographic indices of contractility were considerably better in hypertrophic cardiomyopathy.ConclusionDespite the different mechanisms of cardiac failure and the differences in contractility of the heart we have observed, metabolic changes are very similar in hypertrophic and dilated cardiomyopathy. Depletion of the creatine pool suggests an alteration in the intracellular energy reserves and transfer, whereas the decrease in citrate synthase activity suggests reduced oxidative capacity in both dilated and hypertrophic cardiomyopathy.
Elevation of plasma leptin concentrations in obese hyperinsulinaemic hypothyroidism before and after treatment
Authors: Kautzky‐Willer  , Ludwig  , Nowotny  , Roden  , Huemer  , Widhalm  , Vierhapper  , Waldhäusl  , Roden  
Published: March 2003

BackgroundPlasma leptin is considered to play a role in maintenance of energy balance and body weight by neuroendocrine mechanisms. Thyroid hormones are permissive for adrenergic activation, which in turn has been shown to decrease leptin expression. This study was therefore designed to test the hypothesis that hyperthyroidism results in lower leptin concentrations, whereas hypothyroidism leads to higher plasma leptin concentrations. In addition, the effects of normalization of thyroid function on plasma leptin were investigated.Materials and methodsFasting plasma leptin concentrations and body fat mass (total body electrical conductivity) were measured in patients with overt hypothyroidism and hyperthyroidism before and after successful treatment. Plasma leptin, glucose, insulin and free fatty acid concentrations were monitored during an oral glucose tolerance test (OGTT 75 g).ResultsFasting plasma leptin concentrations were similar in lean patients, independently of their thyroid function (hyperthyroid 12.5 ± 2 ng mL−1, hypothyroid 10.2 ± 2 ng mL−1, euthyroid 12.7 ± 3 ng mL−1). In obese hypothyroid patients, plasma leptin was threefold higher (P < 0.0005) than in lean hypothyroid patients, twofold higher (P < 0.005) than in obese hyperthyroid patients matched for fat mass and 30% increased (P < 0.01) compared with obese euthyroid subjects. There were no differences between fasting and post‐prandial (OGTT) leptin concentrations in any group. Normalization of thyroid function did not affect plasma leptin, which remained elevated (P < 0.005) in formerly obese hypothyroid patients. Plasma leptin was not associated with serum thyroid hormones but highly correlated with body mass index and body fat mass in all patients (r = 0.85, P < 0.001). Plasma leptin correlated with plasma insulin concentration only in hyperthyroid patients (P < 0.01, r = 0.64), who presented with blunted stimulation of insulin release and higher plasma glucose (P < 0.05) than hypothyroid subjects.ConclusionThe results indicate that (a) the correlation of leptin with body fat mass is preserved in thyroid dysfunction, (b) plasma leptin is markedly increased in obese hypothyroid hyperinsulinaemic patients and (c) plasma leptin is not affected by oral glucose loading.
Comparison of bolus versus fractionated oral applications of [13C]‐linoleic acid in humans
Authors: Demmelmair  , Iser  , Rauh‐Pfeiffer  , Koletzko  
Published: March 2003

BackgroundThe endogenous conversion of linoleic acid into long‐chain polyunsaturated fatty acids is of potential importance for meeting substrate requirements, particularly in young infants. After application of [13C]‐linoleic acid, we estimated its conversion to dihomo‐γ‐linolenic and arachidonic acids from only two blood samples.DesignOral tracer doses were given to five healthy adults as a single bolus. In four subjects the tracer was given in nine equal portions over 3 days. Concentration and 13C content of fatty acids from serum phospholipids were analysed by gas chromatography combustion isotope ratio–mass spectrometry. Areas under the tracer–concentration curves were calculated, and fractional transfer and turnover rates estimated from compartmental models.ResultsThe median fractional turnover of linoleic acid was 93.7% per day (interquartile range 25.3) in the bolus group and 80.0% per day (6.3) in the fraction group (NS). Fractional conversion of linoleic to dihomo‐γ‐linolenic acid was 1.5% (0.9) vs. 2.1% (0.7) (bolus vs. fraction, P < 0.05), and fractional conversion of linoleic to arachidonic acid was 0.3% (0.3) vs. 0.6% (0.3) (bolus vs. fraction, NS). In the fraction group conversion was significantly higher based on areas under the curve. The ratio of tracer concentration in conversion products to linoleic acid 48 h after dosing correlated very well (r ≥ 0.94, P < 0.05) with the ratio of areas under the curve.ConclusionsUsing areas under the curve overestimates the conversion, because different residence times are not considered. Estimation of conversion intensity appears possible with only one blood sample obtained after tracer application.
Physiological doses of calcium regulatory hormones do not normalize bone cells in uraemic rats
Authors: Szabó A. , Freesmeyer M. G. , Abendroth K. , Stein G. , Rosivall L. , El‐Shakmak A. , Ritz E. 
Published: March 2003

BackgroundLow bone turnover despite normal parathyroid hormone (PTH) concentrations has been found in many patients with end‐stage renal failure. Hyporesponsiveness to the calcaemic action is also a known feature of uraemia. Hyporesponsiveness of bone surface cells involved in bone modelling has not been demonstrated to date. It was the purpose of this study using a rat model of moderate renal failure to investigate whether doses of PTH and calcitriol that reverse the effect of parathyroidectomy on calcaemia also normalize bone surface cell activity.Materials and methodsSham‐operated pair‐fed male Spraque–Dawley rats were compared with subtotally nephrectomized (SNX), parathyroidectomized (PTX) rats that received either solvent or calcitriol (5 pmol kg −1 h−1) + 1,34 rat PTH (100 ng kg −1 h−1) by osmotic mini‐pump. Histomorphometric measurements were carried out in the vertebral body (L5).ResultsIn SNX/PTX animals, calcitriol + 1,34 rat PTH caused a modest increase in serum calcium (S‐Ca) within the normal range. Osteoclast surface per cent was significantly lower in solvent‐treated SNX/PTX rats than in sham‐operated controls [3.7 ± 2.8 osteoclast surface/bone surface (OcS/BS%) vs. 6.3 ± 3.9], and this was not normalized by PTH + calcitriol (3.3 ± 3). In contrast, osteoblast surface per cent and osteoid surface per cent were increased over values in sham‐operated rats; as a result, co‐administration of calcitriol and 1,34 rat PTH caused a highly significant increase in fractional bone volume (BV/TV).ConclusionsThe results show that administration of PTH and calcitriol in doses that raise serum calcium fails to normalize the percentage of osteoclast surface, but was effective in raising osteoblast number and osteoblast volume in experimental renal failure. The results argue for abnormal response of bone cells to calcium‐regulating hormones and/or the action of factors other than calcium regulatory hormones in the genesis of skeletal abnormalities of renal failure.
Pneumocystis carinii major surface glycoprotein induces interleukin‐8 and monocyte chemoattractant protein‐1 release from a human alveolar epithelial cell line
Authors: Benfield  , Lundgren  , Shelhamer  , Lundgren  
Published: March 2003

BackgroundThe major surface glycoprotein (MSG) is an abundant, immunogenic glycoprotein located on the surface of Pneumocystis carinii. Little is known about the proinflammatory effects of MSG.DesignWe have investigated the effect of human MSG on the secretion of the chemokines interleukin 8 (IL‐8) and monocyte chemoattractant protein‐1 (MCP‐1) from an alveolar epithelial cell line (A549).ResultsIncubation of A549 cells with MSG in concentrations from 0.4 to 10 μg mL−1 for 24 h caused dose‐dependent increases in IL‐8 release (3.4‐fold above control, P < 0.01). Time course experiments showed increases in IL‐8 release at 4 h, 8 h and 24 h compared with control cultures (all P < 0.01). There was a minor (13%) dose‐ and time‐related increase in MCP‐1 release at 24 h (P = 0.02). Co‐incubation of MSG with mannan or β‐glucan decreased IL‐8 release by 48% and 42% respectively, suggesting that MSG stimulates A549 cells in part through carbohydrate moieties. Dexamethasone significantly inhibited MSG‐induced IL‐8 release in concentrations of 10−6–10−8 mol L−1 compared with control experiments (P < 0.01). Ribonuclease protection assays for steady‐state IL‐8 mRNA showed that increases in response to MSG stimulation occurred by 4 h and persisted throughout 8 h of stimulation.ConclusionThese findings suggest that MSG can alter alveolar epithelial cytokine release and may be capable of modulating the local inflammatory response in this manner.