bluuebunny/crossref_metadata_2025_split huggingface dataset:
Varying very low‐density lipoprotein secretion of rat hepatocytes by altering cellular levels of calcium and the activity of protein kinase C
Authors: Björnsson  , Bourgeois  , Gibbons  
Published: March 2003

BackgroundCalcium antagonists lower plasma levels of lipoproteins and suppress hepatic very low‐density lipoprotein (VLDL) secretion. Similar effects have been observed with the calcium ionophore A23187. We studied further the effect of calcium on VLDL metabolism.MethodsHepatocytes from male Wistar rats were isolated and cultured in the presence or absence of calcium‐mobilizing hormones, or compounds that either stimulate or inhibit the activity of protein kinase C. Secreted VLDL (d < 1.006 g mL−1) was isolated by centrifugation (145 000 × g), and lipids and apolipoprotein B were analysed.ResultsVLDL secretion reached maximum in hepatocytes cultured in medium containing calcium 0.8–2.4 mmol L−1. Depleting the cells of calcium by incubating in calcium‐free medium or by treating the cells with the Ca2+‐ATPase inhibitor thapsigargin (5 × 10−7 mol L−1) suppressed lipid secretion to less than 15% of control, and this was accompanied by an increase in cellular levels of triacylglycerol. Calcium loading (medium calcium > 2.4 mmol L−1) suppressed both lipoprotein secretion and cellular levels of lipids, suggesting a reduced overall rate of lipid synthesis. At an extracellular calcium concentration of 0.8 mmol L−1, angiotensin II, vasopressin, endothelin‐1 (10−7 mol L−1) or phenylephrine (10−4 mol L−1) suppressed VLDL secretion (maximum to 37% of control), and elevated medium calcium attenuated this effect. The protein kinase C inhibitor chelerythrine (5 × 10−5 mol L−1) and the protein kinase C activator phorbol 12‐myristate 13‐acetate (PMA) (10−6 mol L−1), suppressed VLDL secretion to 18% and 60% of control, respectively, whereas the protein kinase C‐inactive 4α‐PMA was without an effect. No effect on ketogenesis was observed by these compounds, indicating that suppressed lipid secretion was not due to an enhanced oxidation of lipids.ConclusionsHepatic VLDL secretion can be related to changes in hepatocyte levels of calcium and the activity of protein kinase C.
Mutations in the low‐density lipoprotein receptor gene in Swedish familial hypercholesterolaemia patients: clinical expression and treatment response
Authors: Ekström  , Abrahamson  , Wallmark  , Florén  , Nilsson‐Ehle  
Published: March 2003

BackgroundFamilial hypercholesterolaemia, an autosomal co‐dominant disorder caused by defects in the low‐density lipoprotein receptor gene, is strongly associated with premature development of cardiovascular disease.MethodsIn this study, we have applied a gene screening method in a population of familial hypercholesterolaemia patients in order to describe the genetic background of the disease in southern Sweden. These patients were studied with the aim of relating the presence of the different mutations to the clinical expression of the disease and to the response to pharmacological treatment.ResultsIn 16 out of 21 patients, potentially disease‐causing low‐density lipoprotein receptor gene defects were found, including five not previously described alterations (C240 → F, C122 → stop, C356 → Y, 785insG, 165delG). No defects in apolipoprotein B were found. One group of patients (n = 4) carried the mutation C122 → stop and another group of patients (n = 4) a mutation causing the substitution W66 → G. Patients in the two genotype subgroups were very similar with respect to lipid levels before treatment.ConclusionA tendency towards differential susceptibility to treatment with statins was observed for the patient groups, encouraging further comparative studies of heterozygous FH patients.
Circulating leptin has saturable transport into intrathecal space in humans
Authors: Koistinen  , Karonen  , Iivanainen  , Koivisto  
Published: March 2003

BackgroundLeptin is an adipocyte‐derived hormone that is thought to provide a negative feedback signal to control body fat mass by interacting with its hypothalamic receptor. The present study was undertaken to examine the uptake of leptin in cerebrospinal fluid (CSF) space in humans and whether the transport of leptin into CSF space is an active phenomenon or due to free access through the blood–CSF barrier.MethodsWe determined serum and CSF leptin concentrations by radioimmunoassay in 17 men [42 ± 4 years, mean ± SE; body mass index (BMI) 27.3 ± 1.8 kg m−2] and 22 women (40 ± 3 years, BMI 25.1 ± 1.0 kg m−2). The function of the blood–CSF barrier was evaluated by determining the CSF/serum albumin ratio.ResultsSerum leptin concentration was lower in male (5.8 ± 1.6 μg L−1) than in female subjects (13.1 ± 1.7 μg L−1, P = 0.001), whereas the concentrations of leptin in CSF were virtually identical in male (0.34 ± 0.03 μg L−1) and female (0.36 ± 0.03 μg L−1) subjects. Serum leptin was correlated positively with BMI both in men (r = 0.89, P < 0.01, n = 10) and in women (r = 0.61, P < 0.05, n = 14), whereas no correlation between CSF leptin concentration and BMI was found in either group. The CSF/serum leptin ratio correlated negatively with serum leptin concentration both in men (r = −0.93, P < 0.001) and in women (r = −0.77, P < 0.001) and with BMI both in men (r = −0.75, P = 0.02, n = 10) and in women (r = −0.64, P < 0.02, n = 14). The CSF/serum albumin ratio was not correlated with the CSF/serum leptin ratio in either group. CSF leptin concentrations and the CSF/serum leptin ratio were virtually identical in subjects with impaired and normal blood–CSF barrier function.ConclusionThus, our data support the presence of a saturable and active transporter of leptin from circulation into intrathecal space.
Ureter obliteration transiently depresses erythropoietin production
Authors: Nečas  , Ponka  
Published: March 2003

BackgroundThe erythropoietin (EPO) gene is activated in peritubular cells of the renal cortex in response to hypoxia and EPO is secreted into the circulation. Oxygen tension in the venous blood normally determine EPO elaboration, and, therefore, oxygen consumption in the kidney appears to be an essential part of the oxygen‐sensing physiological mechanism. As renal oxygen consumption is closely linked to urine production, we have compared responsiveness of the EPO gene to diminished oxygen supply in the normal kidney with that of the hydronephrotic kidney, resulting from ureter ligation.MethodsErythropoietin mRNA was determined in RNA extracted from murine kidneys at various times up to 61 days after ureter ligation. Mice were exposed to hypoxia for 4 h before being killed.ResultsUnilateral ureter ligation significantly decreased EPO mRNA levels in the affected kidney. However, the ability to increase EPO mRNA recovered between days 4 and 22, despite persisting ureter ligation.ConclusionOur results demonstrate a dissociation between the excretory functions of the kidney and EPO production. Moreover, they show an early but transient suppression of EPO gene responsiveness to hypoxia after ureter ligation.
The effects of ABT‐229 and octreotide on interdigestive small bowel motility, bacterial overgrowth and bacterial translocation in rats
Authors: Nieuwenhuijs  , Van Duijvenbode‐Beumer  , Verheem  , Visser  , Verhoef  , Gooszen  , Akkermans  
Published: March 2003

BackgroundInterdigestive small bowel motility has a regulatory function on the microflora of the upper small bowel. Here we investigate the effects of ABT‐229 and octreotide on morphine‐induced dysmotility, the accompanying bacterial overgrowth and bacterial translocation.MethodsRats were fitted with jejunal myoelectrodes and a subcutaneous cannula for continuous infusion of saline or morphine. Fasting motility was measured for 6 h on four occasions: one control measurement (day 0) and three measurements on consecutive days (days 1–3) while receiving saline alone (group A), morphine alone (group B), saline + ABT‐229 (group C), morphine + ABT‐229 (group D), saline + octreotide (group E) or morphine + octreotide (group F). Samples from the mesenteric lymph node complex (MLN), liver, spleen, duodenum and ileum were taken for quantitative microbial culturing on day 4.ResultsNeither ABT‐229 nor octreotide increased the number of propagated activity fronts during saline infusion. During morphine‐induced dysmotility, ABT‐229 induced more propagated activity fronts in group D (13.4, 9.8 and 8.8 per 6 h) than in group B (7.0, 4.5, 3.8 per 6 h) on days 1, 2 and 3 (P < 0.05 for all days) Octreotide did not induce more propagated activity fronts. Disruption of small bowel motility by morphine led to bacterial overgrowth in the duodenum. ABT‐229 and octreotide did not reduce the bacterial growth levels. The total incidence of bacterial translocation was significantly higher in the morphine‐treated animals than in the saline‐treated animals. Neither ABT‐229 nor octreotide reduced the bacterial translocation incidence. The number of propagated activity fronts on day 3 and duodenal bacterial growth correlated significantly in groups A, E and F.ConclusionsABT‐229, but not octreotide, reduced morphine‐induced dysmotility. Small bowel bacterial overgrowth and bacterial translocation were not prevented. Fasting small bowel motility has a regulatory function on the intestinal microflora of the upper small bowel.
Expression of genes involved in calcium absorption in human duodenum
Authors: Walters  , Howard  , Lowery  , Mawer  , Legon  
Published: March 2003

BackgroundThe role of vitamin D metabolites in the regulation of expression of genes involved in dietary calcium absorption by the human intestine remains poorly understood despite much work in animals.Materials and methodsTo investigate this, we measured the expression of transcripts for two of these genes, calbindin‐D9k and the basolateral membrane calcium pumping ATPase, PMCA1, in duodenal endoscopic biopsies from 40 subjects. Northern blots were hybridized with previously characterized probes, and the signal was quantified by phosphor imaging. These transcript levels were related to circulating vitamin D metabolites and also analysed according to the vitamin D receptor gene TaqI polymorphism determined in DNA from blood.ResultsPlasma 1,25‐dihydroxycholecalciferol correlated significantly with calbindin‐D9k RNA (r = 0.4, P < 0.02) but not with PMCA1. Plasma 25‐OH‐cholecalciferol was not correlated with transcripts for either gene and, furthermore, the mean levels of these transcripts did not differ significantly when grouped by vitamin D receptor genotype.ConclusionIn normal humans, 1,25‐dihydroxycholecalciferol has a small but significant relationship to duodenal expression of calbindin‐D9k, but not to PMCA1 expression.
Polymorphisms of the endothelial nitric oxide synthase gene — no consistent association with myocardial infarction in the ECTIM study
Authors: Poirier  , Mao  , Mallet  , Nicaud  , Herrmann  , Evans  , Ruidavets  , Arveiler  , Luc  , Tiret  , Soubrier  , Cambien  
Published: March 2003

BackgroundOur aim in the present study was to determine whether endothelial NO synthase gene (ecNOS) polymorphisms are associated with myocardial infarction (MI).MethodsForty chromosomes from patients with MI were screened for polymorphisms of the ecNOS gene using polymerase chain reaction–single‐strand conformation polymorphism (PCR–SSCP) analysis and sequencing. Ten polymorphisms were detected: three in the 5′ flanking sequence at positions −1474, −924 and −788, two in coding sequences 774C → T (silent) and G894 → T (Glu‐298 → Asp) and five in introns 2, 11, 12, 22 and 23. Five hundred and thirty‐one patients with MI and 610 control subjects recruited in France and Northern Ireland in the ECTIM study were genotyped for these polymorphisms.ResultsGlu‐298 homozygotes were more frequent among patients with MI than in control subjects in the French population [OR = 1.47 (1.03–1.97), P < 0.009], but no such difference was observed in Northern Ireland. No significant difference between cases and control subjects was detected for the other polymorphisms. Our search for a possible association of the combination of ecNOS polymorphisms with MI by logistic regression analysis was also negative.ConclusionsWe have explored a set of polymorphisms of the ecNOS gene in a large case–control study of MI and found that the polymorphisms were not consistently associated with MI.
Evidence of circadian rhythm in low‐density lipoprotein apoB catabolism and its impact on the estimation of kinetic parameters
Authors: Weryński  , Nahorski  , Berglund  , Ericsson  , Angelin  , Eriksson  
Published: March 2003

BackgroundCompartmental models with constant parameters are commonly used in kinetic analysis of low‐density lipoproteins (LDLs). Recent studies in animals have demonstrated the existence of circadian rhythms (CRs) in cholesterol synthesis and LDL catabolism. In this study, we investigated the possible existence of a CR in the fractional catabolic rate (FCR) of LDL apoB in man.Materials and methodsRadioactivity data from 45 turnover studies using 125I‐labelled LDL apoB were analysed. In a preliminary analysis the pattern of radioactivity decay was investigated. Kinetic analysis was performed by using one‐ and two‐compartment models with constant parameters (steady‐state, SS, analysis). Parameters were estimated by the use of the whole data set, which included frequent sampling during the first day of the turnover study, or the once‐a‐day data, taken at 08.00 h . The selection of once‐a‐day data allowed elimination of the impact of a CR on parameter evaluation. Furthermore, non‐steady‐state (NSS) analysis was performed in which the FCR of LDL apoB was calculated as a function of time. In one additional subject, the FCR of LDL apoB was calculated separately for the day and the night using the urine‐to‐plasma (U/P) radioactivity ratio.ResultsThe presence of a CR in LDL apoB catabolism, with higher FCR values during the day than during the morning, was demonstrated by the NSS analysis and confirmed by LDL apoB calculation from the U/P ratio. The SS analysis with the whole and the once‐a‐day data sets resulted in similar average FCR of apoB values (0.329 ± 0.076 and 0.321 ± 0.071 respectively) when the two‐compartment model was used. Thus, a CR appeared to have little impact on the average FCR of apoB estimation. However, frequent sampling used in the hope of improving parameter estimation accuracy actually resulted in deterioration of the intercompartmental parameter estimators.ConclusionThe fractional catabolic rate of LDL apoB exhibited a circadian rhythm with higher FCR values during the day than during the morning. The presence of a CR had, however, a limited impact on the overall FCR of apoB values.
Myocardial bradykinin production during coronary balloon angioplasty in humans
Authors: MacCarthy  , Prendergast  , Williams  , Penny  , Shah  
Published: March 2003

BackgroundRecent studies have implicated the peptide bradykinin as a potential trigger of ischaemic preconditioning, the phenomenon whereby a brief episode of myocardial ischaemia induces an increased tolerance to subsequent more prolonged ischaemia. Brief myocardial ischaemia occurring during percutaneous transluminal coronary balloon angioplasty in humans is reported to be capable of inducing preconditioning.DesignWe studied the intracardiac production of bradykinin in eight patients (seven men, mean age 53.5 years) undergoing elective percutaneous transluminal coronary angioplasty for a single left anterior descending coronary artery stenosis. Paired blood samples were obtained from the coronary sinus and the proximal aorta at baseline, immediately before balloon deflation after a 2‐min inflation, and at 1, 3 and 5 min post deflation. Bradykinin levels were measured by radioimmunoassay.ResultsThere was no significant change either in aortic or coronary sinus bradykinin levels at any time point.ConclusionsIntracardiac production of bradykinin is unlikely to be a trigger for ischaemic preconditioning after brief myocardial ischaemia in humans.
Antroduodenal motility and small bowel transit during continuous intraduodenal or intragastric administration of enteral nutrition
Authors: Ledeboer  , Masclee  , Coenraad  , Vecht  , Biemond  , Lamers  
Published: March 2003

BackgroundGastrointestinal intolerance is observed more frequently during intraduodenal (ID) tube feeding than during intragastric (IG) feeding, possibly because it evokes a stronger gastrointestinal response and accelerates small bowel transit. We have investigated whether the accelerated small bowel transit during ID feeding results from alterations in antroduodenal motility pattern.DesignThe effect of IG and ID infusion of a polymeric diet (Nutrison, 125 kcal h−1) on antroduodenal motility, small bowel transit time (SBTT) and gastrointestinal hormone release was studied in nine healthy subjects. These subjects were studied on three occasions for 6 h during fasting, continuous IG or ID feeding.ResultsPhase III recurrence time was significantly prolonged during IG feeding compared with fasting (240 ± 51 vs. 136 ± 24 min; P < 0.05). None of the subjects had recurrence of phase III during ID feeding; the fed motor pattern remained present. Parameters of fed motility (mean amplitude and motility index) were not significantly different between IG and ID feeding, although the frequency of antral and duodenal contractions was lower during ID than during IG feeding. SBTT was significantly accelerated during ID compared with IG feeding and with fasting (58 ± 8 vs. 73 ± 9 and 83 ± 10 min respectively; P < 0.05). Plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) levels were significantly higher during ID than during IG feeding. Peptide YY (PYY) levels were significantly higher during ID than during fasting, but not during IG feedingConclusionsDuring intraduodenal feeding, a fed motility pattern is preserved, whereas during intragastric feeding transition from a fed to a fasting motor pattern is observed in over 50% of the subjects. These differences may be related to augmented hormone release during intraduodenal feeding.
Potent synergistic effect of sho‐saiko‐to, a herbal medicine, during vaccine therapy in a murine model of hepatitis B virus carrier
Authors: Akbar  , Yamamoto  , Abe  , Ninomiya  , Tanimoto  , Masumoto  , Michitaka  , Horiike  , Onji  
Published: March 2003

BackgroundTraditional herbal medicine, sho‐saiko‐to (TJ‐9), improves subjective symptoms, and a recently developed vaccine therapy reduces the viral replication in some chronic hepatitis B virus (HBV)‐carriers. The study presented here considers the impact of a combination of vaccine therapy and TJ‐9 and the mechanism underlying the therapeutic effect of TJ‐9.Materials and methodsHBV‐transgenic mice (HBV‐Tg) expressing similar levels of HBV‐related antigens and HBV DNA were used as an animal model of HBV‐carrier state, and were assigned to receive either a TJ‐9‐enriched diet or a monthly injection of vaccine containing hepatitis B surface antigen (HBsAg), or both, for 12 consecutive months.ResultsTwelve months after starting the therapy, 9% (1 of 11), 61% (11 of 18), and 100% (10 of 10) of HBV‐Tg receiving only the TJ‐9‐treatment, only the monthly vaccine, and both the TJ‐9 and vaccine, respectively, responded to therapy and became completely negative for HBsAg. Spleen lymphocytes and antigen presenting cells (APC) from TJ‐9‐treated HBV‐Tg produced significantly higher levels of IgM, IgG and antibodies to keyhole limpet hemocyanin (KLH) and showed significantly higher stimulatory capacity in allogenic mixed leukocyte reaction (MLR) compared with the spleen cells and APC from HBV‐Tg receiving normal diet without TJ‐9 (P < 0.05).ConclusionThese data confirm the therapeutic role of TJ‐9 during HBV infection and inspire optimism of a widespread use of TJ‐9 during immune therapies.
Performance of the [13C]‐acetate gastric emptying breath test during physical exercise
Authors: Van Nieuwenhoven  , Wagenmakers  , Senden  , Brouns  , Brummer  
Published: March 2003

BackgroundThe gastric emptying rate of liquids can be determined non‐invasively using the [13C]‐acetate breath test at rest. The aims of our study were to validate this test during physical exercise against the double‐sampling method and to evaluate the time needed for intestinal absorption and the delay between absorption and appearance of 13CO2 in breath, both at rest and during exercise.DesignFifteen well‐trained male subjects were investigated. Gastric emptying was determined simultaneously measuring the 13CO2 breath enrichment after intragastric administration of 0.5 L of carbohydrate solution with 150 mg of [13C]‐acetate added and by the double‐sampling technique (n = 9). In separate tests, 150 mg of [13C]‐acetate was also applied intraduodenally and intravenously (n = 6), both at rest and during exercise. Time‐to‐peak (TTP) 13CO2 enrichment was determined using a curve fit and was considered as the parameter for gastric emptying.ResultsTTP enrichment derived from the breath test significantly correlated with the gastric emptying half‐time obtained from the gastric aspirates. During exercise, median TTP enrichment values after intragastric, intraduodenal (i.d.) and intravenous (i.v.) administration of [13C]‐acetate were 22.3, 10.3 and 5.4 min respectively. During exercise, i.d. and i.v. values were reached significantly earlier than at rest.ConclusionThe [13C]‐acetate breath test can be used as a non‐invasive method to determine relative gastric emptying rates of liquids during exercise, but the results are influenced by the rate of absorption and the time needed for subsequent oxidation of [13C]‐acetate and exhalation of 13CO2.
Hepatitis C virus core protein does not inhibit apoptosis in human hepatoma cells
Authors: Dumoulin  , Von Dem Bussche  , Söhne  , Sauerbruch  , Spengler  
Published: March 2003

BackgroundViral persistence is a major problem after infection with the hepatitis C virus. Recently, it has been reported that hepatitis C virus core protein inhibits cis‐platin induced apoptosis in human cervical carcinoma cells and apoptosis induced by overexpression of c‐myc in Chinese hamster ovary cells.Materials and methodsThis study investigated whether different variants of hepatitis C virus core or E2 protein interfere with tumour necrosis factor α or Fas (CD95/ APO‐1) antibody‐induced programmed cell death in transiently transfected human hepatoma (HepG2) cells.ResultsWhile neither full length or C‐terminally truncated variants of hepatitis C virus core protein nor hepatitis C virus E2 protein inhibited tumour necrosis factor α‐ or Fas antibody‐induced apoptosis, a strong inhibition was observed with the cowpox virus cytokine response modifier A protein.ConclusionsThus, it is unlikely that hepatitis C virus core or E2 protein inhibit apoptosis mediated by apoptosis‐signalling pathways sensitive to cytokine response modifier A protein. Discrepancies to previous reports probably reflect specific effects of hepatitis C virus core protein on different apoptotic pathways and/ or cell lines.