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Biomedical subjects

W E Schmidt

Publications and source records attributed to W E Schmidt.

At least 19 recordsLinked to original sources
PubMed2006

Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans.

AIMS/HYPOTHESIS: Diabetic dyslipidaemia contributes to the excess morbidity and mortality in patients with type 2 diabetes. Exogenous glucagon-like peptide 1 (GLP-1) lowers postprandial glycaemia predominantly by slowing gastric emptying. Therefore, the effects of GLP-1 on postprandial lipid levels and gastric emptying were assessed. METHODS: 14 healthy male volunteers were studied with an i.v. infusion of GLP-1 (1.2 pmol kg(-1) min(-1)) or placebo over 390 min in the fasting state. A solid test meal was served and gastric emptying was determined using a (13)C-labelled sodium octanoate breath test. Venous blood was drawn frequently for measurement of glucose, insulin, C-peptide, glucagon, GLP-1, triglycerides and NEFA. RESULTS: GLP-1 administration lowered fasting and postprandial glycaemia (p<0.0001). Gastric emptying was delayed by GLP-1 compared with placebo (p<0.0001). During GLP-1 administration, insulin secretory responses were higher in the fasting state but lower after meal ingestion. After meal ingestion, triglyceride plasma levels increased by 0.33+/-0.14 mmol/l in the placebo experiments (p<0.0001). In contrast, the postprandial increase in triglyceride levels was completely abolished by GLP-1 (change in triglycerides, -0.023+/-0.045 mmol/l; p<0.05). During GLP-1 infusion, plasma concentrations of NEFA were suppressed by 39% in the fasting state (p<0.01) and by 31+/-5% after meal ingestion (p<0.01). CONCLUSIONS/INTERPRETATION: GLP-1 improves postprandial lipidaemia, presumably as a result of delayed gastric emptying and insulin-mediated inhibition of lipolysis. Thus, by lowering both glucose and lipid concentrations, GLP-1 administration may reduce the cardiovascular risk in patients with type 2 diabetes.

Adult↗
PubMed2006

Vascular endothelial growth factor (VEGF164) ameliorates intestinal epithelial injury in vitro in IEC-18 and Caco-2 monolayers via induction of TGF-beta release from epithelial cells.

OBJECTIVE: VEGF is a glycoprotein with various (e.g. angiogenic) activities. So far, research has focused on its angiogenic properties. VEGF receptors are localized on epithelial cells of patients with inflammatory bowel disease (IBD) and also on Caco-2 and IEC-18 cells. Our aim was to evaluate the role of VEGF on intestinal epithelial cell (IEC) migration and proliferation by utilizing an established in vitro model. METHODS: IEC-18 and Caco-2 monolayers were wounded with a razor blade as described previously. Cells were incubated in medium w/o rat VEGF(164). After 24 h, migration was assessed by counting cells across the wound edge. Migration was blocked with neutralizing TGF-beta(1) antibodies. IEC proliferation was assessed using the MTT (3-[4, 5-Dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide) test. Semi-quantitative changes of the TGF-beta(1) mRNA expression were evaluated before and after stimulation of the cells with VEGF(164) by RT-PCR. Statistical analysis was performed with ANOVA and the Wilcoxon test. RESULTS: VEGF(164) significantly induced epithelial cell migration in Caco-2 and IEC-18 cells compared to control. TGF-beta(1) antibodies completely abolished this VEGF-induced cell migration. TGF-beta(1) mRNA significantly increased in IEC-18 and Caco-2 cells after stimulation with VEGF. VEGF significantly inhibited epithelial cell proliferation in IEC-18 and in Caco-2 cells, indicating that the observed effects on cell migration were not due to any proliferate effects. CONCLUSION: VEGF effects on epithelial cell migration play an important part in epithelial cell restitution by maintaining mucosal homeostasis after mucosal injury. This effect is mediated by TGF-beta(1). Our results obtain another possible role for increased VEGF levels in the intestinal mucosa of patients with IBD as reported recently by others.

Animals↗
PubMed2006

Mutations in the calcium-sensing receptor: a new genetic risk factor for chronic pancreatitis?

OBJECTIVE: In 2003 we identified a family with familial hypocalciuric hypercalcemia (FHH) (heterozygous CASR gene mutation L173P) and a mutation in the pancreatic secretory trypsin inhibitor gene (SPINK1) (N34S). While family members with an isolated calcium-sensing receptor gene (CASR) mutation remained healthy, a combination of the CASR and SPINK1 gene mutation caused chronic pancreatitis (CP). We thus speculate that the combination of two genetic defects affecting calcium homeostasis and pancreatic enzyme activation might represent a novel approach in chronic inherited pancreatic disease. We therefore sought to explore whether CASR gene mutations were prevalent in a cohort of patients with CP and confirmed SPINK1 mutations. MATERIAL AND METHODS: A cohort of 19 families (n=170) with a history of idiopathic CP (ICP) was screened for mutations within the CASR gene; 104 members of that cohort had a mutation (N34S) within the SPINK1 gene and 66 of those were suffering from CP. The entire CASR gene was screened for single strand conformation polymorphism under varying polyacrylamide gel conditions and subjected to direct dideoxy nucleotide sequencing of amplified cDNA. RESULTS: Single-strand conformation polymorphisms were observed in 59 samples, clustering of exons 3, 4 and 7. DNA sequence analysis revealed a yet unreported missense mutation in exon 7 (R896H) and two conservative mutations in exon 4 (F391F) and exon 7 (E790E). Furthermore, an intronic polymorphism in nucleotide position 493-19 G>A was detected in 19 out of 170 members of that cohort. CONCLUSIONS: We identified three novel calcium-sensing receptor gene mutations (1 missense mutation, 2 silent mutations and 1 intronic polymorphism) in a cohort of 19 families with ICP. In particular, the kindred with the R896H mutation presenting with a similar pedigree to the family described above may indicate a role for CASR gene mutations in SPINK1-related CP. Again, only the patient with the combination of both CASR and N34S SPINK1 gene mutation developed pancreatitis, whereas in the healthy parents and children only an isolated CASR or N34S SPINK1 gene mutation could be detected. We suggest that the CASR gene is a novel yet undetected co-factor in a multifactorial genetic setting of SPINK1-related pancreatitis that alters the susceptibility for pancreatitis in these patients.

Calcium Signaling↗
PubMed2006

Predictors of gastric emptying in Parkinson's disease.

Predictors of gastric emptying (GE) in patients with idiopathic Parkinson's disease (PD) of a solid and liquid meal are not well defined. For measurement of GE 80 patients with PD were randomly assigned to receive either a solid meal (250 kcal) containing 13C-octanoate (n = 40) or a liquid meal (315 kcal) with 13C-acetate (n = 40). All patient groups were off medication affecting motility and were matched for age, gender, body mass index, disease duration and severity, using Unified Parkinson's Disease Rating Scale (UPDRS). Gastric emptying was compared with a healthy control group (n = 40). Multiple regression analysis was used to determine predictors of gastric emptying. Exactly 88% and 38% of PD patients had delayed GE of solids and liquids respectively. Solid and liquid emptying was similar in women and men. There were no differences in GE in PD patients < 65 years of age when compared with patients > or = 65 years. Multiple regression analysis showed that motor handicaps such as rigour and action tremor are independent predictors of solid GE (r = 0.68, P < 0.001). The severity of motor impairment, but not any other neurological symptom, as assessed by UPDRS is associated with gastroparesis in PD and solid emptying is more likely to be delayed.

Acetates↗
PubMed2005

Sildenafil improves hemodynamic parameters in COPD--an investigation of six patients.

Pulmonary hypertension (PH) is an important predictor of mortality in chronic obstructive pulmonary disease (COPD). The phosphodiesterase 5 inhibitor sildenafil has been demonstrated to reduce pulmonary arterial pressure (PAP) in different diseases. We wanted to investigate the effect of sildenafil on hemodynamic parameters and the 6-min walk test (6 MWT) in six patients with severe COPD and echocardiographically estimated PH. A 6 MWT was performed and hemodynamic parameters were measured by right heart catheterization before and 1 and 12h after injection of 50mg sildenafil intravenously. A 3-months period of peroral sildenafil therapy 50mg twice daily followed and finally hemodynamic parameters and a 6 MWT were repeated. Intravenously applied sildenafil could be demonstrated to reduce PAP and pulmonary vasculature resistance (PVR) significantly. And after 3 months of oral sildenafil, the mean PAP has decreased from 30.2+/-5.5 mmHg (range: 24-39 mmHg) to 24.6+/-4.2 mmHg (range: 20-30 mmHg) (p=0.01). The PVR has decreased from 401+/-108 dyn s cm(-5) (range: 266-558 dyn s cm(-5)) to 264+/-52 dyn s cm(-5) (range: 204-333 dyn s cm(-5)) (p<0.05). Physical conditions improved: the 6-min walk distance increased from 351+/-49 to 433+/-52 m. In conclusion, in six patients suffering from severe COPD we could demonstrate significantly improved hemodynamic parameters after 50 mg sildenafil intravenous application. And after 3 months of oral sildenafil, walking distance in the 6 MWT increased significantly as well as hemodynamic parameters in the five patients who had accepted a second right heart catheterization.

Administration, Oral↗
PubMed2005

Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes.

AIMS/HYPOTHESIS: The insulinotropic effect of gastric inhibitory polypeptide (GIP) is reduced in patients with type 2 diabetes and around 50% of their first-degree relatives under hyperglycaemic conditions. It is unknown whether this is a result of a specific defect in GIP action or of a general reduction in beta cell function. Moreover, impaired secretion of glucagon-like peptide 1 (GLP-1) has been described in patients with type 2 diabetes. Therefore, we studied the insulinotropic effect of GIP in women with previous gestational diabetes (pGDM) under euglycaemic fasting conditions and during a hyperglycaemic clamp experiment. The secretion of GIP and GLP-1 was assessed following oral glucose ingestion. MATERIALS AND METHODS: On separate occasions we performed an OGTT and administered an i.v. bolus of 20 pmol GIP/kg body weight in 20 women with pGDM and 20 control women. An additional hyperglycaemic clamp experiment (140 mg/dl [7.8 mmol/l] over 120 min) with i.v. infusion of GIP (2 pmol kg(-1) min(-1); 30-90 min) was performed in 14 women in each group. Capillary and venous blood samples were drawn for the measurement of glucose (glucose oxidase), insulin, C-peptide, GIP and GLP-1 (specific immunoassays). Indices of insulin sensitivity and beta cell function were calculated. Statistical analyses were carried out using repeated measures ANOVA. RESULTS: Following oral glucose ingestion, plasma glucose, insulin and C-peptide concentrations increased to higher levels in the women with pGDM than in the control women (p<0.05). The women with pGDM were characterised by a higher degree of insulin resistance than the control women (p=0.007 for the Matsuda index), but showed no overt defects in glucose-stimulated insulin secretion (p=0.40 for the insulinogenic index following i.v. glucose). The secretion of GLP-1 and GIP was not different between the groups (p=0.87 and p=0.57, respectively). The insulin secretory response to GIP administration was similar in the two groups both after GIP bolus administration and during the hyperglycaemic clamp experiment (p=0.99 and p=0.88, respectively). A hyperbola-like relationship was found between the degree of insulin sensitivity (Matsuda index) and the insulin secretory response to GIP and i.v. glucose administration. CONCLUSIONS/INTERPRETATION: These results do not support the hypothesis of an early defect in GIP action as a risk factor for subsequent development of diabetes in women with previous gestational diabetes. The inverse relationship between insulin resistance and the insulin secretory response to glucose or GIP suggests that beta cell secretory function in response to different stimuli increases adaptively when insulin sensitivity is diminished.

Adult↗
PubMed2005

Expression of beta-defensin 1 and 2 in nasal epithelial cells and alveolar macrophages from HIV-infected patients.

BACKGROUND: The incidence of respiratory infection is high in HIV-infected patients. beta-defensins are anti-microbial peptides derived from epithelia on the mucosal surfaces of the respiratory, gastrointestinal and urinary tract. Nothing is known about the rate of expression of beta-defensin 1 and 2 mRNAs in nasal epithelial cells and alveolar macrophages in HIV-infected patients. METHODS: Semiquantitative rt-PCR measurement of beta-defensins 1 and 2 and beta-actin were carried out on nasal epithelial cells of 109 patients (76 HIV-infected) and alveolar macrophages from 56 patients (18 HIV-infected). RESULTS: The levels of beta-defensin 1 and 2 mRNAs in nasal epithelial cells did not differ significantly between HIV-infected and non-infected patients. In the nasal epithelial cells of HIV-negative patients who suffered from respiratory infections beta-defensin levels were decreased. beta-defensin 1 mRNA expression was significantly reduced in alveolar macrophages from HIV infected patients. beta-defensin 2 mRNA expression in alveolar macrophages was very low. beta-defensins 1 and 2 mRNA expression did not correlate with CD 4 cell numbers in the blood of HIV-infected patients. CONCLUSION: HIV infection and CD 4 cell numbers in the blood do not influence beta-defensin 1 and 2 expressions in nasal epithelial cells. In alveolar macrophages, beta-defensin 1 expression is decreased in HIV-infected patients.

Adult↗
PubMed2005

[In vitro effects of diclofenac and selective cyclooxygenase-2 inhibitors on prostaglandin release from inflamed bursa subacromialis tissue in patients with subacromial syndrome].

BACKGROUND: To compare the in vitro effects of selective COX-2 inhibitors (L-745,337, NS-398 and DFU) and of COX-unspecific diclofenac on release of PGE(2 )and 6-keto-PGF(1alpha) from inflamed bursa subacromialis tissue (IBST) obtained from a total of 35 patients with shoulder impingement syndrome (SIS). PATIENTS AND METHODS: Bursal specimens were incubated in the presence of drugs (0.01-1000 microM) for 20 min and 16 h. RESULTS: After 20 min 10 microM diclofenac significantly inhibited formation of PGE(2) and 6-keto-PGF(1alpha), whereas L-745,337 and NS-398 (10-1000 microM) induced significant inhibition only at concentrations > or =100 microM. In contrast to equimolar diclofenac, DFU (0.01-10 microM) induced no inhibition of bursal PGE(2) release but a dose-dependent, although statistically not significant inhibition after 16 h. The inhibitory potency of diclofenac (0.01-10 microM) was even more increased during long-term incubation showing greater inhibition than DFU at all concentrations studied. CONCLUSION: The data suggest that in IBST in SIS in vitro the majority of PG is generated via the COX-1 pathway.

Acromion↗
PubMed2005

Identification of a novel calcium-sensing receptor gene mutation causing familial hypocalciuric hypercalcemia by single-strand conformation polymorphism analysis.

Calcium-sensing receptor gene (CASR) mutations that alter the function of the G protein coupled Ca (2+)-sensing receptor are reported in patients with familial hypocalciuric hypercalcemia (FHH), autosomal dominant hypocalcemia (ADH), and neonatal severe hyperparathyroidism (NSHPT). In search for novel disease causing mutations in the CASR gene, we screened exons 2 - 7 of the CASR gene of a family with FHH using single-strand conformation polymorphism analysis. We identified a novel CASR mutation (c.518 T > C; L173 P) in exon 4 encoding for the extracellular domain of the Ca (2+)-sensing receptor. This region seems to represent a hot spot within the CASR gene with at least 13 reported disease causing mutations thus far.

Adult↗
PubMed2004

Glucagon-like peptide 2 improves intestinal wound healing through induction of epithelial cell migration in vitro-evidence for a TGF--beta-mediated effect.

BACKGROUND/AIMS: In vitro studies suggest that glucagon-like peptide 2 (GLP-2), secreted from enteroendocrine cells in the gastrointestinal tract after food intake, is able to ameliorate mucosal injury in settings of human disease characterized by injury and dysfunction of the intestinal mucosal epithelium. We evaluated this potential of GLP-2 after epithelial trauma by using two in vitro models measuring intestinal epithelial cell proliferation and cell migration. MATERIALS AND METHODS: Injuries were induced in confluent monolayers of the small intestinal cells lines IEC-6 and IEC-18, as well as in the colonic cell lines Caco-2 and Colo 320. GLP-2 (50-500 nM) or other peptides were added to the media. Wound healing was investigated after 24 h by quantification of the number of cells migrating across the wound edge. Proliferation of cells was assessed by using photometric mitochondrial incorporation measurement of MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide). Monoclonal TGF-beta antibodies were added to wounded monolayers to examine whether the GLP-2-induced wound healing was TGF-beta-mediated. RESULTS: Migration assessments revealed a significant stimulation of GLP-2-induced migration in IEC-6 and IEC-18 monolayers compared to the placebo group. No effect was observed in the colon cancer cell lines Caco-2 and Colo 320. Results of the proliferation assays show a significant inhibition of proliferation by GLP-2 in small intestinal cell lines whereas a dose-dependent stimulation of proliferation in colonic epithelial cells was observed. Addition of neutralizing TGF-beta1 antibodies to wounded IEC-6 and IEC-18 monolayers incubated with GLP-2 significantly reduced the number of migrating cells to the level of the placebo group. CONCLUSIONS: In our in vitro model, it was shown that the GLP-2-induced improvement of intestinal wound healing is TGF-beta-mediated. These effects were predominant in the epithelium of the small intestine compared to colonic epithelium. Our findings provide further insight into mechanisms leading to GLP-2-induced mucosal wound healing. These results suggest that GLP-2 or analogues of this peptide may potentially be useful for the treatment of intestinal disorders characterized by injury and ineffective repair of the intestinal mucosa.

Animals↗
PubMed2004

Acquired pure megakaryocytic aplasia: a separate haematological disease entity or a syndrome with multiple causes?

We report the case of a patient with acquired pure megakaryocytic aplasia. Until today, less than 20 cases of acquired pure megakaryocytic aplasia have been reported and the disease aetiology still seems to be unclear. This report summarizes the published data concerning possible aetiologies, treatment options and outcome of patients with acquired pure megakaryocytic aplasia. Furthermore, this case report presents an example for a possible disease progression.

Adult↗
PubMed2004

Is impairment of ischaemic preconditioning by sulfonylurea drugs clinically important?

In the UGDP study, published in the 1970s, a high incidence of cardiovascular mortality was found in patients treated with the sulfonylurea agent tolbutamide. Impaired ischaemic preconditioning is presumed to be the most important mechanism for the excess cardiovascular mortality observed. However, as tolbutamide has only a low affinity for cardiac sulfonylurea receptors, interference with ischaemic preconditioning seems unlikely to account for this excess mortality. Several smaller studies also failed to establish a definite link between sulfonylurea treatment before acute myocardial infarction and in-hospital mortality. However, when the myocardium becomes exposed to repeated or prolonged periods of ischaemia, ischaemic preconditioning may become clinically important. Myocardial ischaemia can also develop during emergency or elective angioplasty and during coronary bypass surgery. Therefore discontinuation of sulfonylurea treatment should be considered in these circumstances.

Animals↗
PubMed2003

Inhibition of adenovirus infection by the bronchoalveolar lavage supernatant in vitro.

BACKGROUND: Gene transfer using the adenovirus has been discouraging, since the level of recombinant gene expression was always low. Non-specific and specific immune responses prevent infection or kill infected cells. Most of the specific immune responses against the adenovirus are well known and can be eluded at least in animal models. The non-specific immune response is not so well investigated. We have previously demonstrated a strong anti-adenoviral effect of bronchoalveolar lavage (BAL) supernatants of different patients independent of their content of specific anti-adenoviral immunoglobulins of the subclasses IgA, IgG, and IgM. In this paper we examine the influence of defensins and immunoglobulins within the epithelial lining fluid of the lung on the infection of adenovirus type 5. METHODS: Pooled BAL supernatants were separated by gelchromatography; IgA and IgG, respectively were removed from the BAL supernatants by anti-IgA- and anti-IgG affinity chromatography. RESULTS: The anti-adenoviral capacity could be assigned to the high molecular weight portion including the immunoglobulin- and at a much lower degree the albumin-fractions. All fractions from affinity chromatography; the IgA fraction, the resulting BAL depleted from IgA, the IgG fraction, and the resulting BAL depleted from IgG were highly inhibitory on adenoviral infectivity. CONCLUSION: The main anti-adenoviral component in BAL is part of a high molecular weight complex, either being a large protein itself, or being a small peptide bound unspecifically to different bigger proteins. Defensins are not important factors of anti-adenoviral infectivity in the epithelial linig fluid of our patients.

Adenoviridae↗
PubMed2003

Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia.

AIMS/HYPOTHESIS: In the isolated perfused pancreas, gastric inhibitory polypeptide (GIP) has been shown to enhance glucagon secretion at basal glucose concentrations, but in healthy humans no glucagonotropic effect of GIP has yet been reported. Therefore, we studied the effect of GIP on glucagon secretion under normoglycaemic conditions. METHODS: Ten healthy subjects (9 men, 1 woman; age 33+/-11; BMI 26.8+/-2.2 kg/m(2)) received three different doses of intravenous GIP (7, 20, and 60 pmol/kg body weight) and placebo. Venous blood samples were drawn over 30 min for glucagon and GIP concentrations (specific radioimmunoassays). In addition, 31 healthy subjects (16 men, 15 women; 42+/-11 years; BMI 24.4+/-2.7 kg/m(2)) were studied with 20 pmol GIP/kg. Statistics were done with RM-ANOVA and Duncan's post hoc tests. RESULTS: Gastric inhibitory polypeptide dose-dependently stimulated glucagon secretion ( p=0.019) with a maximal increment after 10 min. Incremental glucagon concentrations (Delta(10-0 min)) were 0.1+/-0.7, 1.4+/-0.5, 2.4+/-0.5, and 3.4+/-0.8 pmol/l (for placebo and for 7, 20, and 60 pmol GIP/kg, respectively; p=0.017). After the injection of 20 pmol GIP/kg b.w. in 31 healthy subjects, glucagon concentrations increased over the baseline from 7.5+/-0.5 to 9.3+/-0.7 pmol/l ( p=0.0082). CONCLUSIONS/INTERPRETATION: Glucagon secretion is dose-dependently stimulated by GIP at basal glucose concentrations. The absence of a glucagonotropic GIP effect in previous studies could be due to the hyperglycaemic conditions used in these experiments. Our results underline differences between GIP and the glucagonostatic incretin GLP-1.

Blood Glucose↗
PubMed2003

[Appetite regulation by ghrelin - a novel neuro-endocrine gastric peptide hormone in the gut-brain-axis].

Ghrelin a novel peptide consisting of 28 amino acids was first identified in the stomach in 1999. It is mainly produced in endocrine cells of the human gastric mucosa, but it was also found in several other tissues e. g. in the pituitary, the hypothalamus and the pancreas. The functional receptor belongs to the family of the 7-transmembrane G-protein receptors and is predominantly detected in the pituitary and at lower levels in hypothalamic nuclei, the stomach, heart, lungs, kidneys, gut, the adipose and many other tissues. According to the widespread distribution of the peptide and its receptor, ghrelin has multiple biological effects: it stimulates the release of growth hormone in the pituitary and induces a rise in the serum concentration of ACTH, cortisol, catecholamines and prolactin. Ghrelin causes an increase of food intake and body weight by stimulating the production of neuropeptide Y (NPY) and agouti-related protein (AGP) in the nucleus arcuatus. It further leads to elevated concentrations of plasma glucose. A physiological antagonism between ghrelin and GLP-1 in the hypothalamic regulation of appetite is being discussed. The basic serum level of ghrelin depends on the state of nutrition and is negatively correlated with the body-mass-index. It shows a certain pattern of variation before and after food intake with a preprandial increase and a postprandial decrease. Ghrelin modulates gastric acid secretion and the gastrointestinal motility via vagal cholinergic pathways. The discovery of ghrelin definitely contributes to the understanding of the growth-hormone secretion and of the regulation of appetite and food intake.

Adrenocorticotropic Hormone↗
PubMed2002

The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cells.

BACKGROUND: Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti-inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase-2 (COX-2) negative colorectal cancer cell lines. MATERIALS AND METHODS: After treatment with various concentrations of ASA, cell proliferation was measured in the human colon cancer cell line SW480. Apoptotic cells were identified by transmission electron microscopy, acridine orange staining, and flow cytometry. The invasive potential of SW480 cells was detected using an in vitro invasion assay. The production of carcinoembryonic antigen was measured by microparticle enzyme immunoassay. Expression of Bcl2, Bax, CD44v6, and nm23 were evaluated by immunocytochemistry. RESULTS: ASA significantly inhibited the proliferation of SW480 cells and stimulated apoptosis. Production of carcinoembryonic antigen and the invasive potential of SW480 cells were also inhibited by ASA. After treatment with ASA, down-regulation of Bcl2 and CD44v6 expression and up-regulation of nm23 expression were observed in SW480 cells. No obvious effect of ASA was found on Bax expression. CONCLUSION: Our findings reveal that ASA inhibits the proliferation and promotes apoptosis in the human colon cancer cell line SW480. Down-regulation of Bcl2 expression might represent a potential mechanism by which ASA induces apoptosis in this COX-2 negative colon cancer cell line. Our results also suggest that ASA decreases the invasive potential of these colon cancer cells. Decreased CEA content and CD44v6 expression and elevated nm23 expression may contribute to the effect of ASA on invasive potential of SW480 colon cancer cells.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Prevalence and risk factors of hepatitis C virus infection in haemodialysis patients: a multicentre study in 2796 patients.

BACKGROUND: Hepatitis C virus (HCV) infection is a significant problem in the management of haemodialysis patients. A high prevalence of HCV infection in haemodialysis patients has been reported. Risk factors such as the number of blood transfusions or duration on haemodialysis have been identified. AIM: To determine the prevalence of HCV by antibody testing and HCV-RNA determination by polymerase chain reaction (PCR) in haemodialysis patients. Furthermore, liver function tests were performed and epidemiological data were obtained to determine risk factors for HCV in this cohort of patients. RESULTS: A total of 2796 patients from 43 dialysis centres were enrolled. The overall prevalence of HCV (HCV antibody and/or HCV-RNA positivity) was 7.0% (195 patients). Antibody positivity occurred in 171 patients (6.1%). Viraemia was detectable in 111 patients (4.0%). Twenty four of 111 HCV RNA positive patients (21.6%) were negative for HCV antibodies. Thus 0.8% of the entire study population was HCV positive but could not be diagnosed by routine HCV antibody testing. Major risk factors identified by a standard questionnaire in 1717 of 2796 patients were the number of blood transfusions individuals had received and duration of dialysis, the latter including patients who received no blood transfusions. Sequencing of the 5'untranslated region of the genome showed a dominant genotype 1 (77.6%) within the cohort. Further reverse transcription-PCR of the NS5b and core region were performed to document phylogenetic analysis. Comparing nucleic acid sequences detected by PCR, no homogeneity was found and thus nosocomial transmission was excluded. CONCLUSIONS: HCV is common in German haemodialysis patients but screening for HCV antibodies alone does not exclude infection with HCV.

Adult↗