Biomedical subjects

Guido Adler

Publications and source records attributed to Guido Adler.

66 records · Page 4Linked to original sources

PubMed2002

Lactose intolerance in active Crohn's disease: clinical value of duodenal lactase analysis.

BACKGROUND: Patients with active Crohn's disease (CD) often report having abdominal symptoms after ingestion of milk products, but the pathomechanism for lactose malabsorption seems to be complex. GOALS: To investigate the prevalence of clinical milk intolerance and to objectify symptoms with hydrogen (H 2 ) breath testing, analysis of lactase protein, and enzyme activity in the duodenal mucosa in patients with CD and in healthy controls. STUDY: In 49 patients with CD and 24 controls, H 2 breath testing was performed. All individuals underwent endoscopy of the upper gastrointestinal tract, in which multiple pinch samples were taken from the distal duodenum. Lactase activity was measured using the method of Dahlquist. The lactase protein expression was analyzed by gel electrophoresis using the monoclonal antibody mlac 10 and by immunochemistry using the monoclonal antibody mlac 4. RESULTS: Prevalence of milk intolerance in healthy controls was 16.6% versus 46.9% in patients with CD, with a high frequency (83.3%) in patients with active disease (CD activity index >150). Milk intolerance was correlated to the duration of inflammatory bowel disease ( p = 0.023) but not to the location or previous bowel resection. Hydrogen breath testing had a moderate sensitivity in detecting lactose maldigestion (70.4%) and a high specificity (95.6%). Duodenal lactase levels were also correlated to disease activity, whereas correlations to clinical symptoms remained poor. Patients with milk intolerance had a significantly reduced bone density at the lumbar spine (z-score, -1.33 +/- 0.92 vs. -0.19 +/- 0.95 [mean +/- SD]; p = 0.002) CONCLUSIONS: Milk intolerance is a frequent problem in active CD, which can be objectified accurately by H 2 lactose breath testing. Decreased lactase levels in the duodenal mucosa may be found during an acute flare but are not the predominant cause of milk intolerance in CD.

Adult↗

PubMed2002

Role of infected parents in transmission of helicobacter pylori to their children.

AIM: Infected parents, especially infected mothers, may play a key role in transmission of Helicobacter pylori within the family. The aim of this population-based study was to determine the role of parental infection status in transmission of H. pylori to the child by taking into consideration the infection status of both parents simultaneously. METHODS: Study subjects were a sample of preschool children in the city of Ulm, located in Southern Germany, who were screened for school fitness between January and July, 1998. The infection status of the children was determined by the 13C-urea breath test (UBT). Parental infection status was determined by measurement of specific H. pylori IgG antibodies in saliva using a modified immunoassay (Milenia H. pylori IgG; DPC, Biermann, Germany). The parents provided additional information through a standardized questionnaire. RESULTS: We included 305 children ages 5 to 7 years (mean age, 5.8 years) and their parents in the analysis. Prevalence of H. pylori infection in children by means of UBT was 10.2% [95% confidence interval (CI) 7.0-14.1%]. The prevalence of infection was 5.1% if the mother showed no salivary antibody response against H. pylori and 17.3% if she did. Prevalence of infection in children was 6.8% if the father showed no salivary antibody response and 19.1% if he did. After adjustment for potential confounders (including infection of the spouse), the odds ratio for H. pylori infection of the child was 3.9 (95% CI 1.4 to 10.6) when the mother was saliva-positive and 2.0 (95% CI 0.8 to 5.3) when the father was saliva-positive. CONCLUSION: This study strengthens previous evidence that in the population studied infected parents, in particular mothers may play a key role in transmission of H. pylori to the child.

Adult↗

PubMed2002

Validation of the EuroQol questionnaire in patients with inflammatory bowel disease.

OBJECTIVE: The EuroQol EQ-5D is a generic questionnaire for describing and valuing patients' health-related quality of life. The purpose of the study was to analyse the construct validity, criterion validity, test-retest reliability and responsiveness of the EQ-5D in patients with inflammatory bowel disease. METHODS: 152 consecutive patients with inflammatory bowel disease (123 with Crohn's disease and 29 with ulcerative colitis) completed the EQ-5D, the SF-36 and the Inflammatory Bowel Disease Questionnaire (IBDQ). Of the study group, 66 patients filled in the EQ-5D a second time after a 2-week gap, including a transition question. Disease activity was measured by the Crohn's Disease Activity Index (CDAI) and by Rachmilewitz's Clinical Activity Index (CAI). RESULTS: The EQ-5D showed a moderate ceiling effect. Correlation between the EQ-5D visual analogue scale (EQ VAS) score and CDAI/CAI was r = -0.65/r = -0.71 (both P < 0.001). Levels of responses to EQ-5D items and the EQ VAS score were significantly better for patients in remission than for patients with active disease (all P < 0.01). For the total sample, coefficients of correlation between the EQ VAS score and SF-36 and IBDQ scores ranged between 0.37 and 0.73 (all P < 0.0001). When repeated, the EQ-5D was reliable in stable patients (intraclass correlation coefficient for EQ VAS = 0.77, kappa statistic for items 0.39 to 1.00); the EQ VAS was responsive in patients who, in the transition question, indicated an improvement in health state (effect size 0.79). CONCLUSIONS: The EQ-5D is reasonably valid, reliable and responsive in patients with inflammatory bowel disease. It can be used to generate preference-based valuations of health-related quality of life in inflammatory bowel disease.

Adolescent↗

PubMed2002

Caspase 8-mediated cleavage of plectin precedes F-actin breakdown in acinar cells during pancreatitis.

Pancreatic acinar cells depend on the integrity of the cytoskeleton for regulated secretion. Stimulation of isolated rat pancreatic acini with the secretagogue CCK serves as a model for human acute edematous pancreatitis. It induces the breakdown of the actin filament system (F-actin) with the consecutive inhibition of secretion and premature activation of digestive enzymes. However, the mechanisms that regulate F-actin breakdown are largely unknown. Plectin is a versatile cytolinker protein regulating F-actin dynamics in fibroblasts. It was recently demonstrated that plectin is a substrate of caspase 8. In pancreatic acinar cells, plectin strongly colocalizes with apical and basolateral F-actin. Supramaximal secretory stimulation of acini with CCK leads to a rapid redistribution and activation of caspase 8, followed by degradation of plectin that in turn precedes the F-actin breakdown. Inhibition of caspase 8 before CCK hyperstimulation prevents plectin cleavage, stabilizes F-actin morphology, and reverses the inhibition of secretion. Thus we propose that the caspase 8-mediated degradation of plectin represents a critical biochemical event during CCK-induced secretory blockade and cell injury.

Actins↗

PubMed2002

Different modes of NF-kappaB/Rel activation in pancreatic lobules.

The eukaryotic transcription factor nuclear factor-kappaB (NF-kappaB)/Rel is activated by a large variety of stimuli. It has been demonstrated that NF-kappaB/Rel is induced during the course of cerulein pancreatitis. Here, we show that NF-kappaB/Rel is differentially activated in pancreatic lobules. Cerulein induces NF-kappaB/Rel via activation of IkappaB kinase (IKK), which causes degradation of IkappaBalpha but not IkappaBbeta. Tumor necrosis factor-alpha-mediated IKK activation leads to IkappaBalpha and IkappaBbeta degradation. In contrast, oxidative stress induced by H(2)O(2) activates NF-kappaB/Rel independent of IKK activation and IkappaBalpha degradation; instead IkappaBalpha is phosphorylated on tyrosine. H(2)O(2) but not cerulein-mediated NF-kappaB/Rel activation can be blocked by stabilizing microtubules with Taxol. Inhibition of tubulin polymerization with nocodazole causes NF-kappaB/Rel activation in pancreatic lobules. These results propose three different pathways of NF-kappaB/Rel activation in pancreatic acinar cells. Furthermore, these data demonstrate that microtubules play a key role in IKK-independent NF-kappaB/Rel activation following oxidative stress.

Animals↗

PubMed2002

Acute experimental pancreatitis and NF-kappaB/Rel activation.

Acute pancreatitis is a serious disease with a high morbidity and an overall mortality rate of about 10%. However, in its most severe form, which is characterized by pancreatic necrosis, 20-30% of the patients die. Death is often the result of multiorgan dysfunction, including acute respiratory, kidney, and hepatic failure as well as generalized diffuse capillary leak water retention, hypoxia, and acid/base disturbance. The mechanisms by which distant organ systems are involved still remain obscure, but several lines of evidence suggest the participation of cytokines (IL-1, IL-6, and TNF-alpha) as a response to local tissue damage. A series of studies have now shed new light on the pivotal pathogenic role of the transcription factor NF-kappaB/Rel that binds to the promoter regions of many proinflammatory genes and regulates their transcription.

Acute Disease↗

PubMed2002

Induction of IkappaB-kinase by cholecystokinin is mediated by trypsinogen activation in rat pancreatic lobules.

BACKGROUND AND AIMS: Supramaximal concentrations of cholecystokinin (CCK) or cerulein induce the intracellular activation of trypsinogen and the transcription factor NF-kappaB, a key regulator of inflammatory gene expression. Both events occur early in the development of an acute pancreatitis. The aim of this study was to examine the relationship between intracellular trypsinogen and NF-kappaB activation. METHODS: We detected NF-kappaB-binding activity in electromobility shift assays, IkappaB proteolysis in Western analysis and endogenous IkappaB-kinase (IKKalpha and beta) activation using immune complex kinase assays following treatment with CCK in rat pancreatic lobules. To block intrapancreatic trypsinogen activation, a potent and cell-permeable serine-protease inhibitor, Pefabloc, was used. RESULTS: CCK-induced IkappaBalpha degradation and subsequent NF-kappaB activation correlated closely with the catalytic activity of IKKs to phosphorylate IkappaBalpha in vitro. Activation is dose-dependent and peaked at 30 min. Doses of Pefabloc sufficient to inhibit trypsin activation reduced CCK-induced activation of NF-kappaB whereas TNF-alpha-induced NF-kappaB activation was not blocked but slightly increased. Moreover, treatment with Pefabloc as well as another serine protease inhibitor, FUT175, inhibited CCK-induced IKK activation. CONCLUSION: These results suggest that intrapancreatic activation of trypsinogen may contribute to NF-kappaB signaling via IKK activation in cerulein pancreatitis. This also explains the fact that only doses of CCK which activate trypsinogen induce NF-kappaB activation in pancreatic acinar cells. Thus, trypsinogen activation is likely to modulate signaling events in acinar cells in the initial phase of acute pancreatitis.

Animals↗

PubMed2002

TGFbeta-induced fibrogenesis of the pancreas.

The biological cause of fibrosis is the accumulation of excessive amounts of extracellular matrix (ECM) which leads to tissue dysfunction and organ failure. A strong correlation can be found between pancreatic diseases and fibrotic processes, in particular chronic pancreatitis and pancreatic cancer. There is growing evidence that pancreatic fibrosis represents a dysregulation of the normal repair processes after injury. This concept is based on the findings that fibrosis and tissue repair involve similar biological reactions regulated by the same group of molecules. The best characterized example for these regulatory molecules are the members of the transforming growth factor beta family (TGFbeta). TGFbeta1 represents the prototype of this family of highly similar growth factors, with the unique ability to stimulate the expression and deposition of extracellular matrix and to inhibit its degradation. Growth factor-induced fibrotic events are targeted by a myofibroblast-like cell called pancreatic stellate cell (PSC). These cells show enhanced expression of all-important ECM proteins after TGFbeta stimulation including collagen, fibronectin and proteoglycans. At the same time TGFbeta inhibits the degradation of ECM by blocking the secretion of proteases and stimulating the production of naturally occurring protease inhibitors.

Collagen↗

PubMed2002

NF-kappaB/Rel transcriptional pathway: implications in pancreatic cancer.

Despite considerable efforts in understanding the cellular mechanisms contributing to pancreatic cancer, the prognosis of this malignant disease is still extremely poor. Although pancreatic cancer is the fifth common cause of cancer death in Western countries, current options in treatment enable a 5-yr survival rate for all stages of less than 5%. In the face fo the fatal outcome, new approaches to the therapy have been established. Based on its role in malignant transformation, apoptosis, and cell proliferation, the transcription factor NF-kappaB/Rel has gained the attention of many laboratories. This review provides basic information for the understanding of the biology of NF-kappaB and aims at presenting experimental data illustrating the involvement of NF-kappaB/Rel in pancreatic cancer.

Apoptosis↗

PubMed2002

Contrast-enhanced power Doppler sonography of the intestinal wall in the differentiation of hypervascularized and hypovascularized intestinal obstructions in patients with Crohn's disease.

OBJECTIVE: To use power Doppler sonography to quantify the vascularization in the area of stenosed bowel segments in patients with Crohn's disease and to draw conclusions from these findings with regard to the development of these stenoses. METHODS: The study collective included 11 patients with confirmed Crohn's disease and sonographically visualized stenoses of the small bowel together with intermittent abdominal cramping as a clinical correlate. Power mode examination was repeated after application of a sonographic signal-enhancing agent. Semiquantitative evaluation based on the sonographically indicated degree of vascularization led to the presumptive diagnosis of either inflammatory or cicatricial intestinal obstruction. Sonographic diagnoses were compared with the findings of surgery and subsequent histologic examination or with patients' clinical responses to conservative therapy. RESULTS: Nine of 11 patients underwent surgery within 1 year of examination. All 3 cases in which sonography had facilitated the diagnosis of cicatricial stenosis were confirmed at postoperative histologic examination; similarly, the surgical and histologic findings in the other 6 patients confirmed the sonographic diagnosis of inflammatory stenosis. CONCLUSIONS: Power Doppler sonography in combination with the use of a signal-enhancing agent appears to be effective in the recognition of predominantly cicatricial stenoses in patients with Crohn's disease.

Adult↗

PubMed2002

Role of neurotrophins in inflammation of the gut.

Until now neurotrophins like nerve growth factor (NGF), brain-derived neurotrophic factor (BDNA), neurotrophin (NT)-3 and neurotrophic factors like glial-derived neurotrophic factor (GDNF) have been almost exclusively investigated concerning their role in differentiation, growth and survival of specific neurons in the peripheral and central nervous system. However, in the last decade several non-neuronal functions of neurotrophins and neurotrophic factors have been characterized. In the gastrointestinal tract, neurotrophins and neurotrophic factors regulate neuropeptide expression, interact with immunoregulatory cells and epithelial cells and regulate motility during inflammation. This highlights this new and complex regulatory system as important and may lead to new options in the treatment of acute and chronic inflammation of the gut.

Animals↗

PubMedDate not supplied

Treatment of chronic hepatitis B with high-dose intravenous N-acetyl-L-cysteine.

BACKGROUND/AIMS: Therapy of hepatitis B with alpha-interferon is only successful in 30-40%; therefore new therapeutic options are needed. N-acetyl-L-cysteine is well known as an antidote against paracetamol intoxication and as mucolytic agent in pulmonary diseases. Furthermore, it restrains human immunodeficiency virus replication and inhibits hepatitis B virus replication at a posttranscriptional level in vitro. This study aims to evaluate the efficacy of N-acetyl-L-cysteine in 5 patients chronically infected with hepatitis B virus. METHODOLOGY: N-acetyl-L-cysteine was given intravenously at a daily dose of 150 mg/kg body weight. Treatment was performed for 28 days. RESULTS: The N-acetyl-L-cysteine infusions were tolerated without any side effects. Except a mild increase in thrombocyte-counts within the last week of N-acetyl-L-cysteine infusion blood tests did not change. We could not detect any changes in quantitative hepatitis B virus-DNA levels as well as in the HBeAg-status. CONCLUSIONS: We conclude from our data that N-acetyl-L-cysteine given in a high dose intravenously for 28 days is well tolerated. In contrast to in vitro studies no significant effects on the hepatitis B-virus load were detectable in vivo.

Acetylcysteine↗