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Biomedical subjects

Thorsten Pohle

Publications and source records attributed to Thorsten Pohle.

12 recordsLinked to original sources
PubMed2006

Beyond gastric acid reduction: proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells.

Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2006

Endoluminal gastroplasty (EndoCinch) versus endoscopic polymer implantation (Enteryx) for treatment of gastroesophageal reflux disease: 6-month results of a prospective, randomized trial.

OBJECTIVES: The aim of this study was to compare and determine the efficiency and safety of two newly introduced endoscopic antireflux procedures in the treatment of gastroesophageal reflux disease (GERD). METHODS: In a prospective, randomized trial, endoluminal gastroplasty (EndoCinch) was compared with polymer injection (Enteryx) employing 51 consecutive patients dependent on proton pump inhibitor therapy. Follow-up evaluation included drug consumption, symptoms, quality-of-life scoring, endoscopy, pH monitoring, manometry, and documentation of adverse events. RESULTS: Twenty-six patients were assigned to EndoCinch treatment, 23 patients received Enteryx implantation, and two patients dropped out before applying endoscopic therapy. At 6 months, proton pump inhibitor therapy could be stopped or dosage was reduced by > or =50% in 20 of 26 (77%) EndoCinch-treated patients and in 20 of 23 patients treated by Enteryx (87%, p= 0.365), which differed significantly in both groups compared to the pre-interventional status (p < 0.0001). Esophageal acid reflux (pH < 4) decreased from 14.5% to 9.6% in EndoCinch-treated patients (p= 0.071) and from 15.5% to 13.9% in patients treated by Enteryx (p= 0.930). Heartburn symptom score, modified DeMeester score, gastrointestinal life quality index, and SF-36 physical health survey score improved significantly in both groups postinterventionally (p < 0.0001). Approximately 25% of the patients in both groups required retreatment in an attempt to achieve symptom control. CONCLUSIONS: This is the first prospective, randomized study directly comparing two endoscopic anti-GERD techniques. EndoCinch and Enteryx seem to be equally successful in the treatment of GERD significantly reducing the proton pump inhibitor dosages, and also by improving symptoms of patients. Both endoluminal antireflux procedures may be promising therapeutic options; long-term evaluation will have to show if the positive initial results can be maintained.

Adult↗
PubMed2005

Identification of metastasis-associated receptor tyrosine kinases in non-small cell lung cancer.

Development of distant metastasis after tumor resection is the leading cause of death in early-stage non-small cell lung cancer (NSCLC). Receptor tyrosine kinases (RTK) are involved in tumorigenesis but only few RTKs have been systematically studied in NSCLC. Here, we provide quantitative real-time reverse transcription-PCR expression data of all RTKs (n=56) in primary tumors of 70 patients with early-stage (I-IIIA) NSCLC. Overall, 33 RTKs were expressed in at least 25% of the patients. Several RTKs were significantly expressed higher in tumors that ultimately metastasized. The hazard risk for metastasis development in stage I/II disease was increased at least 3-fold for tumors with high expression levels of insulin receptor, neurotrophic tyrosine receptor kinase 1, epidermal growth factor receptor, ERBB2, ERBB3, platelet-derived growth factor receptor beta, fibroblast growth factor receptor 1, or leukocyte tyrosine kinase. Relative risks were reduced 3-fold by expression of EPHB6 or DKFZ1. Three members of the epidermal growth factor receptor family were associated with a high risk of metastasis, emphasizing the validity of our data. High ERBB3 expression was significantly associated with decreased survival. Taken together, our genome-wide RTK expression map uncovered the previously unknown value of several RTKs as potential markers for prognosis and metastasis prediction in early-stage NSCLC. The identified RTKs represent promising novel candidates for further functional analyses.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Fibrin glue, healing of gastric mucosal injury, and expression of growth factors: results from a human in vivo study.

BACKGROUND: Fibrin glue is used in the endoscopic therapy of bleeding ulcerations. Accelerated closure of ulcers has been attributed to this treatment; the biologic reason, however, remains unclear. METHODS: Two artificial gastric lesions were induced in healthy, Helicobacter pylori negative volunteers and were treated by injection of either saline solution or fibrin glue. After 72 hours, resulting ulcers were measured and biopsy specimens were taken for immunohistochemistry (to identify proliferating cells and small vessels) and assessment of growth factor messenger RNA (mRNA) expression (platelet derived growth factor, vascular endothelial growth factor, fibroblast growth factor 2 [FGF-2]) by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: After 72 hours, most lesions exposed to fibrin glue were smaller than the corresponding ones treated with saline solution. The ulcer rim was more pronounced; immunohistochemistry revealed more proliferating cells (p < 0.02 compared with saline solution). The number of microvessels also increased, though this difference did not reach statistical significance (p = 0.10). FGF-2 mRNA expression markedly increased (about 7-fold compared with the control [ p < 0.001], and about 5-fold compared with saline solution [ p < 0.015]); whereas, with respect to platelet derived growth factor and vascular endothelial growth factor mRNAs, only small changes occurred. CONCLUSIONS: Fibrin glue positively modulates gastric ulcer healing by causing an increase in the number of proliferating cells in the ulcer margin and also possibly enhances the density of microvessels. These changes are accompanied by an enhanced expression of FGF-2, which is known to exert beneficial effects on ulcer healing.

Adolescent↗
PubMed2005

"Pancreatic lesion" outside the pancreas: value of endoscopic ultrasound.

Tumors of the small intestine are rare as compared to malignant tumors of the pancreas. Here we report on the case of a 61-year-old man suffering from chronic pancreatitis presenting with a lesion projecting into the pancreatic head shown by both computed tomography and transabdominal ultrasound. Pancreatic cancer was suspected, but endoscopic ultrasound revealed this lesion to be situated in the submucosal layer of the duodenal wall. Surgery was performed since biopsy of this lesion was not diagnostic and a malignant leiomyosarcoma could therefore not be excluded. Limited surgery comprised resection of the duodenal lesion, whereas based on computed tomography alone, exploration of the pancreas would have been performed. Thus, in the present case endoscopic ultrasound leads to a more appropriate, less invasive therapeutic measure.

Diagnosis, Differential↗
PubMed2004

Current approaches to prevent NSAID-induced gastropathy--COX selectivity and beyond.

Gastrointestinal (GI) toxicity associated with nonsteroidal anti-inflammatory drugs (NSAIDs) is still an important medical and socio-economic problem--despite recent pharmaceutical advances. To prevent NSAID-induced gastropathy, three strategies are followed in clinical routine: (i) coprescription of a gastroprotective drug, (ii) use of selective COX-2 inhibitors, and (iii) eradication of Helicobacter pylori. Proton pump inhibitors are the comedication of choice as they effectively reduce gastrointestinal adverse events of NSAIDs and are safe even in long-term use. Co-medication with vitamin C has only been little studied in the prevention of NSAID-induced gastropathy. Apart from scavenging free radicals it is able to induce haeme-oxgenase 1 in gastric cells, a protective enzyme with antioxidant and vasodilative properties. Final results of the celecoxib outcome study (CLASS study) attenuated the initial enthusiasm about the GI safety of selective COX-2 inhibitors, especially in patients concomitantly taking aspirin for cardiovascular prophylaxis. Helicobacter pylori increases the risk for ulcers particularly in NSAID-naive patients and therefore eradication is recommended prior to long-term NSAID therapy at least in patients at high risk. New classes of COX-inhibitors are currently evaluated in clinical studies with very promising results: NSAIDs combined with a nitric oxide releasing moiety (NO-NSAID) and dual inhibitors of COX and 5-LOX. These drugs offer extended anti-inflammatory potency while sparing gastric mucosa.

Antacids↗
PubMed2003

Gastroprotection by vitamin C--a heme oxygenase-1-dependent mechanism?

Free oxygen radicals contribute to gastric mucosal damage induced by acetylic-salicylic acid (ASA). Vitamin C has been shown to reduce gastric toxicity of ASA in humans. We intended to assess the role of heme oxygenase-1 (HO-1) in this process by application of these substances to AGS and KATO III cells. HO-1 expression was monitored by real-time RT-PCR, Western blot, and HO activity measurement. HO-1 mRNA was significantly elevated by either ASA or vitamin C in gastric epithelial cells, combination of both substances further increased expression. HO-1 protein and enzyme activity rose in cells exposed to vitamin C alone or combined with ASA, but not after stimulation with ASA alone. In contrast to endothelia, in which ASA simultaneously induces HO-1 mRNA and protein expression, gastric epithelial cells require vitamin C to translate HO-1 mRNA into active protein, which then may exert gastroprotection by its antioxidant and vasodilative properties.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Heme oxygenase-1 induction may explain the antioxidant profile of aspirin.

Aspirin is known to exert antioxidant effects by as yet unidentified mechanisms. In cultured endothelial cells derived from human umbilical vein, aspirin (30-300 microM) increased heme oxygenase-1 (HO-1) protein levels in a concentration-dependent fashion up to fivefold over basal levels. HO-1 induction was accompanied by a marked increase in catalytic activity of the enzyme as reflected by enhanced formation of both carbon monoxide and bilirubin. Pretreatment with aspirin or bilirubin at low micromolar concentrations protected endothelial cells from hydrogen peroxide-mediated toxicity. HO-1 induction and endothelial protection by aspirin were not mimicked by indomethacin, another inhibitor of cyclooxygenase. The nitric oxide (NO) synthase blocker L-NAME prevented aspirin-dependent HO-1 induction. These findings demonstrate that aspirin targets HO-1, presumably via NO-dependent pathways. Induction of HO-1 expression and activity may be a novel mechanism by which aspirin prevents cellular injury under inflammatory conditions and in cardiovascular disease.

Antioxidants↗
PubMed2003

Gastric function measurements in drug development.

The function of the stomach includes initiation of digestion by exocrine secretions such as acid and pepsin, which are under the control of the endocrine secretion of hormones that also coordinate intestinal motility. The stomach also stores and mechanically disrupts ingested food. Various techniques have been developed to assess gastric physiology, the most important of which is assessment of acid secretion, as well as gastric motility and gastric emptying. The influence of drugs on gastric function and the effect of gastric secretion and mechanical actions on the bioavailability of novel compounds are of critical importance in drug development and hence to clinical pharmacologists. The control of acid secretion is essential in the treatment of peptic ulcer disease as well as gastrooesophageal reflux disease (GORD); pH-metry can be used to determine the necessary dose of an acid suppressant to heal mucosal damage. Disturbed gastric myoelectric activity leading to gastroparesis can cause delayed gastric emptying, often found in patients with diabetes mellitus. Electrogastrography (EGG) may be used to evaluate the influence of prokinetics and other drugs on this condition and aid in determining effective therapy.

Endocrine Glands↗