Drugs online research references
charite.de
Since the liver is the main organ involved in the metabolism and the toxicity of xenobiotics, isolated rat hepatocytes have been increasingly used in recent years as a model to identify pharmacological and toxicological responses of drugs. However, it is generally recognised that isolated hepatocytes retain most of their functions only for a short period. For this reason, numerous models and techniques have been developed to study and improve the metabolic capacity of hepatocytes in vitro over an extended time period and in application for drug metabolism studies. In the present study, we compared four different cell culture models to fulfill these requirements and have therefore harvested hepatocytes and cultured them in different culture systems over two weeks. In order to prove certain advantages or disadvantages of each model, we compared the metabolic capacity, albumin secretion, the release of cytosolic and mitochondrial enzymes, as well as the capacity to metabolise diclofenac (DF). We found that rat hepatocytes in all studied culture models (except the Unisyn Bioreactor) were able to metabolise DF to the same extent as found in vivo. However, the concentration of metabolites was found to decrease with culture time using the monolayer although the DF metabolite level in the collagen Sandwich culture was higher than that of the monolayer culture. The 3D-membrane bioreactor preserved the metabolic capacity for a prolonged period of time. The concentrations of DF metabolites in the Unisyn hollow fiber bioreactor were below the detection limit, which corresponded to other parameters such as albumin secretion and cytochrome P450 activity, disqualifying this culture system clearly for the use of in vitro primary hepatocyte cultures. The other three systems all have their place in drug metabolism with different advantages. However, our studies clearly showed that hepatocytes cultured within a collagen sandwich or in the 3D-membrane bioreactor qualify to study various aspects of drug metabolisms over a long time period. Further studies are needed to prove if the later two culture models may really help to reduce animal testing.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11378681&dopt=Abstract
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gihep.uab.edu
BACKGROUND: Unusual resistance to treatment in 5% to 7% of 1,845 peptic ulcers examined under endoscopy from 1987 to 1996 prompted a search for unusual causes. Although some ulcers were caused by Zollinger-Ellison syndrome (ZES), an atypical clinical course in other patients, especially with those with multiple ulcers, suggested abuse of aspirin. STUDY: Patients who did not have ZES were questioned closely regarding aspirin use and were tested for serum salicylate to detect surreptitious abuse. RESULTS: The authors identified 37 patients with aspirin-related ulcers but otherwise intact upper gastrointestinal tracts. There were 12 men and 25 women aged 18 to 73 years; 18 admitted to current aspirin abuse (>1 g/d), but 19 denied it despite objective evidence from elevated serum salicylate (8.4 +/- 1.2 mg/dL). The clinical presentation was atypical, with only 10 patients having single ulcers, whereas 27 had 83 multiple or multiorgan ulcers. Overall, there were 32 duodenal, 57 gastric, and 4 esophageal ulcers. Omeprazole healed 64% of ulcers, but despite follow-up maintenance with H2 receptor antagonists, all ulcers recurred rapidly, often in a new location. Thirty of 37 patients had serious complications: 18 bled; 9 had pyloric and 2, duodenal stenosis; 2, esophageal strictures; and 2, perforation. Six patients who stopped using aspirin healed easily. The 80% who did not stop on advice after diagnosis were considered abusers. CONCLUSION: Patients with aspirin abuse have atypical, often multiple, intractable ulcers with many complications. These ulcers differ from conventional Helicobacter pylori peptic ulcers and also from those found in patients with ZES. Unless aspirin use is stopped, these ulcers remain incurable and dangerous.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11960062&dopt=Abstract
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J Clin Gastroenterol. 2002 May-Jun;34(5):536-40.
Prolonged use of proton pump inhibitors, CagA status, and the outcome of Helicobacter pylori gastritis.
Gudlaugsdottir S, van Dekken H, Stijnen T, Wilson JH.
Department of Internal Medicine, University Hospital Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
GOALS AND BACKGROUND: To assess whether prolonged use of proton pump inhibitors (PPIs) in patients infected with Helicobacter pylori has adverse effects on gastritis. STUDY: We studied 34 H. pylori-positive individuals with reflux esophagitis, Barrett esophagus, or nonulcer dyspepsia. Half of them were on maintenance treatment with PPIs (mean, 8 years) and half were not.H. pylori and CagA status were tested serologically. Gastric biopsies were classified histopathologically by the updated Sydney classification. RESULTS: Proton pump inhibitors in H. pylori gastritis are associated with significantly less antral inflammation and lower H. pylori density, regardless of CagA status. There was a tendency toward more antral atrophy in patients with the CagA strain who were undergoing maintenance treatment with PPIs (p = 0.08), but there was an opposite tendency in CagA-negative individuals (p = 0.08). Intestinal metaplasia was seen more frequently in CagA-positive, treated individuals (p = 0.028). CONCLUSIONS: These findings support the hypothesis that CagA status is important in the progression to atrophy and that maintenance treatment with PPIs accelerate this progression, while reducing inflammatory infiltration.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11960065&dopt=Abstract
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