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Gastrointestinal Mucosa (gastrointestinal + mucosa)
Selected AbstractsLocalization of hepatitis C virus in gastrointestinal mucosa: A possible reservoir for relapseHEPATOLOGY, Issue 3 2003Lucia Miglioresi M.D. No abstract is available for this article. [source] Nitric oxide in inflammatory bowel disease: a universal messenger in an unsolved puzzleIMMUNOLOGY, Issue 4 2004George Kolios Summary In recent years, nitric oxide (NO), a gas previously considered to be a potentially toxic chemical, has been established as a diffusible universal messenger that mediates cell,cell communication throughout the body. Constitutive and inducible NO production regulate numerous essential functions of the gastrointestinal mucosa, such as maintenance of adequate perfusion, regulation of microvascular and epithelial permeability, and regulation of the immune response. Up-regulation of the production of NO via expression of inducible nitric oxide synthase (iNOS) represents part of a prompt intestinal antibacterial response; however, NO has also been associated with the initiation and maintenance of inflammation in human inflammatory bowel disease (IBD). Recent studies on animal models of experimental IBD have shown that constitutive and inducible NO production seems to be beneficial during acute colitis, but sustained up-regulation of NO is detrimental. This fact is also supported by studies on mice genetically deficient in various NOS isoforms. However, the mechanism by which NO proceeds from being an indispensable homeostatic regulator to a harmful destructor remains unknown. Furthermore, extrapolation of data from animal colitis models to human IBD is questionable. The purpose of this review is to update our knowledge about the role of this universal mediator and the enzymes that generate it in the pathogenesis of IBD. [source] State of the art: IBD therapy and clinical trials in IBDINFLAMMATORY BOWEL DISEASES, Issue S1 2005Kim L Isaacs MD Abstract Inflammatory bowel diseases (IBD) encompass Crohn's disease and ulcerative colitis, which are diseases characterized by chronic intestinal inflammation. IBD is believed to result from predisposing genetic and environmental factors (specific antigens and pathogen-associated molecular patterns) acting on the immunoregulatory system and causing inflammation of the gastrointestinal mucosa. IBD may be the result of an imbalance of effector (proinflammatory) and regulatory T-cell responses. Three scenarios indicative of the outcome of this balance exist in animal models: balanced effector and regulatory T cells resulting in a normal controlled inflammation; overactive effector T cells resulting in inflammation and disease; and an absence of regulatory T cells resulting in uncontrolled inflammation and severe, aggressive disease. The number of products under study for the treatment of IBD has increased from 3 products and 1 target in 1993 to more than 30 products and more than 10 targets in 2005. The number of products under development and continued investigations into the pathogenesis of IBD emphasize the need to expand clinical research efforts in IBD. [source] Potential role of the cannabinoid receptor CB1 in the pathogenesis of erosive and non-erosive gastro-oesophageal reflux diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2010C. Calabrese Aliment Pharmacol Ther 2010; 32: 603,611 Summary Background, Cannabinoid (CB) receptors have been located in brain areas involved in the triggering of TLESRs as well as in the nodose ganglion from which vagal afferents emanate. The distribution of CB1 receptors has been investigated in the human gastrointestinal mucosa, as expression of inflammatory process. Aim, To evaluate the CB1 expression in oesophageal mucosa. Methods, A total of 87 consecutive subjects were enrolled: 10 controls, 39 NERD and 38 erosive oesophagitis. Eight specimens were taken from macroscopically normal mucosa. Five were processed by haematoxylin,eosin, MIB1/CB1 evaluation and three for the RNA and proteins extraction. Results, The mean MIB1-LI value was 31% and 22% in NERD and ERD patients, respectively, compared to 68% in the healthy subjects. Mean CB1mRNA/GUSB mRNA value of the controls was 0.66, while in GERD patients, it was 0.28. In NERD and ERD, the mean values of CB1/GUSB were 0.38 and 0.17, respectively, with highly significant differences between the NERD vs. ERD groups. Semi-quantitative analysis of CB1 expression, performed with WB, shows in NERD patients a higher CB1 receptor expression than ERD patients. Conclusions, With this study, we showed for the first time the presence of CB1 receptors in the human oesophageal epithelium. [source] Enhanced plasma and target tissue availabilities of albendazole and albendazole sulphoxide in fasted calves: evaluation of different fasting intervalsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2000S. SÁNCHEZ The influence of different pre- and post-treatment fasting periods on the plasma availability and disposition kinetics of albendazole (ABZ) and its sulphoxide metabolite (ABZSO) in cattle was investigated. The effect of fasting on the distribution of ABZ and ABZSO to different target tissues/fluids was also characterised. In Experiment I, 35 parasite-free Holstein calves were divided into seven groups according to the following feeding conditions and treated intraruminally with ABZ (10 mg/kg): control group (fed ad libitum), 24 h fasting either prior to (24 h pre-) or post (24 h post-) treatment, 24 h fasting with either 6 (6 h pre+18 h post) or 12 h (12 h pre+12 h post-) of feed restriction prior to treatment, 12 h fasting either prior to (12 h pre-) or post (12 h post) treatment. In Experiment II, calves from the same pool of animals were subjected to a 24 h fasting period prior to the same ABZ treatment and killed (two animals) at either 24, 36 or 48 h post-administration to obtain samples of abomasal/intestinal mucosa and fluid contents, bile and lungs. Plasma (Experiment I) and tissues/fluids (Experiment II) samples were analysed by HPLC. All the fasting periods investigated induced marked changes to the plasma availability and disposition kinetics of the ABZSO metabolite. Enhanced plasma availability between 37 and 118%, delayed peak concentrations and extended mean residence times for ABZSO were observed in fasted compared to fed calves. The changes in plasma kinetics, reflecting an altered quantitative gastrointestinal absorption, were reflected in increased availability of ABZ and ABZSO in the target tissues/fluids of fasted calves. The availabilities of ABZ and ABZSO in the gastrointestinal mucosa and fluids in fasted calves were markedly greater than in those fed ad libitum. [source] The pharmacokinetics and effects of intravenously administered carprofen and salicylate on gastrointestinal mucosa and selected biochemical measurements in healthy catsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2000Parton The pharmacokinetics of carprofen, a propionic acid-derived nonsteroidal anti-inflammatory (NSAID), and its effect on gastrointestinal mucosa, complete blood counts (CBC) and biochemical indicators of liver and renal function were investigated in healthy cats using a randomized crossover design. A single dose of 4 mg/kg of carprofen (Zenecarp® Injection), normal saline, or 20 mg/kg of DL-lysine acetyl salicylate (Vetalgine®) was given intravenously (i.v.) to each of five cats with a washout period of 2 weeks between treatments. Endoscopy of the stomach and duodenum 8 h postinjection revealed one acetyl salicylate-(aspirin)-treated cat with minor pinpoint erosions. None of the other cats in the three treatment groups had evidence of bleeding or ulceration. Serum biochemistry measurements of blood urea nitrogen (BUN), alanine transferase (ALT) and alkaline phosphatase (ALP) and complete blood counts (CBC) were not significantly altered from pretreatment values by the single dose of salicylate or carprofen (P < 0.05). Early and extended sample time points suggest that the pharmacokinetics of carprofen in the cat fit a 2-compartment model, with a long elimination half-life (t1/2) of 20.1 ± 16.6 h, an area under the plasma concentration,time curve (AUC) of 637 (± 237) ,g.mL/h and a volume of distribution (Vdss) of 0.14 ± 0.05 L/kg. Intravenously administered aspirin fit a 2-compartment model and had a long elimination half-life (t1/2) of 22.2 ± 3.1 h, an AUC of 3824.2 ± 506.7 ,g.mL/h and a volume of distribution (Vdss) of 0.17 ± 0.01 L/kg. [source] The non-inherited gastrointestinal polyposis syndromesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2002E. M. Ward The non-inherited gastrointestinal polyposis syndromes represent a group of rare disorders characterized by the presence of multiple, non-adenomatous polyps on the gastrointestinal mucosa occurring in unrelated patients. We present here a review of the clinical and histo- pathological aspects of the syndromes to include the Cronkhite,Canada syndrome, hyperplastic polyposis and lipomatous polyposis. While infrequently encoun- tered, these diseases can have devastating clinical effects that may be aggravated by delays in diagnosis and treatment. Prompt accurate diagnosis and treatment of these uncommon disorders depend on a sound working knowledge of the distinct clinical and pathological features described herein. [source] Sensory neurone responses to mucosal noxae in the upper gut: relevance to mucosal integrity and gastrointestinal painNEUROGASTROENTEROLOGY & MOTILITY, Issue 5 2002P. Holzer Abstract ,The digestive tract is supplied by extrinsic and intrinsic sensory neurones that, together with endocrine and immune cells, form a surveillance network that is essential to gut function. This article focuses on the responses of extrinsic afferent neurones to chemical insults of the gastrointestinal mucosa and their pathophysiological relevance to mucosal integrity and abdominal pain. Within the gastroduodenal region, spinal afferents subserve an emergency function because, in case of alarm by influxing acid, they stimulate mechanisms of mucosal protection via an efferent-like release of transmitters. Other sensory neurones signal chemical noxae to the brain, a task that is not confined to spinal afferents because vagal afferents communicate gastric acid and peripheral immune challenges to the brainstem and in this way elicit autonomic, endocrine, affective and behavioural reactions. Emerging evidence indicates that hypersensitivity of extrinsic afferent pathways to mechanical and chemical stimuli makes an important contribution to the abdominal hyperalgesia seen in functional dyspepsia and irritable bowel syndrome. Sensitization may be brought about by inflammatory processes that lead to up-regulation and functional alterations of receptors and ion channels on sensory neurones. Such sensory neurone-specific molecules, which include vanilloid (capsaicin) receptors, may represent important targets for novel drugs to treat abdominal pain. [source] Systemically administered trefoil factors are secreted into the gastric lumen and increase the viscosity of gastric contentsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2006S Kjellev Background and purpose: Trefoil factors (TFFs) secreted by mucus-producing cells are essential for the defence of the gastrointestinal mucosa. TFFs probably influence the viscoelastic properties of mucus, but this has not been demonstrated in vivo. We therefore studied the gastric secretion of systemically administered TFF2 and TFF3, and their influence on the viscosity of the secretions. Experimental approach: Mice and rats under general anaesthesia were injected intravenously with human (h) TFF2, hTFF3 (5 mg kg,1 to mice and 25 mg kg,1 to rats), murine (m) 125I-TFF3, or 125I-hTFF3 (300 000 cpm, mice only). The appearance of TFFs in the gastric mucosa and luminal secretions was analysed by autoradiography, gamma-counting, and ELISA, and the viscosity by rheometry. Key results: 125I-mTFF3 and 125I-hTFF3 were taken up by secretory cells of the gastrointestinal tract and detected at the gastric mucosal surface 15 min after injection. Stressing the stomach by carbachol (3.5 ,g kg,1) and pyloric ligation significantly increased the uptake. Injected hTFF2, hTFF3, and mTFF3 were retrieved from the gastric contents after 4 h. In rats, an approximately seven-fold increase in the viscosity was detected after injection of TFF2 compared to the controls, whereas TFF3 did not increase the viscosity. In mice, TFF2 increased the viscosity approximately 4-fold. Conclusions: These data indicate that systemically administered TFFs are transferred to the gastric lumen in a biologically active form. British Journal of Pharmacology (2006) 149, 92,99. doi:10.1038/sj.bjp.0706840 [source] | ||||||||||