Faecal Matrix Metalloprotease-9 Is a More Sensitive Marker For Diagnosing Pouchitis Than Faecal Calprotectin – Results From a Pilot Study

Background. Potential non-invasive markers of pouchitis would have a great deal of significance within clinical practice. This study is aimed at assessing the diagnostic accuracy of faecal calprotectin and matrix metalloprotease-9 as potential markers in patients both with and without pouchitis. Patients and methods. Stool and blood samples were collected from 33 ileal pouch-anal anastomosis patients before a follow-up pouchoscopy. Biopsy samples were taken for histological purposes. The presence of cuffitis and stenosis was evaluated with an endoscopy. Calprotectin and matrix metalloprotease-9 were quantified with an enzyme-linked immunosorbent assay. Results. Pouchitis was detected in 30.3% of the patients. The levels of faecal calprotectin and matrix metalloprotease-9 increased significantly in patients with pouchitis. The sensitivity and specificity of matrix metalloprotease-9 was higher than that of faecal calprotectin. Only matrix metalloprotease-9 correlated significantly with the severity of pouchitis. Conclusions. Faecal matrix metalloprotease-9 has a high specificity in the diagnosis of pouchitis

Immune activation in irritable bowel syndrome: can neuroimmune interactions explain symptoms?

Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal (GI) tract characterized by pain or discomfort from the lower abdominal region, which is associated with altered bowel habit. Despite its prevalence, there is currently a lack of effective treatment options for patients. IBS has long been considered as a neurological condition resulting from alterations in the brain gut axis, but immunological alterations are increasingly reported in IBS patients, consistent with the hypothesis that there is a chronic, but low-grade, immune activation. Mediators released by immune cells act to either dampen or amplify the activity of GI nerves. Release of a number of these mediators correlates with symptoms of IBS, highlighting the importance of interactions between the immune and the nervous systems. Investigation of the role of microbiota in these interactions is in its early stages, but may provide many answers regarding the mechanisms underlying activation of the immune system in IBS. Identifying what the key changes in the GI immune system are in IBS and how these changes modulate viscerosensory nervous function is essential for the development of novel therapies for the underlying disorder.Patrick A. Hughes, Heddy Zola, Irmeli A. Penttila, L. Ashley Blackshaw, Jane M. Andrews, and Doreen Krumbiege

Diazoxide and dimethyl sulphoxide alleviate experimental cerebral hypoperfusion-induced white matter injury in the rat brain

Aging and dementia are accompanied by cerebral white matter (WM) injury. which is considered to be of ischemic origin. A causal link between cerebral ischemia and WM damage has been demonstrated in rats: however. few attempts appear to have, been made to test potential drugs for the alleviation of ischemia-related WM injury. We induced cerebral hypoperfusion via permanent, bilateral occlusion of the common carotid arteries of rats. A mitochondrial ATP-sensitive potassium channel opener diazoxide (5 or its solvent dimethyl sulphoxide (DMSO) was administered i.p. (0.25 ml) on 5 consecutive. days after surgery. Sham-operated animals served as control for surgery. and non-treated rats as controls for treatments. Thirteen weeks after surgery, the animals were sacrificed and astrocytes and microglia were labeled immunocytochemically in the internal capsule, the corpus callosum and the optic tract. The astrocytic proliferation was enhanced by cerebral hypoperfusion in the optic tract, and reduced by diazoxide in DMSO. but not by DMSO alone in the corpus callosum. After carotid artery occlusion, microglial activation was enhanced two-fold in the corpus callosum and four-fold in the optic tract. DMSO decreased microglial activation in the optic tract, while diazoxide in DMSO. but not DMSO alone.. restored microglial activation to the control level in the corpus callosum. In summary, the rat optic tract appeared to be particularly vulnerable to ischemia. while the effect of diazoxide was restricted to the corpus callosum. We conclude that diazoxide dissolved in DMSO can moderate ischemia-related neuroinflammation by suppressing glial reaction in selective cerebral WM areas. (C) 2004 Elsevier Ireland Ltd. All rights reserved

Proteinase-activated receptor-4 evoked colorectal analgesia in mice: an endogenously activated feed-back loop in visceral inflammatory pain

Background Activation of proteinase-activated receptor-4 (PAR-4) from the colonic lumen has an antinociceptiveeffect to colorectal distension (CRD) in micein basal conditions. We aimed to determine thefunctional localization of the responsible receptorsand to test their role in two different hyperalgesiamodels. Methods Mice received PAR-4 activatingpeptide (PAR-4-AP, AYPGKF-NH2) or vehicle intraperitoneally(IP), and abdominal EMG response toCRD was measured. The next group received PAR-4-AP intracolonically (IC) with or without 2,4,6-triaminopyrimidine,a chemical tight junction blocker,before CRD. The SCID mice were used to test the roleof lymphocytes in the antihyperalgesic effect. Theeffects of PAR-4-AP and PAR-4-antagonist (P4pal-10)were evaluated in water avoidance stress (WAS)model and low grade 2,4,6-trinitrobenzene sulfonicacid (TNBS) colitis. Spinal Fos protein expression wasvisualized by immunohistochemistry. Key Results Theantinociceptive effect of PAR-4-AP disappeared whenwas administrered IP, or with the blockade of colonicepithelial tight junctions, suggesting that PAR-4-APneeds to reach directly the nerve terminals in the colon.The CRD-induced spinal Fos overexpression wasreduced by 43% by PAR-4-AP. The PAR-4-AP was antihyperalgesicin both hyperalgesia models and in micewith impaired lymphocytes. The PAR-4-antagonistsignificantly increased the TNBS, but not the WAS-inducedcolonic hyperalgesia. Conclusions & InferencesThe antinociceptive effect of PAR-4-AP dependson its penetration to the colonic mucosa. The PAR-4activation is endogenously involved as a feedback loopto attenuate inflammatory colonic hyperalgesia toCRD