A. Role of calcitonin receptor-like receptor in colonic motility and inflammation. Am J Physiol Gastrointest Liver Physiol 293: G36-G44, 2007. First published March 15, 2007 doi:10.1152/ajpgi.00464.2006.-Calcitonin gene-related peptide (CGRP) mediates neurogenic inflammation and modulates intestinal motility. The CGRP receptor is a heterodimer of calcitonin receptor-like receptor (CLR) and receptor-associated modifying protein 1. We used RNA interference to elucidate the specific role of CLR in colonic motility and inflammation. Intramural injection of double-stranded RNA (dsRNA) against CLR (dsCLR) into the colonic wall at two sites caused the spatial and temporal downregulation of CLR in the colon within 1 day of dsRNA injection. Knockdown of CLR persisted for 7-9 days, and the effect of knockdown spread to ϳ2 cm proximal and distal to the injection sites, whereas control dsRNA injection did not affect CLR expression. Measurement of isometric contractions of isolated colonic muscle segments revealed that in control dsRNA-injected rats, CGRP abrogated contractions entirely and decreased resting muscular tone, whereas in dsCLRinjected rats, CGRP decreased muscle tone but slow-wave contractions of varying amplitude persisted. In trinitrobenzene sulfonic acidinduced colitis, rats with knockdown of CLR displayed a significantly greater degree of edema and necrosis than saline-or control dsRNAinjected rats. Levels of the proinflammatory cytokines TNF-␣ and IL-6 were markedly upregulated by trinitrobenzene sulfonic acid treatment. TNF-␣ mRNA levels were further increased in CLR knockdown rats, whereas levels of IL-6 were unaltered. Thus this study demonstrates that CLR is a functional receptor for CGRP.calcitonin gene-related peptide; RNA interference; trinitrobenzene sulfonic acid; cytokines; colon-specific; tumor necrosis factor-␣ CALCITONIN GENE-RELATED PEPTIDE (CGRP) is widely distributed in both the central and peripheral nervous systems. In the mammalian gastrointestinal (GI) tract, CGRP immunoreactivity is present in the myenteric and submucosal plexuses as well as in the sensory neurons, whose cell bodies are located in the nodose and dorsal root ganglia (13, 30). The functional CGRP receptor has been proposed to be a heterodimer of calcitonin receptor-like receptor (CLR) and receptor-associated modifying protein (RAMP) 1. Association of CLR with RAMP1 or RAMP2 confers specificity for binding either CGRP or adrenomedullin, respectively (23). Previous colocalization studies have demonstrated the presence of CLR and RAMP1 in enteric neurons, including the neurons in the myenteric plexus (5). Additionally, nerve fibers containing CGRP are found in close association with the CLR-positive neurons, suggesting that the effects of CGRP may be mediated via the CLR-RAMP1 heterodimer complex (5).CLR knockout mice are embryonic lethal with severe cardiovascular defects (6). Pharmacological antagonists for CLR have been reported, but systemic administration of antagonists does not result in tissue-specific inhibition of r...
Pseudoaneurysms are a rare and potentially life-threatening complication that can be caused by trauma, infections, tumors, autoimmune diseases, organ transplants, or idiopathic causes. The management of liver trauma is based on the anatomy of the injury and the patient's physiology. Posttraumatic hepatic artery pseudoaneurysm (HAP) is a life-threatening complication that requires prompt recognition and a multidisciplinary approach in its management. We present a case of HAP rupture two weeks following a gunshot wound to the liver.
In this patient group, DM, HTN, and DYS were poorly compensated, even when pharmacotherapy was consistent with published GL. This may be due to disease burden in bariatric surgery candidates or to inadequate medical management prior to presentation.
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