Dieselengine These are brand new if you have not seen them FYI"MedGenMed GastroenterologyIBS -- Review and What's NewPosted 07/26/2006Amy Foxx-Orenstein, DO, FACG, FACP Abstract"Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal motility disorder broadly characterized by abdominal pain/discomfort associated with altered bowel habits. The chronic and bothersome nature of IBS symptoms often negatively affects patient quality of life and activity level and places a substantial economic burden on patients and the healthcare system. Advances in research have led to a greater understanding of the underlying pathophysiology of IBS, particularly regarding the role serotonin plays in the gastrointestinal tract; the development of stepwise, symptom-based diagnostic strategies that allow for a diagnosis of IBS to be made without the need for extensive laboratory testing; and the development of treatment options targeting underlying pathophysiologic mechanisms that provide relief of the multiple symptoms associated with IBS. This review highlights recent advances in research and discusses how these findings can be applied to daily clinical practice.""Serotonin SignalingOf the putative mechanisms underlying the pathophysiology of IBS, the strongest evidence points to the role of serotonin in the GI tract. The effect of serotonergic mechanisms in the manifestation of IBS symptoms has led to development of a new drug class for the treatment of IBS patients: the GI serotonergic agents.Normal GI function relies on a properly functioning brain-gut axis, which involves the coordinated interplay of the GI musculature, the CNS, the autonomic nervous system, and the enteric nervous system (ENS). The ENS contains millions of neurons embedded in the wall of the digestive tract and functions, at least in part, independently of the CNS. The size, complexity, and independent function of the ENS has resulted in application of the terms "the second brain" and "the mini-brain."[81] Impaired function or coordination of any of these systems, or the communication between these systems and the GI musculature, can lead to symptoms of dysmotility and altered sensory perception, which are characteristic of IBS and select other GI motility disorders.[82]The neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) is a predominant signaling molecule in the ENS. Most (90% to 95%) of the body's serotonin is found in the gut, and smaller amounts are found in the brain (about 3%) and in platelets (about 2%).[83] In the GI tract, serotonin facilitates communication between the ENS and its effector systems (muscles, secretory endothelium, endocrine cells, and vasculature of the GI tract), thus playing a key role in normal GI tract functioning.[84] In addition, serotonin plays a role in the communication between the ENS and the CNS.In the gut, serotonin is synthesized by and stored in the enterochromaffin cells, which are located within the mucosa of the intestinal wall. When material passes through the lumen and the mucosa is stimulated, enterochromaffin cells release serotonin, which then binds to its receptors (primarily 5-HT1P receptors) on intrinsic primary afferent neurons, initiating peristalsis and secretion. Serotonin also binds to 5-HT4 receptors on interneurons, which augments the transmission of signals to motor neurons, resulting in enhanced peristaltic activity. In transgenic mice lacking 5-HT4 receptors, colonic motility is abnormally slow, confirming the role of these receptors in facilitating normal colonic motility.[85] By binding to 5-HT3 receptors on efferent sensory innervations coming from the vagus and the spinal nerves, serotonin mediates signaling between the ENS and the CNS and, thus, modulates pain perception.To regulate the signaling process, excess serotonin must be removed; this is accomplished by the SERT molecule expressed by intestinal epithelial cells.[86] Human studies have shown that defects in serotonin signaling contribute to the pathophysiology of IBS and, potentially, other GI motility disorders. In a recent study by Coates and colleagues,[87] biopsy specimens from patients with IBS showed significantly lower mucosal serotonin concentrations than those from healthy controls, potentially the result of lower mRNA levels for tryptophan hydroxylase (the rate-limiting enzyme in serotonin synthesis), which were also significantly lower in patients with inflammatory bowel disease.[87] There was no significant difference in the number of enterochromaffin cells or in the capacity of these cells to release serotonin under stimulated conditions. In another study, higher serotonin levels were observed in mucosal biopsy samples from patients with IBS with constipation (IBS-C) than in patients with IBS-D or in healthy volunteers.[88]Serotonin levels may also be affected by altering the amount or function of SERT. The study by Coates and colleagues[87] showed a significant decrease in the level of SERT mRNA and SERT protein expressed in the intestinal epithelial cells of IBS patients compared with that of healthy volunteers. In another study,[89] SERT expression and binding capacity in platelets were decreased in women with IBS-D compared with expression and binding capacity in healthy controls. Furthermore, Chen and colleagues[90] showed that mice with a SERT gene deletion had altered colonic motility. It is interesting to note that the mice thrived in laboratory housing conditions, indicating that other transporters could compensate for the lack of SERT. Additional studies have focused on SERT polymorphisms. Yeo and colleagues[91] showed an association between patients with IBS-D and the homozygous short polymorphism of the SERT gene promoter. This mutation results in lower levels of SERT gene transcription and reduced amounts of SERT protein available for reuptake of serotonin. In addition, Camilleri and colleagues[92] showed a possible link between the long promoter polymorphism and patient response to therapy.Thus, a substantially large body of work shows that normal gut physiology is predicated on the interplay between the GI musculature and the ENS, autonomic nervous system, and CNS. One of the central mediators of this complex interplay is the neurotransmitter serotonin. Impairment or imbalance in serotonergic signaling, which can affect GI motility, secretion, and visceral sensitivity, may be affected by defects or deficiencies in serotonin production, specific serotonin receptors, or proteins such as SERT. These changes can manifest in symptoms associated with IBS, including abdominal pain, altered bowel habits (constipation, diarrhea, or alternation between these 2 states), and bloating."
http://www.medscape.com/viewarticle/532089_printThis is very important new info as well.""From Medscape GastroenterologyLiterature Review -- Select Topics in IBS and Chronic ConstipationLatest From the Literature in IBS and Chronic Constipation: September 2006Posted 09/07/2006Brian E. Lacy, MD, PhD "One, it confirms the now widely accepted view that the brain-gut axis is a critical component in IBS. Two, it emphasizes that hypersensitivity is a key underlying pathophysiologic mechanism in the generation of symptoms in IBS patients. And finally, although not evaluated in this study, these findings point out that therapeutic options for patients with IBS should focus on treating both the hypersensitive gut and the hypersensitive CNS."
http://www.medscape.com/viewarticle/544018_2