Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021843 (bowel obstruction)
 9,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whether induced by infection, inflammation, ischemia, and/or surgical injury, peritoneal adhesions are the leading cause of pelvic pain, bowel obstruction and infertility. It is clear that while postsurgical peritoneal wounds heal without adhesions in some patients, others develop severe scarring from seemingly equal procedures; in addition, in the same patient, adhesions can develop at one surgical site and not in another. The mechanisms underlying the predisposition to form adhesions as well as their site specificity are completely unknown. However, a large number of intraperitoneal surgical procedures are performed each day in the USA, and thus many patients are at risk of developing postoperative adhesions. Therefore, understanding of adhesion formation at the molecular level is essential and in the absence of such information, attempts to prevent patients from developing adhesions will remain an empirical process. The unprecedented advancement in molecular biology during the past decade has led to the identification of many biologically active molecules with the potential of regulating inflammatory and immune responses, angiogenesis and tissue remodeling, events that are central to normal peritoneal wound healing and adhesion formation. Although, the insight into their importance in the development of tissue fibrosis has substantially increased, their major roles in peritoneal biological functions and adhesion formation remain at best speculative. This article reviews the clinical implications of adhesions and attempts to highlight some of the key molecules i.e. growth factors, cytokines, chemokines, proteases and extracellular matrix, that are recognized to regulate inflammation, fibrinolysis, angiogenesis, and tissue remodeling, events that are central to peritoneal wound repair and adhesion formation. Finally, the article discusses the potential application and site specific delivery of several active compounds that are developed to alter the local inflammatory and immune response i.e., cytokine/chemokine network, targeted gene delivery and development of a new generation of biomaterials to prevent adhesion formation. Such understanding of peritoneal biology not only assist us to better manage patients with adhesion, but also those with endometriosis and malignant diseases that affect the peritoneal cavity.
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PMID:Peritoneal molecular environment, adhesion formation and clinical implication. 1189 50

Surgical adhesions are a common and often severe complication of abdominal or pelvic injury that cause pelvic pain, bowel obstruction, and infertility in women. Current treatments are of limited effectiveness because little is known about the cellular and subcellular processes underlying adhesiogenesis. Recently, we showed that Th1 alpha beta CD4(+) T cells mediate the pathogenesis of adhesion formation in a rodent model of this disease process. In this study, we demonstrate that in mice these T cells home directly to the site of surgically induced adhesions and control local chemokine production in a manner dependent on the CD28 T cell costimulatory pathway. Conversely, the inhibitory programmed death-1 pathway plays a central role in limiting adhesiogenesis, as programmed death-1 blockade was associated with increased T cell infiltration, chemokine production, and a concomitant exacerbation of disease. Our results reveal for the first time that the development of postsurgical fibrosis is under the tight control of positive and negative T cell costimulation, and suggest that targeting these pathways may provide promising therapies for the prevention of adhesion formation.
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PMID:Regulation of postsurgical fibrosis by the programmed death-1 inhibitory pathway. 1510 Mar 24

Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD), characterized by marked inflammation and severe fibrosis of the peritoneum, and associated with high morbidity and mortality. EPS can occur years after termination of PD and, in severe cases, leads to intestinal obstruction and ileus requiring surgical intervention. Despite ongoing research, the pathogenesis of EPS remains unclear. We performed a global transcriptome analysis of peritoneal tissue specimens from EPS patients, PD patients without EPS, and uremic patients without history of PD or EPS (Uremic). Unsupervised and supervised bioinformatics analysis revealed distinct transcriptional patterns that discriminated these three clinical groups. The analysis identified a signature of 219 genes expressed differentially in EPS as compared to PD and Uremic groups. Canonical pathway analysis of differentially expressed genes showed enrichment in several pathways, including antigen presentation, dendritic cell maturation, B cell development, chemokine signaling and humoral and cellular immunity (P value<0.05). Further interactive network analysis depicted effects of EPS-associated genes on networks linked to inflammation, immunological response, and cell proliferation. Gene expression changes were confirmed by qRT-PCR for a subset of the differentially expressed genes. EPS patient tissues exhibited elevated expression of genes encoding sulfatase1, thrombospondin 1, fibronectin 1 and alpha smooth muscle actin, among many others, while in EPS and PD tissues mRNAs encoding leptin and retinol-binding protein 4 were markedly down-regulated, compared to Uremic group patients. Immunolocalization of Collagen 1 alpha 1 revealed that Col1a1 protein was predominantly expressed in the submesothelial compact zone of EPS patient peritoneal samples, whereas PD patient peritoneal samples exhibited homogenous Col1a1 staining throughout the tissue samples. The results are compatible with the hypothesis that encapsulating peritoneal sclerosis is a distinct pathological process from the simple peritoneal fibrosis that accompanies all PD treatment.
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PMID:Transcriptional patterns in peritoneal tissue of encapsulating peritoneal sclerosis, a complication of chronic peritoneal dialysis. 2341 65