Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A psoas muscle abscess due to Yersinia enterocolitica developed in a 71-year-old man with mild type II diabetes mellitus. There was no evidence of gastrointestinal infection or septicemia, and treatment with computed tomography-directed percutaneous drainage and cefoxitin resulted in cure. This represents the first known reported case of psoas abscess due to Y. enterocolitica.
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PMID:Psoas muscle abscess due to Yersinia enterocolitica. 672 Jul 35

Protein tyrosine phosphatases (PTPs) are important regulators of signal transduction pathways. Potent and selective PTP inhibitors are useful for probing these pathways and also may serve as drugs for the treatment of a variety of diseases including type 2 diabetes and infection by the bacterium Yersinia pestis. In this report Cu(I)-catalyzed 'click' cycloaddition reactions between azides and alkynes were employed to generate two sequential libraries of PTP inhibitors. In the first round library methyl 4-azidobenzoylformate was reacted with 56 mono- and diynes. After hydrolysis of the methyl esters, the resulting alpha-ketocarboxylic acids were assayed in crude form against the Yersinia PTP and PTP1B. Four compounds were selected for further evaluation, and one compound was chosen as the lead for generation of the second round library. This lead compound was modified by conversion of an alcohol into an azide group, and the resulting azide was reacted with the same 56 mono- and diynes that were used in the first generation library. After screening the crude inhibitors against the Yersinia PTP and PTP1B, four compounds were selected and evaluated in pure form against the Yersinia PTP, PTP1B, TCPTP, LAR, and CD45. The best bis(alpha-ketocarboxylic acid) inhibitor 34 had an IC(50) value of 550nM against the Yersinia PTP and an IC(50) value of 710nM against TCPTP. The most potent inhibitor containing a single alpha-ketocarboxylic acid group 32 had IC(50) values of 2.1, 5.7, and 2.6 microM against the Yersinia PTP, PTP1B, and TCPTP, respectively.
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PMID:A two stage click-based library of protein tyrosine phosphatase inhibitors. 1704 67

The healthy human intestine is colonized by as many as 1014 bacteria belonging to more than 500 different species forming a microbial ecosystem of unsurpassed diversity, termed the microbiota. The microbiota's various bacterial members engage in a physiological network of cooperation and competition within several layers of complexity. Within the last 10 years, technological progress in the field of next-generation sequencing technologies has tremendously advanced our understanding of the wide variety of physiological and pathological processes that are influenced by the commensal microbiota (1, 2). An increasing number of human disease conditions, such as inflammatory bowel diseases (IBD), type 2 diabetes, obesity, allergies and colorectal cancer are linked with altered microbiota composition (3). Moreover, a clearer picture is emerging of the composition of the human microbiota in healthy individuals, its variability over time and between different persons and how the microbiota is shaped by environmental factors (i.e., diet) and the host's genetic background (4). A general feature of a normal, healthy gut microbiota can generate conditions in the gut that disfavor colonization of enteric pathogens. This is termed colonization-resistance (CR). Upon disturbance of the microbiota, CR can be transiently disrupted, and pathogens can gain the opportunity to grow to high levels. This disruption can be caused by exposure to antibiotics (5, 6), changes in diet (7, 8), application of probiotics and drugs (9), and a variety of diseases (3). Breakdown of CR can boost colonization by intrinsic pathogens or increase susceptibility to infections (10). One consequence of pathogen expansion is the triggering of inflammatory host responses and pathogen-mediated disease. Interestingly, human enteric pathogens are part of a small group of bacterial families that belong to the Proteobacteria: the Enterobacteriaceae (E. coli, Yersinia spp., Salmonella spp., Shigella spp.), the Vibrionaceae (Vibrio cholerae) and the Campylobacteriaceae (Campylobacter spp.). In general, members of these families (be it commensals or pathogens) only constitute a minority of the intestinal microbiota. However, proteobacterial "blooms" are a characteristic trait of an abnormal microbiota such as in the course of antibiotic therapy, dietary changes or inflammation (11). It has become clear that the gut microbiota not only plays a major role in priming and regulating mucosal and systemic immunity, but that the immune system also contributes to host control over microbiota composition. These two ways of mutual communication between the microbiota and the immune system were coined as "outside-in" and "inside-out," respectively (12). The significance of those interactions for human health is particularly evident in Crohn's disease (CD) and Ulcerative Colitis (UC). The symptoms of these recurrent, chronic types of gut inflammation are caused by an excessive immune response against one's own commensal microbiota (13). It is assumed that deregulated immune responses can be caused by a genetic predisposition, leading to, for example, the impairment of intestinal barrier function or disruption of mucosal T-cell homeostasis. In CD or UC patients, an abnormally composed microbiota, referred to as "dysbiosis," is commonly observed (discussed later). This is often characterized by an increased relative abundance of facultative anaerobic bacteria (e.g., Enterobacteriaeceae, Bacilli) and, at the same time, depletion of obligate anaerobic bacteria of the classes Bacteroidia and Clostridia. So far, it is unclear whether dysbiosis is a cause or a consequence of inflammatory bowel disease (IBD). In fact, both scenarios are equally conceivable. Recent work suggests that inflammatory immune responses in the gut (both IBD and pathogen-induced) can alter the gut luminal milieu in a way that favors dysbiosis (14). In this chapter, I present a survey on our current state of understanding of the characteristics and mechanisms underlying gut inflammation-associated dysbiosis. The role of dysbiosis in enteric infections and human IBD is discussed. In addition, I will focus on competition of enteric pathogens and the gut microbiota in the inflamed gut and the role of dysbiotic microbiota alterations (e.g., "Enterobacterial blooms" (11)) for the evolution of pathogenicity.
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PMID:The Roles of Inflammation, Nutrient Availability and the Commensal Microbiota in Enteric Pathogen Infection. 2618 88