Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the long-term consequences of Type I diabetes is weight loss with muscle atrophy, the hallmark phenotype of cachexia. A number of disorders that result in cachexia are associated with immune deficiency. However, whether immune deficiency is a cause or an effect of cachexia is not known. This study examines the non-obese diabetic mouse, the mouse model for spontaneous Type I diabetes, as a potential model to study lymphopenia in cachexia, and to determine whether lymphopenia plays a role in the development of cachexia. The muscle atrophy seen in patients with Type I diabetes involves active protein degradation by activation of the ubiquitin-proteasome pathway, indicating cachexia. Evidence of cachexia in the non-obese diabetic mouse was determined by measuring skeletal muscle atrophy, activation of the ubiquitin-proteasome pathway, and apoptosis, a state also described in some models of cachexia. CD4+ T-cell subset lymphopenia was measured in wasting and non-wasting diabetic mice. Our data show that the mechanism of wasting in diabetic mice involves muscle atrophy, a significant increase in ubiquitin conjugation, and upregulation of the ubiquitin ligases, muscle RING finger 1 (MuRF1) and muscle atrophy F box/atrogin-1 (MAFbx), indicating cachexia. Moreover, fragmentation of DNA isolated from atrophied muscle tissue indicates apoptosis. While CD4+ T-cell lymphopenia is evident in all diabetic mice, CD4+ T cells that express a very low density of CD44 were significantly lost in wasting, but not non-wasting, diabetic mice. These data suggest that CD4+ T-cell subsets are not equally susceptible to cachexia-associated lymphopenia in diabetic mice.
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PMID:Cachexia in the non-obese diabetic mouse is associated with CD4+ T-cell lymphopenia. 1839 74

SH2 domains provide fundamental recognition sites in tyrosine kinase-mediated signaling pathways which, when aberrant, give rise to disease states such as cancer, diabetes, and immune deficiency. Designing specific inhibitors that target the SH2 domain-binding site, however, have presented a major challenge. Despite well over a decade of intensive research, clinically useful SH2 domain inhibitors have yet to become available. A better understanding of the structural, dynamic, and thermodynamic contributions to ligand binding of individual SH2 domains will provide some insight as to whether inhibitor development is possible. We report the first high resolution solution structure of the apo-v-Src SH2 domain. This is accompanied by the analysis of backbone dynamics and pK(a) values within the apo- and peptide-bound states. Our results indicate that the phosphotyrosine (pY) pocket is tightly structured and hence not adaptable to exogenous ligands. On the other hand, the pocket which accommodates residues proximal and C-terminal of the pY (pY + 3) or so-called specificity determining region, is a large dynamic-binding surface. This appears to allow a high level of promiscuity in binding. Binding of a series of synthetic, phosphotyrosyl, peptidomimetic compounds designed to explore interactions in the pY + 3 pocket further demonstrates the ability of the SH2 domain to accommodate diverse ligands. The thermodynamic parameters of these interactions show dramatic enthalpy/entropy compensation. These data suggest that the v-Src SH2 domain does not have a highly specific secondary-binding site, which clearly presents a major hurdle to design selective inhibitors.
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PMID:Structure, dynamics, and binding thermodynamics of the v-Src SH2 domain: implications for drug design. 1853 14

Acute infectious diarrhoea are common and usually self-limited but their management is often inadequate due to over-prescriptions of stool cultures and antibiotics. From a clinical point of view, the most important point is to promptly identify presentations at risk of complications (severe dehydration, septic shock, surgical complications) such as elderly patients, co-morbidity, diabetes, renal or heart deficiency, immune deficiency...). When the epidemiological context is suggestive, physicians have to systematically consider certain clinical forms potentially at risk of severe outcome: collective food poisoning, E. coli O157:H7 bloody diarrhoea with the risk of hemolytic-uremic syndrome or antibiotic-associated pseudomembranous colitis due to Clostridium difficile. Rehydration, including Na, K and glucose, remains the corner stone of the treatment, symptomatic medications being of limited interest and antibiotics reserved to presentations at risk of complications.
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PMID:[Acute infectious diarrhea in adults]. 1868 13

Wound infections after tooth extraction may occur in up to 5%. A systemic infection is a rare but threatening complication often caused by an underlying immune deficiency (immunosuppression, diabetes, HIV) which requires prompt adequate care. This case report describes bacterial meningitis as a possible systemic complication two days after the extraction of a molar in a patient with previously undiagnosed latent diabetes mellitus.
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PMID:Bacterial meningitis after tooth extraction. 1916 61

Immunosuppression as a result of T- or B-cell dysfunction can be associated with a variety of illnesses as a result of the underlying disease or treatment causing the dysfunction, infection or, indeed, therapy. Immunodeficiency may be primary or secondary. Secondary causes of immune deficiency are more common and more frequently encountered during imaging. Immune deficiency can arise in patients with conditions such as leukemia and lymphoma; from infectious agents such as the human immunodeficiency virus (HIV); from the administration of drugs, including chemotherapy agents and steroids; and as a result of metabolic diseases such as renal failure and diabetes. A condition that often presents challenges in the interpretation of abnormal uptake within radionuclide imaging is the patient with HIV infection. This has been compounded in some ways by the introduction of highly active antiretroviral therapy and the advent of the immune reconstitution inflammatory syndrome. Imaging abnormalities are found in association with the underlying disease, eg, lymphoma, HIV which, on occasion, may be difficult to separate from an opportunistic infection. The primary value of radionuclide imaging and in particular (18)F-fluorodeoxyglucose-positron emission tomography is to rapidly establish the probable site of disease to direct biopsy or aspiration so that the underlying pathology can be confirmed. The value of single-photon emission computed tomography and positron emission tomography has been enhanced by the introduction of hybrid imaging so that the computed tomography element of the scan localizes the site of disease more accurately than imaging without the computed tomography. Interest in monitoring response to treatment of infection is increasing but care has to be taken as inflammatory uptake attributable to immune reconstitution inflammatory syndrome can be similar to a worsening of infective uptake and this can lead to misinterpretation of the effect of treatment. It is important for the imager to be aware of the effects of underlying treatments on functional imaging and therefore to have a full history of the disease and the drug treatments that the patient is taking.
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PMID:Opportunistic infection and nuclear medicine. 1918 2

Diverticular disease has become a very common condition in elder and more recently in younger patients in western countries that emerged at the turn of the 20th century and since then has become epidemic. An increasing incidence and an earlier onset of the disease lead us to update the current therapeutic indications, especially for surgery in elective condition. Whereas elective colectomy was performed for poorly documented suspicions of diverticulitis in the past, a positive diagnosis of diverticulitis on CT scan is needed. Therefore, indications for colectomy are restricted to patients with medical history of related endocarditis, diabetes mellitus, proven structural abnormalities of collagen, immune deficiency, after a second episode of diverticulitis requiring at least an hospitalisation or after a single complicated diverticulitis (abscess, fistula, stricture). A two-months delay between symptoms and surgery is suitable, and permits to perform preoperatively a colonoscopy in a safe condition to rule out concomitant adenoma or colonic cancer. There is no randomised trial of open versus laparoscopic colectomy in this specific indication. As the lesions of resected colon became more severe due to restricted indications, laparoscopic approach will require more surgical skill and conversion rate might increase. In selected cases, open surgery should be preferred.
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PMID:[Colonic diverticulosis: which patients need surgery?]. 1925 74

Meningeal defects and primitive ENT infections are known to promote pneumococcal meningitis. Other risk factors can be identified in the occurrence of community acquired bacterial meningitis (CABM) and play a key role either in the frequency of this kind of infection, the type of bacteria concerned, the prognosis or the risk of recurrence. Thus, epidural infiltrations are rarely responsible for staphylococcal or streptococcal meningitis. Cochlear implants are also known to increase the risk of pneumococcal meningitis. The occurrence in children of aseptic meningitis or meningitis due to Staphylococcus aureus or Enterobacteriaceae is strongly suggestive of congenital spinal or cerebral anomalies (dermal sinus or spina bifida). MRI must be rapidly performed. In cases of splenectomy or asplenism, pneumococcal meningitis is common and must be prevented. According to the larger series available on this topic, age over 60, diabetes mellitus, alcoholism and immune deficiency are found to promote CABM in about 25% of cases. Streptococcus pneumoniae is the most frequent causative bacteria in elderly patients, in case of alcoholism, as well as Listeria monocytogenes and some Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae). L. monocytogenes is frequently isolated in immunodepressed patients and patients treated by anti-TNF molecules (infliximab notably). Finally, some genetic polyphormisms promote CABM: complement and properdin deficiencies (meningococcal meningitis), mannose-binding lectin deficiency, Fcgamma receptors alteration or interleukin-1 and IL-1R polymorphisms. Screening for such genetic disorders may be discussed in case of CABM but is mandatory in case of recurrent meningococcal infections.
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PMID:[Predisposing factors of community acquired bacterial meningitis (excluding neonates)]. 1941 29

Diabetes mellitus is an increasingly common disease that affects people of all ages, resulting in significant morbidity and mortality. Diabetic patients require more frequent hospitalization, have greater lengths of stay, and cost more to manage than non-diabetics. The major risk factors for diabetics undergoing surgery are the end-organ diseases associated with diabetes: cardiovascular disease, autonomic neuropathy and immune deficiency. Physicians should pay extra attention to preoperative and preprocedure evaluation and treatment of these diseases to ensure optimal perioperative management. Furthermore, these patients unexpectedly develop hemodynamic instability in response to vasopressor or vasodilator administration during anesthesia, this being of particular importance in patients with concurrent ischemic heart disease in whom it may have a direct effect on mortality. Recent studies have shown that tight glycemic control in diabetic patients undergoing major surgery has been shown to improve perioperative morbidity and mortality.
Curr Diabetes Rev 2010 Jul
PMID:Perioperative considerations in diabetic patients. 2052 18

Although the main reservoir of Candida spp. is believed to be the buccal mucosa, these microorganisms can coaggregate with bacteria in subgingival biofilm and adhere to epithelial cells. Such interactions are associated with the capacity of Candida spp. to invade gingival conjunctive tissue, and may be important in the microbial colonization that contributes to progression of oral alterations caused by diabetes mellitus, some medications, and immunosuppressive diseases such as AIDS. In addition, immune deficiency can result in proliferation of Candida spp. and germination of forms that are more virulent and have a higher capacity to adhere to and penetrate cells in host tissues. The virulence factors of Candida spp. increase host susceptibility to proliferation of these microorganisms and are likely to be important in the study of periodontal disease. Herein, we briefly review the literature pertaining to the role of Candida spp. in periodontal disease, and consider the main virulence factors, the host immune response to these microorganisms, and the effect of concomitant immunosuppressive conditions.
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PMID:Candida spp. in periodontal disease: a brief review. 2058 40

Infection with the yeast candida is a quite common disease. Its occurrence might be harmless, however, Candida infections often present with an underlying systemic disease. Thus, candidiasis in some cases can be considered as an indicator for e.g. diabetes mellitus or immune deficiency (i.e. HIV or leukaemia). Of note, we have to distinguish the colonisation and the infection with Candida because only the presence of the yeast together with clinical symptoms is an indication for treatment. The latter has to be adapted according to age, localisation and potentially underlying systemic disease. A special form of Candidiasis constitutes the chronic mucocutaneous candidiasis which can occur in line with hereditary immune deficiencies or also isolated. In the present review we discuss the current status of diagnostic and therapy of mucocutaneous candidiasis as well as the (patho-) immunologic background of yeast infections using the example of a special case of chronic mucocutaneous candidiasis.
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PMID:[Mucocutaneous candidiasis]. 2058 86


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