Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased O(2)* and NO production is a key mechanism of mitochondrial dysfunction in myocardial ischemia/reperfusion injury. A crucial segment of the mitochondrial electron transport chain is succinate ubiquinone reductase (SQR or Complex II). In SQR, oxidative impairment and deglutathionylation of the 70-kDa flavin protein occurs in the post-ischemic heart ( Chen, Y. R., Chen, C. L., Pfeiffer, D. R., and Zweier, J. L. (2007) J. Biol. Chem. 282, 32640-32654 ). To gain insights into the oxidative modification of the 70-kDa protein in the post-ischemic myocardium, we used the identified S-glutathionylated peptide ((77)AAFGLSEAGFNTACVTK(93)) of the 70-kDa protein as a chimeric epitope incorporating a "promiscuous" T cell epitope to generate a high titer polyclonal antibody, AbGSC90. Purified AbGSC90 showed a high binding affinity to isolated SQR. Antibodies of AbGSC90 moderately inhibited the electron transfer and superoxide generation activities of SQR. To test for protein nitration, rats were subjected to 30 min of coronary ligation followed by 24 h of reperfusion. Tissue homogenates were immunoprecipitated with AbGSC90 and probed with antibodies against 3-nitrotyrosine. Enhancement of protein tyrosine nitration was detected in the post-ischemic myocardium. Isolated SQR was subjected to in vitro protein nitration with peroxynitrite, leading to site-specific nitration at the 70-kDa polypeptide and impairment of SQR electron transfer activity. Protein nitration of SQR further impaired its protein-protein interaction with Complex III. Liquid chromatography/tandem mass spectrometry analysis indicated that Tyr-56 and Tyr-142 were involved in protein tyrosine nitration. When the isolated SQR was subjected to in vitro S-glutathionylation, oxidative modification and impairment mediated by peroxynitrite were significantly decreased, thus confirming the protective effect of S-glutathionylation from the oxidative damage of nitration.
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PMID:Protein tyrosine nitration of the flavin subunit is associated with oxidative modification of mitochondrial complex II in the post-ischemic myocardium. 1868 92

Patients with multimorbidity and complex health care needs are usually vulnerable elders with several concomitant advanced chronic diseases. Our research aim was to evaluate differences in patterns of multimorbidity by gender in this population and their possible prognostic implications, measured as in-hospital mortality, 1-month readmissions, and 1-year mortality. We focused on a cohort of elderly patients with well-established multimorbidity criteria admitted to a specific unit for chronic complex-care patients. Multimorbidity criteria, the Charlson, PROFUND and Barthel indexes, and the Pfeiffer test were collected prospectively during their stays. A total of 843 patients (49.2% men) were included, with a median age of 84 [interquartile range (IQR) 79-89] years. The women were older, with greater functional dependence [Barthel index: 40 (IQR:10-65) vs. 60 (IQR: 25-90)], showed more cognitive deterioration [Pfeiffer test: 5 (IQR:1-9) vs. 1 (0-6)], and had worse scores on the PROFUND index [15 (IQR:9-18) vs. 11.5 (IQR: 6-15)], all p <0.0001, while men had greater comorbidity measured with the Charlson index [5 (IQR: 3-7) vs. 4 (IQR: 3-6); p = 0.002]. In the multimorbidity criteria scale, heart failure, autoimmune diseases, dementia, and osteoarticular diseases were more frequent in women, while ischemic heart disease, chronic respiratory diseases, and neoplasms predominated in men. In the analysis of grouped patterns, neurological and osteoarticular diseases were more frequent in females, while respiratory and cancer predominated in males. We did not find gender differences for in-hospital mortality, 1-month readmissions, or 1-year mortality. In the multivariate analysis age, the Charlson, Barthel and PROFUND indexes, along with previous admissions, were independent predictors of 1-year mortality, while gender was non-significant. The Charlson and PROFUND indexes predicted mortality during follow-up more accurately in men than in women (AUC 0.70 vs. 0.57 and 0.74 vs. 0.62, respectively), with both p<0.001. In conclusion, our study shows differing patterns of multimorbidity by gender, with greater functional impairment in women and more comorbidity in men, although without differences in the prognosis. Moreover, some of these prognostic indicators had differing accuracy for the genders in predicting mortality.
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PMID:Multimorbidity gender patterns in hospitalized elderly patients. 3199 Sep 11