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)

Excess activated FXIa in plasma indicates hypercoagulability in the early contact phase. We have already developed methods for detecting the hypercoagulable state in clinical samples by our ELISA for complexed FXIa and alpha 1AT, which has been confirmed to be the predominant inhibitor of FXIa. In diabetes, whether the activation of FXI is associated with the development of vascular complications remains unknown, although various hemostatic abnormalities have been described. We tested the complexed FXIa-alpha 1AT level in 45 NIDDM patients, who were divided into three groups according to the development of diabetic nephropathy, as assessed by UAE. Normoalbuminuria was defined as UAE < 15 micrograms/min, microalbuminuria as UAE in the range of 15-200 micrograms/min, and albuminuria as UAE > 200 micrograms/min. In the patients as a whole, FXIa-alpha 1AT and TAT levels were significantly increased compared with these levels in age-matched control subjects (17.3 +/- 5.7 vs. 12.4 +/- 2.4 ng/ml and 2.67 +/- 1.23 vs. 1.93 +/- 0.45 ng/ml, respectively). No significant difference was observed between FXIa-alpha 1AT levels in the control subjects and in the normoalbuminuric group (13.0 +/- 2.1 ng/ml; n = 19). However, in the microalbuminuric (17.9 +/- 3.9 ng/ml; n = 16) and albuminuric (24.1 +/- 5.4 ng/ml; n = 10) groups, FXIa-alpha 1AT levels were significantly increased compared with those in the control and normoalbuminuric group. The TAT level was not correlated with FXIa-alpha 1AT, and no significant differences in its levels were found among these diabetic groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevation of factor XIa-alpha 1-antitrypsin complex levels in NIDDM patients with diabetic nephropathy. 842 59

In an animal model of human non-insulin dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed with sucrose for 8 weeks to obtain severe hyperglycemia. The effects of sucrose administration on peripheral nerve functions, motor nerve conduction velocity (MNCV) and coefficient of variance of R-R interval (CVR-R), were investigated with concomitant measuring of sciatic nerve blood flow (SNBF), ADP-induced platelet aggregation and polyol content in the sciatic nerves. The effects of an aldose reductase inhibitor, TAT, on these parameters were also studied. Administration of sucrose to OLETF rats caused significant body weight reduction and remarkable hyperglycemia. Sucrose-fed OLETF rats demonstrated significantly delayed MNCV, decreased CVR-R, reduced SNBF and increased platelet aggregation activity to ADP. Sorbitol and fructose accumulation, and myo-inositol depletion in sciatic nerves were observed only in sucrose-fed OLETF rats. These abnormalities were all ameliorated by the treatment with TAT. These observations suggest that the sucrose-fed OLETF rat is a useful animal model for studying the pathogenesis of diabetic neuropathy in human NIDDM, and that an aldose reductase inhibitor is a useful therapeutic agent for the treatment of diabetic neuropathy.
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PMID:Diabetic neuropathy in sucrose-fed Otsuka Long-Evans Tokushima fatty rats: effect of an aldose reductase inhibitor, TAT. 915 94

To improve the pharmacological properties of maize ribosome-inactivating protein (maize RIP) for targeting HIV-infected cells, the previously engineered TAT-fused active form of maize RIP (MOD) was further engineered for cysteine-directed PEGylation. In this work, two potential antigenic sites, namely Lys-78 and Lys-264, were identified. They were mutated to cysteine residue and conjugated with PEG5k or PEG20k. The resultant PEG derivatives of MOD variants were examined for ribosome-inactivating activity, circulating half-life and immunogenicity. Our results showed that MOD-PEG conjugates had two- to five-fold lower biological activity compared to the wild-type. Mutation of the two sites respectively did not decrease the anti-MOD IgG and IgE level in mice, but the conjugation of PEG did dramatically reduce the antigenicity. Furthermore, pharmacokinetics studies demonstrated that attachment of PEG20k prolonged the plasma half-life by five-fold for MOD-K78C and 17-fold for MOD-K264C, respectively. The site-specific mutation together with PEGylation therefore generated MOD derivatives with improved pharmacological properties.
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PMID:Improvement of the Pharmacological Properties of Maize RIP by Cysteine-Specific PEGylation. 2776 6