Sitagliptin attenuates cardiomyopathy by modulating the JAK/STAT signaling pathway in experimental diabetic rats.

Sitagliptin, a dipeptidyl peptidase-4 inhibitor, has been reported to promote cardioprotection in diabetic hearts by limiting hyperglycemia and hyperlipidemia. However, little is known about the involvement of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway modulation in the cardioprotective effects of sitagliptin. The current study aimed to investigate the protective effects of sitagliptin against diabetic cardiomyopathy (DCM), focusing on the modulation of the JAK/STAT pathway. Diabetes was induced by streptozotocin injection, and rats received sitagliptin orally and daily for 90 days. Diabetic rats exhibited hyperglycemia, hyperlipidemia, and a significant increase in heart-to-body weight (HW/BW) ratio. Serum troponin I and creatine kinase MB, cardiac interleukin-6 (IL-6), lipid peroxidation, and nitric oxide levels showed significant increase in diabetic rats. In contrast, both enzymatic and nonenzymatic antioxidant defenses were significantly declined in the heart of diabetic rats. Histopathological study revealed degenerations, increased collagen deposition in the heart of diabetic rats. Sitagliptin alleviated hyperglycemia, hyperlipidemia, HW/BW ratio, histological architecture, oxidative stress, and inflammation, and rejuvenated the antioxidant defenses. In addition, cardiac levels of pJAK2 and pSTAT3 were increased in diabetic rats, an effect which was remarkably decreased after sitagliptin treatment. In conclusion, these results confer an evidence that sitagliptin has great therapeutic potential on DCM through down-regulation of the JAK/STAT signaling pathway.

A new generation of biomarkers tests of myocardial necrosis: the real quality a physician can get from the laboratory.

BACKGROUND: Recent guidelines recommended by ESC, ACC, AHA, and WHF concerning biomarkers of myocardial necrosis also apply to the work of clinical laboratories. Methodological modification for tests used in determining cardiac biomarkers reduced the time of the analytical procedure to 9 min (STAT version of the tests). We decided to determine and compare analytical quality of the tests in standard and STAT versions for determining serum level: troponin T, MB isoenzyme of creatine kinase, and myoglobin, as well as to verify whether the TnThs STAT test meets the following requirements: CV<10% at the level close to diagnostic, equal to the 99th percentile of reference population, and turnaround time<60 min. MATERIAL/METHODS: We evaluated real precision and accuracy for both standard and STAT versions of tests as well as the correlation of results of physiological and pathological levels. Additionally, observations of turnaround time were made. RESULTS: Calculated values of total errors did not exceed the recommended acceptable total error (<20%). Comparable precision of the 2 measurement methods (CV=3.07%) was obtained. A strong correlation (R>0.99) between both variants of tests for all the parameters was confirmed. Thanks to the application of new reagent kit, the percentage of results with turnaround time<60 min increased from 40% to 75% (n=115; p=0.000008). CONCLUSIONS: The new generation of STAT cardiac biomarkers has high analytical quality and meets international precision requirements. It guarantees high analytical and clinical reliability of results. Use of the STAT version of biomarkers contributes to a significant decrease in turnaround time and allows obtaining a good result of an analysis.

Artificial-epitope mapping for CK-MB assay.

A quantitative method using artificial antibody to detect creatine kinases was developed. Linear epitope sequences were selected based on an artificial-epitope mapping strategy. Nine different MIPs corresponding to the selected peptides were then fabricated on QCM chips. The subtle conformational changes were also recognized by these chips.