Association of attenuated leptin signaling pathways with impaired cardiac function under prolonged high-altitude hypoxia.

Cardiovascular function and adipose metabolism were markedly influenced under high altitudes. However, the interplay between adipokines and heart under hypoxia remains to be elucidated. We aim to explore alterations of adipokines and underlying mechanisms in regulating cardiac function under high altitudes. We investigated the cardiopulmonary function and five adipokines in Antarctic expeditioners at Kunlun Station (4,087 m) for 20 days and established rats exposed to hypobaric hypoxia (5,000 m), simulating Kunlun Station. Antarctic expeditioners exhibited elevated heart rate, blood pressure, systemic vascular resistance, and decreased cardiac pumping function. Plasma creatine phosphokinase-MB (CK-MB) and platelet-endothelial cell adhesion molecule-1 (sPecam-1) increased, and leptin, resistin, and lipocalin-2 decreased. Plasma leptin significantly correlated with altered cardiac function indicators. Additionally, hypoxic rats manifested impaired left ventricular systolic and diastolic function, elevated plasma CK-MB and sPecam-1, and decreased plasma leptin. Chronic hypoxia for 14 days led to increased myocyte hypertrophy, fibrosis, apoptosis, and mitochondrial dysfunction, coupled with reduced protein levels of leptin signaling pathways in myocardial tissues. Cardiac transcriptome analysis revealed leptin was associated with downregulated genes involved in rhythm, Na+/K+ transport, and cell skeleton. In conclusion, chronic hypoxia significantly reduced leptin signaling pathways in cardiac tissues along with significant pathological changes, thus highlighting the pivotal role of leptin in regulation of cardiac function under high altitudes.

Simultaneous determination of three antituberculosis drugs in the serum of patients with spinal tuberculosis by capillary electrophoresis.

The pharmacokinetic variations of a single drug in an antituberculosis regimen are associated with acquired drug resistance and therapy failure. This study aimed to develop a simple and effective method for monitoring the serum levels of isoniazid (INH), rifampicin (RFP), and pyrazinamide (PZA), three antibiotics used in patients with spinal tuberculosis using capillary electrophoresis (CE). A standard solution of INH, RFP, and PZA was prepared and mixed with serum to prepare the standard curve. The detection limit, quantification limit, precision, stability, repeatability, and sample recovery were determined. Then, INH, RFP, and PZA were measured from the leftover serum samples of all patients with spinal tuberculosis who were treated with 2SHRZ/2.5H2R2Z2 combined with surgery in a tertiary hospital in Qinghai from October 2015 to September 2017. A total of 107 patients with spinal tuberculosis treated using the 2SHRZ/2.5H2R2Z2 regimen combined with surgery were included in this study. All three antibiotics had linear standard curves with high correlation coefficients (R2 = 0.9997, 0.9994, and 0.9986). The recovery rates were 98.1% for INH, 96.5% for PZA, and 97.2% for RFP. The results from the serum samples showed that the plasma concentrations of INH (4.989 ± 1.692 µg mL-1) and RFP (9.400 ± 1.711 µg mL-1) reached effective therapeutic concentrations in all patients, but not PZA (33.860 ± 1.830 µg mL-1). The CE method for measuring INH, RFP, and PZA simultaneously in serum samples of patients with spinal tuberculosis is simple, rapid, and sensitive. This method is suitable for the routine monitoring of INH, RFP, and PZA concentrations in the serum of patients with spinal tuberculosis.