Individualized medication of digoxin based on the serum drug concentration and blood biochemical indexes.

Aim: The dose of digoxin is often difficult to be determined precisely. The aim of this study was to retrospectively investigate the effect of blood biochemical indexes on the serum concentration of digoxin. Materials & methods: We collected the data of hospitalized patients treated orally with digoxin in Nanjing Drum Tower Hospital (Nanjing, China) from 2016 to 2018. Descriptive statistics was used to analyze the patients' comprehensive condition. Results: A total of 425 patients were included in the study. Through analysis, nine factors were included in the regression model of the serum concentration of digoxin, and this regression model showed good predictive performance (r2 = 0.83138; p < 0.001). Conclusion: The regression model for the prediction of serum concentration of digoxin has clinical significance, and can provide research basis for individualized medication of digoxin.

Sucrose Acetate Isobutyrate as an In situ Forming Implant for Sustained Release of Local Anesthetics.

OBJECTIVE: In this study, an injectable Sucrose Acetate Isobutyrate (SAIB) drug delivery system (SADS) was designed and fabricated for the sustained release of Ropivacaine (RP) to prolong the duration of local anesthesia. METHODS: By mixing SAIB, RP, and N-methyl-2-pyrrolidone, the SADS was prepared in a sol state with low viscosity before injection. After subcutaneous injection, the pre-gel solution underwent gelation in situ to form a drug-released depot. RESULT: The in vitro release profiles and in vivo pharmacokinetic analysis indicated that RP-SADS had suitable controlled release properties. Particularly, the RP-SADS significantly reduced the initial burst release after subcutaneous injection in rats. CONCLUSION: In a pharmacodynamic analysis of rats, the duration of nerve blockade was prolonged by over 3-fold for the RP-SADS formulation compared to RP solution. Additionally, RP-SADS showed good biocompatibility in vitro and in vivo. Thus, the SADS-based depot technology is a safe drug delivery strategy for the sustained release of local anesthetics with long-term analgesia effects.

Promoting effects of isobavachin on neurogenesis of mouse embryonic stem cells were associated with protein prenylation.

AIM: Some small molecules can induce mouse embryonic stem (ES) cells to differentiate into neuronal cells. Here, we explored the effect of isobavachin (IBA), a compound with a prenyl group at position 8 of ring A, on promoting neuronal differentiation and the potential role of its protein prenylation. METHODS: The hanging drop method was employed for embryonic body (EB) formation to mimic embryo development in vivo. The EBs were treated with IBA at a final concentration of 10(-7) mol/L from EB stage (d 4) to d 8+10. Geranylgeranyltransferase I inhibitor GGTI-298 was subsequently used to disrupt protein prenylation. Neuronal subtypes, including neurons and astrocytes, were observed by fluorescence microscopy. Gene and protein expression levels were detected using RT-PCR and Western blot analysis, respectively. RESULTS: With IBA treatment, nestin was highly expressed in the neural progenitors generated from EBs (d 4, d 8+0). EBs then further differentiated into neurons (marked by ß-tubulin III) and astrocytes (marked by GFAP), which were both up-regulated in a time-dependent manner on d 8+5 and d 8+10. Co-treatment with GGTI-298 selectively abolished the IBA-induced neuronal differentiation. Moreover, in the MAPK pathway, p38 and JNK phosphorylation were down-regulated, while ERK phosphorylation was up-regulated after IBA treatment at different neuronal differentiation passages. CONCLUSION: IBA can facilitate mouse ES cells differentiating into neuronal cells. The mechanism involved protein prenylation and, subsequently, phos-ERK activation and the phos-p38 off pathway.