Experience of using everolimus in the early stage of living donor liver transplantation.

OBJECTIVES: The aim of our study was to review the experience of early use of everolimus for recipients after adult-to-adult living donor liver transplantation. METHODS: From February 2012 to December 2012, 80 recipients underwent living donor liver transplantation. Forty-three of them used everolimus as an adjunct to the calcineurin inhibitors (CNIs) in the early postoperative period. Thirty-nine patients had hepatocellular carcinoma (HCC) and poor renal function was noted in 9 patients. Ten of them were females and 33 were males. The age varied from 39 to 75 years old. The starting date of use was within 1 week in 33 patients, 2 weeks in 9 patients, and 1 patient was administered on postoperative day 20. The initial doses of everolimus were 0.25 mg every 12 hours and increased to 0.5 mg every 12 hours to target the level at 3-5 ng/mL. Doppler ultrasound was performed regularly postoperative days 1, 4, and 14. RESULTS: The mean time between liver transplantation and everolimus treatment was 12 ± 8 days. The maximum dose of everolimus used was 1 mg/d with a target trough level between 3 and 5 ng/mL. At 3 months, a target trough level of 3 ng/mL was achieved. Six of 9 renal failure patients showed significant recovery of renal function, whereas 3 of them showed further deterioration and 1 required hemodialysis. During the follow-up period of 9 ± 6 months, all showed good patency of hepatic artery without thrombosis. Three patients (7%) developed HCC recurrence, whereas 1 patient died at the 10th month postoperative due to sepsis. Elevation of lipid profile was noted in 5 patients. Stomatitis was the most frequent side effect and occurred in 15 patients. CONCLUSIONS: The early use of everolimus was safe and feasible. Also, it can be safely used in patients with prior renal failure while reducing the doses of CNIs. Although the recurrence rate of HCC was reduced, further study is ongoing to evaluate the long-term impact of everolimus on prevention of HCC recurrence.

Potential modulation on P-glycoprotein and CYP3A by soymilk and miso: in vivo and ex-vivo studies.

P-glycoprotein (P-gp) and CYP3A4 both play very important roles in drug bioavailability, resistance and interactions. Our in vitro studies indicated that P-gp function was activated by many isoflavones. This study investigated the in vivo effects of soymilk and miso, isoflavone-rich soy foods, on P-gp and CYP3A by tracing the pharmacokinetics of cyclosporine (CSP), a probe drug of P-gp. Rats were orally administered CSP with and without soymilk or miso. A specific monoclonal fluorescence polarisation immunoassay was used to determine the blood concentration of CSP. The results showed that soymilk and miso significantly decreased the C(max) of CSP by 64.5% and 78.3%, and reduced the AUC(0-540) by 64.9% and 78.3%, respectively. Mechanism studies revealed that the activities of P-gp and CYP3A4 were induced by soymilk and miso. In conclusion, ingestion of soymilk and miso significantly activated the functions of P-gp and CYP3A.

Study on the secondary structure of protein in amide I band from human colon cancer tissue by Fourier-transform infrared spectroscopy.

BACKGROUND: Fourier-transform infrared spectroscopy (FT-IR) is a powerful tool for study of the secondary conformation of intact protein in biological tissues and for diagnosis of disease states. The purpose of this study is to utilize FT-IR as a diagnostic tool to estimate the secondary structure of amide I in normal and cancer tissue of human colon. METHODS: Pairs of tissue samples from colon cancer and histologically normal mucosa tissue 5-10 cm from the tumor were obtained from a patient who underwent partial colectomy. In the present study we investigated the changes in the secondary structure of amide I of normal and malignant human colon tissue using FT-IR microspectroscopy with attenuated total reflectance. Secondary-derivative analysis relative to the original and curve-fitting analysis infrared spectra were also carried out. RESULTS: The conformational changes of the secondary structure of protein in normal and cancerous human colon tissue were (1) the composition of alpha-helixes increased in human cancerous colon tissue (15.30%) compared to normal colon tissue (11.72%); (2) beta-sheets which were 46.8% in healthy tissue decreased to 30.71% in cancer tissue; (3) beta-turns increased from 26.28% in normal tissue to 38.48% in cancer tissue; and (4) the composition of random coils was not significantly different between normal tissue (15.12%) and cancer tissue (15.51%). CONCLUSION: Our data demonstrate that protein in colon cancer displays abnormal FT-IR spectra. The conformational changes of the secondary structure of this protein in terms of alpha-helixes, beta-sheets and beta-turns were observed in normal and cancerous tissue from the same individual were compared.