鲎试剂用于5％甘露醇注射液的细菌内毒素检测

目的：研究5％甘露醇注射液的细茵内毒素检查方法。方法：通过干扰试验证明5％甘露醇注射液对λ=0.5EU/ml的鲎试剂元抑制和增强作用。结果：使用λ=0.5EU/ml的鲎试荆可直接取样进行检测。结论：5％甘露醇注射液可以甩细茸内毒素检查法取代热原检查法。     

Retroviral transduction of peripheral blood leukocytes in a hollow- fiber bioreactor

BACKGROUND: Peripheral blood white cells (leukocytes) (PBLs) have been used as effective targets for genetic manipulation by transduction with retroviruses in open systems. A semi-closed hollow-fiber bioreactor was tested for culturing and transducing lymphocytes. STUDY DESIGN AND METHODS: PBLs were isolated from five healthy donors, and 5 × 10(7) cells were cultured in hollow-fiber bioreactors for 4 days after stimulation with anti-CD3 in medium containing 200 units per mL of recombinant interleukin 2. Transduction with retroviral vector containing the gene for iduronate-2-sulfatase and G 418 resistance, L2SN, was performed daily on Days 4, 5, 6, and 7, and the cells were expanded for an additional 3 days. RESULTS: PBLs from three donors were harvested from the bioreactor after transduction and expansion, and 4.5 × 10(9), 7.0 × 10(9), and 2.9 × 10(9) cells were recovered, representing 90-, 136-, and 58-fold expansions. The transduction frequency of L2SN was 10, 5, and 1 percent, respectively. For additional expansion of PBLs, in two cases the bioreactor was reinoculated with 5 × 10(7) cells, which were expanded again for 16 and 8 days, respectively, yielding 1.4 × 10(9) and 3.1 × 10(9) cells, which reflected an additional 28- and 62-fold expansion of cells. PBLs from two other donors were transduced and expanded in the bioreactor, and then 0.8 mg per mL of G 418 was added to the medium in an attempt to enrich the transduced population. Although 2.5 and 10 percent of the cells were transduced, cell death and absence of expansion in the presence of G 418 resulted in final cell lots with viabilities of only 4 and 8 percent. In all cases, the harvested cells tested negative in bacterial and fungal cultures. CONCLUSION: Hollow-fiber bioreactors are an efficient and effective system for the retroviral transduction and expansion of PBLs for clinical gene therapy.     

Prognostic implication of early posttransplant hypercholesterolemia in liver transplantation for patients with hepatocellular carcinoma

Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma(HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia. Methods: From January 2015 to December 2017, a...     

The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone

Background and purpose:

There is high interindividual variability in the activity of drug-metabolizing enzymes catalysing the oxidation of oxycodone [cytochrome P450 (CYP) 2D6 and 3A], due to genetic polymorphisms and/or drug–drug interactions. The effects of CYP2D6 and/or CYP3A activity modulation on the pharmacokinetics of oxycodone remains poorly explored.

Experimental approach:

A randomized crossover double-blind placebo-controlled study was performed with 10 healthy volunteers genotyped for CYP2D6 [six extensive (EM), two deficient (PM/IM) and two ultrarapid metabolizers (UM)]. The volunteers randomly received on five different occasions: oxycodone 0.2 mg·kg⁻¹ and placebo; oxycodone and quinidine (CYP2D6 inhibitor); oxycodone and ketoconazole (CYP3A inhibitor); oxycodone and quinidine+ketoconazole; placebo. Blood samples for plasma concentrations of oxycodone and metabolites (oxymorphone, noroxycodone and noroxymorphone) were collected for 24 h after dosing. Phenotyping for CYP2D6 (with dextromethorphan) and CYP3A (with midazolam) were assessed at each session.

Key results:

CYP2D6 activity was correlated with oxymorphone and noroxymorphone AUCs and C_max (−0.71 < Spearman correlation coefficient ρs < −0.92). Oxymorphone C_max was 62% and 75% lower in PM than EM and UM. Noroxymorphone C_max reduction was even more pronounced (90%). In UM, oxymorphone and noroxymorphone concentrations increased whereas noroxycodone exposure was halved. Blocking CYP2D6 (with quinidine) reduced oxymorphone and noroxymorphone C_max by 40% and 80%, and increased noroxycodone AUC_∞ by 70%. Blocking CYP3A4 (with ketoconazole) tripled oxymorphone AUC_∞ and reduced noroxycodone and noroxymorphone AUCs by 80%. Shunting to CYP2D6 pathway was observed after CYP3A4 inhibition.

Conclusions and implications:

Drug–drug interactions via CYP2D6 and CYP3A affected oxycodone pharmacokinetics and its magnitude depended on CYP2D6 genotype.     

Magnetic resonance measurement of coronary blood flow

Recent advances in fast MRI sequences have considerably extended the capabilities of cardiac MRI in the functional assessment of coronary blood flow and flow reserve. The MR measurement of coronary flow reserve can be used to identify restenosis of the left main and left anterior descending coronary arteries after percutaneous interventions in clinical patients. Further refinements in MR pulse sequences, including the use of phase-contrast echo-planar or spiral MR methods, may make it possible to quantify blood flow volume and flow reserve more accurately in all major branches of the coronary arteries.
The MR measurement of blood flow through the coronary sinus allows a noninvasive assessment of global coronary hemodynamics. Because the coronary sinus is larger than the native coronary arteries, the errors in blood flow quantification associated with the limited spatial and temporal resolution of current phase-contrast MR sequences are substantially smaller. The MR quantification of total coronary blood flow and coronary blood flow per gram of myocardium during stress and at rest seems to be an ideal method for evaluating coronary hemodynamics in diffuse myocardial diseases of the heart, such as hypertensive heart diseases and cardiomyopathies, and may be useful in evaluating endothelial dysfunction of the coronary circulation, which develops in the earliest stages of atherosclerotic disease and may precede obstruction of the epicardial coronary arteries.