ABSTRACT
Purpose: This study aimed to characterize the pharmacokinetics of nalbuphine in patients undergoing general anesthesia with varying degrees of liver dysfunction. Patients and Methods: Twenty-four patients were enrolled and divided into three cohorts based on liver function: normal liver function (n = 13), mild liver dysfunction (n = 5), and moderate/severe liver dysfunction (n = 6). During the induction of anesthesia, they received 15 mg of nalbuphine intravenously. Venous blood samples were collected from each patient. The plasma concentration of nalbuphine was determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The pharmacokinetic parameters of nalbuphine were calculated by non-compartmental analysis (NCA) using Phoenix WinNonlin software. Results: Compared with the normal liver function group, the plasma elimination half-life (T1/2) of nalbuphine was increased by approximately 33% in the moderate/severe liver dysfunction group (2.66 h vs 3.54 h, P<0.05), and the volume of distribution (Vd) increased by approximately 85% (100.08 L vs 184.95 L, P<0.05). Multivariate analysis revealed that weight and platelet were associated with clearance (CL); total bilirubin as an independent factor was associated with T1/2, and weight associated with area under the curve (AUC(0â∞)) independently. Conclusion: The T1/2, mean residence time, and Vd of nalbuphine in patients with moderate/severe liver dysfunction were prolonged or increased significantly compared with those in the normal liver function group. These data suggest that it may need to be used with caution when nalbuphine is administered to patients with moderate or severe liver dysfunction.
Subject(s)
Liver Diseases , Nalbuphine , Anesthesia, General/adverse effects , Area Under Curve , Chromatography, Liquid , Humans , Liver Diseases/surgery , Nalbuphine/pharmacokinetics , Tandem Mass SpectrometryABSTRACT
BACKGROUND: Patients with bipolar disorder (BD) present widespread and significant neurocognitive impairments during all stages of the disorder. Repetitive transcranial magnetic stimulation (rTMS) has been used to improve clinical outcomes in common psychiatric diseases, such as depression, anxiety disorders, schizophrenia, and BD. Whether rTMS can improve cognitive function in BD patients remains unclear. The present study explored the regulatory effects of rTMS on cognitive function in patients with BD. METHODS: Fifty-two eligible subjects with BD were randomly assigned to receive active or sham rTMS via high-speed magnetic stimulator with a figure-of-eight coil for 10 consecutive days. In the active rTMS group, a total of 25,000 stimuli were applied over the left dorsolateral prefrontal cortex at 110% of the motor threshold. The sham group received corresponding sham stimulation. Clinical manifestations and cognitive functions were assessed using a modified 24-item Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS), and the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: Ten consecutive days of high-frequency active rTMS improved scores on the Wechsler Memory Scale-III Spatial Span, and the MCCB Category Fluency subtest, without intolerable adverse effects. No significant differences in HDRS or YMRS scores were found between groups. LIMITATIONS: No follow-up after the intervention. The effect of the drug on cognitive function in subjects was not excluded. CONCLUSIONS: Short-term rTMS can improve cognitive function in BD patients.
Subject(s)
Bipolar Disorder/therapy , Cognition , Transcranial Magnetic Stimulation/methods , Adolescent , Adult , Bipolar Disorder/psychology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Single-Blind Method , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Phytohormones are chemical messengers that have a positive effect on biodiesel production of microalgae at low concentrations. However, the effect of phytohormone 6-benzylaminopurine on lipid and docosahexaenoic acid (DHA) production in marine DHA-producer Aurantiochytrium has never been reported. In this study, a GC-MS-based metabolomics method combined with a multivariate analysis is applied to reveal the metabolic mechanism of 6-benzylaminopurine enhancing production of lipid and DHA in Aurantiochytrium sp.YLH70. RESULTS: In total, 71 metabolites were identified by GC-MS. The PCA model revealed that 76.9% of metabolite variation was related to 6-benzylaminopurine treatment, and overall metabolomics profiles between the 6-benzylaminopurine and control groups were clearly discriminated. Forty-six metabolites identified by the PLS-DA model were responsible for responding to 6-benzylaminopurine. Metabolic analysis showed that 6-benzylaminopurine could accelerate the rate of utilization of glucose in Aurantiochytrium sp. YLH70, and the metabolic flux from glycolysis, TCA cycle and mevalonate pathway to fatty acids biosynthesis was promoted. Moreover, the anti-stress mechanism in Aurantiochytrium sp.YLH70 might be induced by 6-benzylaminopurine. CONCLUSION: Metabolomics is a suitable tool to discover the metabolic mechanism for improving lipid and DHA accumulation in a microorganism. 6-benzylaminopurine has the potential to stimulate lipid and DHA production of Aurantiochytrium sp.YLH70 for industrial purposes. © 2015 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
