AIM The effects of GW501516, a peroxisome proliferator-activated receptor β (PPARβ) agonist, in long term diet induced obesity (DIO, high fat and maltose diet for 4 months) mice were evaluated, and the efficacy of GW501516 against insulin resistance and the involved mechanism was investigated. METHODSMice were divided into 3 groups: normal control, DIO model and DIO model+GW501516. GW501516 (10 mg·kg-1·d-1) was administered by ig once a day for 14 d. During the treatment, body weight and food intake were monitored every other day. The oral glucose tolerance test, and the serum biochemical parameters including the serum triglyceride, total cholesterol and high density lipoprotein cholesterol (HDL-C) levels were measured according to the specifications. To confirm the GW501516-mediated PPARβ activation, the mRNA levels of downstream genes related to glucose, lipid metabolism and energy expenditure was measured. RESULTS GW501516 treatment effectively improved the glucose intolerance, increased the area under the glucose curves[DIO model, (32.4±4.6) mmol·h·L-1 compared with DIO model+GW501516, (23.4±2.5) mmol·h·L-1, n=7-8, P<0.05], normalized the fasted blood glucose, and increased serum HDL-C level, besides, histological analysis revealed the decreased hepatic lipid accumulation and hypertrophy of hepatocyte in DIO mice. Moreover, RT-PCR results indicated that carnitine palmitoyltransferase 1b, uncoupling protein 2, uncoupling protein 3 and glucose transport protein 4 were all upregulated. CONCLUSIONGW501516 significantly ameliorates glucose intolerance, decreases fasted blood glucose and hepatic steatosis, which might be related to ① the enhancement of fatty acid oxidation and energy uncoupling in muscle, and ②the improvement of insulin-stimulated glucose transportation in skeletal muscle in the long term DIO mice.

Objective To understand the changing characteristics of drug concentration in the serum and cerebrospinal fluid(CSF) after intravenous (IV) drip of norvancomycin in patients after neurosurgery procedure.Methods Patients with surgical cavity/ventricular drainages after neurosurgery procedure in a hospital in 2014 were selected, and they were divided into 2 groups according to the administration modes (12 in each group), conventional administration group: 0.8 g norvancomycin IV drip for 60 minutes, repeated every 12 hours;continuous administration group, 0.8 g norvancomycin, IV drip for 60 minutes, followed by 0.4 g of IV drip for 11 hours, then 0.4 g for 12 hours, serum and CSF specimens were collected at different time points after administration, concentration of norvancomycin was determined.Results Serum norvancomycin concentration reached a peak of (55.52±26.04) and (59.22±41.88) mg/L in conventional administration group and continuous administration group respectively, 24-hour serum concentration were (8.21±6.04) and (9.11±5.09)mg/L respectively;CSF norvancomycin concentration reached a peak of (16.31±11.15) and (8.82±8.91)mg/L in conventional administration group and continuous administration group respectively, 24-hour CSF concentration were (6.12±2.34)and (5.71±4.72)mg/L respectively;CSF penetration rate of conventional administration group was calculated by ratio of area under curve (AUCCSF/AUCserum), at 0-12 and 12-24 h hour were 63.3% and 59.0% respectively;in continuous administration group were 25.4% and 47.4% respectively.According to 95% of the minimum inhibitory concentration (MIC90) 2 mg/L of target bacteria methicillin-resistant Staphylococcus aureus (MRSA), AUC0-24/MIC90 in conventional administration group and continuous administration group were 192 and 184 respectively.Conclusion For patients who receives early use of standard dose of norvancomycin after neurosurgery procedure, CSF drug concentration after convention and continuous administration of norvancomycin can both reach MIC90 against target bacteria.

Objective To understand teicoplanin concentration in cerebrospinal fluid (CSF)during intravenous in-fusion in patients following neurosurgery operation,and evaluate whether drug concentration can be increased if blood-brain barrier was damaged, and effect of continuous pump of drug on drug concentration in CSF. Methods The post-neurosurgical surgery patients with surgical site/ventricular drainage were enrolled in the study, patients were divided into routine administration group(a dose of teicoplanin of 400 mg/12 h was administered for 30 min)and continuous administration group (a dose of 400 mg teicoplanin was administered for 30 min followed by a continuous infusion of 200 mg/6 h).CSF specimens were collected at respective time points of administration, teicoplanin concentration in specimens was measured.Results For routine administration group,drug concentration in CSF was (0.004 ± 0.0123 )mg/L immediately after teicoplanin was bumped,the peak concentration was (0.712 ± 1.028)mg/L after 1-hour bumping,then concentration decreased gradually,which were (0.254 ±0.222),(0.173 ± 0.152),and (0.355±0.207)mg/L at 12,18,and 24 hours of bumping respectively.For continuous administration group, drug concentration in CSF was(0.017±0.020))mg/L immediately after teicoplanin was bumped,the peak concentration reached (0.587±0.255)mg/L after 4-hour bumping,then concentration were (0.429±0.416),(0.325±0.254),(0.476 ±0.686),and (0.318 ±0.464)mg/L at 6,12,18,and 24 hours of bumping respectively,teicoplanin concentration was relatively stable 6 hours later,which were (0.318±0.464)mg/L-(0.476±0.686)mg/L.The area under the curve during 24 hours (AUC0-24 )in routine administration group and continuous administration group were 5.590 mg/L·h and 9.082 mg/L·h respectively.For two groups of patients,teicoplanin concentration only at the area near peak value a-chieved 50% minimum inhibitory concentration(MIC50 )for coagulase negative staphylococcus (CNS),but the time for a-chieving concentration higher than CNS MIC50 was far less than 50% of total administration time;teicoplanin concentration in CSF of both groups of patients didn’t achieve MIC50 for Staphylococcus aureus .Conclusion After continuous infusion of teicoplanin,drug concentration in CSF can be increased compared with routine administration group,but still can’t achieve the effective MIC;the increase of blood drug concentration is benefit to drug concentration in CSF,it is necessary to in-crease the dose appropriately to achieve clinical effectiveness.