Liraglutide protects against nonalcoholic fatty liver disease in ApoE knockout mice with high-fat diet and silenced Acrp30 by increasing AMPK / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of liraglutide-mediated protection against nonalcoholic fatty liver disease (NAFLD) using aApoE knockout (KO) mouse with high-fat diet (HFD) and Acrp30 knockdown.</p><p><b>METHODS</b>Fifty-six male ApoE KO mice were divided into the following six modeling and experimental groups:regular chow fed (ApoE KO, n=10), HFD fed (HF, n=10), HFD+Adenovirus (Ad)-small hairpin (sh) Acrp30 (Ad-shAcrp30, n=10), HFD+Ad-shGreen Fluorescent Protein (GFP) (Ad-shGFP, n=6), HFD+Ad-shAcrp30+liraglutide (liraglutide, n=10), and HFD+Ad-shAcrp30+saline (saline, n=10). Weight-matched C57BL/6 mice on the regular chow diet were used as the control group (WT control, n=10).All mice were fed their assigned diet for 16 weeks.The Ad-shGFP or Ad-shAcrp30 was injected by tail vein at the end of 14 and 15 weeks.Mice in the liraglutide group received 1 mg/kg of the drug, twice daily, intraperitoneally for a total of 8 weeks (from the 9th to 16th week).Fasting blood samples were collected for testing levels of fasting plasma glucose (FPG), triglycerides (TGs), total cholesterol (TC), free fatty acid (FFA), alanine aminotransferase (ALT), Acrp30 and insulin.Liver tissue was procured for histological examination.Expression of mRNA was detected by real-time RT-PC and of protein was detected by western blot analysis.</p><p><b>RESULTS</b>The Ad-shAcrp30 treated mice had reduced expression of Acrp30 at both the mRNA and protein levels in adipose tissues and plasma, as compared with the AdshGFP treated mice (all P < 0.01).Compared to the WT and ApoE KO groups, the HF group showed higher levels of FPG, FFA, TGs and TC (all P < 0.01); furthermore, the Ad-shAcrp30 treatment compounded these changes.The Ad-shAcrp30 treated group had markedly higher hepatic TC and TGs than the HF group (P < 0.01 and P < 0.05).Oil Red O staining showed that there was more lipid droplets in the liver tissue of the Ad-shAcrp30 treated group than in that of the HF group (P < 0.01), and hematoxylin-eosin staining confirmed these results.Liraglutide treatment prevented the increase in body weight, FPG, FFA, TGs, TC and ALT levels, as compared to the saline controls (all P < 0.01), but the plasma Acrp30 levels and the Acrp30 mRNA and protein expression in adipose tissues were elevated (all P < 0.01).Oil-Red O staining indicated that the liraglutide group had a significantly lower hepatic lipid content than the saline group, and total hepatic TG and TC were reduced in the former group (P < 0.01 and P < 0.05).The liraglutide treatment significantly attenuated the mRNA expression of ACC and FAS (both P < 0.01) but increased AMPK phosphorylation (P < 0.01).</p><p><b>CONCLUSION</b>Administration of liraglutide prevented the development of HFD-and hypoadiponectinemia-induced metabolic disturbance and accumulation of hepatic lipids in this mouse model system of NAFLD.</p>

Clinical characteristics and resistance of wound surface infections causing by Bacillus cereus in the department of orthopaedics / 中国骨伤

<p><b>OBJECTIVE</b>To study clinical characteristics and resistance of wound surface infections, so as to guide clinical diagnosis and rational administration.</p><p><b>METHODS</b>The clinical setting and laboratory results were collected by analyzing 20 strains of Bacillus cereus isolated from clinical samples in patients from our hospital from October 2011 to June 2012, including 18 males and 2 females,ranging in age from 22 to 67 years old, averaged (47.30 +/- 11.16) years old. The courses of disease ranged from 5 to 20 days. All the patients were treated with nutrition support therapy, debridement and the corresponding antibiotic therapy. The patients had anemia, low protein hyperlipidemia and wound contamination history while Bacillus cereus infected. Thirty people were selected as normal group, including 23 males and 7 females,with an average age of (45.20 +/- 15.05) years old. Infection control condition was assessed by comparing culture for pathogens and patients wound redness or exudation cases before and after treatment. Antimicrobial susceptibility test was conducted by K-B method.</p><p><b>RESULTS</b>A total of 20 stains of Bacillus cereus were isolated from wound surface infections in department of orthopedics of our hospital. Among them,the infections were correlated with the wound contamination (16/20), malnutrition (20/20), and open-fracture (20/20), operation time (15 cases > 3 h). The laboratory blood test showed that the levels of TP [(49.94 +/- 8.24) g/L], ALB [(29.54 +/- 5.45 ) g/L] and Hb [(103.20 +/- 11.79) g/L] in the infection group was lower than those of control group; in the contrast, the levels of WBC [(8.35 +/- 2.31) x 10(9)/L], NEUT [(6.98 +/- 1.99) x 10(9)/L], hs-CRP [(73.60 +/- 55.14) mg/L] and CK [(900.10 +/- 1 259.12) IU/L] were higher in the infection group than those of control group, and the differences were statistically significant (P < 0.01). The diameter of inhibition zone in penicillin, cefazolin, cefuroxime, ceftazidime, cefepime, cotrimoxazole, erythromycin were less than 15 mm, and suggested that Bacillus cereus resisted to these antibiotics. However, the diameter of inhibition zone in clindamycin, vancomycin, gentamicin, ciprofloxacin, imipenem were larger than 20 mm and this data indicated that the bacteria were highly sensitive to these antibiotics.</p><p><b>CONCLUSION</b>Orthopedic patients who immunocompromised, hypoproteinemia and accompanied by open wounds and contaminated wound susceptible to infect Bacillus cereus; sensitive antimicrobial drugs should be selected on the basis of supplement albumin, symptomatic and supportive treatment.</p>

Effects of ascorbic acid on relaxation of ex vivo Bufo gastrocnemius during sustained isometric contraction / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of ascorbic acid (VC) on relaxation of ex vivo Bufo gastrocnemius during sustained isometric contraction.</p><p><b>METHODS</b>Dynamic tension of the muscle was recorded under constant voltage stimulation within 7.0 min at 2 s intervals. The rest tension and relaxation rate of the muscle was obtained by weighted fitting to the relaxation process of tension <90% of its peak with a mono-exponential model to characterize the muscular relaxation.</p><p><b>RESULTS</b>VC at 2.0 mmol/L alone or in combination with the inhibitors of the antixoidation enzymes (surperoxide dismutase, glutathione peroxidase and catalase) resulted in negligible alterations in the muscular relaxation kinetics. VC combined with the inhibitor of surperoxide dismutase resulted in significantly lowered relaxation rate while increased rest tension, but VC with the inhibitor of either catalase or glutathione peroxidase showed negligible action. VC combined with the inhibitors of all the 3 enzymes also caused significant effect on the muscular relaxation kinetics, which was similar the effect of VC with superoxide dismutase inhibitor.</p><p><b>CONCLUSION</b>VC at high concentration may result in oxidative toxicity to the biological system rich in transitional metal ion complexes but with low antioxidation capacity by causing superoxide-mediated oxidative damages.</p>

Rest tension-based characterization of isometric contractility of Bufo gastrocnemius ex vivo / 南方医科大学学报

<p><b>OBJECTIVE</b>To characterize the isometric contractility of Bufo gastrocnemius ex vivo in light of the rest tension.</p><p><b>METHODS</b>Bufo gastrocnemius treated with SOD inhibitor and ascorbate was stimulated electrically (12 V DC, 2 ms duration with a 2 s interval) to record the tension within 10 min. Weighted fitting to the relaxation curve of the tension below 90% of the peak tension with a mono-exponential model yielded the rest tension and relaxation rate.</p><p><b>RESULTS</b>The control gastrocnemius showed monotonic decrease of the rest tension, but treatment with SOD inhibitor and ascorbate resulted in a decrease of the rest tension followed by a fast increase within a 1.0 min contraction. The increase of the rest tension at 7.0 min of contraction of the treated muscle was significantly greater than that of the control muscle. The control muscle showed a monotonic decrease of the relaxation rate in 10 min, whereas treatment with SOD inhibitor and ascorbate produced increased relaxation rate followed by monotonic decrease till a plateau was reached. In the course of the 10 min recording, the relaxation rate of the treated muscle was lower than that of the control after the same duration of contraction.</p><p><b>CONCLUSION</b>Rest tension is a characteristic index to represent the skeletal muscle contractility.</p>

A new linearly-combined bi-exponential model for kinetic analysis of the isometric relaxation process of Bufo gastrocnemius under electric stimulation in vitro / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

There was a slow-relaxing tail of skeletal muscles in vitro upon the inhibition of Ca(2+)-pump by cyclopiazonic acid (CPA). Herein, a new linearly-combined bi-exponential model to resolve this slow-relaxing tail from the fast-relaxing phase was investigated for kinetic analysis of the isometric relaxation process of Bufo gastrocnemius in vitro, in comparison to the single exponential model and the classical bi-exponential model. During repetitive stimulations at a 2-s interval by square pulses of a 2-ms duration at 12 V direct currency (DC), the isometric tension of Bufo gastrocnemius was recorded at 100 Hz. The relaxation curve with tensions falling from 90% of the peak to the 15th datum before next stimulation was analyzed by three exponential models using a program in MATLAB 6.5. Both the goodness of fit and the distribution of the residuals for the best fitting supported the comparable validity of this new bi-exponential model for kinetic analysis of the relaxation process of the control muscles. After CPA treatment, however, this new bi-exponential model showed an obvious statistical superiority for kinetic analysis of the muscle relaxation process, and it gave the estimated rest tension consistent to that by experimentation, whereas both the classical bi-exponential model and the single exponential model gave biased rest tensions. Moreover, after the treatment of muscles by CPA, both the single exponential model and the classical bi-exponential model yielded lowered relaxation rates, nevertheless, this new bi-exponential model had relaxation rates of negligible changes except much higher rest tensions. These results suggest that this novel linearly-combined bi-exponential model is desirable for kinetic analysis of the relaxation process of muscles with altered Ca(2+)-pumping activity.