BACKGROUND: Bupivacaine is widely used to alleviate post-operation pain and cure acute and chronic pain caused by inflammation or cancer.Its analgesic time cannot meet the request that drug is released slowly to prolong the analgesic time in clinic.OBJECTIVE: To detect the alleviating effect of bupivacaine polylactic acid microspheres taking high molecular polymer-polylactic acid as vector in rabbits with high performance liquid chromatograph (HPLC) and traditional skin test method.DESIGN: A completely randomized controlled animal experimental study.SETTING: School of Pharmacy, Second Military Medical University of Chinese PLAMATERIALS: Sixteen New Zealand rabbits, weighing (2.58±0.17)kg were used in this experiment.INTERVENTIONS: The experiment was carried out at the Department of pharmaceutics, School of Pharmacy, Second Military Medical University of Chinese PLA between September and November 2002. ① Animal models were established according to traditional skin test method. ② Totally 16 New Zealand rabbits were randomly divided into 2 groups: Group A and Group B, with 8 in each one. 5 mg/kg bupivacaine parenteral solution was injected subcutaneously in Group A, 5 mg/kg bupivacaine polylactic acid microspheres were implanted between subcutaneous tissue and sarcolemma in Group B. We took 1.5 mL blood from ear border vein at 5, 10, 20, 30,45 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours after administration of bupivacaine parenteral solution respectively in Group A and another 1.5 mL at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 3 6, 48 and 60 hours after admistration of bupivacaine microsphere powder for index detection. ③ HPLC method was used to detect the concentration and releasing effect of bupivacaine in blood serum.MAIN OUTCOME MEASURES: Concentration change of bupivacaine in blood serum and efficacy diameter of local anesthetic.RESULTS:All the 16 rabbits entered the stage of result analysis. ①Change of bupivacaine concentration: Plasma bupivacaine concentration in Group A reached the peaked quickly after subutaneous injection with the high concentration of 2.466 4 mg/L, then declined quickly. Plasma bupivacaine concentration in Group B was relative stable, reached a peak much slowly after subcutaneous implantation, with peak concentration of 0.778 1 mg/L, and the plasma bupivacaine concentration maintained a relative low level, the mean retention time was obviously prolonged (P ＜ 0.05).② Alleviating effect of bupivacaine: The analgesic time was significantly longer in the bupivacaine microsphere group than in the bupivacaine parenteral solution group (P ＜ 0.05).CONCLUSION:Bupivacaine polylactic acid microspheres have sustained release effects in rabbits.

To study the effect of exogenous oxygen, we added water solution of paraquat to 7 d cultures of Coriolus versicolor for the next 148 h. Enzyme exudation and biochemical process were investigated on the addition of paraquat. We found that compared with the control (without paraquat), the addition of 30 micromol/L paraquat stimulated the activity of manganese dependent peroxidase (MnP), lignin peroxidase (LiP), and laccases (Lac) 7, 2.5 and 1.3 times, respectively. Also, addition of paraquat enhanced activity of superoxide dismutase (SOD) and catalase (CAT) in the first 48 h. Impact of paraquat on ligninolytic enzymes was significant than that on antioxidant enzyme. Addition of paraquat enhanced phenolic compounds and formaldehyde of cultures too. And concentration of malondialdehyde was increased in the first 24 h. The results showed that addition of paraquat promoted oxidative stress, but the antioxidant systems of the fungal strain are sufficient to prevent mycelia from oxidative stress. As exogenous oxygen, paraquat might be a useful substrate in degradation of lignocellulose.
Fungi ; drug effects ; enzymology ; Lignin ; metabolism ; Oxidative Stress ; Paraquat ; pharmacology ; Peroxidases ; metabolism

Objective To investigate the differentiation of oligodendrocyte precursor cells after neural injury utilizing Sox10 cell lineage tracing in the cortical tissue.Methods C57BL/6 mice and Sox10-CreERT2/red fluorescent protein(RFP)model mice were used in the current study.The Sox10-CreERT2/RFP model mice generated by crossing Sox10-CreERT2 and Ai9 were 8-week-old F1 mice(n=16),which were randomly divided into control group(n=4)and 7 days(n=4),14 days(n=4),and 30 days feed groups(n=4).Tamoxifen(TAM)was used to induce the expression of RFP.The control group received tamoxifen dissolved in sunflower seed oil by gavage(40 mg/kg once daily for three consecutive days)and the brain tissues were obtained after 4 days.The feed group mice were fed with tamoxifen-containing feed to induce RFP expression,and the brain tissues were obtained after 7,14,and 30 days,respectively.Immunofluorescent staining was performed to detect the expressions of neuronal nuclei(NeuN),microtubule-associated protein 2(MAP2),phosphorylated histone 2AX(γ-H2AX),cluster of differentiation 13(CD 13),γ-aminobutyric acid(GABA),glial fibrillary acidic protein(GFAP),cluster of differentiation 11b(CD11b),vesicular glutamate transporter 2(VGLUT2),and adenomatous polyposis coli(APC,CC-1)in the brains of each group mice.The number of positive cells was counted,and the proportion was calculated.Eight-week-old male C57BL/6 mice were randomly divided into wild type(WT)group(n=4)and WT+TAM group(n=4).They were fed with regular feed and tamoxifen-containing feed for 30 days,respectively,and then brain tissues were obtained.Immunofluorescent double-labeling was used to detect the expressions of γ-H2AX positive neurons in the cortex of mice in both groups.Results In the control group,feed 7 days,14 days,and 30 days groups,the proportions of RFP+pericytes among all RFP+cells in the cortical tissue were(0.8±0.1)％,(2.7±0.1)％,(3.2±0.1)％,(4.0±0.1)％,respectively,and the proportion of mature oligodendrocytes(CC-1+RFP+)in the feed 7 days group was(51.2±0.7)％.The proportions of RFP-positive neurons in the cortex after 14 and 30 days of tamoxifen feed were(0.7±0.1)％and(1.5±0.1)％,respectively,while no conversion to RFP-positive neurons was observed in the gavage group and 7 days feed group.RFP cells in the cortex of the 7 days or 30 days feed group did not express GFAP or CD11b.Extensive γ-H2AX+NeuN+staining was observed in the WT group and WT+TAM group.Conclusion Long-term administration of tamoxifen can promote the differentiation of Sox10 cells into pericytes and neurons.Further investigation into the role of OPC in the neurovascular unit repair mechanism may contribute to a better understanding of the pathogenesis underlying AD.