Ganglionic and cortical arteries and arterioles in 15 aging Sprague-Dowley rats were histochemically examined to evaluate their metabolic profiles using bright-field microscopy semiquantitatively. Lactate dehydrogenase showed significant reactivity which increased with vessel diameter in cortical and ganglionic vessels in all groups examined. Suceinate dehydrogenase showed trace to moderate reactivity in both cortical and ganglionic vessels. Glucose-6-phosphate dchydrogenase showed zero to trace reactivity in cortical and ganglionic vessels, suggesting less synthetic capacity of nuclear acids and proteins. Myosin ATPase showed strong to very strong reactivity which decreased slightly with vessel diameter in all groups tested, indicating high rate of utilizing ATP in smooth muscle. Little difference of enzyme reactivity was found among cortical and ganglionic vessels and vessels from different parts of caudatoputamcn. In conclusion, both cortical and ganglionic vessels are metabolically active, with significant anaerobic glycolysis, but with decrease in capacity observable for aerobic metabolism.

OBJECTIVE:To observe the factors that influence the fluctuation of serum concentrations of valproic acid and to improve the effectiveness and usefulness of monitoring the serum concentration.METHODS:The factors that influence the serum concentration of valproic acid were summed up and the countermeasures were put forward.RESULTS:These influencing factors included the drug administration time;the blood sampling time;the right moment for monitoring;the dosage forms and quality of drug;the obedience of patient;combining use of drugs and the physiological and pathological conditions of pa?tients.CONCLUSION:When epileptic patients receive long-term medical treatment,the doctor,the patient and the pharma?cist should communicate mutually,establish the relevant data,pay attention to those factors and ensure the patients safe and effective in use of drug.

OBJECTIVE:To establish the method for the simultaneous determination of clopidogrel (CLO) and its active metabolites (CATM) and inactive metabolites (CCAM),and to conduct pharmacokinetic study. METHODS:The plasma sam-ple had been derivatized by 2-bromine-3′-methoxy acetophenone(MPB),and was precipitated by acetonitrile. Using carbam-azepine as internal standard,UPLC-MS/MS was adopted. The separation was performed on Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of water(containing 0.1% formic acid)-acetonitrile(containing 0.1% formic acid)using a gradient elution program at the flow rate of 0.50 ml/min. The ESI was equipped and quantitative analysis was operated in posi-tive ion and MRM mode. The mass transition ion-pairs were followed as m/z 322.1→211.8(CLO),m/z 504.1→155.0(the alkyl-ation derivatives of CATM,CATMD),m/z 308.3→198.0(CCAM),m/z 273.2→194.3(internal standard). RESULTS:The lin-ear calibration curves for CLO,CATMD and CCAM were obtained in the concentration range of 0.03-20.00 ng/ml,0.30-200.00 ng/ml and 10.00-10 000.00 ng/ml in plasma,respectively;intra-day and inter-day RSD for them were all less than 15%,and relative error(RE)ranged from -3.5% to 5.7%. Main pharmacokinetic parameters of CLO,CATMD and CCAM in 5 healthy volunteers after oral administration of CLO 300 mg were as follows:cmax were(7.89±5.46),(15.58±8.08),(8 023.33± 1 047.39)ng/ml;tmax were(1.25 ± 0.43),(1.25 ± 0.43),(1.67 ± 0.29)h;t1/2 were (2.31 ± 0.61),(0.64 ± 0.08),(6.53 ± 2.55)h;AUC0-t were(17.19±14.59),(21.39±9.58),(30 648.85±8 026.63)ng·h/ml. CONCLUSIONS:The established method is sensi-tive,rapid and convenient,which is suitable for pharmacokinetic study and plasma concentration determination of CLO and its metabolites.

Objective To establish a sandwich enzyme linked immunosorbent assay (ELISA) method for determination of von Willebrand factor propeptide (vWF-pp) in plasma and to determine the levels of plasma vWF-pp in 152 healthy volunteers, 36 patients with coronary heart disease and 38 cases of the normal control group with the same ages.Methods The levels of vWF-pp in 152 healthy volunteers with different ages and different genders and in 36 patients with coronary heart disease were determined with the sandwich enzyme linked immuno-sorbent assay (ELISA).Results The average level of vWF-pp in 152 healthy volunteers was 496.4?167.2 ?g/L.The level of vWF-pp in the 50~60 years old group was significantly higher than that in the less than 40 years old group (P0.05). There was significant difference between the 51～60 years old male group and the other three male groups respectively, the 16～20 years old group, the 21～30 years old group and the 31～40 years old group (P

Objective To analyze the correlation between cerebral atrophy and white matter lesions (WML) in magnetic resonance imaging (MRI) by quantitative and qualitative methods. Methods Two hundred and seventy-two patients with WML admitted to the Department of Neurology of Taizhou Central Hospital from January 2015 to December 2017 were enrolled, by adopting MCMxxxVI 9.0 TM image processing tool and Analyze 9.0TM image editing tool, the volume within the skull, whole brain tissue, cerebrospinal fluid, subarachnoid volume on the surface of the brain, gray matter, normal brain white matter and diseased white matter were quantitatively determined in the MRI, Fazekas visual score was used to qualitatively evaluate the WML of MRI, and the correlation between brain atrophy and WML was analyzed. Results General linear model analysis showed that the WML volume had a negative correlation with total brain atrophy or decreased whole brain volume (β = -0.432, P = 0.004), especially with deep brain atrophy, namely WML volume had a significant positive correlation with the increase of ventricular volume (β = 0.098, P = 0.031), and it had no correlation with superficial brain atrophy or the increase of subarachnoid volume on the surface of the brain (β = 0.088, P = 0.547). Fazekas rating scale used for the correlation analysis of WML and brain atrophy also showed similar results. After adjusting for the gender and skull content volume, it was shown that the WML volume was well fitted with brain volume model, and so was the WML with the following volumes: cerebral white matter volume without any pathological changes, the whole brain tissue volume, gray matter volume models (brain volume R2 = 0.25, cerebral white matter volume with no pathological changes R2 = 0.35, whole brain tissue volume R2 = 0.77, gray matter volume R2 = 0.25, all P < 0.05). Conclusion MRI analysis showed WML was associated with brain atrophy, primarily with deep brain atrophy.

Objective To investigate the effect of XMD17-109 on the viability of glioma cells and its molecular mechanism based on extracellular signal-regulated kinase 5(ERK5)/inositol 1,4,5-trisphosphate receptor-interacting protein(ITPRIP)signaling pathway.Methods U251 glioma cells were routinely cul-tured,and ERK5 activity was inhibited by XMD17-109.ERK5 knockdown and ERK5 overexpression models were constructed by transfection of RNA fragments and plasmids,respectively.Cells were divided divided into the XMD17-109 group,the Control group,the siERK5 group,the siNC group,siERK5-OE group,the Vector group,the ERK5-OE+XMD17-109 group and the Vector+XMD17-109 group.The cell viability was detected by CCK-8,scratch and flow cytometry experiments and so on.The mRNA and protein expression levels of ERK5 and ITPRIP were detected by reverse transcription-quantitative real time PCR(RT-qPCR)and West-ern blot.Results Compared with the Control group,the cell viability of the XMD17-109 group decreased,and the expression level of ITPRIP decreased(P＜0.05).Compared with the siNC group,the cell viability of the siERK5 group was decreased,and the expression level of ITPRIP was decreased(P＜0.05).Compared with the Vector group,the cell viability of the ERK5-OE group was enhanced,and the expression level of ITPRIP was increased(P＜0.05).Compared the with Vector+XMD17-109 group,the cell viability of the ERK5-OE+XMD17-109 group was enhanced,and the expression level of ITPRIP was increased(P＜0.05).Conclusion XMD17-109 can inhibit the viability of glioma cells by inhibiting ERK5/ITPRIP signaling pathway,which is expected to be a potential drug for glioma treatment.