Nimodipine is the second generation of dihydropyridine Ca2+ antagonist. The scope of its clinical application has been expanded because of the excellent curative effects on cerebrovascular diseases. Nimodipine is commonly available on the market as oral or injection preparation,which has to be given several times per day. It may induce peripheral cholinergia side effects and has low bioavailability. Therefore,it is necessary to develop novel drug formulation with optimized delivery system. In the present review, an attempt is made to discuss the current progress of nimodipine in pharmaceutics,including the difference of market situation,safety and efficacy of different dosage forms. Meanwhile,the main research directions of new dosage forms are summarized,which can pro-vide reference for developing more efficient and convenient nimodipine preparations.

Objective To establish a rapid and accurate method for the identification of Mycobacterium species by the gene microarray and to verify its clinical application value .Methods According to the gene sequence of 23 species of Mycobacteria ,the specific probes were designed and the gene chips were prepared .23 Mycobacterial standard strains ,9 non‐mycobacterial strains ,103 clinically isolated mycobacterial strains were detected by PCR‐based reverse blot hybridization assay in the gene chip .Results 23 mycobacterial standard strains ,9 non‐mycobacterial strains were detected by gene chip ,the results showed that the specificity was 100% .Of 103 mycobacterial clinically isolated strains ,87 strains were identified as Mycobacterium tuberculosis compounds (MTC) and 16 strains as non‐tuberculosis mycobacteria (NTM ) including 5 strains of M .abscessus ,3 strains of M .intracellulare ,3 strains of M .avium ,2 strains of M .fortuitum ,1 strain of M .kansas ,1 strain of M .marinum and 1 strain of M .gordonae .The identification results of 103 clinically isolated strains were completely consistent with the sequencing results .The lowest detection limit by this method was 103 copies/mL .Conclusion The gene microarray technique for rapidly identifying Mycobacteria and differentiate MTC and NTM has the advantages of simpleness ,rapidness ,high accuracy ,high specificity and high sensitivity .

OBJECTIVE:To establish a method for simultaneous determination of lysophosphatidyl choline(LPC)and lysophos-phatidyl ethanolamine(LPE)in Nimodipine fat emulsion. METHODS:HPLC was performed on the column of Lichrosher Diol with detector of evaporative light scattering detector with mobile phase A of heptane- isopropyl alcohol solution(43∶57,V/V),mobile phase B n-heptane-isopropyl alcohol-water(29.5∶59∶11.5,V/V/V)(gradient elution)at a flow rate of 1.5 ml/min,column tempera-ture was 40℃,and the injection volume was 20 μl. RESULTS:The linear range was 0.020 0-0.400 0 mg/ml for LPC(r=0.999 0)and 0.010 0-0.200 0 mg/ml for LPE(r=0.999 6),and the logarithm value of concentration and peak area showed good linear relationship;the limit of quantitation was 0.013 4 mg/ml for LPC and 0.013 0 mg/ml for LPE;the limit of detection was 0.007 8 mg/ml for LPC and 0.007 6 mg/ml for LPE;RSDs of precision,stability and reproducibility tests were lower than 2%;recoveries were 95.96%-100.63%(RSD=1.83%,n=9)and 99.22%-101.76%(RSD=0.80%,n=9). CONCLUSIONS:The method is simple,and can be used for the determination of related substance in Nimodipine fat emulsion.

Objective To evaluate the efficacy of dezocine for prevention of postoperative cognitive dysfunction (POCD) in elderly patients undergoing total knee arthroplasty under remifentanil-based anesthesia.Methods Sixty-eight patients of both sexes, aged 65-85 yr, weighing 48-78 kg, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ , undergoing elective unilateral total knee arthroplasty under general anesthesia, were randomly divided into 2 groups (n =34 each) using a random number table: control group (group C) and dezocine group (group D).After induction of anesthesia, the patients were tracheally intubated and mechanically ventilated.Anesthesia was maintained with iv infusion of propofol 0.05-0.06 mg · kg-1 · min-1 and remifentanil 0.05-0.10 μg · kg-1 · min-1, and intermittent iv boluses of vecuronium 0.04 mg/kg.Dezocine 0.1 mg/kg was injected intravenously at 30 min before skin incision in group D.At 1 day before operation (T0) , and 1, 3, 5, 7 days after operation (T1 , T2, T3 , T4) , the blood samples from the central vein were collected for determination of serum cortisol (Cor), neuron specific enolase (NSE) and S-100β protein concentrations.Before operation, and 5 and 7 days after operation, the patients' cognitive function was assessed using Mini-Mental State Examination, and the occurrence of POCD was recorded.Results Compared with the baseline value at T0, the serum Cor, NSE and S-100β protein concentrations were significantly increased at T1-3, and MMSE scores were decreased at T3,4 in the two groups.Compared with group C, the serum Cot, NSE and S-100β protein concentrations were significantly decreased at T1-4, and Mini-Mental State Examination scores were increased at 5 and 7 days after operation, and the incidence of POCD was decreased in group D.Conclusion Dezocine 0.1 mg/kg intravenously injected at 30 min before skin incision can prevent the occurrence of POCD in elderly patients undergoing total knee arthroplasty under remifentanil-based anesthesia.

Objective To compare the curative effect of Epalrestat and mecobalamine .Methods Epalrestat to treat 48 pa-tionts in DPN and mecobalamine to treat 42,measuring blood sugar ,blood pressure, blood fat and body mass index (BMI) prior and post treatment ,and measuring the MCV and SCV of nervus medianus ,nervus peronaeus connunis and nervus tibialis with EMG .Re-sults The symptom of the two sets have all been improved after the treatment ,and the effective power of Epalrestat and mecobalamine is 92.7% and 80.5% respectively.mean while there is improvement in MCV and SCV of nervus medianus ,nervus peronaeus connunis and nervus tibialis,and is more obvious in the set of Epalrestat ( P <0.01).In the whole process of the treat of the two sets ,no one appear to have adverse reactions .Conclusions Epalrestat has significant curative effect with less adverse reactions , and deserves to be spreaded in clinic.

Objective To establish a high performance liquid chromatography method to detect the concentration of lamotrigine in blood dialysate and investigate in vitro recovery of lamotrigine and the factors.Select the microdialysis conditions that apply to the animal experiment and guide the stability study of in vivo recovery.Methods Positive dialysis and retrodialysis were used for the examination of lamotrigine in vitro recovery and the influencing factors such as flow rate, concentration, temperature and time.Filtered out the best conditions that apply to the in vivo experiment.Used the retrodialysis to determine the in vivo recovery and its stability.Results There was no significant difference between relative recovery and relative loss in the same flow rate.The concentration had no obvious effect on relative recovery.At the same condition,relative recovery decreased with the increase of the flow rate and increased with the temperature.The in vivo recovery had a good stability of 6.5 hours when the flow rate and stabilization time were set at 2μL/min and 1.5 h, respectivily.Conclusion Microdialysis technique can be used for the pharmacokinetic study of lamotrigine.Retrodialysis can be used for the determination of the lamotrigine in vivo recovery.

Objective To modify recombinant plasmid construction of BPO trimer,and establish the detec-tion of M2 type anti-mitochondrial antibody (AMA-M2) using ELISA.To modify the recombinant expression vector of the target gene triplet of AMA-M2,and to establish and evaluate an enzyme linked immunosorbent assay (ELISA) for the detection of AMA-M2.Methods The expression vector pGEX 4T 1 BPO was con-structed through the gene amplification of triplet BPO by polymerase chain reaction (PCR),and expressed in E.coli BL21,and the recombinant protein was induced by isopropyl Thioglucoside (IPTG).The target protein was purified by affinity chromatography,and ELISA was established to detect AMA-M2.Results The recom-binant protein with a purity greater than 95% was obtained.326 cases of clinical samples was examined,and in 43 cases of primary biliary cirrhosis (PBC),41 cases showed AMA-M2 positive,the sensitivity was 95.3%(41/43),the specificity was 98.2%(278/283),and the difference of AMA-M2 detection rate between PBC group and non PBC group was statistically significant.Conclusion The target protein obtained by the im-proved technology can be used for AMA-M2 detection.AMA-M2 has high sensitivity and specificity for the clinical diagnosis of PBC.

To study the relation between drug release and the drug status within curcumin-loaded microsphere, SPG (shirasu porous glass) membrane emulsification was used to prepare the curcumin-PLGA (polylactic-co-glycolic acid) microspheres with three levels of drug loading respectively, and the in vitro release was studied with high-performance liquid chromatography (HPLC). The morphology of microspheres was observed with scanning electron microscopy (SEM), and the drug status was studied with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and infrared analysis (IR). The drug loading of microspheres was (5.85 ± 0.21)%, (11.71 ± 0.39)%, (15.41 ± 0.40)%, respectively. No chemical connection was found between curcumin and PLGA. According to the results of XRD, curcumin dispersed in PLGA as amorphous form within the microspheres of the lowest drug loading, while (2.12 ± 0.64)% and (5.66 ± 0.07)% curcumin crystals was detected in the other two kinds of microspheres, respectively, indicating that the drug status was different within three kinds of microspheres. In the data analysis, we found that PLGA had a limited capacity of dissolving curcumin. When the drug loading exceeded the limit, the excess curcumin would exist in the form of crystals in microspheres independently. Meanwhile, this factor contributes to the difference in drug release behavior of the three groups of microspheres.

BACKGROUND: Endothelin(ET) -1 is a peptide with potent actions on blood vessels and nerve system. Its expression increases in the central nervous system(CNS) in a variety of pathological conditions, inducing harmful effects on the nervous tissue. However it is not clearly elucidated whether the over-expressed ET-1 can directly induce neuronal apoptosis.OBJECTIVE: To investigate whether ET-1 can directly induce apoptosis in primarily cultured brain neurons of rat, and which ET receptor subtype(s) is involved in this action.DESIGN: Completely randomized and controlled experimental study based on cells.SETTING: Neurological department in a university hospital, pathological department of a university and laboratory center of tissue transplantation and immunology, life science and technology college.MATERIALS: This study was completed in the Pathology Department, the Institute of Tissue Transplantation and Immunology, the Life Science and Technology College of Jinan University. The subjects were primarily-cultured neurons obtained from cerebral cortex of newborn rats that were provided by the Experimental Animal Center of the Medical College, Sun Yat-sen University.INTERVENTIONS: After culturing for five days, the neurons were treated with ET-1 (0. 2 nmol/L and 20 nmol/L) for 24 hours. Apoptotic neurons were semi-quantitatively measured with Annexin V and Hoechst 33258 staining respectively. ET-1(20 nmol/L), with BQ123(a selective antagonist for ET receptor A, 1 mmol/L) or with BQ788(a selective antagonist for ET receptor B, 1 mmol/L), was added respectively into the cultures simultaneously. And the apoptotic neurons were quantitatively measured with flow cytometry 24 hours later. Equal amount of PBS, instead of ET-1, waw added into the control subjects.MAIN OUTCOME MEASURES: The effect of ET-1 on apoptosis rate of cultured rat cortical neurons, and the ET receptor subtypes involved in this action.RESULTS: Twenty-four hours after treated with 0.2 nmol/L ET-1, the Annexin-V, and Hoechest 33258 positive stained cell rates[ (23.00 ± 9.96)%,(9.82 ±0.95)% ] were of no difference as compared with those of the controls[ (13.50 ± 3.35)%, (8.21 ± 2. 17)% ]. By contrast, after incubation with the higher dose of ET-1 (20 nmol/L), significant higher rate of apoptosis was measured in Annexin V staining[(50.50 ± 10.78)%, P=0.01, n=4] and Hoechest 33258 staining[(13.78±1.52)%, P= 0. 000, n = 8] . Analyzed with flow cytometry, the apoptosis rate was (0.20±0. 15)% in the control group, (26. 11 ±3.28)% in 20 nmol/LET-1 group, and(13.58 ±4. 92)% in BQ123 +ET-1 and(9.99 ±3.30)% in BQ788 +ET-1 respectively, indicating that BQ123 and BQ788 partially-blocked the apoptosis effect of ET-1 on. cultured neurons(BQ123 + ET-1 vs ET-1, P = 0. 005; BQ788 + ET-1 vs ET-1, P = 0. 001, n = 4, respectively).CONCLUSION: The higher dose of ET-1 (20 nmol/L) can directly induce apoptosis of primarily-cultured cerebral neurons of rats. The effect of ET-1 inducing neuronal apoptosis may be mediated via both ET receptors A and B.

AIM: This study is based on the result of the study in HL and ALCL employing gene chip technique, in which writer found that there was distinctly different expression of caspase-4 between HL and ALCL cell lines at the level of mRNA. From the point of view, we try to identify at the level of protein whether there is different expression of this gene in HL and ALCL tissues as well. METHODS: HE staining, the monoclonal antibodies CD30 (BerH2), CD15 (C3D-1), CD20 (L26) and CD45RO (UCHL1) were used for selecting the cases of HL and ALCL. Specific high affinitive anti-caspase-4 polyclonal antibody was used by immunohistochemical staining to analyze the expression of caspase-4 in 18 cases of HL and 15 cases of ALCL. RESULTS: The expression of caspase-4 demonstrated a strong positive staining in all ALCL cases (15/15,100%), whereas negative in 16 HL cases (88 8%), while other two cases were weakly stained (11 2%), showing a distinct difference (P