1.The application of small animal PET in drug development
Hongjuan FANG ; Yanrong DU ; Fang LI ; Fang CHEN
Chinese Pharmacological Bulletin 1987;0(03):-
Small animal PET is a quantitative imaging technique that can noninvasive and dynamically image the distribution of positron-labeled radiopharmaceuticals in vivo,therefore representing a new means of providing information for drug development and evaluation.This article reviews the fundamental basis of PET imaging and their application in preclinical drug discovery and development.
2.Efficacy of Venlafaxine and Reboxitine in treatment of selective serotonin reuptake inhibitors non-responder with major depressive disorder
Xiuying LI ; Hong CHEN ; Fang DU
Chinese Journal of Behavioral Medicine and Brain Science 2009;18(6):502-504
Objective The purpose of this study was to access the efficacy of Venlafaxine and Reboxitine on treatment of depressive patients who had not responded to selective serotonin reuptake inhibitors for eight weeks. Methods 117 cases depressive patients who had not responded to selective serotonin reuptake inhibitors for eight weeks were divided into three Venlafaxine group(n =41),Reboxitine group(n =39),Original medicine group(n =37) by randomly and were treated by corresponding drugs for 8 weeks. The therapeutic response and safety were evaluated by scale of HAMD and TESS at before and after treatment the end of 1,2,4,8 week. Results The score of HAMD in Venlafaxine and Reboxitine groups were significantly lower than Original medicine group at the end of 4,8 weeks after treatment and the score of HAMD in Venlafaxine group were significantly lower than Reboxitine group at the end of 8 weeks after treatment. The score of HAMD in Venlafaxine and Original medicine groups were marked descendanter than before treatment from after treatment second weekend(P <0.01),while reboxitine group did not marked descent until the 4th weekend after treatment. The reduce score of factors in cognition,retardition and desperation of Venlafaxine and Reboxitine groups were significantly higher than Original medicine group at the end of treatment. The curative effect of Venlafaxine group were supper than Original medicine group. The side reaction of three groups were not difference. Conclusions There are obviously curative effect using Venlafaxine to treat the depressive patients who had not responded to selective serotonin reuptake inhibitors. The time of initial effect in Venlafaxine were rapider than Reboxitine group.
3.Simultaneous Determination of Fluoxertine and Olanzapine in Capsules by HPLC
China Pharmacist 2016;19(10):1975-1977
Objective:To establish a method for the simultaneous determination of fluoxertine and olanzapine in capsules by re-versed-phase high performance liquid chromatography ( RP-HPLC) . Methods:The successful separation of fluoxertine and olanzapine was achieved on a Phenomenex C18 column (250 mm × 4. 6 mm, 5 μm) with 10 mmol·L-1 potassium dihydrogen phosphate buffer (pH 4. 0)-acetonitrile-methanol (55 ∶40 ∶5, v/v/v) as the mobile phase. The flow rate was 1. 0 ml·min-1, the detection wave-length was 227 nm, the column temperature was 30℃, and the injection volume was 20 μl. Results:Fluoxertine could be well separa-ted from olanzapine under the chromatographic conditions. The linearity between the peak areas and the concentrations was observed within the range of 5. 0-80. 0 mg·L-1(r=0. 999 9) for fluoxertine and 1. 2-19. 2 mg·L-1(r=0. 999 9) for olanzapine. The mean recovery of fluoxertine and olanzapine was 99. 9%(RSD=0. 94%, n=9) and 100. 2%(RSD=2. 08%, n=9), respectively. Con-clusion:The method is simple, sensitive and accurate, and it can be applied in the content determination of fluoxertine and olanzapine in capsules.
4.Comparative Study on Dissolution Profiles of Ibuprofen Suspension from Different Pharmaceutical Manu-facturers
China Pharmacist 2016;19(9):1804-1807
Objective:To compare the similarity of dissolution curves of domestic ibuprofen suspension and the imported prepara-tion to provide the basis for the comprehensive quality evaluation of ibuprofen suspension. Methods: The in vitro dissolution of the products from four different manufacturers was investigated in pH 7. 2 phosphate buffer solution. The similarity of dissolution behavior was compared with that of the imported preparation in pH 1. 2 hydrochloric acid solution, pH 4. 5 acetate buffer solution, pH 6. 8 phos-phate buffer solution, pH 7. 2 phosphate buffer solution and water, respectively. Results:The dissolution rate of ibuprofen suspension from the four different manufacturers reached above 80% in 60 min. The dissolution profiles of ibuprofen suspension from two different manufacturers were similar with that of the imported preparation. Conclusion: The dissolution behavior of ibuprofen suspension from different manufacturers is significantly different.
5.Changes of thyroid stimulating antibody and thyroid stimulating blocking antibody in treatment of anti-thyroid drugs and combining with levothyrocine to hyperthyroidism
Xiaoming DU ; Ning LI ; Peihua FANG
Chinese Journal of Endocrinology and Metabolism 2017;33(8):662-667
Objective Changes of thyroid stimulating antibody(TSAb) and thyroid stimulating blocking antibody(TSBAb) in the treatment of anti-thyroid drugs(ATDs), and the effect of ATDs combining with levothyrocine(LT4) on TSAb and TSBAb were analyzed. Methods Using recombinant Trxfus. TSHRn protein and Trxfus. TSHRc protein as antigens, and TSH receptor antibody(TRAb)-N(TSAb binding hot spots), TRAb-C(TSBAb binding hot spots)in the serum of thyroid disease patients were measured with ELISA. The changes of TRAb-N, TRAb-C over 36 months in 117 TRAb-N positive Graves′ patients with hyperthyroidism were analyzed retrospectively. In the course of treatment, 41 cases as A group with ATDs and LT4 treatment, 76 cases as B group with only ATDs, The changes of TRAb-N and TRAb-C were observed in the two groups. Results (1)According to the change of TRAb-N, 117 TRAb-N positive Graves′ patients with hyperthyroidism were different. In group Ⅰ, 10 patients continued to have persistently positive TSAb and continued to have hyperthyroidism, remission rate 0%. In group Ⅱ, 17 patients showed complicated TRAb-N changes, 12 of 17 patients got relapse, 5 of 17 patients got remission, remission rate 29.4%. And in group Ⅲ, with TRAb-N dropping gradually, 15 of 89 patients got relapse, 74 of the 89 patients got remission, remission rate 83.1%. Three groups were significantly different with x2 test(P<0.01). One of the 117 TRAb-N positive Graves′ patients with hyperthyroidism developed TRAb-C positive hypothyroidism. (2)According to combining with and without LT4 during the treatment of ATDs,the patients were divided into 2 groups(Group A: ATDs combined with LT4; Group B: only ATDs). These 2 groups were significantly different in TRAb-N at baseline and 3 months(P<0.01), TRAb-C between two groups were not significantly different in all times(P>0.05). Conclusion TSAb and TSBAb can be used to document TRAb-function, which is significant for us to predict the changes of thyroid function. During ATDs treatment, the temporary early low-dose application of LT4 did not significantly affect TSAb and TSBAb.
6.Selection and identification of human monoantibody TRAb Fab fragment
Xiaoming DU ; Ning LI ; Peihua FANG
Tianjin Medical Journal 2017;45(8):851-855
Objective To select and express a human thyrotrophin receptor antibody (TRAb) Fab fragment from phage antibody library constructed with phage display technology. Methods With immobilized antigen, the reconstructed humanized TRAb Fab library was enriched by five rounds panning (adsorption-elution-amplification). The TSAb Fab and TBAb Fab fragment were selected by coated fusion proteins of hTSHRn and hTSHRc. The positive clones were identified and selected by Phage-ELISA. TRAb positive clones were identified by PCR and double restriction enzyme digestion. The soluble TRAb (TSAb, TBAb) Fab fragments were expressed. TRAb (TSAb, TBAb) Fab fragments were identified by Western blotting assay. The DNA fragment was sequenced from the positive clones. Results Following five rounds of biopanning, TRAb (TSAb,TBAb) Fab phage antibody was screened. The enrichment effect reached to 77 times and 94 times. The soluble TRAb (TSAb,TBAb) Fab antibodies were expressed from positive clones and identified by phage ELISA. Western blotting analysis showed that the phage displaying Fab had significant binding activity with antigens. These sequence analysis showed that all of the heavy chain Fd gene and light chain gene were derived from human immunoglobulin variable region. The light chain variable region of the monoclonal 48 was homologous to the immunoglobulin light chain Vλ homology of 94.4%, and the heavy chain variable region of the monoclonal 48 was homologous to the immunoglobulin heavy Fd chain VH4 homology of 88.9%. The light chain variable region of the monoclonal 56 was homologous to the immunoglobulin light chain Vλ homology of 95.6%, and the heavy chain variable region of the monoclonal 56 was homologous to the immunoglobulin heavy Fd chain VH3 homology of 84.6%. Conclusion We have successfully selected TRAb (TSAb, TBAb) Fab fragment from a human phage display immune antibody library.
7.Effects of Artesunate on hepatic fibrosis and its mechanism.
Yan DU ; Li-nan LI ; Bu-wu FANG
Chinese Journal of Applied Physiology 2015;31(1):14-17
OBJECTIVETo investigate the effects of Artesunate(Art) on the LX-2 cell.
METHODSThe cultured hepatic stellate cells were divided into control group and Art-treated groups with 250,350,450 µmol/L. The rate of cellular proliferation was detected by MIT assay, the content of ceramide (Cer)was determined by HPLC method, the content of hydroxyproline (Hyp) was determined by enzyme digestion method, the expressions of PPAR-γ, p53 and Caspase 3 were detected by Western blot.
RESULTSCompared with control group, IX-2 treated with Art were inhibited in a concentration-dependent manner(P < 0.01). Art could significantly increase the content of cerarnide in LX-2 ( P <0.01), and the content of Hyp was significantly decreased (P <0.05, P <0.01). The expressions of PPAR-γ, p53 and Caspase 3 were increased compared with that of control group(P < 0.01).
CONCLUSIONArtesunate could inhibit the proliferation and induce apoptosis of hepatic stellate cells through upregulating ceramide.
Apoptosis ; Artemisinins ; pharmacology ; Caspase 3 ; metabolism ; Cell Line ; Cell Proliferation ; Ceramides ; metabolism ; Hepatic Stellate Cells ; drug effects ; Humans ; Hydroxyproline ; metabolism ; Liver Cirrhosis ; PPAR gamma ; metabolism
8.The differential diagnosis value of detection of platelet specific autoantibody on idiopathic thrombocytopenic
Fang LI ; Wenhua PIAO ; Qin LI ; Jie BAI ; Zongxiao DU
International Journal of Laboratory Medicine 2015;(15):2135-2136
Objective To detect the changes and clinical significance of the expression of anti‐GPⅡb/Ⅲa and anti‐GPⅠb/ⅠX on anti‐secreting B cells in patient with thrombocytopenia .Methods Expression of anti‐GPⅡb/Ⅲa and anti‐GPⅠb/ⅠX specific autoantibodies in thrombocytopenia were tested with (CBA) .Results There were significantly more circulating anti‐GPⅠ b/ⅠX and anti‐GPⅡb/Ⅲa antibody‐producing B cells in primary ITP(P<0 .05) for all comparisons .For diagnosing primary ITP ,the an‐ti‐GPⅠb/ⅠX had 43% sensitivity and 89% specificity ,whereas the anti‐GPⅡ b/Ⅲ a had 86% sensitivity and 83% specificity . When two tests were combined ,the sensitivity improved to 90% without a reduction in specificity .Conclusion The assay for detec‐ting anti‐GPⅠb/ⅠX is useful for identifying patients with ITP ,but its utility for diagnosing ITP is inferior to the anti‐GPⅡb/Ⅲa assay .