Effect of γ-ray on metabolic enzyme CYP3A1 in rat liver on multiple levels / 中国药理学通报

Aim To explore the effect of γ-ray on the mRNA,protein expression levels and metabolic activity level of the key drug metabolic enzyme CYP3A1 in rat liver. Methods Wistar rats were randomly divided into control group, 24 h post-radiation group and 72 h post-radiation group. The experimental group was exposed to total body irradiation of single 6 Gy γ-ray. Blood was collected from the orbital venous plexus for blood routine examination and biochemical analysis 24 h and 72 h after irradiation, and liver tissue was prepared for quantifying expression of CYP3A1 mRNA and liver-specific microRNA (miR-122-5p) through RT-PCR. The expression level of CYP3A1 protein was analyzed by Western blot, and the metabolic activity level of CYP3A1 detected by the specific substrate midazolam combined with LC-MS method. Results Com¬pared with the control group, the weights of the rats in the radiation group significantly decreased, and the number of white blood cells was markedly reduced. Simultaneously, the activities of alanine aminotrans-ferase and alkaline phosphatase continuously descended, as well as the levels of total bilirubin and bile acid significantly increased, which indicated that the liver may be damaged after radiation. The relative expression of CYP3A1 mRNA continued to increase significantly 24 h and 72 h after irradiation. CYP3A1 protein expression and metabolic activity levels showed an obvious increasing trend 24 h after irradiation, and rose significantly 72 h after irradiation compared with the control group. At the same time, the expression of miR-122-5p in liver of rats in the 24 h and 72 h post-radiation group continued to decrease rapidly compared with the control group. Conclusions γ-ray radiation may arouse damage effect on liver, which leads to the continuous up-regulation of the mRNA and protein expression levels of the capital metabolic enzyme CYP3A1 in liver tissue, as well as the elevation of the metabolic activity level. The regulatory mechanism might be related to miR-122-5p.

Pharmacokinetics of two recombinant humanized monoclonal antibodies against ricin in rhesus monkeys / 药学学报

Recombinant humanized anti-ricin monoclonal antibody (MIL50) is a recombinant humanized monoclonal antibody targeting ricin. In this study, an ELISA method was used to establish a method for the determination of MIL50 in macaque serum, and a cross design method was used. Twelve rhesus monkeys were intravenously injected 1 mg·kg-1 test preparation (MIL50 freeze-died powder injection) and reference preparation (MIL50 liquid preparation) to determine the plasma concentration of MIL50 at different time points, and the pharmacokinetic parameters were analyzed to compare the pharmacokinetic characteristics of MIL50 liquid preparation and freeze-died powder injection in rhesus monkeys. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Chinese Academy of Medical Sciences and Use of Laboratory Animals and the regulations derived by the Animal Care and Welfare Committee of the Institute of Radiation Medicine, Academy of Military Medical Sciences (IACUC-DWZX-2020-503). The results showed that there was no significant difference between Cmax and AUC0-5d in the two groups. The liquid preparation was the reference preparation, with Cmax ratio of 101.6% and AUC0-5d ratio of 101.9%, the 90% confidence interval of Cmax was 79.42%-129.92%, and the 90% confidence interval of AUC0-5d was 85.72%-121.18%. These results suggested that different dosage forms of MIL50 had certain differences in the changes of blood drug concentration in rhesus monkeys.

Improvement Effects of β-boswellic Acid on Hippocampal Neurons Cells Injury Induced by Oxygen-glucose Deprivation / 中国药房

OBJECTIVE：To study the imp rovement effects of β-boswellic acid on hippocampal neurons cells injury of rats induced by oxygen-glucose deprivation. METHODS ：The hippocampal neurons cell of rats were divided into normal control group ， model group and β-boswellic acid low-concentration ，medium-concentration and high-concentration groups （1，10，100 μmol/L）. Except for normal control group ，other groups were cultured with relevant medium and given oxygen glucose deprivation to induce oxygen-glucose deprivation induced injury model. MTT assay was adopted to detect cell viability. Chemical colorimetry was used to detect LDH activity in cell culture supernatant. Hoechst-PI staining was used to detect the morphology change of cells. Flow cytometry was used to detect early apoptosis rate of cells. The expression of apoptosis-related protein （Bcl-2，Bax and cleaved caspase-3） were detected by Western blot. RESULTS ：Compared with model group ，the survival rate of cells and protein expression of Bcl- 2 were increased significantly in β-boswellic acid medium-concentration and high-concentration groups （P＜ 0.01），while LDH activity ，early apoptosis rate ，protein expression of cleaved caspase- 3 and Bax were all decreased significantly （P＜0.05 or P＜0.01）. The densely stained nuclei and fragmentation decreased significantly. CONCLUSIONS ：β-boswellic acid can relieve oxygen-glucose deprivation induced injury of hippocampal neurons cells ，the mechanism of which may be associated with down-regulating the protein expression of cleaved caspase- 3 and Bax and up-regulating the protein expression of Bcl- 2.

Practice of Standardizing Rational Use of Proton Pump Inhibitors in Neurosurgery Department of Our Hospital by PDCA Cycle Management / 中国药房

OBJECTIVE： To promote rational use of proton pump inhibitors （PPIs） during perioperative period. METHODS： PDCA （Plan， Do， Check， Action） cycle management was used， the irrational use of PPIs of 300 medical records in neurosurgery department of our hospital were collected. The reasons were analyzed， management target was formulated and measures were implemented. The effects of management were evaluated through comparing the rate of irrational drug use and ratio of irrational type of PPIs in 300 medical records of neurosurgery department during perioperative period after management. RESULTS： Through collecting related data to confirm risk factors of stress ulcer， establishing rationality evaluation criteria for perioperative prophylactic use of PPIs， conducting rational drug use training among medical staff， drawing up various management systems and strengthening supervision and management， the rate of irrational use of PPIs was decreased significantly in our hospital； the number of irrational drug use cases decreased from 240 before management to 156 after management， among which the rate of prophylactic drug use without indication decreased from 37.33％ to 29.00％ （P＜0.05）； the irrational dosage rate decreased from 11.33％ to 6.33％ （P＜0.05）； the rate of irrational dosing frequency dropped from 12.67％ to 5.00％ （P＜0.01）. CONCLUSIONS： PDCA cycle management of our hospital can standardize the prophylactic use of PPIs in neurosurgery department during perioperative period and promote rational use of PPIs.

Effects of Emodin against Renal Tubular Epithelial Cell Fibrosis via the Inhibition of Akt/mTOR Signal Pathway / 中国药师

Objective: To investigate the mechanism of emodin ( EM) in the expression of related protein for the fibrosis of the transforming growth factor-β1(TGF-β1)-stimulated human renal tubular epithelial (HK-2) cells. Methods: HK-2 cells were randomly divided into the normal control group, TGF-β1-stimulated model control group and emodin ( TGF-β1 +EM) group. The contents of Collage Ⅰ and fibronectin in the culture supernatant were determined by ELISA. After HK-2 cells were stimulated with TGF-β1 for 24 h, the cells were collected for immunofluorescence, Western blot and RT-PCR analysis. RT-PCR was used to detect PI3K, p-Akt and mTOR. The protein expressions of PI3K, p-Akt and mTOR were detected by Western blot. Immunofluorescence was used to detect PI3K. Results: Compared with those in the model control group, the contents of CollageⅠand fibronectin in the supernatant of emod-in group significantly decreased (P<0. 05), the expression of PI3K protein was inhibited, the expression of downstream p-Akt protein decreased, and the downstream mTOR decreased (P<0. 05), the expression levels of PI3K, p-Akt and mTOR mRNA decreased, the differences were statistically significant (P<0. 05), and the expression of PI3K decreased. Conclusion: Emodin can alleviate fibrosis of HK-2 cells stimulated by TGF-β1 through the classical Akt/mTOR pathway of autophagy.

Application of Molecular Docking in the Studies on Screening and Mechanism of Pharmacodynamic Sub-stances of Traditional Chinese Medicine / 中国药师

Molecular docking is one of the main methods for computer-aided drug design (CADD). In recent years, molecular doc-king is widely used and has made some progress in the screening of pharmacodynamic substance, the target of finding drugs for diseases, and the mechanism exploration for traditional Chinese medicine. In this review, the principle and mechanism of molecular docking, and some commonly used software were introduced. And the application of molecular docking technology was summarized in the studies on the screening and pharmacodynamic mechanisms of traditional Chinese medicine. Finally, the existing problems were discussed, and the fu-ture trend in this field was looked ahead. The study can provide more scientific basis for the clinical research and development of new drugs.

Expression of interleukin-17 in peripheral blood mononuclear cells of patients with multiple myeloma / 新乡医学院学报

Objective To investigate the expression of interleukin-17 (IL-17) in peripheral blood mononuclear cells (PBMC) of patients with multiple myeloma and analyse it's clinical significance.Methods Thirty patients with multiple myeloma in the Department of Hematopathy,the Third Affiliated Hospital of Xinxiang Medical University from January 2016 to January 2017 were selected as observation group;and thirty healthy donors whose gender and age machted with patients in the observation group were selected as control group.Peripheral blood mononuclear cells were obtained from subjects in observation group and control group by using the method of density gradient centrifugation.The content of IL-17 in supernatant of PBMC culture solution of subjects in the two groups was detected by enzyme linked immunosorbent assay and the expression of IL-17 mRNA in PBMC was detected by quantitative real-time polymerase chain reaction;the cellular morphology of PBMC of subjects in control group was observed by scanning electron microscope after co-culturing with the serum of patients in observation group.Results The content of IL-17 in supernatant of PBMC culture solution of subjects in the observation group and control group was (30.79 ± 4.96),(10.10 ± 4.15) ng · L-1 respectively;the content of IL-17 in supernatant of PBMC culture solution of subjects in the observation group was significantly higher than that in the control group (t =3.412,P ＜ 0.05).The expression of IL-17 mRNA in PBMC in the observation group and control group was 4.28 ± 1.34 and 2.45 ±0.95 respectively;the expression of IL-17 mRNA in PBMC in the observation was significantly higher than that in the control group (t =2.796,P ＜0.05).After co-culturing of PBMC of subjects in the control group with the serum of patients in the observation group,the morphology of PBMC changed obviously,and membrane desquamate,membrane disintegration,even membranolysis were observed in some cells with the prolongation of co-culture time.Conclusion The over-expression of IL-17 in PBMC of patients with multiple myeloma may play a certain role in the occurrence and development of this disease.

Protective effect of emodin on renal interstitial fibrosis in mice of unilateral ureteral obstruction via PI3K/Akt/mTOR signaling pathway / 中华肾脏病杂志

Objective To investigate the effect and mechanism of emodin (EM) in renal interstitial fibrosis of unilateral ureteral obstruction (UUO) mice.Methods Male C57BL/6J mice were randomly divided into 4 groups,including sham operation group (n=8),UUO operation group (n=8),UUO operation+losartan (LST) group (n=8) and UUO operation+EM group (n=8).The mice in each group were ingested the suspensions by gavage for 14 days after surgery.Mice in UUO+LST and UUO+ EM groups were given 10 mg· kg-1· d-1 LST and 20 mg· kg-1 · d-1 EM,respectively.LST and EM were mixed with 0.5％ sodium carboxymethyl cellulose.Mice in sham group and UUO group were given 0.5％ sodium carboxymethyl cellulose.The mice were sacrificed at the 14th day.Interstitial fibrosis was observed by HE,Masson and PAS stain.Real-time PCR was used to detect LC3,Beclin-1 and mTOR mRNA.Protein expressions of TGF-β1,α-SMA,E-cadherin,LC3,Beclin-1,PI3K,p-Akt and mTOR were detected by Western blotting.The autophagy was observed with transmission electron microscopy in the renal tissue.Results Compared with sham mice,UUO mice at the 14th day displayed obvious renal fibrosis.Meanwhile,UUO mice had increased expressions of TGF-β1 and α-SMA (all P ＜ 0.01),and decreased expressions of E-cadherin (P ＜ 0.01).Their renal expressions of PI3K,p-Akt and mTOR were also raised (all P ＜ 0.01).Compared with those in UUO group,in UUO+LST group and UUO+EM group,expressions of autophagy protein LC3 and Beclin-1 were increased (all P ＜ 0.01),and the number of autophagic was increased.Additionally,expressions of TGF-β1 and α-SMA were reduced in UUO+LST group and UUO+EM group (all P ＜ 0.01),while the expression of E-cadherin was increased by emodin treatment (P＜ 0.05).And expressions of PI3K,p-Akt and mTOR were decreased in UUO + LST group and UUO + EM group (all P ＜ 0.05),meanwhile renal tissue fibrosis significantly reduced.Conclusions Emodin can promote autophagy,ameliorate renal interstitial fibrosis and protect renal function through PI3K/Akt/mTOR signaling pathway.

Application of Self-assembling Peptides to Hemostasis / 中国实验血液学杂志

As a widespread phenomenon in living system, molecular self-assembly has become the meeting point of multidisciplinary research including chemistry, biology, materials science and medicine. In recent years, the rapid development in molecular self-assembly of peptide technology is showing a great potential in the application of tissue engineering, drug delivery, bionic medicine, cosmetology field, optical and electronic product development, etc. Especially, the remarkable hemostatic effect of self-assembling peptides (SAP) on organs, nerves and brain wounds successfully promoted its application to the material science and clinical medicine. This review focuses on the hemostatic effects and characteristics of SAP on different bleeding wound models, action mechanism, its benefits and limitations as well as its adrancing trends.

Determination of yogliptin and its metabolite in Wistar rat plasma by liquid chromatography-tandem mass spectrometry / 药学学报

A rapid, sensitive and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous determination of yogliptin and its metabolite in Wistar rat plasma. Linagliptin and dexamethasone were chosen as the internal standards of yogliptin and its metabolite, (R)-8-(3-hydroxypiperidine- -yl)-7-(but-2-yn-1-yl)-1-((5-fluorobenzo[d]thiazol-2-yl)methyl)-3-methyl- H-purine-2, 6 (3H, 7H)-dione, respectively. After a simple protein precipitation using acetonitrile as the precipitating solvent, both analytes and ISs were separated on a Grace Altima HP C18 column (2.1 mm x 50 mm, 5 microm) with gradient elution using methanol (containing 0.1% formic acid, 4 mmol x L(-1) ammonium acetate)-0.1% formic acid (containing 4 mmol x L(-1) ammonium acetate) as the mobile phase. A chromatographic total run time of 4.4 min was achieved. Mass spectrometric detection was conducted with electrospray ionization under positive-ion and multiple-reaction monitoring modes. Linear calibration curves for yogliptin and its metabolite were over the concentration range of 0.5 to 500 ng x mL(-1) with a lower limit of quantification of 0.5 ng x mL(-1). The intra- and inter- assay precisions were all below 14%, the accuracies were all in standard ranges. The method was used to determine the concentration of yogliptin and M1 in Wistar rat plasma after a single oral administration of yogliptin (27 mg x kg(-1)). The method was proved to be selective, sensitive and suitable for pharmacokinetic study of yogliptin and M1 in Wistar rat plasma.

Pharmacodynamics and pharmacokinetics of batroxobin in Beagle dog / 药学学报

Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.

In vitro metabolism of forscolin isolated from Coleus forskohlii / 药学学报

This paper is to report the study of the metabolism of forscolin in plasma and liver microsomes for guiding clinical therapy. Forscolin was quantified by HPLC-MS/MS. The metabolic stability of forscolin in rat, Beagle dog, monkey and human plasma and liver microsomes, mediated enzymes of forscolin and its inhibition on cytochrome P450 isoforms in human liver microsomes were studied. Results showed that forscolin was not metabolized in plasma of the four species but metabolized in liver microsomes of the four species. The t1/2 of forscolin in rat, Beagle dog, monkey and human liver microsomes were (52.0 +/- 15.0), (51.2 +/- 5.9), (6.0 +/- 0.2) and (11.9 +/- 1.8) min; CL(int) were (75.6 +/- 18.7), (60.9 +/- 6.8), (513.8 +/- 14.3) and (176.2 +/- 25.6) mL x min(-1) x kg(-1); CL were (34.8 +/- 4.5), (23.3 +/- 1.0), (40.3 +/- 0.5) and (17.9 +/- 0.3) mL x min(-1) x kg(-1), respectively. Forscolin was metabolized by CYP3A4 in human liver microsomes. There was definite inhibition on CYP3A4 at the concentrations of forscolin between 0.1 ng x mL(-1) and 5 microg x mL(-1). Therefore, forscolin is rapidly excreted from liver microsomes. Attention should be paid to the drug interaction when forscolin was used along with other drugs metabolized by CYP3A4 in clinics.

Lidamycin metabolism in vitro / 药学学报

This paper is to report the study of the metabolism of lidamycin in vitro including in plasma and microsomes to guide clinical therapy. Lidamycin was quantified by detecting its active ingredient using HPLC-MS/MS. The metabolic stability of lidamycin in rat, Beagle dog, monkey and human plasma and liver microsomes, and its inhibition to cytochrome P450 isoforms in human liver microsomes were studied. Results showed that lidamycin was metabolized in the four species of plasma, and the sequence of metabolic rates in plasma were in rat > in dog > in human > in monkey. But among the four species of liver microsomes, lidamycin was metabolized only in monkey liver microsomes. There was almost no inhibition to cytochrome P450 isoforms at the concentrations of between 0.0005 and 10 ng x mL(-1). Therefore, the property of lidamycin metabolism in human is similar with that in dog, and metabolism of other drugs would not be decreased by cytochrome P450 as used along with lidamycin in clinic.

LC-MSn analysis of metabolites of 1,2-bis (1,2-benzisoselenazolone-3(2H)-ketone)-ethane, a novel anti-cancer agent in rat / 药学学报

This study is to elucidate the metabolic pathway of 1,2-[bis (1,2-benzisoselenazolone-3 (2H)-ketone)]-ethane (BBSKE) in rats. Rats were administrated with a single dose of BBSKE 200 mg x kg(-1). The metabolites in rat urine, feces, bile and plasma were identified by LC-MSn analysis. The characterization of fragment ions from LC-MSn chromatography and mass spectrometry was applied to the investigation of structures of metabolites. Three phase I metabolites were detected in rat urine and feces. Two of them were also found in plasma and one existed in bile. These products were derived from oxidized, methylated and S-methylated BBSKE, separately. One phase II glucuronide of BBSKE was also found in bile. Therefore, it is possible that BBSKE was metabolized by oxidization, methylation and glucuronidation.

Rapid pharmacokinetics screening of drug candidates in vitro and in vivo / 药学学报

The paper is to report the pharmacokinetic character of a series of chemical compounds in vitro and in vivo. Metabolism stability of a series of chemical compounds was screened by using rat liver microsomes. The samples of different chemical compounds were combined and then simultaneously detected by LC-MS/MS. Compounds y13, y12 and y11 were screened out by microstability assay in vitro. The pharmacokinetics of compounds y11, y12 and y13 was evaluated by using SD rat. The plasma samples were pooled at the same time. The plasma concentrations were determined by LC-MS/MS. The pharmacokinetic character of two compounds y13, y11 was good by screening in vivo, so they were developed for further research. High-throughput screening of drug candidates in vitro and in vivo was effective, to provide information for the chemical structure information and lower the drug development risk.

Recent advances in research on granulocyte colony-stimulating factor--review / 中国实验血液学杂志

Granulocyte colony-stimulating factor (G-CSF) is a kind of hematopoietic growth factor which is produced by monocytes, fibroblasts and endothelial cells. G-CSF acts on neutrophilic progenitor cells by binding to specific cell surface receptors, thereby stimulates proliferation, differentiation, commitment, and selected end-cell functional activation including enhanced phagocytic ability, priming of the cellular metabolism associated with respiratory burst, antibody dependent killing and the increased expression of some functions associated with cell surface antigens. G-CSF is effective and safe for treatment of neutropenia. In this paper, structure of G-CSF and its mechanism, recent status of research on G-CSF, pharmacokinetics, clinical application, adverse effects and prospect of G-CSF are mainly reviewed.

The effect of p21 on transcription of survivin in hepatocellular carcinoma HepG2 cells and its regulation mechanism / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the inhibitory effect of cyclin-dependent kinase inhibitor p21 on regulation of survivin transcription in human liver cancer HepG cells, and explore the related mechanisms.</p><p><b>METHODS</b>Doxorubicin (DOX) was used to treat HepG cells. Eukaryotic vector pEGFP-C2-p21 was transfected into HepG cells by lipofectamine and positive clones were screened out by G418. The mRNA expression of p21, p53 and survivin were detected by real-time fluorescent quantitative polymerase chain reaction (RQ-PCR). Flow cytometry was used to determine the cell cycle phases, and reverse transcription polymerase chain reaction (RT-PCR) was used to measure the levels of E2F-1 or p300.</p><p><b>RESULTS</b>After treatment with DOX, the expression of p53 and p21 was increased, whereas that of survivin was reduced during 24 hours of the treatment. After transfection the p21 level was 2100.1-fold or 980.9-fold enhanced in comparison with that in HepG2 cells or HepG2-pEGFP cells. Survivin level was markedly down-regulated to 0.5% or 0.6% relative to that in the other two groups, nevertheless, significant p53 changes were not observed. Overexpression of p21 resulted in G1/G0 phase arrest (F = 31.59, P < 0.01), meanwhile, E2F-1 mRNA or p300 mRNA were less expressed compared with that in the other controls (F(E2F-1) = 125.28, P < 0.05; Fp300 = 46.01, P < 0.01).</p><p><b>CONCLUSION</b>p21 could be a potential mediator of survivin suppression at transcription level in HepG2 cells, which might be through the block at G1/G0 phase and down-regulation of transcription factors E2F-1 and p300.</p>

Biotherapy of cancer by anti-EGFR monoclonal antibody / 中国实验血液学杂志

Epidermal growth factor receptor (EGFR) is mutated, dysregulated or overexpressed in many epithelial malignancies, and EGFR activation has been found to be important in tumor growth and progression. Anti-EGFR monoclonal antibodies target the extracellular domain of EGFR; and show promising anti-tumor potential at clinical trials without severe side effects. In this article the pharmacokenetics and clinical study of 3 anti-EGFR monoclonal antibodies (cetuximab, panitumumab and nimotuzomab) were reviewed.

Immunotherapy of non-Hodgkin's lymphomas (NHL) by anti-CD22 antibody--review / 中国实验血液学杂志

CD22 is a transmembrane sialoglycoprotein and a member of the immunoglobulin superfamily. Its expression is restricted to the B cell lineage and a vast majority of B cell NHLs. CD22 plays a key role in B cell development, survival, and function. Humanized anti-CD22 antibodies were developed to minimize the immunogenicity and to enhance effector interactions during their developments of diagnostic and immunotherapeutic agent. Preclinical test with anti-CD22 antibodies indicates that a single, conjugated or radiolabeled agent has shown preliminary antitumor activity in patients with recurrent and heavily pretreated NHL. Anti-CD22 antibodies were well tolerated, without dose-dependant toxicity. Anti-CD22 antibodies are currently being evaluated in combination with rituximab, and the early results suggest that the combination of the two antibodies are well tolerated and may result in better clinical activity than the single agent alone. Thus, anti-CD22 antibodies are theoretically good candidates alone and in combination with other drugs in the treatment of B cell malignancies. In this review, the physiologic function and characteristics of CD22 antigen as target molecule of guide therapy for NHL, the types of anti-CD22 antibodies in therapy of NHL and the combination use with other antibodies were summarized.

Metabolism, Distribution and Excretion of Recombinant Human Thrombopoietin in Mice / 中国实验血液学杂志

The metabolism, distribution and excretion profiles of recombinant human thrombopoietin (rhTPO) in mice were studied by means of (125)I-labeled rhTPO ((125)I-rhTPO) combined with size exclusive high performance liquid chromatography (SHPLC) or trichloroacetic acid (TCA) precipitation analysis. (125)I-rhTPO was prepared by iodogen method. Purification was performed on Sephacryl S-200 HR gel. Radioactive-purity of (125)I-rhTPO identified by SHPLC was (96.9 +/- 1.5)% (n = 3). The proliferation effect of TPO dependent cell line (TD-3) and the increase of peripheral platelet counts in mouse by (125)I-rhTPO demonstrated that (125)I-labeled protein maintained the biological activities of TPO both in vitro and in vivo. SHPLC analysis of serum and urine samples taken after sc 1 micro g/mouse (345 kBq/mouse) of (125)I-rhTPO revealed that there were two lower molecular weight (125)I-degradation metabolites ((125)I-MI and (125)I-MII) other than parent molecule. (125)I-MI was mainly found in urine, and (125)I-MII was detected both in serum and in urine. The maximal concentration of (125)I-rhTPO was reached at 2 hours after injection. The terminal half-life was 10.8 hours, which was much longer than those of other peptides. TCA precipitable radioactivity in tissue showed that the radioactivity in bone marrow was rather high. The highest level was found in urinary system. Levels in adrenals, lymph nodes, and fat were near to that in serum. Lowest was found in brain. The main excretion route was urinary system and (98 +/- 5.6)% of (125)I-rhTPO was excreted within 72 hours after dosing.