Animals ; Blood Chemical Analysis ; Blood Circulation ; physiology ; Blood Physiological Phenomena ; Lymph ; chemistry ; physiology ; Lymphatic System ; physiology ; Male ; Rats ; Rats, Wistar ; Rheology

Objective To study the characteristics of pharmacokinetics and pharmacodynamics of insulin dry powder inhalation and its relative bioavailability as compared with subcutaneous injection of regular insulin. Methods In this open,single-center,randomized,two-period,cross-over,euglycemic glucose clamp study,18 healthy volunteers(14 men and 4 women),aged(24.9?1.7)years,with body mass index(20.6?1.2)kg/m~2, received the insulin dry powder inhalatin(80 U)or regular insulin(15 U)subcutaneous administration.The blood samples of this study at 0,20,30,40,50,60,70,80,90,100,110,120,135,150,165,180,195, 210,225,240,270,300,330,360,390,420,450 and 480 rain were taken for serum insulin measurement, meanwhile,glucose infusion rates(GIR)were determined per 5 minutes over a period of 8 hours.Results The C_(max)were(57.9?17.8 vs 114.5?29.7)mU/L(tested vs reference preparation),T_(max)were(46.7?45.6 vs 107.8?33.7)min,GIR_(max)were(3.35?0.98 vs 5.17?1.75)mg?kg~(-1)?min~(-1)and T_(GIRmax)were(88.3?17.0 vs 151.9?34.6)min.The relative bioavailability was(10.26?2.25)%,and the relative bioefficacy was(14.33?7.26)%.Conclusion The study shows that insulin dry powder inhalation is absorbed via lungs and its action sets in earlier than that of the regular insulin injected subcutaneously.These pharmacokinetie and pharmacodynamic data may provide a reliabe guide for further clinical trial.

Aged ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Cadherins ; metabolism ; Carcinoma, Merkel Cell ; metabolism ; pathology ; Carcinoma, Small Cell ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Female ; Humans ; Lymphoma ; metabolism ; pathology ; Melanoma ; metabolism ; pathology ; Phosphopyruvate Hydratase ; metabolism ; Synaptophysin ; metabolism

This article studies the thermostability and the crystal structure of a new anticancer drug dasatinib. The thermostability of dasatinib was analyzed using the differential scanning calorimeter (DSC) and thermo gravimetric analyzer (TGA), and the structural characteristics of polymorphism and crystalline transformation was determined using the X-ray powder diffractometry (XRD) with in-situ high temperature accessories. The results showed that dasatinib has at least two different crystal forms. The form-I has one crystalline water and form-II one and half, and in a heating-up processing both of them would change their crystal structures. After losing their crystalline water, both would change into the same crystalline form with no crystalline water. Their melting points were almost the same: form-I was 285.68 degrees C and form-II was 285.50 degrees C. The results of the study method would provide a comprehensive reference for the quality evaluation of dasatinib.
Antineoplastic Agents ; chemistry ; Calorimetry, Differential Scanning ; Crystallization ; Dasatinib ; Molecular Structure ; Protein Kinase Inhibitors ; chemistry ; Pyrimidines ; chemistry ; Temperature ; Thermogravimetry ; Thiazoles ; chemistry ; X-Ray Diffraction

Objective To explore the safety of the mobilization of peripheral blood stem cells(PBSC)by granulocyte colony-stimulating factor(G-CSF)in elderly donors.Methods 28 peripheral arteriosclerotic occlusive disease(PAOD)elderly patients(aged≥60 years),and 29 healthy sibling young/adult donors(aged＜60 years)for peripheral allogenic stem cell transplantation were included.Blood samples were collected immediately before starting G-CSF and prior to PBSC collection to analyze the following parameters:the WBC counts,fibrinogen(FIB),D-dimer (D-D),thrombin antithrombin complex(TAT),antithrombin(AT)and yon Willebrand factor antigen(vWF:Ag). Results It had a very significant increase in D-D and vWF:Ag and a very significant decrease of AT(P＜0.01),af- ter mobilization by G-CSF,and a increase in FIB and TAT were also observed(P＜0.05,P＜0.01)in elderly group.In the young/aduh group,the increase in FIB was significant(P＜0.05).The elevating extent of D-D and TAT after G-CSF administration was significantly higher in elderly group than that in young/adult group(P＜0.05).Compared to young/adult group,there was a significant increase in thrombotic events and cerebrovascular ac- cident(P＜0.05).Conclusion In PBCS donorsreceiving G-CSF it reveals activation of both coagulation and en- dothelial cells and inhibition of anticoagulant system that can favor the developing of thrombotic events,which is more remarkable in elderly donors.Therefore a careful monitoring for coagulation system should be considered in those elderly cases.

AIM:To observe the influence of erythropoietin (EPO) on eryptosis and production of reactive oxygen species (ROS) in erythrocytes under stimulation of hydrogen peroxide (H2O2),.and to explore its related mecha-nism. METHODS:The erythrocyte suspension (1%) was cultured in vitro and divided into 3 groups:control group (C group,the culture medium was PBS),H2O2group (H group,the culture medium was PBS containing H2O2at final con-centration of 100 μmol/L) and EPO group (E group,the culture medium was PBS containing H2O2at final concentration of 100 μmol/L and EPO at final concentration of 2×104U/L). The erythrocytes were collected at 24 h and 60 h. The eryptosis was detected by flow cytometry with Annexin V staining. The production of ROS and intracellular calcium ion con-centration (Ca2+]i) were also analyzed by flow cytometry. RESULTS:The eryptosis in C group was increased as the in-cubating time extended. The eryptosis in H group was higher than that in C group (P<0.01),while that in E group was lower than that in H group(P<0.01). Meanwhile,ROS production andCa2+]iwere higher in H group than those in C group (P<0.01), but those were lower in E group than those in H group (P<0.05 or P<0.01). CONCLUSION:EPO inhibits eryptosis induced by H2O2and its mechanism may be related to antioxidant effect and change of Ca2+]i.

The study was aimed to investigate the expression of E2A-PBX1 fusion gene in children with acute lymphoblastic leukemia (ALL). The primers located at different sites of E2A and PBX1 gene were used to screen for the fusion gene in 410 children with ALL, including 362 cases of B cell ALL and 48 cases of T cell ALL. The results showed that 17 children carried the fusion gene. The positive rate was 4.1%. Furthermore, all the positive cases expressed a variant type of fusion transcript. It resulted from different splicing of the 13th exon (159 bp) of E2A gene. Analyses with BLASTn indicated that the variant type of transcript retained the open reading frame. However, the loss of 53 amino acid residues which were located at the 2nd activation domain resulted in the partial deletion of the putative loop-helix (LH) structure as well as the complete deletion of the heptad leucine repeat. It is concluded that all the children with ALL positive for the E2A-PBX1 fusion gene express typical and variant fusion transcripts. The latter resulted from different splicing of the 13th exon (159 bp) of E2A gene. The loss of 53aa would lead to the partial deletion of the putative loop-helix (LH) structure as well as the complete deletion of the heptad leucine repeat.
Amino Acid Sequence ; Base Sequence ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 19 ; genetics ; Female ; Genetic Variation ; Homeodomain Proteins ; genetics ; Humans ; Male ; Molecular Sequence Data ; Oncogene Proteins, Fusion ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Transcription Factors ; genetics ; Transcription, Genetic ; Translocation, Genetic

OBJECTIVEThe purpose of the present study was to identify the relationship between the plasma level of adiponectin and in-stent restenosis of patients with coronary heart disease after coronary stenting.

METHODThe study population comprised 119 individuals (92 men) who underwent stent implantation, including 65 subjects without in-stent restenosis (group A) and 54 patients with in-stent restenosis (group B). The level of plasma adiponectin was measured using ELISA. Coronary angiography was performed immediately before and after implanting stent and 9 - 12 months later.

RESULTSBaseline characteristics including drug use after PCI were similar between the groups. The rate of implanting bare metal stent is 8 (12.31%) and 6 (11.11%), TAXUS drug-eluting stent is 11 (16.92%) and 10 (18.52%) and CYPHER drug-eluting stent is 46 (70.77%) and 38 (70.37%) respectively (all P > 0.05). Plasma level of adiponectin in patient of group A was significantly higher than that in group B [(15.16 +/- 5.02) mg/L vs. (10.01 +/- 4.93) mg/L, P < 0.05]. The quantitative coronary angiography (QCA) showed that lesion length was similar between groups [(15.82 +/- 6.67) mm vs. (13.40 +/- 4.20) mm, P > 0.05], minimum lumen diameter (MLD) and stenosis rate were also similar before and after implanting stent (P > 0.05) and acute gain was (1.48 +/- 0.65) mm vs. (1.19 +/- 0.37) mm (P > 0.05). MLD was higher in group A than that in group B [(2.55 +/- 0.53) mm vs. (0.57 +/- 0.60) mm, P < 0.01] at 9 - 12 months follow up. Restenosis rate [(24.2 +/- 11.2)% vs.(81.0 +/- 19.1)%, P < 0.01] and late lumen loss [(0.50 +/- 0.34) mm vs. (1.60 +/- 0.54) mm, P < 0.01] were lower in group A than in group B.

CONCLUSIONSThe lower plasma adiponectin level might be associated with in-stent restenosis after coronary stenting.

Adiponectin ; blood ; Adult ; Aged ; Coronary Restenosis ; blood ; pathology ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome

OBJECTIVETo develop the certified reference material of mercury in lyophilized human urine.

METHODSHuman urine samples from normal level mercury districts were filtered, homogenized, dispensed, lyophilized and radio-sterilized. Homogeneity test, stability inspection and certification were conducted using a atom fluorescence spectrophotometric method. The physical and chemical stability of the certified reference material were assessed for 18 months. The certified values are based on analysis made by three independent laboratories.

RESULTSThe certified values are as follows: low level was (35.6 ± 2.1) µg/L, high level was (50.5 ± 3.0) µg/L.

CONCLUSIONThe certified reference material of mercury in lyophilized human urine in this research reached the national certified reference material requirements and could be used for the quality control.

Freeze Drying ; standards ; Humans ; Mercury ; urine ; Reference Standards ; Spectrometry, Fluorescence ; Urinalysis ; standards

OBJECTIVETo investigate the relationship between CCR5 delta32 gene polymorphism and condyloma acuminata.

METHODSWe used polymerase chain reaction to amplify the CCR5 gene fragments in 60 patients with condyloma acuminata and 50 age- and sampling date-matched controls, and compared the difference of genotypes between these two groups.

RESULTSNo genotype difference was found between these two groups.

CONCLUSIONCondyloma acuminata are not associated with genetic polymorphism of CCR5 delta32 gene.

Condylomata Acuminata ; genetics ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Genetic ; Receptors, CCR5 ; genetics