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.

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

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

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.

Estrogen has many biological activities and extensive clinical applications.Hemorrhagic shock-in-duced major organ dysfunction and injury,which are related to sex differences,play a triggering role in irreversible shock. The present article reviews the role of estrogen in alleviating hemorrhagic shock-induced organ injury by analyzing and sum-marizing the recent studies,thus expanding the clinical application of estrogen and providing a novel approach for treatment of severe hemorrhagic shock.

OBJECTIVE:To optimize extraction technology of cortex of Berberis dictyophylla by ethanol. METHODS:Using the contents of magnoflorine,jatrorrhizine hydrochloride,palmatine hydrochloride and berberine hydrochloride,the amount of extract as evaluation indexes,the effects of ethanol amount,volume fraction of ethanol and extraction time on extraction technology were investigated by uniform design method-comprehensive scoring method. The extraction methods of first time, second time and third time were investigated by 3 times of uniform design test. The optimal schemes of 3 times of extraction test were determined and validation test was conducted,and the transfer rates were calculated. RESULTS:The optimal technology was as follows as coarse powder of cortex of B. dictyophylla,15-fold 75% ethanol,extracting for 2 times,120 min each time. In validation test,the contents of magnoflorine,jatrorrhizine hydrochloride,palmatine hydrochloride and berberine hydrochloride were 58.96,4.82,3.07,23.29 mg/g after B. dictyophylla was extracted by optimization technology for 2 times. The transfer rates were 93.85%,95.02%,96.28%,94.88%,respectively(RSD=3.87%,2.64%,4.00%,3.91%,n=3). CONCLUSIONS:The optimal ethanol reflux extraction technology of cortex of B.dictyophylla is reasonable and feasible with good stability.