AIMTo investigate the complexation of prostaglandin E1 (PGE1) with hydroxylpropyl-beta-cyclodextrin (HP-beta-CD) in aqueous solutions, inclusion molar ratio of the host and guest molecules and change of thermodynamic parameters during the complexation process.

METHODSThe measurements of the complexation mechanism, inclusion molar ratio of the host and guest molecules and change of thermodynamic parameters were carried out by the following methods separately: phase solubility method, UV absorption spectroscopy, circular dichroism spectroscopy, equimolar series method and thermodynamic method, respectively.

RESULTSThat all the phase solubility diagrams showed a typical AL-type in various pH buffered solutions, suggested the formation of a soluble complex of 1:1 molar ratio. Both UV absorption spectroscopy and circular dichroism spectroscopy confirmed that the significant interaction between the host and guest molecules was probably due to the inclusion of chromophore moiety of PGE1 molecule into the hydrophobic cavity of HP-beta-CD molecule. The change in the thermodynamic parameters suggested that the complexation could proceed spontaneously along with the release of heat and the decrease of entropy.

CONCLUSIONAn 1:1 molar ratio inclusion complex of PGE1 with HP-beta-CD could be formed spontaneously and, hence, the solubility of PGE1 in aqueous solution increased. Appropriate temperature and suitable media pH probably favor the progress of complexation procedure.

2-Hydroxypropyl-beta-cyclodextrin ; Alprostadil ; administration & dosage ; chemistry ; Hydrogen-Ion Concentration ; Solubility ; Technology, Pharmaceutical ; methods ; Temperature ; beta-Cyclodextrins ; administration & dosage ; chemistry

The pharmacodynamics of prostaglandin E1 (PGE1) administered by different routes to rats was investigated in this paper. The hypotensive effect of PGE, was used as an index of drug efficacy, pharmacodynamic parameters such as time to reach peak effect (Tmax), maximal percentage of blood pressure decrease (Emax, %), duration of effect (Td), and the area under the blood pressure decrease percent-time curves (AUC, % x min) were determined after PGE1 given to rats intranasally, sublingually, intraperitoneally (ip), and intramuscularly (im), separately, and compared with those obtained from intravenous (iv) administration. Similar to iv route, the pharmacodynamic parameters of PGE1 from the other administration routes, Emax, Td and in particular AUC values were all increased with increasing doses, showing dose-efficacy relationship. Tmax was found to be approximately 3-4 min for nasal route, 3-8 min for im, 6-8 min for ip and 12-30 min for sublingual route, separately. Thus, the order of magnitude of absorption rate of the drug was as follows: nasal approximately = im > ip > sublingual. If the pharmacological bioavailability (PF) for each administration route was used as a tentative measure of drug absorption extent, the order of magnitude of absolute bioavailability appeared as follows: nasal > im approximately = ip > sublingual. Furthermore, the interindividual difference was found to be larger for im and ip route than that for nasal and sublingual route. These results indicate nasal and sublingual routes are two promising routes for the systemic delivery of PGE1 in clinical applications.
Administration, Intranasal ; Administration, Sublingual ; Alprostadil ; administration & dosage ; pharmacokinetics ; pharmacology ; Animals ; Area Under Curve ; Biological Availability ; Blood Pressure ; drug effects ; Dose-Response Relationship, Drug ; Injections, Intramuscular ; Injections, Intraperitoneal ; Injections, Intravenous ; Male ; Rats ; Rats, Wistar

OBJECTIVETo investigate the drug resistance of imipenem-resistant (IR) Gram-negative bacilli (GNB) in coal workers' pneumoconiosis (CWP)-chronic obstructive pulmonary disease (COPD) patients with lower respiratory tract infection (LRTI) and to provide a basis for clinical treatment.

METHODSSixty-six strains of IR-GNB were isolated from the sputum of CWP-COPD patients with LRTI, and the bacterial spectrum was investigated. The drug resistance of bacterial strains was studied by KB disk diffusion method.

RESULTSAmong the 66 strains of IR-GNB, 29 (43.9%) were Pseudomonas aeruginosa, 17 (25.8%) were Acinetobacter baumannii, and 11 (16.7%) were Stenotrophomonas maltophilia. The drug sensitivity test showed that all bacteria had high drug resistance; Pseudomonas aeruginosa had a susceptibility rate higher than 50% to ciprofloxacin, polymyxin B, fosfomycin, and amikacin, Acinetobacter baumannii had a susceptibility rate higher than 55% to fosfomycin, polymyxin B, and cefoperazone/sulbactam, Stenotrophomonas maltophilia had a susceptibility rate higher than 50% to cotrimoxazole, ciprofloxacin, piperacillin/tazobactam, levofloxacin, polymyxin B, and cefoperazone/sulbactam, and Pseudomonas cepacia had a susceptibility rate higher than 50% to piperacillin/tazobactam, ciprofloxacin, cefoperazone/sulbactam, and polymyxin B.

CONCLUSIONThe main species of IR-GNB are such non-fermentative bacteria as Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia in CWP-COPD patients with LRTI. These bacteria have high drug resistance and are sensitive to only a limited range of antibiotics.

Aged ; Aged, 80 and over ; Anthracosis ; complications ; microbiology ; Drug Resistance, Multiple, Bacterial ; Gram-Negative Bacteria ; drug effects ; Humans ; Imipenem ; pharmacology ; Microbial Sensitivity Tests ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; complications ; microbiology

OBJECTIVETo study the impact of the chloride channel dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) on the cytoskeleton of Sertoli cells in the mouse.

METHODSTM4 Sertoli cells were cultured and treated with CFTR(inh)-172 at the concentrations of 1, 5, 10 and 20 μmol/L for 48 hours. Then the cytotoxicity of CFT(inh)-172 was assessed by CCK-8 assay, the expressions of F-actin and Ac-tub in the TM4 Sertoli cells detected by immunofluorescence assay, and those of N-cadherin, vimentin and vinculin determined by qPCR.

RESULTSCFTR(inh)-172 produced cytotoxicity to the TM4 Sertoli cells at the concentration of 20 μmol/L. The expressions of F-actin and Ac-tub were decreased gradually in the TM4 Sertoli cells with the prolonging of treatment time and increasing concentration of CFTR(inh)-172 (P < 0.05). The results of qPCR showed that different concentrations of CFTR(inh)-172 worked no significant influence on the mRNA expressions of N-cadherin, vimentin and vinculin in the Sertoli cells.

CONCLUSIONThe CFTR chloride channel plays an important role in maintaining the normal cytoskeleton of Sertoli cells. The reduced function and expression of the CFTR chloride channel may affect the function of Sertoli cells and consequently spermatogenesis of the testis.

Actins ; metabolism ; Animals ; Benzoates ; pharmacology ; Chloride Channels ; physiology ; Cystic Fibrosis Transmembrane Conductance Regulator ; antagonists & inhibitors ; Cytoskeleton ; drug effects ; Male ; Mice ; Sertoli Cells ; drug effects ; metabolism ; Spermatogenesis ; Thiazolidines ; pharmacology ; Time Factors

Objective Data on the leukapheresis from 26 pediatric patients with hematologic or solid malignancies was retrospectively evaluated to screen predictive factors affecting the efficacy of peripheral blood stem cell(PBSC) collection from donors,as well as hematopoietic recovery in recipients.Methods We present our experience with 49 apheresis from 26 granulocyte-colory Stimulating factor mobilized donors and analyzed the correlations between the mobilization,the leukocyte count in the donor peripheral blood and the MNC and CD_(34)~+ cell yields in collecting products and the neutrophil and platelet recovery of recipients.Results The process of mobilization and apheresis were well tolerated by our pediatric donors.The median numbers for harvested MNCs and CD_(34)~+ cells were 4.5?10~8/kg and 1.9?10~6/kg of recipient body weight,respectively.Mobilizing dose positively affected the number of mononuclear ceus(MNC) but not CD_(34)~+ cells in the apheresis products.The CD_(34)~+ cell number in the apheresis product was influenced significantly by donor circulating MNC on the day of harvest and correlated with recipient′s engraftment after PBSC was reinfused.Conclusions The MNC yield was stable and met with the demand for autologous stem cell transplantation while the CD_(34)~+ cell number varies obviously from each donor.Since a rapid engraftment was associated with a high number of CD_(34)~+ cells collected,which was in turn predicted by the level of the pre-apheresis CD_(34)~+ cells in the peripheral blood of donors,it is necessary to monitor the donors′ CD_(34)~+ cell during mobilization to determine the optimal time for apheresis.J Appl Clin Pediatr,2006,21(3):148-150

OBJECTIVETo evaluate the applicative value of higenamine used as a new agent for pharmaceutical stress test in detection of coronary artery disease by radionuclide myocardial perfusion imaging.

METHODSThirteen pigs with chronic coronary artery stenosis by placement of the Ameroid constrictor in the middle section of left anterior descending artery were included in this study. Rest, higenamine and dobutamine stress radionuclide myocardial perfusion imaging was performed with Tc-99m-sestamibi.

RESULTSThe sensitivity for detection of coronary artery disease by radionuclide myocardial perfusion imaging was 85% in both higenamine and dobutamine stress imaging. Imaging scores (9.9 +/- 8.5 vs. 9.4 +/- 8.6, P = NS) and defect severity (68% +/- 12% vs. 68% +/- 15%, P = NS) showed no significant difference between higenamine and dobutamine stress test. Agreement of imaging scores between higenamine and dobutamine stress imaging was good (kappa = 0.849, P < 0.0001).

CONCLUSIONOur study demonstrates that detection of coronary artery stenosis and ischemic myocardium by myocardial perfusion imaging with higenamine is highly sensitive.

Alkaloids ; Animals ; Coronary Disease ; diagnostic imaging ; Dobutamine ; Heart ; diagnostic imaging ; Sensitivity and Specificity ; Swine ; Tetrahydroisoquinolines ; Tomography, Emission-Computed, Single-Photon ; methods

AIMTo study the pharmacokinetics and relative bioavailability of probucol inclusion complex capsule.

METHODSFollowing oral administration of a single dose of 250 mg of conventional tablet (formulation A, purchased from the market) and probucol inclusion complex capsule (formulation B, a new formulation for preclinical trial) to each of 6 healthy dogs in a randomized crossover design, the plasma levels of the active drug at different time points were determined by HPLC and the plasma concentration-time profiles of formulation A and B were obtained. The pharmacokinetic parameters as well as relative bioavailability were analyzed.

RESULTSThe concentration-time curves of formulation A and formulation B were found to fit a two-compartment open model. The Tmax values of formulation A and formulation B were (9.3 +/- 2.1) h and (9.3 +/- 2.1) h, the Cmax values were (1.5 +/- 1.0) microgram.mL-1 and (2.3 +/- 0.9) microgram.mL-1 and the AUC0-240 values were (85 +/- 56) microgram.h.mL-1 and (134 +/- 55) microgram.h.mL-1, respectively. The relative bioavailability of formulation B was found to be (198 +/- 90)% compared with formulation A. The results of variance analysis and two one-side t-test showed that there was significant difference between the two formulations in the AUC0-240.

CONCLUSIONThe high bioavailability by the inclusion of formulation B is attributed to the improvement of its water-solubility by the inclusion process and this is supposed to be a key factor for improving drug bioavailability.

Administration, Oral ; Animals ; Anticholesteremic Agents ; administration & dosage ; pharmacokinetics ; Biological Availability ; Capsules ; Dogs ; Female ; Probucol ; administration & dosage ; pharmacokinetics ; Random Allocation ; Tablets

OBJECTIVETo assess the prognostic value of minimal residual disease (MRD) in childhood B-cell acute lymphoblastic leukemia (ALL) after induction chemotherapy.

METHODSFrom September 2001 to October 2004, 102 patients with newly diagnosed B-ALL were enrolled in protocol ALL-XH-99. MRD after induction therapy, before high-dose methotrexate and early intensification as well as at 1 year and 2 year maintenance therapy was detected by multiparameter-flow-cytometry (MP-FCM).

RESULTS(1) The probability of 39-month event-free survival (EFS) for patients with a level of MRD < 10(-4), was significantly higher than for those with a higher MRD [(83.00 +/- 9.90)% vs 0.00%, P < 0.01]. (2) Univariate analysis indicated that the MRD level at achieving complete remission (CR) had no relationship with the biologic features at presentation (gender, age, white blood cells and cytogenetic abnormalities), but did with Philadelphia chromosome, the time reaching CR, ALL-XH-99 risk group and lymphoblasts in bone marrow on day 19 after induction therapy (P < 0.05). (3) Multivariate analysis suggested that MRD level after the first induction course was an independent prognostic factor (hazard ratio, 5.381; 95% CI 0.004 to 0.624; P < 0.05).

CONCLUSIONThe MRD level at achieving CR is one of important prognostic factor in the treatment of childhood B-cell ALL, and might be used to assess the early treatment response.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Leukemia, B-Cell ; drug therapy ; Male ; Neoplasm, Residual ; diagnosis ; Prognosis ; Remission Induction

OBJECTIVETo secreted express envelope glycoprotein (E) of dengue virus type 2 extracellularly.

METHODSThe entire prM/E gene was amplified by RT-PCR. An optimized signal sequence gene from Japanese encephalits virus (JEV, SA14-14-2 strain) was introduced using fusion PCR. The impact of E protein transmembrane and cytoplasmatic domains was compared by amplifying prM and E with full length of E gene, with 20% truncation of the E gene at 3' terminus and one chimeric gene, which was generated by replacing the 3' terminal 20% region of E gene with the corresponding sequence of JEV (SA14-14-2 strain). The PCR segments were inserted into the NheI and NotI sites of pcDNA5/FRT vector or into the NheI and XhoI sites of pAcUW51-M. Then they were transfected into 293T cells or Sf9 cells respectively. The expression and secretion of E protein were detected by immunofluorescence assay (IFA) and Western Blot.

RESULTSAfter transected into 293T cells or Sf9 cells, all constructs expressed E protein intracellularly indentified by IFA while only two plasmids could secret detectable E protein into tissue culture using Western Blot analysis.

CONCLUSIONSignal peptide as well as the transmembrane and cytoplasmatic domains is crucial for the secretion of dengue E protein.

Animals ; Cell Line ; Dengue ; metabolism ; virology ; Dengue Virus ; genetics ; metabolism ; Gene Expression ; Humans ; Protein Structure, Tertiary ; Protein Transport ; Spodoptera ; Viral Envelope Proteins ; chemistry ; genetics ; metabolism

In order to detect the nucleic acid of Puumala hantavirus, RNA was extracted from lungs of bank voles captured in Northeast China, and partial S and M genome segments of Puumala virus were amplified by RT-PCR and sequenced. Phylogenetic analysis suggested that Chinese Puumala virus had diverged from the common node of PUUV, with accumulating nucleotide substitutions and formed a distinct lineage from other Puumala viruses. Newly found Puumala virus was most closely related to the Kamiiso-8Cr-95 and Tobetsu-60Cr-93 strains which came from Japan and the muju strains which came from South Korea. By analysis of S and M genome segments of Puumala virus, we deduced a new Puumala virus subtype did exist in Northeast China.
Animals ; Base Sequence ; Cercopithecus aethiops ; China ; Evolution, Molecular ; Genome, Viral ; Hantavirus ; genetics ; Molecular Sequence Data ; Phylogeny ; Puumala virus ; classification ; genetics ; isolation & purification ; Reverse Transcriptase Polymerase Chain Reaction ; Rodentia ; virology ; Sequence Analysis, DNA ; Vero Cells