Objective To explore the establishment of a rat model of acute radiation-induced liver injury and sig-nificance of the dynamic changes of TGF-β1 expression.Methods Forty healthy 6-week old male SD rats were randomly divided into model group (n=30) and control group (n=10).The right liver of rats in the model group was given a single dose of 25 Gy 6 MV X-ray irradiation.Histopathological examination using HE staining and transmission electron microsco-py were conducted to observe the liver pathological changes in rats at 3, 5, and 10 days after irradiation, serum TGF-β1 was detected, and relevant indicators of liver function ( ALT, AST, ALP) were determined.Statistical analysis was per-formed using SPSS 17.0 software.Results At 3, 5 and 10 days after irradiation, early pathological changes in the liver cells were observed by electron microscopy, the expression of TGF-β1 was gradually increased with the time prolongation, and significant differences were found between the model group and the control group at different time points (P<0.05). The light microscopic observation of liver tissues did not show significant differences between the control group and model group.The liver ALT, AST, ALP at different time points did not show significant differences between the two groups ( P>0.05).Conclusion Electron microscopy can be used to evaluate the early changes of radiation-induced liver injury, pri-or to the alterations visible by routine light microscopy.TGF-β1 can be used to predict the degree of radiation-induced liver injury, and may be used as a sensitive serum cytokine in predicting the degree of radiation-induced acute liver injury.

AIMTo prepare verapamil hydrochloride controlled-onset extended-release pellets (VH-COERP) and study its release behavior in vitro. To compare the pharmacokinetic characteristics and bioavailability in six Beagle dogs after oral administration of VH-COERP and verapamil hydrochloride delayed-release pellets (VH-DRP) as reference.

METHODSThe core of VH-COERP were prepared in the fluidized bed (mini-glatt) by spraying water solution containing drugs onto sucrose-starch pellets with hydroroxy propyl methyl cellulose (HPMC) as the inner coating swelling layer and ethylcellulouse aqueous dispersion as the outer coating controlled layer. Through modifying the coating level of inner and outer layer, the VH-COERP with the optimized cumulative release profile was obtained. The concentration of VH in plasma of six dogs and its pharmacokinetic behaviors after oral administration of VH-COERP and VH-DRP at different times were studied by RP-HPLC. The pharmacokinetic parameters were computed by software program 3P97.

RESULTSThe lag time, the release behavior and the amount of VH from VH-COERP within 24 hours were not influenced by the pH of dissolution medium and post-process, but obviously influenced by the different kinds of added material in swelling layer and the coating level of the inner swelling layer and the outer controlled layer. In vitro the lag time of release profile of VH from VH-COERP was 5 h and then VH was extended release from VH-COERP in the following time. Compared with the VH-DRP, VH-COERP in vivo has an obviously lag time (4 h) , Tmax was also delayed (8 h) and the relative bioavailability was (94.56 +/- 7.64)%.

CONCLUSIONThe release profile of VH from VH-COERP was shown to be extended-release after an conspicuous lag time in vitro and in vivo. So the drug can be taken by the patient before bed time and begin to work at the morning.

Administration, Oral ; Animals ; Biological Availability ; Calcium Channel Blockers ; administration & dosage ; pharmacokinetics ; Cellulose ; analogs & derivatives ; chemistry ; Delayed-Action Preparations ; Dogs ; Drug Stability ; Hypromellose Derivatives ; Methylcellulose ; analogs & derivatives ; chemistry ; Microscopy, Electron, Scanning ; Verapamil ; administration & dosage ; chemistry ; pharmacokinetics

Purpose: Laparoscopy is being increasingly accepted for pancreaticoduodenectomy. Stapled anastomosis (SA) is used extensively to facilitate laparoscopic pancreaticoduodenectomy (LPD); however, the incidence of anastomotic bleeding after stapled gastrointestinal anastomosis is still high. Methods: One hundred and thirty-nine patients who underwent LPD using Whipple method were enrolled in our study. We performed the SA with our reinforced method (n = 68, R method) and without the method (n = 71, NR method). We compared the clinical characteristics and anastomosis methods of patients with or without gastrointestinal-anastomotic hemorrhage (GAH), and operative parameters were also compared between the anastomotic methods. Results: Of the 139 patients undergoing LPD, 15 of them developed GAH. The clinical characteristics of patients with or without GAH were not significantly different except in the anastomotic method (P < 0.001). In the univariate logistic regression analyses, only the anastomotic method was associated with GAH. Furthermore, patients with the NR method had significantly higher incidences of GAH (P < 0.001) and Clavien-Dindo grade ≥ III complications (P < 0.001). Conclusion Our retrospective analysis showed that the SA performed with reinforced method might be a reform of SA without the reinforcement, as indicated by the lower incidence of GAH. However, further research is necessary to evaluate the utility of this reinforced method.

BACKGROUNDThe signal transducer and activator of transcription 6 (STAT6) expression in lung epithelial cells plays a pivotal role in asthma pathogenesis. Activation of STAT6 expression results in T helper cell type 2 (Th2) cell differentiation leading to Th2-mediated IgE production, development of allergic airway inflammation and hyperreactivity. Therefore, antagonizing the expression and/or the function of STAT6 could be used as a mode of therapy for allergic airway inflammation.

METHODSIn this study, we synthesized a 20-mer phosphorothioate antisense oligonucleotide (ASODN) overlapping the translation starting site of STAT6 and constructed STAT6 antisense RNA (pANTI-STAT6), then transfected them into murine spleen lymphocytes and analyzed the effects of antagonizing STAT6 function in vitro and in a murine model of asthma.

RESULTSIn vitro, we showed suppression of STAT6 expression and interleukin (IL)-4 production of lymphocytes by STAT6 ASODN. This effect was more prominent when cells were cultured with pANTI-STAT6. In a murine model of asthma associated with allergic pulmonary inflammation in ovalbumin (OVA)-sensitized mice, local intranasal administration of fluorescein isothiocyanate (FITC)-labeled STAT6 ASODN to DNA uptake in lung cells was accompanied by a reduction of intracellular STAT6 expression. Such intrapulmonary blockade of STAT6 expression abrogated signs of lung inflammation, infiltration of eosinophils and Th2 cytokine production.

CONCLUSIONThese data suggest a critical role of STAT6 in the pathogenesis of asthma and the use of local delivery of STAT6 ASODN as a novel approach for the treatment of allergic airway inflammation such as in asthma.

Animals ; Asthma ; drug therapy ; metabolism ; Blotting, Western ; Cell Differentiation ; drug effects ; Cells, Cultured ; Female ; Interleukin-4 ; metabolism ; Lymphocytes ; drug effects ; metabolism ; Mice ; Mice, Inbred C57BL ; Oligonucleotides, Antisense ; chemistry ; pharmacology ; Phosphates ; pharmacology ; RNA, Antisense ; chemistry ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; STAT6 Transcription Factor ; genetics ; metabolism ; Th2 Cells ; drug effects ; metabolism

Dendritic Cells ; cytology ; metabolism ; Enzyme-Linked Immunosorbent Assay ; HEK293 Cells ; Humans ; Interferon Regulatory Factor-7 ; metabolism ; Interferon Type I ; metabolism ; Interferon-gamma ; analysis ; Interleukin-6 ; analysis ; Oligonucleotides ; metabolism ; RNA Interference ; RNA, Small Interfering ; metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, Tumor Necrosis Factor ; antagonists & inhibitors ; genetics ; metabolism