The paper is to report the study of pharmacokinetics of transdermal administered nicotine in the brain of freely moving rat by using microdialysis with stable labeled isotope as internal standard. The pharmacokinetic behavior of nicotine in Sprague Dawley rat brain was investigated after intranasal administration (3.75 mg). Brain fluid samples were collected by intracerebral microdialysis with DL-nicotine as internal standard. Concentrations of nicotine and DL-nicotine in the sample were measured by HPLC-MS/MS. Main pharmacokinetic parameters were calculated and analyzed by Das 2.0 pharmacokinetic software. The recovery of nicotine and the delivery of DL-nicotine were the same. The fate of absorption and distribution was two compartment model and the values of t1/2alpha was 170.31 min, t1/2beta was 263.30 min and the AUC(0-infinity) was 2.75 x 10(5) microg x L(-1) min separately. DL-nicotine can be used to calibrate the recovery of nicotine, and the new method of stable isotope microdialysis can be used to study the pharmacokinetics of freely moving rat. It will make sense for the treatment of addiction of tobacco and provide a new thought for the research of pharmacokinetics-pharmacodynamic combination.

Humans ; Infant, Newborn ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; congenital

[Objective]To analyze the clinical and pathological characteristics of myoepithelial carcinoma of nasopharynx,as well as its relationship with Epstein-Barr virus.[Methods]We report twelve cases of myoepithelial carcinoma of nasopharynx,study its clinical,histopathologic,and immunohistologic features,follow-up data and EBERS in-situ hybridization.[Results]Among age of patients ranged from 24 to 65 years(mean age=46 years).Imagery data demonstrated an extensive nodosity filling the nasopharynx,Of these 12 cgses,myoepithelial markers such as S-100,SMA,P63,CK14,CK5/6 and epithelial markers such as CK,CKL,CKH were not always all expressed at one case,but at less one of these two kind of markers expressed at one cage.The results of EBERS in-situ hybridization of 12 cases were negative.[Conclusion]Myoepithelial carcinoma is a low malignat tumor.It seldom takes place in nasopharynx,dispite its morphologic heterogeneity it has some special morphologic and immuohistologic characteristics as well as special result of EBERS in-situ hybridization,which may support its diagnosis.The combinde radiotherapy and chemotherapy after surgical removal of the tumor will control the recurrence and metabasis effectively.

Apoptosis of PK-15 cells induced by Foot-and-Mouth Disease Virus (FMDV) in vitro was reported in this paper. Typical cell apoptosis was detected by use of Hoechst 33258 fluorescence probe, agarose gel electrophoresis and in situ end-labeling (TUNEL). After PK-15 cells were infected by titration of 4.8 lg TCID50/mL FMDV for 32 h, apoptosis characteristics of nuclear condensation, fragmentation, accompanied by apoptotic bodies formation (Hoechst 33258 staining), 180-200 integer-fold sized pieces DNA Ladders (agarose gel electrophoresis) and strong green fluorescence dots (TUNEL) were all exhibited, and cell apoptosis was approximately 20%. In addition, the quantitative analysis of apoptosis in PK-15 cells induced by FMDV showed that apoptosis was correlated with infection of virus, and it was also time-dependent. Results indicate that FMDV can induce apoptosis of host cells and apoptosis plays an important role in the cytopathogencity effect of FMDV.

Over-expression of Fas ligand (FasL) on tumor cell surface can induce the apoptosis of specific activated tumor infiltrating lymphocytes (TILs) via the Fas/FasL pathway, leading to the formation of a site of immune privilege surrounding the tumor mass for escaping immune surveillance and promoting tumor proliferation, invasion and metastasis. The blocking effect of miR-21 on FasL-mediated apoptosis in breast cancers was investigated in this study. The expression levels of miR-21 and FasL in human breast carcinoma cell lines were detected by using RT-PCR and Western blotting. FasL as a target gene of miR-21 was identified by Luciferase assay. The apoptosis of Jurkat T lymphocytes induced by MCF-7 cells was determined by flow cytometry. It was found that in four human breast cancer cell lines, FasL expression level in MCF-7 cells was the highest, while miR-21 was down-regulated the most notably. After miR-21 expression in MCF-7 cells was up-regulated, FasL was identified as a target gene of miR-21. When the effector/target (E/T) ratio of MCF-7 cells and Jurkat cells was 10:1, 5:1 and 1:1, the inhibitory rate of apoptosis of Jurkat T lymphocytes induced by MCF-7 cells was 95.81%, 93.16% and 91.94%, respectively. It is suggested that in breast cancers miR-21 expression is negatively associated with FasL expression, and FasL is a target gene of miR-21. miR-21 targeting and regulating FasL-mediated apoptosis will bring us the possibility of a new tumor immunotherapy via breaking tumor immune privilege.

Objective To explore the expressions of Survivin and VEGF and relationship between them in hepatocellular carcinoma(HCC).Methods The expressions of Survivin protein and VEGF protein in 50 HCC.30 cirrhosis and 10 normal tissues were assessed by immunohistochemical method.The expressions of Survivin mRNA and VEGF mRNA in 50 HCC,30 cirrhosis and 10 normal tissues were assessed by in situ hybridization.Results The expressions of Survivin and VEGF in cancer tissues,cirrhosis tissues,normal tissues weresignificantly different. The expression of Survivin in HCC tissues was stronger than that in cirrhosis,but the expreesion of VEGF in cirrho- sis was stronger than that in HCC tissues.Conclusion The expression of survivin.is closely associated with the ex- pression of VEGF in HCC and they take positive correlation.The abnormal expressions of Survivin and VEGF are closely associated with the development of HCC.They may play important roles in the development of HCC.

Aim Through identification of the difunc-tionality of neuroprotection and passage of blood-brain barrier ( BBB) for RDP-BDNF fusion protein to offer a new strategy to treat brain diseases. Methods BDNF was conjugated to a novel cell penetrating peptide known as RDP which was derived from rabies virus gly-coprotein ( RVG) . The fusion protein RDP-BDNF was expressed in E. coli BL21 ( DE3 ) . After the intrave-nous injection of RDP-BDNF, the time effect curve of RDP-BDNF in the brains and serum was examined. Additionally , Morris water maze test was used to evalu-ate the effect of RDP-BDNF on scopolamine-induced amnesic mice, and the mechanism was also studied. Results RDP-BDNF could cross the BBB and exhibi-ted neuroprotective effects on the treatment of cognitive deficit induced by scopolamine in dementia model mice. Conclusions Delivery of protein therapeutics using RDP might offer a new and exciting strategy to treat brain diseases.

Objective To observe the protective effects of roscovitine on the podocyte injury induced by endoplasmic reticulum stress (ERS) caused by tunicamycin. Methods The differentiated podocytes cultured at 37℃were randomly di-vided into:(1) Control group, DMSO group and tunicamycin group (TM, 1.0μmol/L). The treatment was given for 3, 6 and 12 hours in three groups. (2) For control group, tunicamycin group, tunicamycin+roscovitine group (20, 40μmol/L, TM+ROS), the treatment was given for 12 hours. The podocyte apoptosis was detected by flow cytometry and TUNEL method. The ex-pressions of Cdk5, GRP78, Caspase-12 and CHOP were detected by Western blot assay. Results (1) Compared with con-trol group and DMSO group, the podocyte apoptosis was increased significantly in a time dependent manner after tunicamy-cin treatment in TM group;the protein expressions of Cdk5, GRP78, Caspase-12 and CHOP were also up-regulated signifi-cantly in TM group (P<0.05). (2) Flow cytometry and TUNEL analysis showed that tunicamycin induced apoptosis in podo-cytes, which was significantly inhibited by roscovitine in a concentration dependent manner in TM+ROS group as compared to that of TM group (P<0.05). The protein expressions of GRP78, Caspase-12 and CHOP were also significantly decreased in a concentration dependent manner in TM+ROS group compared to those of TM group (P<0.05). Conclusion Roscovi-tine, the inhibitor of Cdk5, can reduce the podocyte apoptosis induced by tunicamycin. The protective effects of roscovitine on podocytes can be a novel approach of treating diabetic nephropathy.

Objective To compare the effects of UVA irradiation on cell morphology,quantity and expression of inducible nitric oxide synthase (iNOS) mRNA and protein in human fibroblasts versus a kerati- nocyte cell line HaCaT.Methods Human fibroblasts and HaCaT cells were cultured and irradiated by 5 J/cm~2 UVA.Then,at 24,48 and 72 h after the stimulation,the cell morphology was observed under an in- verted microscope,and iNOS mRNA and protein were measured by RT-PCR and immunohistochemistry method,respectively.Results After the irradiation,human fibroblasts showed shrinkage at the three time points,the quantities of the cells began to decrease significantly at 24 h (P

Objective To compare the therapeutic effect of angiotensin Ⅱ antagonist (Valsartan)and angiotension-converting enzyme inhibitor (Captopril) for the improvement of left ventricular systolic function(LVSF) after acute myocardial infarction (AMI) at anterior wall. Methods A total of 75 patients with initial AMI at anterior wall were enlisted in the study. Patients were divided randomly into three groups: control group (n = 15), Captopril treated (n =30), and Valsartan treated (n =30). At 1 week and 28 weeks post AMI, the LVSF and left ventricular regional ejection fraction (LrEF) were measured by equilibrium radionuclide angiography (ERNA). The t-test was used to compare the dada. Results ( 1 ) At 28 weeks, left ventricular ejection fraction (LVEF) and left ventricular peak ejection rate (LPER) in Valsartan treated group were significantly increased as compared with those of control: ( 59.4 ± 8.6 ) % vs (44.9 ± 8.4)%, t = 3.87, P ＜ 0.01 for LVEF; (3.89 ± 1.01 ) end-diastolic volume (EDV)/s vs (2.84 ±1.05) EDV/s, t= 4.16, P ＜ 0.01 for LPER). The left ventricular time to peak ejection rate (LTPER) in Valsartan treated group was significantly decreased ( ( 116 ± 16 )ms vs ( 137 ±20) ms, t =2.16, P ＜ 0.05 ) as compared with control. (2)Compared with 1-week, 28-week Valsartan treated group had a significant increase inLrEF2, LrEF4, LrEF5, LrEF6: (71.6±18.8)% vs (57.0±11.4)%, t=2.11, P＜0.05;(78.1 ±16.8)% vs (68.9±21.0)%, t =2.06, P＜0.05; (70.5±16.9)% vs (59.9 ±23.4)%, t=1.99, P ＜ 0.05; and (58.1 ± 9.0) % vs (46.0 ± 18.9) %, t = 2.43, P ＜ 0.05, respectively. Conclusions Valsartan and Captopril are effective for the improvement of LVEF after AMI at anterior wall. The effects of the two drugs are similar.