QT dispersion(QTd,equals maximal minus minimal QT interval on a standard ECG) has been shown to reflect inhomogeneity of myocardial repolarization and cardial electrical instability, hence,been proposed to be associated with ventricular arrhythmias.But the intrinsical mechanism of QTd is incompletely understood. Contributing to QTd are differences of action potential duration(APD) in the three-dimensional structure of ventricular myocardium, which is identified to own three cell subtypes:endocardial, midmyocardial(M cells) and epicardial cells.And findings suggest that regional differences in the duration of the M cell action potential may lead transmural and spatial dispersion of repolarization. Autonomic nerves by combining receptors on the myocardial cells,especially M cells affect significantly the APD.Concordance between heterogeneity of ventricular myocardium and heterogeneity of autonomic innervation in heart provide support for the role of autonomic nerve in the generation of the QT dispersion.

BACKGROUND: Troponin I (Tn I ) could inhibit the growth of vascular endothelial cells, inhibit neovascularization,through which to inhibit the development and metastasis of solid tumor. Similar to Tn I, TnC also exists in non-muscular tissue, but does it has the analogous activity of anticancer like Tn I ?OBJECTIVE: To explore the effect of recombinant human TnC (rhTnC) on the growth of human umbilical vein endothelial cells (HUV-EC) and mouse xenograft tumor.DESIGN: Controlled observation in vivo and in vitro.SETTING: Research Institute of Medicine, Chongqing K.E.W Pharmaceutical Co., Ltd. and Department of Biochemistry of Chongqing Medical University.MATERIALS: The experiment was conducted in the Biochemical Laboratory of Research Institute of Medicine,Chongqing K.E.W Pharmaceutical Co., Ltd. from March 2003 to December 2004. 100 Kunming mice either male or female of 15-22 g purchased from Chongqing Academy of Chinese Materia Medica. E.coli BL21 (DE3)pLysS/pET3b-TnC provided by Chongqing K.E.W Pharmaceutical Co., Ltd. HUV-EC (Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences).METHODS: Human TnC cDNA was obtained from human thymus cDNA library using PCR. The colony was cloned in E.coli and a bacterial strain of gene engineering E.coli BL21 (DE3) pLysS/pET3b-TnC was obtained, which could express hTnC. The recombinant human TnC (rhTnC) was purified with affinity chromatography of Ni-NTA agarose. ①In vitro cell experiment: HUV-ECs were seeded in the 96-well plates at density of 2×103 cells per well and co-cultured with rhTnC of 1, 5, 10, and 50 mg/L for 3 days. The absorption (A value) was detected with microplate reader at 540 nm and the inhibition rate of cell growth was calculated. Meanwhile, the 50% inhibiting dose (IC50 value) was assayed by LOGIT method. ②In vivo animal experiment: Ascites tumor (S-180) that had been inoculated for 7-8 days was harvested. The tumor cells were diluted to 1 ×1010 L-1 and 0.2 rnL was subaxillarily and intraperitoneally injected into each mouse (50 mice in each group). The next day, the mice were randomly divided into 5 groups: rhTnC 20 mg/kg group, rhTnC 10 mg/kg group, rhTnC 5 mg/kg group, Cyclophosphamide (Cy) group and control group with 10 mice in each group. The rhTnC 20,10 and 5 mg/kg groups were given administration at the corresponding doses, once a day for 7 days; 50 mg/kg Cy was given the Cy group one after an interval of day, and the same volume normal saline was given to the control group. One day after the last time of administration, all mice were killed and the tumor was harvested and weighed. The inhibition rate of tumor growth was calculated: tumor inhibition rate=[(Average weight of tumor in control group-Average weight of tumor in drug group)/Average weight of control group]×100%.MAIN OUTCOME MEASURES: Inhibition rate of rhTnC to HUV-EC proliferation in cell experiment in vitro and mouse xenograft tumor in animal experiment in vivo.RESULTS: ①In vitro cell culture showed that rhTnC suppressed HUV-EC proliferation in a dose-dependent manner (IC50=7.5 mg/L). ②Similar to the result of in vitro cell experiment, after intraperitoneal administration, the inhibition rate of rhTnC 5, 10, and 20 mg/kg groups was higher than that of control group (P ＜ 0.01); after subaxillary administration, the inhibition rate of rhTnC 5, 10, and 20 mg/kg groups was also higher than that of control group (P ＜ 0.05-0.01). There was no significant difference in the inhibition rate between two administration approaches (P ＞ 0.05).CONCLUSION: rhTnC is capable of inhibiting the proliferation of HUV-EC dose-dependently, and displays the activities of inhibiting the proliferation of HUV-EC and anti-tumor.

Three encoding sequence genes (Lab, 3C, 3D) from 19 isolates of O-serotype of foot and mouth disease virus(FMDV) were down-loaded from GenBank. And the coding and amino acid sequences of 3 FMDV proteases (Lpro, 3Cpro, 3Dpol) were compared with the FMDV OA/58 serotype Lab, 3C, 3D sequences abstracted in our laboratory and qualified by variance analysis and multiple analysis(Duncan method). The experimental results revealed that the Lab, 3C and 3D genes had similar nucleotide mutation rates(P>0.05). However, overall analysis of the amino acid substitutions revealed that the Lpro- coding region was more prone to amino acid alterations than 3Cpro and 3Dpol- coding regions(P<0.01), but via multiple comparison, at the amino acid mutation, both 3Cpro and 3Dpol showed no significant difference. Depending on Swiss--pdb-Viewer sofe to simulate amino acid alterations at mutation hotspots, the findings showed that these alterations at hotspots failed to ruin the spatial structures of these 3 proteases. This result presents that the nucleotide mutation just acts on dynamics related to FMDV mutation, but the real evolutionary power must depend on the infected host cells to select functions with each viral proteases.

Objective To investigate the role of nuclear factor ?B activation in the onset of acute coronary syndrome(ACS).Methods 76 patients with acute myocardial infraction(AMI),41 patients with unstable angina pectoris(UAP),43 patients with stable angina pectoris(SAP)and 20 normal controls were enrolled.NF-?B activation in monocytes in peripheral blood monocyte was determined by ELISA with the NF-?B p65 Kit the at 3 and 5 days after admission.Results The activity of NF-?B in monocytes of peripheral blood in AMI patients and UAP patients was significantly higher than that in SAP patients and normal controls(P

BACKGROUND: It demonstrated that combined application of thymosin α 1 (TM-α1) and interferon (IFN) can enhance the antiviral activity of IFN.OBJECTIVE: To obtain recombinant fusion protein of TM- α1 and consensus IFN α (IFN α -con) with double activity of antiviral activity and immunity enhancement.DESIGN, TIME AND SETTING: The in vitro contrast experiment was conducted in the Biochemical Laboratory of Research Institute of Medicine, Chongqing K.E.W Pharmaceutical Co., Ltd. from March 2003 to December 2004.MATERIALS: The fusion gene fragment (TM- α 1+IFN α -con) was synthesized by Shanghai Sangon Biological Engineering Technology And Service Co., Ltd, WISH cell, and vesicular stomatitis virus (VSV) was purchased from Institute of Biochemistry and Cell Biology, commercial products of IFN α 1b, IFN α 2a and TM- α 1 was served as reference substance.METHODS: The preference for E. coli of fusion sequence coding TM- α 1 and IFN α -con were cloned into expression vector of pET-22b(+) and expressed in BL21(DE3)-Codon plus-RP-X, which was purified by precipitation of (NH4)2SO4, hydrophobic interaction chromatography, anion-exchange chromatography, cation-exchange chromatography and molecular exclusion chromatography. The antiviral activity of fusion protein was tested by cytopathic-effect inhibition assay, and effect of fusion protein on lymphocyte proliferation was tested by cell proliferative assay.MAIN OUTCOME MEASURES: The specific activity of fusion protein and its biological activity in promoting lymphocyte proliferation.RESULTS: The fusion protein was expressed as a soluble form, accounting for over 20% of the total cell protein in E. coli, which approached 96% after purification. The antiviral activity of fusion protein was superior to IFN α 1b and IFN α 2a. However, the activity of fusion protein for promoting lymphocyte proliferation was similar to TM- α 1.CONCLUSION: The fusion protein of TM- α 1 and IFN α -con expressed in E. coli has both effects on anti-virus and promoting lymphocyte proliferation.

Integrins are members of a ubiquitous membrane receptor family which includes 18 different α subunits and 8 β subunits forming more than 20 α/β heterodimers. Integrins play key functions in vascular endothelial cell and tumour cell adhesion, lymphocyte trafficking, tumor growth and viral infection. Current understanding of the molecular basis of integrins as viral receptors has been achieved through many decades of study into the biology of transmembrane glycoproteins and their interactions with several viruses. This review provides a summary of the current knowledge on the molecular bases of interactions between viruses and integrins, which are of potential practical significance. Inhibition of virus-integrin interactions at the points of virus attachment or entry will provide a novel approach for the therapeutic treatment of viral diseases.

Aim To observe the effect of gypenosides ( GP) on the expression of receptor for advanced gly-cated endproducts ( RAGE ) and transforming growth factor-β1 ( TGF-β1 ) in human mesangial cells( HMCs) induced by AGEs. Methods HMCs were cultured in DMEM of low glucose containing 15% fetal bovine ser-um in vitro, which were divided into four groups: the normal group, model group, GP group and positive control group. In addition to the normal group, the other groups were stimulated by AGEs ( 200 mg · L-1 );furthermore, GP group was intervened with dif-ferent concentrations(25,75,175 mg·L-1) of GP, while control group was given 10 mmol · L-1 of amin-oguanidine hydrochloride. The expression of RAGE and TGF-β1 protein of each group was detected by Western blot; the expression of RAGE and TGF-β1 mRNA of each group was detected by RT-PCR. Re-sults The expression of RAGE, TGF-β1 protein and mRNA in HMCs induced by AGEs in the model group was significantly higher than that of the normal group ( P<0. 01 );compared with the positive control group ( P<0. 01 ) , GP could obviously reduce the expression of RAGE, TGF-β1 protein and mRNA in a dose-de-pendent manner. Conclusion GP can reduce the ex-pression of RAGE in HMCs induced by AGEs, block AGEs-RAGE signaling pathway and decrease the ex-pression of the downstream factor TGF-β1 , therefore, it plays the role in the resistance of rennal fibrosis in DN.

Objective To investigate the protective effect of angiotensin-converting enzyme inhibitor (ACEI) on kidney function in patients with sepsis.Methods Eighty-seven patients with sepsis were randomly (random number) divided into the routine treatment (A group,n ＝45) and the ACEI intervention group (B group,n =42).Patients were managed by international guidelines for sepsis in A group and were treated with benazepril (ACEI) 20 mg a day in addition in B group.Serum creatinine and cystatin C were detected and APACHE Ⅱ scores and urine output were recorded on the 1st,3rd and 7th day.Those laboratory findings and APACH Ⅱ score were compared between two groups.The incidence of acute kidney injury (AKI) and abnormal cystatin C levels were compared between two groups.Results In B group,serum creatinine and cystatin C of patients were lower compared with A group.The incidence of AKI and abnormal cystatin C and APACHE Ⅱ scores were reduced in B group compared with the A group.Conclusions Benazepril improved sepsis-induced AKI and patient conditions.

AIM: To observe and study the influence of cardiac sympathetic nerve on QT dispersion (QTd) and the circadian variations of QTd in experimental rabbits. METHODS: The rabbits were divided into experimental group (without cardiac sympathetic control by operation) and control group (with retained cardiac sympathetic control by operation, sham operation). QTd of both groups were measured and compared before and after the operation. The circadian variations of QTd were also observed in both groups. RESULTS: QTd in experimental group decreased significantly after the cardiac sympathetic nerves were excised (P

Background Nanoemulsions (NEs) is one of the most popular ophthalmic colloidal drug delivery system due to its long-term stability, low toxicity and irritancy, considerable capacity for solubilization of lipophilic drug molecules and great potential in bioavailability improvement.The cornea pathway is the main route of intraocular absorption after topical use of NEs.Though NEs possess numerous physiological and physicochemical advantages,the use of NEs cannot always obtain satisfactory results.Objective This study was to investigate the impacts of epithelium and stroma on the corneal permeation of topical ophthalmic terbinafine hydrochloride nanoemulsions (TH-NEs).Methods TH-NEs was prepared by the self-emulsification method.The size and Zeta potential of the oil droplets in the formulation were analyzed using a dynamic light-scattering particle size analyzer.The high performance liquid chromatography (HPLC) was used for the in vitro release study.Sixty New Zealand albino rabbits were randomly divided into intact cornea group and cornea epithelium debrided group.The cornea epithelium of the left eyes was debrided in the cornea epithelium debrided group.The TH-NEs were instilled into the lower conjunctival sac of left eyes.Six rabbits were executed from each group 15,30,60,120 and 240 minutes after dosing,respectively.The corneas were collected and analyzed by HPLC.The fluorescein diacetate (FDA) was used to label the TH-NEs.Two C57BL/6 mice with left cornea epithelium debrided and 2 normal mice were used for the fluorescence tracing study.The fluorescence distribution of FDA labeled TH-NEs was observed by a two-photon laser confocal scanning microscope 30 minutes and 60 minutes after single instillation.Results The average size and Zeta potential of the oil droplets were 51.37 nm and-0.232 7 mV respectively,and 0.482％ of encapsulated drugs was released from the TH-NEs after 12 hours.The peak concentrations of TH in the intact cornea and epithelium debrided cornea were (17.85 ± 2.79) μg/g and (4.40± 1.75) μg/g respectively, which occurred 15 minutes postdose.The drug concentrations in the intact cornea were significantly higher than that in the debrided cornea 15,30,60 and 120 minutes after dosing, with significant differences between them (t =9.998,8.658,6.903,7.576;all at P=0.000).The fluorescence was observed in the cornea epithelium when the cornea was intact.The fluorescence intensity in the superior layer of corneal epithelium was obviously higher than that in the deep layers of corneal epithelium 30 minutes and 60 minutes after dosing.No fluorescence was observed in the cornea stroma of both eyes.Conclusions The cornea epithelium is the main of absorption and distribution position of TH-NEs.The cornea stroma is the dominating permeation barrier for the intraocular transportation of the TH-NEs.The cornea stroma may stop the permeation of TH-NEs by molecular exclusion mechanism.