Animals ; Genetic Therapy ; Vestibular Diseases ; therapy

BACKGROUND: Temperature-responsive magnetic pluronic nanoparticles possess the capacity of drug release controlled by body temperature and can penetrate blood brain barrier.OBJECTIVE: To detect the capacity of magnetic pluronic nanoparticles to carrying ganglioside-1(GM-1) and its capacity of drug release in vivo, as well as its effects on repair of spinal cord injury.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the key laboratories of Beijing Institute for Neuroscience, Capital Medical University and Institute of Process Engineering, Chinese Academy of Sciences between June 2006 and February 2007.MATERIALS: GM-1 loaded magnetic pluronic nanoparticles were prepared by Laboratory of Separation Science and Engineering State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences. GM-1 was provided by Trb Pharma S.A of Argentina.METHODS: Twenty Sprague-Dawiey rats were developed into acute complete spinal cord injury models and were then evenly MAIN OUTCOME MEASURES: Behavior evaluation and quantitative analysis (nerve fibers and glial cells) at 4 weeks post-surgery.were significantly greater in the treatment group than in the remaining 3 groups (P < 0.05), the control groups exhibited greater numbers of nerve fibers than the sham-operation groups, and the control group 2 had higher levels compared with the control compared with the remaining 3 groups (P < 0.05). In the rostral areas, the control groups exhibited higher area ratio of glial cells than the sham-operation group (P < 0.05), and in the caudal areas, control group 2 displayed higher levels compared with the sham-operation group (P < 0.05).CONCLUSION: Magnetic pluronic nanoparticles possess drug-carrying and drug-releasing capacities. GM-1 loaded magnetic pluronic nanoparticies can repair spinal cord injury and promote nerve regeneration.

OBJECTIVETo investigate the efficacy of a 96-week course of nucleos(t)ide analogue and interferon (IFN) combination therapy for achieving seroconversion at 24 weeks after completion in patients with chronic hepatitis B (CHB).

METHODSOne-hundred-and-thirty-five CHB patients with positivity for hepatitis B e antigen (HBeAg) were recruited for study between January 2005 and December 2008. All patients were given a 96-week course of nucleos(t)ide analogue (lamivudine or adefovir dipivoxil) alone (monotherapy controls, n = 45) or in combination with IFN or Pegylated-IFN-alpha-2a (Peg-IFNa-2a) (n = 90). At treatment weeks 12, 24, 48, 72, and 96, and at 24 weeks after treatment completion, serum samples were collected from all patients for assessment of biochemical, virological and serological responses to treatment. The biochemical response was indicated by normalization of the alanine aminotransferase (ALT) level. The virologic response was indicated by a reduction in the hepatitis B virus (HBV) DNA level to less than 1000 copies/ml. The serological response was indicated by seroconversion of either HBeAg or hepatitis B surface antigen (HBsAg). Statistical analysis was performed with the Chi-squared test.

RESULTSAmong the patients treated with nucleos(t)ide analogue and IFN combination therapy, 41.1% (37/90) achieved HBeAg seroconversion and 18.9% (17/90) achieved HBsAg seroconversion at the end of treatment. However, significantly less of the patients treated with nucleos(t)ide analogue monotherapy achieved HBeAg seroconversion and none achieved HBsAg seroconversion by end of treatment (33.3% and 0%, respectively; x2= 8.08, P less than 0.01 vs. the combination therapy group). Age stratification of the 17 HBsAg-seroconverted patients treated with combination therapy indicated that the HBsAg seroconversion rate was significantly higher in patients less than 30-years-old than those 30 and older (x2= 12.62 and 4.24, respectively, P less than 0.05). At post-treatment week 24, the 17 HBsAg-seroconverted patients treated with combination therapy showed HBsAg titers of less than 250 IU/ml; moreover, 11.8% (2/17) of these patients remained HBeAg-positive and 17.6% (3/17) showed abnormal ALT levels and elevated HBV DNA.

CONCLUSIONProlonged nucleos(t)ide analogue plus IFN combination therapy can significantly improve the rate of HBsAg seroconversion in HBeAg-positive CHB patients, and this treatment regimen is especially efficacious in patients under the age of 30.

Antiviral Agents ; therapeutic use ; Follow-Up Studies ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo investigate the effect of baicalein on the gap junction intercellular communication (GJIC) in the TM4 Sertoli cells of the mouse testis and its related mechanism.

METHODSWe measured the cytotoxicity of different concentrations of baicalein on the TM4 Sertoli cells in the mouse testis by MTT, detected the fluorescence transfer of the TM4 Sertoli cells by parachute assay, and determined the expression of the protein connexin 43 ( Cx43) in the baicalein-treated cells by Western blot and immunofluorescence assay.

RESULTSBaicalein produced no obvious cytotoxicity on the TM4 Sertoli cells at the concentration below 60 µmol/L but significantly increased their GJIC at 0-20 µmol/L (P < 0.01). Western blot and immunofluorescence assay showed that 0-20 µmol/L baicalein remarkably elevated the expression of Cx43 in the TM4 cells (P < 0.01) and on the membrane of the TM4 cells.

CONCLUSIONBaicalein at the concentration of 0-20 µmol/L can significantly enhance GJIC in mouse TM4 Sertoli cells by increasing the expression of the Cx43 protein.

Animals ; Cell Communication ; drug effects ; Connexin 43 ; metabolism ; Flavanones ; administration & dosage ; pharmacology ; Gap Junctions ; drug effects ; Male ; Mice ; Sertoli Cells ; drug effects ; metabolism ; ultrastructure

G protein-coupled receptors (GPCRs) are the largest cell surface receptor family, which mediates activities of almost all known cellular response to ligands, including hormones release, neurotransmitters and sensory input.GPCRs can promote development and progression of gastric cancer, colorectal cancer, lung cancer and breast cancer and other tumors.Tyrosine kinase receptors (RTKs) are another important family of membrane receptors, which can regulate cell proliferation, differentiation, migration and survival.Overexpression of RTKs has been found in many cancer cells.Therefore, GPCRs and RTKs are equally important in the clinical treatment of cancer therapeutic.However, GPCRs and RTKs are not independent, and they can use common signal transduction.The present study show that crosstalk between GPCRs and RTKs can facilitate migration of lung epithelial cells, increasing survival of nerve cells and promoting tumor occurrence and development.This article mainly focuses on crosstalk between GPCRs and RTKs and their roles in tumorigenesis and oncotherapy.

OBJECTIVE:To compare in vivo and in vitro permeation behaviors of the ethosome gels of testosterone,testoster-one propionate and testosterone undecanoate. METHODS:The ethosome gels of testosterone,testosterone propionate and testoster-one undecanoate were prepared. With cumulative permeating amount and permeation rate as the indexes,Franz diffusion cell and HPLC were employed to compare in vitro permeation behaviors of 3 kinds of ethosome gels in mouse skin. With testosterone patch as the positive control drug, electrochemistry method was adopted to detect the concentration of testosterone in plasma 0,3,6, 9,12,24,36 and 48 h after applying such 3 kinds of ethosome gels on the back of rats,and then pharmacokinetic parameters were calculated with DAS 2.0 software. RESULTS:24 h cumulative permeating amounts of the ethosome gels of testosterone,tes-tosterone propionate and testosterone undecanoate were(234.31±13.8),(175.63±41.1)and(72.60±15.3)μg/cm2,and the per-meation rates were(10.25±1.9),(7.64±1.4)and(2.96±0.8)μg/(cm2·h),respectively. The pharmacokinetic parameters of the above-mentioned three kinds of ethosome gels and the positive control drug were respectively as follows as cmax of(20.19±2.57), (17.50±2.91),(0.23±0.04),(14.97±2.12)ng/ml,t1/2Ka of(2.80±0.45),(3.36±0.59),(4.02±0.62),(4.20±0.71)h,AUC0-48 h of(13.85±1.96),(13.93±2.13),(0.35±0.07),(11.76±2.31)ng·h/ml. CONCLUSIONS:in vivo and in vitro permeation behav-iors of the ethosome gels of testosterone and testosterone propionate are fairly good.

JNK is a key protein in the third stages of MAPK pro-tein kinase activation cascade,and is located in the key node of multiple signal transduction network.It plays a pivotal role in the cell proliferation,differentiation,apoptosis and some other important cell biological processes.Therefore it acts as an im-portant factor in regulating the development of some major human diseases,such as cancer.But the functional diversity and com-plexity of three JNK isoforms in different cell types make it diffi-
cult to develop anticancer drugs with JNK as a treatment target. In this review,we summarized the apoptotic signaling network of JNK and the regulation functions of JNK in cell apoptosis and proliferation.We also discuss the different functions of 3 JNK isoforms in human cancer.

The rate of corneal graft rejection is still high for high-risk keratoplasty although immune suppression drug is routinely used.The role of traditional Chinese medicine in corneal transplantation is concerned gradually.Heijingpaichitang on the prevention and treatment of rats with high-risk corneal allograft rejection needs further study.Objective This study was to investigate the inhibitory effect of heijingpaichitang on high-risk corneal transplantation immune rejection in rats.Methods Sixteen female SD rats were used as the donors and 32female Wistar rats were served as recipients.The high-risk corneal trasplantation models were established by corneal suture in 32 Wistar rats,and then homogeneity variant SD-Wistar corneal transplantation was performed.The recipients were randomized into model control group,cyclosporinc A (CsA)group,heijingpaichitang group and CsA +heijingpaichitang group.CsA,heijingpaichitang and CsA + heijingpaichitang was orally administered 4 days after operation once per day for 15 days,and normal saline solution was used at the same way in the model control group.Ocular anterior segment reaction was examined under the slit lamp and corneal opacification,edema and neovasculation were scored based on Larkin' s criteria.Rejection index of the corneal graft was recorded and the graft survival time was calculated.The pathological examination of the corneal graft was carried out in all rats,and the inflammatory cells in the corneas and CD4+ cells in the periphery blood were assayed using flow cytometry.The use of the animals complied with ARVO Statement.Results Corneal graft rejection occurred in 10 days after operation in the model control group,12-13 days in the CsA group and heijingpaichitang group and 22 days in the CsA +heijingpaichitang group.Compared with model control group,the scores of the corneal opacification,corneal edema and neovascularization were significantly lower in the CsA group,heijingpaichitang group and CsA+heijingpaichitang group (P＜0.05),and all the scores were declined in the CsA+ heijingpaichitang group compared with CsA group and heijingpaichitang group(P＜0.01),but no significant differences were seen in the scores between the CsA group and heijingpaichitang group(P＞0.05).The mean survival time of grafts was (10.38 ±1.69)days in the model control group,(22.50 ± 3.07) days in the CsA + heijingpaichitang group,with the significant difference (t =-9.790,P =0.000).The pathological examination of graft showed that the lymphocytes and new blood vessels were less in the CsA+heijingpaichitang group compared with CsA group and heijingpaichitang group 15 days after operation.Flow cytometry verified that the number of lymphocytes in graft,CD4+cells and CD4+/CD8+ in periphery blood were significantly lower in the heijingpaichitang group,CsA group and CsA+heijingpaichitang group compared with model control group (P＜0.05).Conclusions Heijingpaichitang can inhibit immune rejection to certain extent in high-risk corneal transplantation rat and has a similar effect to 0.1％ CsA.Heijingpaichitang and 0.1％ CsA have a synergistic effect.

To discuss the effective method of decreasing the postoperative recurrence rate of recurrent pterygium.
●METHODS:Totally 126 cases (126 eyes) with recurrent pterygium were randomly divided into A group (56 cases) and B group ( 70 cases ). Group A was treated by pterygium conjunctive reverse transplantation combined with amniotic membrane transplantation, group B was treated by amniotic membrane transplantation. The followed-up time after surgery was 6-24mo.
●RESULTS:ln group A, postoperative 5-7d (average 5. 62± 1. 38d), cornea epithelium was repaired. ln group B, postoperative 7- 10d ( average 7. 38 ± 1. 12d), the corneal wound was healed. There was statistical significant difference between two groups (t = 4. 307,P<0. 05). Three cases recurrence were noted in A therapeutic group (56 cases), the recurrent rate was 5. 4%; Twelve cases recurrence were noted in B compared group (70 cases), the recurrent rate was 17. 1%. There was statistical significant difference between two groups(P<0. 05).
●CONCLUSlON: lt is suggested that pterygium conjunctive reverse transplantation combined with amniotic membrane transplantation is effective in the treatment of recurrent pterygium.

The aerolysin genes (aerA) of BZ and NK isolates were cloned and sequenced. The sequence analysis showed that the partial aerA of BZ and NK isolates consisted of 1393 bp, encoding a protein of 464 amino acids. The similarity of nucleotide and amino acid sequences of aerA between BZ and NK isolates was 97.6% and 98.3% respectively. The nucleotide sequence of aerA of BZ strain exhibited 71.6% to 97.5% homology with other Aeromonas isolates, and the amino acid sequence exhibited 68.0% to 98.9% homology. The phylogenetic tree based on aerA nucleotide sequences from Aeromonas isolates was constructed with neighbor-joining method. It showed that there were three branches of aerolysin genes, and a close relation- ship among Aeromonas hydrophila isolates which were clustered into the same branch.