OBJECTIVETo observe the effects of electroacupuncture (EA) at "Dazhui" (GV 14) on Wnt-β-catenin signal pathway in annulus fibrosus cells in intervertebral disc in rats with cervical spondylosis.

METHODSForty SD rats were randomized into a control group, a model group, an EA group and a medication group, 10 rats in each one. Rats in the control group were treated with sham operation, only incision on local skin; rats in the remaining groups were made into cervical spondylosis models. After model establishment, rats in the control group and model group received fixed treatment under identical condition; rats in the EA group were treated with EA at "Dazhui" (GV 14), 30 min per treatment; rats in the medication group were treated with intragastric administration of meloxicam tablets. Treatments were both given once a day, and 14 days were taken as one session; there was an interval of 2 days between two sessions, and totally two sessions were given. After the treatments, immunohistochemistry was applied to measure the expression of Wnt, glycogen synthase kinase-3β (GSK-3β) and Axin in annulus fibrosus cells; western blot was used to test the expression of P-β-catenin.

RESULTSIn the control group, there were more positive cells of Wnt, GSK-3β and Axin, which were intensively distributed, deeply colored, and strongly positive; In the model group, there were less positive cells of Wnt, GSK-3β and Axin, which were sparsely distributed and weakly positive. The expression of Wnt, GSK-3β, Axin and P-β-catenin in the model group was less than that in the control group (all P < 0.05); expression of Wnt, GSK-3β, Axin and P-β-catenin in the EA group and medication group was higher than that in the model group (all P < 0.05); expression of Wnt, GSK-3β, Axin and P-β-catenin was not significantly different between EA group and medication group (all P > 0.05).

CONCLUSIONEA could delay the degeneration of intervertebral disc, which may be related to EA inhibiting signal pathway of Wnt-β-catenin.

Acupuncture Points ; Animals ; Electroacupuncture ; Female ; Fibrosis ; Glycogen Synthase Kinase 3 ; genetics ; metabolism ; Humans ; Intervertebral Disc ; metabolism ; pathology ; Male ; Rats ; Spondylosis ; genetics ; metabolism ; pathology ; therapy ; Wnt Signaling Pathway ; beta Catenin ; genetics ; metabolism

Anion Exchange Protein 1, Erythrocyte ; metabolism ; Breast ; metabolism ; pathology ; surgery ; Cadherins ; metabolism ; Female ; Fibrocystic Breast Disease ; metabolism ; pathology ; surgery ; Follow-Up Studies ; Humans ; Middle Aged ; S100 Proteins ; metabolism

Phytantriol (PT), ethanol (ET) and water were used to prepare in situ cubic liquid crystal (ISV2). The pseudo-ternary phase diagram of PT-ET-water was constructed and isotropic solution formulations were chosen for further optimization. The physicochemical properties of isotropic solution formulations were evaluated to optimize the composition of ISV2. In situ hexagonal liquid crystals (ISH2) were prepared based on the composition of ISV2 with the addition of vitamin E acetate (VitEA) and the amount of VitEA was optimized by in vitro release behavior. The phase structures of liquid crystalline gels formed by ISV2 and ISH2 in excess water were confirmed by crossed polarized light microscopy and small angle X-ray scattering, respectively. Rheological properties of ISV2 and ISH2 were studied by a DHR-2 rheometer. In vitro drug release studies were conducted by using a dialysis membrane diffusion method. Pharmacokinetics was investigated by determination of sinomenine hydrochloride (SMH) concentration in synovial membrane after intra-articular injection of SMH-loaded ISH2 in adjuvant-induced arthritis rats. The optimal ISV2 (PT/ET/water, 64 : 16 : 20, w/w/w) loaded with 6 mg x g(-1) of SMH showed a suitable pH, injectable and formed a cubic liquid crystalline gel in situ with minimum water absorption in the shortest time. The optimal ISV2 was able to sustain the drug release for 144 h. The optimal ISH2 system was prepared by addition of 5% VitEA into PT in the optimal ISV2 system. This ISH2 (PT/VitEA/ET/water, 60.8 : 3.2 : 16 : 20, w/w/w/w) was an injectable isotropic solution with suitable pH. The new ISH2 was able to sustain the drug release for more than 240 h. Local pharmacokinetics study indicated that the retention time and AUC(0-∞) of ISH2 group were increased significantly compared with that of SMH solution group and the AUC(0-∞) of ISH2 group was 6.01 times higher than that of SMH solution group. The developed ISH2 was suitable for intra-articular injection that may apply to patients in the treatment of rheumatoid arthritis.
Animals ; Chemistry, Pharmaceutical ; Diffusion ; Ethanol ; Fatty Alcohols ; Gels ; Injections, Intra-Articular ; Liquid Crystals ; Morphinans ; administration & dosage ; chemistry ; Rats ; Rheology ; Water ; alpha-Tocopherol

Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.
Animals ; Biological Products ; CHO Cells ; Cricetulus ; Drug Interactions ; Fatty Acids, Monounsaturated ; pharmacology ; Flavonoids ; pharmacology ; Indoles ; pharmacology ; Inhibitory Concentration 50 ; Organic Anion Transporters ; genetics ; metabolism ; Rosuvastatin Calcium ; pharmacology ; Structure-Activity Relationship

Antigens, CD20 ; metabolism ; Antigens, CD34 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Diagnosis, Differential ; Doxorubicin ; therapeutic use ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; metabolism ; pathology ; Male ; Melanoma ; metabolism ; pathology ; Middle Aged ; Prednisone ; therapeutic use ; Vascular Neoplasms ; drug therapy ; metabolism ; pathology ; Vincristine ; therapeutic use

In this study, five rhesus macaques were inoculated intravenously with SIVmac251 to establish a model of simian autoimmune deficiency syndrome (SAIDS). Peripheral blood samples were collected at different time points to monitor changes in the total T cell number and T lymphocyte subset. Plasma viral loads, cytokine expression levels and anti-SIV antibody levels were also assayed to acquire certain basic indexes to evaluate disease progression in the rhesus macaque SAIDS model. During the acute stage of infection, plasma viral loads reached a peak at week 1 post-inoculation and lasted for approximately 3 to 44 weeks. The CD3+ CD4+ T lymphocyte count in peripheral blood also transitorily decreased. During the same period, the level of interferon-gamma show an increasing trend, whereas IL-12 levels decreased; IL-2, IL-4, IL-10 and TNF-alpha were maintained at normal levels or could not be detected. During the asymptomatic and ARC phases, plasma viral loads persisted above 10(4) RNA copies/mL and either increased or declined during the later stages of disease; CD3+ CD4+ counts showed a steadily declining trend and the ratio of CD4 to CD8 decreased during late-stage disease. Moreover, antibodies against viral proteins were detected in the plasma and showed a significant increasing trend, while there were no apparently changes in the levels of IFN-gamma, IL-12, IL-2, IL-4, IL-10 and TNF-alpha. In conclusion, the characteristics of the SIV animal models in our study are similar to those of patients with AIDS. Therefore, the rhesus macaque SIVmac251 infection models can be applied for further studies into AIDS.
Animals ; Antibodies, Viral ; blood ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes ; virology ; Cytokines ; genetics ; immunology ; Disease Models, Animal ; HIV Infections ; genetics ; immunology ; virology ; HIV-1 ; physiology ; Humans ; Macaca mulatta ; Male ; Simian Acquired Immunodeficiency Syndrome ; genetics ; immunology ; virology ; Simian Immunodeficiency Virus ; physiology ; Viral Load

Breast Neoplasms ; diagnosis ; pathology ; Female ; Humans ; Leiomyosarcoma ; diagnosis ; pathology ; Middle Aged ; Skin Neoplasms ; pathology ; secondary

Carcinoma, Medullary ; pathology ; Carcinoma, Renal Cell ; diagnosis ; metabolism ; pathology ; radiotherapy ; surgery ; Diagnosis, Differential ; Humans ; Keratins ; metabolism ; Kidney Neoplasms ; diagnosis ; metabolism ; pathology ; radiotherapy ; surgery ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasms, Squamous Cell ; pathology ; Nephrectomy ; Radiotherapy, Adjuvant

Objective To analyse incidence of the severe complications of hypertensive disorder complicating pregnancy and the influence on the outcome of pregnancy.Methods A retrospective study of 4107 cases among 71 020 cases who delivered in hospitals from 1995 to 2004 in Guangzhou was conducted. Results The morbidity of hypertensive disorder complicating pregnancy was 5.78%,in which the morbidity of severe pre-eclampsia was 27.78% (1141/4107),of mitis pre-eclampsia was 72.22% (2966/4107). Maternal mortality rate was 0.19% (8/4107),and the specific mortality rate was 11.26/100 000.The proportion of severe complications of hypertensive disorder complicating pregnancy from high to low was as follows:placental abruption 1.68% (69/4107),DIC 1.36% (56/4107),hypertensive disorder complicating pregnancy induced cardiopathy(induced cardiopathy) 1.05% (43/4107),renal failure 0.97% (40/4107),cerebrovascular accident 0.58% (24/4107),and hemolysis,elevated liver enzymes and low platelet (HELLP) syndrome 0.51% (21/4107).Mortality caused by severe complications of hypertensive disorder complicating pregnancy were as follows:cerebrovascular accident 17% (4/24),HELLP syndrome 10% (2/21),DIC 5% (3/56) and induced cardiopathy 2% (1/43).The proportion of perinatal mortality from severe complications were as follows:placental abruption 43% (33/77),HELLP syndrome 42% (10/ 24),DIC 34% (22/64),renal failure 25% (11/44),cerebro vascular accident 24% (6/25)and induced cardiopathy 16% (8/49).Conclusions (1) The morbidity of severe complications from high to low are: placental abruption,DIC,induced eardiopathy,renal failure,eerebro vascular accident and HELLP syndrome.(2) The main causes of mortality for gravida and puerperant are:cerebro vascular accident, HELLP syndrome,DIC and induced cardiopathy.(3) The major complications harmful to perinatal newborns are in the order of:placental abruption,HELLP syndrome,DIC,renal failure,eerebro vascular accident and induced cardiopathy.

Objective To investigate the importance of plasmid-mediated quinolone resistance in the development of quinolone resistance in clinical isolates of gram-negative bacteria.Methods A total of 541 consecutive clinical isolates of gram-negative ba- cilli resistant or intermediate to ciprofloxacin were screened for the qnrA gene by PCR.Conjugation experiments were carried out with azide-resistant E.coli J53 as a recipient.The aac(6')-Ib-cr gene was detected.The mutations in the quinolone-resist- ance-determining region (QRDR) of the gyrA and parC genes were identified in qnrA positive strains.Results qnrA was identi- fied in 7 of the 541 strains.Among the qnrA positive strains,5 were Enterobacter cloacae.No qnrA was detected in nonfer- menters.Quinolone resistance was transferred in 4 of 7 qnrA positive strains.Transconjugants had 12-to 125-fold increases in MIC of ciprofloxacin relative to that of the recipient.Seven strains contained qnrA with a nucleotide sequence identical to that originally reported.Two transconjugants with higher ciprofloxacin MICs contained aac(6')-Ib-cr gene.Mutations occurred in the QRDR of the gyrA and parC genes in 5 PCR-positive clinical strains.Conclusions Transferable plasmid-mediated quinolone resistance associated with qnrA is highly prevalent in clinical strains of Enterobacter spp.aac(6')-Ib-cr gene and mutations in the quinolone targets may co-exist with qnrA,which may contribute to the further increase of resistance to quinolones.