Background Vancomycin has been increasingly recommended for the management of endophthalmitis,but few research report has been published about the pharmacokinetics of intravitreal vancomycin up to now.It is necessary to have an exact method to measure the concentration of vancomyein in animal eyes after intravitreal injection.Objective This study was to observe and compare the phamacokinetical process of vancomycin in serum,vitreous and aqueous humor between normal and infected rabbit eyes.Methods Seventy-two healthy adult rabbits were randomly divided into normal group and infected group and 36 rabbits for each.The animal models of endophthalmitis were established by intravitreal inoculation of 2000 CFU/ml staphylococcus aureus in the right eyes of rabbits in the infected group.Once endophthalmitis developed,0.1 ml vancomycin ( 10 g/L) solution was injected into the vitreous of every rabbit.The peripheral blood,vitreous and aqueous humor samples were respectively collected in 4 rabbits for each group at 0.5,2,4,6,12,24,48,72 and 84 hours after injection for detection of vancomycin concentration by high performance liquid chromatography(HPLC-UV).3p97 software was used to create fit parameters of pharmacokinetics.This experiment followed the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission (Version 1988).Results The accuracy of HPLC fitted the detecting request of biological specimen.The concentration-time data of vancomycin in normal rabbit aqueous humor and vitreous was subject to two-compartment model.The pharmacokinetic parameters were separately as following:Cmax was 50.16 mg/L and 751.42 mg/L,t1/2was 51.04 hours and 53.21 hours.The concentration-time data of vancomycin in infected rabbit aqueous humor and vitreous was subject to one-compartment model.The pharmacokinetic parameters were separately as following:Cmaxwas 24.94 mg/L and 687.66 mg/L,t1/2was 11.42 hours and 12.91 hours.The concentration of vancomycin in serum was much lower and almost undectable.The concentration of vancomycin in vitreous was gradually reduced as the prolong of time after injection in both normal group and infected group,but a obvious decline after increased level was scen in aqueous humor.Compared with normal group,the concentrations of vancomycin in both vitreous and aqueous humor were reduced at various time points(P＜0.05,P＜0.01 ).Conclusions HPLC is simple,highly sensitive and specific for the pharmacokinetic analysis of vancomycon.These results indicate that pharmacokinetic parameters of vancomycin alter in pathological condition,which is helpful for us to establish the better treatment guidelines for endophthalmitis.

Background Both functional and morphological changes in amblyopic development are known to occur at various levels in the central visual pathway.However,whether the retina is involved or not during amblyopic progression remains controversial.Objective This study was designed to compare the thicknesses of the fovea and retinal nerve fiber layer (RNFL) of the normal fellow eye of amblyopic eye using optical coherence tomography (OCT) in children with myopic anisometropia.Methods Twenty-two patients with unilateral myopic anisometropic amblyopia were included as the anisometropia amblyopia group.Ten unilateral myopic anisometropic amblyopia subjects received treatment and recovered were used as the amblyopic cure group,and 11 individuals with simple myopic anisometropia without amblyopia were enrolled as the control group.OCT was performed on both eyes of all the subjects with informed consent.Fovea retinal thickness and RNFL thickness from the superior,inferior,nasal and temporal quadrants in the peripapillary region were evaluated.The measurement parameters were bilaterally compared in all the individuals by paired t test.The multiple regression model was used to analyze the correlation of retinal thickness with amblyopia patients.This study was approved by the Ethic Committee of this hospital.Written informed consent was obtain from each subject prior to the eye examination.Results Fovea retinal thickness increased in the amblyopic eyes compared with the fellow eyes,showing a statistically significant difference between them (P =0.001).However,no significant differences were found in the fovea retinal thickness between both eyes in the amblyopic cure group and simple myopic anisometropia without amblyopia group (P =0.778,0.943).Among the anisometropia amblyopia group,amblyopia cure group and simple myopic anisometropia without amblyopia group,the RNFL thicknesses of the temporal quadrant was significantly thicker in the higher myopic lateral eyes than those of the fellow eyes (P＜0.001,P =0.003,P =0.046).However,the differences in the superior,inferior,nasal and the average RNFL thickness were not statistically significant between the two eyes (P＞0.05).A negative correlation was found between the inferior retinal thickness with age (r=-0.559,P=0.016).Conclusions The fovea may be affected in unilateral myopic anisometropic amblyopia.There is no significant difference in the RNFL thickness between simple myopic eye and unilateral myopic anisometropia amblyopic eye.Improvement in amblyopia is coming along with the reduction of the thickness of the fovea.

Objective To study CD64 expression in neutrophilic granulocyte and its clinical effect in neonatal infection disease. Methods CD64 was detected among 59 neonatal patients(septicemia group 34 patients, local infection group 25 patients)hospitalized in our neonatal department diagnosed as neonatal infection disease in 48 h after hospitalized,2 weeks after therapy, then the results were compared with 27 patients as non - infection disease during the same period. Results CD64 in septicemia group was (6156. 21?3643. 32) molecula per cell,in local infection group was (2176.19 ? 946. 32)molecula per cell, in non- infection group was (2176. 19 ? 946. 32) molecula per cell.There were significant differences among three groups (all P0.05). Conclusions CD64 expression increases in bacterium infection disease. It is more obvious in widespread infection desease.and it can be the mark in early diagnosis of neonatal infection disease.

Objective To identify the diseases outcome of inpatients of prefectural hospital in Xinjiang,through analyzing the diseases outcome of inpatients of a prefectural hospital in Xinjiang from 2006 to 2008.Methods To analyze the diseases outcome of inpatients(20 533 cases)randomly selectedin hospital from 2006 to 2008 the date were aralgzed.according to year,gender,ethnicity,disease systems.Results The overall cured rate,improved rate,healed rate,fatality rate of inpatients was 42.10％(8663 cases),51.10％(10 463 cases),6.00％(1242 cases),0.80％(165 cases)respectively.The fatality rate of inpatients of above 60 years old,45 ～59 years old,15 ～44 years old is higher in inpatients of various age groups; The fatality rate of inpatients of tumor,circulatory system diseases,symptoms of menopause with the experimental and clinical body seen to be kind to the suffering of its is higher in inpatients of various systemic diseases,binary multinomial logistic regression shows that the disease outcome is influenced by gender,age,disease systems,hospital annual,four single factors,but not influenced by ethnicity.Conclusion The cured rate adding improved rate is over 90％ of common and frequently-occurring diseases in the prefectural hospital of Xinjiang province.The fatality rate is higher in inpatients who suffered from tumor or circulatory system diseases or symptoms of menopause with the experimental and clinical body seen to be kind to the suffering of its and the fatality rate of all age groups over 15 years old is higher.

Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Humans ; K562 Cells ; drug effects ; Phloretin ; pharmacology

OBJECTIVETo observe the effects of panax quinquefolius saponin (PQS) of stem and leaf on glucose-lipid metabolism and insulin signal transduction in the insulin resistant model of adipocytes.

METHODSThe insulin resistant model of differentiated 3T3-L1 adipocytes was established in vitro with free fatty acid. After induction of insulin resistance, cells were treated with metformin or PQS for 2 days. The glucose consumption in culture fluid was detected by glucose oxidase method; the effects of PQS on the lipolysis induced by tumor necrosis factor (TNF-alpha) was observed using colorimetry; and the phospholation of signal proteins was detected by Western-blot.

RESULTSThe amount of glucose consumption (mmol/L) in the model group (5.250 +/- 2. 671) was significantly lower than that in the normal control group (14.133 +/- 1.305, P < 0.01), it increased in the meformin treated group (11.807 +/- 1.358), and the groups treated with high-, middle- and low-dose PQS dose-dependently (10.784 +/- 2.373, 10.217 +/- 1.237 and 9.984 +/- 2.006, respectively), significantly higher than that in the model group (P < 0.01). Upon TNF-alpha treatment, the concentration of free fatty acid (FFA) (nmol/ microg) in culture medium was 2.479 +/- 0.597, predominantly higher than that in the control group (1.320 +/- 0.538, P < 0.01), while it was 1.210 +/- 0.566 in the metformin group, 1.105 +/- 0.631 in high-dose PQS group, 1.108 +/- 0.260 in the middle-dose PQS group, 1.201 +/- 0.593 in the low-dose PQS group, all were lower than that in the TNF-alpha group (P < 0.05 or P < 0.01), and a dose-dependent tendency of PQS's action was seen. The tyrosine phosphorylation of insulin receptor and IRS-1 as well as Ser473 phosphorylation of PKB were lower in the model group than in the control group; they were insignificantly changed in the low-dose PQS group, but did show significant difference in comparing with those in the high-and middle-dose PQS groups or metformin group.

CONCLUSIONPQS can accelerate the glucose utilization and depress the lipolysis in adipocytes induced by TNF-alpha, which may be correlated with its promoting insulin signal transduction and improving insulin resistance in adipocytes.

3T3-L1 Cells ; Adipocytes ; drug effects ; metabolism ; Animals ; Glucose ; metabolism ; Insulin ; metabolism ; Insulin Resistance ; Lipid Metabolism ; drug effects ; Mice ; Saponins ; pharmacology ; Signal Transduction ; drug effects

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

This study was aimed to investigate the differentiation potential after EGFP gene-modified mesenchymal stem cells (MSCs) transfected by lentiviral vector (LV). After isolated, cultured and identified, MSCs were transfected with the lentiviral vector carrying EGFP gene in vitro. The transfection efficiency was measured by observing the expression of green fluorescence protein. At last, the transfected MSCs were induced into adipocytes in adipogenesis supplement medium, the induction level was detected by Sudan fat stain. The results indicated that after transfection for 72 hours, weak fluorescence in MSCs was observed under fluorescence microscope. After 21 days, many lipid droplets with high refractivity occurred in cytoplasm of transfected MSCs, and showed orange in Sudan black stain. There were no significantly differences between transfected and non-transfected cells (p > 0.05). It is concluded that MSCs were successfully transfected by LV carrying EGFP gene. The transfected MSCs maintain multiple differentiation and proliferation potential. In the adipogenesis supplement medium, transfected MSCs also can be induced to differentiate into adipocytes. MSCs can act as target cells for gene therapy.
Bone Marrow Cells ; cytology ; Cell Differentiation ; genetics ; Cells, Cultured ; Genetic Vectors ; Green Fluorescent Proteins ; genetics ; Humans ; Lentivirus ; genetics ; Mesenchymal Stromal Cells ; cytology ; Transfection

Objective To evaluate the correlation between cerebral blood volume and permeability surface by using muhislice CT perfusion imaging with glioma grade.Methods Ninteen patients with gliomas underwent conventional MR and multislice CT perfusion imaging preoperatively.These patients were divided into low grade and high grade groups which were correspond to WHO Ⅱ grade gliomas and WHO Ⅲ or Ⅳ grade gliomas respectively.CT data were transferred to on-line working station and processed to obtain time-signal curves,color perfusion maps and calculated perfusion parameters,including cerebral blood volume(CBV),cerebral blood flow(CBF),mean transit time(MTT)and permeability surfaces (PS)in tumoral parenchyma.Kruskal-Wallis test and correlation of CBV and PS was assessed by using SPSS 11.0 software.Results The median of CBV and PS in low-grade and high-grade glioma were 2.7, 6.5 ml/100 g;0.389,12.810 ml?100 g~(-1)?min~(-1),respectively,corresponding t value were 12.907, 13.500 with P

Objective To investigate the effect of intra-articular carboxymethylated ehitosan(CM- CTS)injection on inducible nitric oxide synthase(iNOS)expression in cartilage at the early stage of os- teoarthfitis(OA).Methods Thirty-two white rabbits were underwent unilateral anterior cruciate ligament transection(ACLT)and were randomly divided into 4 groups 5 weeks after transection.Rabbits of group A re- ceived 0.3 ml of 2% high molecular weight CMCTS(H-CMCTS)once every two weeks.Rabbits in group B were treated using 2% low molecular weight(L-CMCTS)CMCTS at:the same intervals.Group C rabbits were injected intra-articularly with 0.3 ml of 1% sodium hyaluronate(Na-HA)once a week.Animals of group D were not injected.At sacrifice,11 weeks following surgery,the expression of iNOS in cartilages was analyzed by immunohistochemistry and reverse transcription-polymerase chain reaction(RT-PCR)methods.Results Both immunohistochemistry and RT-PCR showed that the level of iNOS expression of cartilage in CMCTS in- jection groups was lower than that in Na-HA injection group and the untreated group.There was no significant difference in iNOS expression between the two different molecular weight CMCTS injection groups. No signifi- cant difference of iNOS expression in cartilage was found between Na-HA injection group and the untreated group.Conclusion CMCTS suppresses iNOS expression in cartilage during the early stage of OA.Na-HA treatment has no effect on iNOS expression in cartilage.