AIM: To study the inhibitory effect of captopril on retinal neovascularization (RNV).METHODS: Sixty seven-day-old mice were randomly divided into treated group and control group with thirty mice in each group. These mice were exposed to 750 50mL/L oxygen for 5 days and then to room air.The treated group had been injected captopril (2.7mL/kg), while control group had been injected 9g/L sodium chloride (2.7mL/kg) by intravitreal for 5 days.The mice were sacrificed at the 17th day after birth and the eyes were enucleated. Adenosine diphosphate-ase(ADPase) stained retina flat-mounts was performed to assess the retinal vascular profiles, Hematoxylin Eosin (HE)staining method was applied to count the number of new vascular cell nuclei and the expression of matrix metalloproteinase-2(MMP-2)and pigment epithelium derived factor (PEDF)was detected by immunohistochemical method.RESULTS: Comparing with control group,regular distributions and good branch and reduced density of RNV were observed in the treated group. The number of nucleus of new vessels vascular endothelial cells breaking through the internal limiting membrane was less in the treated group than in the control group (P<0.05). Stain of retinal MMP-2 was weaker in the treated group than in the control group and stain of retinal PEDF was stronger in the treated group than in the control group.CONCLUSION: Intravitreal injection of captopril (2.7mL/kg) may block the RNV in the oxygen-induced mouse model and may provide an effective method for prevent-ing RNV.

China ; Humans ; Occupational Health Services ; manpower

Breast Neoplasms ; chemistry ; Female ; Humans ; Immunohistochemistry ; methods ; standards ; In Situ Hybridization, Fluorescence ; methods ; standards ; Receptor, ErbB-2 ; analysis ; Stomach Neoplasms ; chemistry

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.

AlM: To explore the expression and significance of cysteine- rich 61 ( CCN1/Cyr61 ) in oxygen - induced retinal neovascularization ( RNV) of mice and study the inhibition effect of CCN1 specific siRNA on RNV.
METHODS:Two hundred healthy C57BL/6J mice were chosen and randomly divided into control group, hyperxia group, hyperxia control group and CCN1 treated group, with 50 mice in each group. The hyperxia control group was treated with vector plasmids by intravitreal injection. The CCN1 treated group received CCN1 siRNA recombinant plasmids by intravitreal injection. Adenosine diphosphate-ase ( ADPase) stained retina flat-mounts was performed to assess the retinal vascular profiles, HE staining was applied to count the number of vascular endothelial cell nuclei breaking through the internal limiting membrane, protein and mRNA level expression of CCN1 were measured by immunohistochemistry, Western blot and RT-PCR.
RESULTS: There were large nonperfusion area and a large number of vascular endothelial cell nuclei breaking through the internal limiting membrane ( 25. 25 ± 1. 26;23. 12 ± 1. 16 ) in the hyperxia group and the hyperxia control group. Regions of nonperfusion and vascular endothelial cell nuclei (8. 47±1. 15) were decreased in the CCN1 treated group compared to the hyperxia group and the hyperxia control group. Compared with the control group, there were high protein and mRNA expression of CCN1 in the hyperxia group and the hyperxia control group. The expression of CCN1 protein and mRNA were decreased in the CCN1 treated group compared with the hyperxia group and hyperxia control group (all P<0. 05).
CONCLUSlON: The abnormal expression of CCN1 has close relation with RNV. The development of RNV can be markedly inhibited by RNA interference targeting CCN1, which, we believe, will provide new molecular targets and a rationale for clinical developing new strategy for ROP therapy.

Accidents, Occupational ; China ; epidemiology ; Humans ; Poisoning ; epidemiology

The new generation cyclooxygenase (COX-2) inhibitor could reduce the gastrointestinal side effect of NSAID drugs, but eventually increase the cardiovascular risk, because its selective inhibition of COX-2 induces the imbalance between PGI2 and TXA2 and the reduction of vasodilatory NO. Under pathological conditions, active oxygen species (O2-*2, etc) were used to induce endo- thelial dysfunction, activate NF-κB to induce expressions of pro-inflammatory cytokines IL-1β and TNF-α, increase ET-1, TXA2 with vasoconstrictor effect, reduce PGI2 and NO with vasodilatory effect, generate further oxidative damage together with NO, and reduce the bioavailability of NO. NO-NSAIDs and NO-Coxibs drugs raised the level of NO by introducing NO-donor (ONO2). NSAIDs drugs enhanced the anti-inflammatory activity of COX-2 and reduced gastrointestinal side effects by inhibiting selectively COX-2. If antioxidant structures with active ingredients of traditional Chinese medicines were introduced to improve the antioxidant activity of NSAIDs, they could scavenge the active oxygen species to protect the normal function of vascular endothelia and enhance the bioavailability of NO, which is conducive to enhance the cardiovascular safety of cyclooxygenase (COX-2) inhibitor.
Anti-Inflammatory Agents ; therapeutic use ; Biomarkers, Pharmacological ; Cardiovascular Diseases ; drug therapy ; enzymology ; immunology ; Cyclooxygenase 2 ; immunology ; Cyclooxygenase 2 Inhibitors ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; NF-kappa B ; immunology ; Reactive Oxygen Species ; immunology ; Tumor Necrosis Factor-alpha ; immunology

Occupational Diseases ; prevention & control ; Occupational Health Services ; Public Health

Objective To observe the effects of standardized three stage rehabilitation treatment on the neu- rological deficit scores (NDS) and ADL performance of ischemic stroke patients.Methods A total of 164 ischemic stroke patients were recruited and randomly divided into a rehabilitation group and a control group.The neurological function and ADL performance of the patients were assessed by using NDS and Modified Barthcl Index (MBI) at the admission,at the end of 1st,3rd and 6th months post stroke.Results No significant differences were found be- tween the rehabilitative and the control groups with regard to NDS and MBI at admission.The NDS demonstrated a decreasing tendency,while the MBI score an increasing tendency in both groups.In the control group,significant difference of NDS was found between admission and the end of 1st month as well as between the end of the 1 st and the 3rd months.In rehabilitation group,significant difference was revealed between all the time points with regard to NDS and MBI scores.At the end of the 1st,3rd and 6th months,the MBI scores of the rehabilitation group were signifi- cantly higher than those of the control group,indicating that the ADL performance of those treated with standardized three-stage rehabilitation protocol was improved quicker than those without the protocol.Conclusion Standardized three-stage rehabilitation treatment could improve the neurological function and ADL performance of the ischemic stroke patients.

Tautomycin is one of well-known specific protein phosphatase inhibitors and exhibiting potent antifungal ability, especially to Sclerotinia sclerotiolum. This article reviews the recent research progress of tautomycin, focusing on its inhibition region and biosynthesis.