OBJECTIVE:To verify the safe dose of cephradine in intravitreal injection. METHODS:After injecting different doses of cephradine(100mu;g,200mu;g,250mu;g,300mu;g,400mu;g)into vitreous cavity of different group of rabbits the activities of the retinal enzymes (SDH,LDH )on different time (Id,3d, 7d ) were determined respectively, and the histological and ultrastructural changes of retinas were also observed simuhaneously. RESULTS:The activity of rellnal SDH and LDH was found to be decreased gradually with tbe icreasing of the dosage of intravitreal cephradine. The activities of SDH and LDH were found in the lowest level on tile 3rd and lsl day,but they recover to normal levels on tile 7th day after intravitreal in}eetion in 100mu;g,200mu;g groups,and still lower tban normal in the other groups. Histologically,retinal edema was found both in 100mu;g and 200mu;g groups,but degradation of retinal cells,and loss of cones and rods were round in the 250mu;g, 300mu;g and 400mu;g groups. CONCLUSION: The safe dose of intravitreal injection of cepbradlnc is 200mu;g. （Chin J Ocul Fundus Dis,1997,13:139-142 ）
Objective To investigate the retinal toxicity and verify the safe dose of intravitreal injection of nonsteroid anti-inflamatory drug,diclofenac sodium.Methods Twenty-eight healthy adult white rabbits were divided at random into 7 groups and received in every right eye the intravitreal injection of a single dose of diclofenac sodium solution ranging from 0.4-0.1 mg/0.1ml respectively ,the left eyes were regarded as conreol ones.Before injection and on the 1st,3rd,7th,14th,21st,and 28th day after injection the electroretinography on both eyes was examined.On the 28th day after injection the retinas of two rabbits of every group were examined by using light microscopy.On the 10th and 30th day after injection the retinal tissues around the optic nerve sisk of two eyes from every group at random were tested by using transmission electron microscopy.Results The retio of amplitude ofb wave of electroretinography in 0.4mg and 0.5mg groups had no sighnificant difference from groups before injection,the retinal tissues showed no structural changes in light and ecectron microscopy examination.The ratio of amplitude ofb wave of photoptic electroretinogrphy in 0.6mg groups in the early stage after injection was markedly reduced（P＜0.05）and returned to that before injection with time,reversible change of the edematou retina was discovered.The ratio of amplitude of b wave of electroretinography in 0.7-1.0mg groups was distinctly descreaded after injection（P＜0.05 or P＜0.01）,the cells of all the retinal layer revealed apparent and irreversible damage.Conclusion The largest dose of safety of intravitreal diclofenac sodium should be not more than 0.6mg.The toxic effect of intravitreal diclofenac sodium on retina is concerned mostly to cones and rods.
Objective To observe the inhibition effect of curcumin on the proliferation of rabbit retinal pigment epithelial (RPE) cells and investigate its mechanism. Methods The 4th generation of RPE cells were selected and divided into curcumin group and blank control group. The concentration of curcumin included 10, 15, and 20 mu;g/ml. The MTT assay was used to evaluate the inhibition effect on the proliferation of RPE cells at the 24th, 48th, 72nd and 96th hour after cultured with curcumin (10, 15, and 20 mu;g/ml). The IC50 value of curcumin at different time points were calculated by Linear Regression. Flow cytometry was used to detect the effect on the cell cycle at the 72nd hour after cultured with curcumin (15 mu;g/ml); the expression and apoptosis of proliferating cell nuclear antigen (PCNA) were also determined at the 24th,48th, and 72nd hour after cultured with curcumin (15 mu;g/ml) respectively. The configuration of RPE cells were observed by transmission electron microscope. Results The IC50 value of curcumin at the 24th,48th, 72nd and 96th hour was 29.31, 17.50, 13.24, and 10.99 mu;g/ml respectively. Cell cycel analysis indicated that curcumin blocked cells in G0/G1 phase. At the 24th, 48th, and 72nd hour after cultured with curcumin (15 mu;g/ml), the expression of PCNA of RPE cells were 565.04plusmn;23.60, 473.61plusmn;36.88, and 396.15plusmn;32.45; the apoptosisrate were （12.83plusmn;0.13）%，（32.27plusmn;4.51）%，（56.81plusmn;8.67）%, respectively. The differeces of curcumin groups compared with the control group were significant (P＜0.05). Apoptosis of RPE cells was observed under transmission electron microscope. Conclusions Curcumin can inhibite the proliferation of RPE cells by inhibit the synthesization of PCNA and inducing the apoptosis of RPE cells. Curcumin may become a potential drug to prevent and treat PVR.
Objective To observe the effects on rabbit corneas and retinas after single intravitreal injection of voriconazole at different doses. Methods According to the randomization table, 25 healthy rabbits were randomly divided into control group, and voriconazole 50, 100, 200, and 400 μg groups. Therefore, there were 5 rabbits in each group. The eyes of control group received intravitreal injection of 0.1 ml balanced saline solution, and those treatment groups received 0.1 ml voriconazole injection of corresponding dose. Before the injection and 1, 7, and 14 days after the injection, endothelial cell counts and corneal thicknesses were measured; full-field electroretinogram were performed and b-wave amplitudes in maximal combined reaction (Max-R) were recorded. On 14 days after the injection, histologic structures were observed by light microscope and transmission electron microscope. Results There was no significant difference in endothelial cell counts (F=0.320, 0.291, 0.467, 0.649) and corneal thicknesses (F=0.214, 0.284, 0.360, 0.225) with those of control group at any time points (P > 0.05). Before and 1 day after the injection, b-wave amplitudes of each voriconazole group had no significant difference compared with those of control group (F=0.220, 0.106; P > 0.05). On 7 days after the injection, b-wave amplitudes decreased significantly at doses of 200 μg and 400 μg (P < 0.05). On 14 days after the injection, there was no significant difference between the the amplitude of 200 μg group and that of control group (P > 0.05). However, the amplitude of the 400 μg group decreased continuously and there was still significant difference (P < 0.05). Light microscopy did not reveal any corneal abnormality in both control group and voriconazole groups. The retinas were normal except that of the 400 μg group, which hadathinner and degenerated inner nuclear layer and disordered photoreceptor layer. Under transmission electron microscope, there were no ultrastructure damages of corneas in both control group and voriconazole groups, either. The rabbit retinas of the 50 μg and 200 μg group have normal inner nuclear layer and photoreceptor layer, but degrees of changes in both layers were observed in the eyes of 200 μg and 400 μg group. Conclusions There is no obvious effects on rabbit corneas and retinas after single intravitreal injection of voriconazole at he dose less than or equal 100 μg. There are no obvious effects on rabbit corneas at the dose of 200 μg and 400 μg, while there are damages to the retinas in both functions and histological structures.
ObjectiveTo evaluate the security of intravitreal injection with ciproflaxacin to retina.MethodsTweenty-four rabbits were randomly divided into 4 groups with 6 rabbits in each group. 0.1 ml ciproflaxacin in doses of 2 500,5 000,and 10 000 μg was intravitreally injected into the rabbits eyes, retrospectively. And 0.1 ml saline solution was injected into the vitreous body of the rats in the control group. Indirect microscope, light microscope and electroretinogram (ERG) were used to observe the changes of ocular fundus.ResultsNormal results of light microscopy and ultrastructure were found in 250 μg and 500 μg groups; irregularly arranged outer and inner nuclear layers, dropsical or even lost ganglion cells, and ultrastructural changes were in 1 000 μg group. There was no apparent difference of ERG′s a and b amplitudes before and after intravitreal injection with ciproflaxacin in each group.ConclusionIntravitreal injection with ciproflaxacin is safe, and 500 μg or less is the secure dosage in rabbits' eyes. (Chin J Ocul Fundus Dis, 2005,21:180-182)
Objective To observe the efficacy of the anti-tumor necrosis factor-alpha; monoclonal antibody (TNF-alpha; MCAb) in the treatment of experimental autoimmune uveoretinitis (EAU). Methods EAU animal models were induced by interphotoreceptor retinoid-binding protein (IRBP) R16 peptide with immunization. The rats were divided into 2 groups according to the injection times. TNF-alpha; MCAb was administered intravenously on day 6 or 4, 6 and 8 post-immunization respectively, and then to observe the clinical expression by slit-lamp microscope. Meanwhile, take the rats which did not accept TNF-alpha; MCAb as control group. Delayed type hypersensitivity (DTH) responses were measured on day 13 post-immunization of IRBP R16; the rats were killed on day 14 post-immunization of IRBP R16, and then enucleated the eyes for histopathological examination. To detect the cytokine level of IFN-gamma;, IL-4 in serum and IFN-gamma; in aqueous humor by enzyme-liked immunosorbent assay (ELISA) on day 14 post-injection. The hyperplasia responses of antigen specific lymphocyte of draining lymph node cells were detected. Results The TNF-alpha; MCAb group had mitigated ocular inflammation and decreased pathological grades compared with the control group; the IFN-gamma; concentrations in aqueous humor and serum were decreased, IL-4 was increased in serum; DTH responses were decreased; the hyperplasia responses of draining lymphocytes to IRBP R16 peptide were decreased, all the differences were statistically significant (P＜0.01). The rats accepted TNF-alpha; MCAb thrice had much better curative effect than the rats injected once (P＜0.05). Conclusions Injection of TNF-alpha; MCAb can inhibit ocular inflammation and specific immune cells of EAU remarkably and change the Th1/Th2 balance. Many times injections of TNF-alpha; MCAb were more effective than once.
Objective To observe the influence of interleukin-1beta; (IL-1beta;) on the expression of phosphorylated signal transducers and activators of transcription 3 (pSTAT 3) in rat retinal Muuml;ller cells.Methods For in vitro study cultured Muuml;ller cells were treated with IL-1beta; of different concentrations (0, 0.1, 1, 5 and 10 ng/ml) for 24 hours. For in vivo study, 32 Sprague-Dawley（SD）rats were divided into 4 groups randomly (control group，100，500 and 1000 ng/ml group) with 8 rats in each group. After 24 hours of injection with phosphate buffered solution (PBS), or 100,500,1000 ng/ml IL-1beta; into the vitreous cavities of the above rats, retinas were harvested. The expressions of pSTAT3 in cultured Muuml;ller cells or treated retinas were evaluated by indirect immunofluorescence and western blotting.Results After 24 hours of incubation without IL-1beta;, pSTAT3 has little expression in cultured Muuml;ller cells, but was upregulated by 1 ng/ml or higher IL-1beta; in a dosagedependent manner (F=46.64, 43.78;P＜0.01). pSTAT3 was not expressed in adult rat retina, but was upregulated by vitreous injection of 100 ng/ml or higher IL-1beta; in a dosagedependent manner (F=73.53,43.70;P＜0.01).pSTAT3 expressed mainly in inner nuclear layer and ganglion cell layer. Doublelabeling showed that there was no costaining of pSTAT3 and glial fibrillary acidic protein (GFAP) in retina of control group, but there were many costained Muuml;ller cells in retinas treated with IL-1beta;.Conclusions Expression of pSTAT3 in Muuml;ller cells could be activated by IL-1beta; which may represent one pathway link to reactive gliosis.
ObjectiveTo carry out the work of overseeing transparent administration of clinical department affairs, have clear knowledge on the progress of making clinical department affairs public, and find out problems the staff focus most. MethodQuestionnaire survey was used, combined with the participation of various meetings, interviews with staff, access to documents and other ways between November and December 2013. ResultsIt showed that the rate of transparent administration of clinical department affairs was (78.39±18.55)%. Among all the affairs, policy ones had the highest scores (over 85%), while the rates of research and academic tenure, financial transactions and remuneration allocation, personnel arrangements and training were the lowest (below 75%), and faculty focused on these affairs. ConclusionsFive methods can improve the rate of transparent administration of clinical department affairs effectively:enough attention from clinical departments, concerning what employees focus on, utilizing methods rationally, strong supervision and making full use of monitoring.
Objective Tissue engineering advance in supplying the reparative and reconstructive medicine with promising tissue engineered medical products(TEMPs) and the new therapy alternative. The related supervision and administration of TEMPs is being developed and the standard research of TEMPs is also in progress. The Food and Drug Administration(FDA) of the United States has treated TEMPs as combined products and supervised them according to the level of risk to patients. Lately, FDA has determined that the Center for Devices and Radiological Health (CDRH) should take charge of examination and approval of TEMPs, with the cooperation of the Center for Biological Evaluations and Research(CBER). The regulatory controls have been established respectively in European Union and Japan. In China, TEMPs are identified as medical devices combined with cells. The Department of Medical Device of the State Food and Drug Administration (SFDA) is responsible for the examination and approval of TEMPs, and National Institute for the Control of Pharmaceutical amp; Biological Products(NICPBP) is responsible for evaluation tests. The standards of TEMPs are formulated mainly by the American Society of Testing Materials(ASTM) and International Standardization Organization(ISO).
Objective To observe the effects of intravenous thrombolysis with urokinase for central retinal artery occlusion (CRAO). Methods A total of 115 CRAO patients diagnosed by fluorescence fundus angiography (FFA) were enrolled in this study. The patients included 61 males and 54 females, with a mean age of (56.7plusmn;15.2) years (from 41 to 75 years). The duration ranged from 1 to 30 days. All the patients were affected unilaterally. All the patients were received the treatment of intravenous thrombolysis with urokinase (3000 U/kg, two times per day, continuous treatment for six to seven days) and retrobulbar injection of dexamethasone 2.5 mg (one time per day, continuous treatment for 14 days). Following that, 1.2 mg/kg brain protein hydrolysate (nerve nutrition) and 360 mg troxerutin (vasodilator) were given by intravenous drip (one time per day, continuous treatment for 14 days). Effectiveness of the thrombolytic and subsequent treatments including the recovery of vision and retinal arterial filling time before and after treatment were observed. Comparing the visual acuity of post-treatment and pre-treatment, improving three lines or more is considered as effective markedly, improving two lines as effective, no change or a decline as no effect. With FFA as the retinal circulation recovery index, the arm-retinal circulation time (A-Rct ) le; 15s and all branches of central retinal artery were filled with fluorescence within 2s filling (normal) as effective markedly; A-Rct improved but was in 15 - 20s range, all branches of central retinal artery were filled with fluorescence within 3～8s as effective; A-Rct improved but was still ge; 21s, all branches of central retinal artery were filled with fluorescence within ge;9s as no effect. The relationship between age, gender, the disease course, subsequent treat time and curative effectiveness were analyzed. Results There were 79 patients were examined for FFA again after thrombolysis treatment which including 11 patients with complete obstruction and 68 patients with incomplete obstruction. In 11 patients with complete obstruction, eight patients showed that optic disc vascular retrograde filling disappeared, A-Rct was 28-54s, and the filling time from retinal artery to tip was 18 - 55s; three patients showed persistent optic disc vascular retrograde filling within 3 - 4 minutes of FFA. In 68 patients with incomplete obstruction, A-Rct returned to normal in 35 patients (51.4%), effective in 18 patients (26.5%) and no effect in 15 patients (22.1%). Retinal circulation time was shorter than that before thrombolysis treatment (chi;2=11.4, Plt;0.05). Comparison of distribution of visual acuity before and after thrombolysis treatment, the difference was statistically significant (chi;2=12.1, Plt;0.05). Comparison of distribution of final visual acuity after subsequent treatment with that of after thrombolysis treatment, 48 eyes improved two lines or more, the efficiency was 41.7%, the difference was statistically significant (chi;2=14.6, Plt;0.05). Comparison to that of before treatment, vision changes showed effect markedly in 58 patients (50.4%), effective in 35 patients (30.4%), no effect in 22 patients (19.2%), the difference was statistically significant (chi;2=44.5, Plt;0.05). Comparison the average age to that of effective, valid and invalid patients, the difference was not statistically significant (t=0.98, 1.17, 0.55; Pgt;0.05). There was no relationship between effectiveness and gender (chi;2=2.6, Pgt;0.05). In 76 patients with duration within seven days, 43 patients were effective markedly and 22 patients were effective, the efficiency was 85.5%. In 25 patients with duration of 8 - 15 days, 11 patients were effective markedly and eight patients were effective, the efficiency was 76.0%. In 34 patients who received subsequent treatment 8 - 14 days, 18 patients were effective markedly and nine patients were effective, the efficiency was 79.4%. In 51 patients who received subsequent treatment 15-21 days, 27 patients were effective markedly and 18 patients were effective, the efficiency was 88.2%. Conclusion Intravenous thrombolysis with urokinase was effective in the treatment of CRAO.