Recovery of visual field function in the optic neuritis treatment trial

PURPOSE: To assess the pattern of recovery of the visual field of patients with optic neuritis and to determine whether all affected portions of the visual field recover similarly or certain portions of the visual field have greater recovery. METHODS: We reviewed the Humphrey Visual Field (Allergan-Humphrey Inc, San Leandro, California) data from the initial and 6-month examination for the involved and fellow eyes of patients enrolled in the Optic Neuritis Treatment Trial (ONTT). The average threshold for each patient was calculated for the entire tested field and for locations within concentric rings having a radius 3, 9, 15, 21, and 27 degrees from fixation. The absolute amount of improvement and percentage improvement in average threshold between entry and the 6-month follow-up examination were determined for each patient. These measurements were compared within the concentric rings to assess patterns of recovery. RESULTS: Patients with localized defects recovered 86%+/-20% of their initial defect in average threshold, whereas those having diffuse defects recovered an average of 85%+/-23%. The area about fixation had the greatest relative recovery of threshold (87%+/-21% at 3 degrees); the relative recovery decreased with increasing eccentricity from fixation (P<.01). CONCLUSIONS: Patients with optic neuritis have a marked return of visual field function that does not appear to differ between patients with diffuse or localized field defects. The reduced redundancy of axons in the periphery of the field compared with near fixation may be responsible for the greater relative recovery of threshold near fixation.     

An Experimental Study on Homoharringtonine Liposome and Glaucoma Filtration Surgery

Purpose: To observe the inhibitory action of homoharringtonine liposome during the healing process of wounds in the filtering sitesMethods: posterior sclerectomies were performed in 14 rabbits. Postoperatively one eye of each rabbit received subconjunctival injections of HH liposome and fellow eye received saline injection in a randomized masked fashion.Results; Fourteen days after operation the IOP of experimental eyes reduced significantly (P < 0.01) as compared with the controlled eyes, and the number of remaining filtering blebs increased noticeably (P< 0.05). Pathohistological examination revealed that the number of fibroblasts per square micron in the filtering sites and the thickness of the scars in the center of the filtering sites of the experimental eyes were less than those of the controlled eyes. No serious ocular toxic and side effects were found.Conclusion : This experiment suggests that homoharringtonine liposome can markedly inhibit the scar formation of filtering sites after glaucoma fi     

Immunocytochemical Study of Cells in the Vitreous of Proliferative Virteoretretinopathy

Purpose: To identify the cellular components of vitreous samples obtained during vit-rectomy for proliferative vitreoretinopathy(PVR).Methods: With the use of three intermediate filament (IF) proteins, vimentin, glialfibrillary acidic protein (GFAP), and cytokeratin (CK), cytocentrifuge slides of 14fresh vitreous aspirates were detected with immunohistochemical technique.Results: All the specimens contained epithelial-like proliferative cells with or withoutpigment and some membrane-like pieces. Immunocytochemical staining showed that76.0-90.0% cells stained for CK, 17.4-29.6% cells expressed GFAP, and 80.1-91.0% cells were positive for vimentin.Conclusions : Majority of cells in the vitreous samples originated from retinal pigmentepithelial cells (RPE) and glial cells in PVR. Expression of IF proteins may be determinedby tissue of origin and local microenvironment. Eye Science 1999 ; 15; 13 - 16.     

Influences of methylcellulose on corneal epithelial wound healing.

We performed a study to evaluate the influence of methylcellulose (MC) on the corneal epithelial wound healing. A precise epithelial wound 2.0 mm in diameter and 70 microm in depth was created by an excimer laser on the cornea of a pig's eyeball. After treatment, the eyeballs were cultured in the incubator and perfused with TC-199 medium into the vitreous cavity. Topical MC with eight different combinations of concentrations and viscosities for experimental groups and BSS for the control group were applied on the epithelial defects three times. Wounds were evaluated 24 hours later with fluorescein stain and recorded with a scoring system. All of the experimental groups except one showed a more statistically significant superior wound-healing rate than the control group. MC possesses the effect to accelerate corneal epithelial wound healing.     

Incidence of presumed cytomegalovirus retinitis in HIV-infected pediatric patients.

INTRODUCTION: Large population studies of adult patients suggest an incidence of cytomegalovirus (CMV) retinitis as high as 19% to 20% as a late complication of adult HIV infection. We conducted this prospective study of a large cohort of HIV-infected children to determine the incidence of CMV retinitis in HIV-infected children. METHODS: From January 1984 to August 1997, 173 HIV-infected children were followed up for an average of 55.3 months (13-164 months). The patients were seen in the Department of Pediatrics at least once every 6 months. Ophthalmologic examinations were initiated when a patient's CD4 count dropped below 50 or sooner if required for ophthalmologic or other indications. Ophthalmologic examination was then repeated every 6 months. RESULTS: A total of 116 (67%) of 173 patients underwent ophthalmologic examination. Four (3.4%) of 116 patients had CMV retinitis at a mean time of 17.3 months (8-38 months) after their CD4 counts dropped below 20. None of the 4 patients with CMV retinitis had subjective visual complaints despite advanced retinitis. Three patients had bilateral and 1 patient had unilateral CMV retinitis. CONCLUSIONS: CMV retinitis occurred infrequently in HIV-infected pediatric patients and was diagnosed only in patients with a CD4 count below 20. Routine ophthalmologic screening examinations may not be necessary in pediatric patients until the CD4 count is below 20. Because children may not complain of decreased vision, at-risk children should undergo frequent ophthalmologic examination.     

Suppression of nitric oxide synthase and the down-regulation of the activation of NFkappaB in macrophages by resveratrol

Resveratrol, naringenin and naringin are naturally occurring flavonoids in grapes and grapefruits. The anti-inflammatory effects of these flavonoids have been well documented, but the mechanism is poorly characterized. High concentration of NO are produced by inducible NO synthase (iNOS) in inflammation, and the prevention of the expression of iNOS may be an important anti-inflammatory mechanism. In this study, the effects of these flavonoids on the induction of NO synthase (NOS) in RAW 264.7 cells activated with bacterial lipopolysaccharide (LPS, 50 ng ml(-1)) were investigated. Resveratrol was found strongly to inhibit NO generation in activated macrophages, as measured by the amount of nitrite released into the culture medium, and resveratrol strongly reduced the amount of cytosolic iNOS protein and steady state mRNA levels. However, the inhibitory abilities of naringenin were lower, and the inhibitory abilities of naringin were almost negligible. In electrophoretic mobility shift assays, the activation of NFkappaB induced by LPS for 1 h was inhibited by resveratrol (30 microM). Furthermore, in immunoblotting analysis, cells treated with LPS plus resveratrol showed an inhibition of phosphorylation as well as degradation of IkappaBalpha, and a reduced nuclear content of NFkappaB subunits. The flavonoids may be of value for inhibiting the enhanced expression of iNOS in inflammation through down-regulation of NFkappaB binding activity.     

PKCbetaI mediates the inhibition of P2Y receptor-induced inositol phosphate formation in endothelial cells.

1. Bovine pulmonary artery endothelium (CPAE) expresses phospholipase C (PLC)-linked P2Y1 and P2Y2 receptors, for them 2-methylthio-ATP (2MeSATP) and UTP are respective agonists. Here, we have investigated the particular protein kinase C (PKC) isoform(s) responsible for the inhibition of P2Y1 and P2Y2 receptor-evoked inositol phosphate (IP) formation by phorbol 12-myristate 13-acetate (PMA). 2. Although short-term (20 min) pretreatment of cells with PMA attenuated 2MeSATP- and UTP-induced phosphoinositide (PI) breakdown, this inhibition was lost after 15 h. Preincubation with PMA for 24 h, on the contrary, potentiated 2MeSATP and UTP responses. The IP formation stimulated by NaF was unaltered by PMA pretreatment. 3. Western blot analysis showed that treatment of CPAE with PMA resulted in a rapid translocation of PKC isoform betaI, epsilon and mu, but not lambda, from the cytosol to the membrane fraction. 4. Pretreatment of the selective PKC inhibitor Ro 31-8220 attenuated the inhibitory effect of PMA on IP formation. Go 6976 (an inhibitor of conventional PKCalpha, beta and gamma) and LY 379196 (a selective PKCbeta inhibitor) also dose-dependently inhibited the PMA-mediated desensitization. 5. Transfection of PKCbeta-specific antisense oligonucleotide reduced PKCbetaI protein level and inhibited PMA-mediated PI reduction. 6. RT - PCR analysis showed that PMA treatment for 4 - 24 h up-regulated P2Y1 and P2Y2 receptors at the mRNA levels. 7. These results suggest that PKCbetaI may exert a negative feedback regulation on endothelial P2Y1 and P2Y2 receptor-mediated PI turnover. The down-regulation of PKCbetaI and enhanced P2Y receptor expression together might contribute to the late PI enhancing effect of PMA.     

Protection against ischemic damage by adenosine amine congener, a potent and selective adenosine A1 receptor agonist

Although the selectivity and potency of adenosine amine congener (ADAC) at adenosine A1 receptors are similar to other highly selective agonists at this receptor type, the chemical structure of the N6 substituent is completely different. We now demonstrate that the characteristics of the therapeutic profile of ADAC are distinct from those observed during our previous studies of adenosine A1 receptor agonist-mediated neuroprotection. Most significantly, chronic treatment with low microgram doses of ADAC (25-100 microg/kg) protects against both mortality and neuronal damage induced by 10 min bilateral carotid occlusion in gerbils. At higher chronic doses, the statistical significance of the protective effect is lost. Acute preischemic administration of the drug at 75-200 microg/kg also results in a statistically significant reduction of postischemic mortality and morbidity. These data indicate that, contrary to other adenosine A1 receptor agonists whose chronic administration enhances postocclusive brain damage, ADAC may be a promising agent in treatment of both acute (e.g., cerebral ischemia) and chronic (seizures) disorders of the central nervous system in which adenosine A receptors appear to be involved.     

Luteolytic effects of DL111-IT in pregnant rats

The present studies were conducted to evaluate the effects of DL111-IT [3-(2-ethyl phenyl)-5-(3-methoxy phenyl)-1H-1,2,4 triazol] on ovaries of pregnant rats. Pregnant rats were i.m. treated with DL111-IT 2.5 mg kg(-1) day(-1) or camellia oleum (vehicle control) 0.2 ml/day from day 6 of pregnancy for 1, 3 or 5 days. Blood and ovaries were collected 24 h after the last injection. Ovarian fresh weight and protein contents, activities of the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) in ovaries, and cell apoptosis of corpus luteum (including hematoxylin-eosine stain, in situ 3'-end labeling and nucleosomal banding) were estimated. Compared with that in the control group, ovarian fresh weight declined 11% and 22% after DL111-IT-3 days and -5 days; protein content dropped 29% after 5-day administration. DL111-IT for 3 days provoked a marked decrease of serum progesterone, by 31% of the control; the activity of 3beta-HSD decreased 34.4% after i.m. DL111-IT for 5 days, while that of 20alpha-HSD increased dramatically after only one injection of DL111-IT (P < 0.01). Histological analysis and in situ 3'-end DNA labeling indicated that DL111-IT induced the pyknosis of cells and the formations of apoptotic bodies and intense oligonucleosomes in luteal cells of pregnant rats. The cell apoptosis induced by DL111-IT was further confirmed by evaluation of nucleosomal DNA fragmentation by agarose gel electrophoresis in cultured luteal cells exposed to DL111-IT for 24 h. In conclusion, all results, including shrunken luteal cells, decreased concentration of protein content and serum progesterone, changed activities of 3beta-HSD and 20alpha-HSD and formation of DNA fragments in luteal cells, showed the luteolytic effect of DL111-IT in pregnant rats.