Malondialdehyde and antioxidant enzyme levels in the aqueous humor of rabbits in endotoxin-induced uveitis.

PURPOSE: To investigate the role of oxidative stress in endotoxin-induced uveitis. METHODS: Lipopolysaccharide was injected intravitreally into the right eyes of rabbits. Sterile saline was injected intravitreally into the left eyes as a control. Inflammation was assessed according to clinical score, aqueous humor cell count, and protein levels. Malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, and nitrite levels were measured in the aqueous humor. RESULTS: The clinical grade (p < 0.01), inflammatory cell count (p < 0.001), and protein content (p < 0.001) were significantly higher in the aqueous humor of eyes with uveitis than in that of controls. Malondialdehyde (p < 0.01) and nitrite (p < 0.001) levels in the aqueous humor of eyes with uveitis were significantly higher than in the control group. Superoxide dismutase (p < 0.001), glutathione peroxidase (p < 0.001), and catalase (p < 0.001) levels were significantly lower in the aqueous humor of eyes with uveitis than in that of the controls. CONCLUSIONS: Oxygen free radicals may be implicated as a mediator of inflammation in endotoxin-induced uveitis. The increase in free radicals in the aqueous humor may play a role in the pathogenesis of endotoxin-induced uveitis.

Corneal thickness in trachomatous dry eye.

PURPOSE: To investigate the effect of severe desiccation on corneal thickness in scarring trachoma by comparing the thickness of normal and trachomatous dry eye corneas. METHODS: Ultrasonic pachymetry was used to measure the corneal thickness at nine points in the central and peripheral cornea (superior, superonasal, nasal, inferonasal, inferior, inferotemporal, temporal, superotemporal) in 45 eyes of 27 patients with trachomatous dry eye and 54 eyes of 31 normal subjects. RESULTS: The average thickness of the nine sites in the central and midperipheral cornea was significantly less in trachomatous dry eyes than normal eyes. The superior cornea was the thickest area in both groups, measuring 574.03+/-31.62 microm in trachomatous dry eyes and 611.33+/-34.99 microm in normal eyes (p<0.001). The centre of the cornea was the thinnest, measuring 510.43+/-32.12 microm in trachomatous dry eyes and 546.27+/-36.20 microm in normal eyes (p<0.001). CONCLUSIONS: The thickness of the central and midperipheral cornea was significantly reduced in patients with trachomatous dry eye. The chronic state of severe desiccation, tear film instability and increased immune activation in trachomatous dry eye may contribute to this thinning.

The treatment of severe trachomatous dry eye with canalicular silicone plugs.

PURPOSE: To evaluate the effects of temporary canalicular occlusion with silicone plugs on trachomatous dry eye patients who were on maximal tolerable medical therapy. METHODS: Forty-four trachomatous dry eye patients who had Schirmer testing with topical anaesthetic measuring 5 mm or less and a tear film break-up time of 5 s or less were included. After the lacrimal efficiency test with dissolvable collagen punctal plugs, silicone canalicular plugs were placed in 22 trachomatous dry eye patients. The other 22 patients in the untreated control group were allowed to continue their medical therapy. Pretreatment and post-treatment evaluations included subjective patient assessment, rose Bengal and fluorescein staining, tear film break-up time, Schirmer testing, conjunctival impression cytology and goblet cell counting. RESULTS: Six months after plug placement, 18 eyes (82%) of 22 patients had subjective improvement and all these patients successfully wore plugs for at least 6 months. There were statistically significant differences between the pretreatment and post-treatment test results including rose Bengal and fluorescein staining scores, tear film break-up times and Schirmer testing measurements. Impression cytology showed improvement of squamous metaplasia in 17 eyes (77%). Eight of the patients (36%) were able to decrease dependency on topical therapy. Ten of the patients (45%) completely stopped using artificial tears. There were statistically significant differences between the two groups in the total symptom scores, staining scores, tear film break-up time, Schirmer testing, impression cytology scores and goblet cell counts. CONCLUSION: In cases where topical tear supplementation is insufficient to relieve the signs and symptoms of severe dry eye and the lacrimal puncta have not already been closed by the trachomatous cicatrising process, occlusion of the canaliculi may be useful to prevent drainage of both natural and artificial tears. Canalicular occlusion improves the objective signs and subjective symptoms and may significantly decrease dependency on tear supplements in selected patients.

Increase of free oxygen radicals in aqueous humour induced by selective Nd:YAG laser trabeculoplasty in the rabbit.

PURPOSE: To investigate the impact of selective Nd:YAG laser trabeculoplasty on free oxygen radicals and antioxidant enzymes of the aqueous humour in the rabbit. METHODS: One eye of 18 rabbits was subjected to 360 degrees selective laser trabeculoplasty (LT) with a frequency-doubled Nd:YAG laser (532 nm). The anterior chamber aqueous humour was aspirated 3, 12 hours and 1, 3, 7, 10 days after treatment. Lipid peroxide (LPO) and glutathione S transferase (GST) levels and superoxide dismutase (SOD) activities of aqueous humour were measured. RESULTS: Concentrations of LPO in the aqueous humour of the treated eyes were significantly higher than the untreated eyes until the 7th day. Aqueous SOD activity significantly decreased 3 hours after LT and remained low until day 7. Aqueous GST levels were significantly decreased between 12 hours and 7 days after the LT. CONCLUSIONS: Selective LT was followed by an immediate increase in the aqueous humour LPO concentration and decreases of SOD and GST in the rabbit, probably due to photovaporization and photodisruption caused by the frequency-doubled Nd:YAG laser. The increased aqueous LPO levels suggest that free oxygen radicals are formed in the pigmented trabecular meshwork during LT, and may be responsible for the inflammatory complications of this procedure.

Indocyanine green angiographic findings in young patients with Grönblad-Strandberg syndrome.

PURPOSE: The objective of the present investigation was to define the indocyanine green (ICG) angiographic features of angioid streaks (AS) in young patients with Grönblad-Strandberg syndrome and to compare them with findings on fluorescein angiography (FA) and red-free photographs. METHODS: Complete ophthalmological examination, red-free photography, FA and ICG angiography were performed on 6 patients, 4 women and 2 men, ranging in age from 21 to 33 years, with Grönblad-Strandberg syndrome. RESULTS: ICG angiography showed AS in the form of hypofluorescent lines with numerous associated hyperfluorescent foci. The AS were more clearly visualized and were seen to be more numerous and larger by ICG angiography. Choroidal neovascularization (CNV) and macular involvement had become bilateral in all of the cases. ICG angiography allowed precise localization of CNV in some cases, but it was not much superior to FA in the determination of CNV and the visualization of 'peau d'orange'. CONCLUSIONS: ICG angiography provides some information different from FA in the evaluation of AS, but usually neovascular complications and peau d'orange appearance could be seen more clearly in the red-free photographs and FA. The hypofluorescent AS pattern was significantly observed in young patients with Grönblad-Strandberg syndrome.

Endothelin-1 increase in aqueous humour caused by frequency-doubled Nd:YAG laser trabeculoplasty in rabbits.

PURPOSE: To study the effect of Nd:YAG laser trabeculoplasty (LT) on endothelin-1 (ET-1) concentration of aqueous humour and intraocular pressure (IOP) in rabbits. METHODS: One eye of each of 18 pigmented rabbits was subjected to 360 degrees LT with a frequency-doubled Nd:YAG laser (532 nm), and IOP was measured with a Tono-Pen tonometer before treatment. Post-LT IOP measurements followed by aqueous humour aspiration were performed under general anaesthesia at 3 and 12 h and 1, 3 and 7 days after the treatment. The concentration of ET-1 in aqueous humour was measured by means of a radioimmunoassay. RESULTS: In the eyes that had undergone LT, the concentrations of ET-1 in the aqueous humour were significantly increased at 3, 12 and 24 h after the treatment compared with the contralateral eyes. ET-1 concentrations at 3 and 7 days after LT, however, did not differ significantly from the corresponding contralateral control values. IOP increased following the treatment at 3 and 12 h. IOP values were significantly lower in the treated eyes at 1, 3 and 7 days after the treatment than in the control eyes. CONCLUSIONS: The results show that LT in rabbits was followed by an immediate and short-term increase in aqueous humour ET-1 that might be caused by leakage from uveal tissue. This may be responsible for the release of prostaglandins causing the IOP increase and inflammatory complications of LT.

Ketorolac-tobramycin combination vs fluorometholone-tobramycin combination in reducing inflammation following phacoemulsification cataract extraction with scleral tunnel incision.

OBJECTIVE: The objective of this study was to compare the efficacy of ketorolac-tobramycin combination with fluorometholone-tobramycin combination in the control of ocular inflammation after endocapsular phacoemulsification cataract surgery with scleral tunnel incision. PATIENTS AND METHODS: This was a prospective, randomized, investigator masked, 2-week, single-center study. Ocular examinations were carried out preoperatively and postoperatively on days 1 (baseline), 2, 3, 7, and 14. There were 60 patients (30 in each treatment group) undergoing uncomplicated cataract-lens implant surgery enrolled and randomized in the study. The baseline parameters were similar in the two study groups. At each visit comprehensive ocular examinations were performed and a 4-point (0 to 3) grading system was used to record findings of the burning/stinging sensation, blurred vision, ocular discomfort, conjunctival hyperemia, anterior chamber flare, and anterior chamber cells. RESULTS: There was no statistically significant difference between the treatment groups in the findings of the ocular inflammation at any of the postoperative visits. Both treatments were equally well tolerated. CONCLUSIONS: This study suggests that ketorolac may be an alternative to some corticosteroids (fluorometholone). It is generally accepted that fluorometholone is not as potent an anti-inflammatory as prednisolone the most commonly used steroid following cataract extraction.

Three-day course of oral azithromycin vs topical oxytetracycline/polymyxin in treatment of active endemic trachoma.

PURPOSE: The aim of this study on endemic trachoma was to carry out a comparison of azithromycin (3-day course, oral dose of 10 mg/kg per day) with conventional treatment (topical oxytetracycline/polymyxin ointment; twice a day for 2 months) in a rural area near Sanliurfa, Turkey. METHODS: Ninety-six subjects with active trachoma were randomly assigned conventional or azithromycin treatment. Subjects were examined 1, 2, 3, and 6 months after the start of treatment. Clinical findings were recorded for each eye. Swabs were taken from upper eyelids 3 and 6 months after the start of treatment for direct fluorescein antibody test. RESULTS: By six-month follow-up, trachoma had resolved clinically in 43 (89.58%) of the 48 subjects who received azithromycin, compared with 33 (68. 75%) of the 48 who were treated conventionally. Microbiological success rates (direct fluorescein antibody test negativity) were 83. 33% in the azithromycin group and 62.50% in the conventional therapy group. Compliance with both treatments was good. By 6 months, 14.58% of the subjects in azithromycin group and 33.33% of the subjects in the topical treatment group were reinfected. There were significant differences in the efficacy of the treatment effects and the re-emergence of disease between the two treatment groups. Azithromycin was well-tolerated. CONCLUSIONS: These results indicate that azithromycin may be an effective alternative for patients with active trachoma. As a systemic treatment, a 3-day course oral dose has important potential for trachoma control.

BAG1L enhances trans-activation function of the vitamin D receptor.

The vitamin D receptor (VDR) is a member of the steroid/retinoid receptor superfamily of nuclear receptors that has potential tumor-suppressive functions. We show here that VDR interacts with and is regulated by BAG1L, a nuclear protein that binds heat shock 70-kDa (Hsp70) family molecular chaperones. Endogenous BAG1L can be co-immunoprecipitated with VDR from prostate cancer cells (ALVA31; LNCaP) in a ligand-dependent manner. BAG1L, but not shorter non-nuclear isoforms of this protein (BAG1; BAG1M/Rap46), markedly enhanced, in a ligand-dependent manner, the ability of VDR to trans-activate reporter gene plasmids containing a vitamin D response element in transient transfection assays. Mutant BAG1L lacking the C-terminal Hsc70-binding domain suppressed (in a concentration-dependent fashion) VDR-mediated trans-activation of vitamin D response element-containing reporter gene plasmids, without altering levels of VDR or endogenous BAG1L protein, suggesting that it operates as a trans-dominant inhibitor of BAG1L. Gene transfer-mediated elevations in BAG1L protein levels in a prostate cancer cell line (PC3), which is moderately responsive to VDR ligands, increased the ability of natural (1alpha,25(OH)(2) vitamin D(3)) and synthetic (1alpha, 25-dihydroxy-19-nor-22(E)-vitamin D(3)) VDR ligands to induce expression of the VDR target gene, p21(Waf1), and suppress DNA synthesis. Thus, BAG1L is a direct regulator of VDR, which enhances its trans-activation function and improves tumor cell responses to growth-suppressive VDR ligands.

A survey of trachoma: the histopathology and the mechanism of progressive cicatrization of eyelid tissues.

The aim of this study is to demonstrate the spectrum of conditions encompassed by the term 'trachomatous cicatrization of eyelid tissue', to discuss the mechanisms of scar tissue formation and to describe sequelae in this potentially blinding condition. Specimens of eyelid tissues were taken from 27 upper eyelids of 21 patients with entropion who underwent surgical procedures and 2 post-mortem upper eyelids with severe trachomatous entropion. Upper palpebral conjunctival swabs and biopsy specimens were taken from 5 patients with active trachoma and they were examined by fluorescence microscopy and routine histopathological methods. Conjunctival impression cytology samples were collected in all patients. In specimens taken from patients with active trachoma the inflammatory infiltrate was organized as lymphoid follicles in the underlying stroma and impression cytology showed cytoplasmic elementary bodies. In specimens taken from patients with scarring trachoma light microscopy studies showed subepithelial fibrous membrane formation, squamous metaplasia and loss of goblet cells, pseudogland formation in conjunctiva, degeneration of orbicularis oculi muscle fibres, subepithelial vascular dilatation, localized perivascular amyloidosis and subepithelial lymphocytic infiltration. Accessory lachrymal glands and the ducts of glands were compromised by subepithelial infiltration and scarring. The contraction of the subepithelial fibrous tissue formed by collagen fibres and anterior surface drying are the main factors contributing to the chronic cicatrization and entropion formation.

Pretarsal and marginal orbicularis oculi muscle fiber changes in trachomatous cicatricial entropion: histopathological evaluation.

PURPOSE: To evaluate the histopathological changes of pretarsal and orbicularis muscle fibers in trachomatous cicatricial entropion. METHODS: Orbicularis muscle tissue specimens were histopathologically evaluated in 17 eyes of 11 cases in which anterior lamellar reposition and/or wedge-shaped tarsal resection or Wies procedure were performed. RESULTS: Degeneration of orbicularis muscle fibers, atrophy, connective tissue increase between muscle fibers and edema were observed in 13 tissue specimens. Muscle fiber changes were more commonly observed in cases with severe entropion, in which Wies procedure was performed. CONCLUSIONS: These histopathological changes, which may develop secondary to other structural changes that can cause entropion in the eyelid and weaken the orbicularis muscle, may be a co-factor influencing the severity of entropion more than causing entropion alone.

Microbiologic analysis of aqueous humor in phacoemulsification.

PURPOSE: This study was designed as a microbiologic survey of the fluids aspirated from the anterior chamber at the end of cataract extraction performed by phacoemulsification, and to correlate the contamination rate of the anterior chamber to the surgical technique used. METHODS: One hundred and one consecutive patients (126 eyes) who underwent cataract extraction by phacoemulsification and posterior chamber intraocular lens implantation were included in the study. Microscopical examination, culture, and determination of the number of colonies were carried out on the bacteria and fungi in the anterior chamber fluids aspirated at the end of surgery, before final suture placement. RESULTS: Anterior chamber fluids yielded positive cultures in nine specimens (8.14%), six of which were identified as coagulase-negative staphylococci. Quantification disclosed colony counts ranging between 2-10 and 10-40 per mL. CONCLUSIONS: Preliminary results in a small population show that the contamination of the aqueous humor is significantly less frequent if the cataract extraction is performed by phacoemulsification.

Effects of frequency-doubled Nd:YAG laser trabeculoplasty on diurnal intraocular pressure variations in primary open-angle glaucoma.

In order to investigate the effects of laser trabeculoplasty (LT) on diurnal intraocular pressure (IOP) variations in 36 eyes of 30 cases with primary open-angle glaucoma (POAG) in which medical treatment was terminated, the IOP curves, recorded 24 h before as well as 24 h and 12 weeks after LT were compared. Twelve weeks after LT, significant IOP decreases were observed: 36.42% in the mean IOP, 29. 77% in the mean peak IOP and 50.04% in the mean pressure range. LT might therefore have beneficial effects on the diurnal IOP variations in cases with POAG.

Combinational effects of vitamin D3 and retinoic acid (all trans and 9 cis) on proliferation, differentiation, and programmed cell death in two small cell lung carcinoma cell lines.

The effects of a combination of vitamin D3 [1,25(OH)2D3] and retinoic acid (RA) on proliferation, differentiation, and apoptosis of the human small cell lung carcinoma (SCLC) cell lines NCI-H82 and NCI-H209 were evaluated. Cell proliferation was inhibited by 1,25(OH)2D3 and RA alone. The combination of 1,25(OH)2D3 and the cis form of retinoic acid resulted in an additive decrease in cell proliferation and the induction of apoptosis in various concentrations. Moreover, 3H-thymidine incorporation was inhibited and the number of viable cells was decreased. The characteristics of the apoptotic cells were examined and confirmed by morphologic analysis, light and electron microscopy, and fluorescence detection. It was concluded that 1,25(OH)2D3 and RA exert additive effects on the inhibition of proliferation and the induction of apoptosis in both the NCI-H82 and the NCI-H209 SCLC cell lines. This finding has important implications for the use of retinoids and 1,25(OH)2D3 in cancer prevention and in the therapy of small cell lung carcinoma.

Effects of retinoic acid (all-trans and 9-cis) on tumor progression in small-cell lung carcinoma.

The two stereoisomers of retinoic acid (RA), all-trans and 9-cis-RA, are regulators of cell proliferation, differentiation and apoptosis. In this study, the aim was to evaluate the effects of all-trans-and 9-cis-RA on cell growth, proliferation, and on the induction of apoptosis in the human small cell lung carcinoma (SCLC) cell lines NCI-H82 and NCI-H209. The application of various concentrations of all-trans and 9-cis-RA were able to inhibit cell growth and proliferation. Moreover, 3H-thymidine incorporation was inhibited and the number of viable cells decreased, suggesting that all-trans-RA and 9-cis-RA can inhibit cell proliferation in a dose dependent manner. Morphological examinations (light, electron and fluorescence microscopy) demonstrated that both retinoids had profound effects on the induction of apoptosis. Our investigation also showed that, compared to all-trans-RA, 9-cis-RA is a stronger inducer for the inhibition of cell growth and proliferation and that it is more effective in the induction of apoptosis in small cell lung carcinoma cells in culture.

A group of deltanoids (vitamin D analogs) regulate cell growth and proliferation in small cell carcinoma cell lines.

A group of deltanoids has been used for studying the inhibition of cell growth and proliferation in two small cell lung carcinoma (SCLC) in vitro. The biologically active deltanoid, 1,25 dihydroxyvitamin D3 (1,25 (OH)2D3), has functions beyond its classical roles of stimulating calcium transport and serum calcium. It also causes the differentiation of a variety of precursor cells and suppresses growth. Although 1,25(OH)2D3 has an inhibitory effect on growth of certain malignant cells, its hypercalcemic effect has prevented clinical applications. Several new deltanoids, which showed comparable or even greater abilities to induce differentiation and to inhibit proliferation, have been identified. Furthermore, these synthetic deltanoids have been shown to be less effective on calcium metabolism and less hypercalcemic. We have selected four synthetic deltanoids; MC-903, 1 alpha-OH-pregnacalciferol, 19-nor-24 homo, and 19-nor-22(E). When compared with 1,25 (OH)2D3, these deltanoids showed considerable potency on cell growth and proliferation in the NCI-H82 and the NCI-H209 SCLC lines. Cells were treated with various concentrations of deltanoids. They inhibited the growth and proliferation of both SCLC cells in vitro in a time-and dose-dependent manner, as determined by cell number and 3H-thymidine uptake. 19-nor-22(E) showed an antiproliferative effect significantly comparable to 1,25(OH)2D3 in the NCI-H82 cell line 1 alpha-OH-pregnacalciferol, 19-nor-24 homo, and 19-nor-22(E) inhibited the cell growth in the NCI-H209 cells within the same significance as 1,25 (OH)2D3. The degree of the suppressive effect of the deltanoids was cell line dependent.