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Adrenomedullin and leptin levels in diabetic retinopathy and retinal diseases
(Karger, 2005) Er, H; Doganay, S; Özerol, E; Yürekli, M
Purpose: Proliferative and vascular retinal diseases are important cause of irreversible blindness. Consistent features of these diseases are endothelial dysfunction and angiogenesis. Adrenomedullin (ADM) is a multifunctional vasorelaxant peptide. Leptin is a recently discovered metabolic peptide that regulates energy metabolism in human In the present study, we aimed to investigate the possible roles of adrenomedullin and leptin in the pathophysiology of diabetic and proliferative diseases. Methods: Ten patients with proliferative diabetic retinopathy (57.1 years, 5 female and 5 male) and 8 patients (51 years, 5 female and 3 male) with other retinal diseases including macular hole and epiretinal membrane were included in this study. All the patients had undergone pars plana vitrectomy for complications of the diseases. Vitreous samples were collected by vitreous tap during the vitrectomy. Adrenomedullin analysis was made by using reverse-phase high-performance liquid chromatography (HPLC). Leptin was measured by enzyme-linked immunosorbent assay (ELISA). Body mass index (BMI) [weight (kg)/height (m(2))] was calculated for each group. The Mann-Whitney U test was used for statistics. Results: The age, gender ratio and BMI were not substantially different between the two groups. The mean vitreous adrenomedullin levels (63.9 +/- 7.1 pmol/l) were significantly higher (p < 0.05) in group I than in group II (34.25 +/- 3.0 pmol/l). Leptin levels in vitreous (4.54 +/- 1.6 ng/ml) were also significantly higher (p < 0.05) in patients with diabetic retinopathy than in those without diabetes (1.83 +/- 0.5 ng/ml). Conclusion: Increased adrenomedullin and leptin levels in vitreous humor might be a possible newly associated factor in the course of vascular and proliferative retinal diseases. Copyright (C) 2005 S. Karger AG, Basel.
Aqueous humor adrenomedullin levels differ in patients with different types of glaucoma
(Springer Japan Kk, 2002) Evereklioglu, C; Doganay, S; Er, H; Yurekli, M
Purpose: Adrenomedullin is a multifunctional 52 amino acid large peptide. Recent studies have reported that it is expressed in the iris-ciliary body in the eye and that it decreases intraocular pressure (IOP) by increasing outflow facility via specific adrenomedullin receptors, suggesting a role for this peptide in controlling IOP. In the present study, we aimed to explore clinically the possible involvement of adrenomedullin in the pathophysiology of glaucoma. Methods: Reverse-phase high-performance liquid chromatography was used to determine the aqueous humor adrenomedullin levels in 41 patients (41 eyes) undergoing elective surgery for a variety of ocular diseases in the Research Hospital of Inonu University Medical Faculty between 1999 and 2000. The ocular diseases of the patients included primary open-angle glaucoma (POAG, n = 16), neovascular glaucoma (NG, n = 11). and cataract (n = 14). The study was an open trial with purposive sampling. Aqueous humor samples were taken by paracentesis. Mann-Whitney U-test was used in the statistical analysis and P < .05 was considered as significant. Results were expressed as mean +/- SE. Results: The mean age and sex distribution between groups were comparable. Mean adrenomedullin levels in patients with POAG (22.3 +/- 0.6 pmol/L) were significantly higher than those in patients with NG (5.6 +/- 0.2. pmol/L; P < .001) and cataract (11.9 +/- 0.5, pmol/L., P < .001). On the other hand, the mean aqueous humor adrenomedullin levels in patients with NG were significantly (P < .001) lower than those in cataract patients. Conclusions: This first clinical in vivo study on aqueous humor adrenomedullin levels showed that this peptide may be involved in the pathophysiology of glaucoma. Increased aqueous humor adrenomedullin levels in patients with POAG may indicate a compensatory defense response against increased IOP to slow the formation and progression of a vicious cycle, On the other hand, there may be deficient production of the peptide in patients with NG, or adrenomedullin-producing cells may be lost because of very high IOP during the course of the disease. The control of adrenomedullin levels in the eve might be a target that could be considered in the therapeutic strategies for glaucoma. Further studies in this respect are needed. (C) 2002 Japanese Ophthalmological Society.
Audio-vestibular evaluation in patients with Behcet's syndrome
(Headley Brothers Ltd, 2001) Evereklioglu, C; Cokkeser, Y; Doganay, S; Er, H; Kizilay, A
A prospective controlled clinical study was carried out at the Department of Ophthalmology and ENT, Inonu University Medical Faculty, Turgut Ozal Medical Center, Research Hospital, to evaluate the audiovestibular involvement in patients with Behcet's syndrome compared with controls. Twenty-five consecutive patients with Behcet's syndrome (mean age :+/- SD, 34.96 +/- 8.50) and 20 ageand sex-matched healthy volunteers (hospital staff) as control subjects (mean age +/- SD, 34.45 +/- 9.16) were included in this study. Behcet's patients were divided into two groups according to the number of criteria, complete (all four major criteria) and incomplete (three major criteria without ocular involvement). The groups were compared with each other or controls regarding inner ear involvement. Audiometric pure-tone thresholds at 125 to 8000 Hz were obtained in all subjects in both groups, and pure tone average (PTA) hearing thresholds were calculated for the middle, high and low frequencies. In addition, short increment sensitivity index (SISI), tone decay and BERA examinations were performed in all Behcet's patients. Sensorineural hearing loss (SNHL) was present in six of 25 patients with Behcet's syndrome. Two Behcet's patients had unilateral total SNHL, two had bilateral moderate level SNHL, one had bilateral low-frequency SNHL and one bilateral high frequency SNHL. In two, BERA, and in five SISI, examination disclosed inner ear involvement. In control subjects, the past medical history was normal and there was no consistent audio-vestibular complaint. Their PTA thresholds were all in the normal range. Otoscopic examination findings were normal, with intact, mobile tympanic membranes in both groups. The present study showed that audio-vestibular involvement is not infrequent in Behcet's syndrome compared with age-and sex-matched healthy controls, and it is under-estimated. All Behcet's patients should regularly be followed by an otolaryngologists and be given information about the possibility of inner ear involvement. According to our results, hearing loss occurs more often in older patients and also in the complete form of Behcet's syndrome.
Autonomic nervous system function in childhood migraine
(Blackwell Science Asia, 1999) Yakinci, C; Mungen, B; Er, H; Durmaz, Y; Karabiber, H
Background: Although the pathogenesis of migraine is controversial, autonomic nervous system (ANS) dysfunction has been reported in patients with adult migraine in recent years. The present study was planned to investigate ANS function in childhood migraine. Methods: The migraine and control groups consisted of 25 migraineur and 30 healthy children, respectively. Orthostatic test, sustained handgrip, Valsalva ratio, 30/15 ratio and heart rate responses to deep breathing were used as non-invasive ANS function tests in both groups. Results: In the orthostatic test, systolic (SBP) and diastolic blood pressures (DBP) were higher in the upright than the supine position in the migraine group, but were higher in the supine than upright position in the control group. In the sustained handgrip test, the mean difference in SEP was higher in the migraine than the control group (P = 0.0278), but there was no significant difference in DBP between migraine and control groups (P = 0.107). The Valsalva ratio was higher in the migraine than the control group (P = 0.0002), as was the 30/15 ratio (P = 0.0108). Heart rate responses to deep breathing were not different between the migraine and control groups (P = 0.749). Conclusions: Our results demonstrate ANS dysfunction, with hyperactivity of both the sympathetic and parasympathetic nervous system, in children with migraine.
Bilateral myopia following blunt trauma to one eye
(Wichtig Editore, 2001) Doganay, S; Er, H; Hepsen, IF; Evereklioglu, C
PURPOSE. To evaluate bilateral myopia following blunt trauma to one eye. CASE REPORT. Traumatic myopia is a rare transient situation which may be seen in the injured eye or both eyes after blunt ocular trauma. We examined one case with transient myopia in the left eye which had been exposed to a blunt ocular injury. Myopia was also observed in the right eye 12 hours after the trauma. The right eye and left eye had reverted to emmetropia respectively two and six weeks after trauma. DISCUSSION. The myopia may have been due to ciliary spasm arising from stimulation of the efferent autonomic system in the right eye and ciliary body edema in the left eye. CONCLUSIONS. To our knowledge, this is the first reported case developing bilateral transient myopia after the blunt trauma to only one eye.
Comparative external versus endoscopic dacryocystorhinostomy: Results in 115 patients (130 eyes)
(Mosby, Inc, 2000) Cokkeser, Y; Everelkioglu, C; Er, H
BACKGROUND: Epiphora is an annoying symptom, embarrassing the patient both socially and functionally. The two widely accepted treatment modalities of epiphora resulting from obstruction of the nasolacrimal ductus are external and endoscopic dacryocystorhinostomy (DCR). OBJECTIVE: The aim was to compare the results, operative time, and complications of external and videoendoscopic endonasal DCR performed between December 1994 and December 1998, METHODS: In group 1, conventional primary external DCR with or without silicone tube intubation was performed in 79 patients (66 women and 13 men) with unilateral dacryocystitis, In group 2, endoscopic primary endonasal DCR with hammer-chisel removal of bone located over the lacrimal sac was performed in 51 eyes of 36 patients, 33 women and 3 men (15 bilateral procedures). RESULTS: The follow-up period was 6 to 48 months (mean 25 months) after surgery. The age range was from 4 to 76 years (mean 38.5 years). The success rates of external and endoscopic hammer-chisel DCR were found to be 89.8% and 88.2%, respectively. A lower complication rate was observed in the endoscopic group, with minimal morbidity and shorter operative time compared with the external approach. CONCLUSIONS: Hammer-chisel endoscopic DCR is practical, less traumatic, less time-consuming, and cosmetically more convenient than the external approach. The success rate of the endoscopic DCR procedure is comparable with that of traditional external DCR, and it also allows simultaneous correction of any intranasal pathology.
Comparison of secondary implantation of flexible open-loop anterior chamber and scleral-fixated posterior chamber intraocular lenses
(Elsevier Science Inc, 2003) Evereklioglu, C; Er, H; Bekir, NA; Borazan, M; Zorlu, F
Purpose: To analyze and compare the outcomes and complication rates of secondary implantation of flexible, open-loop, anterior chamber intraocular lenses (AC IOLs) and single-piece, scleral-fixated, posterior chamber IOLs (PC IOLs). Setting. Departments of Ophthalmology, Gaziantep University Medical Faculty, Research Hospital, Gaziantep, and Inonu University Medical Faculty, Research Hospital, Malatya, Turkey. Methods: This study comprised 124 eyes of 113 aphakic patients (61 men, 52 women) with insufficient capsule support who had secondary IOL implantation from January 1997 to June 2001. In Group 1 (n = 73 eyes), a flexible, open-loop AC IOL was implanted and in Group 2 (n = 51 eyes), a single-piece, scleral-fixated PC IOL. The mean follow-up was 34 months (range 6 to 53 months) and took place at several different clinical settings. The mean interval between the initial cataract operation and secondary IOL implantation was 63 months (range 6 months to 12 years). The postoperative outcomes, safety, efficacy, and complication rates were analyzed, and the preoperative and postoperative best spectacle-corrected visual acuities (BSCVAs) were compared. Results. The postoperative mean BSCVA was 20/34.8 +/- 45.2 (SD) in Group 1 and 20/32.1 +/- 33.7 in Group 2; the difference was not significant (P =.718). A BSCVA of 20/40 or better was achieved in 62 eyes (84.9%) in Group 1 and 45 eyes (88.2%) in Group 2. A BSCVA of 20/25 or better was achieved in 40 eyes (54.8%) and 33 eyes (64.7%), respectively. The difference between the 2 groups was not significant (P =.472). Complications occurred in 25 eyes (34.2%) in Group 1 and 13 eyes (25.5%) in Group 2 (P >.05). The most frequent complications in Group 1 were early transient corneal edema, intraocular pressure elevation, cystoid macular edema, hyphema, secondary glaucoma, and iris capture or pupil decentration and in Group 2, suture erosion, a tilted or decentered IOL, fibrin reaction, and vitreous prolapse into the anterior chamber. Conclusions: The AC IOLs and PC IOLs were safe and effective for secondary implantation to correct aphakia. Secondary implantation of the scleral-fixated PC IOL seemed to provide a more favorable outcome and a lower complication rate than the open-loop AC IOL in complicated cataract cases with inadequate capsule and zonular support. As scleral-fixated PC IOL implantation is technically more difficult than AC IOL implantation, the decisive factor in choosing a secondary IOL is surgical experience. Long-term comparison of both techniques is required.
Comparison of serum NO, TNF-?, IL-1?, sIL-2R, IL-6 and IL-8 levels with grades of retinopathy in patients with diabetes mellitus
(Nature Publishing Group, 2002) Doganay, S; Evereklioglu, C; Er, H; Türköz, Y; Sevinç, A; Mehmet, N; Savli, H
Background Vitreal interleukin (IL)-1beta (IL-1beta), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels have previously been determined in patients with proliferative diabetic retinopathy (PDR). However, at present there is no cohort study linking serum levels of NO and many inflammatory cytokines such as TNF-alpha, IL-1beta, soluble IL-2 receptor (sIL-2R), IL-6 and IL-8 to the grade of the microvascular complications. Purpose To determine the relation between the stages of DR and the levels of serum NO, TNF-alpha, IL-1beta, sIL-2R, IL-6 and chemokine IL-8 in patients with diabetes compared with healthy controls. Methods Fifty-three consecutive patients with diabetes (25 men, 28 women) with or without DR and 15 non-diabetic healthy subjects (seven men, eight women) as controls were included in this prospective study. As an indicator for NO, serum total nitrite (NO2- + NO3-) levels (end-product of NO) were measured by the Griess reaction. Serum TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels were determined by a spectrophotometric technique using an Immulite chemiluminescent immunometric assay. The patients with diabetes were classified into three groups according to the stage of DR: no DR (NDR; n = 16), non-proliferative DR (NPDR; n = 18) and PDR (n = 19). The data were analysed using a Mann-Whitney U-test and the results were expressed as mean +/- SE (range). Results The levels of IL-1beta and IL-6 were below the detection limits of the assay (for each, <5.0 pg/ml) in all patients with diabetes and controls. Soluble IL-2R levels ranged from 260 to 958 U/ml, with the highest values observed in the patients with PDR. In 47 of the 53 samples (89%) tested for diabetic patients, IL-8 levels were above the detection limits of the assay (5.0 pg/ml). IL-8 levels ranged from <5.0 to 25.0 pg/ml, with the highest mean values observed in PDR patients. TNF-alpha was detectable in 46 of 53 patients with diabetes (87%), ranging from <4.0 to 26.4 pg/ml, with again the highest values obtained in the patients with PDR. Serum NO levels ranged from 80 to 188 mumol/l, with the highest values obtained in patients with PDR. Taken together, the mean serum NO, sIL-2R, IL-8 and TNF-alpha levels increased with the stage of DR and the highest levels were found in patients with PDR. The PDR patients had significantly (for each, P < 0.001) higher serum NO (166.8 +/- 3.2 mumol/l), sIL-2R (807.9 +/- 33.3 U/ml), IL-8 (17.9 +/- 0.4 pg/ml) ;and TNF-alpha (15.0 +/- 0.8 pg/ml) levels compared with NPDR patients (149.5 +/- 2.1, 659.4 +/- 23.4, 12.9 +/- 1.1, 11.5 +/- 0.6, respectively), NDR patients (115.9 +/- 5.8, 373.8 +/- 15.0, 8.3 +/- 1.0, 6.6 +/- 0.9, respectively) and controls (116.6 +/- 2.3, 392.4 +/- 16.6, 7.2 +/- 0.3, 7.3 +/- 0.3, respectively). Serum levels of these parameters for NPDR patients were also significantly (for each, P < 0.01) higher compared with those of NDR patients and controls. On the other hand, serum NO, sIL-2R, IL-8 and TNF-alpha levels of patients with NDR were comparable with those of controls (for each, P > 0.05). Conclusion The results of the present study suggest that NO, sIL-2R, IL-8 and TNF-alpha may play important roles in the pathophysiology and progression of DR. We think that these potentially inflammatory cytokines and NO with their endothelial implications may act together during the course and progression of DR. These molecules may serve as therapeutic targets for the treatment and/or prevention of diabetes with its systemic and ocular microvascular complications.
Comparison of the effects of Argon and Neodymium: YAG laser iridotomy on cytokines in the rabbit aqueous humor
(Wichtig Editore, 2002) Er, H; Doganay, S; Evereklioglu, C; Turkoz, Y; Gündüz, A; Borazan, M; Ozyalin, F
PURPOSE. We compared the effects in rabbits of iridotomy using the argon or Nd:YAG laser on cytokines such as interleukin 1-beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha). METHODS. Twenty pigmented rabbits (20 eyes) underwent argon and Nd:YAG iridotomy under general and topical anesthesia. Group 1 (10 right eyes) was treated with the argon laser and group 2 (10 right eyes) with the Nd:YAG laser, using an equal number of shots and the same laser parameters for each group. Left eyes in both groups were evaluated as controls. Aqueous humor specimens were collected from each eye preoperatively and 1 and 3 days postoperatively. RESULTS. Aqueous IL-6 and TNF-a levels rose more on day 1 in the Nd:YAG group than the argon group. IL-6 and TNF-a levels were significantly higher on days 1 and 3 than the pre-operative and control levels (p<0.05). TNF-alpha levels on day 1 were significantly lower in the Nd:YAG than the argon group. There were no significant differences between the two laser groups for IL-6 on days 1 and 3. IL-1beta and IL-8 did not change CONCLUSIONS. Our findings suggest that cytokines, particularly IL-6 and TNF-alpha, may be inflammatory mediators in the early inflammation following argon and Nd:YAG laser iridotomies. These results also indicate that cytokines contribute to the acute effects of Nd:YAG and argon laser applications on inflammation.
Craniofacial anthropometry in a Turkish population
(Alliance Communications Group Division Allen Press, 2002) Evereklioglu, C; Doganay, S; Er, H; Gunduz, A; Tercan, M; Balat, A; Cumurcu, T
Objective: To present norms and demonstrate the anthropometric variations in fronto-occipital circumference, inner and outer canthal distances, near and distant [far] anatomical interpupillary distance, canthal index, and circumference-interorbital index across age and sex in urban Turkish subjects. Participants: Three thousand four hundred forty-eight subjects (1852 male, 1596 female) aged 7 to 40 years were included in this study. Methods: Three age groups were studied: children aged 7 to 15 years, young adults aged 16 to 25 years, and adults aged 26 to 40 years. Mean values for each measured parameter were determined at each age between 7 and 25 years. Subjects were also divided into nine age subgroups to observe the change of each parameter with advancing age. Results: The fronto-occipital circumference and outer canthal distance of males was significantly (p < .001) wider than females in all age groups. The near and distant interpupillary distances of male subjects were, on average, wider than the female subjects with greater differences with advancing age. Across all subjects aged 7 to 40 years, the mean of all measured parameters and calculated indexes of men and boys was significantly different from girls and women (p < .001). The mean for interpupillary distances in our study in both sexes were found to be similar to Arabian, Hong Kong, and British children; larger than those of Chinese, Black, Indian, and Caucasians; and smaller than those of Mexican children and a mixed European population. Conclusion: This study clearly shows the anthropometric variation for fronto-occipital circumference, inner canthal distance, outer canthal distance, near and distant interpupillary distance, canthal index, and circumference-interorbital index with age. These developmental data and the normal values of these measurements in healthy subjects are useful for dysmorphologists in the early identification of some craniofacial syndromes, hyper- and hypotelorism, and congenital or posttraumatic telecanthus and of planning surgical intervention. We suggest that the comparison of craniofacial dimensions of a patient must be performed with normal standards specific for age as well as sex and race.
Decreased nitric oxide production in primary open-angle glaucoma
(Wichtig Publ, 2002) Doganay, S; Evereklioglu, C; Turkoz, Y; Er, H
PURPOSE. Raised intraocular pressure (IOP) is the major risk factor responsible for optic nerve damage in primary open-angle glaucoma (POAG). The trabecular meshwork acts as a valve in aqueous outflow and relaxes with nitric oxide (NO) agonists. Since NO is synthesized by endothelium and smooth muscle elsewhere in the body, this study investigated the NO levels in the aqueous humor of patients with POAG compared with cataract patients. MATERIALS AND METHODS. Aqueous humor samples were taken by paracentesis from 16 consecutive patients with POAG (9 male and 7 female; mean age 69.0 +/- 3.4 yrs) and 14 age and sex-matched controls with cataract (8 male and 6 female; mean age 66.7 +/- 4.1 yrs) during elective surgery. As an indicator for NO, aqueous total nitrite levels (end - product of NO) were measured by Greiss reaction. The Mann-Whitney U test was used for statistical analysis and P <0.05 was considered significant. RESULTS. The mean age and sex in two groups were comparable. The mean aqueous humor NO levels were significantly (P = 0.001) lower in patients with glaucoma (72.72 +/- 11.21 mumol/L) than in patients with cataract and no glaucoma (86.92 +/- 11.23 mumol/L). CONCLUSIONS. Decreased NO production in patients with POAG indicates that NO-producing cells may be lost as the disease progresses. The control of NO levels in the eye might be a therapeutic target in glaucoma.
Effect of nitric oxide synthase inhibition in experimental Pseudomonas keratitis in rabbits
(Wichtig Editore, 1998) Er, H; Turkoz, Y; Ozerol, IH; Uzmez, E
Purpose. The aim of this study was to assess the efficacy of the nitric oxide synthase inhibitor L-NG-nitro-arginine-methyleser (L-NAME) in the treatment of experimental Pseudomonas keratitis. Methods. Twelve young New Zealand white rabbits were given intrastromal injections of Pseudomonas aeruginosa strains. Twenty-four hours later, the rabbits were randomly divided into four groups: group I was treated with topical 0.3% ciprofloxacin drops and a single subconjunctival injection of L-NAME (150 mg/kg); group 2 received topical 0.3% ciprofloxacin drops alone; group 3 received a single subconjunctival injection of L-NAME alone; group 4, the control group, was treated with topical balanced salt solution (BSS) drops. One drop of either ciprofloxacin of BSS was applied at each treatment interval. Twenty-six hours after the start of treatment, the eyes were examined by slit lamp to assess inflammation. Aqueous humor specimens were collected from each eye to measure the nitric oxide concentration. Corneas were removed to count bacteria results. Results. Slit lamp examination cell scores were significantly lower for groups 1 and 3 than groups 2 and 4 eyes (p = 0.002 to p = 0.004). No Viable bacteria were detected in the corneas of groups 1 and 2. Group 3 corneas had significantly fewer bacteria (6.33 +/- 0.42 x 10(3)) than group 4 (5.94 +/- 0.16 x 10(4)) (p < 0.05). Nitric oxide levels in the aqueous humor were significantly lower for group I eyes than for groups 2, 3, or 4 (p = 0.02, p = 0.01, and p = 0.003, respectively). Conclusions. We conclude that nitric oxide synthase inhibitors may be a useful adjunct but are not a replacement for traditional antibiotic drop therapy.
The effect of topical parasympathomimetics on corneal epithelial healing in rabbits
(Kluwer Academic Publ, 1997) Er, H
Corneal wound healing is an important process that involves interaction between the different corneal cell layers, growth factors, and environmental conditions. More powerful therapies for the treatment of delayed epithelial wound healing are still being proposed. The objective of this study is to investigate the effects of the direct-acting parasympathomimetic agents on the healing process of corneal epithelium in rabbits. The corneal epithelial defects, 10 mm in diameter, were created in 32 eyes of 16 island rabbits by combination of chemical debridement using n-heptanol and mechanical scraping. Animals were randomly divided into four groups. Groups 1, 2 and 3 were treatment groups; each group consisted of four rabbits (8 eyes). The animals in these groups were treated with topical 1% acetylcholine (ACh), 2% pilocarpine, and 0.75% carbachol drops respectively. In group 4, four rabbits (8 eyes) were used as control group and left for spontaneous healing. The length acid area of the defect were measured at days 3,6,9,12,15,18 and 22 after wounding. Areas of the photographically documented fluorescein-stained defects were measured by planimetry. All eyes in the treatment groups reepithelialized completely. The duration for reepithelialization in Groups 1 and 2 was 12 days, and 18 days for Group 3. In the control group reepithelialization occurred within 22 days. The healing rates of corneal epithelium were statistically significantly faster in all treatment groups as compared with the control group at all times (p=0.0001 to 0.0.0279). Although the rates of wound healing varied, all of the parasympathomimetics used in the present study were found to facilitate wound healing. Our results indicate that direct-acting cholinergic agents, especially ACh and pilocarpine, may have an important therapeutic role in the treatment of severe corneal epithelial injury.
Effects of L-NAME and timolol on aqueous IL-1?, IL-6 IL-8, TNF-? and NO levels after Nd:YAG laser iridotomy in rabbits
(Sage Publications Ltd, 2002) Er, H; Doganay, S; Evereklioglu, C; Cekmen, M; Daglioglu, MC; Isci, N
PURPOSE. Pro-inflammatory cytokines are produced by tissues and play a vital role in the host inflammatory response and uveitis. Nitric oxide (NO) can be produced in large amounts as a response to experimentally-induced uveitis or cytokines. In this study, we measured the levels of pro-inflammatory cytokines such as interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha and free-radical in aqueous humor after Nd:YAG laser iridotomy in rabbits, and investigated whether timolol maleate an anti-glaucoma drug, or a NO synthase inhibitor, NG-nitro-L-arginine methyl esther (L-NAME) had an inhibitory effect on these molecules, since L-NAME is a known anti-inflammatory agent in rabbits. METHODS. Bilateral experimental Nd:YAG laser iridotomy (power 7.5 mJ, mode single burst, aiming beam 4) was performed on 18 rabbits under general plus topical anesthesia. Aqueous humor samples were taken by clear corneal paracentesis preoperatively, and 1 and 24 h postoperatively. Six rabbits (12 eyes) were given bilateral topical timolol maleate 0.5% (Timoptic(R)) drop b.i.d (group 1), six rabbits (12 eyes) received bilateral 0.1 ml subconjuntival injections of L-NAME (150 mg/kg) (group 2), and six rabbits (12 eyes) were treated with topical balanced salt solution (BSS) b.i.d. (control). RESULTS. Preoperative cytokine and NO levels were comparable in the three groups, with no significant differences. In addition, there was no significant difference in baseline cytokine levels between the right and left eyes. In all groups, pre- and postoperative mean IL-1beta levels were below the:detection limit of the assay (< 5.0 pg/ml). In the control group, postoperative mean IL-6, IL-8 and NO levels were significantly higher after Nd: YAG laser iridotomy than before (for each, p < 0.01). Timolol and L-NAME both inhibited the rise in IL-8 and TNF-alpha levels. Timolol also inhibited the rise in IL-6 but not NO. L-NAME had an inhibitory effect against NO, but not IL-6. CONCLUSIONS. L-NAME has an inhibitory effect on IL-8, TNF-alpha and NO, but not on IL-6. Timolol had inhibitory effects on IL-6, IL-8 and TNF-alpha. but not on NO. These preliminary experimental results might help in assessing the effect of Nd: YAG laser iridotomy in aqueous humor, and to understand the inhibitory effects of timolol and L-NAME against these molecules.
Effects of NG-nitro L-arginine and corticosteroids on aqueous humor levels of nitric oxide and cytokines after cataract surgery
(Elsevier Science Inc, 1999) Er, H; Gündüz, A; Turkoz, Y; Çigli, A; Isci, N
Purpose: To assess the efficacy of nitric oxide synthesis (NOS) inhibitor, topical steroids, and nonsteroidal anti-inflammatory drugs on aqueous levels of nitric oxide (NO) and cytokines after cataract surgery. Setting: Research Laboratory, Inonu University Turgut Ozal Medical Center, Malatya, Turkey. Methods: Fifteen rabbits had intercapsular phacoemulsification and were randomly divided into 3 treatment groups: Group 1 was treated with topical prednisolone acetate 1% drops 5 times a day for 1 week; Group 2, flurbiprofen 0.03% drops 5 times a day for 1 week; Group 3, a 0.1 cc subconjunctival injection of NG-nitro L-arginine (L-NAME) (150 mg/kg) 1 day and 3 days after surgery. Three rabbits serving as controls received a subconjunctival injection of an equal volume of balanced salt solution (BSS(R)) at the same times as the L-NAME injections. Aqueous humor specimens were collected from each eye to determine NO and cytokine levels including interleukin-1-beta (IL-1 beta), interleukin-2R (IL-2R), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), Results: The levels of IL-1 beta and IL-6 were higher in Group 2 and the control group than in Groups 1 and 3 at ail times. The differences were not statistically significant (P <.05), Nitric oxide and TNF-alpha levels in Groups 1 and 3 were significantly lower than in Groups 2 and the controls 1, 3, and 7 days postoperatively (P <.05). Conclusion: These findings suggest a strong inhibitory effect of NOS inhibitors and corticosteroids on aqueous levels of TNF-alpha and NO and no inhibitory effect on IL-1 beta and IL-6 levels after cataract surgery. J Cataract Refract Surg 1999; 25:794-799 (C) 1999 ASCRS and ESCRS.
Effects of transforming growth factor-beta 2, interleukin 6 and fibronectin on corneal epithelial wound healing
(Sage Publications Ltd, 1998) Er, H; Uzmez, E
Purpose. The aim of this study was to compare the effects of topically applied transforming growth factor-beta 2 (TGF-beta 2) and interleukin 6 (IL-6), alone and combined with fibronectin, on the rate of corneal wound healing in rabbits. Methods. Twenty-eight rabbits were used for the experiment. After the right eye of each rabbit was debrided with n-heptyl alcohol, the animals were divided into four treatment groups (six rabbits per group) and one control group (four rabbits). The debrided eyes were treated, beginning immediately after wounding and continuing every 2 hours from 8 a.m. to 8 p.m. for 48 hours. Group 1 received TGF-beta 2; group 2 IL-6; group 3, TFR-beta 2 and purified fibronectin; group 4, IL-6 and fibronectin; control group, balanced salt solution. At set intervals each eye was stained with fluorescein and photographed; epithelial defects were measured with a computer-assisted digitizer. The healing rate was calculated by linear regression analysis. Results. The mean healing rates in groups 1, 2, 3, 4, and controls were respectively 1.65 +/- 0.16, 1.68 +/- 0.11, 1.99 +/- 0.12, 2.23 +/- 0.09, and 0.93 +/- 0.18 mm(2)/h. Mean epithelial healing rates for all drug-treatment groups were significantly faster than controls. The healing rates of groups 3 and 4 were significantly faster than groups 1 and 2. Conclusions. We conclude that cytokines, in combination with extracellular matrix proteins, facilitate corneal epithelial wound healing in vivo, possibly by making corneal epithelial cells more sensitive to fibronectin receptors.
Features associated with surgical outcome in patients with stages 4 and 5 retinopathy of prematurity
(Lippincott Williams & Wilkins, 2004) Er, H
[Abstract Not Available]
Histopathologic comparison of conventional radial keratotomy and minimally invasive radial keratotomy in rabbits
(Elsevier Science Inc, 1997) Er, H; Mizrak, B
The aim of the present study was to compare conventional radial keratotomy (RK) with minimally invasive RK (mini-RK) in terms of achieved incisional depth as well as the histopathologic changes in the rabbit corneal structures. Four conventional RK incisions were performed on the right eye and four mini-RK incisions were performed on the left eye of 12 Island rabbits using a centripetal cutting technique. The corneas were excised 20 days after the procedure and examined by light microscopy. Histopathologic examination showed that the mean achieved incisional depth (73.47%) in conventional RK was consistent with the intended incisional depth (80%), However, the mean achieved incisional depth (47.28%) was far from the intended incisional depth (80%) in eyes receiving mini-RK. The difference be tween achieved incisional depth of the two surgical techniques was statistically significant (t = 10.70, P < 0.05). Corneal structural changes and epithelial plug formations were less in eyes in mini-RK than in conventional RK. These findings suggested that the refractive results in mini-RK may be less effective than conventional RK. On the other hand, in the mini-RK group, less epithelial plug formation and limited histopathologic structural alterations may have an important role in preventing long-term overcorrection and corneal rupture after ocular trauma demonstrated in conventional RK technique. (C) 1997 Japanese Ophthalmological Society.
Increased corneal thickness in active Behcet's disease
(Sage Publications Ltd, 2002) Evereklioglu, C; Er, H
PURPOSE. To measure central corneal thickness (CCT) in patients with Behcet's disease (BD), particularly in the active disease. MATERIALS AND METHODS. We measured CCT by ultrasound pachymetry in 64 patients with Behcet's disease and in 20 healthy controls. Forty-one of the patients with BD had ocular involvement and 23 none; 19 of the 41 with ocular involvement were in an active period and 22 had inactive disease. RESULTS. The mean CCT in the group with active ocular involvement was significantly higher (589 +/- 27 mum) than in the control group (553 +/- 21 mum) (p = 0.003), the group with inactive ocular involvement (560 26 mum) (p < 0.001), and the group with no ocular involvement (558 +/- 25 mum) (p < 0.001). After appropriate treatment of patients with active ocular involvement, the mean CCT returned nearly to normal (563 +/- 20 mum) and the difference from controls was not significant. There was no significant difference for the mean CCT between controls and the patients with no ocular involvement or with inactive ocular involvement. CONCLUSIONS. Behcet's patients with active ocular involvement have a thicker CCT than patients with inactive ocular involvement. There was no difference in CCT between controls and patients with no ocular involvement. The CCT of patients with active ocular involvement returned to nearly normal after treatment. CCT must be taken into account when developing a managing and following approach for Behcet's patients with active ocular involvement.
Increased nitric oxide production in patients with Behcet's disease: Is it a new activity marker?
(Mosby, Inc, 2002) Evereklioglu, C; Turkoz, Y; Er, H; Inaloz, HS; Ozbek, E; Cekmen, M
Background. The origin of Behcet's disease (BD) is unclear. One of the prominent features of BD is vasculitis and thrombosis as a result of endothelial dysfunction. Because nitric oxide (NO) is synthesized by endothelium, we considered it as an interesting target of investigation in BD. Objective: Our purpose was to define the level of NO in the serum of patients with BD and its relation with disease activity. Methods: As an indicator for NO, serum total nitrite levels (end product of NO) were measured by Griess reaction in 52 consecutive patients with BD and compared with 32 age- and sex-matched healthy staff volunteers. Serum NO levels of active and inactive patients were compared. Results: The overall serum nitrite levels in patients with BD (40.25 +/- 10.51 mumol/L) were significantly higher (P < .001) than those in healthy volunteers (25.09 +/- 5.33 mumol/L). The difference in serum total nitrite levels among patients with active BD (46.74 +/- 10.62 mumol/L) and inactive BD (33.24 +/- 3.73 mumol/L) was significant (P < .001). Significant differences were observed in serum nitrite between patients in the inactive period of BD and the control group (P < .001). Conclusion: Increased NO production might be responsible for the inflammatory process of BD, NO seems to be related to disease activity.

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