Turgut Yilmaz

Moderate Exercise Combined with Dietary Vitamins C and E Counteracts Oxidative Stress in the Kidney and Lens of Streptozotocin-induced Diabetic Rat

Oxidative stress has a key role in the pathogenesis of diabetes-induced cataract formation and nephropathy. Daily moderate exercise and vitamins C and E (VCE) supplementation can be beneficial to diabetes due to reducing blood glucose and free radical production. The aim of this study was to analyze the effect of moderate exercise with vitamin VCE on lipid peroxidation (LP) and antioxidative systems in the kidneys and lens of streptozotocin-induced diabetic rats. Forty female Wistar rats were used. They were randomly divided into four groups. The first and second groups were used as control and diabetic groups. The third group was the diabetic-exercise group. VCE-supplemented feed was given to diabetic-exercise rats constituting the fourth group. Animals in the exercised groups were moderately exercised daily on a treadmill for three weeks (five days a week). Diabetes was induced on day zero of exercise. Body weights in the four groups were recorded weekly. Lens and kidney samples were taken from all animals on day 20. Glutathione peroxidase (GSH-Px), reduced glutathione (GSH), vitamin E, and beta-carotene levels in kidney and lens, albumin in plasma, and body weight were significantly lower in the diabetic group than in the control group, whereas there was a significant increase in LP of kidney and lens as well as plasma glucose, urea, and creatinine levels in the diabetic group. The decrease in antioxidant enzymes, vitamins, and albumin and the increase in LP and glucose levels in diabetic rats were significantly improved with exercise and VCE supplementation. In the diabetic animals, the decreased beta-carotene and vitamins A levels in kidney did not improve through exercise only, although their levels were increased by exercise plus VCE supplementation. In conclusion, these data demonstrate that lipid peroxidation increases in the lens and kidney of diabetic animals and this could be due to decreases in antioxidant vitamins and enzymes. However, dietary VCE with moderate exercise may strengthen the antioxidant defense system through the reduction of ROS and blood glucose levels. The VCE supplementations with exercise may play a role in preventing the development of diabetic nephropathy and cataract formation in diabetic animals.

Effects of melatonin, vitamin E and octreotide on lipid peroxidation during ischemia-reperfusion in the guinea pig retina

Purpose The purpose of this study is to provide evidence that free radical damage is a component of retinal ischemia-reperfusion (I/R) injury, and to determine whether melatonin, vitamin E and octreotide can protect the retina from this injury. Methods The right eyes of 50 male guinea pigs weighing 500–600 g were used. The animals were randomly assigned to group 1 (control), group 2 (I/R), group 3 (melatonin + I/R), group 4 (vitamin E + I/R) and group 5 (octreotide + I/R). Groups 3, 4 and 5 received four subcutaneous injections with a 6-h interval for a total daily dose of 10 mg/kg melatonin, 150 mg/kg vitamin E and 22 μg/kg octreotide. The first dose of each substance was administered 5 minutes before retinal ischemia, which was induced for 1.5 hours, followed by reperfusion for 24 hours. All three substances were repeated for 6, 12 and 18 hours during reperfusion. The animals were killed at 24 hours of reperfusion. Retinas were isolated and processed for the quantification of malondialdehyde (MDA). Results The compounds had the following relationships: melatonin more than vitamin E more than octreotide in preventing retinal damage by ischemia-reperfusion. All three gave significant protection against the formation of MDA (10.4±2.3, 12.4±2.4, 13.9±1.5 nmol/100 mg tissue wet weight, respectively) compared to the control (3.7±1.3 nmol/100 mg tissue wet weight) and I/R groups (22.7±6.2 nmol/100 mg tissue wet weight). Conclusions This study demonstrates the inhibitory effect of melatonin, vitamin E and octreotide on MDA levels during retinal ischemia-reperfusion injury.

Plasma and vitreous homocysteine concentrations in patients with proliferative diabetic retinopathy.

Purpose: An increase in plasma concentrations of homocysteine (Hcy) in proliferative diabetic retinopathy (PDR) has been described. The aim of this study was to investigate vitreous Hcy levels in patients with PDR. Methods: Plasma and vitreous samples were obtained simultaneously at the time of vitreoretinal surgery from 20 patients with PDR and 12 nondiabetic patients with nonproliferative ocular diseases. Hcy levels were determined by high-performance liquid chromatography. Results: The mean vitreous and plasma Hcy concentrations for the diabetic group were 3.64 ± 0.65 &mgr;mol/L and 16.04 ± 2.75 &mgr;mol/L, respectively. The mean intravitreal and plasma Hcy concentrations for the control group were 1.08 ± 0.45 &mgr;mol/L and 9.18 ± 3.91 &mgr;mol/L, respectively. Both plasma and vitreous Hcy concentrations for the diabetic group were significantly higher than those for the control group (P < 0.001). A statistically significant correlation between vitreous and plasma Hcy concentrations was present only for the diabetic group (r = 0.525; P = 0.017). Conclusion: Vitreous Hcy concentrations were elevated in patients with PDR probably due to breakdown of the blood–retina barrier.

The protective effects of melatonin, vitamin E and octreotide on retinal edema during ischemia-reperfusion in the guinea pig retina

PURPOSE The purpose of this study is to provide evidence that free radical damage is a component of retinal ischemia-reperfusion (I/R) injury, and to determine whether melatonin, vitamin E and octreotide can protect retina from this injury. METHODS The right eyes of 50 male guinea pigs weighing 500-600 g were used. The animals were randomly assigned to group 1 (control), group 2 (I/R), group 3 (melatonin + I/R), group 4 (vitamin E + I/R) and group 5 (octreotide + I/R). Groups 3, 4 and 5 received four subcutaneous injections at six-hour intervals for total dosage of 10 mg/kg melatonin, 150 mg/kg vitamin E and 22 g/kg octreotide respectively. The first dose of each substance was administered 5 minutes before retinal ischemia. Retinal ischemia was induced for 1.5 hours, then followed by reperfusion for 24 hours. Infections of all three substances were repeated at 6, 12 and 18 hours during reperfusion. The animals were killed at 24 hours of reperfusion. Sagittal sections of 4 m were cut and stained with hematoxylin and eosin for light microscopic evaluation. The average thickness (edema) of the inner plexiform layer for each eye was measured in sagittal sections near the optic nerve and expressed in microns. RESULTS The efficacy of each compound had the following relationships: melatonin>vitamin E>octreotide in preventing retinal damage by ischemia-reperfusion. The mean thickness of the inner plexiform layer was 13.3 0.8 m, 25.9 2.0 m, 20.0 0.7 m, 21.6 0.7 m, 23.9 0.8 m respectively in the control, I/R, I/R plus melatonin, I/R plus vitamin E and I/R plus octreotide groups. The thickness of the inner plexiform layer in group 1 (control) was significantly less than the other groups (p<0.001). The inner plexiform layer was thicker in the I/R group than with I/R plus melatonin, I/R plus vitamin E and I/R plus octreotide (all p <0.01). The inner plexiform layer was thicker in the I/R plus octreotide group than the I/R plus vitamin E and I/R plus melatonin groups both (p<0.05). Compared to the I/R plus melatonin group, the inner plexiform layer was significantly thicker in the I/R plus vitamin E group (p<0.05). CONCLUSIONS This study demonstrates a protective effect of melatonin, vitamin E and octreotide on the retina during retinal ischemia-reperfusion injury. (Eur J Ophthalmol 2002; 12: 443-9).

The Inhibitory Effects of Trastuzumab on Corneal Neovascularization

PURPOSE To investigate the effect of systemic administration of trastuzumab in the prevention of experimentally induced corneal neovascularization in a rat model. DESIGN An experimental animal study. METHODS Sixteen male Wistar-Albino rats weighing 250 g to 300 g were used in the study. Silver nitrate sticks (75% silver nitrate, 25% potassium nitrate) were used to induce chemical cauterization on the corneas of 16 eyes. The rats were randomized to 1 of 2 groups: Group 1 (n = 8) received intraperitoneally 1 ml (4 mg/kg) trastuzumab and Group 2 (n = 8) received 1 ml saline. The corneal surface covered with neovascular vessels was measured on the photographs as the percentage of the total area of the cornea by using computer imaging analysis on the eighth day. The corneas obtained from rats were evaluated for vascular endothelial growth factor (VEGF) immunostaining semicantitatively. The number of the corneal neovascularizations were also determined on slides. The results were evaluated with the Mann-Whitney U test. RESULTS The burn stimulus was similar between groups. The average neovascularization area in treatment group was statistically smaller than control (P = .008). The mean VEGF staining intensity of epithelial and endothelial layers of cornea in treatment group was less than control (P = .038 and P = .041, respectively). The stroma of the treatment group showed less staining, but the difference was not significant (P = .056). The number of corneal neovascularizations on slides in trastuzumab treated eyes were less than the control group (P = .02). CONCLUSION Systemic administration of trastuzumab is effective in prevention of the corneal neovascularization.

Delayed Trigeminocardiac Reflex Induced by an Intraorbital Foreign Body

Objective: To emphasize the importance of the mechanism and surgical approach to trigeminocardiac reflex (TCR) developing 48 h after orbital trauma due to a foreign body. Case Report: After gunshot injury of a 17-year-old male patient, computerized tomography evaluation revealed a right globe perforation and an intraorbital metallic foreign body in the right orbita adjacent to the lateral wall. The ocular perforation was repaired, but the foreign body was not removed. Constant bradycardia (45/min) developed 48 h after the operation. Since there were no cardiological findings, a temporary cardiac pacemaker was inserted and on the 6th postoperative day, the foreign body was removed through orbitolateral approach. After the removal of the foreign body, bradycardia completely recovered. Conclusion: In the presence of an intraorbital foreign body accompanied by globe perforation, TCR may develop 48 h after the trauma and insertion of a temporary pacemaker may be required to control the cardiac rhythm. In this paper, the delayed TCR complication presented an indication for the removal of the intraorbital foreign body.

Effects of Vitamin E, Pentoxifylline and Aprotinin on Light-Induced Retinal Injury

Purpose: A considerable amount of clinical and experimental evidence exists suggesting the involvement of reactive oxygen species (ROS) in the etiology of light-induced retinal injury. The aim of this study was to investigate the protective role of vitamin E, pentoxifylline (PTX) and aprotinin against light-induced retinal injury in guinea pigs. Methods: Thirty adult male guinea pigs were divided into 5 groups of 6 animals each. The first group was used as control. The guinea pigs were kept in cyclic light for 2 weeks before the experiments. The animals were maintained in 12-hour light-dark cycles, before and after exposure to intense white fluorescent light, for as long as 12 h and then returned to cyclic light. Groups 3–5 received intraperitoneal injections of vitamin E, PTX and aprotinin, respectively. One eye of each animal was selected for histopathological evaluation and the other for biochemical assay. Retinal malondialdehyde (MDA) levels and the thickness of the outer nuclear layers were measured. Results: The compounds had the following relationships: vitamin E more than PTX more than aprotinin in preventing light-induced retinal damage. All 3 gave significant protection against the formation of MDA. Retinas of all 3 treatment groups had been protected from light-induced injury. Conclusion: The intraperitoneal vitamin E, PTX and aprotinin supplementations may strengthen the antioxidant defense system because of decreased ROS, and these agents may play a role in treating light-induced retinal injury.

The role of nystagmus in silicone oil emulsification after pars plana vitrectomy and silicone oil injection for complex retinal detachment

Purpose The purpose of this study was to determine whether nystagmus has a role in silicone oil emulsification after pars plana vitrectomy and silicone oil injection for complex retinal detachment. Methods A retrospective review was conducted of the clinical and operative records of eight eyes with nystagmus that underwent pars plana vitrectomy and silicone oil injection for repair of retinal detachment associated with proliferative vitreoretinopathy. Three male (37.5%) and 5 female (62.5%) patients were included in this study. The mean age was 36.4 years (range, 19 to 54 years) and the mean follow-up time was 18.3 months (range, 5 to 49 months). Results Three eyes underwent combined lensectomy and vitrectomy. During the initial postoperative period, retinal attachment was obtained in 6 (75%) patients. Two of eight eyes required further surgery. Silicone oil emulsification occurred in all eyes to different degrees in the 1- to 3-month postoperative period. No inverse hypopyon was observed in any of patients. Three of eight eyes developed open angle glaucoma due to silicone oil emulsification before the silicone oil removal. In these patients, intraocular pressure was controlled successfully by medical therapy. Silicone oil removal was performed before the planned time because of early emulsification. After the removal of silicone oil, two of three eyes had established open angle glaucoma and medical therapy was maintained. After the removal of silicone oil, recurrent retinal detachment developed in two eyes and one of them developed phthisis bulbi. Conclusions Silicone oil emulsification may develop earlier than expected in patients with nystagmus who underwent pars plana vitrectomy combined with silicone oil injection.

Aprotinin reduces ischemia-reperfusion injury in the retina of guinea pigs.

PURPOSE The aim of this study was investigate the role of aprotinin on retinal lipid peroxidation and histopathological changes during ischemia/reperfusion (I/R) of guinea pigs. METHODS Three groups of seven pigmented guinea pigs each were formed: a control (group 1), ischemia/saline (group 2) and ischemia/aprotinin (group 3). One eye of each animal was selected for histopathological evaluation and the other for biochemical assay. Bilateral pressure-induced retinal ischemia was instigated for 90 min and was followed by 24 hours of reperfusion. Animals in the ischemia/aprotinin and ischemia/saline groups received either 20,000 KIU/kg of aprotinin or saline, repeated four times at 6-hour intervals, with the first dose administered 5 min prior to the ischemic insult. The animals were killed at 24 hours of reperfusion. Retinal malondialdehyde (MDA) levels and the thickness of the inner plexiform layers were measured. RESULTS The level of MDA in group 1 was significantly (p<0.001) lower than the other groups. The mean MDA level in group 2 was significantly (p<0.01) higher than in group 3. The inner plexiform layer in group 1 was significantly (p<0.001) thinner than in the other groups. The mean thickness of the inner plexiform layer in group 2 was significantly (p<0.01) higher than in group 3. CONCLUSIONS These data indicate that intraperitoneally administrated aprotinin has a protective effect against I/R injury in the retina of guinea pig as evidenced by reduced retinal MDA level and retinal thickness. (Eur J Ophthalmol 2003; 13: 642-7).

Pigmented Paravenous Retinochoroidal Atrophy

Seven patients (4 men and 3 women, ranging in age from 27 to 64 years) with pigmented paravenous retinochoroidal atrophy, a rare disorder of unknown origin, were studied. The mean follow-up time was 18.5 months. Fundus examinations were performed, and color fundus photographs were taken. In addition to fluorescein angiography, visual field examinations, color vision and electroretinographic tests were performed. All 7 patients were asymptomatic, with visual acuities ranging from 3/10 to 10/10. Both fundi showed patches of retinochoroidal atrophy and pigmentation along the retinal veins in all patients. Fluorescein angiography showed hyperfluorescence due to the pigment epithelial atrophy together with hypofluorescence corresponding to bone spicule pigment clumping. Visual field tests showed scotomas corresponding with areas of atrophy along the retinal veins. The electroretinography showed reduced responses in 2 cases. Color vision was normal in all cases. The patients had no history of trauma or a previous inflammatory process. Serology for syphilis, Toxoplasma and cytomegalovirus as well as a skin test for tuberculosis were negative. When the patients were seen at the end of the follow-up period, no variation of the findings was noted. Although the fundus abnormalities can be mild or severe, retinal function tests indicated that this is a geographic and not a generalized disorder.