Anti-inflammatory effect of lycopene on endotoxin-induced uveitis in rats / Efeito anti-inflamatório do licopeno na uveíte induzida por endotoxina em ratos

ABSTRACT Purpose: We evaluated the efficacy of lycopene, a dietary carotenoid and potent antioxidant, against ocular inflammation and oxidative stress in an experimental uveitis model. Methods: Endotoxin-induced uveitis (EIU) was induced in Sprague-Dawley rats by a single subcutaneous injection of 200 μg lipopolysaccharide (LPS). Induction of EIU was preceded by daily intraperitoneal injection of 10 mg/kg lycopene for three consecutive days (Lycopene + LPS group) or equivolume vehicle (Vehicle + LPS group). A positive control group received 1 mg/kg dexamethasone pretreatment (DEX + LPS), and a negative control group received daily vehicle injection but no LPS (Vehicle Control). Twenty-four hours after LPS or final vehicle administration, eyes were enucleated, and aqueous humor was collected for measurement of the number of infiltrating cells, total protein concentration, and levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and oxidative stress markers. Inflammatory response severity was compared among groups clinically and histopathologically. Results: Infiltrating cell number, total protein concentration, and NO, TNF-α, and IL-6 levels were significantly elevated in the aqueous humor of Vehicle + LPS group rats compared to Vehicle Controls. Compared to the Vehicle + LPS group, lycopene pretreatment significantly reduced aqueous humor concentrations of oxidative stress markers, NO (0.29 ± 0.1 μM vs. 0.19 ± 0.1 μM, p=0.003), TNF-α (71.0 ± 22.3 ng/ml vs. 50.1 ± 2.1 ng/ml, p=0.043), and IL-6 (121.6 ± 3.0 pg/ml vs. 111.1 ± 5.6 pg/ml, p=0.008). Inflammatory score was also reduced (2.0 ± 0.0 vs. 0.4 ± 0.5, p=0.001). Lycopene reduced the infiltrating cell count and protein concentration, but differences did not reach significance. Most lycopene effects were equivalent to dexamethasone. Conclusions: Lycopene may aid in the clinical management of uveitis by suppressing inflammation and oxidative stress.

RESUMO Objetivo: Avaliamos o efeito do licopeno, um carotenóide dietético e um potente anti-oxidante, sobre a inflamação ocular e estresse oxidativo em modelo de uveíte experimental. Métodos: Uveíte foi induzida por endotoxina (EIU) em ratos Sprague-Dawley por uma única injeção subcutânea de 200 ug de lipopolissacárido (LPS). A indução de EIU foi precedida por injeção intraperitoneal de licopeno em uma dose de 10 mg/kg (grupo LPS + Licopeno) ou veículo de mesmo volume (grupo LPS + Veículo), durante 3 dias consecutivos. O grupo controle positivo recebeu uma dose de 1 mg/kg de Dexametasona (grupo DEX + LPS) e o grupo controle negativo recebeu doses diárias de veículo mas sem LPS (grupo Controle Veículo). Vinte e quatro horas após a administração do LPS, os olhos foram enucleados, humor aquoso foi recolhido, e o número de células infiltrativas, a concentração de proteína, assim como os níveis de óxido nítrico (NO), fator de necrose tumoral α (TNF-α), interleucina-6 e marcadores de estresse oxidativo foram determinados no humor aquoso. Além disso, a resposta inflamatória foi avaliada clinicamente e histologicamente. Resultados: As células infiltrativas, concentração de proteína, o NO, TNF-α, interleucina-6 foram significativamente elevados no humor aquoso de ratos do grupo Grupo LPS + Veículo quando comparados ao Grupo Controle Veículo. O tratamento com licopeno diminuiu significativamente estes aumentos. Comparado ao Grupo LPS + Veículo, o licopeno reduziu significativamente as concentrações no humor aquoso dos marcadores de estresse oxidativo e NO (de 0,29 ± 0,1 μM para 0,19 ± 0,1 μM, p=0,003), o TNF-α (de 71,0 ± 22,3 ng/ml para 50,1 ± 2,1 ng/ml, p=0,043), interleucina-6 (de 121,6 ± 3,0 pg/ml para 111,1 ± 5,6 pg/ml, p=0,008). Do mesmo modo, o aumento do número de células infiltrativas no tecido uveal em seções histológicas foi significativamente inibido pelo licopeno, a pontuação inflamatória diminuiu de 2,0 ± 0,0 para 0,4 ± 0,5, p=0,001. Embora, não tenha sido estatisticamente significativo, o licopeno reduziu a contagem de células infiltrativas e a concentração de proteínas no humor aquoso. Conclusões: Estes resultados sugerem que o licopeno pode ter efeitos benéficos no tratamento da inflamação ocular, através dos seus efeitos anti-inflamatórios e antioxidantes.

Serum levels of homocysteine, asymmetric dimethylarginine and nitric oxide in patients with Parkinson's disease.

OBJECTIVES: Endothelial dysfunction has been implicated as a crucial event in the development of several neurodegenerative diseases. The aim of this study was to investigate the serum homocysteine, asymmetric dimethylarginine (ADMA) and nitric oxide (NO) levels in patients with Parkinson's disease (PD) and to compare the results with data from healthy controls. METHODS: A total of 132 subjects, including 82 idiopathic PD patients who were newly diagnosed and untreated (47 males, 35 females, mean age of 60.8 ± 7.1 years) and 50 healthy controls (28 males, 22 females, mean age of 60.2 ± 6.7 years) were enrolled in this study. The serum ADMA and NO levels were determined using enzyme-linked immunosorbent assay (ELISA), while the homocysteine levels were determined by chemiluminescent microparticle immunoassay. RESULTS: The ADMA and NO levels of the PD patients were significantly higher than those of the healthy controls. The serum ADMA levels were 0.70 ± 0.15 µmol/L in the PD patients and 0.50 ± 0.12 µmol/L in the healthy controls (p < 0.001). The serum NO levels were 78.7 ± 10.3 µmol/L in the PD patients and 59.9 ± 9.5 µmol/L in the healthy controls (p < 0.001). In addition, the ADMA and NO levels were significantly correlated with the serum homocysteine levels in patients with PD (r = 0.874, p < 0.001, r = 0.803, p = 0.005, respectively). CONCLUSION: In our study, the high ADMA and NO levels of patients with PD indicate endothelial dysfunction, and this dysfunction may play a role in PD pathogenesis. Larger studies, including randomised clinical trials in humans and animal studies, are needed to validate our findings and help in developing a better understanding of the pathogenesis of PD.

The effect of anterior transposition of the inferior oblique muscle on eyelid configuration and function.

PURPOSE: To evaluate the alteration of lower lid configuration and function with anterior transposition surgery of the inferior oblique (IO) muscle. PATIENTS AND METHODS: A prospective clinical trial was conducted on a consecutive series of patients underwent anterior transposition of the IO as a sole operation. All patients received a thorough ophthalmic examination 1 day before and 3 months after surgery. Output parameters were consisted of palpebral fissure, margin reflex distance 1-2, lower lid function, hertel value, and lower lid crease. The differences of the collected data were calculated for statistical significance by using the Wilcoxon test. RESULTS: A total of 19 eyes of 16 consecutive patients were included. The median preoperative grade of IO overaction was 3.5 (ranging from 3 to 4), which decreased to 0 (ranging from 0 to 2) postoperatively (P < 0.05). No significant change was observed in all parameters 3 months postoperatively (P > 0.05). CONCLUSION: In this study, no significant effect on lower lid configuration and function was observed following IO anterior transposition in which the disinserted muscle was placed posterior to inferior rectus insertion.

Spontaneous Regression of Over-elevation in Adduction Following Esotropia Surgery.

PURPOSE: To evaluate the course of over-elevation in adduction in patients who had esotropia following correction of horizontal deviation. METHODS: The review of the medical files identified 28 patients who had esotropia with over-elevation in adduction. Data collected from the patients' full ophthalmological examinations included visual acuity, ocular alignment, duction, versions and sensory tests for binocularity and stereopsis, cycloplegic retinoscopy, and fundus evaluation. Oblique muscle function was graded on a scale of -4 to +4. The primary outcome measure was the amount of improvement in over-elevation in adduction following esotropia surgery. RESULTS: Of the 28 patients (mean age: 53.5 ± 53.7 months), 13 were males and 15 were females. Of these, 22 (78.6%) had infantile esotropia and 6 (21.4%) had partial accommodative esotropia. The mean follow-up was 16.3 ± 7.9 months. All patients underwent bilateral medial rectus recession for correction of esotropia. The mean preoperative inferior oblique overaction was +2.1 ± 0.7 and the final postoperative value was +0.8 ± 0.9 (P < .001). There was a statistically significant decrease in postoperative over-elevation in adduction at all postoperative visits compared to the preoperative value (P < .001 at 3- and 6-month and final visits). Over-elevation in adduction regressed in 42 eyes (80.8%). Of these, 18 eyes (34.6%) completely resolved without any additional surgery to the inferior oblique muscle. CONCLUSIONS: Spontaneous regression in over-elevation in adduction was observed after esotropia surgery without additional inferior oblique weakening surgery. This may affect presurgical evaluation of and surgical planning for patients.

Anti-inflammatory effect of lycopene on endotoxin-induced uveitis in rats.

PURPOSE:: We evaluated the efficacy of lycopene, a dietary carotenoid and potent antioxidant, against ocular inflammation and oxidative stress in an experimental uveitis model. METHODS:: Endotoxin-induced uveitis (EIU) was induced in Sprague-Dawley rats by a single subcutaneous injection of 200 µg lipopolysaccharide (LPS). Induction of EIU was preceded by daily intraperitoneal injection of 10 mg/kg lycopene for three consecutive days (Lycopene + LPS group) or equivolume vehicle (Vehicle + LPS group). A positive control group received 1 mg/kg dexamethasone pretreatment (DEX + LPS), and a negative control group received daily vehicle injection but no LPS (Vehicle Control). Twenty-four hours after LPS or final vehicle administration, eyes were enucleated, and aqueous humor was collected for measurement of the number of infiltrating cells, total protein concentration, and levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and oxidative stress markers. Inflammatory response severity was compared among groups clinically and histopathologically. RESULTS:: Infiltrating cell number, total protein concentration, and NO, TNF-α, and IL-6 levels were significantly elevated in the aqueous humor of Vehicle + LPS group rats compared to Vehicle Controls. Compared to the Vehicle + LPS group, lycopene pretreatment significantly reduced aqueous humor concentrations of oxidative stress markers, NO (0.29 ± 0.1 µM vs. 0.19 ± 0.1 µM, p=0.003), TNF-α (71.0 ± 22.3 ng/ml vs. 50.1 ± 2.1 ng/ml, p=0.043), and IL-6 (121.6 ± 3.0 pg/ml vs. 111.1 ± 5.6 pg/ml, p=0.008). Inflammatory score was also reduced (2.0 ± 0.0 vs. 0.4 ± 0.5, p=0.001). Lycopene reduced the infiltrating cell count and protein concentration, but differences did not reach significance. Most lycopene effects were equivalent to dexamethasone. CONCLUSIONS:: Lycopene may aid in the clinical management of uveitis by suppressing inflammation and oxidative stress.

Tear Film and Serum Prolidase Activity and Oxidative Stress in Patients With Keratoconus.

PURPOSE: To determine and compare the serum and tear film prolidase activity (PA) between patients with keratoconus and healthy subjects. Also, we aimed to evaluate the serum oxidative stress level and the correlation with serum PA in patients with keratoconus. METHODS: This prospective, comparative clinical study included 31 patients with keratoconus and 33 age-matched and sex-matched control subjects. All participants underwent a detailed ophthalmologic examination. Serum and tear samples were obtained from all participants. Tears and serum PA and serum oxidative stress markers were measured. RESULTS: No significant differences in demographic characteristics were detected between groups (P > 0.05). The serum PA was significantly lower in the keratoconus group than in the control group (895.6 ± 198.7 vs. 1145.9 ± 285.4 U/L, P < 0.001). A tear film comparison showed that PA was lower in the keratoconus group than in the control group; however, this difference was not significant (3075.4 ± 672.2 vs. 3225.8 ± 903.2 U·L⁻¹·g⁻¹ protein, P = 0.45). Oxidative stress markers, such as total oxidant status and oxidative stress index, were found to be significantly higher in the keratoconus group (P < 0.001). CONCLUSIONS: The serum PA was found to be lower in patients with keratoconus than in the controls. Additionally, serum oxidative stress markers were found to be higher than those of the controls. Thus, prolidase and systemic oxidative stress may have a role in the pathogenesis of keratoconus.

Comparison of refractive error and central corneal thickness in neonates of diabetic and healthy mothers.

PURPOSE: To determine the refractive error and central corneal thickness of neonates born to diabetic mothers and to compare these parameters with those of healthy neonates born to healthy mothers. METHODS: This prospective, cross-sectional study was conducted on 16 consecutive full-term neonates born to diabetic mothers and 17 full-term healthy neonates. The neonates underwent ophthalmic examination within the first week of life. Refractive measurements were assessed by retinoscopy. Central corneal thickness was recorded by using ultrasound pachymeter. RESULTS: The mean spherical equivalent for both eyes in the diabetic group was +2.9 ± 2.6 and significantly greater than that of the nondiabetic group (+1.3 ± 2.1 D) (p = 0.008). The mean sphere value was +2.6 ± 2.4 D in the diabetic group and +1.0 ± 2.0 D in the nondiabetic group, significantly higher in the diabetic group (p = 0.008). In both groups, mean astigmatism was less than 1.00 D, it was lower in the diabetic group, and there was no statistically significant difference between groups (p = 0.95). There were 2 patients in each group with anisometropia. The mean central corneal thickness in the nondiabetic group was 542.9 ± 21.9 µm whereas it was 592.0 ± 40.2 µm in the diabetic group, which was significantly thicker (p = 0.05). CONCLUSIONS: Our study revealed that neonates of diabetic mothers seem to be more hypermetropic compared to full-term healthy neonates; however, we did not observe any significant astigmatism in either group. Neonates of diabetic mothers had thicker corneas.

Improvement in levator function after anterior levator resection for the treatment of congenital ptosis.

PURPOSE: To evaluate the surgical outcome of levator resection in congenital ptosis, and to assess the change in levator function (LF) after surgery, as well as its effect on surgical outcomes. METHODS: The charts of patients who underwent an anterior levator resection for congenital ptosis between January 2010 and February 2013 were retrospectively reviewed. Preoperative and postoperative grades of blepharoptosis, margin-reflex distance, LF, and reoperation status were noted, and postoperative outcomes were evaluated. RESULTS: A total of 42 eyelids of 37 patients were included of which 32 eyelids (76.2%) had severe ptosis while 10 eyelids (23.8%) had moderate ptosis. The mean follow up was 11.0 ± 7.2 months. The overall success rate after initial surgery was 78.6%, and undercorrection was the leading course of surgical failure, with a rate of 14.3% (6 eyelids) at the final visit. Lagophthalmus and/or overcorrection occurred in 7.1% (3 eyelids) at the final visit, respectively. The mean preoperative LF was 6.8 mm ± 3.1 mm, which increased postoperatively to 8.7 mm ± 3.4 mm (p < 0.05) at month 1 and 9.6 mm ± 3.8 mm (p < 0.05) at the final visit. The mean LF improvement following surgery was 2.9 mm ± 2.2 mm. CONCLUSIONS: The levator resection surgery was observed to be an effective treatment for congenital ptosis, including severe ptosis with poor LF. Levator resection resulted in substantial improvement of postoperative levator muscle functioning, which might have an additive effect on the surgical success, especially for those with poor LF.

Low-density lipoprotein subfraction, carotid artery intima-media thickness, nitric oxide, and tumor necrosis factor alpha are associated with newly diagnosed ischemic stroke.

OBJECTIVES: Small dense (sd) low-density lipoprotein (LDL), tumor necrosis factor (TNF) alpha (α), and nitric oxide (NO) have recently emerged as important stroke risk factors. The aim of the study was to investigate the effects of increased levels of small LDL particle size, TNF-α and NO on the developed ischemic stroke and increased carotid artery intima-media thickness (CIMT). MATERIALS AND METHODS: A total of 29 women and 25 men (a total of 54 ischemic stroke patients) and a similar age group of 50 controls (29 females and 21 males) were included in the study. CIMT, C-reactive protein (CRP), TNF-α, NO, and lipid subfraction test of the two groups were measured. RESULTS: The mean LDL particle size was smaller in patients with stroke than in the controls (26.8 ± 0.31 nm vs. 27.0 ± 0.31 nm, P = 0.003). sd-LDL, TNF-α, NO, CRP, right CIMT, and left CIMT were higher in patients with stroke than in the controls (respectively; 8.2 ± 7.8 mg/dL vs. 3.3 ± 3.5 mg/dL, P < 0.001;75.6 ± 25.0 pg/mL vs. 65.4 ± 9.1 pg/mL, P = 0.009;76.4 ± 53.3 mmol/L vs. 41.5 ± 27.0 mmol/L, P < 0.001;1.9 ± 2.6 mm vs. 0.4 ± 0.3 mm P < 0.001;0.97 ± 0.38 mm vs. 0.83 ± 0.15 mm, P = 0.007;1.04 ± 0.44 mm vs. 0.87 ± 0.19 mm, P = 0.010). CONCLUSION: These results show that sd-LDL is independently associated with the incidence of stroke and may be a risk factor in the development of stroke. In addition, TNF-α, NO, right CIMT, and left CIMT may be a risk factor in the development of ischemic stroke.