IL28B Genetic Variations in Patients with Recurrent Herpes Simplex Keratitis

Background and objectives: Recurrent herpes simplex keratitis (HSK) is the most common cause of corneal blindness in the developed world. A relationship between host gene polymorphisms and the recurrence of herpes simplex virus (HSV) infection has previously been proposed. Thus, the aim of this study was to investigate a potential association between the IL28B host genotype and recurrent HSK. Materials and Methods: Eighty patients older than 18 years of age of both genders with a history of recurrent herpes simplex labialis (HSL) were considered for inclusion. Seventy-five of these patients were found to be seropositive for HSV-1 and were subsequently enrolled in the study. Twenty-four of the enrolled patients also had a history of recurrent HSK associated with severe corneal scarring and visual acuity deterioration. Total DNA was isolated from whole blood samples. A single-nucleotide polymorphism (SNP) rs12979860 near the IL28B gene on chromosome 19 was genotyped. Results: A significant association was observed between recurrent HSK and two SNPs of the IL28B genotype (CCrs12979860 and CTrs12979860, p < 0.01). The variation CCrs12979860 showed a significantly greater association with HSK (16 out of 26 patients) compared with CTrs12979860 (8 out of 34 patients). Conclusion: Seropositive individuals with a history of recurrent HSK are likely to have the CC IL28B genotype. This genotype may be related to incomplete control of the infection and more frequent periodical viral shedding along the first nerve branch of the trigeminal ganglion, which clinically manifests as recurrent herpes keratitis. The clinical manifestation of recurrent HSV-1 infection seems to be influenced by polymorphism of the IL28B genotype

The effect of subchronic supplementation with folic acid on homocysteine induced seizures

Influence of folic acid on the CNS is still unclear. Folate has a neuroprotective effect, while on the other hand excess folate can exacerbate seizures in epileptics. The aim of the present study was to examine the effect of subchronic administration of folic acid on behavioural and electroencephalographic (EEG) characteristics of DL homocysteine thiolactone induced seizures in adult rats. The activity of Na+/K+-ATPase and Mg2+-ATPase in different brain regions was investigated. Adult male Wistar rats were divided into groups: 1. Controls (C, 0.9% NaCl); 2. DL homocysteine-thiolactone 8.0 mmol/kg (H); 3. Subchronic supplementation with folic acid 5 mg/kg for 7 days (F) and 4. Subchronic supplementation with F + single dose of H (FH). Seizure behaviour was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0–4. For EEG recordings, three gold-plated recording electrodes were implanted into the skull. Subchronic supplementation with folic acid did not affect seizure incidence, median number of seizure episodes and severity in FH, comparison with H (p > 0.05). The majority of seizure episodes in all groups were of grade 2. There were no significant differences in lethal outcomes at 24 h upon H injection in the FH vs. H group. The activity of Na+/K+-ATPase and Mg2+-ATPase was significantly increased in almost all examined structures in the FH vs. H group. Subchronic folic acid administration did not exacerbate H induced seizures and completely recovered the activity of ATPases

Modulation of Epileptic Activity in Rats: Focus on Sleep, Physical Exercise and Nitric Oxide–mediated Neurotransmission in a Model of Homocysteine Thiolactone–induced Seizures

Epilepsija je hronično neurološko oboljenje koje karakteriše rekurentna pojava epileptičnih napada. Razumevanje menahizama nastanka i širenja epileptične aktivnosti, kao i foktora modulacije ovih procesa, od izuzetnog je naučnostručnog značaja. Eksperimentalni modeli epilepsije su značajni za razumevanje upravo ovih mehanizama

Different Sensitivity of Various Brain Structures to Thioacetamide-Induced Lipid Peroxidation

Thioacetamide (TAA) exerts hepatotoxic, neurotoxic and carcinogenic effects. The aim of our study was to investigate the effects of TAA on lipid peroxidation and catalase activity in various rat brain regions. Male Wistar rats were divided into following groups: 1. control, saline-treated; 2. thioacetamide-treated groups, TAA(300) (300 mg/kg), TAA(600) (600 mg/kg) and TAA(900) (900 mg/kg). Daily dose of TAA (300 mg/kg) was administered intraperitoneally once (TAA(300)), twice (TAA(600)) and three times (TAA(900)) in consecutive days. Brain samples were collected 24 h after the last dose of TAA and malondialdehyde (MDA) level and catalase activity were determined in cortex, brainstem and hippocampus. MDA level was significantly increased while catalase activity was significantly lower in all brain regions in TAA(900) group in comparison with control group. In TAA(600) MDA level was increased in the brainstem and cortex when compared to control (p LT 0.01). The same dose of TAA(600) mg/kg induced a significant decline in catalase activity in the brainstem and cortex and an increase in its activity in the hippocampus when compared to control (p LT 0.01). In TAA(300) an increase in MDA level was evident only in the brainstem. Catalase activity was significantly higher in the cortex and hippocampus in TAA(300) group in comparison with control (p LT 0.01). Based on these results, it may be concluded that various rat brain regions have different sensitivity to TAA-induced lipid peroxidation with hippocampus being less sensitive than cerebral cortex and brainstem

The activity of erythrocyte and brain Na+/K+ and Mg2+-ATPases in rats subjected to acute homocysteine and homocysteine thiolactone administration

Hyperhomocysteinemia is associated with various pathologies including cardiovascular disease, stroke, and cognitive dysfunctions. Systemic administration of homocysteine can trigger seizures in animals, and patients with homocystinuria suffer from epileptic seizures. Available data suggest that homocysteine can be harmful to human cells because of its metabolic conversion to homocysteine thiolactone, a reactive thioester. A number of reports have demonstrated a reduction of Na+/K+-ATPase activity in cerebral ischemia, epilepsy and neurodegeneration possibly associated with excitotoxic mechanisms. The aim of this study was to examine the in vivo effects of d,l-homocysteine and d,l-homocysteine thiolactone on Na+/K+- and Mg2+-ATPase activities in erythrocyte (RBC), brain cortex, hippocampus, and brain stem of adult male rats. Our results demonstrate a moderate inhibition of rat hippocampal Na+/K+-ATPase activity by d,l-homocysteine, which however expressed no effect on the activity of this enzyme in the cortex and brain stem. In contrast,d,l-homocysteine thiolactone strongly inhibited Na+/K+-ATPase activity in cortex, hippocampus and brain stem of rats. RBC Na+/K+-ATPase and Mg2+-ATPase activities were not affected by d,l-homocysteine, while d,l-homocysteine thiolactone inhibited only Na+/K+-ATPase activity. This study results show that homocysteine thiolactone significantly inhibits Na+/K+-ATPase activity in the cortex, hippocampus, and brain stem, which may contribute at least in part to the understanding of excitotoxic and convulsive properties of this substance