Betül Çevik

Montelukast Inhibits Pentylenetetrazol-Induced Seizures in Rats

Background Montelukast is an antiinflammatory drug with an antioxidant property. In this study, we aimed to reveal whether montelukast has a preventive effect against seizures and post-seizure oxidative stress in pentylenetetrazol (PTZ)-induced seizures in rats. Material/Methods Of the 48 male Sprague-Dawley rats used in the study, 24 were assigned to EEG recordings (group A) and 24 were assigned to behavioral studies (group B). In group A, the electrodes were implanted on dura over the left frontal cortex for EEG recording. After 10 days, in group A, i.p. saline, 25, 50, or 100 mg/kg montelukast+35 mg/kg PTZ was administered to the rats. EEG was recorded and spike percentage was evaluated. In group B, i.p. saline, 25, 50, or 100 mg/kg montelukast+70 mg/kg PTZ was administered to the rats. Racine’s Convulsion Scale (RCS) and onset times of first myoclonic jerk (FMJ) was used to evaluate the seizures. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined in the brain tissue of animals. Results Animals treated with 50 or 100 mg/kg montelukast had significantly lower RCS and significantly increased FMJ onset time compared to the saline-treated animals. Moreover, groups given 25, 50, or 100 mg/kg montelukast had significantly lower MDA and higher SOD levels compared to the saline-treated group. The differences were more pronounced in the 100 mg/kg montelukast-pretreated group (p<0.001). Conclusions Montelukast showed anticonvulsant action and led to amelioration of oxidative stress markers in PTZ-induced seizures in rats.

Central corneal thickness and its relationship to Parkinson's disease severity

OBJECTIVE To investigate the effect of Parkinsons disease (PD) on blink rate (BR), tear breakup time test (TBUT), Schirmers test, and corneal thickness, and the relationship of these effects with disease severity. DESIGN Prospective controlled study. PARTICIPANTS Fifty-five eyes from 55 patients with PD and 40 eyes from 40 healthy subjects were analyzed in the study. METHODS The patients were divided into 2 groups according to their Hoehn-Yahr (H-Y) scores; patients classified as H-Y 1-2 were designated as the mild group, and those classified as H-Y 3-5 were designated as the moderate group. Subjects were screened for BR, TBUT, and Schirmers test, and the central corneal thickness (CCT) was measured. RESULTS The BR, Schirmers test, TBUT, and CCT values of the patient group were significantly lower than those of the control group. The BR and TBUT of the mild group were significantly lower than those of the control group, but the decreases in the Schirmers test values and CCT were not statistically significant. In addition, significant decreases in the BR, TBUT, Schirmers test scores, and CCT were observed in the patient group as the H-Y score increased. CONCLUSIONS A reduced BR and poor tear quality in the early stages of PD, as well as decreased tear production as the disease progresses, can result in reduced CCT. The possibility of a thin cornea should be taken into consideration while measuring the intraocular pressure in patients with severe PD.

Analysis of MMP2-1306C/T and TIMP2G-418C polymorphisms with relapsing remitting multiple sclerosis

Aims Multiple sclerosis (MS) is an autoimmune, inflammatory disease characterized by loss of myelin forming oligodendrocytes and changes in the blood–brain barrier. Matrix metalloproteinase (MMP) -2 and -9 are known to cause disruption of the blood–brain barrier, remodeling of the basal lamina, regeneration of axons, and remyelination in MS. The imbalance between MMPs and tissue inhibitor metalloproteinases (TIMPs) may lead to the emergence of pathological processes such as MS. The roles of MMP2-1306 C/T and TIMP2-418 G/C genetic variants in MS have not been studied before. We aimed to investigate whether MMP2-1306C/T and TIMP2-418 G/C gene variants are risk factors for patients with relapsing remitting multiple sclerosis (RRMS). Methods The study included 102 RRMS and 102 healthy controls. Genomic DNA was extracted from peripheral leukocytes from ethylenediaminetetraacetic acid anticoagulated blood. Genotyping of the MMP2-1306C/T and TIMP2G-418C polymorphisms was performed using real-time PCR. Results There were significant differences in terms of distribution of genotype (MMP2-1306- CT, TT) and T allele frequency between the patients with RRMS and the control group (p<0.0001; p<0.0001). The groups were not different in terms of TIMP2G-418C polymorphisms. Conclusions In the RRMS group, the genotype and allele frequencies of MMP2-1306C/T polymorphism showed significant differences from the controls. These results indicate that MMP2 might play a role in the pathogenesis of MS even during the inflammation stage.

Clinical, demographic and prognostic features of sporadic amyotrophic lateral sclerosis in Northern Turkey

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease for which progression cannot be prevented. In this study, we evaluated 37 patients diagnosed with sporadic definitive-probable ALS who were monitored in our neurology clinic between 2002 and 2012 in terms of age, gender, profession, onset, and clinical course within the disease process. The hospital ethics committee approved the study. Nineteen female and 18 male patients diagnosed with sporadic definitive or probable ALS were evaluated for age, gender, level of education, residence, onset of disease, the time between the first symptom and diagnosis, and average lifetime after diagnosis. Twenty-eight of the patients had graduated from primary-secondary school, six were illiterate, and three of them were college graduates. Eighteen patients were living in city center, 19 were living in the country. Fourteen patients were farmers, 11 were housewives, and the remaining was working in various different occupations. The age of onset was 62.13. The men and women were diagnosed 10.27 months and 17.91 months after the first symptom, respectively (p = 0.001). The average survival time after diagnosis was 36.70 months for males and 49.80 months for females (p < 0.05). This difference was particularly evident among patients from rural areas. In addition, our female patients required interventions such as ventilation at a later period than did males. In conclusion, female gender seems to be one of the good prognostic factors for our ALS patients. This may be due to the protection by hormonal mechanisms in women or differences in their responses to exogenous toxins.

Neuroprotective effects of erythropoietin on Alzheimer’s dementia model in rats

BACKGROUND Although Alzheimers disease (AD) is the most common age-related neurodegenerative disease and characterized by memory impairment, only symptomatic treatments are available. OBJECTIVES Because recombinant human erythropoietin (rhEPO) has various neuroprotective effects and improves cognitive function in animal models of neurodegenerative disorders, we investigated the therapeutic effects of rhEPO in an intracerebroventricular (ICV)-streptozotocin (STZ) animal model of sporadic-AD. MATERIAL AND METHODS A total of 24 Sprague-Dawley adult rats were divided into 4 groups of naive control (n = 6), sham-operated (n = 6), ICV-STZ + saline (n = 6) and ICV-STZ + rhEPO (n = 6). Twelve rats with Alzheimers disease, induced by STZ injection (3 mg/kg) into both lateral ventricles using a stereotaxic frame (bilaterally ICV-STZ), were divided into 2 groups 5 days after the STZ injection: one treated with rhEPO 5000 (IU/kg/day, i.p.) and the other with 0.9% NaCl (1 mL/kg/day, i.p.) for 2 weeks. The sham-operated rats received bilaterally ICV-0.9% NaCl. No surgical operation or treatment was given to the naive-control animals. On day 20, a passive avoidance learning (PAL) test was used followed by sacrification and removal of the brain tissue in all animals. Brain TNF-α and ChAT levels were determined, and neurons in the hippocampal CA1 and CA3 regions were counted by Cresyl violet staining. RESULTS ICV-STZ was found to significantly shorten the latency time on the PAL, increase brain TNF-α level, and decrease brain ChAT activity and the number of neurons in the hippocampal CA1 and CA3 regions. On the other hand, rhEPO significantly attenuated all these detrimental effects induced by STZ. CONCLUSIONS RhEPO treatment significantly prevented the ICV-STZ-induced memory deficit by attenuating the hippocampal neuronal loss, neuroinflammation and cholinergic deficit in rats. This result suggests that rhEPO may be beneficial for treating AD.

The Effect of Autologous Fat Graft with Different Surgical Repair Methods on Nerve Regeneration in a Rat Sciatic Nerve Defect Model.

Background: The aim of this study was to evaluate the efficacy of autologous fat graft with different surgical repair methods on reconstruction of a 10-mm-long rat sciatic nerve defect model. Methods: One hundred forty-four sciatic nerves were operated on in 72 Wistar rats. The right limbs were assigned as group A (n = 72) and the left limbs as group B (n = 72). In group B, autologous fat graft was added to the surgical area so as to stay in contact with the coaptation site. Nerve regeneration was evaluated by walking track analysis, Sciatic Functional Index, pin-prick, and electrophysiologic and histologic tests at commencement and at 4 and 12 weeks after the operation. Results: The rats receiving fat graft showed better regeneration, but the difference was only significant according to Sciatic Functional Index and pin-prick test (p < 0.05). Primary repair, autogenous nerve graft, acellularized nerve graft, vein filled with fresh and denatured muscle graft subgroups in group B showed significantly better regeneration than those in group A according to the Sciatic Functional Index (p < 0.05). In terms of latency and amplitude, all subgroups in groups A and B were found significantly different from the commencement of the study, but there was no difference between groups A and B (p < 0.05). Conclusions: Although there was no significant difference between the groups, rats receiving autologous fat graft showed better regeneration. Combined use of autologous fat graft with surgical repair methods induced significantly better regeneration. It was concluded that autologous fat grafting may have a beneficial effect on nerve regeneration when it is present in the coaptation site during healing.

Hypokalemia and hypomagnesaemia related to levetiracetam use

Levetiracetam (LEV), used for both partial and generalized seizures, is a frequently preferred antiepileptic because of its few side effects. We present a 23-year-old man who developed hypokalemia after switching from valproate to LEV. The patient was sent to our clinic due to hypokalemia 1 month after initiation of LEV, and his neurological examination was normal. Further examinations revealed hypokalemia (3.1 mmol/L) and hypomagnesaemia (0.56 mmol/L). His hemogram, blood urea nitrogen, creatinine, total cortisol, thyroid function tests, creatinine clearance, and renal Doppler ultrasound were normal. LEV was tapered off and treatment with 200mg/day lamotrigine begun. Potassium and magnesium levels returned to normal ranges in subsequent tests. While hypokalemia and hypomagnesaemia have not been reported before to our knowledge, interstitial nephritis and renal failure after the use of LEV have been. Hypokalemia, found in the early period in this case, may be an indicator of a recently developed renal tubular disorder. This experience indicates that unpredictable side effects of increasingly used new antiepileptic drugs should be taken into consideration.

Association of interleukin (IL)-4 gene intron 3 VNTR polymorphism with multiple sclerosis in Turkish population

OBJECTIVE Genetic risk factors are known to contribute to the etiology of multiple sclerosis (MS). Interleukin (IL)-4 gene polymorphisms have been associated with immune-mediated diseases. The aim of this study was to explore the frequency of IL-4 gene intron 3 VNTR (variable number tandem repeat) polymorphism in a cohort of Turkish patients with MS. METHODS The study included 125 patients with MS and 160 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses for the IL-4 gene intron 3 VNTR polymorphism. RESULTS The distribution of genotype and allele frequencies of IL-4 gene intron 3 VNTR polymorphism was statistically different between MS patients and control group (p = 0.003 and p = 0.002, respectively). There were no statistically significant association between IL-4 VNTR polymorphism and clinical and demographical characteristics of MS patients. CONCLUSION The results of this study suggest that intron 3 VNTR polymorphism of the IL-4 gene was positively associated with predisposition to develop MS in Turkish population.

ERLIN1 mutations cause teenage-onset slowly progressive ALS in a large Turkish pedigree

Amyotrophic lateral sclerosis (ALS) is a late-onset motor neuron disease with mostly dominant inheritance and a life expectancy of 2–5 years; however, a quite common occurrence of atypical forms of the disease, due to recessive inheritance, has become evident with the use of NGS technologies. In this paper, we describe a family with close consanguinity for at least four generations, suffering from a slowly progressive form of ALS. Spastic walking is observed since teenage years, while bulbar symptoms start much later, at the fifth or sixth decade of life. Patients usually die because of respiratory failure. Using whole-exome sequencing, we identified a novel homozygous p.(Val94Ala) (c.281T>C) (NG_052910.1) (NM_006459) variation in the endoplasmic reticulum lipid raft associated protein 1 (ERLIN1) gene, which segregates with the disease in the family. Here we suggest that ERLIN1 variants, previously shown in juvenile hereditary spastic paraplegia cases, may also be the cause of a slowly progressive early-onset ALS, starting with upper motor neuron features and developing into classical ALS with the addition of lower motor neuron dysfunction. We also demonstrate that ATP-binding cassette subfamily C member 2 (ABCC2) gene, responsible for hyperbilirubinemia, is linked to ERLIN1.

Sexual dysfunction in women with migraine and tension-type headaches

Primary headaches (PHAs) prominently affect the performance and life quality of people. Sexual dysfunction (SD) is an important health problem caused by several factors. This study aimed to compare the sexual function of women who have PHAs. Forty-one female patients who were diagnosed with migraine, 39 female patients who were diagnosed with tension-type headache (TTHA) and 41 healthy subjects were included in study. Sexual function of the cases were evaluated by using the ‘Female Sexual Function Index (FSFI)’. Beck Depression Scale was applied to subjects and those who were diagnosed with depression were excluded from the study. SD was detected in both the migraine and TTHA groups. FSFI subgroup scores were statistically significantly lower in the migraine and TTHA groups compared with the control group. No significant differences were detected between the migraine and TTHA groups in terms of FSFI and its components. In addition, no significant differences were detected between the blood prolactin levels or SD and headache. It was concluded that primary headaches (which are chronic diseases) itself may cause SD in female patients with migraine and TTHA independently of factors that may cause development of SD such as comorbid condition, depression, drug use and age.