Aylin Akcali

Detection of Metastases in Patients with Cutaneous Melanoma Using FDG-PET/CT

This study aimed to detect metastases in patients with stage III or IV cutaneous melanoma by 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT). Thirty-nine patients with clinically evident stage III or IV melanoma underwent whole-body FDG-PET/CT scans for metastatic disease and these results were compared with those of biopsy. Scans for 38 of the patients were evaluated; one patients scan could not be evaluated. There were 11 true-positive, two false-positive, 24 true-negative and one false-negative scans for the detection of melanoma metastases, with sensitivity 91%, specificity 92%, accuracy 92%, and positive and negative predictive values 84% and 96%, respectively. False-positive FDG-PET/CT scans were due to sarcoidosis in the lung and infected cyst in the liver. It is concluded that FDG-PET/CT scanning has high sensitivity and specificity for detecting stage III or IV metastatic melanoma.

Association of macrophage migration inhibitory factor gene promoter polymorphisms with multiple sclerosis in Turkish patients.

Elevated levels of macrophage migration inhibitory factor (MIF) have been observed in the cerebrospinal fluid of patients with multiple sclerosis. This study was designed to determine if MIF gene polymorphisms are associated with multiple sclerosis and disease severity. In total, 120 relapsing-remitting patients with multiple sclerosis and 120 control subjects were enrolled in the study. There was a statistically significant increase in the MIF −173 CC genotype in patients with multiple sclerosis compared with the control subjects. The MIF −794 6/7 genotype had a significantly lower progression index compared with MIF −794 6/6. Patients with the MIF −173 CC genotype had a significantly lower age of disease onset compared with those with the MIF −173 CG and MIF −173 GG genotypes. Additionally, patients with the MIF −794 5/6 genotype had a significantly later age of disease onset. This study indicates that the MIF −173 CC genotype may cause susceptibility to multiple sclerosis in the white Turkish population and a younger age of disease onset is associated with this polymorphism.

Contribution of KCNJ10 Gene Polymorphisms in Childhood Epilepsy

The purpose of this study was to investigate the possible association between childhood epilepsy and KCNJ10 gene polymorphisms (rs61822012 and rs2486253). A total of 200 epileptic cases and 200 healthy controls enrolled to this study. Genomic DNAs from the patients and control cases were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism methods. There were significant associations between the G/T genotype of KCNJ10 gene rs2486253 polymorphism in the idiopathic generalized epilepsy group (P = .037) and in subjects with generalized tonic-clonic seizures (P = .0015). T allele was also increased in patients with generalized tonic-clonic seizures (P = .0158). However, no statistically significant association was found between rs61822012 polymorphism and epilepsy. Our data suggest that G/T genotype of the KCNJ10 gene rs2486253 polymorphism affects risk for development of common types of childhood epilepsy. The T allele of this polymorphism was found to be a seizure-susceptibility allele for tonic-clonic epilepsy.

TNF-α promoter polymorphisms in multiple sclerosis: no association with -308 and -238 alleles, but the -857 alleles in associated with the disease in Turkish patients.

Dysregulation in the expression of pro‐ and anti‐inflammatory cytokines is one of the milestones in multiple sclerosis (MS) development and progression. Tumour necrosis factor (TNF‐α), a proinflammatory cytokine is believed to play an important role in MS pathogenesis. The objective of this study is to investigate the association between TNF‐α promoter region (TNF‐α−238, −308 and −857) and susceptibility to MS and clinical course of the disease. Eighty‐six relapsing remitting MS patients and 150 sex‐, age‐ and ethnic‐matched controls were enrolled in the study. Genotyping was performed by PCR‐RFLP method. We observed a statistically significant increase in TNF‐α 857 CC genotype in MS patients than controls (P < 0.001) while TNF‐α 857 CT genotype showed a significant negative correlation with MS patients (P = 0.033). No differences in the distribution of the TNF‐α−238 and −308 alleles were observed. None of the three polymorphisms (−238, −308 and −857) did not show relation with disease duration, Expanded Disability Status Scale or age of onset. On the other hand, significant difference of TNF −857 CC genotype was identified with the low disease index (P = 0.025). Although the study group is small, the results indicate that TNF‐α 857 CC genotype may cause susceptibility to MS in the Turkish population.

Lack of Association Between the C276T Polymorphism of the Neuronal Nitric Oxide Synthase Gene and Migraine

ABSTRACT A migraine attack is a spectacularly complex brain event that can produce a wide array of neurological and systemic symptoms. The molecular mechanisms and genetics of migraine have not yet been clarified. The objective of this study was to analyze the genotype distributions and allele frequencies for the C276T polymorphism of the neuronal nitric oxide synthase (nNOS) gene among the patients with migraine. The diagnosis of migraine was made clinically based on questionnaires. One hundred and twenty patients with migraine were genotyped for the C276T polymorphism of the nNOS gene and compared with 185 age-matched healthy controls. Genomic DNA from migraine patients and controls was analyzed by polymerase chain reaction (PCR). A PCR–restriction fragment-length polymorphism analysis of nNOS gene polymorphism was performed, and the results were compared. Neither genotype distributions nor the allele frequencies for the C276T polymorphism showed a significant difference between the groups. Additionally, there was no marked differences in genotype distribution or allele frequencies for the migraine without aura and migraine with aura subgroups when compared to control group. These results suggested that migraine of the Turkish population seemed to develop without any alterations in nNOS C276T polymorphism. Our data showed that there is no marked association between the C276T polymorphism of the nNOS gene and migraine.

The Effect of Circadian Melatonin Levels on Inflammation and Neurocognitive Functions Following Coronary Bypass Surgery

PURPOSE In this study, the relationship between the plasma levels of melatonin and intercellular adhesion molecule-1 (ICAM-1), which plays role in several intercellular interactions including inflammatory and immune responses, and early neurocognitive functions associated with ischaemia-reperfusion injury during open heart surgery is examined. METHODS Forty patients who were to undergo elective coronary artery bypass grafting (CABG) were divided into two groups, those who underwent their operations at 8 AM (group I; n = 20) and those who underwent their operations at 1 PM (group II; n = 20). Blood samples were collected prior to surgery (S1), when the aortic cross clamp was removed (S2) and 4 (S3) and 24 h after the surgery (S4). Neuropsychiatric assessment was conducted one day before and seven days after surgery. RESULTS Melatonin levels measured during and after surgery were also significantly higher in Group 1. ICAM-1 levels were significantly lower in Group 1 at S2 and S3. Significant deterioration was observed in postoperative neurocognitive function compared with preoperative functions in Group 2 more than Group 1. CONCLUSION We hypothesise that the greater preservation of neurocognitive functions in the morning patients is associated with elevated melatonin levels, which reduce the damage from ischaemia-reperfusion injury.

Fatigue in Multiple Sclerosis: Is it related to cytokines and hypothalamic-pituitary-adrenal axis?

BACKGROUND Fatigue is a common symptom of Multiple Sclerosis (MS) that diminishes the quality of life of patients, but its exact mechanism remains poorly understood. There is not a generally adopted scale to determine MS fatigue. Studies that investigated physiopathology of fatigue symptom have shown dysregulation of hypothalamic-pituitaryadrenal (HPA) axis. In the current study, we aimed to compare the results obtained with two separate scales, namely the Fatigue Severity Scale (FSS) and the Neurological Fatigue Index-Multiple Sclerosis (NFI-MS), and assess the relationship between fatigue and serum IL-1β, TNF-α, IL-35, IL-2, IL-10, ACTH, cortisol, α-MSH, β-MSH, γ-MSH and CLIP (Corticotropinlike intermediate lobe peptide) in MS patients categorized as fatigued and non-fatigued on the basis of FSS scores. METHODS For the study, a total of 54 (29 females, 25 males) patients diagnosed with RRMS including 26 with fatigue symptom (48.1%), and 26 healthy controls (13 females, 13 males) were enrolled. A FSS score ≥36 was considered as cut-off score to separate fatigued patients from nonfatigued patients. RESULTS A significant positive correlation was determined between FSS score and NFI-MS scale, NFI-MS 1, NFI-MS 2, NFI-MS 3 and NFI-MS 4 scores. IL-1β, IL-10 and TNF-α levels did not differ between patient and control groups. IL-35 and IL-2 levels were significantly higher among MS patients (p<0.01). However, no difference was observed between fatigued and nonfatigued patients in the cytokines and HPA parameters studied. ACTH, cortisol and α-MSH were significantly higher in MS group (p=0.02, p<0.01 and p<0.01, respectively). CLIP level was significantly low in MS patient group (p<0.01). CONCLUSION NFI-MS scale is equally sensitive as FSS scale for assessment of MS fatigue; thus, it may also be widely used to evaluate that symptom. Generally HPA axis is hyperactive in MS patients, but it is not correlated with fatigue in our study. For the first time, levels of CLIP (a type of melanocortin) are studied, and determined to be lower among MS patients. Elevated levels of IL-35 and IL-2 suggest that these cytokines may have a prominent role in MS pathophysiology and can be investigated as potential targets for development of novel therapies.

Investigation of the Rho-kinase 2 gene Thr431Asn polymorphism in migraine

BACKGROUND Migraine has a complex etiology determined by genetic and environmental factors, but the molecular mechanisms and genetics of this disease have not yet been fully clarified. AIM This case/control study was designed to analyze the genotype distributions and allele frequencies for the Rho-kinase 2 (ROCK2) gene Thr431Asn polymorphism among the migraine patients. MATERIALS AND METHODS A total of 155 migraine patients and 155 healthy age and sex matched controls were included in this study. Genomic deoxyribonucleic acid from migraine patients and controls was analyzed by real-time polymerase chain reaction. RESULTS Neither genotype distributions nor the allele frequencies for the Thr431Asn polymorphism showed a significant difference between the groups. In addition, there were no marked differences in genotype and allele frequencies for the migraine without aura and migraine with aura subgroups when compared with control group. CONCLUSION This is the first study to show that the ROCK2 gene Thr431Asn polymorphism is not a risk factor for the migraine in the Turkish population.