Increased visinin-like protein-1, YKL-40, lipocalin-2, and IL-23 levels in patients with migraine.

BACKGROUND: Migraine is a type of primary headache caused by changes in the trigeminal system and has been reported to be associated with neurovascular inflammation of cerebral and extracerebral vessels. OBJECTIVE: It is known that inflammation is an important process in the pathogenesis of migraine. It has been shown that the molecules of visinin-like protein 1 (Vilip-1), YKL-40, lipocalin-2 and interleukin (IL)-23 play a role in the inflammatory process. Our aim is to investigate the role of this molecule in the metabolic pathway of migraine disease. METHODS: Fifty migraine patients with and without aura in the interictal period were included in the study. Vilip-1, YKL-40, lipocalin-2, and IL-23 levels were measured by ELISA method. RESULTS: Serum vilip-1, YKL-40, lipocalin-2, and IL-23 levels were found to be significantly higher in migraine patients compared to the control group. We found that this molecule increased significantly in migraine subgroups compared to the control group (p < 0.001). A positive significant correlation was found between vilip-1 level and YKL-40 and lipocalin-2 levels in migraine patients. In addition, a positive correlation was observed between visual analogue scale score, number of days with pain and vilip-1 level (p < 0.01). The results of our study showed that activation of inflammatory mediators may play a role in the pathogenesis of migraine disease. In addition, our study is valuable in that inflammatory molecules are high in the interictal period and these biomarkers have never been analyzed in migraine patients. However, we still believe that larger studies are needed to explain the role of vilip-1, YKL-40, lipocalin-2, and IL-23 in the molecular mechanism of migraine disease.

Cerebrospinal fluid levels of sortilin-1, lipocalin-2, autotaxin, decorin and interleukin-33 in patients with idiopathic intracranial hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is characterized by increased cerebrospinal fluid (CSF) pressure of unknown cause. It has been suggested that the inflammatory process plays a role in the pathophysiology of the disease. Sortilin-1, lipocalin-2, autotaxin, decorin, and interleukin-33 (IL-33) are among the factors involved in inflammatory processes. OBJECTIVE: To investigate the CSF levels of sortilin-1, lipocalin-2, autotaxin, decorin, and IL-33 in patients with IIH. METHODS: A total of 24 IIH patients and 21 healthy controls were included in the study. Demographic characteristics of the patients and of the control group as well as CSF pressures were evaluated. Sortilin-1, lipocalin-2, autotaxin, decorin and IL-33 levels in the CSF were measured. RESULTS: The CSF levels lipocalin-2, sortilin-1, autotaxin, IL-33 and CSF pressure were significantly higher in the patients group compared with the control group (p < 0.001). Decorin levels were reduced in patients (p < 0.05). There was no correlation between the autotaxin and IL-33 levels and age, gender, CSF pressure, and body mass index. The results of our study showed that inflammatory activation plays an important role in the development of the pathophysiology of IIH. In addition, the fact that the markers used in our study have never been studied in the etiopathogenesis of IIH is important in explaining the molecular mechanism of this disease. CONCLUSION: Studies are needed to evaluate the role of these cytokines in the pathophysiology of the disease. It is necessary to evaluate the effects of these molecules on this process.

ANTECEDENTES: A hipertensão intracraniana idiopática (HII) é caracterizada pelo aumento da pressão do líquido cefalorraquidiano (LCR) de causa desconhecida. Tem sido sugerido que o processo inflamatório desempenha um papel na fisiopatologia da doença. Sortilina-1, lipocalina-2, autotaxina, decorina e interleucina-33 (IL-33) estão entre os fatores envolvidos nos processos inflamatórios. OBJETIVO: Investigar os níveis de sortilina-1, lipocalina-2, autotaxina, decorina e IL-33 no LCR de pacientes com HII. MéTODOS: Um total de 24 pacientes com HII e 21 controles saudáveis foram incluídos no estudo. Foram avaliadas as características demográficas dos pacientes e do grupo controle, bem como as pressões liquóricas. Os níveis de sortilina-1, lipocalina-2, autotaxina, decorina e IL-33 no LCR foram medidos. RESULTADOS: Os níveis no líquido cefalorraquidiano lipocalina-2, sortilina-1, autotaxina, IL-33 e pressão liquórica foram significativamente maiores no grupo de pacientes em comparação com o grupo controle (p < 0,001). Os níveis de decorina foram reduzidos nos pacientes (p < 0,05). Não houve correlação entre os níveis de autotaxina e IL-33 e idade, sexo, pressão liquórica e índice de massa corporal. Os resultados do nosso estudo mostraram que a ativação inflamatória desempenha um papel importante no desenvolvimento da fisiopatologia da HII. Além disso, o fato de os marcadores utilizados em nosso estudo nunca terem sido estudados na etiopatogenia da HII é importante para explicar o mecanismo molecular dessa doença. CONCLUSãO: Estudos são necessários para avaliar o papel dessas citocinas na fisiopatologia da doença. É necessário avaliar os efeitos dessas moléculas nesse processo.

Changes in serum albumin levels and neutrophil-lymphocyte ratio in patients with convulsive status epilepticus.

AIM: Inflammation may be involved in the ictogenesis and development of some partial epilepsies. Serum albumin levels and the neutrophil-lymphocyte ratio (NLR) are markers of inflammation. The aim of this study was to investigate the ability of serum albumin levels and NLR to predict inflammation in patients with convulsive status epilepticus (CSE). METHODS: This retrospective study was conducted on 58 patients who were diagnosed with CSE and control group comprised of 58 healthy individuals. Albumin levels and NLR were evaluated during both the acute and subacute periods of CSE. RESULTS: The average serum albumin levels were 3.27 ± 0.62 g/dL during the acute period and 3.4 ± 0.67 g/dL in the subacute period in the patient group and 3.92 ± 0.52 g/dL in the control group. Neutrophil counts were higher in patients in the acute phase of CSE, but lymphocyte counts were lower compared to the control group and the subacute phase. The average NLR values were 4.83 ± 5.1 in the acute period, 3.07 ± 3.02 during the subacute period and 1.98 ± 0.42 in the control group. Serum albumin and NLR levels were significantly different between the patients in the subacute and acute periods of CSE and the control group (p < 0.05). There were significant negative correlational relationships between serum albumin and NLR levels (p < 0.05). CONCLUSION: We found serum albumin levels were significantly lower and the NLR was significantly higher in the acute period of CSE. Neutrophil-mediated inflammation may be important in the aetiopathogenesis of CSE.

Association between sequence variations of the Mediterranean fever gene and the risk of migraine: a case-control study.

Migraine pathogenesis involves a complex interaction between hormones, neurotransmitters, and inflammatory pathways, which also influence the migraine phenotype. The Mediterranean fever gene (MEFV) encodes the pyrin protein. The major role of pyrin appears to be in the regulation of inflammation activity and the processing of the cytokine pro-interleukin-1ß, and this cytokine plays a part in migraine pathogenesis. This study included 220 migraine patients and 228 healthy controls. Eight common missense mutations of the MEFV gene, known as M694V, M694I, M680I, V726A, R761H, K695R, P369S, and E148Q, were genotyped using real-time polymerase chain reaction with 5' nuclease assays, which include sequence specific primers, and probes with a reporter dye. When mutations were evaluated separately among the patient and control groups, only the heterozygote E148Q carrier was found to be significantly higher in the control group than in the patient group (P=0.029, odds ratio [95% confidence interval] =0.45 [0.21-0.94]). In addition, the frequency of the homozygote and the compound heterozygote genotype carrier was found to be significantly higher in patients (n=8, 3.6%) than in the control group (n=1, 0.4%) (P=0.016, odds ratio [95% confidence interval] =8.57 [1.06-69.07]). However, there was no statistically significant difference in the allele frequencies of MEFV mutations between the patients and the healthy control group (P=0.964). In conclusion, the results of the present study suggest that biallelic mutations in the MEFV gene could be associated with a risk of migraine in the Turkish population. Moreover, MEFV mutations could be related to increased frequency and short durations of migraine attacks (P=0.043 and P=0.021, respectively). Future studies in larger groups and expression analysis of MEFV are required to clarify the role of the MEFV gene in migraine susceptibility.

Association of brain-derived neurotrophic factor and nerve growth factor gene polymorphisms with susceptibility to migraine.

Migraine is one of the most common neurological diseases worldwide. Migraine pathophysiology is very complex. Genetic factors play a major role in migraine. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), play an important role in central nervous system functioning, development, and modulation of pain. This study investigates whether polymorphisms in the BDNF and NGF genes are associated with migraine disease in a Turkish case-control population. Overall, 576 subjects were investigated (288 patients with migraine and 288 healthy controls) for the following polymorphisms: rs6265(G/A), rs8192466(C/T), rs925946(G/T), rs2049046(A/T), and rs12273363(T/C) in the BDNF gene, and rs6330(C/T), rs11466112(C/T), rs11102930(C/A), and rs4839435(G/A) in the NGF gene using 5'-exonuclease allelic discrimination assays. We found no differences in frequency of the analyzed eight polymorphisms between migraine and control groups. However, the frequency of minor A alleles of rs6265 in BDNF gene was borderline significant in the patients compared with the healthy controls (P=0.049; odds ratios [ORs] [95% confidence intervals {CIs}] =0.723 [0.523-0.999]). Moreover, when the migraine patients were divided into two subgroups, migraine with aura (MA) and migraine without aura (MO), the minor TT genotype of rs6330 in NGF was significantly higher in MA patients than in MO patients (P=0.036) or healthy controls (P=0.026), and this disappeared after correction for multiple testing. Also, the rs6330*T minor allele was more common in the MA group than in the MO group or controls (P=0.011, ORs [95% CIs] =1.626 [1.117-2.365] or P=0.007, ORs [95% CIs] =1.610 [1.140-2.274], respectively). In conclusion, this is the first clinical study to evaluate the association between BDNF and NGF polymorphisms in migraine patients compared with health controls. Our findings suggest that the NGF rs6330*T minor allele might be nominated as a risk factor for developing aura in migraine disease. Our results should be considered as preliminary, and they need to be confirmed by future studies.

Investigation of PON1 activity and MDA levels in patients with epilepsy not receiving antiepileptic treatment.

PURPOSE: There are many studies dedicated to researching the etiopathogenesis of epilepsy. In such research, oxidative and antioxidant indicators of etiopathogenesis have also been examined under the scope. Drawing on a group of patients with epilepsy who were receiving no treatment, we have tried to evaluate whether or not an increase in oxidative indicators is linked directly with the disorder, independent of epileptic medicaments. METHODS: Thirty people in good health and 30 newly diagnosed with epilepsy and who received ambulatory treatment in the polyclinic of the Neurology Department took part in the study. The tests relating to serum malondialdehyde (MDA) levels and paraoxonase 1 (PON1) activity were carried out in the biochemistry laboratory. RESULTS: Even though the levels of MDA in the patient group (14.34±3.59 nmol/mL) were found to be high compared to those of the control group, which consisted of people in good health (13.53±3.56 nmol/mL), there was no statistically significant difference. PON1 activity in the serum taken from people in the patient group (0.65±0.17) was lower in comparison to that observed in the serum of the control group (0.71±0.17 U/L). Nonetheless, it was not so low as to have significance from a statistical point of view. CONCLUSION: We conclude that such a high level of oxidative parameters should have been related to the disease and that statistically significant findings that emerged in some other studies could have been related to an antiepileptic treatment.

Protective effects of l-glutamine against toxicity of deltamethrin in the cerebral tissue.

BACKGROUND: Deltamethrin (DLM) is a broad-spectrum synthetic dibromo-pyrethroid pesticide that is widely used for agricultural and veterinary purposes. However, human exposure to the pesticide leads to neurotoxicity. Glutamine is one of the principal, free intracellular amino acids and may also be an antioxidant. This study was undertaken in order to examine the neuroprotective and antioxidant potential of l-glutamine against DLM toxicity in female Wistar albino rats. MATERIALS AND METHODS: The rats were divided into the following groups (n=10): Group I: control (distilled water; 10 mL/kg, po one dose), Group II: l-glutamine (1.5 g/kg, po one dose), Group III: DLM (35 mg/kg, po one dose), and Group IV: DLM (35 mg/kg, po one dose) and l-glutamine (1.5 g/kg, po one dose after 4 hours). Total oxidant status (TOS), total antioxidant status (TAS), tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 levels and apoptosis were evaluated in brain tissue. RESULTS: DLM-treated animals had a significant increase in brain biochemical parameters, as well as TOS and TAS. Furthermore, the histopathological examination showed neuronal cell degeneration in the cerebral tissue. l-Glutamine treatment decreased the elevated brain levels of TOS and neuronal cell degeneration. There was no difference in tumor necrosis factor-α, IL-1ß, and IL-6 levels between the groups. CONCLUSION: l-Glutamine may reduce the toxic effects of DLM in the cerebral tissue through antioxidant properties.

The relationship between fibrinogen to albumin ratio and severity of coronary artery disease in patients with STEMI.

OBJECTIVE: Previous studies show that serum fibrinogen levels are established risk factors for coronary artery disease (CAD) and that serum albumin levels are of a higher specificity and sensitivity in ST-elevation myocardial infarction (STEMI). In this study, we sought to evaluate the association between fibrinogen to albumin ratio (FAR) and the extent and severity of CAD evaluated by TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries (SYNTAX) Score (SS) in patients with STEMI. METHODS: A total of 278 patients with STEMI were included in the study. FAR was calculated using specified variables. The extent and severity of CAD were evaluated using the SS. The patients were divided into low- (SS <22) and high- (SS ≥22) risk groups. A Spearman rank correlation coefficient analysis was used for the relationship between FAR and SS. The cutoff points for sensitivity and specificity of FAR in predicting SS were estimated by performing a receiver operator characteristic curve analysis. RESULTS: There were significant differences in the mean age (P=.016), admission serum albumin (P=.041), serum fibrinogen (P<.001), FAR (P<.001), and SS risk groups. Positive correlation was detected between FAR and SS (r=0.458, P<.001). A cutoff level of >87 FAR predicted SS (sensitivity, 70%; specificity, 70%), and an area under the curve of 0.758 serum fibrinogen and albumin level was an independent predictor for SS in patients with STEMI (b=0.039; 95% confidence interval, 0.016-0.062; P=.001 and b=-6.906; 95% confidence interval, -12.284 to -1.527; P=.013, respectively). CONCLUSION: In the present study, we showed that FAR is significantly related to SS in predicting the severity of CAD in patients with STEMI.

Relation between electrophysiological findings and diffusion weighted magnetic resonance imaging in ulnar neuropathy at the elbow.

AIM: As only a limited number of studies have used diffusion-weighted imaging (DWI) and conventional magnetic resonance imaging (MRI) in patients with ulnar neuropathy at the elbow (UNE), the present study aimed to investigate the diagnostic value of the non-invasive DWI technique in patients with UNE. METHODS: A total of 26 elbows in 19 healthy controls (age range: 22-56 years) with no symptoms and 24 elbows in 21 symptomatic patients (age range: 21-46 years) with cubital tunnel syndrome underwent DWI. The electrophysiological and clinical criteria for the diagnosis of UNE were examined. RESULTS: No pathological signal from the ulnar nerve was detected in the healthy controls, whereas there was an increase in signals on DWI in all patients with UNE. On T2-weighted (T2W) imaging, there was increased signal intensity in 20 elbows, while low signal intensity was observed in the remaining four. A positive correlation was found between disease duration and presence of hyperintensity (P=0.044, r=0.42) on T2W images. CONCLUSION: DWI can be used together with electrophysiological methods for the diagnosis of UNE. Furthermore, DWI might be preferred in some cases, as it is non-invasive compared with the electrophysiological method for UNE diagnosis.

Relationship of cognitive performance with prolidase and oxidative stress in Alzheimer disease.

Glutamate excitotoxicity and oxidative stress are held responsible for the pathogenesis of Alzheimer's disease (AD). Prolidase is known to have a crucial part in the recycling of proline for collagen synthesis. Elevated proline levels have been shown to increase glutamate concentration. To our knowledge, prolidase activity in AD has not yet been studied. In this study, we aimed to reveal the relationship of AD with oxidative stress and collagen turnover by comparing AD patients and healthy control group with regard to total antioxidant status (TAS), total oxidant status (TOS), and prolidase levels. Fifty patients (mean age, 72.5 ± 8.9 years) diagnosed with AD and a control group comprised of 39 healthy individuals (mean age, 69.1 ± 7.1 years) were compared relative to serum TAS, TOS, and prolidase levels. The relationship of cognitive performance with prolidase, TAS, and TOS was evaluated by Mini mental state examination (MMSE). Alzheimer's disease group demonstrated statistically significantly higher prolidase and TOS levels as compared to the control group (p = 0.01, p = 0.018, respectively). Total antioxidant status level was significantly lower in the dementia group than in the control group (p = 0.032). MMSE manifested a negative correlation with prolidase and TOS levels (p = 0.001, r = -0.33; p = 0.002, r = -0.32, respectively), while displaying a positive correlation with TAS levels (p = 0.002, r = 0.32). In conclusion, elevated prolidase and TOS levels along with reduced TAS concentrations suggest that oxidative stress and collagen breakdown are involved in the cognitive impairment in AD.

Diagnostic value of F-wave inversion in patients with early carpal tunnel syndrome.

Routine electrophysiological studies usually give normal results in patients with early stage carpal tunnel syndrome (CTS). Diagnostic significance of the F-wave inversion (the median of F-wave minimal latencies (FWML) exceeds a normal ipsilateral ulnar FWML by 1ms) has not been previously reported in early stage CTS. In this study, our primary aim was to investigate the diagnostic value of F-wave inversion in early stage CTS. Additionally, we aimed to demonstrate any possible relationship between F-wave inversion and symptom scores of the Boston questionnaire and functional capacity in early stage CTS. The study included 60 early stage CTS patients who presented with a median sensory nerve conduction velocity of ≥50m/s. The symptom severity and functional status of the patients were assessed by using the Boston questionnaire. The control group consisted of 45 healthy volunteers. We compared early stage CTS patients and healthy control subjects in terms of the results obtained from median-ulnar FWML. Existence of F-wave inversion was found in 32 (53.3%) of the early stage CTS patients and in 3 (8.7%) of the healthy controls (p=0.001). It was also found to be positively correlated with the Boston questionnaire scores (p=0.001, r=0.41) and functional capacity scores (p=0.001, r=0.41). The sensitivity and specificity of F-wave inversion for the diagnosis of early stage CTS were calculated as 53.3% and 93.3%, respectively. The addition of F-wave inversion measurement to the set of the routine nerve conduction studies can increase the reliability of the electrophysiological studies in patients with early stage CTS.

Serum levels of calcification inhibitors in patients with intracerebral hemorrhage.

The vascular calcification regulators and inflammatory markers including fetuin-A, osteopontin (OPN), and matrix Gla protein (MGP) may play an important role in the development of intracerebral hemorrhages (ICHs). So far, the relationship between these parameters and ICH has not been studied. Therefore, this study was designed to elucidate whether fetuin-A, MGP, and OPN are involved in the pathophysiology of ICH. The ICH group consisted of 27 consecutive patients with spontaneous ICH evaluated in the neurology intensive care unit within the first 24 hours from the onset of the stroke. The serum OPN levels were significantly increased in patients with ICH compared to the controls. On the other hand, the serum MGP and fetuin-A levels were significantly decreased in the patients with ICH in comparison to the controls. In the patients with ICH, the serum MGP levels of the nonsurvivors were statistically significantly lower than the MGP levels of the survivors. In conclusion, the change in serum fetuin-A, MGP, and OPN levels after ICH indicates that these parameters play a role in the pathophysiological processes leading to an ICH. Measurement of the serum MGP levels may also be of value to estimate mortality.

Ellagic acid attenuates oxidative stress on brain and sciatic nerve and improves histopathology of brain in streptozotocin-induced diabetic rats.

The aim of this study was to investigate the possible effects of ellagic acid in brain and sciatic nerve tissues of diabetic rats. Also, the impact of ellagic acid on catalase and paraoxonase (PON-1) activities, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA) and nitric oxide (NO) were examined. The rats were randomly divided into four groups, with eight rats each: Normal controls (not diabetic), only ellagic acid treated (ellagic acid controls, not diabetic), Diabetic controls (streptozotocin, diabetic), ellagic acid-treated diabetic (streptozotocin + ellagic acid). After a 4 week experiment, rats were sacrificed, and biomarkers for oxidative stress in the brain and sciatic nerve tissues of the rats were measured. There was significant depletion in the PON-1, catalase, and TAS levels in the brain and sciatic nerve tissues compared to the control groups (for both parameters, p<0.05). The values of catalase, PON-1 and TAS reversed back to normal levels in ellagic acid-treated diabetic rats compared to untreated diabetic rats (for both parameters, p<0.05). The levels of MDA, TOS, NO and, OSI in the brain and sciatic nerve tissues were higher in untreated diabetic rats compared to control group (for both parameters p<0.05). However, MDA, TOS, OSI, and NO levels were found to be significantly reduced in the ellagic acid-treated diabetic group compared to the untreated diabetic group in these tissues (for both parameters, p<0.05). In conclusion, the results of the present study suggested that ellagic acid exhibits neuroprotective effects against oxidative damage in diabetic rats.

Increased asymmetric dimethylarginine and nitric oxide levels in patients with migraine.

Asymmetric dimethylarginine (ADMA) has been found as correlated with endothelial dysfunction and oxidative stress. There are few studies regarding ADMA and nitric oxide (NO) levels in patients with migraine and alterations of ADMA and NO levels during migraine attack are not well-known. Therefore, in present study, we aimed to measure NO and ADMA levels in patients with migraine and compare them with the control group to investigate the correlation between migraine, oxidative stress and endothelial dysfunction. The migraine group consisted of 59 patients, including 22 suffering from migraine with aura and 37 suffering from migraine without aura. The control group consisted of 31 healthy volunteers without headache. The patients in migraine group were divided into subgroups based on whether attack period was present or not and whether it was migraine with or without aura. Plasma ADMA levels were measured using an enzyme-linked immunosorbent assay method. Migraine patients had higher concentrations of NO (35.6±7.7, 31.0±6.2 µmol/L, respectively, p=0.005) and ADMA (0.409±0.028, 0.381±0.044 µmol/L, respectively, p = 0.001) levels when compared with the healthy controls. During migraine attack, NO and ADMA levels were found to be significantly higher in migraine group as compared to control group (respectively, p=0.015, p=0.014). Similarly, NO and ADMA levels in the patients with migraine in the interictal period were found to be significantly higher as compared to control group (p=0.011, p=0.003). In conclusion, higher ADMA and NO levels of patients with migraine supported that oxidative stress and endothelial dysfunction may have a role in migraine pathogenesis.