Circulatory Levels of C-X-C Motif Chemokine Ligands 1, 9, and 10 Are Elevated in Patients with Ischemic Stroke.

OBJECTIVE: Inflammation plays a significant role in the development of ischemic stroke. CXC chemokines play pleiotropic roles in prolonged leukocyte locomotion, astrocyte migration/activation, and neural attachment/sprouting in response to focal stroke. In this study, we aimed to explore the changes in serum levels of three chemokines, C-X-C motif chemokine ligand 1 (CXCL1), C-X-C motif chemokine ligand 9 (CXCL9), and C-X-C motif chemokine ligand 10 (CXCL10), in ischemic stroke patients at the time of admission and before discharge from the hospital ward. MATERIALS AND METHODS: In this study, we recruited 43 unrelated ischemic stroke patients using an easy convenience method or accidental sampling which is a type of non-probability sampling that involves the sample being drawn from that part of the population that is close to hand. We also enrolled 50 genetically unrelated healthy controls showing no history of neurologic, cardiovascular, or inflammatory diseases. Serum levels of the considered chemokines were measured by enzyme-linked immunosorbent assay (ELISA) in patients and healthy controls. RESULTS: No significant difference was observed in ischemic stroke patients following hospitalization and prior discharging from the hospital; however, there was a significant difference in serum levels of CXCL9 and CXCL10 between patients and healthy controls. We also found that the level of the chemokine was not related to gender or medical therapy. It appears that CXCL9 and CXCL10 are more predisposing factors and play a direct role in stroke considering that they were higher in patients than in healthy controls. CONCLUSION: We believe that this study might be used as a basis for further studies on more effective medication regimens to prevent the onset and subsequent complications of stroke. However, these mediators are useful diagnostic and prognostic tools rather than therapeutic tools.

Involvement of central TRPV1 receptors in pentylenetetrazole and amygdala-induced kindling in male rats.

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel that is involved in modulation of diverse physiological processes. The role of this receptor in epilepsy has not been studied well. Therefore, we investigated the role of central TRPV1 receptors on the development of pentylenetetrazole (PTZ) and amygdala-induced kindling in rats. Male Wistar rats received subconvulsive dose of PTZ intraperitoneally, every other day. TRPV1 receptor agonist, OLDA and its antagonist, AMG-9810 were injected intracerebroventricularly 30 min prior to PTZ administration. In electrical kindling, stimulating and recording electrodes were implanted in the right amygdala of male rats. After kindling, the effect of TRPV1 receptor agonist or antagonist on afterdischarge duration (ADD), latency to the onset of bilateral forelimb clonuses (S4L) and duration of loss of equilibrium (stage 5 seizures, S5D) were measured. The results demonstrated that, OLDA at the doses of 0.01, 0.1 and 1 µg/rat, significantly accelerated the incidence of all seizure stages, increased S5D and decreased S4L in the PTZ model of kindling. Also, in amygdala kindling, S5D and ADD were significantly reduced following the administration of AMG-9810. In contrast, OLDA significantly aggravated the indices of seizure in both models of epileptic seizure. This study demonstrated that central TRPV1 receptors may be involved in the development of electrical and PTZ-induced kindling.

The SDF-1α3'A genetic variation is correlated with susceptibility of asthma in Iranian patients.

BACKGROUND AND AIM: Chemokine/receptor axis is a predominant actor of clinical disorders. They are key factors of pathogenesis of almost all clinical situations including asthma. Correspondingly, CXCL12 is involved in the immune responses. Therefore, this study was designed to explore the association between gene polymorphism at position +801 of CXCL12, known as SDF-1α3'A, and susceptibility to asthma in Iranian patients. MATERIAL AND METHODS: In this experimental study, samples were taken from 162 asthma patients and 189 healthy controls on EDTA. DNA was extracted and analyzed for CXCL12 polymorphisms using PCR-RLFP. The demographic information was also collected in parallel with the experimental part of the study by a questionnaire which was designed specifically for this study. FINDINGS: Our results indicated a significant difference (P < 0.0001) between the A/A, A/G, and G/G genotypes and A and G alleles of polymorphisms at position +801 of CXCL12. We also showed an elevated level of CXCL12 circulating level in Iranian asthma patients. CONCLUSION: Our findings suggest that SDF-1α3'A (CXCL12) polymorphism plays a role in pathogenesis of asthma. It can also be concluded that circulatory level of CXCL12 presumably can be used as one of the pivotal biological markers in diagnosis of asthma.

Temporal expression profile of CXC chemokines in serum of patients with spinal cord injury.

Chemokines, a subclass of cytokine superfamily have both pro-inflammatory and migratory role and serve as chemoattractant of immune cells during the inflammatory responses ensuing spinal cord injury (SCI). The chemokines, especially CXCL-1, CXCL-9, CXCL-10 and CXCL-12 contribute significant part in the inflammatory secondary damage of SCI. Inhibiting chemokine's activity and thereby the secondary damage cascades has been suggested as a chemokine-targeted therapeutic approach to SCI. To optimize the inhibition of secondary injury through targeted chemokine therapy, accurate knowledge about the temporal profile of these cytokines following SCI is required. Hence, the present study was planned to determine the serum levels of CXCL-1, CXCL-9, CXCL-10 and CXCL-12 at 3-6h, 7 and 28days and 3m after SCI in male and female SCI patients (n=78) and compare with age- and sex-matched patients with non-spinal cord injuries (NSCI, n=70) and healthy volunteers (n=100). ANOVA with Tukey post hoc analysis was used to determine the differences between the groups. The data from the present study show that the serum level of CXCL-1, CXCL-9 and CXCL-10 peaked on day 7 post-SCI and then declined to the control level. In contrast, significantly elevated level of CXCL-12 persisted for 28 days post SCI. In addition, post-SCI expression of CXCL-12 was found to be sex-dependent. Male SCI patients expressed significantly higher CXCL-12 when compared to control and SCI female. We did not observe any change in chemokines level of NSCI. Further, the age of the patients did not influence chemokines expression after SCI. These observations along with SCI-induced CSF-chemokine level should contribute to the identification of selective and temporal chemokine targeted therapy after SCI.

The SDF-1 3'A genetic variation is correlated with elevated intra-tumor tissue and circulating concentration of CXCL12 in glial tumors: a study on Iranian anaplastic astrocytoma and glioblastoma multiforme patients.

Immunological factors are important in pathogenesis of various malignancies, including neural cancers. The CXC chemokine CXCL12 is involved in the immune responses. Therefore, the aim of the present study was to investigate the association between tumor tissue and circulating concentrations of CXCL12 as well as its genetic variation at position +801 known as(the SDF-1 3'A), in Iranian patients suffering from malignant glial tumors. In this study, stereotactic tumor biopsy specimens in parallel with peripheral blood samples were collected from 123 patients and 189 healthy controls. The serum level of CXCL12 was measured by ELISA and tumor tissues were subjected to Western blotting for intra-tumor CXCL12 detection; we also employed PCR-RFLP to detect the SDF-1 3'A polymorphism. Demographic data were collected by a researcher-designed questionnaire. These results demonstrated a significant difference between the A/A, A/G, and G/G genotype and A and G alleles of polymorphisms at position +801 of CXCL12. We also indicated elevated levels of CXCL12 in circulation and tumor tissue obtained from in patients suffering from malignant glial tumors. Based upon the results of this investigation, we propose that CXCL12 and its SDF-1 3'A polymorphism play a fundamental part in the pathogenesis of malignant glial tumors. It is also noteworthy that CXCL12 could probably be utilized as a beneficial biological marker in the diagnosis of these tumors.

A Case Of Conversion Disorder Associated With An Arachnoid Cyst

Objective: This case report highlights arachnoid cyst, a rare benign space-occupying lesions (SOL) formed by an arachnoid membrane containing cerebrospinal fluid (CSF) which in most cases, are identified by accident. Conversion disorder is characterized as a deficit or distortion in neurological functioning, or symptoms suggesting a general medical condition that is not referable to an organic lesion. Methods: We report a case of a 24 year old woman who came to a psychiatrist with history of suicide attempt. She had a history of failed marriage but no history of substance abuse. She had a history of dizziness, light-headedness, blurred vision, seizure and headache for a while. Seizure was identified to be pseudo seizures in further assessments. Results: Diagnosis of Conversion Disorder with Adjustment Disorder was revealed. In Barin Computerized Tomography (CT) scan there was an extra axial cystic lesion with the height, frontooccipital and lateral size of approximately 6.4 cm by 4 cm by 2.5 cm respectively in the left anterior middle fossa and Sylvian fissure. Based on patient's history, the arachnoid cyst and its symptoms may have a synergistic effect on patient's symptoms of conversion disorder. Conclusion: This case reflects the importance of ruling out medical problems in patients with psychiatric symptoms.

I405V and -629C/A polymorphisms of the cholesteryl ester transfer protein gene in patients with coronary artery disease.

BACKGROUND: Cholesteryl ester transfer protein (CETP) plays a main role in high-density lipoprotein metabolism. CETP gene possesses several single nucleotide polymorphisms which have been associated with plasma high-density lipoprotein cholesterol (HDL-C) concentrations. The aim of this study was to determine the association of CETP -629C/A and I405V polymorphisms with coronary artery disease (CAD) in Iranian population. METHODS: The presence of two CETP gene polymorphisms -629C/A and I405V were studied in 187 unrelated CAD cases and 136 controls. All the samples were clinically examined and lipid profile was estimated. Genotyping was performed using polymerase chain reaction/restriction fragment length polymorphism method. RESULTS: The frequency of -629C/A and I405V allelic variants were found to be 0.732 and 0.366 in cases and 0.658 and 0.348 in controls, respectively. The frequency of A allele of -629C/A polymorphism in cases was significantly higher than that of controls. HDL-C in AA genotype was higher than CA and CC genotypes in controls. No significant effect of II, IV and VV genotypes was found in lipid profiles. CONCLUSION: No significant association was found between CETP I405V polymorphism and increased risk of CAD in Azeri population studied. AA genotype of -629C/A increased HDL but the risk of CAD in this genotype might be higher than CC genotype.