فهرست مطالب eskandar kamali-sarvestani

Edaravone is a free radical scavenger which is used as a drug for the treatment of cerebral infarction and amyotrophic lateral sclerosis. Edaravone is distributed widely in the body and its effects are not limited to the neural tissue. Many studies indicate that edaravone has some nitric oxide synthase (NOS) modulating properties. In this research we evaluated the effects of edaravone (1, 5 and 10 mg/kg) alone or in concombination with diphenyliodonium chloride (a specific endothelial NOS inhibitor) or aminoguanidine (a specific inducible NOS inhibitor) on oxidative stress, and renal tissue and function in a model of acute kidney injury induced by a single intramuscular injection of hypertonic glycerol solution. Effects of edaravone on gene expressions of eNOS and iNOS (by RT-PCR) were also investigated. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey’s test. At the end of this study, edaravone attenuated oxidative stress and improved renal tissue damage and dysfunction. Aminoguanidine enhanced the renoprotective effects of edaravone. Edaravone showed no remarkable effect on the expression of eNOS gene but it reduced the induction of iNOS gene significantly. The results of this study showed that edaravone could protect against rhabdomyolysis-induced acute kidney injury using its antioxidant activity and inhibiting effect on iNOS gene expression.

In addition to pro-inflammatory role, dendritic cells (DCs) can also be anti-inflammatory when they acquire tolerogenic phenotype. In this study we tested the role of CD40 and IL-23p19 in antigen presenting function of bone marrow-derived DCs (BMDCs) by comparing BMDCs derived from CD40 knockout (CD40KO-DCs) and IL-23p19 (IL-23p19KO-DCs) knockout mice with those from C57BL/6 mice (Cont-DCs). We have focused on CD40 and IL-23, as these molecules have well established pro-inflammatory roles in a number of autoimmune and inflammatory diseases.

The expression of maturation markers MHC II and co-stimulatory molecules CD40, CD80, and CD86 was analyzed by flow cytometry, while the expression of CD40 and IL-23p19 was measured by RT-PCR. The capacity of BMDCs to activate CD4+ T cells was evaluated by 3H-thymidine incorporation, and the capacity of BMDCs to uptake antigen was evaluated using fluorescent OVA and flow cytometry.

The lack of CD40 or IL-23p19 had no effect on uptake of FITC-OVA by the DCs, confirming their immature phenotype. Moreover, CD40KO-DCs had significantly reduced capacity to stimulate proliferation of CD4+ T cells. CD4+ T cells activated by CD40KO-DCs and IL-23p19KO-DCs produced significantly less IFN-γ (P-value ≤0.05), while CD4+ T cells stimulated by IL-23p19KO-DCs produced less GM-CSF and more IL-10 than Cont-DCs.

This study shows that CD40KO-DCs and IL-23p19KO-DCs have a marked tolerogenic potency in vitro. Future in vivo studies should determine if and to what extent DCs lacking CD40 or IL-23 have a potential to be useful in therapy of autoimmune inflammation.

Microchimerism is defined as the presence of non-self and circulating cells in a host. The current study aimed to assess the effect of microchimerism on scleroderma major organ involvements. This cross-sectional study was conducted on 56 scleroderma patients registered in a tertiary rheumatology center of Shiraz University of Medical Sciences. Information on the patients’ demographics and disease complications was gathered through a review of medical records. Skin score was applied to better assess skin thickening. High Resolution CT-scan as well as pulmonary function test (PFT) results were also used to investigate pulmonary involvement in patients. Y chromosome serum levels were measured using Phenol Chloroform Extraction protocol and following real-time PCR. Fifty-six scleroderma patients with a mean age of 46±10 years were recruited in this study (58.9% with diffuse scleroderma and 41.07% with limited scleroderma). Other than skin thickening, the most common clinical presentation among the patients was interestitial lung disease (67.8%). No significant difference was found between Y chromosome levels of patients with either lung, cardiac, renal, or gastrointestinal involvement and those who did not have these complications. Y chromosome serum levels based on the results of PFT were also shown to have no significant difference. Moreover, no association was demonstrated between serum Y chromosome and skin score. The serum level of chromosome Y has no impact on the severity and frequency of major organ involvement in Iranian scleroderma patients.

This study aimed to determine the serum levels of prolactin and dehydroepiandrosterone (DHEA) in systemic sclerosis (SSc) and their correlation with disease duration and clinical manifestations. This case control study investigated 26 scleroderma patients and 26 healthy individuals adjusted for age and sex with the case group as controls. Serum levels of DHEA using radioimmunoassay (RIA) and prolactin using immune radiometric assay (IRMA) were measured in both groups. Clinical manifestations of the disease, disease duration, and fertility status at the time of the study were also determined for each scleroderma patient. The findings on 26 scleroderma patients (20 females and 6 males with mean age of 44 years and mean disease duration of 5±3 years) demonstrated that serum levels of DHEA were significantly lower in scleroderma patients than controls based on gender (males, p= 0.02) and fertility (fertile women, p= 0.01; menopausal women, p= 0.008). However, no significant difference was found in prolactin serum levels between the case and control groups. Moreover, only serum PRL levels correlated significantly with disease duration in fertile women. Contrary to previous studies, this study manifested that serum PRL did not differ between scleroderma patients and normal individuals. Yet, serum DHEA was shown to be significantly lower in scleroderma patients. Only PRL levels correlated significantly with disease duration.

Multiple Sclerosis (MS) with four different types is one of the well studied autoimmune diseases of the central nervous system. Generally, two-thirds of MS patients are females who are at risk of pregnancy-related complications. Inappropriate responses of mother’s immune system, such as antibody production against placental proteins, may lead to pregnancy-related disorders. The association between pregnancy complications and some autoantibodies including anti-phospholipid and anti-angiotensin II type-1 receptor antibodies are clear examples in this regard.

To investigate the probable placental antigens that might be targeted by the antibodies in the sera of MS patients.

Total placental proteins were extracted from normal fresh placentas and were separated using two-dimensional gel electrophoresis (2-DE) technique. The separated proteins were transferred onto a Polyvinylidene Fluoride (PVDF) membrane and blotted with the pooled sera of MS women or healthy controls (20 individuals in each group). The differentially blotted spot was identified by mass spectrometry and confirmed by western blot technique.

The results indicated that the women afflicted with MS had an antibody against placental HSP70kDa protein 5 (GRP78).

In the present study, a new placental autoantigen candidate, which was targeted by antibody present in MS women sera, was found. The clinical importance of this finding regarding pregnancy complications in MS patients should be investigated by further experiments.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and cytokines may play a role in the development of MS lesions.
To determine levels of different cytokines in patients with relapsing-remitting MS (RR-MS) compared to healthy controls.
Profiles of pro-inflammatory, Th1-, Th2-, and Th17-related cytokines were compared by quantitative multiplexed ELISA-based chemiluminescent assay in 44 RR-MS and 44 healthy age- and sex-matched individuals from the same ethnicity.
Among pro-inflammatory cytokines, the levels of IL-6 (p=0.003), IL-8 (p=0.05) and TNF-α (p=0.002) were higher in patients than controls, though IL-4 and IL-10 as well as ΣTh2 cytokines were lower in patients (p=0.05, p=0.02 and p=0.05, respectively). After gender classification, the higher levels of IL-4 in male patients remained significant and IL-13 also showed significantly higher levels in male patients compared to male controls (p=0.003 and p=0.05, respectively). A significant negative correlation was detected between EDSS and IL-10 or ΣTh2 levels (p=0.005). In addition, IL-1α (r=0.4, p=0.05) and IFN-γ (r=0.35, p=0.05) were also directly correlated with EDSS in female patients.
Patients with RR‑MS who are in the relapse clinical phase exhibit higher levels of pro-inflammatory cytokines and reduction in protective Th2-related cytokines.

Ruptured cerebral aneurysms (ICAs) are the most common non-traumatic cause of subarachnoid hemorrhage (SAH) that is associated with life threatening complications such as Vasospasm, Infarction, and Hydrocephalus (HCP). The active participation of macrophage/monocyte-mediated inflammatory response in the pathogenesis of cerebral aneurysm as labeled with Monocyte Chemoattractant Protein-1 (MCP-1) is suggested. To measure the serum level of MCP-1 in ruptured CAs in different time intervals. We measured the serum levels of MCP-1 in SAH patients who had CAs and compared it with that of MCP-1 in two control groups: including patients with SAH without CAs, and the normal population of blood donors. We also measured the MCP-1 levels in patients with CAs one week afterward to evaluate the effect of treatment. Serum level of MCP-1 was measured by a commercial ELISA assay. Mean serum MCP-1 level in patients with SAH and CAs was 188.2168 Pg/ml and 331.3982 Pg/ml in the normal population. There was no statistically significant difference between serum levels of MCP-1 on the first (mean=188.2168 Pg/ml) and 7th days after SAH onset (mean=171.8450 Pg/ml) (p=0.739). Serum level of MCP-1 increased significantly as Glasgow Coma Scale decreased (p=0.078) and Hunt and Hess score increased (p=0.089). Our results did not show an increasing MCP-1 serum level in patients with aneurysmal SAH. There was a relationship between poor clinical grade and MCP-1 levels in patients with CAs. MCP-1 may be a local inflammatory marker for cerebral aneurysms without systemic manifestation. Rahmanian A, et al. Iran J Immunol. 2015; 12(4):302-310.

One of the major challenges in the field of vaccine design is choosing immunogenic antigens which can induce a proper immune response against complex targets like malignant cells or recondite diseases caused by protozoan parasites such as leishmaniasis. The aim of this study was to find a way to construct artificial liposome-based cells containing fragments of target’s cell membrane. This structure not only mimics the real biological properties of proteins in the cell membrane of target cells, but also may induce the required immune responses, which culminate in eradication of target cells. Five different techniques have been investigated to engraft the plasma membrane’s vesicles (PMVs) derived from a characterized Leishmania parasite into liposomes. The most efficient method was tested again on the PMVs derived from well-known breast cancer cell line SK-BR-3. The percentage of engraftment was determined by two-color flowcytometry after staining the engrafted dioctadecyl-3,3,3''3''-tetramethylindocarbocyanine DiI[FA1] -labeled liposomes with FITC-labeled PMVs. Among the investigated techniques, freeze-drying method with 91±2% and 90±3% of engraftment for Leishmania and SK-BR-3 derived PMVs, respectively, showed superiority over the other methods. In addition, after 9 weeks storage in refrigerator, freeze-dried fused particles kept their original size (660±350 nm) and fusion efficiency (94±3%). Among five different engraftment techniques, freeze-drying is preferred over the other methods due to its simplicity, more fusion efficiency and stability of produced particles during storage.

This cross-sectional study is conducted to determine the prevalence of asymptomatic cervical spine subluxation in rheumatoid arthritis patients by plain radiographs and its relation to demographic and clinical characteristics, disease activity measures and medications. 100 rheumatoid arthritis patients (18 male and 82 female) were selected randomly, according to the American college of Rheumatology Criteria, who were under follow up in the rheumatology clinic. A complete history was taken, and physical examination has been done with focus on the cervical spine to determine their demographic data, disease duration, age of disease onset, drug history, swollen and tender joint counts, and ESR, Hb, CRP, RF levels. The disease activity of patients with rheumatoid arthritis was measured using the disease activity score 28. Radiographs of the cervical spine included lateral views taken in flexion, extension, neutral position of the neck and anterioposterior and odontoid projection view. Asymptomatic cervical spine subluxation was found in 17 of the 100 patients (17%). The prevalence of, anterior atlantoaxial subluxation, atlantoaxial impaction and subaxial subluxation was 10(10%), 5(5%) and 6(6%), respectively. Posterior subluxation was not detected. The only characteristic that showed meaningful relationship with cervical spine subluxation was CRP (P=O.036). Our results showed that patients with RA, who have cervical spine subluxation cannot be distinguished on the basis of symptoms. Cervical spine involvement is common and may be asymptomatic, indicating routine cervical spine imaging is needed in patients with RA.

Multiple sclerosis (MS) is a complex polygenic disease in which gene-environment interactions are important. A number of studies have investigated the association between tumor necrosis factor-α (TNF-α) -308 G/A polymorphism (substitution G→A, designated as TNF1 and TNF2) and MS susceptibility in different populations, but the results of individual studies have been inconsistent. Therefore, performing a systematic review and meta-analysis of the published studies is desirable. We sought to quantitatively summarize the association between TNF-α-308 G/A polymorphism and MS. The Medline and Scopus databases were searched to identify potentially relevant case-control studies published in English journals up to January 2010. A meta-analysis of these studies was performed. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under fixed and random effects models. Twenty-one eligible studies, comprising 2880 patients with MS and 3579 controls, were included in the meta-analysis. The overall pooled ORs (95%CI) for TNF2 versus TNF1 and TNF2 carriers (2/2+2/1) versus non-carriers (1/1) were 1.02 (0.86-1.21) and 0.99 (0.8-1.24), respectively. In the European populations, the pooled ORs (95%CI) for TNF 2/1 versus 1/1 were 0.85 (0.73-0.98), which was statistically significant. However, the other results did not support this finding. The pooled ORs (95%CI) for TNF 2/1 versus 1/1 and TNF 2/2 versus 2/1 were not statistically significant in the overall population. In addition, the pooled ORs for TNF2/2 versus TNF2/1+1/1 and TNF2/2 versus TNF1/1 were not statistically significant. Our meta-analysis does not support the role of TNF-α -308 G/A polymorphism in developing MS.

Hepatitis C virus (HCV) infection is the main cause of chronic liver disease and to date there has been no vaccine development to prevent this infection. Among non-structural HCV proteins, NS3 protein is an excellent goal for a therapeutic vaccine, due to its large size and less variation in conserved regions. The immunogenic properties of heat shock proteins (HSPs) for instance GP96 have prompted investigations into their function as strong adjuvant to improve innate and adaptive immunity.. The aim of this study was to examine additive effects of recombinant GP96 (rGP96) fragments accompanied by rNS3 on expression levels of α5integrin and pro-inflammatory cytokines, IL-12 and TNFα, in Antigen Presenting Cells (APCs).. Recombinant viral proteins (rNS3 and rRGD-NS3), N-terminal and C-terminal fragments of GP96 were produced and purified from E. coli in order to treat the cells; mouse spleen Dendritic Cells (DCs) and THP-1 macrophages.. Our results showed that rNT-GP96 alone significantly increases the expression level of IL-12, TNFα and α5integrin in THP-1 macrophages and DCs, while IL-12 and TNFα expression levels were unaffected by either rNS3 or rRGD-NS3. Interestingly, the co-addition of these recombinant proteins with rNT-GP96 increased IL-12, TNFα and α5integrin expression. Pearson Correlation showed a direct association between α5integrin with IL-12 and TNF-α expression.. we have highlighted the role of rNS3 plus rNT-GP96 mediated by α5integrin in producing IL-12 and TNFα. It can be suggested that rNT-GP96 could enhance immunity characteristic of rNS3 protein via production of pro-inflammatory cytokines..

To investigate the correlation between IL-8 (-251 A/T) gene polymorphism and susceptibility to chronic periodontitis as well as different clinical parameters and severity of the condition in patients referred to dental school, Shiraz University of Medical Sciences, Shiraz, Iran. In this randomized cross sectional study, 227 non-smoking patients with chronic periodontitis (test) and 40 healthy individuals (control) were enrolled in this experiment and the following clinical parameters were employed in the study: Periodontal Pocket Depth (PPD), Clinical Attachment Level (CAL) and Bone Loss (BL). All participants underwent the PCR (Polymerase Chain Reaction) test to detect 251 A/T Single Nucleotide Polymorphism of IL8 gene. No significant correlation was perceived between different genotypes of IL-8 and the severity of the periodontal condition (P= 0.164), neither did we detect any substantial association between different IL-8 genotypes and the mean PPD (P=0.525), CAL (P=0.151), BL (P=0.255), PI (P=0.087), BOP (P=0.265) and the average number of teeth (P=0.931). The results implied that there was no explicit correlation between 251 (A/T) IL-8 gene polymorphism and the severity of the chronic periodontal disease or to the susceptibility to it.

Systemic Sclerosis (SSc) is a systemic connective tissue disease. In this study, we compared the serum Homocystein (Hcy) level between patients with SSc and normal control group.. The current study was conducted to determine whether serum Hcy levels are elevated in SSc patients and whether there is any correlation between Hcy levels and RP, Gastro intestinal and lung involvement..Patients and Forty one patients who fulfilled the diagnostic criteria for SSc (39 females and 5 males) and Forty four community-based healthy individuals (sex and age matched) were enrolled in to the study. Serum Hcy, vitamin B12, and folate levels were determined.. Thirty three patients (70.45%) had GI involvement, twenty two patients (50%) had lung involvement and twenty seven patients (61.36%) had Raynaud’s phenomena. Mean serum Hcy level in control group was 22.78 ± 6.018 μmol/L and in case group was 19.43 ± 7.205 μmol/L, shows that the serum Hcy level in control group was significantly higher than patients (P = 0.020).. Serum Hcy level is significantly lower in SSc patients than in control group. There is no statistically significant correlation between serum Hcy level and organ involvements..

T helper 1 and T helper 17 cells play important roles in immunity against foreign invaders. Differentiation of these Th subsets is affected by state of maturation and cytokines that are produced by dendritic cells (DCs). Curdlan is a linear (1→3) -β-glucan and has shown activity against tumors and infectious agents. This study aims to investigate whether curdlan plays its role through affecting the maturation and cytokine production by DCs. DCs were isolated from the spleen of BALB/c mice by MACS method. After an overnight culture of DCs in the presence of curdlan، the expression levels of CD40، CD86، and MHC-II molecules were determinedby flow cytometry. The production of cytokines involved in Th1 and Th17 celldifferentiation (IL-12 and IL-6، respectively) was also evaluated by ELISA. Lipopolysaccharide (LPS) treated and untreated cells were considered as positive and negative controls، respectively. The results of this study did not show a significant difference in the levels of surface expression of CD40 (p=0. 82)، CD86 (p=0. 79)، and MHC class II (p=0. 84) molecules upon exposure to curdlan. However،LPS increased the intensity of CD40 expression on dendritic cells (p=0. 04). In addition،it was revealed that curdlan-exposed DCs are not able to produce a significant amount of IL-6 and IL-12 cytokines. Conversely، LPS-treated DCs were able to make a significant amount of IL-12 (p=0. 005). The results of the present study suggest that curdlan has no effect on Th1 or Th17 differentiation while LPS may induce Th1 deviation by induction of CD40 expression and IL-12 production.

IL-8 is one of the pro-inflammatory cytokines which can play an essential role in the pathogenesis of chronic rhinosinusitis (CRS) as well as nasal polyposis (NP). The ability of individuals in producing IL-8 is partially determined by IL-8-251 A/T polymorphism. Hence, the aim of the present study was to investigate the association between IL-8-251 A/T and CXCR2 +1208 C/T genes polymorphisms and susceptibility to CRS and NP. Two hundred and forty fiveCRS patients and 204 healthy controls were included in this study. CRS patients were categorized by the existence or absence of NP. IL-8 promoter-251 A/T and CXCR2 +1208 C/T gene polymorphisms were genotyped via the allele specific PCR (AS-PCR) method. While no remarkable difference was demonstrated between patients and controls for both CXCR2 +1208 C/T and IL-8 -251 A/T polymorphisms, a significant increase in IL-8-251 AA genotype was detected in CRS patients with NP compared to those without it (29.3% and 16.2%, respectively; P=0.03). Interestingly, this association got far stronger when only non-asthmatic CRS patients were taken into consideration (P=0.001). The results of the present study indicate that the inheritance of IL-8-251 Aallele is associated significantly with NP development in CRS patients. Therefore, NP formation might be a result of the exposure to an intense inflammatory environment, which is more likely in genetically susceptible CRS patients.

Human cornea expresses functional Fas-ligand capable of killing Fas+ activated lymphocytes. Fas expression is partly regulated by -670 A/G polymorphism in the promoter region of Fas gene. The aim of the present study is to determine the association between Fas-670A/G polymorphism and survival of corneal transplantation. In 276 graft recipients who mainly underwent penetrating keratoplasty because of keratoconus, bullous keratopathy and corneal opacity, Fas -670 A/G polymorphism was determined by allele specific oligonucleotide polymerase chain reaction (ASO-PCR) techniques. There was no statistically significant relationship between Fas -670 A/G polymorphism and rejection episode (p=0.35). Moreover, the relationship between this polymorphism and rejection episode outcome (transplant recovery vs failure) was not statistically significant (p=0.13). The results of the present study show no significant correlation between corneal graft rejection, rejection recovery and Fas -670A/G gene polymorphism.

Multiple Sclerosis (MS), the most common demylinating disease of the CNS, is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of IgG (FcγR) might induce inflammatory responses through linking the humoral and cellular immune responses by targeting immune complexes to effector cells. Polymorphisms in some FcγR genes are associated with various infectious and autoimmune diseases, probably due to their effects on different binding capacities of encoded receptors for IgG containing immune complexes. To investigate the importance of FcγR polymorphisms in susceptibility to MS. One hundred and fifty MS patients and 136 age and sex matched controls were genotyped for FcγRIIA and FcγRIIIA gene polymorphisms using PCR-RFLPmethod. The allelic and genotypic frequencies of the FcγRIIA and FcγRIIIA did not differ significantly between the MS patients and controls. There was no associationbetween allelic polymorphism of FcγRIIIA and severity of disease based on Expanded Disability Status Scale (EDSS) score. However, significant association between inherited FcγRIIA genotype and disease activity (p=0.001) or progression index was revealed (p=0.014). EDSS values showed that FcγRIIA (H/H) and (H/R) genotypes were associated with a lower EDSS score in relapsing-remitting MS and in the total MS population (P=0.001) but not (R/R) genotype. Considering the detrimental role of autoantibodies in the pathogenesis of MS, our results suggest that the inherited FcγRIIA alleles could affect the severity of MS by influencing the clearance rate of immune complexes and autoantibodies. The results of the present study add the FcγRIIA gene to the gene networks which determine the severity of MS in southern Iran.

Prostate-specific antigen (PSA) was purified to homogeneity from human seminal plasma by ion-exchange chromatography on a CM-Sephadex C-50 and by gel filtration on a Sephacryl S-200 column. A single 33-kDa protein band appeared in SDS-PAGE. High pressure liquid chromatography (HPLC) of the purified protein produced a single peak, while isoelectric focusing demonstrated the presence of five different isoforms of this protein. The immunoreactivity of the purified PSA was checked by Western blotting. This simple two-step method can be used for a large-scale preparation of the purified PSA for the clinical tests and also for further investigative studies on the biological properties of this protein