A modified schedule of multiple aeroallergen ultra-rush immunotherapy in perennial allergic rhinitis: safety, efficacy, and T lymphocyte cell population studies.

BACKGROUND: This study assessed whether a modified immunotherapy schedule for allergic rhinitis could be safe and efficient. Ultra-rush immunotherapy (URIT) rapidly desensitizes patients to aeroallergens. OBJECTIVE: We aimed to develop a modified URIT protocol in 3 days to achieve the target dose while observing whether it could improve this situation and decrease the time to achieve the maintenance dose. METHODS: The URIT was exercised in 21 patients with perennial allergic rhinitis. Premeditations were given to the patients 3 days prior to the immunotherapy and during the 3 days injections immunotherapy: pred nisolone, ranitidine, and Airokast/montelukast. Finally, the T cell population frequencies of patients prior to and after immunotherapy, including T helper 1, T helper 2, cytotoxic T lymphocytes, and regulatory T cells, were studied using flow cytometry. During the URIT protocol, 21 patients received 291 injections. RESULT: Six patients (28.6%) showed systemic reactions in our study. All systemic reactions occurred on the third day by the 1:1 dilution of the maintenance dose. These systemic reactions occurred in three patients after 13 injections, and the three remaining patients showed systemic reactions following the last injection. No systemic reaction was observed on the first and second day of the therapy, and the risk of systemic reaction with every injection was about 2%. Among the T cell populations, CD3+ and CD8+ cells decreased significantly. CONCLUSION: The findings emphasized that URIT, alongside premedication with a high dose of antihistamine, helped to achieve the maintenance dose and control clinical manifestations.

Evaluation of Serum Substance P Level in Chronic Urticaria and Correlation with Disease Severity.

Substance P (SP) is a neurotransmitter emitted from neurons that plays a role in the pathogenesis of itching conditions including chronic urticarial (CU). The present research aims to investigate the serum level of S.P among CU patients and compare them with healthy subjects and explore how it correlates with the severity of urticaria. The present research was conducted on 87 CU patients who visited the allergy clinic of Ghaem Hospital, Mashhad, Iran from October 2017 to June 2018. Besides, 86 healthy subjects were recruited as the control group. Background information of patient was collected including age, sex, duration of the disease and the co-occurrence of angioedema. S.P serum level was measured in two groups by ELISA method. In the patients group, the autologous serum skin test (ASST) was performed along with the urticaria evaluation questionnaire include Urticaria Activity Score 7 (UAS7), Urticaria Control Test (UCT) and Chronic Urticaria Quality of Life (CU-Q2OL). Among the patients, the SP serum level showed to be about two times higher than the healthy subjects (p˂0.001). SP showed to be increased as patients' age grew (p=0.010). In patients with a positive ASST, SP level was higher (p=0.012). No correlation was found between SP and the presence of angioedema among patients. There was no correlation between the SP serum level and the scores obtained from urticaria evaluation questionnaires. SP among CU patients was higher than healthy subjects. SP was also higher among female, older and positive ASST patients. The SP value was not correlated with the severity of urticaria, angioedema. In conclusion, Using SP antagonist drugs could be a potential treatment for chronic urticaria.

The Role of Interleukin-4 and 13 Gene Polymorphisms in Allergic Rhinitis: A Case Control Study.

BACKGROUND: Allergic Rhinitis (AR) is an IgE-mediated inflammatory disorder with high morbidity rates. The eitiology of this disease is understood to occur from a complex interaction between genetic and environmental factors. T helper type 2 cells have been shown to have a crucial role in atopic disease due to their production of the cytokines, intelukin (IL)-13 and IL-4, involved in inflammation. Research has shown single nucleotide polymorphisms (SNP) of the IL-13 and IL-4 genes to be associated increased levels of IgE and with allergic diseases such as, allergic rhinitis, asthma, and atopic dermatitis. Specifically, the rs2243250 SNP of IL-4 and the rs20541 SNP of IL-13 have been shown to be associated with AR. METHODS: A case-control study was designed to investigate the relationship between the two SNPs rs2243250 and rs20541 with the incidence of AR. The SNPs were examined in patients with AR and healthy controls (86 patients and 86 controls). Blood samples were collected and DNA was extracted to evaluate the SNPs by RFLP-PCR. RESULTS: Recessive analysis model of the IL-13 gene (GG vs. AA+AG) revealed that the GG genotype was more common in AR patients (P=0.36) )OR=0.8 [81% CI 0.38-1.6]). For the IL-4 gene (TC vs. TT+CC), the TC genotype was more common in AR patients (P = 0.0022)) OR=0.71 [60% CI 1.41-5.02]). Furthermore, in the IL-4 gene, the 590 T>C polymorphism had a significant association with AR. However, no association was found between AR and the IL-13 rs20541 polymorphism. CONCLUSION: Our findings suggest that the IL-13 polymorphism (rs20541, Exo 4, G>A, Arg130Gln) and IL-4 polymorphism (rs2243250= C-590T, promoter, T>C) are co-associated with AR and sensitivity to aeroallergens. However, this study used a cohort of AR patients and healthy controls from the northeast of Iran. Given the influence of ethnicity and environment on genetics, further investigation is needed to elucidate the role of SNPs in IL-4 and IL-13 in AR among different populations.

A significant increase in expression of FOXP3 and IL-17 genes in patients with allergic rhinitis underwent accelerated rush immunotherapy.

OBJECTIVES: Allergic rhinitis (AR) is a common hypersensitivity disease worldwide. Immunotherapy has been performed as the best treatment for years. This study aimed to study the gene expression pattern of immune system cells following an accelerated rush immunotherapy protocol (ARIT) in patients with AR. MATERIALS AND METHODS: Fifteen patients with AR (15-55 years old) resident in Mashhad, Iran, with positive prick test to regional aeroallergens (weed mix, grass mix, tree mix, and Salsola) enrolled in this study. All patients were treated for three months with 3-day ARIT protocol between July 2015 and August 2016. Clinical symptoms and quality of life were recorded by two questioners. The expression levels of FOXP3, TGF-ß, IL-10, IL-17, IL-4, and IFN-γ genes in patient's peripheral blood mononuclear cells were evaluated by SYBR Green real-time RT-PCR technique. RESULTS: The severity of disease and quality of life showed significant improvement following ARIT (P-value<0.05). Gene expression of IFN-γ and IL-10 was increased whereas TGF-ß and IL-4 down-regulated, following ARIT, but these changes were not significant. However, gene expression of FOXP3 and IL-17 was significantly increased after intervention when compared with the baseline (P-value< 0.002). CONCLUSION: Significant up-regulation of FOXP3 and IL-17 genes, additionally, a significant improvement in the clinical signs following ARIT might be related to increases in HLA-DR- and FOXP3+ Treg population at the initiation phase of ARIT. Employing the flow cytometry technique to study the phenotype of these cells is suggested for future studies.

Effects of Serum Vitamin D and Efficacy of Subcutaneous Immunotherapy in Adult Patients With Allergic Rhinitis.

Immunotherapy is the standard of treatment for long-life relief of symptoms of allergic rhinitis. Vitamin D may affect the outcomes of treatment. This study evaluated the clinical efficacy of subcutaneous allergen immunotherapy in adult patients with allergic rhinitis based on the serum level of vitamin D. Patients with persistent allergic rhinitis and positivity for skin prick test were evaluated by Sino-nasal Outcome Test (SNOT-22) and Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) before subcutaneous allergen immunotherapy and during the maintenance phase to assess the relation of the serum level of vitamin D and the clinical efficacy of immunotherapy. After immunotherapy, the greatest reduction in SNOT-22 scores were reported in patients with vitamin D sufficiency (39.0 ± 9.2), followed by vitamin D suboptimal provision (35.1 ± 12.1), insufficiency (25.0 ± 7.5), and deficiency (18.3 ± 6.0) (P < 0.001). The MiniRQLQ reduction in patients with vitamin D sufficiency, suboptimal provision, insufficiency, or deficiency was 30.7 ± 8.7, 27.1 ± 8.7, 20.0 ± 8.6, or 17.4 ± 7.1, respectively (P < 0.001). Both of SNOT-22 and MiniRQLQ scores decreased significantly following immunotherapy in patients with different levels of vitamin D. However, these effects were more pronounced when the level of vitamin D was sufficient.

A Biographical History of Some Iranian Pioneers in Medical Immunology and Allergy.

The oldest literature that mentioned the immunity was related to the plague of Athens in 430 BC. The germ theory had more influence on the description of the discrimination between self and non-self which is the core concept of immunology. Allergic diseases were known from 2,000 years ago while Rhazes wrote the first medical monograph about seasonal allergic rhinitis. In Iran, Dr. Mohammad Kermanshahi introduced the basic concepts of serology in 1900. The first Department of Serology was established at Tehran University, Faculty of Medicine in 1951 by Prof. Dr. Hassan Mirdamadi. After that, immunology entered into the cellular and molecular period. Prof. Mohammad Ali Maleki established the first Iranian Society of Allergy and then Prof. Abolhassan Farhoodi found the first Department of Clinical Immunology and Allergy at Tehran University. In this paper, we review the role of famous Iranian scientists and physicians in the progress of modern immunology and allergy from a historical perspective.

HTLV-1-host interactions facilitate the manifestations of cardiovascular disease.

Atherosclerosis is a multifactorial life-threatening disease which an epidemiologic study in Northeastern Iran showed its association with HTLV-1 infection. Therefore, a cross-sectional study of 39 newly diagnosed subjects with angiography test in three groups including 14 coronary artery disease+HTLV-1+ (CAD+HTLV-1+), 8 CAD-HTLV-1+, and 17 CAD+HTLV-1- patients and 11 healthy subjects (CAD-HTLV-1-) were conducted. In the present study, Tax and proviral load (PVL) as HTLV-1 virulence factors, along with host chemokine receptor 1 (CCR1), and CCR2 were investigated. Real-time PCR TaqMan method was carried out for PVL measurement and HTLV-1-Tax, CCR1, and CCR2 expressions in peripheral blood mononuclear cells (PBMCs). Furthermore, the main risk factors, lipid profile, and complete blood count (CBC) were assessed. Expression of CCR1 in CAD+HTLV-1+ group was higher than CAD-HTLV-1+ (P = 0.01) and healthy subjects (P = 0.02). Expression of CCR1 in CAD+HTLV-1+ was higher in comparison with CAD+HTLV-1-group but did not meet 95% CI (P = 0.02), but meaningful at 91% CI. In addition, expression of CCR2 in CAD+HTLV-1+ subjects was higher than CAD-HTLV-1+ and CAD+HTLV-1- (P = 0.001, P = 0.005, respectively). In CAD+HTLV-1- subjects, CCR2 was higher than CAD-HTLV-1+ (P = 0.03). The mean PVL in CAD+HTLV-1+ group is more than CAD-HTLV-1+ (P = 0.041). In HTLV-1+ patients Tax had a positive correlation with cholesterol (R = 0.59, P = 0.01), LDL (R = 0.79, P = 0.004) and a negative correlation with HDL (R = -0.47, P = 0.04). These correlations were stronger in CAD+HTLV-1+. Findings showed that HTLV-1 could alter the expression of CCR2 and, less effect, on CCR1. Moreover, the strong correlation between CCR2 and HTLV-1-Tax with cholesterol, LDL and HDL showed that Tax as the main HTLV-1 virulence factor in cytokine deregulation might be had indirect effects on cholesterol, LDL, and HDL levels.

Evaluation of Sub cutaneousRush Immunotherapy Effectiveness in Perennial Allergic Rhinitis after a Year from Treatment.

INTRODUCTION: Allergen immunotherapy is an effective treatment for allergic rhinitis. Conventional immunotherapy takes at least 5 to 6 months to reach the maintenance dosage; nonetheless, rush immunotherapy accelerates to reach the maintenance dose several months earlier. However, the safety and efficacy of this treatment has not been widely investigated. The objective of the present study was to determine the efficacy of subcutaneous rush immunotherapy in the patients with perennial allergic rhinitis after a year from treatment. MATERIALS AND METHODS: This study was carried out on a total of 15 patients with allergic rhinitis who received rush immunotherapy and were evaluated for the quality of life and clinical symptoms improvement with Sino-Nasal Outcome Test Questionnaire (SNOT-22) and Mini Rhino conjunctivitis Quality of Life Questionnaire (RQLQ) before and after a year from treatment. Moreover, specific weed mix Immunoglobulin E (IgE) was measured before and after a year from treatment. Statistical analysis was performed using SPSS software (version 16) (P<0.05). RESULTS: The comparison of specific IgE indicated a significant reduction between before and after a year from treatment (P=0.005for pigweed)(P=0.022 for salsola). There was a significant decrease in clinical symptoms according to SNOT-22 Questionnaire [(mean score: 46.00, before the treatment) and (mean score: 14.06, after the treatment)]. The quality of life for most of the patients was moderate (46.7%) before the treatment and good (80%) after the treatment, which was considered statistically significant (P>0.001). CONCLUSION: Rush immunotherapy is an effective treatment in the patients with allergic rhinitis. It seems to be an alternative treatment in cases that need more rapid treatment. However, it is recommended to carry out other studies on the control group.

Evaluation of the frequency of invariant natural killer T (iNKT) cells in nasal polyps.

Nasal polyps (NP) are associated with inflamed mucosa of unknown etiology. The role of T cells in nasal polyposis is unclear. Invariant natural killer T cells (iNKT) can promote Th2 responses and have been implicated in some types of asthma. As there are shared inflammatory pathways involved in asthma and NPs, we evaluated the frequency of iNKT in 17 patients with NPs, but without asthma. A median of 6% polyp cells were T lymphocytes, of which iNKT were 0 to 2.38% (mean 0.674%). In the matched group (n = 10), iNKT in NPs was significantly higher than PBMCs (1.057% vs 0.155%, P < 0.05). Relative expression of Vα24 to TCR-beta genes in polyps (n = 14) was higher than blood in matched samples (n = 4). The presence of greater proportions of iNKT in NPs than in blood suggests that iNKT may play a role in the pathogenesis of nasal polyposis.

The Most Common Allergenic Tree Pollen Grains in the Middle East: A Narrative Review.

Allergy is becoming a major disease burden globally. Pollens are considered as the main component of aeroallergens that lead to rhinitis and asthma. Due to the lack of a comprehensive investigation on most allergic pollens of trees in the Middle East, the present study aimed to conduct a comprehensive literature review on this topic. The main goal of the study was to provide a checklist for allergists and patients to easily identify the commonest allergic pollens in their locality. The present review provides a broad range of information on the types and geographic locations of the most common allergic pollens of trees in each studied country. In general, among the 23 studied countries, palm and mesquite trees were the common producers of pollen allergen in the Persian Gulf region. Olive tree is common in Turkey, Palestine, and Israel, whereas sycamore tree is the common allergen pollen in Iran. Considering the uneven geographical distribution of these trees in the world, allergists are unable to accurately select the appropriate extracts for the skin prick test based on the information from the neighboring countries. This scenario becomes more complicated if one adds the imported ornamental trees in the picture.

CD14 as A Serum Immune Biomarker and Genetic Predisposition Factor for Allergic Rhinitis.

INTRODUCTION: Allergic Rhinitis (AR) is a common inflammatory disease of the nasal mucosa. The CD14 is a receptor for lipopolysaccharide and inhaled endotoxin which can stimulate the production of interleukins by antigen presenting cells. Accordingly, CD14 plays an important role in allergic and atopic diseases, which can be one of the etiological factors for allergic diseases. The present study investigated the association between the CD14 gene polymorphism C-159T and AR and aimed to detect the correlation between serum levels of CD14 and AR. MATERIALS AND METHODS: This study was conducted on two groups of participants. The experimental group consisted of 125 patients with AR referring to Ghaem Hospital, Mashhad University of Medical Sciences in Mashhad, Iran, and the control group included 125 healthy subjects from Mashhad National Blood Center, Iran. Serum CD14 levels were measured by enzyme-linked immunosorbent assay. Polymerase chain reaction-restriction fragment length polymorphism was employed to detect C-159T gene polymorphism in the CD14 promoter region. RESULTS: There was a significant association between CD14 C-159T gene polymorphism and AR (P<0.001). The results of the statistical analysis showed that the TT genotype could significantly increase the risk of AR (P<0.001). Additionally, a significant association was observed between C-159T gene polymorphism and the serum level of CD14 (P<0.001). Regardless of the genotypes, the serum CD14 levels were significantly higher in AR patients than in those of the participants in the controls (P=0.007). CONCLUSIONS: According to the obtained results of this study, CD14 in serum might be a potential marker for the diagnosis of AR, and in genetic levels it might be a predictive factor for the disease.

Determination of Optimum Excipients for Platanus orientalis Pollen Extract by Accelerating Chemical Stability Test and Their Synergistic Effect.

BACKGROUND: The quality of extracts used in the skin prick test directly influences the interpretation of the test. Accordingly, the outcomes and effectiveness of immunotherapy for the management of IgE-mediated allergies depend on the quality of the extracts used. Excipients, which are pharmacologically inert ingredients, are intentionally added to the active ingredients. The aim of this study was to address optimum excipients for stability Platanus (P.) orientalis extract. METHODS: In this study the excipients examined were l-lysine (20 mM), l-cysteine (20 mM), albumin (0.5%), sorbitol (2%), sucrose (750 mM), trehalose (20 mM), D-mannitol (2% w/v), urea (100 mM) and Tween-20 (0.1%). Their effects on P. orientalis extract stability were analyzed using an inhibition enzyme linked immune assay at 37 °C. RESULTS: A mixture of lysine (20 mM), trehalose (20 mM), and D-mannitol (2% w/v) conferred the greatest stability on the P. orientalis extract. CONCLUSION: The P. orientalis extract stability was increased by a mixture of lysine (20 mM), trehalose (20 mM), and D-mannitol.

Common solvents for making extraction of allergenic proteins from plants' pollens for prick tests and related factors: a technical review.

Collecting information on influencing factors in developing consistent and high-quality extracts results in accurate diagnosis and effective treatment of type I allergy (IgE mediated). Furthermore, considering that a large number of allergens are currently in practice, any attempt to develop a more effective procedure for preparing extract may be useful. Nowadays, different saline solvents, temperature, incubation time, and PH are being incorporated for preparing allergen extracts. The objective of the current study was to clear and address the commonest of solvent buffers and allied conditions for making extracts of pollens of grasses, trees, and weeds. The literature review was done in Jan 2016 on PubMed and Google Scholar medical search engines without any time limitation. After reading abstracts of 87 articles, finally 37 relevant papers were selected and their full texts were retrieved. In conclusion, 24 full-text papers were recognized appropriate and chosen. The extracted information for papers has been described fully in the text. On the basis of these data, PBS buffer with PH 7.4, temperature of 4 °C and with overnight incubation time, may be the optimized condition in order to have a proper extract for carrying out skin prick tests.

Report of Common Aeroallergens among Allergic Patients in Northeastern Iran.

INTRODUCTION: The prevalence of atopic diseases has increased in recent decades dramatically. The most common aeroallergens in Northeastern Iran have not been fully defined. Determining the most common aeroallergens in allergic patients based on the skin prick test (SPT) was aimed in this investigation. MATERIALS AND METHODS: This cross-sectional study enrolled 1,006 allergic patients (aged 1-86 years) from October 2010 to February 2014 referred to the Allergy clinics of Mashhad University of Medical Science. After completing a checklist including demographic information, the SPT was performed according to the patients' history of aeroallergen sensitivity. RESULTS: Patients with symptoms of asthma, allergic rhinitis, atopic dermatitis, and urticaria were enrolled. Ninety seven percent of patients had a positive skin test to at least one aeroallergen. The most prevalent allergens were Russian thistle (Salsola kali) (50.2%), ash (Fraxinus excelsior) (36.7%), grass mix (29.1%), tree mix (21.6%), and pigweed mix (19.5%). Common allergens in patients with different symptoms of allergic disorders were as follows: asthma (Russian thistle, grass mix, ash, tree mix, and Dermatophagoides pteronyssinus); allergic rhinitis (Russian thistle, ash, grass mix, tree mix, and pigweed mix); urticaria (Russian thistle, ash, grass mix, pigweed mix, and tree mix) and atopic dermatitis (Russian thistle, grass mix, ash, tree mix, and pigweed mix). In the spring, the most prevalent allergens were Russian thistle, ash, grass mix, tree mix, and pigweed mix. In the summer, Russian thistle, ash, grass mix, tree mix, and pigweed mix accounted for the most prevalent allergens. During the autumn, Russian thistle, ash, grass mix, pigweed mix and lamb's quarter were the most common aeroallergens, while in the winter, Russian thistle, ash, grass mix, pigweed mix, and tree mix were shown to be the most common aeroallergens. CONCLUSION: Determination of the most common aeroallergens in this area is unavoidable in the diagnosis and management of allergic disorders. Understanding the prevalence of the most common aeroallergens such as Russian thistle in 50.2% of people or other common aeroallergens can help patients and specialists to more easily identify suspected allergens, reduce costs, and support immunotherapy of allergic patients in this area. Moreover, it is helpful in avoiding pollens or cross-reactions.

Downregulation of immune responses in asthmatic humans by ES products of Marshallagia marshalli.

BACKGROUND AND AIMS: Helminths and their products are considered to possess therapeutic capability to control or even prevent immune-mediated diseases. Studies suggest that helminths induce a systemic immunomodulatory network, including regulatory T cells and anti-inflammatory interleukin-10 (IL-10), which might play a key role in the protection against the allergic phenotype. Thus, helminthic therapy is becoming of a major interest, and several researchers are enthusiastically tended to explore its role in allergic diseases. METHODS: Peripheral blood mononuclear cells (PBMCs) from 25 asthmatic and 25 healthy human were collected. After isolation of PBMCs, they were stimulated with excretory/secretory (ES) antigen of M. marshalli, in incubator with 5% CO2 , 37°C. Total RNA was isolated from all cells from antigen stimulated and non-stimulated control PBMC in asthmatic and healthy human after 6 h. The concentration of Th1 type cytokines [interferon-γ (IFN-γ)] and Th2 type cytokines (IL-4) and T-reg cytokines [transforming growth factor-ß (TGF-ß), IL-10] was determined using real-time polymerase chain reaction. RESULTS: Results showed that the IFN-γ expression was significantly decreased in culture condition with ES Ag of M. marshalli in healthy and asthmatic patients (P < 0.05). Similar data were obtained for IL-4 expression in both healthy individuals (<0.006) and asthmatic patients (<0.001). The increment of regulatory cytokines IL-10 and TGF-ß expression was considerably increased in our investigation. CONCLUSION: To our knowledge, this is the first report to document the suppressive effect that the M. marshalli ES product has on PBMSC cell culture of asthmatic patients. The present study provides new insights into understanding the immune modulation governed by parasite-derived products and the development of new asthma treatment strategies.

Approach to Patients with Severe Asthma: a Consensus Statement from the Respiratory Care Experts' Input Forum (RC-EIF), Iran.

Challenges in the assessment, diagnosis and management of severe, difficult-to-control asthma are increasingly regarded as clinical needs yet unmet. The assessments required to determine asthma severity, comorbidities and confounding factors, disease phenotypes and optimal treatment are among the controversial issues in the field. The respiratory care experts' input forum (RC-EIF), comprised of an Iranian panel of experts, reviewed the definition, appraised the available guidelines and provided a consensus for evaluation and treatment of severe asthma in adults. A systematic literature review followed by discussions during and after the forum, yielded the present consensus. The expert panel used the appraisal of guidelines for research and evaluation-II (AGREE-II) protocol to define an initial locally-adapted strategy for the management of severe asthma. Severe asthma is considered a heterogeneous condition with various phenotypes. Issues such as assessment of difficult-to-control asthma, phenotyping, the use of blood and sputum eosinophil count, exhaled nitric oxide to guide therapy, the position of anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty as well as the use of established, recently-developed and evolving treatment approaches were discussed and unanimously agreed upon in the panel. A systematic approach is required to ensure proper diagnosis, evaluate compliance, and to identify comorbidities and triggering factors in severe asthma. Phenotyping helps select optimized treatment. The treatment approach laid down by the Global Initiative for Asthma (GINA) needs to be followed, while the benefit of using biological therapies should be weighed against the cost and safety concerns.

Association between Cytokine production and disease severity in Alzheimer's disease.

The role of transforming growth factor (TGF)-ß1, interferon (IFN)-γ, interleukin (IL)-2, IL-3, and IL-6 in the pathogenesis of Alzheimer's Disease (AD) has long been reported in literature. In this case-control study, the concentrations of these cytokines in altered T lymphocytes, as well as serum vitamin B12, have been compared in terms of factors such as, age, the clinical course and the patients' disease risk. 40 patients who met the DSM-IV-TR criteria of AD were selected and an age- and gender-matched control group was recruited. The participants' cognitive performance was measured according to the Mini Mental State Examination (MMSE), the Global Deterioration Scale (GDS) and Clinical Dementia Ratio (CDR). The levels of cytokines were measured in supernatants of lymphocytes culture, using assays of ELISA and atomic absorption. Higher levels of IL-6 and IFN-γ were found more in the altered T lymphocytes of the AD patients rather than in the control individuals. Furthermore, a marginal significant difference was found between the TGF-ß levels of the two study groups. Regression analysis of CDR score and cytokines showed the inverse significant correlation between CDR score and IFN-γ levels. Furthermore, the relation between MMSE scores and IFN-γ was significant, meaning that by increasing MMSE score, IFN-γ level was significantly increased. This study suggests that the levels of IL-6 and IFN-γ are significantly increased in altered T lymphocytes of AD patients, as compared to those who are not inflicted with AD, and that they are related to the patient's age. Also, IFN-γ is related to the severity stage of the AD.

Tumor necrosis factor-alpha polymorphism at position -238 in preeclampsia.

BACKGROUND: Preeclampsia is the most common serious disorder during pregnancy and studies show several immune-related processes in its pathophysiology. The role of cytokines and their expression remains controversial in this field. One of the cytokines of interest in recent studies has been TNF-α, which has been shown to have a higher level in maternal plasma of preeclamptic women. OBJECTIVES: This study was designed to evaluate the role of TNF-α polymorphism at position -238 in the risk of developing preeclampsia during pregnancy. PATIENTS AND METHODS: One hundred fifty three preeclamptic cases and 140 healthy pregnant women were retrieved from two major hospitals of Mashhad, Iran. Methods a case-control study were designed. Anyone with a history of inflammatory disease, hypertension, or chronic kidney disease was excluded. DNA was extracted from peripheral blood leukocytes. Both groups were genotyped for the polymorphism of the TNF-α gene at position -238 by the RFLP method with Ava II enzyme. Allele and genotype frequencies were compared using one-way ANOVA and the Fisher's exact test. RESULTS: There were significant differences between the two groups in TNF-α genotype at position -238 (P < 0.001). In the preeclamptic group, the frequency of the AA genotype was higher (P < 0.001) and the frequency of the GG genotype was lower (P < 0.001). The overall prevalence of the A allele at position -238 was higher in preeclamptic cases (P < 0.001). CONCLUSION: In this study group, TNF-α -238 polymorphism was shown to be different in preeclamptic and non-preeclamptic pregnant women. The AA genotype and the A allele may carry an increased risk for developing of preeclampsia.

Sera of patients with thromboangiitis obliterans activated cultured human umbilical vein endothelial cells (HUVECs) and changed their adhesive properties.

INTRODUCTION: The aim of this study was to investigate the impact of thromboangiitis obliterans (TAO) sera on activation of primary cultures of human umbilical vein endothelial cells (HUVECs) as a model for vascular endothelial cells. METHODS: Study subjects included 21 TAO patients as the case group and 20 healthy smokers and 17 healthy non-smokers as control groups. Case and control groups were matched based on their age, socioeconomic status and smoking habit. HUVECs were incubated with the sera of case and control groups and gene expression of intercellular adhesion molecule (ICAM-1) and vascular adhesion molecule (VCAM-1) were evaluated by real-time polymerase chain reaction, TaqMan method. RESULTS: The expression of ICAM-1 and VCAM-1 were significantly higher in HUVECs after incubation with TAO sera compared to control groups (P < 0.05). VCAM-1 had a significant correlation with duration of smoking (P < 0.001, R = 0.672), while the expression of ICAM-1 had a significant correlation with the number of cigarettes smoked daily (P = 0.04, R = 0.421). CONCLUSION: Sera from TAO patients could activate HUVECs. This same activation might occur in vivo by the responsible cytokines, in particular those released from activated platelets, free oxygen radicals, and possibly low levels of nitric oxide (NO) of the sera of TAO patients, as a consequences of chronic cigarette smoking and of endothelial NO synthase polymorphism. Therefore, plasma exchange might be helpful in acute phase of the disease for saving the limbs and administration the combinations of exogenous NO with anti-oxidants might be helpful in long-term management of TAO patients to reduce the risk and rate of amputation.