Single nucleotide polymorphisms in the FOXP3 gene are associated with increased risk of relapsing-remitting multiple sclerosis.

BACKGROUND: Although Multiple Sclerosis (MS) is an autoimmune multifactorial disease with unknown etiology, various genetic and environmental factors are known to contribute to the pathogenesis of the disease. OBJECTIVE: Recent studies have confirmed that the suppressive function of regulatory T cells (T (reg)) is impaired in MS patients and that the FOXP3 gene is a crucial transcription factor in the regulation of CD4+CD25+FOXP3+ Treg cells. Polymorphisms in the promoter region of the FOXP3 gene may alter the gene expression level and, therefore, contribute to the disease susceptibility. METHODS: The present study aimed to investigate the possible association between single nucleotide polymorphisms (SNPs) rs3761548 and rs2232365 in the FOXP3 gene and predisposition to MS. We conducted a case-control study on 410 patients with sporadic MS and 446 healthy controls. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Significant differences in distribution of both rs3761548 and rs2232365 A allele were found in MS patients in comparison to controls. Haplotype frequencies were also different among the studied groups. The A-A and C-G haplotype blocks showed a significant difference between case and controls. CONCLUSION: we have provided further evidence for the association between genetic variations and haplotypes in FOXP3 and MS in Iranian population.

Frequency of viral infections and environmental factors in multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is a complicated disease which occurs due to relationship between genes and environmental factors that causes tissue damage by autoimmune mechanisms.We investigated and illustrated the hypotheses correlated to the evidence of several putative environmental risk factors for MS onset and progression in this part of Iran. MATERIALS AND METHODS: Univariate logistic regression was used to detect the effects of environmental factors on the risk of MS. Data were analyzed using SPSS version 16. RESULTS: The childhood history of patients with rubella, measles and chickenpox increased the risk of MS significantly. Moreover, low consumption of dairy products, avoidance of seafood consumption, cigarette smoking and exposure to tobacco smoke, stress, anxiety disorders, depress and disturbing thoughts, negative and disturbing thoughts, developing a sudden shock upon hearing bad news, having obsessive-compulsive and being depressed increased the risk of MS significantly. CONCLUSIONS: The results of the current research partially solved the puzzling question of complex interplay between environmental factors and MS disease in this part of Iran. Incorporating these factors enables more powerful and accurate detection of novel risk factors with diagnostic and prognostic methods.

Herpes simplex virus encephalitis in hamadan, iran.

BACKGROUND AND OBJECTIVES: Encephalitis can cause a severe public health problem. The main aim of this research was to evaluate the medical laboratory results of patients with Herpes Simplex Virus (HSV) encephalitis. MATERIALS AND METHODS: Diagnosis of encephalitis for these patients was firstly based on a clinical profile for Herpes Simplex Encephalitis (HSE), plus either a detected HSV1&2-DNA by PCR in CSF or brain neuro-imaging results. RESULTS: Molecular testing on CSF showed that 15 patients (15%) had HSV infection, 5 patients (5%) had Varicella Zoster Virus (VZV) and one case was positive for Human Immunodeficiency Virus (HIV)-RNA in CSF. The cause of encephalitis in 79 out of 100 patients (79%) was unknown. The comparison of CSF analysis in HSV positives and negatives showed a significant increase of glucose and protein levels in HSV positives than negatives. The mortality rate was 46.6% (7/15) in patients with HSV encephalitis compared to 11.4% (10/85) in non-HSV encephalitis (P = 0.003). CONCLUSIONS: In the current study, 15% of cases were diagnosed as having HSV.

Prediction of time to recurrence and influencing factors for gastric cancer in Iran.

BACKGROUND: The patterns of gastric cancer recurrence vary across societies. We designed the current study in an attempt to evaluate and reveal the outbreak of the recurrence patterns of gastric cancer and also prediction of time to recurrence and its effected factors in Iran. MATERIALS AND METHODS: This research was performed from March 2003 to February 2007. Demographic characteristics, clinical and pathological diagnosis and classification including pathologic stage, tumor grade, tumor site and tumor size in of patients with GC recurrent were collected from patients' data files. To evaluate of factors affected on the relapse of the GC patients, gender, age at diagnosis, treatment type and Hgb were included in the research. Data were analyzed using Kaplan-Meier and logistic regression models. RESULTS: After treatment, 82 patients suffered recurrence, 42, 33 and 17 by the ends of first, second and third years. The mean ( SD) and median ( IQR) time to recurrence in patients with GC were 25.5 (20.6-30.1) and 21.5 (15.6-27.1) months, respectively. The results of multivariate analysis logistic regression showed that only pathologic stage, tumor grade and tumor site significantly affected the recurrence. CONCLUSIONS: We found that pathologic stage, tumor grade and tumor site significantly affect on the recurrence of GC which has a high positive prognostic value and might be functional for better follow-up and selecting the patients at risk. We also showed time to recurrence to be an important factor for follow-up of patients.

Needlestick and sharp object injuries among health care workers in Hamadan Province, Iran.

INTRODUCTION: Exposure to septic fluids through mucus and needlestick injuries is of great concern among health care workers (HCWs). The purpose of this study was to acquire epidemiological data, including occupation, level of education, and mode of exposure, in HCWs. METHODS: The data on this group was gathered during 6 months and analyzed using SPSS version 16. RESULTS: In this study, we detected 89 cases of needlestick injuries and exposure to septic body fluids in the health care centers. Nurses were the most exposed group (39.3%). The most exposed age group was 25-34 years (51.6%). Of those injured, 51.7% were evaluated for antibody titration after vaccination, and of them, 47.2% had titration above 10 mIU/mL and the remaining had titration below 10 mIU/mL. DISCUSSION: Numerous educational programs on care are still necessary to inform active workers in the health system about the warning trends and consequences in this part of Iran.

Prognostic impact of risk factors in patients with gastric cancer in Iran.

BACKGROUND: Gastric cancer (GC) is one the most common causes of death worldwide. Despite the decreasing rate of GC in the world through recent years, it is still the most common cancer in men and the fourth in the general population in Iran. This study aimed to assess the survival of patients with GC and to determine prognostic factors. MATERIALS AND METHODS: A total of 471 patients with GC were followed from 21 March 2003 to 21 March 2007 in the Cancer Institute of Imam Khomeini Hospital. The patients' survival rate was determined by periodical refers. The survival period considered as the time from diagnosis up to death or the end of the study. The effects of gender, age at diagnosis, tumor site, pathologic stage of disease, type of treatment used, and metastasis were evaluated by log-rank test in a univariate analysis. In addition, all the variables were evaluated simultaneously by the Cox proportional hazard (PH) model. Data were analyzed using SPSS 16 software. RESULTS: 357 (75.8%) out of 471 patients were male and 153 cases (32.5%) experienced death. The mean and median ages at diagnosis were 58.5 and 60.7 years respectively. Also, the survival mean and median were 41.8 ( 3.1) and 27 (1.7) months respectively. Gender, type of treatment, pathologic stage, the degree of differentiation were significantly related to survival. CONCLUSIONS: There was a potential effective role of age at diagnosis, gender of patients and pathologic stage of disease in cancer therapy in this part of Iran. Therefore, to reduce the risk of death in patients with GC, early diagnosis of patients at a younger age and also in primary stages must be targeted.

A study of HDV in HBsAg positive patients in Tabriz, Northwestern Iran.

BACKGROUNDS AND AIMS: Hepatitis Delta Virus (HDV) is a defective ssRNA virus requiring the provision of hepatitis B virus (HBV) for packaging of new HDV virions. Since the epidemiological features of HDV in this part of Iran seem to be unknown, the aim of this research was to determine the seroprevalence of HDV of hepatitis B surface antigen positive (HBsAg+) in blood donors, injecting drug users, hemophiliacs, hemodialysis and thalassemic patients in the city of Tabriz in northwestern Iran. METHODS: The numbers of patients who were screened in the years 2006-2007 were 100 hemodialysis patients, 165 blood donors and 90 intravenous drug users, or a total of 355 patients who were HBsAg+ and randomly selected at the Tabriz Regional Educational Blood Center. Anti-HDV antibodies (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum samples were measured. RESULTS: Eight of the hemodialysis patients (8%), 3 of the 165 blood donors (1.8%) and 9 intravenous drug addicts (10%) were HDV-IgM antibody-positive. Out of 152 serum samples collected in the hemophiliac population, only 11 samples were HBsAg+ (7.23%), and anti-HDV IgM antibodies were detected in just 2 cases. Also out of 112 thalassemic patients' sera specimens, only 2 samples was HBsAg+, and HDV-IgM antibodies were negative. The seropositivity of anti- HDV antibodies was 6.01%. The study of serum ALT levels in HBV-positive and HDV-positive patients showed obvious elevation in more than 95% of cases. CONCLUSIONS: The results show the endemicity of HDV infection in Tabriz. HDV infection in Iran could be controlled by nationwide HBV vaccination.

Epidemiologic study of human immunodeficiency virus (HIV) Infection in the patients referred to health centers in Hamadan province, Iran.

Acquired immunodeficiency syndrome (AIDS) is one of the most important infectious diseases threatening the world's population today. The main aim of this study was to assess the epidemiologic features of HIV/AIDS from January 1989 to March 2007 in Hamadan province, Iran. In a cross-sectional study, epidemiodemographic characteristics of HIV/AIDS-positive patients during a period of 17 years were collected from health centers in Hamadan province. This study showed that about 1.8% of HIV/AIDS cases in Iran involved people who lived in Hamadan province. Further study is needed to determine the reasons for this. From January 1989 to March 2007, 285 individuals including 275 males and 10 females were infected with HIV in this province. The study showed that 88% of patients lived in urban areas while 12% involved a rural population. Hamadan city had the highest rate of HIV/AIDS infection and death with 191 and 33 individuals, respectively. The main transmission route was intravenous drug use with 78%. From 28 patients who were entered into the AIDS phase, only 10 patients returned to health centers to be covered under definite treatment. The establishment of the Triangular Clinic can be presented as the starting point in the organization of infected people to detect HIV/AIDS. Altogether, efforts in reducing the impact of HIV in this province to date can be considered beneficial. Continuous laboratory diagnostic strategies may lead in time to therapeutic approaches that result in appropriate outcomes.

The effect of garlic consumption on Th1/Th2 cytokines in phytohemagglutinin (PHA) activated rat spleen lymphocytes.

The balance and regulation of T helper 1 (Th1) and Th2-type cytokines are important in the effective immune response to different diseases. To clarify the effect of garlic (Allium sativum L.) consumption on the Th1/Th2 balance, the secretion of gamma interferon (IFN-gamma) and interleukin-4 (IL-4), as two prototypes of Th1/Th2 cytokines, were compared in serum and supernatant of in vitro phytohemagglutinin activated rat spleen lymphocytes. Thirty male rats were divided equally into two groups. The treatment group received garlic solution in water (600 mg/kg/4 mL) and controls received distilled water by gavage. After 1 month, serum and supernatant of PHA activated spleen lymphocytes were analysed for IFN-gamma and IL-4 by the enzyme-linked immunosorbent assay test and thymus and spleen weights were measured. The garlic treatment group showed significantly decreased production of IFN-gamma from 101.73 +/- 4.62 to 74.64 +/- 4.64 pg/mL and significantly increased IL-4 production from 26.75 +/- 3.35 to 83.92 +/- 6.56 pg/mL (p < 0.001) in the supernatant of PHA induced spleen lymphocytes. The serum level of these cytokines was undetectable. The mean weight of thymuses in the garlic fed animals was significantly reduced from 0.456 +/- 0.016 to 0.368 +/- 0.023 g compared with the control group (p < 0.005). There were no significant differences between the spleen weights in the two groups. In conclusion, oral garlic treatment may favor a Th2 or humoral immune response.

The full length hepatitis C virus polyprotein and interactions with the interferon-beta signalling pathways in vitro.

BACKGROUND: Hepatitis C is a global health problem. The exact mechanisms by which hepatitis C virus (HCV) can evade the host immune system have become controversial. Whether HCV polyproteins modulate IFN signalling pathways or HCV proteins are responsible for such a property is the subject of interest. Therefore, an efficient baculovirus delivery system was developed to introduce the whole genome of HCV1B minus 3'untranslated region (UTR) (HCV1BΔ3'UTR) into hepatoma cells. METHODS: The whole genome of HCV genotype 1b was developed into hepatoma cells. Also, two replicon constructs were used in this research: a recombinant baculovirus containing the culture adapted sub-genomic replicon (Fk5.1) derived from HCV genotype 1b, and a mutant form containing an inactivating mutation within the non-structural protein 5B (NS5B). RESULTS: As expected, the baculovirus carrying the FK5.1 replicon induced the production of IFN-beta as judged by the use of an IFN-beta promoter luciferase reporter construct, whereas the GND baculovirus (a control polymerase knock-out replicon) and the full-length 3'UTR deletant failed to induce luciferase expression. The activation of both IFN regulatory factor 3 (IRF3) and nuclear factor kappaB (NFkappaB), two transcription factors induced by dsRNA signalling were examined. Both the wild type and GND-mutant replicon blocked the dsRNA-induced activation of IRF3 and NFkappaB. CONCLUSION: Inhibition of the transcriptional response to IRF3 and NFkappaB seems to be one of the multiple mechanisms which HCV employs to escape the host immune defense. In contrast, the full length 3'UTR deletant had no significant effect on either transcription factor. These results may be attributed to the function of HCV subgenomic replicons when compared with full length 3'UTR deletant.

Designing E1 deleted adenoviral vector by homologous recombination.

BACKGROUND: Adenoviruses are used extensively to deliver genes into mammalian cells, particularly where there is a requirement for high-level expression of transgene products in cultured cells, or for use as recombinant viral vaccines or in gene therapy. In spite of their usefulness, the construction of adenoviral vectors (AdV) is a cumbersome and lengthy process that is not readily amenable to the generation of large collection of clones. METHODS: In this project, to delete E1 gene in adenovirus, an adenoviral plasmid containing lateral sites of E1 region of adenovirus was made and recombination in the 293A cells between the homologous region of this linearized plasmid and the adenovirus genome resulted in the formation of the complete adenoviral recombinant. RESULTS: This recombination resulted in loss of E1 region and we constructed a recombinant adenovirus type 5 vector that E1 gene was deleted by homologous recombination. CONCLUSION: Homologous recombination is more easy and fast technique in the production of AdV.