Mutations in the coding regions of the hepatocyte nuclear factor 4 alpha in Iranian families with maturity onset diabetes of the young

Hepatocyte nuclear factor 4α (HNF4α) is a nuclear receptor involved in glucose homeostasis and is required for normal β cell function. Mutations in the HNF4α gene are associated with maturity onset diabetes of the young type 1 (MODY1). The aim of the present study was to determine the prevalence and nature of mutations in HNF4α gene in Iranian patients with a clinical diagnosis of MODY and their family members. Twelve families including 30 patients with clinically MODY diagnosis and 21 members of their family were examined using PCR-RFLP method and in case of mutation confirmed by sequencing techniques. Fifty age and sex matched subjects with normal fasting blood sugar (FBS) and Glucose tolerance test (GTT) were constituted the control group and investigated in the similar pattern. Single mutation of V255M in the HNF4α gene was detected. This known mutation was found in 8 of 30 patients and 3 of 21 individuals in relatives. Fifty healthy control subjects did not show any mutation. Here, it is indicated that the prevalence of HNF4α mutation among Iranian patients with clinical MODY is considerable. This mutation was present in 26.6% of our patients, but nothing was found in control group. In the family members, 3 subjects with the age of ≤25 years old carried this mutation. Therefore, holding this mutation in this range of age could be a predisposing factor for developing diabetes in future

Nitric oxide contributes to learning and memory deficits observed in hypothyroid rats during neonatal and juvenile growth

INTRODUCTION: Severe cognitive impairment follows thyroid hormone deficiency during the neonatal period. The role of nitric oxide (NO) in learning and memory has been widely investigated. METHODS: This study aimed to investigate the effect of hypothyroidism during neonatal and juvenile periods on NO metabolites in the hippocampi of rats and on learning and memory. Animals were divided into two groups and treated for 60 days from the first day of lactation. The control group received regular water, whereas animals in a separate group were given water supplemented with 0.03% methimazole to induce hypothyroidism. Male offspring were selected and tested in the Morris water maze. Samples of blood were collected to measure the metabolites of NO, NO2, NO3 and thyroxine. The animals were then sacrificed, and their hippocampi were removed to measure the tissue concentrations of NO2 and NO3. DISCUSSION: Compared to the control group's offspring, serum thyroxine levels in the methimazole group's offspring were significantly lower (P<0.01). In addition, the swim distance and time latency were significantly higher in the methimazole group (P<0.001), and the time spent by this group in the target quadrant (Q1) during the probe trial was significantly lower (P<0.001). There was no significant difference in the plasma levels of NO metabolites between the two groups; however, significantly higher NO metabolite levels in the hippocampi of the methimazole group were observed compared to controls (P<0.05). CONCLUSION: These results suggest that the increased NO level in the hippocampus may play a role in the learning and memory deficits observed in childhood hypothyroidism; however, the precise underlying mechanism(s) remains to be elucidated

The frequency of HBeAg and relation with serum level of aminotransferase in chronic hepatitis B

زمینه و هدف: ویروس هپاتیت B (HBV) شایع ترین علت بیماری کبدی حاد و مزمن در جهان به شمار می رود. در افراد ناقل HBV می بایست وضعیت تکثیر ویروسی با استفاده از مارکرهای مناسب از جمله HbeAg مورد بررسی قرار گیرد تا در صورت مثبت بودن و همچنین بالا بودن آنزیم های کبدی افراد مبتلا به هپاتیت مزمن شناسایی شده و سپس تحت درمان قرار گیرند. لذا این مطالعه با هدف تعیین فراوانی مارکر HBeAg و ارتباط آن با سطح ترانس آمینازهای کبدی در افراد HBsAg مثبت انجام گرفت. روش بررسی: در این مطالعه توصیفی – تحلیلی 144 فرد آلوده به ویروس هپاتیت B در مراجعین به بیمارستان امام رضا(ع) شهر مشهد در سال 1385 انتخاب و سپس در سرم این افراد، HBeAg و آنزیم های کبدی با روش الایزا و تست های بیوشیمیایی اندازه گیری شدند. داده ها با استفاده از آزمون های آماری من ویتنی و کای دو تجزیه و تحلیل شد. یافته ها: فراوانی افراد 94 نفر مذکر و 50 نفر مونث بود. این افراد در محدوده سنی 85-2 با میانگین 3/2±4/37 سال قرار داشتند. 18 (26 نفر) دارای HBeAg در سرم بودند. میانگین آنزیم آسپارتات آمینو ترانسفراز (AST) در گروه HBeAg مثبت IU/L 83 و در گروه HBeAg منفی IU/L 2/56 بود (01/0

Immunotherapy in Allergic Rhinitis: It's Effect on the Immune System and Clinical Symptoms

BACKGROUND: Allergic rhinitis is one of the most common allergic diseases and characterised by sneezing, rhinorrhea, nasal congestion and nasopharyngeal itching. Subcutaneous immunotherapy (SCIT) for specific allergens is an effective treatment and induces the inhibitory effect of T regulatory lymphocytes and decreases clinical symptoms in allergic rhinitis. AIM: In this study effect of subcutaneous immunotherapy with specific allergens on clinical symptoms and T regulatory and T Helper cells cytokines, in patients with allergic rhinitis are evaluated. METHODS: In this study, 30 patients with moderate to severe allergic rhinitis according to clinical criteria and positive skin prick test for aeroallergens were selected and treated by SCIT. Clinical symptoms and T cells cytokines IL4, IL17, IFN gamma, TGF beta, GITR, FOXP3 and IL-10 (by RT-PCR) were evaluated before and one year after initiation of treatment. RESULTS: Thirty (30) patients with allergic rhinitis at age range 15-45 years old were treated by SCIT, and 23 (14 female, 9 male) patients continued the study, and 7 patients did not continue treatment. After immunotherapy, clinical symptoms decreased significantly. The specific cytokines TGF beta and IL10 levels increased and changes were statistically significant. (Respectively P = 0.013 and P = 0.05) The IL17 level was also increased, but not statistically significant. (P = 0.8) IFN gamma, IL4, GITR, FOXP3, all decreased, but the changes were not statistically significant (P > 0.05). CONCLUSION: Subcutaneous Immunotherapy for specific allergens decreases clinical symptoms in patients with allergic rhinitis and induces tolerance in T lymphocytes, especially by increasing T regulatory cells cytokines, TGF beta and IL10

Immunotherapy in Allergic Rhinitis: It’s Effect on the Immune System and Clinical Symptoms

BACKGROUND: Allergic rhinitis is one of the most common allergic diseases and characterised by sneezing, rhinorrhea, nasal congestion and nasopharyngeal itching. Subcutaneous immunotherapy (SCIT) for specific allergens is an effective treatment and induces the inhibitory effect of T regulatory lymphocytes and decreases clinical symptoms in allergic rhinitis. AIM: In this study effect of subcutaneous immunotherapy with specific allergens on clinical symptoms and T regulatory and T Helper cells cytokines, in patients with allergic rhinitis are evaluated. METHODS: In this study, 30 patients with moderate to severe allergic rhinitis according to clinical criteria and positive skin prick test for aeroallergens were selected and treated by SCIT. Clinical symptoms and T cells cytokines IL4, IL17, IFN gamma, TGF beta, GITR, FOXP3 and IL-10 (by RT-PCR) were evaluated before and one year after initiation of treatment. RESULTS: Thirty (30) patients with allergic rhinitis at age range 15-45 years old were treated by SCIT, and 23 (14 female, 9 male) patients continued the study, and 7 patients did not continue treatment. After immunotherapy, clinical symptoms decreased significantly. The specific cytokines TGF beta and IL10 levels increased and changes were statistically significant. (Respectively P = 0.013 and P = 0.05) The IL17 level was also increased, but not statistically significant. (P = 0.8) IFN gamma, IL4, GITR, FOXP3, all decreased, but the changes were not statistically significant (P > 0.05). CONCLUSION: Subcutaneous Immunotherapy for specific allergens decreases clinical symptoms in patients with allergic rhinitis and induces tolerance in T lymphocytes, especially by increasing T regulatory cells cytokines, TGF beta and IL10

Association of Pulmonary Function Tests and Serum Vitamin D Levels in Asthmatics With Vitamin D Deficiency

Objective: The effects of serum vitamin D levels on the evolution or severity of asthma have been widely researched; however, conflicting results have been achieved. This study was designed to evaluate the relationship between serum vitamin D levels and pulmonary function tests in asthmatic and non-asthmatic people with vitamin D deficiency.Materials and Methods: This was a prospective cross-sectional study on healthy adults and asthmatic patients. Standard spirometry and serum 25-hydroxyvitamin D test were performed for all participants.Results: Forty asthmatic patients and 40 healthy controls were tested. The mean age of participants was 42.86 ± 1.6. High prevalence of vitamin D deficiency was found in both the asthmatic and control groups. No significant correlation was found between serum vitamin D levels and spirometry parameters in either of the groups (P = 0.83). Conclusion: Serum levels of 25-hydroxyvitamin D were not correlated with the severity of asthma as evaluated by pulmonary function tests in asthmatics

Immunotherapy in Allergic Rhinitis: It’s Effect on the Immune System and Clinical Symptoms

BACKGROUND: Allergic rhinitis is one of the most common allergic diseases and characterised by sneezing, rhinorrhea, nasal congestion and nasopharyngeal itching. Subcutaneous immunotherapy (SCIT) for specific allergens is an effective treatment and induces the inhibitory effect of T regulatory lymphocytes and decreases clinical symptoms in allergic rhinitis.AIM: In this study effect of subcutaneous immunotherapy with specific allergens on clinical symptoms and T regulatory and T Helper cells cytokines, in patients with allergic rhinitis are evaluated.METHODS: In this study, 30 patients with moderate to severe allergic rhinitis according to clinical criteria and positive skin prick test for aeroallergens were selected and treated by SCIT. Clinical symptoms and T cells cytokines IL4, IL17, IFN gamma, TGF beta, GITR, FOXP3 and IL-10 (by RT-PCR) were evaluated before and one year after initiation of treatment.RESULTS: Thirty (30) patients with allergic rhinitis at age range 15-45 years old were treated by SCIT, and 23 (14 female, 9 male) patients continued the study, and 7 patients did not continue treatment. After immunotherapy, clinical symptoms decreased significantly. The specific cytokines TGF beta and IL10 levels increased and changes were statistically significant. (Respectively P = 0.013 and P = 0.05) The IL17 level was also increased, but not statistically significant. (P = 0.8) IFN gamma, IL4, GITR, FOXP3, all decreased, but the changes were not statistically significant (P &gt; 0.05).CONCLUSION: Subcutaneous Immunotherapy for specific allergens decreases clinical symptoms in patients with allergic rhinitis and induces tolerance in T lymphocytes, especially by increasing T regulatory cells cytokines, TGF beta and IL10

The combination of arsenic, interferon-alpha, and zidovudine restores an “immunocompetent-like” cytokine expression profile in patients with adult T-cell leukemia lymphoma

BACKGROUND: HTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis due to chemo-resistance and immuno-compromised micro-environment. The combination of zidovudine and interferon-alpha (IFN) significantly improved survival in ATL. Promising results were reported by adding arsenic trioxide to zidovudine and IFN. RESULTS: Here we assessed Th1/Th2/T(reg) cytokine gene expression profiles in 16 ATL patients before and 30 days after treatment with arsenic/IFN/zidovudine, in comparison with HTLV-I healthy carriers and sero-negative blood donors. ATL patients at diagnosis displayed a T(reg)/Th2 cytokine profile with significantly elevated transcript levels of Foxp3, interleukin-10 (IL-10), and IL-4 and had a reduced Th1 profile evidenced by decreased transcript levels of interferon-γ (IFN-γ) and IL-2. Most patients (15/16) responded, with CD4(+)CD25(+) cells significantly decreasing after therapy, paralleled by decreases in Foxp3 transcript. Importantly, arsenic/IFN/zidovudine therapy sharply diminished IL-10 transcript and serum levels concomittant with decrease in IL-4 and increases in IFN-γ and IL-2 mRNA, whether or not values were adjusted to the percentage of CD4(+)CD25(+) cells. Finally, IL-10 transcript level negatively correlated with clinical response at Day 30. CONCLUSIONS: The observed shift from a T(reg)/Th2 phenotype before treatment toward a Th1 phenotype after treatment with arsenic/IFN/zidovudine may play an important role in restoring an immuno-competent micro-environment, which enhances the eradication of ATL cells and the prevention of opportunistic infections

An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis

Background Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that significantly affected spinal cord, nevertheless, the pathogenesis pathway and reliable biomarkers have not been well determined. This study aimed to employ high throughput meta-analysis to find major genes that are possibly involved in the pathogenesis of HAM/TSP. Results High-throughput statistical analyses identified 832, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. The protein-protein interactions between DEGs were identified in STRING and further network analyses highlighted 24 and 6 hub genes for normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. Moreover, four biologically meaningful modules including 251 genes were identified for normal vs. ACs. Biological network analyses indicated the involvement of hub genes in many vital pathways like JAK-STAT signaling pathway, interferon, Interleukins, and immune pathways in the normal vs. HAM/TSP group and Metabolism of RNA, Viral mRNA Translation, Human T cell leukemia virus 1 infection, and Cell cycle in the normal vs. ACs group. Moreover, three major genes including STAT1, TAP1, and PSMB8 were identified by network analysis. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P = 0.01 and P = 0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P = 0.04 and P = 0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P = 0.008 and P = 0.02, respectively). No significant difference was found among three groups in terms of the percentage of T helper and cytotoxic T lymphocytes (P = 0.55 and P = 0.12). Conclusions High-throughput data integration disclosed novel hub genes involved in important pathways in virus infection and immune systems. The comprehensive studies are needed to improve our knowledge about the pathogenesis pathways and also biomarkers of complex diseases.Peer reviewe