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Sulfur mustard (SM) exposure has delayed harmful effects, including premature biological aging. This study aimed to evaluate the expression of aging markers (i.e., ANRIL, P16INK4a, TBX2, and TERRA) and assess their correlation with the severity of SM exposure in the long term. The study was conducted on two volunteer groups. 1) SM-exposed group, exposed to SM once in 1987 during the war; divided into three subgroups based on the injury severity, asymptomatic (without any clinical signs), mild, and severe; 2) Non-exposed group. In the SM-exposed group, ANRIL transcript was decreased, especially in subgroups of mild and severe. TBX2 transcript was also decreased in the total SM-exposed group. This decrease was more significant in the mild and severe subgroups than in asymptomatic ones. P16INK4a transcript was increased in the SM-exposed group, especially in the asymptomatic subgroup. The increase in TERRA transcript was also significant in all subgroups. There was a positive correlation between the TERRA transcript and the severity of injury, while this correlation was negative for the ANRIL. It is concluded that the delayed toxicity of SM may be associated with dysregulation of aging markers leading to premature cellular aging. These markers' alterations differed according to the severity of SM injury.

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BACKGROUND: Sulfur mustard (SM) is a toxic gas that causes chronic inflammation and oxidative stress leading to cell senescence. This study aimed to evaluate two indicators of biological aging (i.e., serum lipofuscin level and leukocyte telomere length) and assess their relationship based on the severity of SM exposure in the long term. METHODS: The study was performed on two groups of male participants. 1) SM-exposed group (exposed to SM once in 1987), 73 volunteers. 2) Non-exposed group, 16 healthy volunteers. The SM-exposed group was categorized into three subgroups based on the severity of SM exposure and body damage (asymptom, mild, and severe). The blood sample was prepared from members of each group. The serum lipofuscin, TGF-ß, malondialdehyde (MDA), c-reactive protein (CRP), and leukocyte telomere length (TL) were measured in all participants. RESULTS: The MDA level was increased in the SM-exposed group (mean = 39.6 µM, SD = 16.5) compared to the non-exposed group (mean = 21.1 µM, SD = 10.3) (P < 0.05). The CRP level was also increased in the SM-exposed group (mean = 5.12 mg/l, SD = 3.36) compared to the non-exposed group (mean = 3.51 mg/l, SD = 1.21), while the TGF-ß level was decreased (P < 0.05) in the SM-exposed group (mean = 52.6 pg/ml, SD = 18.7) compared to the non-exposed group (mean = 68.9 pg/ml, SD = 13.8). The relative TL was shorter in the SM-exposed group (mean = 0.40, SD = 0.28) than in the non-exposed group (mean = 2.25, SD = 1.41) (P < 0.05). The lipofuscin level was higher in the total SM-exposed group (mean = 1.44 ng/ml, SD = 0.685) than in the non-exposed group (mean = 0.88 ng/ml, SD = 0.449) (P < 0.05). The MDA and CRP levels were increased in the SM-exposed subgroups of asymptom, mild, and severe than the non-exposed group, while TGF-ß level and TL were decreased in those subgroups. The lipofuscin level was higher in the SM-exposed subgroups of mild and severe than in the non-exposed group. The regression analysis determined a negative correlation between lipofuscin level and TL. The lipofuscin/TL ratio was higher in the total SM-exposed group (mean = 6.36, SD = 5.342) than in the non-exposed group (mean = 0.51, SD=0.389). This ratio was also higher in the SM-exposed subgroups of asymptom, mild, and severe than in the non-exposed group. The lipofuscin/TL ratio did not differ between mild and severe subgroups. CONCLUSION: The delayed toxicity of SM is associated with chronic oxidative stress, continuous inflammatory stimulation, increased lipofuscin, and telomere shortening. Future studies are needed to verify the suitability of serum lipofuscin to telomere length ratio in determining the severity of SM toxicity.

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Sulfur mustard (SM) is a toxic gas that has been used as a chemical weapon in wars. After many years, SM-exposed people are still suffering from its side effects such as biological and premature aging. This study was aimed to evaluate biological aging rate via involving biological health scoring (BHS), relative telomere length (TL) and different physical/social variables i.e. marital and smoking statuses, body mass index, salary and educational levels. BHS was calculated according to measurement of 18 biomarkers related to function of four physiological systems (endocrine, inflammatory, cardiovascular and metabolic systems) and two organs (liver and kidney). The volunteers were 442 individuals exposed to SM gas in 1987 and 119 healthy individuals as non-exposed group. Each group was divided based on leukocyte relative TL (short, intermediate and long). Our data showed an inverse correlation between BHS and relative TL in two groups. The BHS was significantly higher in SM-exposed group than non-exposed group, especially in the participants with short and intermediate TL. The BHS had also a positive correlation with smoking and BMI parameters, and a negative correlation with salary and educational levels in the participants with shorter telomeres; and SM strengthened these correlations in the shorter telomeres. It is concluded that the higher BHS along with shorter relative TL that are indices for lower health quality and biological aging, could be used in the health evaluation of non- and SM-exposed people; and involving of BHS, TL and physical/social covariates could be useful to make this evaluation more accurate.

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BACKGROUND: Mustard gas as a chemical weapon has been used in wars and its long-term side effects are substantial in the human body. This study was aimed to apply an extension of allostatic load, known as synthetic biological health score (BHS), including the wear-and-tear of four physiological systems (endocrine, inflammatory, cardiovascular and metabolic systems) and two organs (liver and kidney) to estimate biological aging caused by sulfur mustard (SM) gas poisoning. METHODS: The plasma samples were prepared from two following groups of people; 1) 446 individuals exposed to SM gas in 1987. 2) 115 healthy members, at the same range of age and residence, as the non-exposed group. These people were chosen from the same patients' families and have not had any exposure to SM or pulmonary dysfunction. To estimate BHS, 18 blood-derived biomarkers of the mentioned systems and organs were measured and the relative contribution of many social and body parameters across the age groups was explored. RESULTS: It was revealed, in BHS calculation, the cardiovascular system had the most effect. Also, in the SM group, BHS was significantly higher than in the control group. This feature has a positive correlation with physical parameter (BMI) and a negative correlation with social parameters (salary and educational levels). CONCLUSION: The multisystem BHS could be useful in the evaluation of biological aging due to SM exposure. Social (education, good-paying job) and physical (BMI) parameters could influence BHS and the higher BHS indicates the progress of biological aging due to mustard gas.

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OBJECTIVES: Our aim was to answer the following questions: (1) Can mental health variance be partitioned to individual and higher levels (e.g., neighborhood and district); (2) How much (as a percentage) do individual-level determinants explain the variability of mental health at the individual-level; and (3) How much do determinants at the neighborhood- or district-level explain the variability of mental health at the neighborhood- or district-level? METHODS: We used raw data from the second round of the Urban Health Equity Assessment and Response Tool in Tehran (in 2012-2013, n=34 700 samples nested in 368 neighborhoods nested in 22 districts) and the results of the official report of Tehran's Center of Studies and Planning (in 2012-2013, n=22 districts). Multilevel linear regression models were used to answer the study questions. RESULTS: Approximately 40% of Tehran residents provided responses suggestive of having mental health disorders (30-52%). According to estimates of residual variance, 7% of mental health variance was determined to be at the neighborhood-level and 93% at the individual-level. Approximately 21% of mental health variance at the individual-level and 49% of the remaining mental health variance at the neighborhood-level were determined by determinants at the individual-level and neighborhood-level, respectively. CONCLUSIONS: If we want to make the most effective decisions about the determinants of mental health, in addition to considering the therapeutic perspective, we should have a systemic or contextual view of the determinants of mental health.

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Objective: The present study was conducted to investigate the effect of Viola odorata extracted syrup on the quality and patterns of sleep in patients with depression or obsessive-compulsive disorder (OCD) as add-on therapy. Design: A pilot double-blind randomized placebo-controlled trial. Settings/Location: Psychiatric Clinic of Imam Hossein Hospital, Tehran, Iran. Subjects: Participants were 16-15 years of age with mild and moderate depression or OCD having insomnia. Interventions: This pilot study was conducted on patients with insomnia divided into two groups with depression (40 patients) or OCD (43 patients). Each group randomly assigned into two arms with the same conditions at baseline. The intervention arm daily received 5 mL V. odorata syrup every 12 h for 4 weeks, and the control arm received 5 mL placebo syrup every 12 h for 4 weeks. None of the participants was deprived of their routine treatment for depression or OCD. Outcome measures: The scores of insomnia symptoms were evaluated using total score of the Pittsburgh Sleep Quality Index (PSQI) and the scores of its components, the depression score using the final Beck depression inventory-II (BDI-II) score, and OCD score using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Results: The total PSQI score was found to be improved significantly in the intervention arms with depression or OCD (p < 0.001) compared with the corresponding control arms. Significant improvements were also observed in the final mean difference of BDI-II (p = 0.009) and YBOCS (p = 0.001) scores in the intervention arms. Conclusions: V. odorata syrup significantly improved insomnia symptoms and the scores of depression and OCD.

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BACKGROUND: Health systems have a set of limited resources for meeting the needs of communities. Health priority setting based on criteria and values is inevitable in such situation. This paper aims to identify the social values that are considered in Iranian health system. METHODS: This qualitative study was conducted in 3 steps including collecting national documents and literature review, interviewing key informants, and a 2 round Delphi. Interviews and documents were analyzed through thematic framework analysis. Statistical guidance was applied for determining consensus cut-off in Delphi technique. RESULTS: Five social values including freedom of choice, equity, solidarity, severity of disease(s), and burden of disease(s) were considered more important than other values in the health priority setting decisions. Moreover, 2 non-value based factors including conflict of interest and lobbying had a high effect on decision making. CONCLUSION: Most health policy makers decide based on Egalitarian school, but restriction of resources in the country decreases the outcome. Moreover, personal judgments and preferences sometimes affect their decisions. It seems that developing a value-based framework and making it as a national guidance could have affirmative effect on health administers decisions.

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Background: Health is an essential component of human rights and the rights are interdependent, indivisible, and correlated. The present study aimed at codifying a multidimensional health index according to multistage index development and describing the status of this index in 22 municipal districts of Tehran. Methods: This study was conducted using the data collected in the second round of Urban HEART Project of Tehran (2012-2013). The sample size was 34 700. To develop a multidimensional health index (MDHI), the nine steps of the Organization for Economic Cooperation and Development (OECD) were followed, from codifying theoretical framework to introducing the index. Results: According to the constructed MDHI, the districts no. 13, 10, 17, 1, 3, 4, and 22 had the best status and the district no. 8 the worst status. With respect to physical health, the districts no. 13, 17, 1, 3, 10, and 18 had the best status and the district no. 8 the worst. Concerning mental health, the districts no. 3, 6, 1, and 10 had the best status and the districts no. 8 and 12 the worst status. With respect to social health, the districts no. 10, 22, and 21 had the best status and the districts no. 6, 7, 12, and 14 the worst status. The analysis of sensitivity indicated that the MDHI was more sensitive towards physical health. Based on the mean, minimum, and maximum scores on each indicator of the questionnaires, the physical, mental, social, and MDHI status of Tehran residents (2012-2013) was high-medium, medium, low-medium, and high-medium, respectively. Conclusion: The right to health should be widely investigated, as it is a primary principle needed for sustainable development, which can be accomplished when the attitudes of different organizations towards the health construct are multidimensional rather than unidimensional.

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BACKGROUND: To estimate and compare prevalence of overweight and obesity among adult people across the 22 districts of Tehran in 2011. METHODS: This was a cross-sectional study using data on 47,406 women and 47,525 men aged≥ 15 years from a large population-based survey (Urban HEART-2). Age-standardized prevalence (ASP) of overweight (25≤BMI<30) and obesity (BMI≥30) were estimated for the Tehran's districts. Pearson Chi2 tests and logistic regression were used to examine any significant differences in prevalence of these disorders across sociodemographic groups. RESULTS: ASPs of overweight were 36.5% and 32.0 % among men and women, respectively (p<0.001). These figures for obesity were 10.7% and 15.3% among men and women, respectively (p<0.001). Crude prevalence of overweight and obesity rose with age up to the age of 54 years and decreased thereafter. Across education groups, the lowest prevalence of overweight/obesity was seen among most educated people. The results showed that being young, single and student were associated with lower odds of overweight/obesity. CONCLUSION: This study showed a high prevalence of overweight and obesity among adult in Tehran. There were significant associations between sociodemographic characteristics and prevalence of overweight/obesity among adults in Tehran. The results of this study might be used in identifying high risk groups of overweight and obesity in Tehran.

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Cardiovascular disorders continue to constitute major causes of morbidity and mortality in diabetic patients. In this study, the effect of chronic administration of sesame (Sesamum indicum L) seed feeding was studied on aortic reactivity of streptozotocin (STZ)-diabetic rats. Male diabetic rats received sesame seed-mixed food at weight ratios of 3% and 6% for 7 weeks, one week after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation response to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to PE was significantly lower in sesame-treated diabetic rats (at a ratio of 6%) relative to untreated diabetics and endothelium removal abolished this difference. Endothelium-dependent relaxation to ACh was also significantly higher in sesame-treated diabetic rats (at a ratio of 6%) as compared to diabetic rats and pretreatment of rings with nitric oxide synthase inhibitor, N(G)-nitro-l-arginine methyl ester (L-NAME) significantly attenuated the observed response. Two-month diabetes also resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity and sesame treatment significantly reversed the increased MDA content and restored activity of SOD. We thus conclude that chronic treatment of diabetic rats with sesame seed could in a dose-manner prevent some abnormal changes in vascular reactivity through nitric oxide and via attenuation of oxidative stress in aortic tissue and endothelium integrity is necessary for this beneficial effect.

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Sulfur mustard (SM) is a strong toxic agent that causes acute and chronic health effects on a myriad of organs following exposure. Although the primary targets of inhaled mustard gas are the epithelia of the upper respiratory tract, the lower respiratory tract is the focus of the current study, and upper tract complications remain obscure. To our knowledge there is no study addressing the secretory IgA (S-IgA), C5a, alpha 1 antitrypsin (A1AT) in the saliva of SM-exposed victims. In this study, as many as 500 volunteers, including 372 SM-exposed cases and 128 control volunteers were recruited. A 3 ml sample of saliva was collected from each volunteer, and the level of secretory IgA, C5a, and alpha 1 antitrypsin in the samples were compared between the two groups. The SM-exposed group showed a significantly higher amount of salivary alpha 1 antitrypsin and secretary IgA compared to the control group (p<.006 and p<.018 respectively). The two groups showed no significant difference (p=0.192) in the level of C5a. The results also showed that the level of salivary A1AT is more than that of IgA in severely injured cases. The findings presented here provide valuable insight for both researchers and practitioners dealing with victims of the chemical warfare agent, sulfur mustard. This research indicates that certain branches of the inflammatory processes mandate serious attention in therapeutic interventions.

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Sulfur mustard (SM) is a potent alkylating vesicant warfare chemical agent which causes severe damages to the interface organs, skin, lungs and eyes. The most common chronic skin lesions are mustard scars, xerosis, eczema, seborrheic dermatitis, cherry angioma and hyperpigmentation. This study is part of Sardasht-Iran Cohort Study (SICS) which was performed to compare the serum levels of inflammatory cytokines in SM-exposed individuals (n=372) with long-term relevant skin findings versus unexposed controls (n=128). Serum levels of pro-inflammatory cytokines including IL-1α, IL-1ß, IL-1Ra, IL-6, and TNF (tumor necrosis factor) were titrated using ELISA method, 79.9% (n=290) of the exposed group and 60.5% (n=98) of the control group showed skin findings. In the exposed group, 52.1% (n=189) had only skin findings (OSFE) and in the control group, 32% (n=41) had no problem (NC, normal). Median serum levels of cytokines IL-1α, IL-1ß, IL-1Ra, IL-6 and TNF-α in the OSFE group were: 1.077, 1.745, 25.640, 0.602 and 12.768 pg/ml, respectively. These values in normal controls were 1.889, 1.896, 32.190, 1.022 and 23.786 pg/ml, respectively which are higher than the corresponding values in the OSFE group, the differences were statistically significant only for IL-1α and TNF-α. This may be due to a damage incurred upon precursors of cytokine producing cells or failure of their functions, increase in suppressive mediators or other mechanisms which are not well known. More studies are needed in molecular dimensions of the immune and cytokine responses in the SM-exposed patients.

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Exposure to SM leads to short and long term adverse effects on various organs including the skin. Cherry angioma is one of the late skin disorders in SM exposed individuals. The pathogenesis of abnormal angiogenesis in cherry angioma is not well known but the role of inflammatory mediators and certain hormones, including prolactin, in the regulation of angiogenesis in other diseases has been reported. Alterations in serum levels of prolactin and chemokines in SM-exposed victims and the impact on angiogenesis are indications of the role in SM-induced cherry angioma. As part of the SICS, this study seeks to evaluate the possible association of prolactin and chemokines in the emergence of SM-induced cherry angioma. The serum concentrations of prolactin, IL-8/CXCL8, RANTES/CCL5, MCP-1/CCL2, and fractalkine/CX3CL1 were titrated using sandwich ELISA technique. There was a significant difference in the level of prolactin between the exposed subgroups (with cherry angioma n=72; mean: 10.13) and without cherry angioma (n=268; mean: 13.13, p<0.0096). Median of the serum levels of CCL2 in the exposed patients with cherry angioma was significantly higher than exposed patients without cherry angioma (median=203.5 pg/ml and median=187.10 pg/ml respectively, p=0.035). There was no significant difference in the serum levels of IL-8, RANTES and CX3L1 between the exposed subgroups with cherry angioma and without cherry angioma. This finding serves as a basis for further research on the molecular mechanisms and pathways involved in the pathogenesis of cherry angioma and other related disorders.

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The effect of chronic daidzein, a soybean isoflavone, on aortic reactivity of streptozotocin-diabetic rats was studied. Male diabetic rats received daidzein for 7 weeks a week after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation response to acetylcholine (ACh) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to PE was significantly lower in daidzein-treated diabetic rats relative to untreated diabetic rats, and endothelium removal abolished this difference. Endothelium-dependent relaxation to ACh was significantly higher in daidzein-treated diabetic rats as compared with diabetic rats and pretreatment of rings with nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester and/or indomethacin attenuated it. Two-month diabetes also resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity, and daidzein treatment significantly reversed the increased MDA content and reduced activity of SOD. Therefore, chronic treatment of diabetic rats with daidzein could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and prostaglandin-related pathways, and via attenuation of oxidative stress in aortic tissue and endothelium integrity seems essential for this effect.

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The effect of chronic administration of sesamin was studied on aortic reactivity of streptozotocin diabetic rats. Male diabetic rats received sesamin for 7 weeks after diabetes induction. Contractile responses to KCl and phenylephrine and relaxation response to acetylcholine were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to phenylephrine was significantly lower in sesamin-treated diabetic rats relative to untreated diabetics and endothelium removal abolished this difference. Meanwhile, endothelium-dependent relaxation to acetylcholine was significantly higher in sesamin-treated diabetic rats as compared to diabetic ones and pretreatment of rings with nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester significantly attenuated the observed response. Two-month diabetes also resulted in an elevation of malondialdehyde and decreased superoxide dismutase activity and sesamin treatment significantly improved these changes. Therefore, chronic treatment of diabetic rats with sesamin could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and via attenuation of oxidative stress and tissue integrity of endothelium is necessary for its beneficial effect.

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BACKGROUND: Insights into long-term clinical consequences of sulfur mustard have emerged from some investigations but less is known about the basic and molecular mechanisms of these complications. Sardasht-Iran Cohort Study is a comprehensive historical cohort study on Sardasht chemical victims' population which was designed to find out the long-term complications of sulfur mustard exposure and the basic mechanisms underlying clinical manifestations. This paper describes the design and methodology of Sardasht-Iran Cohort Study. METHODS: In Sardasht-Iran Cohort Study, 500 individuals including 372 subjects from Sardasht, as the exposed group, and 128 subjects from Rabat, as the unexposed age-matched control group were evaluated. The exposed group was divided into two groups based on the severity of clinical complications at the time of exposure. Different samples including blood, sputum, saliva, tear, urine, and semen were collected for immunologic, hematologic, biochemical, and other laboratory analysis. Data were gathered from medical records, clinical examinations, laboratory tests, and questionnaires for psychological and lifestyle situations. CONCLUSION: The important distinctions setting this study apart from the previous ones are discussed. The Sardasht-Iran Cohort Study provides important information on various aspects of long-term consequences of sulfur mustard exposure. This database will provide a better position to suggest guidelines for the diagnosis, treatment, and prevention of delayed complications in the patients exposed to sulfur mustard.

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