Effect of a Persian metabolic diet on the functional dyspepsia symptoms in patients with postprandial distress syndrome: a randomized, double-blind clinical trial.

OBJECTIVES: Postprandial distress syndrome (PDS) is associated with food indigestion. Efficacy of drugs used against PDS is limited whereas dietary modifications were shown to have important beneficial effects. Traditional Persian Medicine (TPM) sages suggested a dietary regimen known as Persian metabolic diet (PMD) for the management of PDS patients. In this study, the efficacy of PMD in alleviating the symptoms of PDS was explored. METHODS: This single-center, parallel-group, randomized clinical trial included 56 patients whom were randomly allocated to PMD group (29 participants) and Optional diet (OD) group (27 participants). They were instructed to follow the protocol for two weeks. Using a standard validated questionnaire, all outcomes were evaluated at baseline, end of the intervention period, and end of follow-up time. RESULTS: At the end of the intervention period, comparing the changes of severity scores between the groups showed a statistically significant difference in week 2 (p-value<0.001) and week 8 (p-value<0.001) follow-up comparing to the baseline. Similarly, at the end of the follow-up period, epigastric fullness, epigastric discomfort, and bloating were significantly improved in the PMD group (p<0.001). CONCLUSIONS: This diet prepared based on Persian medicine seems to be effective in relieving the symptoms of patients with PDS.

Sexual health outcomes of PLISSIT-based counseling versus grouped sexuality education among Iranian women with breast cancer: A randomized clinical trial.

In-person, individual counseling using the PLISSIT model is a well-known approach to help people with sexual problems. Evidence suggests that Grouped Sexuality Education (GSE) can be as effective as in-person sexuality education. The efficacy of PLISSIT versus GSE has not previously been evaluated in women with Breast Cancer (BC). In this paper, we report on the effect of PLISSIT versus GSE on self-reported sexual behaviors experienced by women after a BC diagnosis (n = 75). The women were randomly allocated into three groups, with 25 women in each arm. Data analysis of the intention-to-treat population (n = 65) revealed efficacy of both GSE and PLISSIT in improving sexual behaviors (p < 0.0001) with a positive change in sexual capacity, motivation and performance after 6- and 12-weeks post-intervention follow ups. We found the GSE model showed a greater efficacy than the PLISSIT model. Due to the substantial needs faced by women with cancer and the cost associated with implementing the PLISST model, GSE seems to be more effective. We recommend GSE for Iranian communities where management of sexual problems is at an early stage and where the sexuality of women with cancer is routinely overlooked.

Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spread rapidly all over the world in late 2019 and caused critical illness and death in some infected patients. This study aimed at examining several laboratory factors, especially inflammatory and immunological mediators, to identify severity and mortality associated biomarkers. Ninety-three hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) were classified based on disease severity. The levels of biochemical, hematological, immunological, and inflammatory mediators were assessed, and their association with severity and mortality were evaluated. Hospitalized patients were mostly men (77.4%) with an average (standard deviation) age of 59.14 (14.81) years. The mortality rate was significantly higher in critical patients (85.7%). Increased serum levels of blood sugar, urea, creatinine, uric acid, phosphorus, total bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-oxaloacetic transaminase, lactic dehydrogenase, C-reactive protein, ferritin, and procalcitonin were significantly prevalent (p=0.002, p<0.001, p<0.001, p=0.014, p=0.047, p=0.003, p<0.001, p<0.001, p<0.001, p<0.001, P<0.001, and p<0.001, respectively) in COVID-19 patients. Decreased red blood cell, hemoglobin, and hematocrit were significantly prevalent among COVID-19 patients than healthy control subjects (p<0.001 for all). Troponin-I, interleukin-6, neutrophil/lymphocyte ratio (NLR), procalcitonin, and D-dimer showed a significant association with the mortality of patients with specificity and sensitivity more than 60%. Age, sex, underlying diseases, blood oxygen pressure, complete blood count along with C-reactive protein, lactic dehydrogenase, procalcitonin, D-dimer, and interleukin-6 evaluation help to predict the severity and required management for COVID-19 patients. Further investigations are highly recommended in a larger cohort study for validation of the present findings.

Association between ST-segment resolution after primary angioplasty and short-term outcomes in patients with acute myocardial infarction.

BACKGROUND: The aim of this study was to evaluate the relationship between the early/late complete ST-resolution and short-term cardiovascular outcomes in patients undergoing primary angioplasty. METHODS: This was a prospective cross-sectional study of patients with acute myocardial infarction who candidate for primary percutaneous coronary intervention (PCI) during 1 year. An ECG obtained at the time of admission, 90 minutes and 24 hour after PCI. Patients were followed up for in hospital and 1-year outcomes and then data assessed according to the ST segment resolution (STR) (complete ≥70% and incomplete <70% STR). RESULTS: Overall, 124 patients included in the study. The rates of complete STR were 44.4% after 90 minutes and 82.3% after 24 hours. Patients with early complete STR had significant lower rates of heart failure after 1-year follow-up (32% versus 46%, OR: 1.88, 95% CI: 1.42-2.50, P=0.005) but not like patients with late STR. No significant relationship was observed between early/late complete STR and re-infarction, stroke, re-hospitalization and death during 1-year follow-up (P>0.05). Moderate correlations were found between percentage of ST resolution after 90 minutes and EF before discharge and final EF (correlation coefficient: 0.395 and 0.488, respectively, P<0.001). CONCLUSIONS: Early complete STR can be an indicator for development of heart failure after 1-year follow-up.

Effect of topical marshmallow (Althaea officinalis) on atopic dermatitis in children: A pilot double-blind active-controlled clinical trial of an in-silico-analyzed phytomedicine.

Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease, which primarily affects infants and young children. Due to the side effects of commonly used drugs for its treatment, the development of safer therapeutic strategies is needed. There are many reports on the topical use of marshmallow (Althaea officinalis) for a range of skin diseases in Persian medicine. The main aim of the present investigation was evaluating the efficacy of marshmallow in children with mild-to-moderate atopic dermatitis. Another aim of the study was screening the anti-allergic and anti-inflammatory potential of phytocomponents against target proteins, including TNF-alpha, IL6, and PDEs A, B, and D enzymes with PDB IDs: 2AZ5, 1P9M, 3I8V, 4KP6, and 1Y2K, respectively, along with their respective standard ligands using computational docking analysis. A pilot clinical trial was designed to investigate the safety and efficacy of Althaea officinalis in children with AD. The diagnosis of AD was made according to the criteria of Hanifin and Rajka. Children between 3 months and 12 years old were participated in this trial and randomly allocated into two parallel intervention and control groups. The intervention group used Althaea officinalis 1% ointment while the positive control group used Hydrocortisone 1% ointment twice a day for a week and after that, three times per week for a period of 3 weeks. The severity of AD was measured using the SCORAD score at the end of each assessment visits. A total number of 22 patients completed the study. A significant decrease of the SCORAD score was observed in both groups. At the end of the study, this score change, which indicates the improvement of the patients was significantly higher in the intervention group in comparison to the baseline (p-value = .015) and week 1 (p-value = .018). In the docking analysis of the study, 33 phytochemical compounds were identified, which were docked into the active site of IL6, TNF-alpha, and human PDE4 isoenzymes. Affinity toward the selected enzymes was significantly higher in glycosylated compounds. The results of this pilot study showed that the efficacy of Althaea officinalis 1% ointment in a decrease of disease severity is more than Hydrocortisone 1% in children with AD. However, further studies are needed to confirm this finding. Moreover, the docking analysis revealed that the inhibitory activity of compounds with free hydroxyl groups such as glycosylated compounds was better than others, probably due to the hydrogen bond interaction of hydroxyl groups of the ligands with the enzymes.

Evaluation of Drug and Alcohol Abuse in People Aged 15 Years and Older in Iran.

BACKGROUND: Drug addiction is known as one of the health, medical and social problems of the present century. Beyond the harmful physical and mental consequences for addicts, drug abuse can cause serious social problems. The aim of this study was to evaluate drug and alcohol abuse in individuals aged 15 yr and over in Iran in 2015. METHODS: This descriptive cross-sectional study was done on individuals aged 15 yr and older who lived in urban and rural areas of Iran. Overall, 36,600 individuals were selected by systematic and cluster random sampling. The postal code was used to access the samples in 31 provinces of Iran. In each province 1200 individuals (50% men, 50% women) were evaluated. The used instrument was the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), and data were analyzed using SPSS software. RESULTS: The results showed 4.6% of individuals used Opium and its derivatives, 0.4% used Cannabis, 0.4% used Amphetamine stimulants, 6.1% used Sedative drugs, and 2.6% used Alcoholic beverages on a regular basis. Within the last 12 months, 3.9% of individuals used Opium and its derivatives, 0.4% used Cannabis, 0.3% used Amphetamine stimulants, 5.8% used Sedative drugs, and 1.9% used Alcoholic beverages. With the exception of Sedatives drugs men used more drugs than women and residents of rural areas used more opium and its derivatives than other groups of drugs. Based on the provincial distribution, Kerman and Qom used the highest and lowest prevalence percentage of Opium and its derivatives respectively. CONCLUSION: Overall, 2340000 individuals were addicts used Opium and its derivatives in 2015, therefore, medical and health officials should take all necessary measures to deal with these serious social problems.

A double-blind, randomized pilot study for comparison of Melissa officinalis L. and Lavandula angustifolia Mill. with Fluoxetine for the treatment of depression.

BACKGROUND: Depression has rapidly progressed worldwide, and the need for an efficient treatment with low side effect has risen. Melissa officinalis L and Lavandula angustifolia Mill have been traditionally used in Asia for the treatment of depression. Many textbooks of traditional Persian medicine refer to these herbs for the treatment of depression while there are no adequate clinical trials to support this claim. The present study aimed to evaluate the efficacy of M. officinalis and L. angustifolia compared to fluoxetine for the treatment of mild to moderate depression in an 8-week randomized, double-blind clinical trial. METHODS: Forty-five adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) for major depression, were randomly assigned to 3 groups to daily receive either M. officinalis (2 g) or L. angustifolia (2 g) or fluoxetine (20 mg) and were assessed in weeks 0, 2, 4 and 8 by the Hamilton Rating Scale for Depression (HAM-D) including 17 items. RESULTS: Our study showed that M. officinalis and L. angustifolia effect similar to fluoxetine in mild to moderate depression. (F = 0.131, df = 2,42, p = 0.877). CONCLUSION: Due to some restrictions in this study including absence of placebo group, large-scale trials are needed to investigate the anti-depressant effect of these two herbs with more details. TRIAL REGISTRATION: IRCT2014061718126N1 . Registration date: 2015-06-04-"Retrospectively registered".

Effect of the Nurse-Led Sexual Health Discharge Program on the Sexual Function of Older Patients Undergoing Transurethral Resection of Prostate: A Randomized Controlled Trial.

Background: Sexual dysfunction is a complication of transurethral resection of prostate (TURP). There is a lack of knowledge of the effect of discharge programs aiming at improving sexual function in older patients undergoing TURP. Objective: To investigate the effect of the nurse-led sexual health discharge program on the sexual function of older patients undergoing TURP. Methods: This randomized controlled clinical trial was conducted on 80 older patients undergoing TURP in an urban area of Iran. Samples were selected using a convenience method and were randomly assigned into intervention and control groups (n = 40 in each group). The sexual health discharge program was conducted by a nurse in three sessions of 30-45 min for the intervention group. Sexual function scores were measured using the International Index of Erectile Function (IIEF) Questionnaire, one and three months after the intervention. Results: The intervention significantly improved erectile function (p = 0.044), sexual desire (p = 0.01), satisfaction with sexual intercourse (p = 0.03), overall satisfaction with sexual function (p = 0.01), and the general score of sexual function (p = 0.038), three months after the program. In the first month after the intervention, except in sexual desire (p = 0.028), no statistically significant effect of the program was reported (p > 0.05). Conclusion: The nurse-led sexual health discharge program led to the improvement of the sexual function of older patients undergoing TURP over time. This program can be incorporated into routine discharge programs for the promotion of well-being in older patients.

Hab-o Shefa, a Persian Medicine Compound for Maintenance Treatment of Opioid Dependence: Randomized Placebo-Controlled Clinical Trial.

Objectives: The major problem in maintenance treatment of opioid use disorder is craving and relapse. The utilization of herbal compounds and complementary therapy for treatment of disease and addiction has been widely expanding. Considering the significant effect of Hab-o Shefa in detoxification phase, this clinical trial has explored the influence of this compound on maintenance treatment of opioid-dependent patients. This product is made of four herbs, including Datura stramonium L., Rheum palmatum L., Zingiber officinale Roscoe, and Acacia senegal L. Design: The authors conducted a two-group parallel randomized double-blind clinical trial on 81 opioid-dependent patients within 12 weeks. After medically assisted detoxification, participants were assigned randomly to Hab-o Shefa (n = 41) and placebo (n = 40). Outcome measures included craving assessed by craving beliefs questionnaire, self-reported opioid use, and lapse (any opioid-positive urine test) according to urinalysis and addiction severity index-lite questionnaire, retention in treatment, and depression and anxiety scores on the Hamilton's anxiety and depression scales. Results: Forty-one participants completed the study for 12 weeks, 21 subjects in the drug group and 20 subjects in the placebo group. The rates of opioid-positive urine tests and self-reported opioid use were significantly lower in Hab-o Shefa group (f = 8.41, p = 0.001). Hab-o Shefa also indicated a significant superiority over placebo in the effect of treatment by time interaction for craving (f = 5.91, p = 0.001), depression (f = 3.40, p = 0.01), and anxiety (f = 2.58, p = 0.035). The retention time was 66.6 days for drug group and 59.6 days for placebo one. Although the causes for dropping out in two groups were different, there was no significant difference (p = 0.623). The side effects of the two groups were not significantly different. Conclusion: Results indicated that Hab-o Shefa could be useful for opioid maintenance treatment, and it can also be considered as a new promising drug for prevention of craving and relapse.

Effects of Viola odorata as an Add-On Therapy on Insomnia in Patients with Obsession or Depression: A Pilot Randomized Double-Blind Placebo-Controlled Trial.

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.

A Review on the Hypotheses about Arterial Hypertension from the Viewpoint of Traditional Persian Medicine.

Hypertension is one of the most common chronic diseases in recent decades worldwide. It has been distinguished as the main risk factor of coronary artery disease, aortic dissection, heart failure, renal failure, cerebrovascular diseases, and death. In recent years, the global attention has been paid to complementary medicine to preventive, diagnostic and treatment strategies for hypertension, in previous studies, the history of hypertension from the viewpoint of traditional Persian medicine have been reviewed and several hypotheses raised. In this article, we present the concept of an Iranian physician namely Ali ibn Sahl Rabban al-Tabari on hypertension, which has not been considered properly until now. He defined a state called "Hayajan al-dam" that has clinical manifestations similar to hypertension, although these are not the same, also, we reviewed the viewpoint of other Persian medicine scholars namely Rhazes, Haly Abbas, Akhawayni and Avicenna for this topic.

Alteration in serum levels of immunoglobulins in seriously eye-injured long-term following sulfur-mustard exposure.

INTRODUCTION: Sulfur mustard (SM) is a potent toxic agent that cause local and systemic changes in the human body such as dysregulation of the immunological system. This gas affects different organs such as lungs, skin, eyes and the gastrointestinal tract. METHODS: 128 veterans with SM-induced eye injuries were examined and compared to 31 gender- and age-matched healthy controls. Serum levels of IgM, IgE, IgA, IgG, and IgG subclasses were measured using ELISA method. RESULTS: There was no significant difference in IgM level between two groups with abnormal and normal ocular conditions except for those having bulbar conjunctiva-limbal ischemia and bulbar conjunctiva-hyperemia abnormalities. There were not significant difference in IgA, IgE, and IgG levels between two groups with and without ocular problem also between study groups. IgG1 level in some ocular abnormalities were significantly lower than the healthy control groups. IgG2 level in SM-exposed participants with stromal abnormality was higher in the SM-exposed groups without this problem. IgG2 levels in the exposed group with some ocular problems were significantly increased compared with control. IgG3 level in all patients did not reveal any significant changes compared with the controls except the fundus abnormality. IgG4 level was not significantly different between two groups with normal and abnormal ocular conditions. Nonetheless, IgG4 level in the exposed participants with some ocular abnormalities significantly increased compared with the controls. CONCLUSION: The results showed SM exposure could alter immunoglobulins level compared with healthy controls and the changes of IgG2 and IgG1 levels were associated with some ocular problems.

Speech-evoked auditory brainstem response; electrophysiological evidence of upper brainstem facilitative role on sound lateralization in noise.

BACKGROUND AND AIM: Sound lateralization/localization is one of the most important auditory processing abilities, which plays approved role in auditory streaming and speech perception in challenging situations like noisy places. In addition to the main role of lower brainstem centers like superior olivary complex in sound lateralization, efferent auditory system effects on improving auditory skills in everyday auditory challenging positions were revealed. This study evaluated noise effects on lateralization scores in correlation with an objective electrophysiologic test (Speech-ABR in noise), which objectively shows cumulative effects of the afferent and efferent auditory systems at the inferior colliculus and upper brainstem pathway. METHOD: Fourteen normal-hearing subjects in the age range of 18 to 25 participated in this study. Lateralization scores in the quiet and noisy modes were evaluated. Speech-ABR in both ears for quiet mode and three different contralateral noise levels (SNR = + 5, 0, - 5) were recorded, too. Correlation of lateralization scores and Speech-ABR changes in noise was studied. RESULTS: Significant decrease of lateralization scores with latency increase and amplitude decrease of Speech-ABR transient peaks (V, A, O) was seen with noise presentation. A high positive correlation between lateralization decrease with latency increase of onset peaks (V, A) and amplitude decrease of transient peaks (V, A, O) was found in low signal-to-noise ratios. CONCLUSION: The study revealed that in high challenging auditory situations like auditory lateralization in noise, upper brainstem centers and pathways play a facilitative role for main auditory lateralization centers in lower levels.

L-lysine protects C2C12 myotubes and 3T3-L1 adipocytes against high glucose damages and stresses.

Hyperglycemia is a hallmark of diabetes, which is associated with protein glycation and misfolding, impaired cell metabolism and altered signaling pathways result in endoplasmic reticulum stress (ERS). We previously showed that L-lysine (Lys) inhibits the nonenzymatic glycation of proteins, and protects diabetic rats and type 2 diabetic patients against diabetic complications. Here, we studied some molecular aspects of the Lys protective role in high glucose (HG)-induced toxicity in C2C12 myotubes and 3T3-L1 adipocytes. C2C12 and 3T3-L1 cell lines were differentiated into myotubes and adipocytes, respectively. Then, they were incubated with normal or high glucose (HG) concentrations in the absence/presence of Lys (1 mM). To investigate the role of HG and/or Lys on cell apoptosis, oxidative status, unfolded protein response (UPR) and autophagy, we used the MTT assay and flow cytometry, spectrophotometry and fluorometry, RT-PCR and Western blotting, respectively. In both cell lines, HG significantly reduced cell viability and induced apoptosis, accompanying with the significant increase in reactive oxygen species (ROS) and nitric oxide (NO). Furthermore, the spliced form of X-box binding protein 1 (XBP1), at both mRNA and protein levels, the phosphorylated eukaryotic translation initiation factor 2α (p-eIf2α), and the Light chain 3 (LC3)II/LC3I ratio was also significantly increased. Lys alone had no significant effects on most of these parameters; but, treatment with HG plus Lys returned them all to, or close to, the normal values. The results indicated the protective role of Lys against glucotoxicity induced by HG in C2C12 myotubes and 3T3-L1 adipocytes.

Tear and serum interleukin-8 and serum CX3CL1, CCL2 and CCL5 in sulfur mustard eye-exposed patients.

BACKGROUND: The serum and tear levels of four inflammatory chemokines were evaluated in sulfur mustard (SM)-exposed with serious ocular problems. MATERIALS AND METHODS: In this study, 128 SM-exposed patients and 31 healthy control participants participated. Tear and serum levels of chemokines were assessed by ELISA method. RESULTS: There was no significant difference in the serum level of IL-8/CXCL8, CX3CL1/fractalkine, CCL2/MCP-1, and CCL5/RANTES between all SM-exposed subjects and control groups. The tear level of IL-8 in the SM-exposed group was lower than the control group, but the difference was not significant. In the SM-exposed group with the abnormalities in tear breakup time (TBUT) test, fundus and pannus formation were significantly higher than SM-exposed patients without these problems. CX3CL1 levels have significantly increased in SM-exposed group with blepharitis, pterygium, and conjunctival pigmentation as compared with the control group. Besides, significantly higher levels of CX3CL1 were observed in SM-exposed group with or without bulbar conjunctival hyperemia and abnormal vessels a well as with fundus abnormality compared to the control group. Only, SM-exposed group with subconjunctival fibrosis had significantly lower levels of CCL5 than SM-exposed group without this problem. CONCLUSION: The higher level of CX3CL1 and consistent levels of IL-8/CXCL8, MCP-1/CCL2, and RANTES/CCL5 in SM-exposed individuals may indicate an anti-inflammatory response against the destructive effects of SM gas. High tear level of IL-8/CXCL8 reflects the severity of ocular surface abnormalities, yet significantly low tear level found in mild SM-exposed subgroup compared with the control group. The lower levels of CX3CL1 and RANTES/CCL5 may represent the different pathophysiology which requires further studies.

Tear and serum MMP-9 and serum TIMPs levels in the severe sulfur mustard eye injured exposed patients.

INTRODUCTION: Sulfur mustard (SM) intoxication produces local and systemic changes in the human body. In this study, the relationship between tear and serum matrix metalloproteinase (MMP)-9 and serum tissue inhibitors of metalloproteinases (TIMPs) are assessed in serious eye-injured SM-exposed casualties. METHODS: A group of 128 SM-exposed patients with serious ocular injuries in three subgroups (19 mild, 31 moderate, and 78 severe cases) is compared with 31 healthy controls. Tear and ocular status and serum MMPs and MMP-9/TIMPs complex levels were evaluated using enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum level of MMP-9 was significantly higher in the SM-exposed group compared to the control group (P = 0.009). Mean serum MMP-9 level in the SM-exposed group with ocular abnormalities was significantly higher than that in the SM-exposed group without ocular abnormalities. SM-exposed people with corneal calcification had significantly higher serum MMP-9/TIMP-1 level compared to the SM-exposed ones without this problem (P = 0.045). The SM-exposed group with severe ocular injuries had significantly higher MMP-9/TIMP-1 than the controls (P = 0.046). The SM-exposed group had significantly lower levels of MMP-9/TIMP-4 complex than the controls (P < 0.001). The SM-exposed group with tear meniscus and fundus abnormality had significantly higher MMP-9/TIMP-4 levels than the SM-exposed group without these problems (P = 0.009 and P = 0.020). CONCLUSION: Serum MMP-9 level had increased in SM-exposed groups with ocular problems, while TIMP-1 and TIMP-2 levels had remained unchanged. Serum TIMP-4 drastically decreased in SM-exposed group, which clearly explains the severity of the systemic and ocular damages.

Serum and sputum levels of IL-17, IL-21, TNFα and mRNA expression of IL-17 in sulfur mustard lung tissue with long term pulmonary complications (28 years after sulfur mustard exposure).

BACKGROUND: Iranian veterans who had exposed to Sulfur Mustard (SM) suffer from long term complications such as Chronic Obstructive Pulmonary Disease (COPD) and bronchiolitis obliterate (BO). Th17 cells product IL-17A, IL-17F, IL-21, and IL-22. They have important roles in chronic inflammatory diseases. Also, TNFα has a major part in pathobiological processes of COPD. In this study, we evaluate the serum and sputum levels of IL-17, IL-21, TNF-α, and mRNA expression of IL-17 in the lung tissue of the patients 28 years after SM exposure. MATERIAL AND METHOD: The cytokine levels of IL-17, IL-21 and TNFα were measured by ELISA method in serum and sputum of 455 SM-exposed and 123 unexposed people participated in Sardasht-Iran Cohort Study (SICS) of chemical victims. The mRNA expression of IL-17 was evaluated with qRT-PCR in lung biopsies (SM-exposed =52, control =33). Analyses of all data were accomplished with the SPSS software with P value ≤05. RESULT: The results show the sputum level of IL-17 in the exposed group decreased significantly compared to control group (P = 0.007) and Veterans and Martyrs Affair Foundation (VMAF) assessment was significantly lower in abnormal/exposed than normal/exposed group (P = 0.042). There were no significant differences between control and exposed groups in serum level of IL-17; also serum and sputum levels of IL-21, TNF-α, and IL-17 mRNA expression. CONCLUSION: Conclusively, The IL-17 level decreased in the exposed group. This decline could cause by mutation on transcription factors like Signal transducer and activator of transcription 3 gene (STAT3) or CCL20 as a chemokine.

Expression of miR-15b-5p, miR-21-5p, and SMAD7 in Lung Tissue of Sulfur Mustard-exposed Individuals with Long-term Pulmonary Complications.

Sulfur mustard (SM)-exposed individuals develop late pulmonary complications, which are associated with chronic inflammation and fibrotic changes in the lung tissue. MicroRNAs are known to act as important regulators of inflammatory responses, including inflammation and fibrosis-related cytokine signaling. In this study, we investigated the expression miR-15b-5p and miR-21-5p, two regulators of TGF-ß signaling, as well as their target molecule, SMAD7, in lung tissues from SM-exposed and control individuals. Total RNA was extracted from formalin-fixed paraffin-embedded (FFPE) lung tissue biopsies obtained during surgery from SM-exposed (n=20) or control (n=20) cases. Quality of the extracted RNA was evaluated by an Agilent Bioanalyzer and RNA was quantified using a NanoDrop. MiR-21-5p, miR-15b-5p and SMAD7 expression levels were measured by real-time RT-PCR. miR-21-5p expression levels were significantly decreased (2.7 fold) in the lung tissues from SM-exposed individuals compared with tissues obtained from the control group (p=0.02). There were no significant differences in miR-15b-5p expression levels between the two groups (p=0.94). Interestingly, SMAD7 expression levels were significantly higher (5.8 fold) in SM-exposed individuals' lung tissues compared with the control group (p=0.045). Our data indicate that exposure to sulfur mustard affects the expression of miR-21-5p as well as its target, SMAD7, in lung tissues many years after exposure. Considering the role of SMAD7 in the regulation of TGF-ß signaling, these changes might point to a potential mechanism by which SM-exposure regulates inflammatory/fibrotic alterations in lung tissue.

Serum Concentration of Thyroid Hormones Long-Term after Sulfur Mustard Exposure.

BACKGROUND: Despite several reports on the clinical manifestations of sulfur mustard (SM) intoxication, there is no study on serum concentrations of thyroid hormones long-term after SM exposure. In this study, the changes in thyroid functioning parameters 20 yr after SM exposure were evaluated. METHODS: This study is a part of a larger historical cohort study conducted in 2007 following 20 years of the exposure to SM, called Sardasht-Iran cohort study (SICS). We (SICS) comprised an SM-exposed group from Sardasht City, West Azerbaijan Province, Iran (n=169 as hospitalized group and n=203 as non-hospitalized exposed group); and control participants were selected from Rabat, a town near Sardasht (n=126). Peripheral blood samples were taken in fasting state and then the sera were separated. T4, T3, TSH, antithyroglobulin (anti-Tg), and antithyroid peroxidase (anti-TPO) concentrations in the sera were measured by the ELISA method. RESULTS: The mean of T3 concentration was significantly higher in the exposed than control group (0.88 ± 0.26 nmol/L vs 0.8 ± 0.25 nmol/L, P<0.001). The levels of TSH, T4, and T3up were not significantly different between the exposed and control groups. Thyroglobulin level was significantly higher in the exposed non-hospitalized group (56.07 ± 140.22 µg/L vs 17.66 ± 41.49 µg/L, P=0.004), but the level of anti-Tg and anti-TPO showed no significant differences between the two groups. CONCLUSION: More studies are needed on the alterations in thyroid hormones, their gene expressions, and mechanisms involved in SM exposure to clarify the causes of these alterations.

Circulating mesenchymal stem cells in sulfur mustard-exposed patients with long-term pulmonary complications.

Sulfur mustard (SM) is a toxic agent that causes acute and long-term pulmonary complications. Recent evidence has shown the impact of SM on mesenchymal stem cells (MSCs). These cells have a critical role in repairing the damaged tissues. In this study, we evaluated the mobilization of MSCs in SM-exposed patients with long-term pulmonary complications. Fifty-nine SM-injured patients with prolonged pulmonary complications and 20 healthy individuals were included. Patients were classified based on taking drugs, having comorbidities, and severity of respiratory consequence. MSCs with phenotype of CD45-CD44+CD29+CD105+ were evaluated in peripheral blood using flow cytometry. Circulating MSCs were lower in SM-exposed patients compared to the control group (0.93 vs. 2.72 respectively, P = 0.005). No significant difference was observed in the MSC count between patients taking corticosteroids or antibiotics and those patients not taking them. Comorbidities like liver and kidney diseases had changed the count of MSCs in SM-exposed subjects. In addition, the frequency of MSCs did not show any association with the severity of long-term pulmonary complications. In conclusion, SM-exposure causes a decline in the frequency of circulating MSCs in survivors. The lower number of the peripheral MSC population in SM-exposed patients was not affected by taking corticosteroids or antibiotics, but comorbidities are probably involved in MSC frequency. The decreases observed in the number of circulating MSCs was not associated with the severity of the pulmonary complications; however, further studies in mustard lung models are required to demonstrate the therapeutic or pathologic role of MSCs in SM injuries.