The Serum Levels of CCL2 and CCL16 Expression in Patients with Irritable Bowel Syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by altered bowel habits and abdominal pain in the absence of a recognizable structural anomaly. The pathogenesis of IBS has been associated with inflammation and the expression of pro-inflammatory chemokines, such as CCL2 and CCL16. Our study aimed to investigate the relationship between the serum levels of CCL2 and CCL16 and IBS. Additionally, we examined how serum levels of these chemokines relate to IBS subtypes. METHODS: Patients with IBS diagnosed according to the Rome III criteria participated in this study (n= 96). Healthy individuals with no history of allergic, autoimmune, chronic or active gastrointestinal infectious diseases were used as controls (n= 44). The serum levels of CCL2 and CCL16 was measured via enzyme-linked immunosorbent assay (ELISA). RESULTS: A significant decrease in the serum levels of CCL16 and CCL2 was observed in the patients with IBS. Additionally, the serum levels of CCL16 in IBS patients with diarrhea (D-IBS) was significantly higher than those with the mixed IBS (M-IBS) subtype. CONCLUSION: The significant increase in the serum levels of CCL-16 in patients with D-IBS compared to patients with M-IBS suggests that CCL-16 may be used as an immunological biomarker to differentiate between these two subtypes.

Clinical Significance of Serum IL-6 and TNF-α Levels in Patients with Metabolic Syndrome.

BACKGROUND: Several components of metabolic syndrome (MetS) facilitate its diagnosis, including abdominal obesity, hyperlipidemia, high blood pressure, and insulin resistance. The production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) seem to be associated with MetS components. The aim of this study was to evaluate the correlation between IL-6 and TNF-α serum levels with MetS and its components. METHODS: This case-control study investigated 250 subjects, comprising 125 healthy controls from the Kerman Blood Transfusion Organization and 125 MetS patients. Serum IL-6 and TNF-α levels were measured using the enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum IL-6 and TNF-α levels were greater in MetS patients than in controls. However, no correlation was observed between MetS components and IL-6 or TNF-α serum levels. CONCLUSION: Patients with MetS had significantly greater serum IL-6 and TNF-α levels than the controls, supporting the evidence that inflammation plays an important role in the immunopathogenesis of the disease. Additionally, IL-6 and TNF-α serum levels may predict MetS. The lack of association between IL-6 and TNF-α serum levels and MetS components remains to be investigated by further research.

Serotonin Transporter Gene (SLC6A4) Polymorphism and Mucosal Serotonin Levels in Southeastern Iranian Patients with Irritable Bowel Syndrome.

BACKGROUND Irritable bowel syndrome (IBS) is a digestive system disorder with an unknown etiology. Serotonin has a key role in the secretion and motility of the intestine. Polymorphism in serotonin re-uptake transporter (SERT or SLC6A4) gene may have a functional role in the gut of patients with IBS. The aims of the present study were to investigate the association between SLC6A4 gene polymorphism and IBS and to detect the correlation between rectal serotonin levels and IBS sub-types. METHODS SLC6A4 gene polymorphism in 131 patients with IBS and 211 healthy controls were analysed using the quantitative polymerase chain reaction high-resolution melting (qPCR-HRM) curve technique. Serotonin was measured in rectal biopsies of patients with IBS using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS The patients were categorized into three groups: IBS with diarrhoea (IBS-D): 70 patients, IBS with constipation (IBS-C): 18 patients, and IBS with mixed symptoms (IBS-M): 43 patients. The frequency of SLC6A4 s/s and l/s genotypes was significantly higher in IBS-C than IBS-D, IBS-M, and controls (p=0.036). Serotonin levels were similar in IBS sub-types. CONCLUSION SLC6A4 polymorphism is a possible candidate gene associated with the pathogenesis of IBS-C. Although serotonin levels did not differ in rectal biopsies of IBS sub-types, further investigation is recommended.

Lead poisoning among opium users in Iran: an emerging health hazard.

BACKGROUND: Lead (Pb) poisoning among people using opium has been an increasing problem in Iran. The present study highlights the clinical effects of lead toxicity associated with opium use in Iran, Kerman province. METHODS: Between January 2016 and June 2016, patients with signs and symptoms of Pb poisoning were questioned to assess whether they had a history of opium dependency. In total, 249 patients were enrolled onto this cross-sectional study, all were opium dependent. Para-clinical data including blood lead level (BLL), demographic information, user preferences, and symptoms were obtained. RESULTS: The patients used either opium (83.9%), refined opium (6.4%) or a combination of both (9.7%) via ingestion (71.9%), smoking (8.4%) or a combination of both (19.7%). The overall median BLL was 80.0 µg/dL [IQR: 51.7-119.0]. The median BLL did not differ significantly between opium and refined opium users. Further, BLL was not significantly affected by the type of substance, route of use, duration of use, or daily quantity consumed. Common symptoms included abdominal pain (86.9%), constipation (75.8%), anorexia (71.5%) and nausea (54.7%). Linear regression analysis showed log of BLL was significantly associated with abdominal pain, myalgia and anorexia. CONCLUSIONS: The study unravelled an increase in opium-related Pb poisoning in the Kerman province. Raised awareness of this emerging Pb source and investigation of its aetiology is recommended. Pb poisoning should be considered among the primary differential diagnosis of opium users with gastrointestinal symptoms.

Effect of Apium graveolens and Trachyspermum copticom on clinical symptoms of patients with functional dyspepsia.

OBJECTIVES: This study aimed at investigating the effect of Iranian traditional remedy prepared from Apium graveolens and Trachyspermum copticom (AT) on the severity and frequency of symptoms in patients with functional dyspepsia (FD). MATERIAL AND METHODS: In total, 150 FD patients were included in this randomized double-blind trial, based on the ROME III diagnostic criteria, and they were divided into three intervention groups namely, AT, Placebo and omeprazole. Then, severity and frequency of symptoms during this eight-week trial were measured. Obtained information was analyzed using Chi-square test and repeated measures test. RESULT: In general, the severity and frequency of symptoms after the 4th week significantly decreased in the AT group as compared to the omeprazole and placebo groups, and continued to reduce by the end of the eighth week. General reduction of symptom severity and frequency in the omeprazole group was significantly different from the placebo group by the end of the 4th and 8th weeks. With respect to each individual symptom, AT markedly improved symptoms, such as burning, pain, early satiation, fullness, bloating, belching and nausea, as compared to placebo-treated group. Moreover, AT significantly improved symptoms, like vomiting, and nausea, except for pain, as compared to omeprazole-treated subjects. CONCLUSION: According to the results, AT, as Iranian traditional remedy, was more effective than omeprazole and placebo in reducing the symptoms in FD patients.

Serum immune biomarkers in irritable bowel syndrome.

BACKGROUND AND OBJECTIVES: Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal (GI) disorder, which presents with abdominal pain and changes in the bowel habits. Although the exact cause of IBS remains uncertain, some studies have shown that the inflammation and cytokine imbalance may act as potential etiological factors. The aim of our study is to compare the serum levels of interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor-alpha (TNF-α) in patients with IBS with the healthy controls. The other aim of this study is to evaluate possible association between above-mentioned cytokines and IBS subtypes. METHODS: Seventy-four IBS patients diagnosed based on Rome III criteria and 75 gender and age-matched healthy controls were included in this study. Cytokines were measured in the serum using enzyme-linked immunosorbent assays (ELISA). RESULTS: Patients were classified into groups of IBS with diarrhea (IBS-D): 34, IBS with constipation (IBS-C): 29, and IBS with mixed symptoms (IBS-M): 11. The serum levels of IL-6, IL-8 and TNF-α were significantly higher in patients with IBS as compared to controls (P<0.001). There was no difference in serum levels of cytokines based on IBS subtypes. CONCLUSIONS: Higher serum level of IL-6, IL-8 and TNF-α in IBS suggests an important role of cytokines as immune mediators in the pathogenesis of this functional GI disorder. To understand any association between cytokines and IBS subtypes, further investigations with larger sample sizes are desired.

Determination of Vitamin D Serum Levels and Status of the C3435T Polymorphism of Multidrug Resistance 1 Gene in Southeastern Iranian Patients with Ulcerative Colitis.

BACKGROUND Ulcerative colitis (UC) is a multi-factorial autoimmune disease. P-glycoprotein is encoded by the multidrug resistance 1 (MDR1) gene. The C3435T polymorphism in the MDR1 gene is correlated with low P-glycoprotein expression. Additionally, vitamin D has regulatory effects on the immune system. The aim of our study was to determine the association between the C3435T MDR1 polymorphism and UC and to detect the vitamin D serum levels in patients with UC. METHODS One hundred healthy controls and 85 patients with UC were evaluated. Polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) was used to detect the C3435T MDR1 polymorphisms. Serum levels of vitamin D were measured by Enzyme-linked immunosorbent assay (ELISA). The research was performed in Kerman, Iran, from 2011 to 2013. RESULTS We could not find any association between the C3435T MDR1 polymorphism and susceptibility to UC. There was a significant decrease in serum levels of vitamin D in patients with UC compared with healthy controls (p<0.001). CONCLUSION Controversies regarding the association between the C3435T MDR1 polymorphism with UC have been reported in different populations. The difference between our results and others may be attributed to the heterogeneity of the Iranian population and the sample size. Additionally, our data indicated that UC might be correlated with vitamin D insufficiency. Therefore, the administration of vitamin D might be suggested as a valuable treatment for patients with UC.

Association of HLA-DRB1 Alleles with Ulcerative Colitis in the City of Kerman, South Eastern Iran.

The association of HLA class II genes with ulcerative colitis (UC) as an autoimmune disease has been investigated for several years. However, factors responsible for genetic predisposition of this disease have so far not been clearly understood. In this study, for the first time, we aimed to investigate the association between HLA-DRB1 types and UC in the population of Kerman, a city southeast Iran. HLA typing was performed among 85 UC patients and 95 healthy controls using PCR amplification, employing sequence specific primers (PCR-SSP). The DRB1 frequencies were determined in the patients and controls. HLA-DRB1*04 was negatively associated with UC. Furthermore, HLA-DRB1*13 was significantly associated with severity of the disease (p=0.01) among UC patients. This is the novel result that describes an association of HLA-DRB1*13 with UC and also shows the protective role of HLA-DRB1*04 against the disease in people of Kerman.

Effects of Pentoxifylline on Non-Alcoholic Steatohepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial in Iran.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease. Several studies suggest that pentoxifylline (PTX) can improve the disease outcome. OBJECTIVES: We aimed to compare the effect of pentoxifylline with placebo on liver aminotransferases and cytokines, including interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 8 (IL-8) in patients with NASH. PATIENTS AND METHODS: Thirty patients with NASH were included in the study, based on ultrasonography and 1.5-fold mean change from baseline serum levels of liver aminotransferases. Patients with NASH were randomized to receive 1200 mg PTX (the intervention group) or placebo (the placebo group) for 6 months. The serum levels of liver aminotransferases and cytokines were compared between the intervention and placebo groups, at various time points. RESULTS: The serum levels of liver aminotransferases were significantly reduced at 3 months and at 6 months, compared with baseline, in both groups. The serum levels of IL-6 were significantly decreased, in both groups, only at 6 months, compared with baseline. Compared to the placebo group, the serum level of TNF-α was significantly decreased in the intervention group, at 6 months. The serum level of IL-8 was increased, in both groups, after 6 months, without reaching clinical significance. There was no significant difference in serum levels of liver aminotransferases and cytokines, between intervention and placebo groups. CONCLUSIONS: Decreases in the serum levels of liver aminotransferases and cytokines, in both groups, are related to low-calorie diets and exercise, rather than PTX.

Interleukin-17 serum levels and TLR4 polymorphisms in ulcerative colitis.

BACKGROUND: Inflammatory bowel disease, an autoimmune disease, has two clinical manifestations including Crohn's disease and ulcerative colitis (UC). IL-17 has been the target of intensive research in autoimmune diseases. The influence of Toll like receptor 4 (TLR-4) gene polymorphisms on IL-17 production has also been revealed in UC patients and tissue inflammation in mice. OBJECTIVES: To investigate the association between the TLR-4 gene polymorphisms, Asp299Gly and Thr399Ile and IL-17 serum levels with ulcerative colitis. Additionally, we aimed to study modulation effects of forenamed gene polymorphisms on IL-17 serum levels in UC patients and controls. METHODS: A total of 256 healthy controls and 85 UC patients enrolled in our study. DNA was extracted and PCR-RFLP technique was employed to determine Asp299Gly and Thr399Ile polymorphisms in TLR-4 gene and IL-17 serum levels were measured by ELISA method. RESULTS: There was no significant difference between the frequency of Asp299Gly A>G and Thr399Ile C>T in UC patients and controls. While IL-17 serum levels in UC patients were significantly higher than controls (p=0.003), no significant difference in IL-17 levels between different genotypes existed. Additionally, a significant inverse relationship was observed between hemoglobin level and IL-17 serum levels in UC patients (p=0.039). CONCLUSIONS: Increased IL-17 serum levels in our UC patients might be explained through the synergistic activity of IL-17/IL-23 axis and pro-inflammatory cytokines, causing severe clinical outcome in patients with IBD. The prolonged excretion of blood in stool driven by inflammatory process which causes iron metabolism disorder and anemia may elucidate the inverse correlation between hemoglobin and IL-17 serum levels in UC patients. Lack of association between the TLR-4 gene polymorphisms and UC in our study was consistent with the results from other Caucasian populations.

IL-23 receptor gene rs7517847 and rs1004819 SNPs in ulcerative colitis.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are two major clinical presentations of inflammatory bowel disease (IBD). Many novel candidate genes have been found to be associated with increased risk for IBD. Recently IL-23 receptor gene is identified as an IBD associated gene in genome-wide studies. OBJECTIVE: To ascertain whether rs7517847 and rs1004819 SNPs in the IL-23 receptor gene are associated with UC in our population in Kerman, south east of Iran. METHODS: A total of 85 patients with UC and 100 healthy controls enrolled in our study. Endoscopic procedure was performed for all patients to determine their disease severity. IL-23 receptor genotyping at positions rs7517847 and rs1004819 was done by PCR-RFLP technique. RESULTS: The results of this study showed no association between the studied polymorphisms in the IL-23 receptor gene and UC in our population. However, we found a significant association between rs7517847 gene polymorphism in IL-23 receptor and two important clinical variables including blood in stool and bowel movements in UC patients. CONCLUSION: The rs7517847 gene polymorphism in IL-23R may be related to the presence of blood in stool and bowel movements in patients with UC. Further functional analysis with other known IL-23 receptor genotypes and/or other candidate genes is necessary to confirm any genetic association with UC in our population.

Serum interleukin-23 levels in patients with ulcerative colitis.

BACKGROUND: Patients with ulcerative colitis are at increased risk of inflammation. Interleukin 23 (IL-23) is a newly identified cytokine with increased expression in inflamed biopsies of colon mucosa in patients with Crohn's disease; however, there is inconsistent evidence on its role in ulcerative colitis. OBJECTIVE: We aimed to compare serum IL-23 level in patients with ulcerative colitis and normal controls and determine if serum IL-23 level increases with the severity of disease according to endoscopic findings. METHODS: We quantified serum IL-23 levels from 60 patients with ulcerative colitis and 20 control individuals. All patients underwent endoscopic procedure to define the severity of disease. Patients were then stratified into 2 groups of "Mild" and "Severe" according to the endoscopic findings. RESULTS: For comparison of serum IL-23 levels, Platelet count, ESR and CRP between the groups, Mann-Whitney U test and independent sample t test were employed, as appropriate. Pearson's and spearman's correlation tests were employed to test the association of IL-23 with platelet count, CRP and ESR in patients. Our findings showed that serum IL-23 levels were increased in patients with ulcerative colitis compared to normal controls. Moreover, patients in "Severe" group had higher serum IL-23 levels and ESR compared with those in "Mild" group. There was no significant sexual dimorphism in any of studied variables. CONCLUSION: We suggest that IL-23 plays an important role in the pathogenesis of ulcerative colitis and is a marker of disease activity in these patients.