ABSTRACT
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
ABSTRACT
Ulcerative colitis [UC] is a multi-factorial autoimmune disease. P-glyco-protein 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. One hundred healthy controls and 85 patients with UC were evaluated. Polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] 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. 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]. 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
ABSTRACT
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. 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. 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. 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]. 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
ABSTRACT
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. 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. 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. 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. 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
ABSTRACT
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. 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. 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. 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 control. 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. 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
ABSTRACT
The pathogenesis of many diseases is correlated to irregularity in vascular endothelial growth factor [VEGF] expression. Results from several association studies show that variation in the level of VEGF expression is related to polymorphic sequences within the VEGF gene. Additionally, there are many studies showing that some gene polymorphisms significantly influence the pharmacokinetics of immunosuppressive drugs. The aim of this study was to determine the influence of immunosuppressive drugs on VEGF production in individuals with different VEGF genotypes. ARMS-PCR was used to genotype VEGF polymorphisms at positions -1154 and -2578 within the promoter of VEGF gene. A VEGF-specific ELISA was used to determine the influence of immunosuppressive drugs on VEGF production in PBMCs of individuals with different VEGF genotypes. Suppressive effect of mycophenolic acid was observed just in individuals with GG -1154/CC -2578, GG -1154/CA -2578 and GA -1154/CC -2578 haplotypes. Additionally, VEGF was significantly suppressed in all individuals after treatment with rapamycin except those who had AA -1154/CA -2578 and AA -1154/AA -2578 VEGF genotype combinations. Results of a recent study revealed that MMF treatment might be effective in preventing chronic renal rejection only in recipients with IL-10 high producer genotype. Additionally result of another study showed that CYP3A5 genotype markedly influences the pharmacokinetics of rapamycin in kidney transplant recipients. Therefore with regard to our results, different suppressive effect of mycophenolic acid and rapamycin on VEGF production might also be dependent on VEGF genotype
ABSTRACT
Vascular endothelial growth factor [VEGF] has a key role in angiogenesis and in transplantation. The level of VEGF is related to the differences in the DNA sequence of its promoter region. In this study, the association between the combination of VEGF -1154 G and -2578 C alleles and VEGF production by LPS-stimulated PBMCs was investigated. In addition; the relationship between VEGF polymorphisms and the influence of TNF-alpha and IL-4 on VEGF production was studied. VEGF -1154 G/A and -2578 C/A were detected using ARMS-PCR. To determine the impact of combinations of these two polymorphisms on VEGF production; PBMCs were stimulated by LPS and VEGF production was measured by ELISA. The combinations of -1154 GG/-2578 CC and -1154 GG/-2578 CA were significantly associated with higher VEGF production [p<0.0001]. Production of VEGF was significantly influenced by TNF-alpha in individuals who had certain VEGF genotype combinations. Although VEGF production was dramatically suppressed by IL-4, it was not dependent on VEGF genotype. Since TNF-alpha has influence on the graft outcome, to avoid allocation of grafts from high TNF-alpha producer donors to recipients, it might be useful to predict and minimize graft rejection by having prior knowledge of TNF-alpha and also VEGF genotypes especially -1154 G/A and -2578 C/A VEGF
Subject(s)
Humans , Male , Female , Vascular Endothelial Growth Factor A/genetics , Polymorphism, Genetic , Tumor Necrosis Factor-alpha/pharmacology , Leukocytes, Mononuclear/drug effects , Interleukin-4/pharmacology , Alleles , Gene FrequencyABSTRACT
Background: in this study, using a modified microtitre plate and scanning electron microscope, we investigated biofilm production by Pseudomonas aeruginosa .biofilm productions are difficult to eradicate with antimicrobial treatment and up to 60% of all human infections are caused by biofilms. Bacterial biofilms may be found at various sites, including mucus membrane, teeth and indwelling medical devices. Pseudomonas aeruginosa is one of the most important opportunistic bacteria and producing biofilm. It has been reported that biofilm forming bacteria are more resistance to antibiotic treatment and immunologic attack
Materials and methods: clinical isolates of P.aeruginosa were collected from hospital and identified by biochemical tests. A modified microtitre plate as described by stepanovic was used to determine the biofilm formation capacity of P.aeruginosa and measured using ELISA reader. The bacteria biofilm on the Teflon sheets and cather were fixed by modified method described by Ishila. They were observed with scanning electron microscope
Results: the results demonstrated that Pseudornonas aeruginosa strain M214 denser biofilm formation compared with other strain, with OD=2.89 using modified microtitre plate test. Scanning electron micrograph of bacteria on the Teflon and catherter that had been incubated with P.aeruginosa M214 for 1 and 7 days were investigated. The results showed biofilm formation on catherter was denser that Teflon sheets. The bacteria incubated for 7 days on Teflon and catherter were covered with thick membranous and fibrous structure, unlike bacteria incubated for 1 day
Conclusion: It seems modified microtitre plate is better and easier way to use in diagnostic labratories regard to treatment difficulteis, it strongly recommend to study the biofilm before antibiotic adminstration
ABSTRACT
Background: in this study, using a modified microtitre plate and scanning electron microscope, we investigated biofilm production by Pseudomonas aeruginosa .biofilm productions are difficult to eradicate with antimicrobial treatment and up to 60% of all human infections are caused by biofilms. Bacterial biofilms may be found at various sites, including mucus membrane, teeth and indwelling medical devices. Pseudomonas aeruginosa is one of the most important opportunistic bacteria and producing biofilm. It has been reported that biofilm forming bacteria are more resistance to antibiotic treatment and immunologic attack
Materials and Methods: clinical isolates of P. aeruginosa were collected from hospital and identified by biochemical tests. A modified microtitre plate as described by stepanovic was used to determine the biofilm formation capacity of P. aeruginosa and measured using ELISA reader. The bacteria biofilm on the Teflon sheets and cather were fixed by modified method described by Ishila. They were observed with scanning electron microscope
Results: the results demonstrated that Pseudomonas aeruginosa strain M214 denser biofilm formation compared with other strain, with 00=2.89 using modified microtitre plate test. Scanning electron micrograph of bacteria on the Teflon and catherter that had been incubated with P. aeruginosa M214 for 1 and 7 days were investigated. The results showed biofilm formation on catherter was denser that Teflon sheets. The bacteria incubated for 7 days on Teflon and catherter were covered with thick membranous and fibrous structure, unlike bacteria incubated for 1 day
Conclusion: It seems modified microtitre plate is better and easier way to use in diagnostic labratories regard to treatment difficulties, it strongly recommend to study the biofilm before antibiotic adminstration