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1.
Objective
Bactericidal/permeability increasing protein (BPI) gene polymorphisms have been extensively investigated in terms of their associations with inflammatory bowel disease (IBD), with contradictory results. The aim of this meta-analysis was to evaluate associations between BPI gene polymorphisms and the risk of IBD, Crohn’s disease (CD), and ulcerative colitis (UC).Methods
Eligible studies from PubMed, Embase, and Cochrane library databases were identified.Results
Ten studies (five CD and five UC) published in five papers were included in this meta-analysis. G645A polymorphism was associated with a decreased risk of UC in allele model, dominant model, and homozygous model.Conclusions
Our data suggested that BPI G645A polymorphism was associated with a decreased risk of UC; the BPI G645A polymorphism was not associated with the risk of CD.2.
Background
Identifying patient-level and disease-specific predictors of healthcare utilization in inflammatory bowel disease (IBD) may allow targeted interventions to reduce costs and improve outcomes.Aim
To identify demographic and clinical predictors of healthcare utilization among veterans with IBD.Methods
We conducted a single-center cross-sectional study of veterans with IBD from 1998 to 2010. Demographics and disease characteristics were abstracted by manual chart review. Annual number of IBD-related visits was estimated by dividing total number of IBD-related inpatient and outpatient encounters by duration of IBD care. Associations between predictors of utilization were determined using stepwise multivariable linear regression.Results
Overall, 676 patients (56% ulcerative colitis (UC), 42% Crohn’s disease (CD), and 2% IBD unclassified (IBDU)) had mean 3.08 IBD-related encounters annually. CD patients had 3.59 encounters compared to 2.73 in UC (p < 0.01). In the multivariable model, Hispanics had less visits compared to Caucasians and African-Americans (2.09 vs. 3.09 vs. 3.42), current smokers had more visits than never smokers (3.54 vs. 2.43, p = 0.05), and first IBD visit at age <40 had more visits than age >65 (3.84 vs. 1.75, p = 0.04). UC pancolitis was associated with more visits than proctitis (3.47 vs. 2.15, p = 0.04). CD penetrating phenotype was associated with more encounters than inflammatory type (4.68 vs. 4.15, p = 0.04).Conclusions
We found that current tobacco use, age <40 at first IBD visit, UC pancolitis, and CD fistuilizing phenotype in addition to Caucasian and African-American race were independent predictors of increased healthcare utilization. Interventions should be targeted at these groups to decrease healthcare utilization and costs.3.
Pablo M. Linares Alicia Algaba Ana Urzainqui Mercedes Guijarro-Rojas Rafael González-Tajuelo Jesús Garrido María Chaparro Javier P. Gisbert Fernando Bermejo Iván Guerra Víctor Castellano María-Encarnación Fernández-Contreras 《Digestive diseases and sciences》2017,62(10):2744-2754
Background
Data supporting a role of female hormones and/or their receptors in inflammatory bowel disease (IBD) are increasing, but most of them are derived from animal models. Estrogen receptors alpha (ERα) and beta (ERβ) participate in immune and inflammatory response, among a variety of biological processes. Their effects are antagonistic, and the net action of estrogens may depend on their relative proportions.Aim
To determine the possible association between the balance of circulating ERβ and ERα (ERβ/ERα) and IBD risk and activity.Methods
Serum samples from 145 patients with IBD (79 Crohn’s disease [CD] and 66 ulcerative colitis [UC]) and 39 controls were retrospectively studied. Circulating ERα and ERβ were measured by ELISA. Disease activities were assessed by clinical and endoscopic indices specific for CD and UC.Results
Low values of ERβ/ERα ratio were directly associated with clinical (p = 0.019) and endoscopic (p = 0.002) disease activity. Further analyses by type of IBD confirmed a strong association between low ERβ/ERα ratio and CD clinical (p = 0.011) and endoscopic activity (p = 0.002). The receiver operating curve (ROC) analysis showed that an ERβ/ERα ratio under 0.85 was a good marker of CD endoscopic activity (area under the curve [AUC]: 0.84; p = 0.002; sensitivity: 70%; specificity: 91%). ERβ/ERα ratio was not useful to predict UC activity.Conclusions
An ERβ/ERα ratio under 0.85 indicated CD endoscopic activity. The determination of serum ERβ/ERα might be a useful noninvasive screening tool for CD endoscopic activity.4.
Nagesh Kamat C. Ganesh Pai M. Surulivel Rajan Asha Kamath 《Digestive diseases and sciences》2017,62(9):2318-2326
Background
Frequent relapses sometimes necessitating hospitalization and the absence of pharmacological cure contribute to substantial healthcare costs in inflammatory bowel diseases (IBDs). The costs of health care in Indian patients with IBD are unknown.Aim
To evaluate the annual costs for treating Crohn’s disease and ulcerative colitis.Methods
A prevalence-based, micro-costing method was used to assess the components of annual costs in a prospective, observational study conducted in a tertiary healthcare center enrolled over a 24-month period beginning of July 2014.Results
At enrollment, 43/59 (72.88%) patients with UC and 18/25 (72%) with CD were in remission. The annual median (IQR) cost per UC and CD patient in remission was INR 43,140 (34,357–51,031) [USD $707 (563–836)] and INR 43,763.5 (32,202–57,372) [USD $717 (527–940)], respectively, and in active disease was INR 52,436.5 (49,229–67,567.75) [$859 (807–1107)] and INR 72,145 (49,447–92,212) [USD $1182 (811–1512)], respectively. Compared with remission, active disease had a 1.4-fold higher cost for CD as compared to UC. In both groups, the greatest component of direct costs was drugs. Thirteen (22%) and 7 (28%) patients with UC and CD needed hospitalization accounting for 23.1 and 20.4% of the total costs, respectively. At one year, direct costs surmounted indirect costs in UC and CD (p < 0.001). Productivity losses contributed to 18.5 and 16% of the overall costs for UC and CD, respectively.Conclusion
This first, panoptic, health economic study for IBD from India shows that the costs are driven by medication, productivity losses, and not merely hospitalization alone.5.
Purpose of Review
Inflammatory bowel diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing diseases with unknown etiologies. The purpose of this review is to present the natural disease course evidenced in the latest epidemiology data.Recent Findings
The prevalence of IBD is rapidly increasing, affecting five million patients worldwide with the highest incidence observed in Northern Europe and Northern America. It has been shown that both CD and UC patients are at an increased risk for developing cancer of the gastrointestinal tract compared to the general population. Though the disease course of IBD is unpredictable, the rate of surgical treatment has declined potentially as a consequence of the introduction of immunomodulators and new biologic treatment options.Summary
Treatments with biological agents and/or immunosuppressive drugs as well as disease monitoring with eHealth devices seem to have a positive impact on the disease course. However, long-term follow-up studies are still lacking and therefore no reliable conclusions can be drawn as of yet. Medical compliance is paramount in the treatment of IBD, and continuous research focusing on approaches that increase compliance is also necessary.6.
Anjali D. Amarapurkar Deepak N. Amarapurkar Pravin Rathi Prabha Sawant Nikhil Patel Praful Kamani Krishnakant Rawal Rajiv Baijal Ameya Sonawane Nitin Narawane Samrat Kolekar Naveen Totla 《Indian journal of gastroenterology》2018,37(3):189-195
Introduction
Environmental risk factors have been associated with inflammatory bowel disease (IBD). With rising incidence, it is important to know risk factors associated with IBD in our population. This study was aimed to evaluate risk factors for IBD from western India.Methods
This was prospective, multi-center case-control study which included 1054 patients with IBD of which 765 (72.5%) were ulcerative colitis (UC) and 289 (27.4%) Crohn’s disease (CD). Asymptomatic individuals without a history of any major illness served as controls. The questionnaire containing risk factors for IBD was given to patients and control group. Odds ratio and 95% confidence interval were calculated for each variable.Result
Significant numbers of patients with CD were from rural area. Rural environment (OR 1.071, 0.82–1.38 and OR 1.441, 1.02–2.02), higher education (OR 1.830, 1.52–2.19 and OR 1.519, 1.16–1.97), professional by occupation (OR 1.754, 1.46–2.09 and OR 1.293, 0.99–1.67), annual family income >100,000 Indian national rupees (OR 2.185, 1.52–3.13 and OR 4.648, 3.10–6.95), history of appendectomy (OR 3.158, 1.71–5.80 and OR 3.158, 1.71–5.80), and family history of IBD (OR 4.510, 2.19–9.25 and OR 3.972, 1.58–9.96) were the risk factors for UC and CD, respectively. Vegetarian diet was protective factor for UC (OR 0.29, 0.27–0.39) and risk for CD (OR 1.179, 0.88–1.57). Smoking and chronic alcoholism were not found to be the risk factors.Conclusion
This study highlights association between socioeconomic, dietary factors, appendectomy, and family history as risk factors for IBD.7.
Rasika Bhamre Sangeet Sawrav Shilpa Adarkar Rishika Sakaria Shobna J Bhatia 《Indian journal of gastroenterology》2018,37(4):307-312
Background
Psychiatric comorbidities are associated with inflammatory bowel disease (IBD). We conducted an observational study to evaluate the prevalence of depression and anxiety in patients with IBD.Methods
Seventy consecutive consenting patients with IBD (62 ulcerative colitis [UC], 8 Crohn’s disease [CD]; 40 males, mean age [SD] 36.2 [11.3] years) and 100 healthy volunteers (44 males, age 31.22 [SD] [10.5] years) as controls were enrolled. All participants were directed to take self-assessment tests, Patient Health Questionnaire -9 (PHQ-9) and Symptom Checklist Anxiety Scale (SCL-A20). Participants having a score ≥ 10 on PHQ-9, or ≥ 29 on SCL-A20 were administered the Hamilton Depression Rating Scale (HAM-D) or Hamilton Anxiety (HAM-A) scales, respectively. The severity of depression and anxiety was graded with HAM-D and HAM-A scales, respectively. The protocol was approved by the Institutional Ethics Committee.Results
The prevalence of depression (34.3% vs. 5%, p?<?0.0001, OR 9.7) and anxiety (18.6% vs. 2%, p?=?0.0002, OR 11.17) was higher in patients with IBD as compared to controls. The severity of depression was higher in patients compared to controls (mean rank 17 vs. 7, p?=?0.04). The prevalence of depression was not different between UC and CD; all IBD patients with anxiety had UC. The mean duration of disease and history of corticosteroid treatment or surgery for IBD were not associated with the presence of depression or anxiety. Patients with severe CD (Crohn’s disease activity index, CDAI?>?450) had more severe depression. The severity of UC did not correlate with severity of anxiety or depression in UC.Conclusions
Anxiety and depression are more prevalent in IBD patients as compared to healthy individuals.8.
Tao Ji Chao Xu Lihua Sun Min Yu Ke Peng Yuan Qiu Weidong Xiao Hua Yang 《Digestive diseases and sciences》2015,60(7):1958-1966
Background and Aims
The pathogenesis of inflammatory bowel disease (IBD) is associated with dysregulation of intestinal immune system. Aryl hydrocarbon receptor (AHR) is believed to control the chronic inflammation in the gut. Besides, interleukin-7 (IL-7) is proved to be an important cytokine that activates mucosal inflammation in IBD. Moreover, intraepithelial lymphocytes (IELs) are one of the key immunological compartments involved in regulating intestinal inflammation. In this study, we investigated the function of 6-formylindolo (3,2-b) carbazole (Ficz), a ligand of AHR, on IL-7, colitis, and IEL phenotypes.Methods
Colitis was induced by administration of dextran sulfate sodium (DSS) to wild-type C57BL/6J mice for 7 days. Mice were weighted, colon tissues were collected and measured, and histology analyses were performed. IELs were isolated from colon, and the phenotype and activation of IELs were examined using flow cytometry detection. The expression of AHR and IL-7 was measured by immunofluorescence, Western blot, and RT-PCR.Results
Ficz down-regulated epithelial-derived IL-7 expression in mice with DSS-induced colitis and ameliorated DSS-induced colitis. Ficz also decreased CD8αβ+ and CD8+ IEL subpopulations, enhanced TCRγδ+ IEL subpopulation, and reduced the percentage of activated CD4+ and CD8+ subpopulations.Conclusions
Ficz could down-regulate epithelial-derived IL-7 expression in mice with DSS-induced colitis and inhibit inflammation in the gastrointestinal tract of mice. AHR-related compounds might be the new and promising therapeutic medicaments for the treatment of patients with IBD.9.
Background
COPD represents a multifactorial lung disorder with high morbidity and mortality. Despite intensive research concerning the underlying disease mechanisms, the involvement of the CD200/CD200R axis in supporting or preventing the onset of COPD has not yet been addressed. Since the CD200/CD200R axis is crucially implicated in the maintenance of pulmonary immune homeostasis, we hypothesized that it might be involved in controlling the onset of COPD.Methods
To address this, we analyzed the serum samples from COPD patients and normal controls for soluble (s) CD200 and correlated the data to COPD-relevant clinical parameters. In addition, basic studies were conducted in CD200-deficient and wild-type mice in which COPD-like inflammation was induced with elastase/LPS followed by lung and serum component analysis.Results
We observed a positive correlation between serum sCD200 and IL-6 levels as well as a trend toward a negative correlation of sCD200 with vitamin D3 in COPD patients. Further investigations in mice revealed that despite elevated serum concentration of MMP-9 in CD200KO mice, the early onset of COPD-like lung inflammation was similar in CD200-deficient and wild-type animals in terms of immune cell infiltration, emphysematous changes, and mucus overproduction.Conclusions
While our murine studies suggest that the co-inhibitory molecule CD200 does not appear to play a prominent role in the early onset of COPD-like features, correlation of sCD200 serum levels with COPD-related parameters in humans with established disease revealed that the CD200/CD200R axis may be mechanistically linked to the disease course in COPD patients.10.
11.
Seong Ran Jeon Jocelyn Chai Christiana Kim Christine H. Lee 《Current infectious disease reports》2018,20(8):21
Purpose of Review
Fecal microbiota transplantation (FMT) has been investigated as a potential treatment for inflammatory bowel disease (IBD). This review examines current evidence around the efficacy and safety of FMT for patients with IBD.Recent Findings
Randomized controlled trials (RCTs) and meta-analyses have suggested that FMT may facilitate clinical and endoscopic remission in patients with active ulcerative colitis (UC). Although the evidence for FMT in Crohn’s disease (CD) is more limited, positive outcomes have been observed in small cohort studies. Most adverse events (AEs) were mild and included transient gastrointestinal symptoms. Serious adverse events (SAEs) did not differ significantly between the FMT and control groups, and a marginal increased rate of IBD flares following FMT was observed. Microbiota analysis following FMT showed increased intestinal bacterial diversity and a shift towards the donor microbial profile in recipients’ stools.Summary
FMT for patients with IBD is promising as RCTs have shown the benefit of FMT for UC, although the efficacy of FMT for CD is less clear. Further large and well-designed trials are necessary to resolve critical issues such as the donor selection, the ideal route of administration, duration, frequency of FMT, and the long-term sustained efficacy and safety.12.
Background
Inflammatory bowel disease (IBD) is an intestinal disorder, involving chronic and relapsing inflammation of the digestive tract. Dysregulation of the immune system based on genetic, environmental, and other factors seems to be involved in the onset of IBD, but its exact pathogenesis remains unclear. Therefore, radical treatments for ulcerative colitis and Crohn’s disease remain to be found, and IBD is considered to be a refractory disease.Aims
The aim of this study is to obtain novel insights into IBD via metabolite profiling of interleukin (IL)-10 knockout mice (an IBD animal model that exhibits a dysregulated immune system).Methods
In this study, the metabolites in the large intestine and plasma of IL-10 knockout mice were analyzed. In our analytical system, two kinds of analysis (gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry) were used to detect a broader range of metabolites, including both hydrophilic and hydrophobic metabolites. In addition, an analysis of lipid mediators in the large intestine and ascites of IL-10 knockout mice was carried out.Results
The levels of a variety of metabolites, including lipid mediators, were altered in IL-10 knockout mice. For example, high large intestinal and plasma levels of docosahexaenoic acid (DHA) were observed. In addition, arachidonic acid- and DHA-related lipid cascades were upregulated in the ascites of the IL-10 knockout mice.Conclusions
Our findings based on metabolite profiles including lipid mediators must contribute to development of researches about IBD.13.
Holger Schäffler Annika Kaschitzki Christian Alberts Peggy Bodammer Karen Bannert Thomas Köller Philipp Warnke Bernd Kreikemeyer Georg Lamprecht 《International journal of colorectal disease》2016,31(5):961-971
Introduction
Changes in the intestinal bacterial composition seem to play a major role in the pathogenesis and in the clinical course of inflammatory bowel diseases (IBD), which consist of Crohn’s disease (CD), and ulcerative colitis (UC). Mutations in the NOD2 gene are the most important genetic risk factors for the development of CD. In this study, the association between mucosal biopsies and the mucosa-associated bacterial composition from CD and UC patients regarding their genetic risk factors (mutations in the NOD2 gene), their endoscopic activity, and their medical therapy (TNF-α blocking therapy) was examined.Material and methods
Seventy biopsies from routine colonoscopies from 33 IBD patients (26 CD and 7 UC) were obtained. Disease activity and clinical characteristics were assessed. Seven different bacterial strains (Bacteroides fragilis, Escherichia coli, Prevotella melaninogenica, Clostridium coccoides, Clostridium difficile, Bifidobacterium bifidum, and Faecalibacterium prausnitzii) were quantified using real-time PCR. NOD2 genotyping from patients with CD was performed.Results
Five of the 24 patients were positive for at least one mutation in the NOD2 gene. The bacterial composition was different in CD compared to UC, in macroscopic healthy compared to macroscopic inflamed biopsies, in NOD2 mutated compared to NOD2 wildtype patients, and in patients receiving TNF-α blocking therapy compared to patients without this treatment.Conclusion
This study further characterizes the mucosa-associated bacteria in IBD patients. Different clinical situations lead to an altered mucosa-associated bacterial composition. The analyzed bacteria could be promising targets for cost-effective surveillance or therapies in IBD patients.14.
Anat Yerushalmy-Feler Sharona Kern-Isaacs Shlomi Cohen 《Current gastroenterology reports》2018,20(4):13
Purpose of Review
Patients with inflammatory bowel disease (IBD) are predisposed to infections. Cytomegalovirus (CMV) colitis in adult IBD patients, particularly ulcerative colitis (UC), is related to severe or steroid-refractory disease. The aim of this review is to summarize the data on the prevalence and role of CMV colitis in children with IBD.Recent Findings
Data on CMV colitis in children continue to be very limited due to its rarity. As in adults, children with coexisting UC and CMV tend to have more severe colitis, are resistant to corticosteroids, and are at high risk for colectomies on short- and long-term follow-up.Summary
In children, as in adults, the significance of CMV colitis, in terms of whether CMV is a pathogen that aggravates acute severe colitis or simply reflects disease severity, is still unknown.15.
YinHua Tang YingYing Chen Xi Wang Guang Song YongGuo Li LiJun Shi 《Digestive diseases and sciences》2015,60(7):1948-1957
Background
Bone marrow mesenchymal stem cells sometimes improve symptoms of inflammatory bowel disease.Aim
To test the effects of combined granulocyte colony-stimulating factor (G-CSF) and MSC therapy in a rat model of ulcerative colitis (UC).Methods
Seventy-two rats with TNBS-induced UC were divided into control or treatment groups: control (no disease and no treatment), no treatment (model), 5-aminosalicylate (5-ASA) enema, or MSCs (labeled with BrdU) with (MSC/GCSF) or without (MSC) G-CSF, and G-CSF alone (GCSF). On days 14 and 28 post-treatment, macroscopic and histological appearances were assessed and the disease activity index (DAI) scored to evaluate the severity of disease. BrdU-labeled MSCs were identified by immunofluorescence to confirm transplantation and their location. The inflammatory profile of each group was evaluated by measuring expression of nuclear NF-κB p65, serum TNF-α, and IL-10 and by activity of mucosal myeloperoxidase (MPO).Results
Rats receiving MSC and G-CSF combination therapy had increased recruitment of MSCs to the colonic mucosa compared with rats receiving MSC transplantation alone. On day 28, the DAI, MPO activity, serum TNF-α and IL-10 levels, and NF-κB p65 expression in the combination therapy group were significantly lower compared to animals receiving no treatment, MSCs alone, or G-CSF alone (P < 0.05).Conclusion
Intravenously transplanted MSCs migrate and distribute to the colon to effectively alleviate the symptoms of UC, while G-CSF enhances this effect via an anti-inflammatory effect and improvement in the pathologic features of UC. G-CSF may be a promising therapeutic regulator of MSCs that can improve therapeutic outcomes in patients with UC.16.
Background and objectives
The pathophysiological mechanism of sarcopenia in the elderly has not yet been fully understood. Here, we aim to explore the relationship between sarcopenia and the inflammatory cytokine interleukin-6 (IL-6), and the anti-inflammatory cytokine interleukin-10 (IL-10) in an elderly population.Methods
Our study comprised 118 males and 46 females aged between 61 and 90 who had received a general medical examination in Tianjin First Central Hospital. Subjects were divided into a sarcopenia group and a non-sarcopenia group, defined according to the criteria of the Asian Working Group for Sarcopenia (AWGS). We compared body composition, handgrip strength (HS), gait speed (GS), biochemical indexes, levels of IL-6 and IL-10, living habits, and disease status between these groups.Results
Non-sarcopenia subjects undertook more regular physical exercise than sarcopenia patients. Sarcopenia subjects had higher nutrition risk but lower body mass index (BMI), serum albumin (ALB), triglyceride (TG), and creatinine (Cr) levels compared to non-sarcopenia subjects. Sarcopenia subjects were older and had higher visceral fat tissue (VFA) than non-sarcopenia subjects (P?<?0.05), along with higher IL-6 and IL-10 levels. Furthermore, IL-6/IL-10 ratios were higher in subjects with sarcopenia (P?<?0.05). Age, BMI, levels of physical activity, nutritional risk, VFA, IL-6, IL-10, IL-6/IL-10 ratio were independently associated with the presence of sarcopenia in univariate regression analyses. Following adjustment for confounding factors, the presence of sarcopenia was positively correlated with IL-6, IL-10, IL-6/IL-10 ratio and inversely correlated with BMI. Age is associated with increased presence of sarcopenia.Conclusions
The levels of inflammation cytokine IL-6, anti-inflammatory IL-10 and IL-6/IL-10 ratio were increased in elderly sarcopenia subjects. Sarcopenia was associated with increased levels of inflammatory cytokine IL-6, anti-inflammatory cytokine IL-10, and IL-6/IL-10 ratios.17.
Mathew Philip Philip Augustine Varghese Thomas G. N. Ramesh K. R. Vinayakumar T. M. Ramachandran Ismail Siyad Roy J. Mukkada R. Sobhana Devi Antony P. Chettupuzha Varghese A. Jaison M. Ramesh P. Mahadevan Abraham Koshy the Kerala Inflammatory Bowel Disease Study Group 《Indian journal of gastroenterology》2017,36(6):459-467
Background
Inflammatory bowel disease (IBD) is considered uncommon in Asia. The aim of this study was to document the demographic characteristics and clinical aspects of ulcerative colitis (UC) and Crohn’s disease (CD) in Kerala, India.Methods
A survey of IBD in Kerala was performed. All gastroenterologists in the region were invited. From May 2013 to October 2015, data were collected in a standardized pro-forma.Results
Forty-seven doctors in 34 centers contributed data. A total of 2142 patients were analyzed. This is the largest state-wide survey of IBD in India. Ulcerative colitis was diagnosed in 1112 (38 new), Crohn’s disease in 980 (53 new), and 50 were unclassified (5 new). The district-wise distribution of IBD cases correlated with the District-wise Gross State Domestic Product (r =?0.69, p <?0.01). Three percent was below the age of 18. Patients with UC had more diarrhea (73% vs. 51%), bleeding PR (79% vs. 34%), and intermittent flares (35% vs. 13%) (all p <?0.01). Patients with CD had more abdominal pain (62% vs. 46%), weight loss (53% vs. 40%), fever (28% vs. 18%), and history of antituberculosis treatment (21% vs. 5%) (all p <?0.01). Compared to adults, children (below 18 years) were more likely to have extensive UC (58% vs. 34%, p <?0.01) and unclassified IBD (15% vs. 2%, p <?0.01).Conclusion
Inflammatory bowel disease is common in Kerala, India. The disease characteristics of patients with IBD are almost similar to those from other parts of the country. Both UC and CD were seen in equal proportion in Kerala.18.
Background
Neuromediators produced by enteric nervous system regulate inflammatory processes via interacting with enteric immune system. Role of γ-aminobutyric acid (GABA), which is also a neuromediator, has been implicated in autoimmune diseases like multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, where they modulate the immune responses. However, its role in ulcerative colitis (UC) has not been defined.Aims
This study was carried out to investigate the role of GABA and its signaling components in pathogenesis of UC.Methods
Peripheral blood, colon mucosal biopsy, and fecal specimens were collected from UC and control groups. Quantification of GABA was done using ELISA. Expression of GABAergic signal system components was analyzed through RT-PCR analysis. Enumeration of GABA-producing bacteria was done by qPCR analysis. Activity of p38 MAPK and expression of proinflammatory cytokines were determined by immunohistochemistry and RT-PCR analysis, respectively.Results
GABA levels were significantly reduced in patients with UC as compared to control group when measured in serum and colon biopsy. Altered expression of GABAergic signal system was observed in UC patients. Reduced abundance of selected GABA-producing bacteria was detected in stool samples of UC patients as compared to control. p38 MAPK activity and expression of its downstream effector cytokines were found to be increased in UC patients as compared to control.Conclusions
Reduced levels of GABA were observed in patients with UC, and this leads to hyperactivation of p38 MAPK and overexpression of downstream effector cytokines suggesting a role of GABA in pathogenesis of UC.19.
Background
Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting.Methods
The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained.Results
Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased.Conclusions
In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage.20.
Yoon Seok Roh Surim Park Chae Woong Lim Bumseok Kim 《Digestive diseases and sciences》2015,60(7):2009-2018