DNA was isolated from approximately one million cells from the EBV-transformed cell lines using Qiagen columns following the manufacturer’s instructions (Qiagen, Valencia, CA). Genotyp- ing was performed using the ImmunoChip (Illumina, San Diego, CA) developed by an international consortium of investigators studying major immune-related diseases such as Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, autoimmune thyroid disease, celiac disease, and multiple sclerosis.  Because the iChip is a custom designed chip and the Puerto Rican and HGDP subjects are very genetically diverse, quality control included testing for overall intensity of dye reactions, for balance between both dyes in this two-dye system, for differential missing data across genotyping runs, for adequate separation between genotype clusters as well as number of clusters, for Hardy-Weinberg equilibrium, and for abnormal cluster patterns indicating missing alleles or other assay problems due to genetic variation across the various populations. Monomorphic SNPs or SNPs with a minor allele frequency (MAF) less than 0.005 were also removed. Over 12,000 cluster plots were manually reviewed for this study, many by more than one investigator. As a final quality control measure, all SNPs in this report have been reviewed again prior to publication. A dataset of 1159 Puerto Rican and 832 HGDP samples for 155,868 SNPs was available to this study.
In the present study, we found a statistically significant association between CMV viral replication and the use of combined therapy, consisting of biological therapy (infliximab or adalimumab) plus an immunosuppressive drug (azathioprine or methotrexat). We believe that higher immunosuppression favors viral replication. However, the increase in CMV replication was not accompanied by a greater intestinal inflammatory activity, as evidenced by fecal the calprotectin levels. The present findings further support the hypothesis that CMV is a spectator of the inflammatory process in IBD. The higher the degree of immunosuppressive state caused by the therapy and/or disease is, the greater the chance for CMV replication; however, this finding did not seem to worsen the IBD activity.
In fact, we could not ignore the fact that the most com- mon occurrence of isotretinoin prescription is in young adult- hood, which also corresponds to the peak age for IBD on- set. Knowing that abnormalities may not appear until months to years after its discontinuation, the associationwith prior isotretinoin use can easily go unnoticed (2). So, besides a thorough history of IBD risk factors before isotretinoin pre- scription, gastroenterologists must be aware of this fact and ask for newly diagnosed patients with IBD about previous isotretinoin use.
Cohorts of CD (n = 778) and UC (n = 759) patients were screened for the DECTIN-1 c.714T.G polymorphism and compared to a group of healthy subjects (n = 772). Subsequently, these genetic data were correlated with clinical parameters reflecting disease severity. This analysis revealed no statistical significant association between the prevalence of the DECTIN-1 c.714G allele and IBD, neither indisease occurrence nor indisease severity. However, one can observe that homozygous individuals bearing the DECTIN-1 polymorphism were twice as frequent in healthy controls compared to IBD patients. This may suggest that complete absence of dectin-1 function could protect against IBD. It is important to realize that the only two dectin- 1 isoforms capable of binding b-glucans (isoforms A and B) are structurally equally affected by the DECTIN-1 c.714T.G polymor- phism. The occurrence of splicing isoforms with residual function could therefore be excluded. The potential mechanism of protection are likely to include the lower production of pro-inflammatory cytokines, including IL-17, in the individuals with defective dectin-1. In these series, statistical power to preclude any functional difference is insufficient due to the low prevalence of homozygous individuals. Additional studies in homozygous and heterozygous subpopulations are needed to confirm the reported observations.
Because commensal microbes produce numerous active metabolites, the microbiome is essential for several aspects of host health, such as metabolism, immune response, and physiology. Members of the Firmicutes phylum, which, as described earlier, are reduced in IBD (15), are known producers of short-chain fatty acid (SCFA) metabolites such as acetate and butyrate, which play an anti-inflammatory role in the gut (23). These are a preferred nutrient source for epithelial cells in the gastrointestinal tract, and their deficiency can induce a dysfunction, with subsequent disruption of the epithelial barrier. The commensal microbe-derived nutrient, buty- rate, also plays an immune regulatory function, because it can drive the differentiation of regulatory T (Treg) cells in vivo andin vitro by inducing the acetylation of histone H3 in the promoter of Foxp3 locus (23). As described in detail later, the balance between regulatory and effector responses is crucial to the outcome ofinflammatory diseases like IBD, and Treg cells expressing the transcription factor Foxp3 are one of the main regula- tory mechanisms required for disease control. In fact, by inducing Treg cells, butyrate can ameliorate colitis in mice, caused by adoptive transference of CD4 + CD45RB hi T cells into Rag1 –/– – mice (23). Another bacterial intestinal product that potentiates Treg cell development in the periphery is propionate, a SCFA with epigenetic effects similar to butyrate, i.e., the inhibition of histone deacetylase (24).
Exposure to aluminium may occur through ingested foods, water, beverages, or drugs. Aluminium has no known biological function and its accumulation can be extremely toxic, especially at the neurological level (42). However, studies indicate that 40% of ingested aluminium accumulates in the intestinal mucosa. A study conducted in the laboratory with mice proved that aluminium has the ability to modulate intestinal inflammation in vivo. The results demonstrated a worsening of colitis, delayed mucosal recovery accompanied by inflammation, specific antigen response by T cells and increased production ofinflammatory cytokines. Aluminium has also been shown to have the ability, either alone or with the support of bacteria, to induce the formation of granulomas (43). In the studies of water exposure, aluminium didn’t present an associationwithInflammatoryBowelDisease (17,31). Although in this systematic review the importance of aluminium was only described by Powel et al (1996) and Gatti (2004).
It is inevitable to encounter genetic heterogeneity in any disease identification strategy . As exemplified in the present study, frequency of -260T allele in patients differed remarkably between Caucasians and Asians (65.98% vs. 48.47% in UC, 54.76% vs. 48.82% in CD), leaving open the question that divergent genetic backgrounds or linkage disequilibrium patterns may account for this difference. Meanwhile, the possibility of CD14 gene C-260T being in close linkage with different nearby causal variants in different populations cannot be excluded. Additionally, it is widely believed that genetic markers in predisposition to IBD vary across geographical and racial groups. As evidenced, nucleotide oligo- merization domain (NOD)2/caspase-activation recruitmentdo- mains (CARD)-15 polymorphisms have been strongly associated Figure 2. Begg’s funnel plots of publication bias test for CD14 C-260T polymorphism with UC (a. -260T vs.-260C allele; b. -260TT vs. -260CC; c. dominant model; d. recessive model). Vertical axis represents the log of OR; horizontal axis represents the SE of log(OR). Funnel plots are drawn with 95% confidence limits. OR, odds ratio; SE, standard error. The graphic symbols represents the data in the plot be sized proportional to the inverse variance.
The presence of adhesions and the determination of myeloperoxidase activity provide an indication that ASC have the ability to promote and/or accelerate the regeneration pro- cess in inflamed intestinal mucosae. However, methodological adjustments should be included in future projects. Among the propositions of readjustment, there should be included an evaluation of the effectiveness of cell therapy for a longer period of time; cell infusion by other routes of administration, in addition to intravenous route; and feasibility of this therapy through co-infusion of ASC inassociationwith hematopoietic stem cells (HSC).
One of the objectives of this investigation was to evaluate asso- ciations between hematological abnormalities and some clinical characteristics of IBD. No association was observed between hema- tological abnormalities and the clinical activity index in CD, prob- ably because most patients (75%) were in remission. Interestingly, there was a high prevalence of hematological abnormalities in patients in remission (69.7%) andin those presenting clinical activity (90.9%) (Table 4). In contrast, an association between clin- ical-laboratory activity and the presence of hematological abnor- malities was found in the UC group (Table 5), such that 93% of the patients with hematological abnormalities presented mild or moderate activity, whereas three of the eight patients in remission presented hematological abnormalities (iron deiciency as etiol- ogy). he other patients with iron deiciency, as well the patients with ACD, FID and the patient with macrocytosis, presented mild
Results and Discussion: Anti-tumor necrosis factor α agents are efficient treatments for moderate-to-severe inflammatoryboweldiseaseand may ensure remission during pregnancy. Although these drugs cross the placenta, they are considered safe for both the mother and the fetus. Furthermore, up-to-date guidelines support therapy continuation during pregnancy aiming for disease control. The same guidelines also consider stopping treatment during the third trimester to limit maternal-fetal drug transfer. However, data shows that this strategy does not completely prevent fetus exposure. In addition, stopping treatment incurs in risk ofdisease flare and threatens subsequent therapy response. Fetus drug exposure has not showed an associationwith adverse childhood development. However, as infant drug levels could be detected up to seven months after birth, postponement of live virus vaccination is recommended. Conclusion: There should be no disagreement among the medical community as to the need to maintain therapy aiming for disease remission during gestation ininflammatoryboweldisease. Anti-tumor necrosis factor α agents are safe for both the mother and the fetus.
Inflammation is the driving force ininflammatoryboweldisease (IBD) and its link to oxidative stress and carcinogenesis has long been accepted. The antioxidant system of the intestinal mucosa in IBD is compromised resulting in increased oxidative injury. This defective antioxi- dant system may be the result of genetic variants in antioxidant genes, which can represent susceptibility factors for IBD, namely Crohn’s disease (CD) and ulcerative colitis (UC). Sin- gle nucleotide polymorphisms (SNPs) in the antioxidant genes SOD2 (rs4880) and GPX1 (rs1050450) were genotyped in a Portuguese population comprising 436 Crohn’s diseaseand 367 ulcerative colitis patients, and 434 healthy controls. We found that the AA genotype in GPX1 is associated with ulcerative colitis (OR = 1.93, adjusted P-value = 0.037). More- over, we found nominal significant associations between SOD2 and Crohn’s disease sus- ceptibility anddisease subphenotypes but these did not withstand the correction for multiple testing. These findings indicate a possible link between disease phenotypes and antioxidant genes. These results suggest a potential role for antioxidant genes in IBD pathogenesis and should be considered in future association studies.
Data were analyzed with SPSS 18.0. For continuous variables, mean and standard deviation were calculated. For categorical variables, percentages were provided. Categorical variables were compared with Chi-square test, andin cases where the premises of this test were not met (no more than 20% of cells with expected frequencies less than 5) was used the Fisher’s exact test. A p value < 0.05 was considered statistically significant. Binary logistic regression was used to determine the association between demographic variables and Table 1 - Clinical and demographic characteristics of patients who complete the questionnaire
3mg/L, respectively . Furthermore, hs-CRP test is cost effective and has a generally acceptable precision and reproducibility in coronary heart disease risk profiling . de Luka et al also pointed out that high hs-CRP is associated with coronary heart disease independent of traditional risk markers, viral load, CD4 count and the combination of antiretroviral therapy . Use of hs-CRP in the HIV-infected population is however subject to debate, since levels may be elevated pre- antiretroviral therapy and during therapy regardless of regimen . hsCRP levels also seem to remain elevated despite normalised CD4 cell count and suppressed viral load . A cohort study done amongst HIV infected patients in South Africa showed elevated levels of hs-CRP and other biomarkers pre-antiretroviral therapy . hs-CRP levels may be falsely elevated due to tissue injury, recent infection or general inflammation, andin individuals taking non-steroidal inflammatory drugs such as: aspirin, ibuprofen and naproxen . Levels are also elevated in arthritic patients while anti- inflammatory drugs and statins reduce hs-CRP levels . In some studies, changes in regimen have shown to be associated with increases in hs-CRP therefore use of hs-CRP may be more useful in those on stable antiretroviral therapy , . In contrast to some of the editorial commentary that has expressed concerns about the robust predictive value of hs-CRP testing for risk assessment, in a comprehensive 2007 review of available published CRP study data, Ridker supported the use of hs-CRP as a consistently additive and independent inflammatory predictor of future coronary heart events, while refuting some of the critical commentary directed at certain ‘negative’ studies . Results from an analysis in a cohort study done by Boger et al. , also gave evidence for use of hs-CRP as a more reliable estimate of coronary heart disease risk in people with well-controlled HIV infections than standard risk markers . The study also traced significant correlation between hs-CRP and triglycerides, cholesterol, and body mass index (BMI). The study by Boger et al. also showed the following prevalence (as %): hs-CRP >3mg/L (high risk)- 47%, hs-CRP between 1 and 3mg/L (average risk)-26%, and hs-CRP <1mg/L (low risk)-25% . Though BMI were less predictive of coronary heart diseasein HIV-infected patients there were indications that higher BMI is correlated with hs- CRP . The aim of the current study was to evaluate the risk of coronary heart diseasein both antiretroviral-naïve and antiretroviral-experienced HIV-infected patients using highly- sensitive C-reactive protein and lipid profiles.
This patient had enteritis prior to reactive arthritis onset and jointsymptoms accompanied intestinal symptoms and persisted over the time. They were probably triggered by the persistent habit of sucking contaminated water from an aquarium with tropical fish. However, we cannot exclude another source of Salmonella goldcoast infection, since no cultures of the aquarium water were made to confirm that hypothesis. Arthritis may also occur as an extraintestinal mani- festation ofinflammatoryboweldisease (IBD), making differential diagnosis sometimes challenging. There are no pathognomonic findings to distinguish arthritis as- sociated with IBD from reactive arthritis, thus it re- mains a diagnosis of exclusion. Acute phase reactants usually reflect the activity of the intestinal diseaseand are not useful in assessing peripheral arthritis or spondylitis. Radiograph study of the sacroiliac joints often presents abnormal findings even in IBD patients without gastrointestinal symptoms. Plain radiographs of the peripheral joints may present soft-tissue swelling, juxta-articular osteoporosis and mild periostitis usual- ly without erosions or destruction 14,15 .
13 is arthritis, followed by uveitis, spondylitis and erythema nodosum . Arthritis in IBD is classified as a seronegative spondyloarthropathy, associated with a positive HLA-B27 genotype and occurs in up to 30% of IBD patients . It is often divided into two categories, peripheral and axial arthritis, according to the joints involved. Peripheral arthritis can be subdivided into type I, a pauci/oligoarticular arthritis particularly affecting the larger joints of the lower extremities, and type II, a polyarticular arthritis of symmetrical distribution and affecting the upper limbs predominantly . The axial pattern of distribution includes sacroiliitis, inflammatory back pain (IBP) and ankylosing spondylitis. Type I peripheral arthritis is acute in onset, correlates with IBD activity and tends to improve upon commencement of IBD-directed therapy. Type II peripheral arthritis and axial arthritis are independent ofdisease activity require specific treatment other than that initiated for IBD. NSAID’s, corticosteroids and analgesics are the three most commonly prescribed drug classes for the management of IBD arthritis. NSAID’s are particularly nefarious in the elderly patient. Pharmacokinetic and pharmacodynamic changes that occur in this age group increase the sensitivity of the patient to this drug class and lead to increased risk of cardiovascular, neurological, renal and hepatic side effects . Therefore, prescribing for an elderly IBD patient must take into consideration the risk vs benefit ratio of each drug class employed.
InflammatoryBowel Diseases - ulcerative colitis and Crohn’s disease- are chronic gastrointestinal inflammatory diseases of unknown etiology. Decreased oral intake, malabsorption, accelerated nutrient losses, increased requirements, and drug- nutrient interactions cause nutritional and functional deficiencies that require proper correction by nutritional therapy. The goals of the different forms of nutritional therapy are to correct nutritional disturbances and to modulate inflammatory response, thus influencing disease activity. Total parenteral nutrition has been used to correct and to prevent nutritional disturbances and to promote bowel rest during active disease, mainly in cases of digestive fistulae with high output. Its use should be reserved for patients who cannot tolerate enteral nutrition. Enteral nutrition is effective in inducing clinical remission in adults and promoting growth in children. Due to its low complication rate and lower costs, enteral nutrition should be preferred over total parenteral nutrition whenever possible. Both present equal effectiveness in primary therapy for remission of active Crohn’s disease. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted, especially in patients presumed to need total parenteral nutrition. Recent research has focused on the use of nutrients as primary treatment agents. Immunonutrition is an important therapeutic alternative in the management ofinflammatorybowel diseases, modulating the inflammation and changing the eicosanoid synthesis profile. However, beneficial reported effects have yet to be translated into the clinical practice. The real efficacy of these and other nutrients (glutamine, short-chain fatty acids, antioxidants) still need further evaluation through prospective and randomized trials.
the IBD patients developing psoriasis during infliximab the- rapy must be treated by the conventional psoriasis approach (topical corticosteroids, phototherapy, vitamin-D analogs, methotrexate and/or cyclosporine) without the need to sus- pend infliximab. The discontinuation of infliximab infusions must be considered, especially in generalized, recalcitrant cases of psoriasis with important impact on quality of life. After the resolution of skin lesions, the reintroduction of biological therapy must be considered. In cases where it is necessary to suspend the biological, but IBD is aggressive, and infliximab withdrawal may lead to clinical deteriora- tion, the adoption of alternative therapeutic forms (e.g., antibiotics, mesalazine, or azathioprine) for IBD control, or infliximab replacement for another inhibitory molecule must be considered. Although the administration of syste- mic corticosteroids has been used in some cases (2, 23, 41, 44) , its
13. Caprilli R, Gassull MA, Escher JC, Moser G, Munkholm P, Forbes A, Hommes DW, Lochs H, Angelucci E, Cocco A, Vucelic B, Hildebrand H, Kolacek S, Riis L, Lukas M, de Franchis R, Hamilton M, Jantschek G, Michetti P, O’Morain C, Anwar MM, Freitas JL, Mouzas IA, Baert F, Mitchell R, Hawkey CJ; European Crohn’s and Colitis Organisation. European evidence based consensus on the diagnosis and management of Crohn’s disease: special situations. Gut. 2006;55(suppl 1):i36-i58.
A cross-sectional and retrospective study was conducted through a descriptive research, with an analysis of the medi- cal records entered in a database, performed in patients with IBD who were registered and who renewed their processes in the Program of Exceptional Medications of the Department of Health in the period from January 2008 to December 2016, that is, the period in which the medical records of the available data began.