Two-dimensional grayscale ultrasound and spectral Doppler waveform evaluation of dogs with chronic enteropathies

Sonography is an important diagnostic tool to examine the gastrointestinal tract of dogs with chronic diarrhea. Two-dimensional grayscale ultrasound parameters to assess for various enteropathies primarily focus on wall thickness and layering. Mild, generalized thickening of the intestinal wall with maintenance of the wall layering is common in inflammatory bowel disease. Quantitative and semi-quantitative spectral Doppler arterial waveform analysis can be utilized for various enteropathies, including inflammatory bowel disease and food allergies. Dogs with inflammatory bowel disease have inadequate hemodynamic responses during digestion of food. Dogs with food allergies have prolonged vasodilation and lower resistive and pulsatility indices after eating allergen-inducing foods.

Antibodies to flagellin indicate reactivity to bacterial antigens in IBS patients

One of the several possible causes of irritable bowel syndrome (IBS) is thought to be low-grade mucosal inflammation. Flagellin, the primary structural component of bacterial flagellae, was shown in inflammatory bowel disease patients to activate the innate and adaptive immunity. It has not yet been conclusively established if IBS patients show reactivity to luminal antigens. In 266 patients [112 IBS, 61 Crohn's disease (CD), 50 ulcerative colitis (UC) and 43 healthy controls (HC)], we measured antibodies to flagellin (FAB, types A4-Fla2 and Fla-X), anti-Saccharomyces cerevisiae antibodies (ASCA) (both ELISA), antipancreas antibodies (PAB) and perinuclear antineutrophil cytoplasmatic antibodies (p-ANCA) (both IF). All IBS patients had normal fecal calprotectin (mean 21 microg mL(-1), SD 6.6) and fulfilled the ROME II criteria. Frequencies of antibodies in patients with IBS, CD, UC and HC, respectively, are as follows (in per cent): antibodies against A4-Fla2: 29/48/8/7; antibodies against Fla-X: 26/52/10/7; ASCA: 6/59/0/2; p-ANCA: 0/10/52/0; and PAB: 0/28/0/0. Antibodies against A4-Fla2 and Fla-X were significantly more frequent in IBS patients than in HC (P = 0.004 and P = 0.009). Antibodies to A4-Fla2 and Fla-X were significantly more frequent in IBS patients with antecedent gastroenteritis compared to non-postinfectious IBS patients (P = 0.002 and P = 0.012). In contrast to ASCA, PAB and p-ANCA, antibodies against A4-Fla2 and Fla-X were found significantly more often in IBS patients, particularly in those with postinfectious IBS, compared to HC. This observation supports the concept that immune reactivity to luminal antigens has a putative role in the development of IBS, at least in a subset of patients.

MR colonography: 1.5T versus 3T

MR colonography is a powerful noninvasive method to image colorectal masses and inflammatory bowel disease. This article describes current techniques of MR colonography and compares its implementation at 1.5T and 3T.

Extra-adrenal glucocorticoid synthesis in the intestinal epithelium: more than a drop in the ocean?

Glucocorticoids (GC) are lipophilic hormones commonly used as therapeutics in acute and chronic inflammatory disorders such as inflammatory bowel disease due to their attributed anti-inflammatory and immunosuppressive actions. Although the adrenal glands are the major source of endogenous GC, there is increasing evidence for the production of extra-adrenal GC in the brain, thymus, skin, vasculature, and the intestine. However, the physiological relevance of extra-adrenal-produced GC remains still ambiguous. Therefore, this review attracts attention to discuss possible biological benefits of extra-adrenal-synthesized GC, especially focusing on the impact of locally synthesized GC in the regulation of intestinal immune responses.

Lack of TNFR2 expression by CD4(+) T cells exacerbates experimental colitis

TNF plays fundamental roles in the induction and perpetuation of inflammation. The effects of TNF are mediated through TNF receptor (TNFR) 1 or 2. As these two receptors mediate different functions, selective targeting of one receptor may represent a more specific treatment for inflammatory disorders than the complete blocking of TNF. TNFR2 expression is up-regulated in inflammatory bowel disease. Hence, we directly assessed the role of TNFR2 signaling in the CD4(+) T-cell transfer model of colitis using TNFR2(-/-) or WT mice as donors of colitogenic CD4(+)CD45RB(hi) T cells for transfer into syngeneic RAG2(-/-) or RAG2(-/-)TNFR2(-/-) recipient mice. Although the absence of TNFR2 expression by non-lymphoid cells of the recipient mice does not influence the course of colitis, transfer of TNFR2(-/-) CD4(+) T cells leads to an accelerated onset of disease and to more severe signs of inflammation. The enhanced colitogenic potential of TNFR2(-/-) CD4(+) T cells is associated with reduced activation-induced cell death, resulting in an increased accumulation of TNFR2(-/-) CD4(+) T cells. Hence, TNFR2 signaling is crucial for the TNF-dependent contraction of the disease-inducing T cells. Therefore, a selective blocking of TNFR2 may lead to exacerbation rather than attenuation of T-cell-mediated inflammatory disorders.

Deciphering microRNA code in pain and inflammation: lessons from bladder pain syndrome

MicroRNAs (miRNAs), a novel class of molecules regulating gene expression, have been hailed as modulators of many biological processes and disease states. Recent studies demonstrated an important role of miRNAs in the processes of inflammation and cancer, however, there are little data implicating miRNAs in peripheral pain. Bladder pain syndrome/interstitial cystitis (BPS/IC) is a clinical syndrome of pelvic pain and urinary urgency/frequency in the absence of a specific cause. BPS is a chronic inflammatory condition that might share some of the pathogenetic mechanisms with its common co-morbidities inflammatory bowel disease (IBD), asthma and autoimmune diseases. Using miRNA profiling in BPS and the information about validated miRNA targets, we delineated the signaling pathways activated in this and other inflammatory pain disorders. This review projects the miRNA profiling and functional data originating from the research in bladder cancer and immune-mediated diseases on the BPS-specific miRNAs with the aim to gain new insight into the pathogenesis of this enigmatic disorder, and highlighting the common regulatory mechanisms of pain and inflammation.

Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer

Dysfunction of Paneth and goblet cells in the intestine contributes to inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). Here, we report a role for the NAD+-dependent histone deacetylase SIRT1 in the control of anti-bacterial defense. Mice with an intestinal specific Sirt1 deficiency (Sirt1int-/-) have more Paneth and goblet cells with a consequent rearrangement of the gut microbiota. From a mechanistic point of view, the effects on mouse intestinal cell maturation are mediated by SIRT1-dependent changes in the acetylation status of SPDEF, a master regulator of Paneth and goblet cells. Our results suggest that targeting SIRT1 may be of interest in the management of IBD and CAC.

Loss of bone strength in HLA-B27 transgenic rats is characterized by a high bone turnover and is mainly osteoclast-driven

Objective Although osteopenia is frequent in spondyloarthritis (SpA), the underlying cellular mechanisms and association with other symptoms are poorly understood. This study aimed to characterize bone loss during disease progression, determine cellular alterations, and assess the contribution of inflammatory bowel disease (IBD) to bone loss in HLA-B27 transgenic rats. Methods Bones of 2-, 6-, and 12-month-old non-transgenic, disease-free HLA-B7 and disease-associated HLA-B27 transgenic rats were examined using peripheral quantitative computed tomography, μCT, and nanoindentation. Cellular characteristics were determined by histomorphometry and ex vivo cultures. The impact of IBD was determined using [21-3 x 283-2]F1 rats, which develop arthritis and spondylitis, but not IBD. Results HLA-B27 transgenic rats continuously lost bone mass with increasing age and had impaired bone material properties, leading to a 3-fold decrease in bone strength at 12 months of age. Bone turnover was increased in HLA-B27 transgenic rats, as evidenced by a 3-fold increase in bone formation and a 6-fold increase in bone resorption parameters. Enhanced osteoclastic markers were associated with a larger number of precursors in the bone marrow and a stronger osteoclastogenic response to RANKL or TNFα. Further, IBD-free [21-3 x 283-2]F1 rats also displayed decreased total and trabecular bone density. Conclusions HLA-B27 transgenic rats lose an increasing amount of bone density and strength with progressing age, which is primarily mediated via increased bone remodeling in favor of bone resorption. Moreover, IBD and bone loss seem to be independent features of SpA in HLA-B27 transgenic rats.

European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa

Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly the axillae, inguinal and anogenital regions. A mean disease incidence of 6.0 per 100,000 person-years and an average prevalence of 1% has been reported in Europe. HS has the highest impact on patients' quality of life among all assessed dermatological diseases. HS is associated with a variety of concomitant and secondary diseases, such as obesity, metabolic syndrome, inflammatory bowel disease, e.g. Crohn's disease, spondyloarthropathy, follicular occlusion syndrome and other hyperergic diseases. The central pathogenic event in HS is believed to be the occlusion of the upper part of the hair follicle leading to a perifollicular lympho-histiocytic inflammation. A highly significant association between the prevalence of HS and current smoking (Odds ratio 12.55) and overweight (Odds ratio 1.1 for each body mass index unit) has been documented. The European S1 HS guideline suggests that the disease should be treated based on its individual subjective impact and objective severity. Locally recurring lesions can be treated by classical surgery or LASER techniques, whereas medical treatment either as monotherapy or in combination with radical surgery is more appropriate for widely spread lesions. Medical therapy may include antibiotics (clindamycin plus rifampicine, tetracyclines), acitretin and biologics (adalimumab, infliximab). A Hurley severity grade-relevant treatment of HS is recommended by the expert group following a treatment algorithm. Adjuvant measurements, such as pain management, treatment of superinfections, weight loss and tobacco abstinence have to be considered.

Alcoholic Cirrhosis Increases Risk for Autoimmune Diseases: A Nationwide Registry-Based Cohort Study

BACKGROUND & AIMS Alcoholic cirrhosis is associated with hyperactivation and dysregulation of the immune system. In addition to its ability to increase risk for infections, it also may increase the risk for autoimmune diseases. We studied the incidence of autoimmune diseases among patients with alcoholic cirrhosis vs controls in Denmark. METHODS We collected data from nationwide health care registries to identify and follow up all citizens of Denmark diagnosed with alcoholic cirrhosis from 1977 through 2010. Each patient was matched with 5 random individuals from the population (controls) of the same sex and age. The incidence rates of various autoimmune diseases were compared between patients with cirrhosis and controls and adjusted for the number of hospitalizations in the previous year (a marker for the frequency of clinical examination). RESULTS Of the 24,679 patients diagnosed with alcoholic cirrhosis, 532 developed an autoimmune disease, yielding an overall increased adjusted incidence rate ratio (aIRR) of 1.36 (95% confidence interval [CI], 1.24-1.50). The strongest associations were with Addison's disease (aIRR, 2.47; 95% CI, 1.04-5.85), inflammatory bowel disease (aIRR, 1.56; 95% CI, 1.26-1.92), celiac disease (aIRR, 5.12; 95% CI, 2.58-10.16), pernicious anemia (aIRR, 2.35; 95% CI, 1.50-3.68), and psoriasis (aIRR, 4.06; 95% CI, 3.32-4.97). There was no increase in the incidence rate for rheumatoid arthritis (aIRR, 0.89; 95% CI, 0.69-1.15); the incidence rate for polymyalgia rheumatica decreased in patients with alcoholic cirrhosis compared with controls (aIRR, 0.47; 95% CI, 0.33-0.67). CONCLUSIONS Based on a nationwide cohort study of patients in Denmark, alcoholic cirrhosis is a risk factor for several autoimmune diseases.

DSS induced colitis increases portal LPS levels and enhances hepatic inflammation and fibrogenesis in experimental NASH

Intestinal bacterial overgrowth and increased permeability are features of non alcoholic steatohepatitis (NASH). Bacterial endotoxin has been shown to promote NASH progression. Application of dextran sulfate sodium (DSS) is a colitis model in mice characterized by damage of the intestinal barrier. This study was designed to investigate if application of DSS aggravates experimental NASH.

Small-bowel MRI in children and young adults with Crohn disease: retrospective head-to-head comparison of contrast-enhanced and diffusion-weighted MRI

Small-bowel MRI based on contrast-enhanced T1-weighted sequences has been challenged by diffusion-weighted imaging (DWI) for detection of inflammatory bowel lesions and complications in patients with Crohn disease.

Efficacy and safety of certolizumab pegol induction therapy in an unselected Crohnʼs disease population

Switzerland was the first country to approve certolizumab pegol (Cimzia, CZP) for the treatment of patients with moderate to severe Crohn's disease (CD) in September 2007. This phase IV study aimed to evaluate the efficacy and safety of CZP in a Swiss multicenter cohort of practice-based patients.

Effects of social support on the clinical course of Crohn's disease

Social support has been found to be protective from adverse health effects of psychological stress. We hypothesized that higher social support would predict a more favorable course of Crohn's disease (CD) directly (main effect hypothesis) and via moderating other prognostic factors (buffer hypothesis).

Efficacy and safety of certolizumab pegol in an unselected crohn's disease population: 26-week data of the FACTS II survey

Certolizumab pegol (Cimzia, CZP) was approved for the treatment of Crohn's disease (CD) patients in 2007 in Switzerland as the first country worldwide. This prospective phase IV study aimed to evaluate the efficacy and safety of CZP over 26 weeks in a multicenter cohort of practice-based patients.