Anna Zielińska

Oxidative stress (OS) has been proposed as a significant causative and propagating factor in inflammatory bowel diseases (IBDs). Modulation of OS is possible through antioxidants and inhibition of oxidizing enzymes. Thirty-one IBD patients and thirty-two controls were included in the study. The aim was to examine the levels of OS in colonic tissue of IBD requiring surgical intervention and control group, and their association with pain intensity. Total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT) activity, glutathione (GSH) and oxidized glutathione (GSSG) levels, and glutathione peroxidase (GPX) activity as markers of antioxidant defense were determined. Cyclooxygenases activities (Total COX, COX-1 and COX-2) were measured as prooxidant enzymes. Thiobarbituric acid reactive substances (TBARS) concentrations were measured to evaluate lipid peroxidation. Disease activity was assessed, and each subject filled out VAS and Laitinen’s pain assessment scales. Correlation between the OS, pain intensity, disease activity parameters, C-reactive protein (CRP), number of stools passed daily, disease duration, and dietary habits was investigated. No TAC differences were found between the groups. A significant decrease of SOD activity and GSH and GSSG levels was seen in IBD patients vs. controls, while GPX activity was diminished significantly only in CD patients. CAT and COX-1 activity was increased, and COX-2 significantly decreased in IBD. TBARS were significantly higher in CD patients compared to control group. No correlation was found between pain scores, inflammatory status, disease activity, disease duration, or dietary habits and OS markers. In our study, OS did not influence pain sensation reported by IBD patients.

Chitinases belong to the evolutionarily conserved glycosyl hydrolase family 18 (GH18). They catalyze degradation of chitin to N-acetylglucosamine by hydrolysis of the β-(1-4)-glycosidic bonds. Although mammals do not synthesize chitin, they possess two enzymatically active chitinases, i.e., chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase), as well as several chitinase-like proteins (YKL-40, YKL-39, oviductin, and stabilin-interacting protein). The latter lack enzymatic activity but still display oligosaccharides-binding ability. The physiologic functions of chitinases are still unclear, but they have been shown to be involved in the pathogenesis of various human fibrotic and inflammatory disorders, particularly those of the lung (idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, sarcoidosis, and asthma) and the gastrointestinal tract (inflammatory bowel diseases (IBDs) and colon cancer). In this review, we summarize the current knowledge about chitinases, particularly in IBDs, and demonstrate that chitinases can serve as prognostic biomarkers of disease progression. Moreover, we suggest that the inhibition of chitinase activity may be considered as a novel therapeutic strategy for the treatment of IBDs.

Due to its immunomodulatory effect, vitamin D has been associated with clinical parameters and outcomes in inflammatory bowel diseases (IBDs) which are chronic conditions of the gastrointestinal tract. Upon synthesis or digestion, vitamin D is metabolized in the liver to form 25(OH)D3, the major circulating metabolite. Further renal hydroxylation generates 1,25(OH)2D3, the most potent metabolite. Our aim was to examine the association between vitamin D levels, and its supplementation and pain intensity in 39 IBD patients and 33 healthy individuals. 25(OH)D3 and 1,25(OH)2D3 serum levels were measured. Each subject filled out visual analog scale (VAS) and Laitinen’s pain assessment scales. Laboratory results were obtained, and disease activity was assessed. Linear regression was employed to investigate the correlation between 25(OH)D3, 1,25(OH)2D3 and pain intensity, clinical activity parameters, C-reactive protein, disease duration, and dietary habits. In IBD patients, 25(OH)D3 was increased, whereas 1,25(OH)2D3 was not. Vitamin D3 supplementation did not influence their levels. No correlation was found between pain scores, disease activity, inflammatory status, disease duration or dietary habits and both forms of vitamin D. Elevated 25(OH)D3 and normal 1,25(OH)D3 were found in IBD patients as compared to the controls. We discovered no effect from supplementation and no association between pain severity and vitamin D.

Background: The role of sleep disturbances in patients with inflammatory bowel disease (IBD) remained relatively unknown. The aim of this study was to identify the adipokine profile in the patients with IBD and its relationship with the circadian rhythm disorders. Methods: Prospective, observational cohort study was performed. In all the enrolled adult IBD patients, the disease activity was assessed by using Crohn’s Disease Activity Index (CDAI) for Crohn’s disease (CD) and Partial Mayo Score for ulcerative colitis (UC), respectively. All patients were also asked to respond to a questionnaire to define Pittsburgh Quality Sleep Index (PSQI). From all the enrolled patients, 15 mL venous blood was taken to determine adipokine levels and perform standard laboratory tests. Results: Sixty-five IBD patients were enrolled in our study: 30 with CD and 35 with UC. Poor sleep was noted in 69.2% patients with clinically active and in 7.7% patients with inactive disease (p = .0023). In the group of IBD patients with poor sleep, the significantly higher level of serum resistin (p = .0458), and lower level of serum adiponectin and leptin (p = .0215, p = .0201; respectively) were observed. In the IBD patients with exacerbation, the significantly higher level of serum resistin (p = .0396), significantly lower serum level of leptin (p = .0453) and tendency to lower serum level of adiponectin (p = .1214) were recorded. Conclusions: The relationship between circadian rhythm abnormalities and specific adipokine profile may show us a risk factor of developing inflammatory intestinal lesions in IBD patients. This knowledge may allow the treatment of sleep disturbances, body weight-control and dietary habits become new targets in IBD therapy.

Introduction: Irritable bowel syndrome (IBS) is a complex functional gut disorder that typically manifests in early adult years. More than a third of IBS patients are diagnosed with predominant constipation subtype (IBS-C). This syndrome has a distressing impact on the quality of life and is challenging both for patients and physicians. Areas covered: This review focuses on the pathophysiology of constipation in IBS and presents current management options. It also covers the latest findings that may lead to novel pharmacological options in IBS-C management. The authors intend to highlight the results of published research including abstracts, records from the clinicaltrials.gov database (second and third phases of the study) and information from original FDA documents. Expert opinion: Current therapeutic options for IBS-C treatment are based on linaclotide, lubiprostone, plecanatide, and the reintroduced tegaserod. Drugs present on the market as well as those in pre-clinical development should increase the lower esophageal sphincter pressure, promote gastric motility, accelerate gastric emptying and improve gastro-duodenal coordination. Most significantly, they shall not induce severe side effects.

Crohn's disease (CD) is a chronic, immune system-mediated inflammatory disease affecting gastrointestinal (GI) tract. The pathogenesis of the intestinal lesions is not entirely explained and understood: excessive activation of the immune system may come as a result of the interaction of environmental, genetic and infectious factors and the mediation of abnormal intestinal flora. The main objective of the current study is to further identify the role of adipose tissue in the pathogenesis of CD. Alterations in body fat distribution, accumulation of intra-abdominal white adipose tissue (WAT) and mesenteric obesity are well-known features of CD. Up to date, data concerning the role of WAT in the pathogenesis of CD is limited with only a few studies on the relationship between WAT and the course of the disease, as well as pro- and anti-inflammatory cytokine profile and general immune system functioning. In this review, we focus on the importance of physiological and pathophysiological WAT functions and secreted adipokines, which seem to have a vital role in the inflammatory and fibrotic processes in CD sufferers.

Introduction Visceral pain is a symptom reported by over 70% of inflammatory bowel disease (IBD) sufferers. So far, a single, specific cause of this debilitating state has not been established. Chronic pain is one of the most important factors decreasing the quality of life in IBD course. Concurrently, management of pain is the most challenging issue encountered by clinicians in IBD treatment. Areas covered This review focuses on pathophysiology of inflammatory bowel disease-caused visceral pain and explores currently available approaches to its management. We also covered recent pharmacological developments in the field. Conclusions Pain-related disability has major effects on quality of life and on functional and social outcomes in IBD patients. Currently, there is no one standardized method of managing chronic visceral pain in IBD. Therefore, future development, focusing primarily on alleviating the pain, but also on reducing inflammation, is essential.

Introduction: Irritable bowel syndrome (IBS) is a functional gut disorder that typically manifests in early adult years. One of the two major symptoms of the disease is chronic, visceral pain. The patients report pain as the most distressing symptom with the greatest impact on quality of life, challenging both to patients and healthcare providers. Areas covered: This review focuses on the pathophysiology of abdominal pain in IBS and describes current treatment possibilities. It also covers latest findings that may lead to novel pharmacological options in IBS pain management. Expert commentary: Pain is the main contributor to severity in IBS. Seeking pain alleviation is the most common reason that IBS sufferers consult with their physicians. Not all patients report being satisfied with available treatments for pain in IBS and there is a pressing need to find new, more efficient therapies for this syndrome.

Anti-tumour necrosis factor alpha drugs (anti-TNF-α) effectively reduce the risk of surgery in Crohn's disease (CD). Unsatisfactory response to anti-TNF-α agents leads to the development of disease complications in a great percentage of patients. Simultaneously, possible predictive factors for ares during biological treatment remain uncertain. To investigate the incidence rate of intestinal resection during biological treatment and search for predicting factors for ares demanding a surgical intervention. A retrospective study of 68 patients qualified for anti-TNF-alpha therapy. The data consisting of demographic details, disease duration and laboratory results before the first drug administration and at the post induction period were collected. The association between these parameters and loss of response (LOR) demanding a surgical intervention was evaluated. LOR to the anti-TNF-alpha therapy was observed in 10/68 patients (14.7%). Mean disease duration at initiation of therapy was statistically longer in operated patients (8.8 ± 2.04 y vs. 4.93 ± 4.29 y; p < 0.02). That group revealed higher CRP values in post induction period compared to group with sustained response (48.24 ± 61.99 mg/l vs. 7.29 ± 13.43 mg/l; p < 0.05), contrary to hematocrit levels, which were lower in this group at each point of the study (30.58 ± 6.19% vs. 36.69 ± 16.0%; p = 0.04) (18.62 ± 18.19% vs. 40.27 ± 4.72%; p < 0.05) (4.01 ± 0.9 x106/μl; p = 0.009) (40.27 ± 4.72 g/dl vs. 18.62 ± 18.19 g/dl; p < 0.05). CDAI was significantly higher at post induction evaluation in the group with LOR (260.75 ± 98.1 vs. 118.12 ± 4.59; p < 0.05). CRP and CDAI, expressing in ammation severity, RBC, Hgb, Hct and the disease duration may serve as predictive factors for LOR to biological therapy.