Correlation of ex vivo cytokine secretion profiles with scoring indices in ulcerative colitis.

BACKGROUND: In ulcerative colitis, the complexity of mucosal cytokine secretion profiles and how they correlate with endoscopic and clinical scores is still unclear. METHODS: In this study, we collected fresh biopsies from UC patients to investigate which cytokines are produced in ex vivo culture conditions, a platform increasingly used for testing of novel drugs. Then, we correlated cytokine production with several scoring indices commonly used to assess the severity of the disease. RESULTS: Increased levels of IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNFα and IFNÉ£ were produced by biopsies of UC patients compared to non-IBD controls. Our results show a better correlation of cytokine levels with Mayo Endoscopic Subscore (MES) and Mayo score, than the more complex Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Out of 10 measured cytokines, eight correlated with MES, six with Mayo score and only three with UCEIS, due to the partial increase in cytokine secretion observed in donors with UCEIS = 7-8. When we analysed individual subscores within the UCEIS, Vascular Network subscore showed a correlation similar to MES (7/10 cytokines), while Bleeding as well as Erosions and Ulcers subscores correlated with only 3/10 cytokines, similarly to the total UCEIS. CONCLUSIONS: Our findings suggest that choosing biopsies from donors with MES = 2-3 and UCEIS = 2-6 from areas with no bleeding and no superficial and/or deep ulcers could enable a deeper insight into the cytokine profile of the inflamed tissue and represent a better tool for studying potential therapeutic targets and evaluation of novel therapies.

Absence of Oral Opportunistic Infections in Patients with Inflammatory Bowel Disease Receiving Anti-TNF-α and Anti-Integrin-α4ß7 Therapy.

Biological therapy of inflammatory bowel disease (IBD) carries an increased risk for the development of opportunistic infections due to immunomodulation. The aim of this study was to determine the prevalence and types of oral infections in IBD patients treated with biological (anti-TNF-α and anti-integrin-α4ß7) and conventional medication protocols. The study included 20 IBD patients receiving anti-TNF-α therapy, 20 IBD patients receiving anti-integrin-α4ß7 therapy and 20 IBD patients without immunomodulatory therapy. Participants completed questionnaires on medical information, oral lesions and symptoms. For each patient, clinical examination and a salivary flow rate test were performed, followed by a swab of the oral mucosa. The swab samples were cultured to identify Candida spp. and oral bacteria. No bacterial opportunistic infections were detected. Candidiasis was detected in four participants, with no significant difference between groups (p = 0.765). Hyposalivation was most common in the anti-TNF-α group, with a significant difference between groups (p = 0.036). There were no significant differences between groups in self-reported oral mucosal lesions and symptoms (p > 0.05), or in the distribution of oral mucosal lesions (p > 0.05). This study suggests that IBD patients receiving biological therapy are at no greater risk of developing oral opportunistic infections than IBD patients not receiving immunomodulatory therapy.

Claudins: Beyond Tight Junctions in Human IBD and Murine Models.

Claudins are transmembrane proteins constituting one of three tight junction protein families. In patients with inflammatory bowel disease (IBD), disease activity-dependent changes in expression of certain claudins have been noted, thus making certain claudin family members potential therapy targets. A study was undertaken with the aim of exploring expression of claudins in human disease and two different animal models of IBD: dextrane sulfate sodium-induced colitis and adoptive transfer model of colitis. The expression of sealing claudin-1, claudin-3, claudin-4, and claudin-8, and pore-forming claudin-2 in humans and rodents has been evaluated by immunohistochemistry and quantitative polymerase chain reaction. Claudins were expressed by epithelial and cells of mesodermal origin and were found to be situated at the membrane, within the cytoplasm, or within the nuclei. Claudin expression by human mononuclear cells isolated from lamina propria has been confirmed by Western blot and flow cytometry. The claudin expression pattern in uninflamed and inflamed colon varied between species and murine strains. In IBD and both animal models, diverse alterations in claudin expression by epithelial and inflammatory cells were recorded. Tissue mRNA levels for each studied claudin reflected changes within cell lineage and, at the same time, mirrored the ratio between various cell types. Based on the results of the study, it can be concluded that 1) claudins are not expressed exclusively by epithelial cells, but by certain types of cells of mesodermal origin as well; 2) changes in the claudin mRNA level should be interpreted in the context of overall tissue alterations; and 3) both IBD animal models that were analyzed can be used for investigating claudins as a therapy target, respecting their similarities and differences highlighted in this study.

Oral pathology in inflammatory bowel disease.

The incidence of inflammatory bowel diseases (IBD) - Crohn's disease (CD) and ulcerative colitis (UC) - has been increasing on a global scale, and progressively, more gastroenterologists will be included in the diagnosis and treatment of IBD. Although IBD primarily affects the intestinal tract, extraintestinal manifestations of the disease are often apparent, including in the oral cavity, especially in CD. Specific oral manifestations in patients with CD are as follows: indurate mucosal tags, cobblestoning and mucogingivitis, deep linear ulcerations and lip swelling with vertical fissures. The most common non-specific manifestations, such as aphthous stomatitis and angular cheilitis, occur in both diseases, while pyostomatitis vegetans is more pronounced in patients with UC. Non-specific lesions in the oral cavity can also be the result of malnutrition and drugs. Malnutrition, followed by anemia and mineral and vitamin deficiency, affects the oral cavity and teeth. Furthermore, all of the drug classes that are applied to the treatment of inflammatory bowel diseases can lead to alterations in the oral cavity due to the direct toxic effects of the drugs on oral tissues, as well as indirect immunosuppressive effects with a risk of developing opportunistic infections or bone marrow suppression. There is a higher occurrence of malignant diseases in patients with IBD, which is related to the disease itself and to the IBD-related therapy with a possible oral pathology. Treatment of oral lesions includes treatment of the alterations in the oral cavity according to the etiology together with treatment of the primary intestinal disease, which requires adequate knowledge and a strong cooperation between gastroenterologists and specialists in oral medicine.

Cannabis-induced acute pancreatitis.

Acute pancreatitis is a common disease. Despite the frequent use of cannabis worldwide, only six reports have described cases of acute pancreatitis secondary to the use of tetrahydrocannabinoid (THC). Here we describe two cases of THC-induced pancreatitis. The first case occurred in a 38-year-old man with multiple admissions for THC-induced pancreatitis; the second case involved a 22-year-old man with no previous medical history. In both cases, other possible causes of acute pancreatitis were ruled out.

Celiac disease associated with autoimmune hepatitis and autoimmune hyperthyroidism.

Although celiac disease (CD) may occur in patients with other immune-mediated disorders, its coexistence with multiple autoimmune diseases is not frequently described. We report the case of a 23-year-old woman referred to our centre because of jaundice and diarrhoea, who was diagnosed with CD in childhood. She complied with a gluten-free diet until puberty. Laboratory tests and liver biopsy were performed to establish the diagnosis of autoimmune hepatitis. Her thyroid- specific peroxides levels and thyroid gland function tests were altered as well, indicating the presence of an autoimmune disorder of the thyroid gland. Immunosuppressive treatment led to normalization of transaminases levels and bilirubin. In conclusion, other autoimmune diseases should be ruled out in patients with CD.

Splenic hematoma as a first manifestation of cytomegalovirus infection.

Splenic rupture is rare but life threatening complication of mononucleosis syndrome. It has been suggested that subcapsular splenic hematoma formation precedes rupture. The case of 44-year-old, previously healthy, male with splenic hematoma occurring after rising of heavy cargo is reported. Mononucleosis syndrome was suggested based on routine laboratory tests (elevated white blood cell count with predominance of lymphocytes and raised serum transaminases) and CMV infection was confirmed by serological test. Nonoperative management was used since the patient was hemodynamically stable with no further signs of splenic rupture. The same approach has been used in growing number of cases of patients with spontaneous splenic rupture in mononucleosis syndrome. Importance of considering splenic hematoma and/or rupture if abdominal pain occurs in the course of mononucleosis syndrome is outlined as well as importance of routine laboratory tests in suspecting mononucleosis syndrome in otherwise clinically silent patient.

Pyostomatitis vegetans associated with inflammatory bowel disease--report of two cases.

Pyostomatitis vegetans (PV) is a rare, chronic mucocutaneous disorder associated with inflammatory bowel disease (IBD). Oral lesions of PV are distinct and present as multiple white or yellow pustules with an erythematous base that coalesce and undergo necrosis to form a typical "snail tracks" appearance. Two cases of PV associated with IBD--one with Crohn's disease (CD) and the other with ulcerative colitis (UC) are reported. In the first case, adalimumab therapy brought the oral and gastrointestinal manifestations to complete remission. In the second case, the remission was achieved with systemic steroid therapy, but the disease relapsed after therapy discontinuation. Azathioprine was added leading to sustained remission of PV. Because of persistent active intestinal manifestation of UC, in spite of immunosuppressive therapy, infliximab was introduced. With the therapy remission of intestinal manifestation of UC was achieved as well. Our cases confirm previously reported good experience with immunomodulators and biologics in the treatment of PV. But, before using them we have to exclude an infectious etiology of oral lesions.

Inequalities in health related quality of life in Primorsko-goranska County, Croatia. How healthy are people using primary health care?

We present a cross sectional study on health related quality of life and EQ5D questionnaire practical use in Primorsko-goranska County in Croatia and inequalities in health between its sub regions with a potential application in regional policies social and healthcare organisation. Of 1066 participants that were patients at 42 family health physician's waiting room, women stood for 636 (59.7%) and men for 430 (40.3%). The most commonly reported problem was "Pain/discomfort" with 634 (59.5%) of all respondents and "Anxiety/depression" with 496 (46.6%). The worst health was reported within older age group and in a group with the lowest socio-economic status. Sub regional differences were found. The best health was reported in the suburbs of the town Rijeka and on the Islands, while the worst was reported in the Mountains. EQ5D is a simple and cost-effective instrument for measuring health related quality of life and recognising subgroups for identification of inequalities in the population.

3,4-methylenedioxymethamphetamine (MDMA): an important cause of acute hepatitis.

BACKGROUND: MDMA, i.e. 3,4-methylenedioxymethamphetamine ("Ecstasy"), occasionally produces significant hepatotoxicity in humans. It is characterized by a wide range of variability in clinical expression, ranging from asymptomatic liver injury, as observed by altered liver function tests, to acute hepatic failure. Prognostic factors that may predict the outcome of this condition remain unknown. CASE REPORT: We report a case of a 19-year-old male who presented deeplyjaundiced two weeks after ingestion of two tablets of Ecstasy. The clinical picture, laboratory data, and morphological studies were consistent with acute hepatitis. There was no evidence for a viral, alcoholic, metabolic, or autoimmune etiology of the disease. A mild clinical course with complete recovery after two months was observed. The presence of All molecule was confirmed in the patient. CONCLUSIONS: The possible association of specific human leukocyte antigen (HLA) phenotypes and MDMA-induced hepatotoxicity needs future evaluation.