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‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, IL‐12, IL‐13, TNFα and IFNɣ 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.
We correlated the amount of cytokines secreted by mucosal biopsies in ex vivo culture conditions overnight with disease activity scoring indices commonly used in the clinic (Mayo score, MES and UCEIS). We found that MES correlated with most measured cytokines. Contrarily, total UCEIS score correlated with the fewest of the measured cytokines, mostly due to two of its individual subscores, UCEIS Bleeding and UCEIS Erosions and Ulcers. Based on this, we propose UCEIS as a more subtle differentiator of donors with abundant tissue damage. (Created with BioRender.com)
Oral pathology in inflammatory bowel disease Miranda Muhvi?-Urek Marija Tomac-Stojmenovi? Brankica Mijandru?i?-Sin?i?
World journal of gastroenterology : WJG,
07/2016, Letnik:
22, Številka:
25
Journal Article
Odprti dostop
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.
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.
Gluten je bjelančevina koja se nalazi u pšenici, dok se u raži, ječmu i zobi nalaze slične bjelančevine. Zajedničkim imenom one se nazivaju gluten i mogu uzrokovati više različitih poremećaja koji se ...dijele na autoimune, alergijske i neautoimune – nealergijske. Samo se celijakija pojavljuje u genetski predisponiranih osoba te se manifestira crijevnim, ali i brojnim izvancrijevnim manifestacijama. Važno je točno dijagnosticirati poremećaje povezane s glutenom jer je njihovo liječenje različito. Velik broj ljudi samoinicijativno se odlučuje za bezglutensku dijetu pod utjecajem popularne literature. No, na taj se način otežava postavljanje točne dijagnoze i odgovarajuće terapije.
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-α4β7) and conventional medication protocols. The study included 20 IBD patients receiving anti-TNF-α therapy, 20 IBD patients receiving anti-integrin-α4β7 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.
The aim of this study was to investigate the presence of microaggregates of macrophages (CD68 positive cells) in macroscopically normal buccal mucosa in patients with inflammatory bowel disease ...(IBD). Fifty two patients with clinically and pathohistologically diagnosed IBD, thirty patients with Crohn's disease (CD), twenty two patients with ulcerative colitis (UC), and twenty five controls, matched for sex and age, were involved. The occurrence of CD-68 positive cells microaggregates was more frequent in CD patients comparing with UC patients (P = 0.0093), and the controls (P = 0.0001) respectively. There was no statistically significant difference in occurrence of CD-68 positive microaggregates in patients with positive microbiological findings (P = 0.8258). The results suggest that microaggregates of macrophages are more frequently present in apparently normal buccal mucosa in patients with CD than in patients with UC independently of microbiological findings. Therefore, it could be a potential marker for differentiating patients with Crohn's disease from UC patients, when standard tools failed. (doi: 10.5562/cca1779) Keywords: CD-68 microaggregates, buccal mucosa, CD, UC, predictive factors
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.
Cilj: Prikazati bolesnika s hepatocelularnim karcinomom koji je izravno invadirao desni atrij, a inicijalno se prezentirao bezbolnom žuticom i kardijalnom insuficijencijom. Prikaz slučaja: Na Zavod ...za gastroenterologiju zaprimljen je sedamdesetsedmogodišnji bolesnik zbog bezbolne žutice i kardijalne insuficijencije. U fizikalnom statusu uočeni su edemi obiju potkoljenica i natkoljenica te hepatomegalija. Laboratorijskom analizom utvrđene su povišene vrijednosti kreatinina u serumu, ukupnog bilirubina, jetrenih enzima te produženo protrombinsko vrijeme i aktivirano parcijalno tromboplastinsko vrijeme. Nativna snimka abdomena pokazala je uredan nalaz. U daljnjoj obradi učinjen je ultrazvuk abdomena na kojem je prikazana uvećana jetra, nepravilnije površine, difuzno hiperehogena, inhomogena, bez vidljivih fokalnih lezija uz proširenje intrahepatičnih žučnih vodova. Test na markere hepatitisa B i C bio je negativan. Zbog razjašnjavanja uzroka bilijarne opstrukcije indicirana je magnetska rezonancija abdomena i magnetnorezonantna kolangiopankreatografija (MRCP). Otkrivena je infiltrativna tumorska tvorba koja opsežno zahvaća žučne vodove, invadira donju šuplju venu i direktno prodire u desni atrij. Širokoiglenom biopsijom i patohistološkom analizom dijagnosticiran je hepatocelularni karcinom (HCC). Tijekom hospitalizacije ordinirana je kardijalna terapija, niskomolekularni heparin, supstitucija albumina i antibiotska terapija zbog infekcije bakterijom Clostridium difficile. Usprkos intenzivnom liječenju pacijent je preminuo s kliničkom slikom višeorganskog zatajenja. Zaključak: Izravna penetracija HCC-a u desni atrij rijedak je entitet. U bolesnika koji se prezentiraju bezbolnom žuticom uz negativan nalaz ultrazvuka, potrebno je proširiti slikovnu dijagnostiku na magnetsku rezonanciju i MRCP zbog superiornosti u procjeni bilijarnog stabla. Iako je žutica rijetka prva manifestacija hepatocelularnog karcinoma, ne treba isključiti taj entitet, posebice u bolesnika s jetrenom cirozom.
Aim: To report a case of a patient with hepatocellular carcinoma that directly invaded the right atrium, initially manifested with painless jaundice and cardiac insufficiency. Case report: A seventy-seven-year-old patient was admitted to the Department of Gastroenterology due to painless jaundice and cardiac insufficiency. Edema of both lower legs and thighs and hepatomegaly were observed in the physical status. Laboratory analysis revealed elevated serum creatinine, total bilirubin, liver enzymes and prolonged prothrombin time and activated partial thromboplastin time. Radiographic tomography showed no pathological finding. In further procedure, abdominal ultrasound was performed which revealed the enlarged liver with irregular surface, diffusely hyperechoic, inhomogeneous, without visible focal lesions with dilation of the intrahepatic bile ducts The test for hepatitis B and C markers were negative. To clarify the cause of biliary obstruction, abdominal magnetic resonance imaging and magnetic resonance cholangiopancreatography (MRCP) were indicated. An infiltrative tumor was detected that extensively affected the bile ducts, invaded the inferior vena cava, and penetrates directly into the right atrium. Hepatocellular carcinoma (HCC) was confirmed by core needle biopsy and histopathological examination. During hospitalization, cardiac therapy, low molecular weight heparin, albumin substitution, and antibiotic therapy for Clostridium difficile infection were prescribed. Despite the efforts and treatment, the patient passed away because of multiple organ failure. Conclusion: The extension of hepatocellular carcinoma per continuitatem into the right atrium is a rare entity. In the case of painless jaundice and negative ultrasound findings, it is necessary to extend the imaging diagnostics to magnetic resonance imaging and MRCP which is superior in the assessment of the biliary tree. Although jaundice is a rare manifestation of hepatocellular carcinoma, this entity should not be ruled out, especially in patients with liver cirrhosis.
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