Bisphosphonate’s effect in hepatic rat cells: An electron microscopy study

Σκοπός: Τα διφωσφονικά αποτελούν εκλεκτικούς αναστολείς της οστικής απορρόφησης και η μακροχρόνια χρήση τους έχει συσχετισθεί με ανεπιθύμητες επιδράσεις στο γαστρεντερικό σύστημα. Σκοπός της εργασίας είναι η διερεύνηση των πιθανών επιδράσεων των διφωσφονικών στη δομή των ηπατικών κυττάρων. Υλικά και μέθοδος: Ελήφθησαν δείγματα ηπατικού ιστού από δέκα θηλυκά ποντίκια Wistar ηλικίας δώδεκα μηνών που έλαβαν Αλενδρονάτη από του στόματος για 13 εβδομάδες και από δέκα θηλυκά ποντίκια Wistar ηλικίας δώδεκα μηνών που δεν έλαβαν το φάρμακο και χρησιμοποιήθηκαν ως μάρτυρες. Τα δείγματα μελετήθηκαν με το ηλεκτρονικό μικροσκόπιο. Αποτελέσματα: Στα ηπατικά κύτταρα των ποντικιών που έλαβαν Αλενδρονάτη βρέθηκαν εκτεταμένη απώλεια γλυκογόνου, διαφόρου μεγέθους κενοτόπια, διευρυμένα κολπώδη τριχοειδή, καθώς και απουσία των μικρολαχνών σε πολλά σημεία του χώρου του Disse. Συμπέρασμα: Πρόκειται για την πρώτη μελέτη με ηλεκτρονικό μικροσκόπιο ηπατικών δειγμάτων μετά τη χορήγηση διφωσφονικών, η οποία υποδεικνύει ήπια ηπατική βλάβη. Μια πιθανή συσχέτιση μεταξύ της χρήσης της Αλενδρονάτης και της ηπατικής λειτουργίας καθίσταται εμφανής. Ωστόσο, εξαιτίας του μικρού αριθμού δειγμάτων περισσότερες μελέτες είναι απαραίτητες ώστε να διαλευκανθεί αυτή η συσχέτιση.Purpose: Bisphosphonates (BPs) are selective inhibitors of osteoclast mediated bone resorption, used for the treatment of bone disorders as well as for tumors, whereas long-term bisphosphonate use is associated with adverse gastrointestinal effects. The objective of the study is to investigate the possible effects of BPs in hepatic structure. Materials and methods: Specimens from the liver of ten female 12-month old Wistar rats were used as control group and of ten female 12-month old Wistar rats to which Alendronate (Fosamax, Merck) was administered per os for 13 weeks, were used as experimental group. Samples were observed under a Transmission Electron Microscope. Results: In the experimental group, extensive depletion of the glycogen, different sized vacuoles and enlarged sinusoids were found in hepatic cells. Furthermore, there was lack of microvilli of hepatocytes in the Disse’s space. The same findings were reported in all sections of the experimental group. Conclusion: This is the first study of liver structure after the administration of bisphosphonates, with electron microscopy. This report, indicate the presence of mild hepatic damage in liver tissues studied. Our study demonstrates a possible correlation between alendronate administration and hepatic cell function, nevertheless due to the small specimen further research is needed

Acute severe ulcerative colitis flare complicated by myopericarditis and infliximab-induced hepatitis

Ulcerative colitis (UC) is an autoimmune disease associated with both intestinal and extraintestinal manifestations. The latter may include heart complications, such as myopericarditis leading to life-threatening arrythmias. Nowadays, UC is commonly treated with biologic medications and infliximab is the first line therapy in an outpatient setting, while it is also used as rescue therapy in acute severe UC. However, it has been associated with severe immunosuppression, cytomegalovirus (CMV) reactivation and drug-induced hepatitis. We report a case of UC flare in a biologic naïve patient admitted with myopericarditis, which was further complicated by positive CMV biopsies and infliximab-induced transaminitis

The importance of markers HLA6 and CD68 in placenta tissues of recurrent pregnancy loss

Introduction: Recurrent pregnancy loss of unknown etiology is correlated with immunological factors during pregnancy. Changes in leukocyte subpopulations and HLA (Human Leukocyte Antigen) expression take place in pregnant uterus on both decidua basalis and decidua parietalis in order to carry the semiallogenic embryo. These changes affect the pregnancy course.Objective: Our research is focused to enlighten the immunological changes that take place in the uterus of women with recurrent abortions of unknown etiology during first trimester of pregnancy.Materials and methods: The miscarriage group was obtained from 25 women who miscarried between the ages of 35 to 42 years and controls consisted of 25 healthy women between the ages of 27 to 39 years, who had electively terminated their pregnancies during first trimester of pregnancy. The abortion was processed and specimens taken were studied, using immunohistochemical methods. Specimens were taken from decidua basalis and decidua parietalis. Monoclonal antibodies were used against HLAG (Human Leukocyte Antigen G) and CD68 (Cluster of Differentiation 68). The results were statistically analysed with Mann-Whitney test.Results: HLA-G expression in decidua basalis from miscarriage group was found decreased.CD68 + cell expression was found increased in both deciduas from the miscarriage group.Conclusion: The immunological profile of women with recurrent miscarriage is quite different comparing with controls. A possible role of CD68+cells in RPL was observed .Changes in HLA-G expression was observed

Insulin receptor (IR) expression in human trophoblasts of recurrent pregnancy loss (RPL)

Purpose: Insulin and glucose pathways play a key role to fetal viability and growth. The focus of the study is to investigate the potential differences of immunohistochemical expression of IR in trophoblastic and decidual cells between women who had recurrent pregnancy loss and women that underwent an abortion. Materials and methods: Trophoblastic and decidual tissues from fifty (50) women with elective abortion used as control group and from fifty (50) women with recurrent miscarriages were collected during gestational weeks 6 to 12. IR antibodies were used as immunohistochemical staining markers. Nuclear and cytoplasmic expression was evaluated. Results: No IR immunohistochemical expression was detected in both trophoblastic cells of the implantation site and deciduas basalis of the two study groups. Conclusion: The effort made to enhance our knowledge on the physiology and histology of IR expression in connection with pregnancy was halted because the results were inconclusive. While studying, though, the correlation of recurrent miscarriage with IR expression, it became evident that a lot of hormones and pathways form the weave of gestational pathology and its delicate harmony. Every piece of knowledge may clarify this still obscure field

Interleukin expression in IBD patients and healthy controls before and after biologics

Interleukins are considered as targets for future IBD treatments. IL-19 and IL-24 are members of IL-10 family and through the JAK-STAT pathway induce proinflammatory cytokine production. IL-21 has proven to be involved in effector Th1, Th2 and Th17 responses. Similarly, IL-33, a newly identified cytokine, has been shown to control the Th1 effector response and the action of the colonic Tregs in animal models of colitis and patients with IBD. In this retrospective, single center immunohistochemistry study, IL-19, IL-24, IL-21and IL-33 expression was measured in 121 patients with moderate to severe IBD, before and 12 months after treatment with biologics. The results were statistically processed using SPSS. An increased IL-19 expression was found in IBD and CD group versus healthy controls. In the CD group, the IL-19 expression was related with the Harvey Bradshaw disease activity score, post biologic treatment. IL-24 was highly expressed in patients with active UC and CD and was increased post treatment. Its’ expression in UC post treatment was statistically related with the Mayo Score. Increased IL-21 expression was found in the UC and CD groups versus controls with no further correlation with disease activity before or after biologic treatment. The IL-33 expression was found to be increased in UC and CD groups post biologic treatment, suggesting a possible protective role of this interleukin against bowel inflammation. IL-21, IL-24, IL-19 και IL-33 are pivotal in IBD related intestinal inflammation and this was one of the first human studies to suggest that. An immunosuppressive role of IL-24 in UC patients and IL-19 in CD patients was suggested with statistical correlation with disease activity. An immunosuppressive role of IL-33 in both UC and CD patients was also suggested. A likely proinflammatory action of IL-21 was proposed, compared with healthy controls with no relation to disease activity or phenotype. This study supports a promising future use of these interleukins as diagnostic tools, biomarkers of severe disease and response to treatment and as potential therapeutic targets for novel monoclonal antibodies.Οι ιντερλευκίνες θεωρούνται μόρια-στόχοι για μελλοντικές θεραπείες στην ΙΦΝΕ. Οι IL-19 και IL-24 είναι μέλη της οικογένειας της IL-10 και μέσω του JAK-STAT προκαλούν την έκκριση προφλεγμονωδών κυτταροκινών, η ακριβής δράση τους όμως στην εντερική φλεγμονή δεν έχει αποκωδικοποιηθεί. Η IL-21 έχει αποδειχθεί ότι εμπλέκεται στις ανοσιακές απαντήσεις τύπου Th1, Th2 και Th17 ως προφλεγμονώδης κυτταροκίνη. Παρομοίως η IL-33, ρυθμίζει την έκφραση των Th1 κυτταροκινών και την λειτουργία των εντερικών Τ-ρυθμιστικών κυττάρων σε χημικά μοντέλα κολίτιδας και ασθενείς με ΙΦΝΕ. Σε αυτή την μελέτη, η έκφραση των IL-19, IL-24, IL-21 και IL-33, ταυτοποιήθηκε με την χρήση ανοσοϊστοχημείας σε 121 ασθενείς με μέτρια έως σοβαρή ΙΦΝΕ, πριν και μετά από 12 μήνες υπό αγωγή με βιολογικούς παράγοντες. Τα αποτελέσματα αναλύθηκαν στατιστικά με την χρήση SPSS. Μία αυξημένη έκφραση IL-19 βρέθηκε στην ομάδα των ασθενών με ΙΦΝΕ και ΝΚ σε σύγκριση με υγιείς μάρτυρες. Ειδικότερα, στην ομάδα ασθενών με ΝΚ, η έκφραση της IL-19 πριν και μετά την χορήγηση αγωγής, σχετίστηκε σημαντικά με το Harvey-Bradshaw Index score (HBI). Επιπλέον η IL-24 βρέθηκε αυξημένη σε ασθενείς με ενεργό ΕΚ και ΝΚ μετά την θεραπεία και η έκφρασή της στην ΕΚ βρέθηκε να σχετίζεται σημαντικά με το Mayo σκορ. H IL-21 βρέθηκε αυξημένη στους ασθενείς με ΙΦΝΕ σε σχέση με τους υγιείς μάρτυρες χωρίς όμως να συσχετίζεται με την χορήγηση αγωγής ή με την ενεργότητα της νόσου. Η έκφραση της IL-33 διαπιστώθηκε αυξημένη μετά την χορήγηση αγωγής στους ασθενείς με ΕΚ και ΝΚ, προτείνοντας ότι δρα πιθανότατα προστατευτικά στον εντερικό βλεννογόνο. Ειδικότερα στην ΝΚ, τα επίπεδα έκφρασης της IL-33 σχετίστηκαν στατιστικά με την ενεργότητα της νόσου σύμφωνα με το HBI. H συγκεκριμένη μελέτη αποτελεί μία από τις πρώτες μελέτες σε ανθρώπους, σχετικά με την ανοσοϊστοχημική έκφραση των IL-21, IL-24, IL-19 και IL-33 στον εντερικό βλεννογόνο ασθενών με ΙΦΝΕ και καταδεικνύει την σημασία τους στην εντερική φλεγμονή, υποστηρίζοντας την μελλοντική χρήση τους ως θεραπευτικούς στόχους, διαγνωστικούς δείκτες ή ως βιοδείκτες ανταπόκρισης στην αγωγή με βιολογικούς παράγοντες

Virtual Chromoendoscopy in Capsule Endoscopy: A Narrative Review

The usefulness of virtual chromoendoscopy (VC) in capsule endoscopy (CE) isa controversial issue, with conflicting studies regarding its efficacy. FICE and a blue filter were embedded in the PillCamTM software, with the aim to assist readers in identifying the source of obscure gastrointestinal (GI) bleeding (OGIB), coeliac disease mucosal changes and other small and large bowel lesions, including polyps and tumors. This review aims to summarize the existing evidence on the value of VC in the visualization and identification of different types of pathology. Overall, VC in CE with FICE 1 and 2 can be a useful adjunctive tool and may increase the visibility of pigmented lesions, such as angiectasias and ulcers. However, it does not appear to improve the detection of polyps or tumors. On the other hand, the role of FICE 3 and the blue filter appears to be limited. FICE may also be helpful in differentiating hyperplastic and adenomatous colonic polyps during colon capsule endoscopy, although more evidence is needed

Bioaccessibility and Oxidative Stability of Omega-3 Fatty Acids in Supplements, Sardines and Enriched Eggs Studied Using a Static In Vitro Gastrointestinal Model

Modern dietary habits have created the need for the design and production of functional foods enriched in bioactive compounds for a healthy lifestyle. However, the fate of many of these bioactive compounds in the human gastrointestinal (GI) tract has not been thoroughly investigated. Thus, in the present study, the bioaccessibility of omega-3 fatty acids was examined. To that end, different foods and supplements underwent simulated digestion following the INFOGEST protocol. The selected samples were foods rich in omega-3 fatty acids both in free and bound form—i.e., dietary fish oil supplements, heat-treated fish, and eggs enriched with omega-3 fatty acids. The oxidation of polyunsaturated fatty acids (PUFAs) was measured at each stage of the digestion process using peroxide value (PV) and TBARS and by quantifying individual omega-3 fatty acids using a gas chromatograph with flame ionization detector (GC-FID). The final bioaccessibility values of omega-3 fatty acids were determined. Changes in the quantity of mono-saturated fatty acids (MUFAs) and saturated fatty acids (SFAs) were recorded as well. The results indicated a profound oxidation of omega-3 fatty acids, giving rise to both primary and secondary oxidation products. Additionally, stomach conditions seemed to exert the most significant effect on the oxidation of PUFAs during digestion, significantly decreasing their bioaccessibility. The oxidation rate of each fatty acid was found to be strongly correlated with its initial concentration. Finally, the oxidation pattern was found to be different for each matrix and emulsified lipids seemed to be better protected than non-emulsified lipids. It is concluded that digestion has a profound negative effect on omega-3 bioaccessibility and therefore there is a need for improved protective mechanisms

Pyloric and foveolar type metaplasia are important diagnostic features in Crohn’s disease that are frequently missed in routine pathology

Pyloric type metaplasia (PYME) as evidence of chronic mucosal damage, is one of the main histopathological findings for diagnosing Crohn’s Disease (CD) in terminal ileum biopsies, according to the latest guidelines but still frequently underdiagnosed in routine pathology. Foveolar metaplasia (FOME) changes in mucosa, another aspect of the chronic post - inflammatory Ulcer Associated Cell Lineage (UACL), have only been reported in a few cases. However, their clinical significance has not been investigated in depth except in pouchitis. The aim of this study was to investigate the importance of meticulous study of terminal ileum biopsies for the recognition of PYME/FOME as an adjunct finding helpful for the diagnosis of CD. In the present study, two experienced gastrointestinal pathologists, have reviewed 105 terminal ileum biopsies from 105 patients with CD, using a protocol of 15 sections on average per biopsy. In 21% (22/105) of cases PYME was recognized and in 4% (4/105) FOME was also present. PYME/FOME had not been detected in 83% of these cases in the original reports. FOME was also identified in terminal ileum biopsies, a feature not reported previously in CD. Conclusively, PYME/FOME can be easily missed in terminal ileum biopsies from patients with suspected or known CD unless a meticulous study of the histologic material is carried out combined with awareness of the pathologist about its importance

Expression of peroxisome proliferator activation receptors (PPARs) and TNFα in placenta tissues in unexplained recurrent pregnancy loss: An immunohistochemical study

Introduction. PPAR expression in placenta tissues regulates proinflammatory cytokine production and preserves the quiescence of the uterus during pregnancy. PPAR-γ regulates inflammatory response during gestation while PPAR-δ and TNFα play a central role at implantation, decidualization and placentation. However, their expression levels affect normal pregnancy and may cause gestational complications and miscarriage. The aim of this report is to investigate the relationship of these molecules with unexplained recurrent miscarriage. Materials-methods. The miscarriage group was obtained from 12 women, between the ages of 35 to 42 years, who miscarried during the 1st trimester of gestation and controls consisted of 12 healthy women, between the ages of 27 to 39 years, who had electively terminated their pregnancies, during the 1st trimester of gestation. The abortion material was processed and specimens taken were studied using immunohistochemical methods. Specimens were taken from decidua basalis and decidua parietalis. Monoclonal antibodies were used against PPAR-γ (Peroxisome Proliferator Activation Receptor γ), PPAR-δ and TNFα (Tumor Necrosis Factor alpha). The results were statistically analyzed with Mann-Whitney test. Results. Our research identified PPAR-γ expression in decidua basalis and decidua parietalis from control group and decidua basalis from miscarriage group. PPAR-δ expression was also identified in both deciduas from both groups. Statistically, no significant change in PPAR-γ and PPAR-δ expression was observed between recurrent miscarriage group and controls. On the contrary, a statistically significant upregulation of TNFα was identified in both deciduas between miscarriage group and controls (p<0.05). Conclusions. Our evidence did not support a possible role of PPARs expression in recurrent pregnancy loss. However, a potential involvement of TNFα in the syndrome was reported. Further research should be performed due to insufficient bibliographic data

Is Panenteric Pillcam^TM Crohn’s Capsule Endoscopy Ready for Widespread Use? A Narrative Review

Patients diagnosed with Crohn’s disease are increasingly subjected to repeat colonoscopic and radiological examinations to assess the extent of the disease severity and the effects of treatment. PillcamTM Crohn’s video capsule, a modified colon capsule, was developed to generate a minimally invasive mouth to rectum video of the gastrointestinal tract. The capsule provides a wide-angle panoramic mucosal view to assess inflammation, ulceration, stenosis, disease extent, and effect of treatment. This review summarizes the evidence of its utility in both adult and paediatric Crohn’s disease and reviews the scoring systems used to quantify findings. The literature survey indicates that the PillcamTM Crohn’s capsule offers high sensitivity and specificity for the detection of inflammatory lesions and the extent and distribution of disease, and it could be considered a reliable imaging modality in both adults and childhood with Crohn’s disease