Fibroblasts Express Immune Relevant Genes and Are Important Sentinel Cells during Tissue Damage in Rainbow Trout (Oncorhynchus mykiss)

Fibroblasts have shown to be an immune competent cell type in mammals. However, little is known about the immunological functions of this cell-type in lower vertebrates. A rainbow trout hypodermal fibroblast cell-line (RTHDF) was shown to be responsive to PAMPs and DAMPs after stimulation with LPS from E. coli, supernatant and debris from sonicated RTHDF cells. LPS was overall the strongest inducer of IL-1β, IL-8, IL-10, TLR-3 and TLR-9. IL-1β and IL-8 were already highly up regulated after 1 hour of LPS stimulation. Supernatant stimuli significantly increased the expression of IL-1β, TLR-3 and TLR-9, whereas the debris stimuli only increased expression of IL-1β. Consequently, an in vivo experiment was further set up. By mechanically damaging the muscle tissue of rainbow trout, it was shown that fibroblasts in the muscle tissue of rainbow trout contribute to electing a highly local inflammatory response following tissue injury. The damaged muscle tissue showed a strong increase in the expression of the immune genes IL-1β, IL-8 and TGF-β already 4 hours post injury at the site of injury while the expression in non-damaged muscle tissue was not influenced. A weaker, but significant response was also seen for TLR-9 and TLR-22. Rainbow trout fibroblasts were found to be highly immune competent with a significant ability to express cytokines and immune receptors. Thus fish fibroblasts are believed to contribute significantly to local inflammatory reactions in concert with the traditional immune cells

Dissecting the physiology and pathophysiology of glucagon-like peptide-1

Copyright © 2018 Paternoster and Falasca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. An aging world population exposed to a sedentary life style is currently plagued by chronic metabolic diseases, such as type-2 diabetes, that are spreading worldwide at an unprecedented rate. One of the most promising pharmacological approaches for the management of type 2 diabetes takes advantage of the peptide hormone glucagon-like peptide-1 (GLP-1) under the form of protease resistant mimetics, and DPP-IV inhibitors. Despite the improved quality of life, long-term treatments with these new classes of drugs are riddled with serious and life-threatening side-effects, with no overall cure of the disease. New evidence is shedding more light over the complex physiology of GLP-1 in health and metabolic diseases. Herein, we discuss the most recent advancements in the biology of gut receptors known to induce the secretion of GLP-1, to bridge the multiple gaps into our understanding of its physiology and pathology

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Bisfosfonatindusert osteonekrose i kjevene : Litteraturstudie og pasientundersøkelse

Osteonekrose i kjeven ved bruk av bisfosfonater (BONJ) ble først beskrevet av kjevekirurgen R.E. Marx i 2003 [27]. Siden da har det vært en eksponentiell økning i antall rapporterte tilfeller, og det har den siste tiden blitt klart at også osteoporosepasienter utgjør en andel av de som er rammet. Hittil har man ikke klart å finne noen kurativ behandling. Det ble skrevet en oppgave om bisfosfonater av to studenter på foregående kull. Noe av tanken var at vi skulle bygge videre på denne, først og fremst ved å gå gjennom den nye litteraturen som er tilkommet i løpet av 2007. Vi ville forsøke å ha en annen vinkling på vår oppgave ved å belyse andre deler av temaet. Videre ønsket vi å undersøke om det var flere fellestrekk ved de pasientene på bisfosfonatterapi som utviklet osteonekrose i kjevene. Derfor hadde vi også som mål å følge opp pasienter med bisfosfonatindusert osteonekrose, som behandles ved Det Odontologiske Fakultet i Oslo. Selv om forekomsten er lav i Norge, er dette en alvorlig diagnose og påvirker livskvaliteten for de som rammes. Vi hadde hatt noe undervisning om emnet, men følte oss ikke kompetente til å møte problemet i praksis

Musculoskeletal manifestations in inflammatory bowel disease and their association with health-related quality of life and fatigue: Results after 20 years of follow-up in the prospective and population-based IBSEN study

Patients with inflammatory bowel disease (IBD), a chronic gastrointestinal disease, often suffer from extraintestinal manifestations. These present most commonly as musculoskeletal conditions encompassing axial and peripheral spondyloarthritides. IBD, spondyloarthritides and pain may all have a negative impact on physical health as well as quality of life. The aims of this thesis were to investigate the occurrence of musculoskeletal manifestations in IBD patients after long-term disease, and to assess whether such manifestations were associated with quality of life and fatigue. This thesis emanates from the IBSEN study, a prospective population-based cohort following IBD patients for 20 years after diagnosis. The classification of musculoskeletal manifestations, as well as quality of life and fatigue, were based on questionnaires and clinical assessments at pre-scheduled follow-ups. After 20 years, 599 (79.2 %) from the original cohort were alive, of whom 470 (78.5 %) participated at the final follow-up. A detailed rheumatic questionnaire enabled classification of the musculoskeletal conditions, and the 441 patients (93.8 %) who completed this, were included in this thesis. Ankylosing spondylitis (Bekhterev’s disease) was found in 4.5 % of the patients, axial spondyloarthritis in 7.7 %, and peripheral spondyloarthritis in 27.9 %, while ongoing arthralgia (joint pain) or back pain was reported by more than 45 % of the patients. Arthralgia and back pain were associated with reduced quality of life and fatigue, but after adjusting for possible confounders, the diagnosis spondyloarthritis (axial and peripheral combined) was not. A high occurrence of musculoskeletal symptoms and diagnoses was found in IBD patients 20 years after diagnosis. The impact these symptoms can have on quality of life, underlines the importance of awareness regarding the coexistence of IBD with musculoskeletal manifestations in both clinical follow-up and treatment