| 1. |
- Bagge, Jasmine, et al.
(författare)
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Mucosal Recovery after Intestinal Transplantation in the Rat: A Sequential Histological and Molecular Assessment
- 2023
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Ingår i: European Surgical Research. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 64:2, s. 201-210
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Intestinal cold ischemia and subsequent reperfusion during transplantation result in various degrees of mucosal injury ranging from mild edema to extensive mucosal loss. Mucosal barrier impairment favours bacterial translocation and fluid loss and raises nutritional challenges. The injured intestine also releases proinflammatory mediators and upregulates various epitopes towards an inflammatory phenotype. We studied the process of mucosal injury and repair during the early period after intestinal transplantation from a histological and molecular standpoint.Materials and Methods Adult Sprague Dawley rats were used as donors and recipients. Donor intestines were perfused and stored in saline for 3 hours, then transplanted heterotopically using microvascular anastomoses. Intestinal graft segments were obtained after 20 minutes, 6 hours, 12 hours, and 24 hours after reperfusion. Histology studies (goblet cell count, morphometry), immunofluorescence and western blot for several tight junction proteins, apoptosis and inflammation related proteins were performed.Results Cold storage led to extensive epithelial detachment, whereas reperfusion resulted in extensive villus loss (about 60 % of the initial length) and goblet cell numbers were drastically reduced. Over the first 24 hours, gradual morphologic and molecular recovery was noted, although several molecular alterations persisted (increased apoptosis and inflammation, altered expression of several tight junctions).Conclusions The current data suggest that a near-complete morphologic recovery from a moderate mucosal injury occurs within the first 24 hours after intestinal transplantation. However, several molecular alterations persist and need to be considered when designing intestinal transplant experiments and choosing sampling and endpoints.
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| 2. |
- Oltean, Mihai, 1976, et al.
(författare)
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Covid-19 in kidney transplant recipients: a systematic review of the case series available three months into the pandemic.
- 2020
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Ingår i: Infectious diseases (London, England). - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 52:11, s. 830-7
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) ranges from a mild illness to acute respiratory distress syndrome (ARDS), multiorgan dysfunction, and death. Transplant recipients are vulnerable due to comorbidities and immunosuppressants that render them susceptible to infections. The information on COVID-19 in kidney transplant recipients remains limited to small case series.A systematic literature search was conducted, and 12 case series totalling 204 kidney transplant recipients with COVID-19 were identified. Data were extracted, pooled and analysed.Most patients (74%) were men. The most frequent symptoms were fever (76%), cough (64%) and dyspnoea (43%). At admission, over 70% of the patients had abnormal radiological findings. Leukocyte counts were in the lower normal range. C-reactive protein, ferritin, and D-dimer were consistently increased. Treatments included lowering immunosuppression, hydroxychloroquine, antivirals, tocilizumab and intravenous immunoglobulins. Thirty-one percent of the patients were admitted to intensive care units (ICUs), and 16% required intubation. The overall mortality was 21.2%. Patients who died were significantly older than those who survived (61±12 vs. 51±15, p<.01). Logistic regression revealed that the odds for death increased by 4.3% for each additional year of age (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.005-1.083, p value=.0265).No substantial conclusions could be drawn on the efficacy of any particular treatment. More rigorous patient stratification is needed when analysing and reporting data to facilitate future meta-analyses.
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| 3. |
- Oltean, Mihai, 1976, et al.
(författare)
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The proteomic signature of intestinal acute rejection in the mouse
- 2022
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal acute rejection (AR) lacks a reliable non-invasive biomarker and AR surveillance is conducted through frequent endoscopic biopsies. Although citrulline and calprotectin have been suggested as AR biomarkers, these have limited clinical value. Using a mouse model of intestinal transplantation (ITx), we performed a proteome-wide analysis and investigated rejection-related proteome changes that may eventually be used as biomarkers. ITx was performed in allogenic (Balb/C to C57Bl) and syngeneic (C57Bl) combinations. Graft samples were obtained three and six days after transplantation (n = 4/time point) and quantitative proteomic analysis with iTRAQ-labeling and mass spectrometry of whole tissue homogenates was performed. Histology showed moderate AR in all allografts post-transplantation at day six. Nine hundred and thirty-eight proteins with at least three unique peptides were identified in the intestinal grafts. Eighty-six proteins varying by >20% between time points and/or groups had an alteration pattern unique to the rejecting allografts: thirty-seven proteins and enzymes (including S100-A8 and IDO-1) were significantly upregulated whereas forty-nine (among other chromogranin, ornithine aminotransferase, and arginase) were downregulated. Numerous proteins showed altered expression during intestinal AR, several of which were previously identified to be involved in acute rejection, although our results also identified previously unreported proteome changes. The metabolites and downstream metabolic pathways of some of these proteins and enzymes may become potential biomarkers for intestinal AR.
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| 4. |
- Söfteland, John M., 1977, et al.
(författare)
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Luminal polyethylene-glycol solution delays the onset of preservation injury in the human intestine.
- 2021
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Ingår i: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. - : Elsevier BV. - 1600-6143. ; 21:6, s. 2220-2230
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Tidskriftsartikel (refereegranskat)abstract
- The organ damage incurred during the cold storage (CS) of intestinal grafts has short and long-term consequences. Animal studies suggest that additional luminal preservation (LP) with polyethylene-glycol (PEG) may alleviate this damage. This study aims to validate these findings using human intestines. Ileal segments, perfused intravascularly with IGL-1 solution, were procured from 32 multiorgan donors and divided into two parts: one containing a PEG 3350-based solution introduced luminally (LP group) and another one without luminal treatment (control). Sampling was performed after 4h, 8h, 14h, and 24h of CS. Histology was assessed using the Chiu/Park score. Tight junctions (TJ), several inflammatory markers, and transcription factors were examined by immunofluorescence, ddPCR, and Western blot. Tissue water content (edema) was also measured. Apoptotic activity was assessed with caspase 2,3 and 9 assays. LP significantly lowered mucosal injury at all time points. Redistribution of TJ proteins occurred earlier and more severely in the control group. After 24h of CS, LP intestines showed an emerging unfolding protein response. Increased caspase-3 and -9 activity were found in the control group. The current results indicate that luminal PEG is safe and effective in reducing damage to the intestinal epithelium during CS.
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