ORCID Profile
0000-0001-9076-9793
Current Organisations
University Medical Centre Ljubljana
,
University of Ljubljana
,
University of Leeds
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Publisher: Oxford University Press (OUP)
Date: 27-01-2017
Publisher: Oxford University Press (OUP)
Date: 23-02-2023
Abstract: Solid organ transplantation, with the exception of liver, has rarely been reported in patients affected by inflammatory bowel diseases [IBD]. This is an ECCO-CONFER project collecting cases of solid organ transplants [with the exclusion of liver] that were performed in IBD patients. We evaluated the change in the IBD therapy, need for bowel resection due to medically refractory IBD, or need for hospitalisation due to IBD relapse [‘severe IBD course’] before and after transplantation. in total, 34 organ transplantations [28 kidney, five heart, one lung] in 33 IBD patients were collected [67% male, 55% Crohn’s disease, mean age 53 ± 16 years]. The median follow-up was 4.3 years (interquartile range [IQR] 3.2–10.7) 29 patients [87.9%] were treated with tacrolimus, 25 [76%] with systemic steroids, 22 [67%] with mycophenolate mofetil, 11 [33%] with everolimus, six with cyclosporine [18%]. One patient was treated with infliximab, two patients with adalimumab, two patients with vedolizumab, one patient with ustekinumab. Overall, a severe IBD course was observed in three [9.3%] patients before transplantation and in four [11.7%] in the post-transplant setting [p = 0.26]. Three cases of cancer [excluding skin non-melanoma] [9.1%] were recorded in the post-transplantation period versus two in the pre-transplantation period [6.1%, p = 0.04]. Six patients [18.2%] died during the period of observation. No deaths were associated with IBD or complications of the transplant. In IBD patients, solid organ transplantation does not seem to impact on the IBD severity. However, the risk of malignancy needs further investigation.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1FD90068D
Publisher: Elsevier BV
Date: 07-2021
Publisher: MDPI AG
Date: 03-05-2020
Abstract: Investigative systems for purified membrane transporters are almost exclusively reliant on the use of phospholipid vesicles or liposomes. Liposomes provide an environment to support protein function however, they also have numerous drawbacks and should not be considered as a “one-size fits all” system. The use of artificial vesicles comprising block co-polymers (polymersomes) offers considerable advantages in terms of structural stability provision of sufficient lateral pressure and low passive permeability, which is a particular issue for transport assays using hydrophobic compounds. The present investigation demonstrates strategies to reconstitute ATP binding cassette (ABC) transporters into hybrid vesicles combining phospholipids and the block co-polymer poly (butadiene)-poly (ethylene oxide). Two efflux pumps were chosen namely the Novosphingobium aromaticivorans Atm1 protein and human P-glycoprotein (Pgp). Polymersomes were generated with one of two lipid partners, either purified palmitoyl-oleoyl-phosphatidylcholine, or a mixture of crude E. coli lipid extract and cholesterol. Hybrid polymersomes were characterised for size, structural homogeneity, stability to detergents, and permeability. Two transporters, NaAtm1 and P-gp, were successfully reconstituted into pre-formed and surfactant-destabilised hybrid polymersomes using a detergent adsorption strategy. Reconstitution of both proteins was confirmed by density gradient centrifugation and the hybrid polymersomes supported substrate dependent ATPase activity of both transporters. The hybrid polymersomes also displayed low passive permeability to a fluorescent probe (calcein acetomethoxyl-ester (C-AM)) and offer the potential for quantitative measurements of transport activity for hydrophobic compounds.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1FD90066H
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Paul Beales.