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- Gramignoli, R, et al.
(författare)
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Effects of Pro-Inflammatory Cytokines on Hepatic Metabolism in Primary Human Hepatocytes
- 2022
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 23:23
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Tidskriftsartikel (refereegranskat)abstract
- Three decades of hepatocyte transplantation have confirmed such a cell-based approach as an adjunct or alternative treatment to solid organ transplantation. Donor cell survival and engraftment were indirectly measured by hepatospecific secretive or released metabolites, such as ammonia metabolism in urea cycle defects. In cases of sepsis or viral infection, ammonia levels can significantly and abruptly increase in these recipients, erroneously implying rejection. Pro-inflammatory cytokines associated with viral or bacterial infections are known to affect many liver functions, including drug-metabolizing enzymes and hepatic transport activities. We examined the influence of pro-inflammatory cytokines in primary human hepatocytes, isolated from both normal donors or patients with metabolic liver diseases. Different measures of hepatocyte functions, including ammonia metabolism and phase 1–3 metabolism, were performed. All the hepatic functions were profoundly and significantly suppressed after exposure to concentrations of from 0.1 to 10 ng/mL of different inflammatory cytokines, alone and in combination. Our data indicate that, like phase I metabolism, suppression of phase II/III and ammonia metabolism occurs in hepatocytes exposed to pro-inflammatory cytokines in the absence of cell death. Such inflammatory events do not necessarily indicate a rejection response or loss of the cell graft, and these systemic inflammatory signals should be carefully considered when the immunosuppressant regiment is reduced or relieved in a hepatocyte transplantation recipient in response to such alleged rejection.
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- Davis, A. M., et al.
(författare)
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Evaluating the responsiveness of the ICOAP following hip or knee replacement
- 2010
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 18:8, s. 1043-1045
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Intermittent and Constant Osteoarthritis (OA) Pain (ICOAP) questionnaire evaluates the constructs of 'intermittent' and 'constant' pain. Theses are conceptually different from 'pain on activity' and pain 'intensity' as measured by the WOMAC and Chronic Pain Grade (CPG), measures commonly used in OA. The purpose of this study was to evaluate the responsiveness of the ICOAP, and different pain constructs in primary total hip (THR) and total knee (TKR) replacement. Methods: Patients completed the ICOAP, WOMAC and HOOS/KOOS pain and the CPG pre- and 6 months post surgery. Scores were standardized to 0 to 100, where higher scores indicate worse pain. Descriptive statistics were calculated for all data. The standardized response mean (SRM) was calculated for each measure as were correlations of change scores. Results: The THR group (n = 34) ranged in age from 37-85 years with 74% male. The TKR group (n = 44) ranged in age from 45-86 years with 75% female. Both groups had significant improvement (p < .0001) on all pain measures but the TKR group had smaller improvements. For THR, the SMR was 1.50, 2.31 and 2.29 for constant, intermittent and total scores and for TKR, was 0.84, 1.02 and 1.02 respectively. The SMR ranged from 2.05 to 2.99 for the other measures for THR and from 1.13 to 1.44 for TKR patients. Correlations of the change scores were ranged from 0.26 to 0.81. Conclusion: Multi-faceted constructs of pain are effectively relieved through joint replacement and all measures including the ICOAP demonstrated responsiveness. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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