ORCID Profile
0000-0002-8273-5048
Current Organisation
University of Adelaide
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Publisher: Wiley
Date: 30-07-2020
DOI: 10.1002/JCP.29976
Publisher: Wiley
Date: 19-03-2021
DOI: 10.1111/BCP.14806
Abstract: Long‐term use of the immunosuppressant tacrolimus is limited by nephrotoxicity. Following renal transplantation, the risk of nephrotoxicity may be determined more by allograft than by blood tacrolimus concentrations, and thus may be affected by donor CYP3A5 and ABCB1 genetics. Little is known regarding factors that determine tacrolimus intrarenal exposure. This study investigated the relationship between trough blood ( C 0Blood ) and allograft ( C Graft ) tacrolimus concentrations and tacrolimus dose, haematocrit, genetics, acute nephrotoxicity, rejection status, delayed graft function, and time post‐transplant. C 0Blood and C Graft were quantified in 132 renal transplant recipients together with recipient and donor CYP3A5 (rs776746) and ABCB1 3435 (rs1045642) genotypes. C 0Blood ranged from 2.6 to 52.3 ng/mL and C Graft from 33 to 828 pg/mg tissue. Adjusting for dose, recipients who were CYP3A5 expressors had lower C 0Blood compared to nonexpressors, whilst delayed graft function was associated with higher C 0Blood . Linear regression showed that the significant predictors of C Graft were C 0Blood (point‐wise P = 7 × 10 −10 ), dose ( P = .004) acute nephrotoxicity ( P = .002) and an interaction between C 0Blood and acute tacrolimus nephrotoxicity ( P = .0002), with an adjusted r 2 = 0.35 and no contribution from donor or recipient CYP3A5 or ABCB1 genotype. The association between C Graft and acute nephrotoxicity depended on one very high C Graft (828 pg/mg tissue). Recipient and donor CYP3A5 and ABCB1 3435C T genotypes are not determinants of allograft tacrolimus exposure in kidney transplant recipients. However, tacrolimus dose and C 0Blood were significant predictors of C Graft , and the relationship between C 0Blood and C Graft appeared to differ in the presence or absence of acute nephrotoxicity.
Publisher: MDPI AG
Date: 26-10-2021
Abstract: Gulf War illness (GWI) encompasses a constellation of persistent debilitating symptoms associated with significant changes in central nervous system (CNS) and immune functioning. Currently, there is no validated biomarker for GWI risk susceptibility. Given the impact of immune responses linked to GWI symptomology, genetic variability that causes persistent inflammatory/immune alterations may be key. This Boston University-based Gulf War Illness Consortium (GWIC) study investigated the impact of single nucleotide polymorphisms (SNPs) in variants of immune and pain genetic markers IL1B, IL2, IL6, IL6R, IL10, TNF, TGF, TLR2, TLR4, MD2, MYD88, BDNF, CRP, ICE, COMT and OPRM1 on GWI occurrence in a Caucasian subset of Gulf War (GW) veterans with (cases, n = 170) and without (controls, n = 34) GWI. Logistic regression modeling created a prediction model of GWI risk that associated genetic variability in TGF (rs1800469, p = 0.009), IL6R (rs8192284, p = 0.004) and TLR4 (rs4986791, p = 0.013) with GWI occurrence. This prediction model was specific and sensitive, with a receiver operator characteristic area under the curve of 71.4%. This is the first report of immune genetic variability being predictive of GWI and warrants validation in larger independent cohorts. Future reports will present interactions of these genetic risk factors with other characteristics of GW service.
Publisher: Wiley
Date: 24-07-2019
DOI: 10.1111/BCP.14034
Publisher: MDPI AG
Date: 28-08-2023
Abstract: Adverse effects are a common consequence of cytotoxic cancer treatments. Over the last two decades there have been significant advances in exploring the relationship between the gut microbiome and these adverse effects. Changes in the gut microbiome were shown in multiple clinical studies to be associated with the development of acute gastrointestinal adverse effects, including diarrhoea and mucositis. However, more recent studies showed that changes in the gut microbiome may also be associated with the long-term development of psychoneurological changes, cancer cachexia, and fatigue. Therefore, the aim of this review was to examine the literature to identify potential contributions and associations of the gut microbiome with the wide range of adverse effects from cytotoxic cancer treatments.
No related grants have been discovered for Janet Coller.