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Retention of indoxyl sulfate in different genotypes of may explain variation in tacrolimus pharmacokinetics.
PeerJ
December 2024
Department of Pharmacy, Nanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
Background: Microbiota-derived toxins indoxyl sulfate and hippuric acid were previously reported to be associated with altered pharmacokinetics of the immunosuppressant tacrolimus in liver transplant recipients, and ABC transporter proteins are likely to be involved in the transport of such substances, but the role has not been elucidated. The aim of this study was to assess the retention of indoxyl sulfate and hippuric acid in the plasma of liver transplantation subjects carrying different genotypes of and (changes in transporter activity due to genetic variation), and to explore whether genetic variation is involved in altering the relationship between microbe-derived toxins and tacrolimus pharmacokinetics.
Methods: Liver transplantation subjects treated with the immunosuppressive regimen tacrolimus, corticosteroids, and mycophyolate mofetil were included and divided into normal renal function group and chronic kidney disease group.
Unlabelled: Genome-wide association studies have identified as an important non-MHC gene for islet autoimmunity and type 1 diabetes (T1D). In this study, we found a single haplotype significantly associated with increased risk for human T1D, and this haplotype carries the single nucleotide variant rs3184504*T in To better characterize the role of SH2B3 in T1D, we used mouse modeling and found a T cell-intrinsic role for SH2B3 regulating peripheral tolerance. SH2B3 deficiency had minimal effect on TCR signaling or proliferation across antigen doses, yet enhanced cell survival and cytokine signaling including common gamma chain-dependent and interferon-gamma receptor signaling.
View Article and Find Full Text PDFWhole body resistance training on functional outcomes of patients with Stage 4 or 5 chronic kidney disease: A systematic review.
Physiol Rep
August 2024
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Chronic kidney disease (CKD) causes skeletal muscle wasting, resulting in reduced function and inability to live independently. This systematic review critically appraised the scientific literature regarding the effects of full-body resistance training on clinically-relevant functional capacity measures in CKD. The study population included studies of people with Stage 4 or 5 CKD and a mean age of 40+ years old.
View Article and Find Full Text PDFThe reduced function allele SLCO1B1 c.521T>C is of no practical relevance for the renal graft function over the first post-transplant year in patients treated with mycophenolic acid.
Pharmacogenet Genomics
September 2024
Department of Pharmacology, Zagreb University School of Medicine, Zagreb Croatia.
Objective: It is unclear whether renal transplant recipients treated with mycophenolic acid (MPA) who carry the reduced-function allele at polymorphism SLCO1B1 c.521T>C differ from their wild-type peers regarding renal outcomes and tolerability. We aimed to estimate the effect of this polymorphism on the graft function (estimated glomerular filtration rate, eGFR) over the first 12 post-transplant months in patients on MPA-based maintenance immunosuppression.
View Article and Find Full Text PDFImpact of gallbladder hypoplasia on hilar hepatic ducts in biliary atresia.
Commun Med (Lond)
June 2024
Department of Veterinary Anatomy, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Background: Biliary atresia (BA) is an intractable disease of unknown cause that develops in the neonatal period. It causes jaundice and liver damage due to the destruction of extrahepatic biliary tracts,. We have found that heterozygous knockout mice of the SRY related HMG-box 17 (Sox17) gene, a master regulator of stem/progenitor cells in the gallbladder wall, exhibit a condition like BA.
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