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indoxyl sulfate

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https://www.readbyqxmd.com/read/28934349/the-association-between-acute-graft-versus-host-disease-and-antimicrobial-peptide-expression-in-the-gastrointestinal-tract-after-allogeneic-stem-cell-transplantation
#1
Daniela Weber, Katrin Frauenschläger, Sakhila Ghimire, Katrin Peter, Isabella Panzer, Andreas Hiergeist, Markus Weber, Daniel Kutny, Daniel Wolff, Matthias Grube, Elisabeth Huber, Peter Oefner, Andre Gessner, Thomas Hehlgans, Wolfgang Herr, Ernst Holler
Intestinal microbiota disruption is associated with acute gastrointestinal (GI) Graft-versus-Host Disease (GvHD) and poor outcome after allogeneic stem cell transplantation (ASCT). Here, in a retrospective analysis of 200 patients undergoing ASCT at the Regensburg University Medical Center, we assessed the relative expression of Paneth cell antimicrobial peptides (AMPs), Human Defensins (HD) 5 and 6 and regenerating islet-derived 3α (Reg3α), in 292 human intestinal biopsies as well as Reg3α serum levels in relation to acute GI GvHD...
2017: PloS One
https://www.readbyqxmd.com/read/28905671/microbiota-derived-uremic-retention-solutes-perpetrators-of-altered-nonrenal-drug-clearance-in-kidney-disease
#2
Alexander J Prokopienko, Thomas D Nolin
Scientific interest in the gut microbiota is increasing due to improved understanding of its implications in human health and disease. In patients with kidney disease, gut microbiota-derived uremic toxins directly contribute to altered nonrenal drug clearance. Microbial imbalances, known as dysbiosis, potentially increase formation of microbiota-derived toxins, and diminished renal clearance leads to toxin accumulation. High concentrations of microbiota-derived toxins such as indoxyl sulfate and p-cresol sulfate perpetrate interactions with drug metabolizing enzymes and transporters, which provides a mechanistic link between increases in drug-related adverse events and dysbiosis in kidney disease...
September 14, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28904431/role-of-gut-derived-uremic-toxins-on-oxidative-stress-and-inflammation-in-patients-with-chronic-kidney-disease
#3
S Gouroju, P V L N Srinivasa Rao, A R Bitla, K S Vinapamula, S M Manohar, S Vishnubhotla
Several cardiovascular disease (CVD) risk factors have been identified among patients with chronic kidney disease (CKD). Gut-derived uremic toxins (GDUT) are important modifiable contributors in this respect. There are very few Indian studies on GDUT changes in CKD. One hundred and twenty patients older than 18 years diagnosed with CKD were enrolled along with forty healthy subjects. The patients were classified into three groups of forty patients based on stage of CKD. Indoxyl sulfate (IS), para cresyl sulfate (p-CS), indole acetic acid (IAA), and phenol were estimated along with the assessment of oxidative stress (OS), inflammatory state, and bone mineral disturbance...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28888762/probiotic-supplementation-in-chronic-kidney-disease-a-double-blind-randomized-placebo-controlled-trial
#4
Natália A Borges, Flávia L Carmo, Milena B Stockler-Pinto, Jessyca S de Brito, Carla J Dolenga, Dennis C Ferreira, Lia S Nakao, Alexandre Rosado, Denis Fouque, Denise Mafra
OBJECTIVE: The objective of the study was to evaluate the effects of probiotic supplementation on the gut microbiota profile and inflammatory markers in chronic kidney disease patients undergoing maintenance hemodialysis (HD). DESIGN AND METHODS: This was a randomized, double-blind, placebo-controlled study. Forty-six HD patients were assigned to receive 1 of 2 treatments: probiotic (n = 23; Streptococcus thermophilus, Lactobacillus acidophilus e Bifidobacterialongum, 90 billion colony-forming units per day) or placebo (n = 23) daily for 3 months...
September 6, 2017: Journal of Renal Nutrition
https://www.readbyqxmd.com/read/28887287/characterization-of-simvastatin-acid-uptake-by-organic-anion-transporting-polypeptide-3a1-oatp3a1-and-influence-of-drug-drug-interaction
#5
Amandla Atilano-Roque, Melanie S Joy
Human organic anion transporting polypeptide 3A1 (OATP3A1) is predominately expressed in the heart. The ability of OATP3A1 to transport statins into cardiomyocytes is unknown, although other OATPs are known to mediate the uptake of statin drugs in liver. The pleiotropic effects and uptake of simvastatin acid were analyzed in primary human cardiomyocytes and HEK293 cells transfected with the OATP3A1 gene. Treatment with simvastatin acid reduced indoxyl sulfate-mediated reactive oxygen species and modulated OATP3A1 expression in cardiomyocytes and HEK293 cells transfected with the OATP3A1 gene...
September 6, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28871178/a-novel-mathematical-model-of-protein-bound-uremic-toxin-kinetics-during-hemodialysis
#6
Vaibhav Maheshwari, Stephan Thijssen, Xia Tao, Doris Fuertinger, Franz Kappel, Peter Kotanko
Protein-bound uremic toxins (PBUTs) are difficult to remove by conventional hemodialysis; a high degree of protein binding reduces the free fraction of toxins and decreases their diffusion across dialyzer membranes. Mechanistic understanding of PBUT kinetics can open new avenues to improve their dialytic removal. We developed a comprehensive model of PBUT kinetics that comprises: (1) a three-compartment patient model, (2) a dialyzer model. The model accounts for dynamic equilibrium between protein, toxin, and the protein-toxin complex...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28854439/mpges-1-derived-pge2-contributes-to-indoxyl-sulfate-induced-mesangial-cell-proliferation
#7
Shuzhen Li, Zhenzhen Sun, Guixia Ding, Wei Gong, Jing Yu, Weiwei Xia, Songming Huang, Aihua Zhang, Yue Zhang, Zhanjun Jia
BACKGROUND/AIMS: We previously reported that indoxyl sulfate (IS) could cause mesangial cell (MC) proliferation via a cyclooxygenase (COX)-2-dependent mechanism. However, the specific prostaglandin contributing to COX-2 effect on IS-induced MC proliferation remained unknown. Thus, the present study was undertaken to examine the role of microsomal prostaglandin E synthase-1 (mPGES-1)-derived Prostaglandin E2 (PGE2) in IS-induced MC proliferation. METHODS: IS was administered to the MCs with or without mPGES-1 siRNA pretreatment to induce the MC proliferation which was determined by cell cycle analysis, DNA synthesis, and the expressions of cyclins...
August 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28842637/untargeted-metabolomic-analysis-in-naturally-occurring-canine-diabetes-mellitus-identifies-similarities-to-human-type-1-diabetes
#8
Allison L O'Kell, Timothy J Garrett, Clive Wasserfall, Mark A Atkinson
While predominant as a disease entity, knowledge voids exist regarding the pathogenesis of canine diabetes. To test the hypothesis that diabetic dogs have similar metabolomic perturbations to humans with type 1 diabetes (T1D), we analyzed serum metabolomic profiles of breed- and body weight-matched, diabetic (n = 6) and healthy (n = 6) dogs by liquid chromatography-mass spectrometry (LC-MS) profiling. We report distinct clustering of diabetic and control groups based on heat map analysis of known and unknown metabolites...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811853/effects-of-sevelamer-hydrochloride-on-uremic-toxins-serum-indoxyl-sulfate-and-p-cresyl-sulfate-in-hemodialysis-patients
#9
Cheng-Jui Lin, Chi-Feng Pan, Chih-Kuang Chuang, Hsuan-Liang Liu, Sung-Fa Huang, Han-Hsiang Chen, Chih-Jen Wu
BACKGROUND: Beside the phosphate binding effect, non-calcium non-aluminum phosphate binder, namely sevelamer hydrochloride (SH), has many other effects in dialysis patients. It can absorb many other compounds, decrease low-density lipoprotein cholesterol (LDL-C) level, and attenuate the progression of vascular calcification; it has been reported to have anti-inflammatory effect. However, it is not clear whether it has any effect on uremic toxins, i.e. serum indoxyl sulfate (IS) and p-cresyl sulfate, (PCS) in hemodialysis (HD) patients...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28791957/aryl-hydrocarbon-receptor-ahr-and-its-endogenous-agonist-indoxyl-sulfate-in-chronic-kidney-disease
#10
REVIEW
Tomasz Kamiński, Małgorzata Michałowska, Dariusz Pawlak
The indoxyl sulfate (IS, indoxyl sulphate) is the end product of dietary tryptophan degradation by indole pathway and significantly higher serum and tissue concentrations of this compound is observed in patients with impaired renal function. Despite the high albumin binding affinity, the remaining free fraction of IS has a number of biological effects related to the generation of oxidative stress andactivation of signaling pathways related to NF-кB, p53 protein, STAT3, TGF-β and Smad2/3. IS induces the inflammatory process, exerts nephrotoxic activity and is also a factor impairing the cardiovascular system...
July 30, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28781957/indoxyl-sulfate-a-uremic-toxin-in-chronic-kidney-disease-suppresses-both-bone-formation-and-bone-resorption
#11
Kenta Watanabe, Tsukasa Tominari, Michiko Hirata, Chiho Matsumoto, Junya Hirata, Gillian Murphy, Hideaki Nagase, Chisato Miyaura, Masaki Inada
Abnormalities of bone turnover are commonly observed in patients with chronic kidney disease (CKD), and the low-turnover bone disease is considered to be associated with low serum parathyroid hormone (PTH) levels and skeletal resistance to PTH. Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood of patients with CKD. Recently, we have reported that IS exacerbates low bone turnover induced by parathyroidectomy (PTX) in adult rats, and suggested that IS directly induces low bone turnover through the inhibition of bone formation by mechanisms unrelated to skeletal resistance to PTH...
August 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28754616/role-of-uremic-toxin-indoxyl-sulfate-in-the-progression-of-cardiovascular-disease
#12
REVIEW
Huichang Gao, Shan Liu
The prevalence of cardiovascular disease (CVD) among patients with chronic kidney disease (CKD) is relatively high. Deterioration of renal function in CKD leads to accumulation of indoxyl sulfate, a tryptophan metabolite produced by gut microbiota. It is acknowledged that indoxyl sulfate is capable to stimulate oxidative stress, which in turn contributes to the progression of vascular disorders and its resultant coronary artery disease. Recent research have demonstrated the adverse effects of indoxyl sulfate on the heart, together with the acceleration of vascular dysfunction, suggesting that indoxyl sulfate might contribute to high prevalence of CVD in CKD...
July 25, 2017: Life Sciences
https://www.readbyqxmd.com/read/28753957/the-uremic-toxin-indoxyl-sulfate-accelerates-thrombotic-response-after-vascular-injury-in-animal-models
#13
Malgorzata Karbowska, Tomasz W Kaminski, Natalia Marcinczyk, Tomasz Misztal, Tomasz Rusak, Lukasz Smyk, Dariusz Pawlak
Chronic kidney disease (CKD) patients are at high risk for thrombotic events. Indoxyl sulfate (IS) is one of the most potent uremic toxins that accumulates during CKD. Even though IS is associated with an increased risk for cardiovascular disease, its impact on thrombotic events still remains not fully understood. The purpose of the study was to evaluate the direct effect of IS on thrombotic process. We examined the impact of acute exposure to IS on thrombus development induced by electric current in Wistar rats, intravital thrombus formation after laser-induced injury in the mice endothelium, coagulation profile, clot formation dynamics, platelet aggregations, and erythrocyte osmotic resistance...
July 19, 2017: Toxins
https://www.readbyqxmd.com/read/28747155/indole-3-acetic-acid-indoxyl-sulfate-and-paracresyl-sulfate-do-not-influence-anemia-parameters-in-hemodialysis-patients
#14
Stanislas Bataille, Marion Pelletier, Marion Sallée, Yvon Berland, Nathalie McKay, Ariane Duval, Stéphanie Gentile, Yosra Mouelhi, Philippe Brunet, Stéphane Burtey
BACKGROUND: The main reason for anemia in renal failure patients is the insufficient erythropoietin production by the kidneys. Beside erythropoietin deficiency, in vitro studies have incriminated uremic toxins in the pathophysiology of anemia but clinical data are sparse. In order to assess if indole 3-acetic acid (IAA), indoxyl sulfate (IS), and paracresyl sulfate (PCS) -three protein bound uremic toxins- are clinically implicated in end-stage renal disease anemia we studied the correlation between IAA, IS and PCS plasmatic concentrations with hemoglobin and Erythropoietin Stimulating Agents (ESA) use in hemodialysis patients...
July 26, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28739139/results-of-the-hemo-study-suggest-that-p-cresol-sulfate-and-indoxyl-sulfate-are-not-associated-with-cardiovascular-outcomes
#15
Tariq Shafi, Tammy L Sirich, Timothy W Meyer, Thomas H Hostetter, Natalie S Plummer, Seungyoung Hwang, Michal L Melamed, Tanushree Banerjee, Josef Coresh, Neil R Powe
Cardiovascular disease, the leading cause of mortality in hemodialysis patients, is not fully explained by traditional risk factors. To help define non-traditional risk factors, we determined the association of predialysis total p-cresol sulfate, indoxyl sulfate, phenylacetylglutamine, and hippurate with cardiac death, sudden cardiac death, and first cardiovascular event in the 1,273 participants of the HEMO Study. The results were adjusted for potential demographic, clinical, and laboratory confounders. The mean age of the patients was 58 years, 63% were Black and 42% were male...
July 21, 2017: Kidney International
https://www.readbyqxmd.com/read/28727768/benign-and-tumor-parenchyma-metabolomic-profiles-affect-compensatory-renal-growth-in-renal-cell-carcinoma-surgical-patients
#16
Barak Rosenzweig, Nimrod D Rubinstein, Ed Reznik, Roman Shingarev, Krishna Juluru, Oguz Akin, James J Hsieh, Edgar A Jaimes, Paul Russo, Katalin Susztak, Jonathan A Coleman, A Ari Hakimi
BACKGROUND AND OBJECTIVES: Pre-operative kidney volume is an independent predictor of glomerular filtration rate in renal cell carcinoma patients. Compensatory renal growth (CRG) can ensue prior to nephrectomy in parallel to tumor growth and benign parenchyma loss. We aimed to test whether renal metabolite abundances significantly associate with CRG, suggesting a causative relationship. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Tissue metabolomics data from 49 patients, with a median age of 60 years, were previously collected and the pre-operative fold-change of their contra to ipsi-lateral benign kidney volume served as a surrogate for their CRG...
2017: PloS One
https://www.readbyqxmd.com/read/28706886/the-effects-of-indoxyl-sulfate-induced-endothelial-microparticles-on-neointimal-hyperplasia-formation-in-an-ex-vivo-model
#17
Jung-Hwa Ryu, HeeJung Park, Seung-Jung Kim
PURPOSE: Neointimal hyperplasia (NH) is considered to be one of the main causes of vascular access occlusion in patients receiving hemodialysis. Endothelial injury and TGF-β-mediated proliferation of vascular smooth muscle cells (VSMCs) induce NH. Endothelial microparticles (EMPs) are also increased by endothelial injury. We aimed to investigate the effects of EMPs and TGF-β expression on VSMC proliferation and their contributions to NH formation in an ex vivo model. METHODS: EMPs were collected from the culture media of human umbilical vein endothelial cells treated with indoxyl sulfate (IS, 250 µg/mL) after ultracentrifugation at 100,000 × g...
July 2017: Annals of Surgical Treatment and Research
https://www.readbyqxmd.com/read/28696247/microrna-92a-mediates-endothelial-dysfunction-in-ckd
#18
Fenqing Shang, Shen-Chih Wang, Chien-Yi Hsu, Yifei Miao, Marcy Martin, Yanjun Yin, Chih-Cheng Wu, Yun-Ting Wang, Gaihong Wu, Shu Chien, Hsien-Da Huang, Der-Cherng Tarng, Yan-Ting Shiu, Alfred K Cheung, Po-Hsun Huang, Zhen Chen, John Y-J Shyy
CKD is an independent risk factor for cardiovascular disease (CVD). The accumulation of uremic toxins in CKD induces oxidative stress and endothelial dysfunction. MicroRNA-92a (miR-92a) is induced by oxidative stress in endothelial cells (ECs) and involved in angiogenesis and atherosclerosis. We investigated a role for oxidative stress-responsive miR-92a in CKD. Our study of patients at three clinical sites showed increased serum miR-92a level with decreased kidney function. In cultured ECs, human CKD serum or uremic toxins (such as indoxyl sulfate), compared with non-CKD serum, induced the levels of miR-92a and suppressed the expression of miR-92a targets, including key endothelial-protective molecules...
July 10, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28694431/key-role-for-the-organic-anion-transporters-oat1-and-oat3-in-the-in-vivo-handling-of-uremic-toxins-and-solutes
#19
Wei Wu, Kevin T Bush, Sanjay K Nigam
In vitro data indicates that the kidney proximal tubule (PT) transporters of uremic toxins and solutes (e.g., indoxyl sulfate, p-cresol sulfate, kynurenine, creatinine, urate) include two "drug" transporters of the organic anion transporter (OAT) family: OAT1 (SLC22A6, originally NKT) and OAT3 (SLC22A8). Here, we have examined new and prior metabolomics data from the Oat1KO and Oat3KO, as well as newly obtained metabolomics data from a "chemical double" knockout (Oat3KO plus probenecid). This gives a picture of the in vivo roles of OAT1 and OAT3 in the regulation of the uremic solutes and supports the centrality of these "drug" transporters in independently and synergistically regulating uremic metabolism...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28659803/indoxyl-sulfate-affects-glial-function-increasing-oxidative-stress-and-neuroinflammation-in-chronic-kidney-disease-interaction-between-astrocytes-and-microglia
#20
Simona Adesso, Tim Magnus, Salvatore Cuzzocrea, Michela Campolo, Björn Rissiek, Orlando Paciello, Giuseppina Autore, Aldo Pinto, Stefania Marzocco
Indoxyl sulfate (IS) is a protein-bound uremic toxin resulting from the metabolism of dietary tryptophan which accumulates in patients with impaired renal function, such as chronic kidney disease (CKD). IS is a well-known nephrovascular toxin but little is known about its effects on central nervous system (CNS) cells. Considering the growing interest in the field of CNS comorbidities in CKD, we studied the effect of IS on CNS cells. IS (15-60 μM) treatment in C6 astrocyte cells increased reactive oxygen species release and decreased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation, and heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 expression...
2017: Frontiers in Pharmacology
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