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Renal proximal tubule

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https://www.readbyqxmd.com/read/28077323/high-glucose-down-regulates-microrna-181a-5p-to-increase-pro-fibrotic-genes-expression-by-targeting-early-growth-response-factor-1-in-hk-2-cells
#1
Ping Xu, Mei-Ping Guan, Jian-Gang Bi, Dan Wang, Zong-Ji Zheng, Yao-Ming Xue
Tubulointerstitial fibrosis (TIF) plays an important role in the progression of renal fibrosis in diabetic nephropathy (DN). Accumulating evidence supports a crucial effect of early growth response factor 1 (Egr1) on renal fibrosis in DN, but the underlying mechanisms are not entirely clear. Here, we explored the aggravating role of Egr1 and identified microRNA-181a-5p (miR-181a-5p) as an upstream regulator of Egr1 in TIF of DN. We demonstrated that overexpression of Egr1 enhanced, whereas small interfering RNA targeting Egr1 decreased the expressions of transforming growth factor β1 (TGF-β1) and fibrosis-related genes including fibronectin and collagen I in human proximal tubule cell line (HK-2) cells...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28076831/dosing-time-dependent-oxidative-effects-of-an-immunosuppressive-drug-mycophenolate-mofetil-on-rat-kidneys
#2
Ichrak Dridi, Wafa Ben-Cherif, Hassiba Chahdoura, Zohra Haouas, Mossadok Ben-Attia, Karim Aouam, Alain Reinberg, Naceur A Boughattas
This study investigates whether the toxicity in kidneys as well as oxidative stress varied according to the dosing time of an immunosuppressive agent "mycophenolate mofetil (MMF)" in Wistar Rat. 300mg/kg of MMF was injected by intraperitonal at four different circadian stages (1, 7, 13 and 19h after light onset, HALO). Rats were sacrificed after 3days, and the kidneys were removed for determination of oxidative stress and histological analysis. Biochemical variable (creatinine, urea) was performed. Statistical analysis showed that MMF administration at 7 HALO produced a renal toxicity assessed by the significant increase in both blood creatinine and urea and antioxidant activity assessed by malondialdehyde and protein carbonyl levels indicating an induction of lipid peroxidation in oxidative damage...
January 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28074976/utility-of-urinary-markers-in-the-assessment-of-renal-dysfunction-in-canine-babesiosis
#3
Dagmara Winiarczyk, Łukasz Adaszek, Michał Bartnicki, Beata Abramowicz, Paweł Łyp, Jacek Madany, Stanisław Winiarczyk
OBJECTIVE: Canine babesiosis is a common and clinically significant tick-borne disease caused by haemoprotozoan parasites of the genus Babesia. Acute renal failure is considered to be one of the most prevalent complications of canine babesiosis. This complication leads to a decrease in the glomerular filtration rate and in consequence causes azotemia and uremia. The objective of this study was to assess the localization and extent of renal damage in dogs infected with Babesia canis using an urinary marker for glomerular (urinary immunoglobulin G, uIgG), proximal tubular dysfunction (urinary retinol binding protein, uRBP) and distal tubular dysfunction (urinary Tamm-Horsfal protein, uTHP)...
January 11, 2017: Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere
https://www.readbyqxmd.com/read/28074668/in-vivo-evidence-of-nephrotoxicity-and-altered-hepatic-function-in-rats-following-administration-of-diglycolic-acid-a-metabolite-of-diethylene-glycol
#4
Corie N Robinson, Brian Latimer, Fleurette Abreo, Kiera Broussard, Kenneth E McMartin
CONTEXT: Diglycolic acid (DGA) is one of the two primary metabolites of diethylene glycol (DEG). DEG is an industrial solvent that has been implicated in mass poisonings resulting from product misuse in the United States and worldwide, with the hallmark toxicity being acute kidney injury, hepatotoxicity, encephalopathy and peripheral neuropathy. Our laboratory has generated in-vitro evidence suggesting that DGA is the metabolite responsible for the proximal tubule necrosis and decreased kidney function observed following DEG ingestion...
January 11, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28062568/renal-collectrin-protects-against-salt-sensitive-hypertension-and-is-downregulated-by-angiotensin-ii
#5
Pei-Lun Chu, Joseph C Gigliotti, Sylvia Cechova, Gabor Bodonyi-Kovacs, Fang Chan, Donna Lee Ralph, Nancy Howell, Kambiz Kalantari, Alexander L Klibanov, Robert M Carey, Alicia A McDonough, Thu H Le
Collectrin, encoded by the Tmem27 gene, is a transmembrane glycoprotein with approximately 50% homology with angiotensin converting enzyme 2, but without a catalytic domain. Collectrin is most abundantly expressed in the kidney proximal tubule and collecting duct epithelia, where it has an important role in amino acid transport. Collectrin is also expressed in endothelial cells throughout the vasculature, where it regulates L-arginine uptake. We previously reported that global deletion of collectrin leads to endothelial dysfunction, augmented salt sensitivity, and hypertension...
January 6, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28057840/delineating-the-role-of-various-factors-in-renal-disposition-of-digoxin-through-application-of-physiologically-based-kidney-model-to-renal-impairment-populations
#6
Daniel Scotcher, Christopher R Jones, Aleksandra Galetin, Amin Rostami-Hodjegan
Development of sub-models of organs within physiologically-based pharmacokinetic (PBPK) principles and beyond simple perfusion limitations may be challenging because of underdeveloped in vitro-in vivo extrapolation approaches or lack of suitable clinical data for model refinement. However, the advantage of such models in predicting clinical observations in divergent patient groups is now commonly acknowledged. Mechanistic understanding of altered renal secretion in renal impairment is one area that may benefit from such models, despite knowledge gaps in renal pathophysiology (Rowland Yeo et al...
January 5, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28057514/systemic-effects-of-subtilase-cytotoxin-produced-by-escherichia-coli-o113-h21
#7
E Abril Seyahian, Gisela Oltra, Federico Ochoa, Santiago Melendi, Ricardo Hermes, James C Paton, Adrienne W Paton, Nestor Lago, Mauricio Castro Parodi, Alicia Damiano, Cristina Ibarra, Elsa Zotta
: Subtilase cytotoxin (SubAB) is a member of the AB5 cytotoxin family and is produced by certain strains of Shiga toxigenic Escherichia coli. The toxin is known to be lethal to mice, but the pathological mechanisms that contribute to Uremic Hemolytic Syndrome (HUS) are poorly understood. In this study we show that intraperitoneal injection of a sublethal dose of SubAB in rats triggers a systemic response, with ascitic fluid accumulation, heart hypertrophy and damage to the liver, colon and kidney...
January 2, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28053556/assessment-of-the-effect-of-antiretroviral-therapy-on-renal-and-liver-functions-among-hiv-infected-patients-a-retrospective-study
#8
Habtamu Wondifraw Baynes, Birhanemeskel Tegene, Mikiyas Gebremichael, Gebrehawaria Birhane, Wabe Kedir, Belete Biadgo
BACKGROUND: The emergence of highly active antiretroviral therapy (HAART) has dramatically improved quality of life in prolonging survival of human immunodeficiency virus (HIV)-infected patients on treatment in developed as well as developing countries. However, the main shortcoming of HAART in long-term use is its potential to cause liver and kidney derangements that may be life threatening. The drugs are actively accumulated in the proximal renal tubule resulting in functional disturbance with mitochondrial injury being one of the most important targets recognized...
2017: HIV/AIDS: Research and Palliative Care
https://www.readbyqxmd.com/read/28052987/megalin-blockade-with-cilastatin-suppresses-drug-induced-nephrotoxicity
#9
Yoshihisa Hori, Nobumasa Aoki, Shoji Kuwahara, Michihiro Hosojima, Ryohei Kaseda, Sawako Goto, Tomomichi Iida, Shankhajit De, Hideyuki Kabasawa, Reika Kaneko, Hiroyuki Aoki, Yoshinari Tanabe, Hiroshi Kagamu, Ichiei Narita, Toshiaki Kikuchi, Akihiko Saito
Nephrotoxicity induced by antimicrobial or anticancer drugs is a serious clinical problem. Megalin, an endocytic receptor expressed at the apical membranes of proximal tubules, mediates the nephrotoxicity of aminoglycosides and colistin, key antimicrobials for multidrug-resistant organisms. The mechanisms underlying the nephrotoxicity induced by vancomycin, an antimicrobial for methicillin-resistant Staphylococcus aureus, and cisplatin, an important anticancer drug, are unknown, although the nephrotoxicity of these drugs and gentamicin, an aminoglycoside, is suppressed experimentally with cilastatin...
January 4, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28039413/urat1-inhibition-by-alpk1-is-associated-with-uric-acid-homeostasis-alpk1-and-slc22a12-in-uric-acid-homeostasis
#10
Tzer-Min Kuo, Chung-Ming Huang, Hung-Pin Tu, Albert Min-Shan Ko, Shu-Jung Wang, Chi-Pin Lee, Ying-Chin Ko
OBJECTIVE: The aim of this study was to identify a protein for urate transporter 1 (URAT1) regulation. METHODS: The clinical dataset consisted of 492 case-control samples of Han Chinese (104 gout and 388 controls). Three alpha kinase 1 (ALPK1) and SLC22A12 loci associated with high gout risk and uric acid levels were genotyped. The overexpression of ALPK1 on URAT1 protein expression was evaluated in vivo in hALPK1 transgenic mice. The in vitro protein levels of ALPK1 and URAT1 in ALPK1 small interfering RNA-transfected human kidney-2 cells with MSU crystal stimulation were examined...
December 30, 2016: Rheumatology
https://www.readbyqxmd.com/read/28031320/tetraspanin-cd63-controls-basolateral-sorting-of-organic-cation-transporter-2-in-renal-proximal-tubules
#11
Ulf Schulze, Sabine Brast, Alexander Grabner, Christian Albiker, Beatrice Snieder, Svenja Holle, Eberhard Schlatter, Rita Schröter, Hermann Pavenstädt, Edwin Herrmann, Carsten Lambert, Gilles A Spoden, Luise Florin, Paul Saftig, Giuliano Ciarimboli
CD63 is a ubiquitously expressed member of the tetraspanin superfamily. Using a mating-based split-ubiquitin-yeast 2-hybrid system, pull-down experiments, total internal reflection fluorescence microscopy, Förster resonance energy transfer, and biotinylation assays, we found that CD63 interacts with human organic cation transporter 2 (hOCT2), which transports endogenous and exogenous substrates, such as neurotransmitters and drugs in several epithelial cells. CD63 overexpression affects cellular localization of hOCT2 expressed in human embryonic kidney (HEK)293 cells...
December 28, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28012971/effects-of-a-human-recombinant-alkaline-phosphatase-during-impaired-mitochondrial-function-in-human-renal-proximal-tubule-epithelial-cells
#12
Esther Peters, Tom Schirris, Alexander H van Asbeck, Jelle Gerretsen, Jennifer Eymael, Angel Ashikov, Merel J W Adjobo-Hermans, Frans Russel, Peter Pickkers, Rosalinde Masereeuw
Sepsis-associated acute kidney injury is a multifactorial syndrome in which inflammation and renal microcirculatory dysfunction play a profound role. Subsequently, renal tubule mitochondria reprioritize cellular functions to prevent further damage. Here, we investigated the putative protective effects of human recombinant alkaline phosphatase (recAP) during inhibition of mitochondrial respiration in conditionally immortalized human proximal tubule epithelial cells (ciPTEC). Full inhibition of mitochondrial oxygen consumption was obtained after 24h antimycin A treatment, which did not affect cell viability...
December 22, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28011955/the-protective-effects-of-zinc-in-experimental-gentamicin-induced-acute-renal-failure-in-rats
#13
O Teslariu, A S Pasca, L Mititelu-Tartau, C E Schiriac, C Gales, P M Saftencu, M Nechifor
This study investigates the effects of zinc in acute kidney injury induced by gentamicin (Ge). We used Wistar male rats distributed in 4 groups of 12 animals each, treated intraperitoneally as follows: Group I (Control) treated with distilled water; Group II (Ge) with experimental induced acute renal failure with Ge; Group III (Ge + Zn) administration of ZnCl2 in animals with experimental induced renal failure with Ge, Group IV (Zn) treated with ZnCl2 as positive control. We measured serum levels of urea, creatinine, total antioxidant status, superoxide dismutase, glutathione peroxidase and urinary proteins before the nephrotoxicity induction (baseline) and 3, 7 and 10 days after Ge administration...
October 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28001174/impact-of-gender-in-early-structural-changes-of-contrast-induced-nephropathy-in-rats
#14
José Carlos Carraro-Eduardo, Mariana Franco Ferraz Santino, Heloisa Werneck de Macedo, Licínio Esmeraldo da Silva
INTRODUCTION: Contrast-induced nephropathy (CIN) is a major iatrogenic cause of acute kidney injury. Experimental studies have shown that intravascular injection causes intense vacuolization of the contrast agent in the proximal renal tubules cells, preceding the increase in serum creatinine, and that the female may be at a higher risk for CIN. OBJECTIVE: To study the early kidney histomorphometric changes in contrast-induced nephropathy according to the gender...
December 2016: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/27998362/seasonal-and-morphological-variations-of-brown-trout-salmo-trutta-f-fario-kidney-peroxisomes-a-stereological-study
#15
Albina D Resende, Alexandre Lobo-da-Cunha, Fernanda Malhão, Eduardo Rocha
Literature about fish kidney peroxisomes is scarce. To tackle this caveat, a stereological approach on renal peroxisome morphological parameters was performed for the first time in a fish, establishing correlations with maturation stages as it was previously done in brown trout liver. Three-year-old brown trout males and females were collected at the major seasons of their reproductive cycle. Trunk kidney was fixed and processed for catalase cytochemistry. Classical stereological methods were applied to electromicrographs to quantitate morphological parameters...
December 2016: Microscopy and Microanalysis
https://www.readbyqxmd.com/read/27995443/pseudohypoparathyroidism-one-gene-several-syndromes
#16
REVIEW
O Tafaj, H Jüppner
Pseudohypoparathyroidism (PHP) and pseudopseudohypoparathyroidism (PPHP) are caused by mutations and/or epigenetic changes at the complex GNAS locus on chromosome 20q13.3 that undergoes parent-specific methylation changes at several sites. GNAS encodes the alpha-subunit of the stimulatory G protein (Gsα) and several splice variants thereof. Heterozygous inactivating mutations involving the maternal GNAS exons 1-13 cause PHP type Ia (PHP1A). Because of much reduced paternal Gsα expression in certain tissues, such as the proximal renal tubules, thyroid, and pituitary, there is little or no Gsα protein in the presence of maternal GNAS mutations, thus leading to PTH-resistant hypocalcemia and hyperphosphatemia...
December 19, 2016: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/27994478/dialysis-related-amyloidosis-challenges-and-solutions
#17
REVIEW
R Scarpioni, M Ricardi, V Albertazzi, S De Amicis, F Rastelli, L Zerbini
Amyloidosis refers to the extracellular tissue deposition of fibrils composed of low-molecular-weight subunits of a variety of proteins. These deposits may result in a wide range of clinical manifestations depending upon their type, location, and the amount of deposition. Dialysis-related amyloidosis is a serious complication of long-term dialysis therapy and is characterized by the deposition of amyloid fibrils, principally composed of β2 microglobulins (β2M), in the osteoarticular structures and viscera...
2016: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/27991910/establishment-and-characterization-of-bhd-f59rsvt-an-immortalized-cell-line-derived-from-a-renal-cell-carcinoma-in-a-patient-with-birt-hogg-dub%C3%A3-syndrome
#18
Mitsuko Furuya, Hisashi Hasumi, Masaya Baba, Reiko Tanaka, Yasuhiro Iribe, Takahiro Onishi, Yoji Nagashima, Yukio Nakatani, Yasuhiro Isono, Masahiro Yao
Hereditary renal cell carcinomas (RCCs) are life-threatening disorders not only for the patients but also for their relatives. Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN). The protein product, FLCN, functions as a tumor suppressor, and the affected patients have high risks of developing multiple RCCs. The carcinogenic mechanisms stemming from FLCN dysfunction have been investigated using rodent models and human RCC tissues. However, very limited information has been available about in vitro signaling of human renal cells with genetically mutant FLCN...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27990015/the-renal-fanconi-syndrome-in-cystinosis-pathogenic-insights-and-therapeutic-perspectives
#19
REVIEW
Stephanie Cherqui, Pierre J Courtoy
Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders. It is caused by a defect in the lysosomal cystine transporter, cystinosin, which results in an accumulation of cystine in all organs. Despite the ubiquitous expression of cystinosin, a renal Fanconi syndrome is often the first manifestation of cystinosis, usually presenting within the first year of life and characterized by the early and severe dysfunction of proximal tubule cells, highlighting the unique vulnerability of this cell type...
December 19, 2016: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/27984186/immunolocalization-of-glutaryl-coa-dehydrogenase-gcdh-in-adult-and-embryonic-rat-brain-and-peripheral-tissues
#20
Olivier Braissant, Paris Jafari, Noémie Remacle, Hong-Phuc Cudré-Cung, Sonia Do Vale Pereira, Diana Ballhausen
Glutaryl-CoA dehydrogenase (GCDH) is a mitochondrial enzyme that is involved in the degradation of tryptophan, lysine and hydroxylysine. Deficient enzyme activity leads to glutaric aciduria type-I (GA-I). This neurometabolic disease usually manifests with acute encephalopathic crises and striatal neuronal death in early childhood leading to an irreversible dystonic-dyskinetic movement disorder. Fronto-temporal atrophy and white matter changes are already present in the pre-symptomatic period. No detailed information on GCDH expression during embryonic development and in adulthood was available so far...
October 27, 2016: Neuroscience
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