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https://www.readbyqxmd.com/read/29679893/identification-of-homocysteine-suppressive-mitochondrial-etc-complex-genes-and-tissue-expression-profile-novel-hypothesis-establishment
#1
Ramon Cueto, Lixiao Zhang, Hui Min Shan, Xiao Huang, Xinyuan Li, Ya-Feng Li, Jahaira Lopez, William Y Yang, Muriel Lavallee, Catherine Yu, Yong Ji, Xiaofeng Yang, Hong Wang
Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease (CVD) which has been implicated in matochondrial (Mt) function impairment. In this study, we characterized Hcy metabolism in mouse tissues by using LC-ESI-MS/MS analysis, established tissue expression profiles for 84 nuclear-encoded Mt electron transport chain complex (nMt-ETC-Com) genes in 20 human and 19 mouse tissues by database mining, and modeled the effect of HHcy on Mt-ETC function. Hcy levels were high in mouse kidney/lung/spleen/liver (24-14 nmol/g tissue) but low in brain/heart (~5 nmol/g)...
April 4, 2018: Redox Biology
https://www.readbyqxmd.com/read/29679077/proteome-wide-analysis-of-cysteine-oxidation-reveals-metabolic-sensitivity-to-redox-stress
#2
Jiska van der Reest, Sergio Lilla, Liang Zheng, Sara Zanivan, Eyal Gottlieb
Reactive oxygen species (ROS) are increasingly recognised as important signalling molecules through oxidation of protein cysteine residues. Comprehensive identification of redox-regulated proteins and pathways is crucial to understand ROS-mediated events. Here, we present stable isotope cysteine labelling with iodoacetamide (SICyLIA), a mass spectrometry-based workflow to assess proteome-scale cysteine oxidation. SICyLIA does not require enrichment steps and achieves unbiased proteome-wide sensitivity. Applying SICyLIA to diverse cellular models and primary tissues provides detailed insights into thiol oxidation proteomes...
April 20, 2018: Nature Communications
https://www.readbyqxmd.com/read/29677309/vitamin-d-calcium-or-combined-supplementation-for-the-primary-prevention-of-fractures-in-community-dwelling-adults-us-preventive-services-task-force-recommendation-statement
#3
David C Grossman, Susan J Curry, Douglas K Owens, Michael J Barry, Aaron B Caughey, Karina W Davidson, Chyke A Doubeni, John W Epling, Alex R Kemper, Alex H Krist, Martha Kubik, Seth Landefeld, Carol M Mangione, Michael Silverstein, Melissa A Simon, Chien-Wen Tseng
Importance: Because of the aging population, osteoporotic fractures are an increasingly important cause of morbidity and mortality in the United States. Approximately 2 million osteoporotic fractures occurred in the United States in 2005, and annual incidence is projected to increase to more than 3 million fractures by 2025. Within 1 year of experiencing a hip fracture, many patients are unable to walk independently, more than half require assistance with activities of daily living, and 20% to 30% of patients will die...
April 17, 2018: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29677110/dietary-treatment-of-metabolic-acidosis-in-chronic-kidney-disease
#4
REVIEW
Roswitha Siener
Chronic kidney disease and reduced glomerular filtration rate are risk factors for the development of chronic metabolic acidosis. The prevention or correction of chronic metabolic acidosis has been found to slow progression of chronic kidney disease. Dietary composition can strongly affect acid⁻base balance. Major determinants of net endogenous acid production are the generation of large amounts of hydrogen ions, mostly by animal-derived protein, which is counterbalanced by the metabolism of base-producing foods like fruits and vegetables...
April 20, 2018: Nutrients
https://www.readbyqxmd.com/read/29676858/effects-of-prebiotic-fiber-xylooligosaccharide-in-adenine-induced-nephropathy-in-mice
#5
Jieping Yang, Qing Li, Susanne M Henning, Jin Zhong, Mark Hsu, Rupo Lee, Jianfeng Long, Brenda Chan, Glenn T Nagami, David Heber, Zhaoping Li
SCOPE: We evaluated the effect of the prebiotic fiber xylooligosaccharide (XOS) on kidney function and gut microbiome in mice with adenine-induced chronic kidney disease (CKD). METHOD AND RESULTS: Mice were fed the control diet containing adenine for three weeks to induce CKD and switched to XOS supplemented (2 or 7%) or control diets for another 3 weeks. Mice with CKD exhibited increased BUN, creatinine and kidney histopathology. XOS significantly reversed kidney injuries in CKD mice...
April 20, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29676238/effect-of-cyp2d6-poor-metabolizer-phenotype-on-stereoselective-nebivolol-pharmacokinetics
#6
Carolina P Vieira, Daniel V Neves, Eduardo B Coelho, Vera Lucia Lanchote
BACKGROUND: Nebivolol is a drug available as a racemate of d-nebivolol (SRRR) and l-nebivolol (RSSS). In human liver microsomes CYP2D6 mainly catalyses the metabolism of l-nebivolol, while CYP2C19 catalyses the metabolism of d-nebivolol. Nebivolol stereoselective pharmacokinetics has been described only for extensive metabolizers (EM). OBJECTIVE: To describe the stereoseletive nebivolol pharmacokinetics in CYP2D6 poor metabolizers (PM) and to assess whether the phenotype has an impact on nebivolol pharmacokinetics ...
April 19, 2018: Drug Metabolism Letters
https://www.readbyqxmd.com/read/29675448/intestinal-farnesoid-x-receptor-activation-by-pharmacologic-inhibition-of-the-organic-solute-transporter-%C3%AE-%C3%AE
#7
Sandra M W van de Wiel, D Rudi de Waart, Ronald P J Oude Elferink, Stan F J van de Graaf
Background & Aims: The organic solute transporter α-β (OSTα-OSTβ) mainly facilitates transport of bile acids across the basolateral membrane of ileal enterocytes. Therefore, inhibition of OSTα-OSTβ might have similar beneficial metabolic effects as intestine-specific agonists of the major nuclear receptor for bile acids, the farnesoid X receptor (FXR). However, no OSTα-OSTβ inhibitors have yet been identified. Methods: Here, we developed a screen to identify specific inhibitors of OSTα-OSTβ using a genetically encoded Förster Resonance Energy Transfer (FRET)-bile acid sensor that enables rapid visualization of bile acid efflux in living cells...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29674492/11beta-hydroxysteroid-dehydrogenase-1-human-tissue-distribution-selective-inhibitor-and-role-in-doxorubicin-metabolism
#8
Xin Yang, Wenyi Hua, Sangwoo Ryu, Phillip Yates, Cheng Chang, Hui Zhang, Li Di
11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) is mainly distributed in the human liver with no detectable levels in the intestine or kidney based on a newly developed proteomic approach. 11β-HSD1 is mostly membrane bound and retained in the liver microsomal faction. Inter-individual variability of 11β-HSD1 is relatively low with about a three-fold difference. A significant correlation was not observed between various demographic variables (ethnicity, gender, age, weight, smoking, and alcohol use) and 11β-HSD1 protein expression or activity based on data from thirty-one donors...
April 19, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29674245/effects-of-multiple-life-stage-exposure-to-the-fungicide-prochloraz-in-xenopus-laevis-manifestations-of-antiandrogenic-and-other-modes-of-toxicity
#9
Jonathan T Haselman, Patricia A Kosian, Joseph J Korte, Allen W Olmstead, Sigmund J Degitz
The Larval Amphibian Growth and Development Assay (LAGDA) is an internationally harmonized testing guideline for evaluating effects of chronic chemical exposure in amphibians. In order to evaluate the effects of chronic exposure to an antiandrogenic chemical in an amphibian model, prochloraz was tested using a variation of the LAGDA design. Exposure was initiated with <1d post-fertilization embryos at nominal concentrations of 0, 6.7, 20, 60 and 180 μg/L (0, 18, 53, 159, 478 nM) and continued in flow-through conditions until two months following the median time that controls completed metamorphosis...
April 3, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29671959/renal-sulfate-reabsorption-in-healthy-individuals-and-renal-transplant-recipients
#10
Adrian Post, Isidor Minović, Else van den Berg, Manfred L Eggersdorfer, Gerjan J Navis, Johanna M Geleijnse, Reinold O B Gans, Harry van Goor, Joachim Struck, Casper F M Franssen, Ido P Kema, Stephan J L Bakker
Inorganic sulfate is essential for normal cellular function and its homeostasis is primarily regulated in the kidneys. However, little is known about renal sulfate handling in humans and particularly in populations with impaired kidney function such as renal transplant recipients (RTR). Hence, we aimed to assess sulfate reabsorption in kidney donors and RTR. Plasma and urinary sulfate were determined in 671 RTR and in 251 kidney donors. Tubular sulfate reabsorption (TSR) was defined as filtered load minus sulfate excretion and fractional sulfate reabsorption (FSR) was defined as 1-fractional excretion...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29671764/evaluation-of-factors-associated-with-hypermetabolism-and-hypometabolism-in-critically-ill-aki-patients
#11
Cassiana R de Góes, André Luis Balbi, Daniela Ponce
Acute kidney injury (AKI) is a frequent and serious condition with high mortality. The presence of hypermetabolism may be a factor related to poorer prognosis. This study evaluated the resting energy expenditure (REE) of intensive care unit (ICU) patients with severe AKI using indirect calorimetry (IC) and identified factors associated with metabolism categories. Patients were evaluated through measurement of REE and estimation of basal energy expenditure (BEE) using the Harris⁻Benedict equation. Metabolism categories were as follows: hypermetabolism (REE/BEE > 1...
April 19, 2018: Nutrients
https://www.readbyqxmd.com/read/29670389/fgf23-modulates-the-effects-of-erythropoietin-on-gene-expression-in-renal-epithelial-cells
#12
Mitsuru Yashiro, Masaki Ohya, Toru Mima, Yumi Ueda, Yuri Nakashima, Kazuki Kawakami, Yohei Ishizawa, Shuto Yamamoto, Sou Kobayashi, Takurou Yano, Yusuke Tanaka, Kouji Okuda, Tomohiro Sonou, Tomohiro Shoshihara, Yuko Iwashita, Yu Iwashita, Kouichi Tatsuta, Ryo Matoba, Shigeo Negi, Takashi Shigematsu
Background: FGF23 plays an important role in calcium-phosphorus metabolism. Other roles of FGF23 have recently been reported, such as commitment to myocardium enlargement and immunological roles in the spleen. In this study, we aimed to identify the roles of FGF23 in the kidneys other than calcium-phosphorus metabolism. Methods: DNA microarrays and bioinformatics tools were used to analyze gene expression in mIMCD3 mouse renal tubule cells following treatment with FGF23, erythropoietin and/or an inhibitor of ERK...
2018: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/29668565/the-effects-of-genetic-3-mercaptopyruvate-sulfurtransferase-deficiency-in-murine-traumatic-hemorrhagic-shock
#13
Michael Gröger, Martin Wepler, Ulrich Wachter, Tamara Merz, Oscar McCook, Sandra Kress, Britta Lukaschewski, Sebastian Hafner, Markus Huber-Lang, Enrico Calzia, Michael Georgieff, Noriyuki Nagahara, Csaba Szabó, Peter Radermacher, Clair Hartmann
INTRODUCTION: Hemorrhagic shock is a major cause of death after trauma. An additional blunt chest trauma independently contributes to mortality upon the development of an acute lung injury (ALI) by aggravating pathophysiological consequences of hemorrhagic shock. The maintenance of hydrogen sulfide availability is known to play an important role during hemorrhage and ALI. We therefore tested the impact of a genetic 3-mercaptopyruvate sulfurtransferase mutation (Δ3-MST) in a resuscitated murine model of traumatic-hemorrhagic shock...
April 17, 2018: Shock
https://www.readbyqxmd.com/read/29667921/glycemic-control-of-type-2-diabetes-mellitus-across-stages-of-renal-impairment-information-for-primary-care-providers
#14
Lili Tong, Sharon Adler
Chronic kidney disease (CKD) is a frequent complication of type 2 diabetes mellitus (T2DM) and elevates individuals' risk for cardiovascular disease, the leading cause of morbidity and mortality in T2DM. Achieving and maintaining tight glycemic control is key to preventing development or progression of CKD; however, improving glycemic control may be limited by effects of renal impairment on the efficacy and safety of T2DM treatments, necessitating dosing adjustments and careful evaluation of contraindications...
April 18, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29667913/ubiquitin-c-terminal-hydrolase-l1-deletion-is-associated-with-urinary-%C3%AE-klotho-deficiency-and-perturbed-phosphate-homeostasis
#15
Naomi C Boisvert, Chet E Holterman, Alexey Gutsol, Josee Coulombe, Wanling Pan, R Todd Alexander, Douglas A Gray, Chris R Kennedy
Loss of ubiquitin C-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme required for neuronal function, led to hyperphosphatemia accompanied by phosphaturia in mice, while calcium homeostasis remained intact. We therefore investigated the mechanisms underlying the phosphate imbalance in Uchl1-/- mice. Interestingly, phosphaturia was not a result of lower renal brush border membrane sodium-phosphate cotransporter expression as sodium-phosphate cotransporter 2a and 2c expression levels were similar to wild type levels...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29666405/mediators-of-the-effects-of-gender-on-uric-acid-nephrolithiasis-a-novel-application-of-structural-equation-modeling
#16
Hao-Wei Chen, Yu-Chen Chen, Frances M Yang, Wen-Jeng Wu, Ching-Chia Li, Yong-Yuan Chang, Yii-Her Chou
Numerous epidemiological studies have shown that male patients with uric acid nephrolithiasis outnumber female patients. To our knowledge, no research exists evaluating the reasons gender affects the development of uric acid nephrolithiasis. We hereby used a novel application of structural equation modeling to analyze the mediators of the effects of gender on uric acid nephrolithiasis. In 1,098 patients with nephrolithiasis between 2012 and 2016, male gender was found to have a statistically significant positive indirect effect on the development of uric acid nephrolithiasis, which was mediated by lower urine pH (estimate: 0...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29666303/a-gallium-67-68-labeled-antibody-fragment-for-immuno-spect-pet-shows-low-renal-radioactivity-without-loss-of-tumor-uptake
#17
Tomoya Uehara, Miki Yokoyama, Hiroyuki Suzuki, Hirofumi Hanaoka, Yasushi Arano
PURPOSE: This study was undertaken to evaluate the renal radioactivity levels of a newly designed 67 Ga-labeled antibody fragment with a linkage cleaved by enzymes present on the brush border membrane (BBM) lining the lumen of the renal tubule. EXPERIMENTAL DESIGN: 67 Ga-labeled S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bn-NOTA) was conjugated with an antibody Fab fragment through a Met-Val-Lys linkage (67 Ga-NOTA-MVK-Fab) considering that a Met-Val sequence is a substrate of enzymes on the renal BBM and 67 Ga-NOTA-Met is excreted from the kidney into the urine...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29665472/off-line-solid-phase-extraction-and-liquid-chromatography-tandem-mass-spectrometry-method-for-the-quantitation-of-brivaracetam-acid-metabolites-method-validation-and-application-to-in-vitro-metabolism-assays
#18
Emmanuel Bourgogne, Benoit Culot, Sylvie Dell'Aiera, Hugues Chanteux, Armel Stockis, Jean-Marie Nicolas
Brivaracetam (BRV) is a new high affinity synaptic vesicle protein 2A ligand recently approved for adults with partial-onset seizures. As a support to in vitro metabolism assays, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method coupled to off-line solid phase extraction (SPE) was developed to quantify BRV acid metabolites, that is, BRV-AC (carboxylic derivative derived from BRV hydrolysis) and BRV-OHAC (corresponding to hydroxylated BRV-AC). The method was validated for various incubates (liver and kidney tissue homogenates and blood, all from humans) and applied to in vitro metabolism assays...
April 10, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29665413/genetic-risk-factors-for-post-transplantation-diabetes-mellitus-in-chinese-han-renal-allograft-recipients-treated-with-tacrolimus
#19
Xiaoming Zhang, Tongyi Men, Haitao Liu, Xianduo Li, Jianning Wang, Jiaju Lv
BACKGROUND: Post-transplantation diabetes mellitus (PTDM) is a serious metabolic complication after kidney transplantation. The aim of this study was to explore the association of clinical variables and five selected single nucleotide polymorphisms (SNPs) with PTDM in Chinese Han renal allograft recipients taking tacrolimus (TAC). METHODS: A total of 129 non-diabetic, primary, Chinese Han renal allograft recipients treated with TAC were enrolled. Five SNPs (CYP3A5 rs776741, rs776746, rs15524, CYP24A1 rs2296241, and PPARG rs1801282) were genotyped and analyzed...
April 14, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29663413/predicting-pharmacokinetics-pharmacodynamics-in-the-individual-patient-separating-reality-from-hype
#20
REVIEW
Leslie Z Benet
Individualization of patient drug dosing to maximize efficacy and minimize toxicity is the goal of clinical pharmacology. Here we review the history of drug dosing individualization from early predictions for renally eliminated drugs based on kidney function through the introduction of clearance concepts for metabolic processes, the differentiation of volume of distribution between pharmacokinetics and chemistry, the role of transporters, the unique pharmacokinetic aspects of oral dosing, and the relevance of protein binding to the emergence of pharmacogenomics...
April 17, 2018: Journal of Clinical Pharmacology
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