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Citrulline AND kidney

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https://www.readbyqxmd.com/read/27890855/linker-stability-influences-the-anti-tumor-activity-of-acetazolamide-drug-conjugates-for-the-therapy-of-renal-cell-carcinoma
#1
Samuele Cazzamalli, Alberto Dal Corso, Dario Neri
Small molecule-drug conjugates (SMDCs) are increasingly being considered as an alternative to antibody-drug conjugates (ADCs) for the selective delivery of anticancer agents to the tumor site, sparing normal tissues. Carbonic anhydrase IX (CAIX) is a membrane-bound enzyme, which is over-expressed in the majority of renal cell carcinomas and which can be efficiently targeted in vivo, using charged derivatives of acetazolamide, a small heteroaromatic sulfonamide. Here, we show that SMDC products, obtained by the coupling of acetazolamide with monomethyl auristatin E (MMAE) using dipeptide linkers, display a potent anti-tumoral activity in mice bearing xenografted SKRC-52 renal cell carcinomas...
November 24, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27714515/human-splanchnic-amino-acid-metabolism
#2
Evelien P J G Neis, S Sabrkhany, I Hundscheid, D Schellekens, K Lenaerts, S W Olde Damink, E E Blaak, C H C Dejong, Sander S Rensen
Plasma levels of several amino acids are correlated with metabolic dysregulation in obesity and type 2 diabetes. To increase our understanding of human amino-acid metabolism, we aimed to determine splanchnic interorgan amino-acid handling. Twenty patients planned to undergo a pylorus preserving pancreatico-duodenectomy were included in this study. Blood was sampled from the portal vein, hepatic vein, superior mesenteric vein, inferior mesenteric vein, splenic vein, renal vein, and the radial artery during surgery...
October 6, 2016: Amino Acids
https://www.readbyqxmd.com/read/27427341/presence-of-citrullinated-histone-h3-positive-neutrophils-in-microscopic-polyangiitis-from-the-early-phase-an-autopsy-proven-case
#3
Yoko Matsuda, Hideki Hamayasu, Atsuko Seki, Keisuke Nonaka, Tan Wang, Takumi Matsumoto, Yoshitomo Hamano, Hiroyuki Sumikura, Toshio Kumasaka, Shigeo Murayama, Akihiko Ishizu, Akira Shimizu, Takahiko Sugihara, Tomio Arai
A 76-year-old man was admitted with general fatigue, weight loss, fever, headache, renal failure, and a high serum level of myeloperoxidase-antineutrophil cytoplasmic antibody. Biopsy revealed citrullinated histone H3 (citH3)-positive neutrophils adherent to the temporal artery endothelium. Three days after completing pulse steroid therapy, he suffered from a sudden disturbance of consciousness and died. On autopsy, the kidneys showed the most severe vasculitis with dense infiltration of citH3-positive neutrophils...
August 2016: Pathology International
https://www.readbyqxmd.com/read/27335376/peptidyl-arginine-deiminase-4-deficient-mice-are-protected-against-kidney-and-liver-injury-after-renal-ischemia-and-reperfusion
#4
May Rabadi, Mihwa Kim, Vivette D'Agati, H Thomas Lee
We previously demonstrated that renal peptidyl arginine deiminase-4 (PAD4) is induced after renal ischemia and reperfusion (I/R) injury and exacerbates acute kidney injury (AKI) by increasing the renal tubular inflammatory response. Here, we tested whether genetic ablation of PAD4 attenuates renal injury and inflammation after I/R in mice. After renal I/R, PAD4 wild-type mice develop severe AKI with large increases in plasma creatinine, neutrophil infiltration, as well as significant renal tubular necrosis, apoptosis, and proinflammatory cytokine generation...
August 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27194717/perioperative-glutamine-supplementation-restores-disturbed-renal-arginine-synthesis-after-open-aortic-surgery-a-randomized-controlled-clinical-trial
#5
Saskia J H Brinkmann, Nikki Buijs, Mechteld A R Vermeulen, Efraim Oosterink, Henk Schierbeek, Albertus Beishuizen, Jean-Paul P M de Vries, Willem Wisselink, Paul A M van Leeuwen
Postoperative renal failure is a common complication after open repair of an abdominal aortic aneurysm. The amino acid arginine is formed in the kidneys from its precursor citrulline, and citrulline is formed from glutamine in the intestines. Arginine enhances the function of the immune and cardiovascular systems, which is important for recovery after surgery. We hypothesized that renal arginine production is diminished after ischemia-reperfusion injury caused by clamping of the aorta during open abdominal aortic surgery and that parenteral glutamine supplementation might compensate for this impaired arginine synthesis...
September 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27051449/a-transmembrane-polymorphism-of-fc%C3%AE-receptor-iib-is-associated-with-kidney-deficiency-syndrome-in-rheumatoid-arthritis
#6
Na Mo, Ruogu Lai, Shizi Luo, Jianglin Xie, Xizi Wang, Lijuan Liu, Xiaoling Liu, Guangxing Chen
Objective. The purpose is to investigate the role of kidney deficiency and the association between kidney deficiency and a polymorphism FcγRIIb 695T>C coding for nonsynonymous substitution IIe232Thr (I232T) in rheumatoid arthritis (RA). Methods. Clinical parameters and autoantibodies were analyzed and genotyping was performed in 159 kidney deficiency and 161 non-kidney-deficiency RA patients. Results. The age of disease onset and disease duration exhibited significant differences between two groups (P < 0...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27001421/augmentation-of-phosphate-induced-osteo-chondrogenic-transformation-of-vascular-smooth-muscle-cells-by-homoarginine
#7
Ioana Alesutan, Martina Feger, Rashad Tuffaha, Tatsiana Castor, Katharina Musculus, Salvatore S Buehling, Christian L Heine, Makoto Kuro-O, Burkert Pieske, Kurt Schmidt, Andreas Tomaschitz, Winfried Maerz, Stefan Pilz, Andreas Meinitzer, Jakob Voelkl, Florian Lang
AIMS: Reduced homoarginine plasma levels are associated with unfavourable cardiovascular outcome in chronic kidney disease (CKD). Cardiovascular events in CKD are fostered by vascular calcification, an active process promoted by hyperphosphatemia and involving osteo-/chondrogenic transformation of vascular smooth muscle cells (VSMCs). The present study explored the effect of homoarginine on phosphate-induced osteo-/chondrogenic signalling and vascular calcification. METHODS AND RESULTS: Experiments were performed in hyperphosphatemic klotho-hypomorphic mice (kl/kl), in subtotal nephrectomy and vitamin D3-overload mouse calcification models and in primary human aortic smooth muscle cells (HAoSMCs)...
June 1, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/26840412/circulating-level-of-neutrophil-extracellular-traps-is-not-a-useful-biomarker-for-assessing-disease-activity-in-antineutrophil-cytoplasmic-antibody-associated-vasculitis
#8
Huan Wang, Li-Li Sha, Tian-Tian Ma, Lu-Xia Zhang, Min Chen, Ming-Hui Zhao
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of life-threatening disorders, and frequently affects the kidneys. This study investigated whether the circulating neutrophil extracellular traps (NETs) levels were associated with disease activity of AAV. We collected serum samples from 34 patients with AAV in active stage and 62 patients with AAV in remission. Cell free DNA in serum was quantified using the Quant-iT PicoGreen assay. NETs associated MPO-DNA complexes, citrullinated-histone H3-DNA (cit-H3-DNA) complexes and the concentration of deoxyribonuclease I (DNase I) were quantified using ELISA...
2016: PloS One
https://www.readbyqxmd.com/read/26833773/myeloperoxidase-anti-neutrophil-cytoplasmic-antibody-affinity-is-associated-with-the-formation-of-neutrophil-extracellular-traps-in-the-kidney-and-vasculitis-activity-in-myeloperoxidase-anti-neutrophil-cytoplasmic-antibody-associated-microscopic-polyangiitis
#9
Masaharu Yoshida, Muneharu Yamada, Yasuyo Sudo, Tadasu Kojima, Tomohiro Tomiyasu, Noriko Yoshikawa, Takashi Oda, Michiyuki Yamada
Anti-neutrophil cytoplasmic antibody (ANCA) is associated with small-vessel vasculitis particularly in the kidneys and can induce the formation of neutrophil extracellular traps (NETs) from primed neutrophils. Recently we have reported that the induction of NETs correlates with ANCA affinity for myeloperoxidase (MPO) and disease activity in patients with MPO-ANCA-associated microscopic polyangiitis. To investigate whether MPO-ANCA affinity is associated with the formation of NETs in vivo, we examined the occurrence of NETs in the renal tissues of patients with MPO-ANCA-associated microscopic polyangiitis and ANCA affinity by double immunofluorescence staining for NET components of citrullinated histone, MPO and PAD4 and by ELISA competition with MPO, respectively...
July 2016: Nephrology
https://www.readbyqxmd.com/read/26712746/reprogramming-a-preventive-strategy-in-hypertension-focusing-on-the-kidney
#10
REVIEW
You-Lin Tain, Jaap A Joles
Adulthood hypertension can be programmed in response to a suboptimal environment in early life. However, developmental plasticity also implies that one can prevent hypertension in adult life by administrating appropriate compounds during early development. We have termed this reprogramming. While the risk of hypertension has been assessed in many mother-child cohorts of human developmental programming, interventions necessary to prove causation and provide a reprogramming strategy are lacking. Since the developing kidney is particularly vulnerable to environmental insults and blood pressure is determined by kidney function, renal programming is considered key in developmental programming of hypertension...
December 25, 2015: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/26712087/low-urinary-citrulline-arginine-ratio-associated-with-blood-pressure-abnormalities-and-arterial-stiffness-in-childhood-chronic-kidney-disease
#11
I-Chun Lin, Chien-Ning Hsu, Mao-Hung Lo, Shao-Ju Chien, You-Lin Tain
Arginine (ARG) and citrulline (CIT) are essential for nitric oxide (NO) synthesis. Their metabolites are interrelated, and involved in blood pressure (BP) control, chronic kidney disease (CKD), and cardiovascular disease (CVD). Although CVD is the leading cause of mortality in CKD, little is known about subclinical CVD in early-stage childhood CKD. Twenty-four-hour ambulatory BP monitoring and arterial stiffness assessment allows the earlier possible detection of subclinical CVD. We investigated whether urinary CIT and ARG metabolites and their ratios are correlated with BP load and vascular abnormalities in children and adolescents with early-stage CKD...
February 2016: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/26674221/l-arginine-metabolism-in-cardiovascular-and-renal-tissue-from-hyper-and-hypothyroid-rats
#12
Isabel Rodríguez-Gómez, Juan N Moliz, Andrés Quesada, Sebastian Montoro-Molina, Pablo Vargas-Tendero, Antonio Osuna, Rosemary Wangensteen, Félix Vargas
This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC)...
March 2016: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/26628794/nitric-oxide-status-in-patients-with-chronic-kidney-disease
#13
Y S Reddy, V S Kiranmayi, A R Bitla, G S Krishna, P V L N Srinivasa Rao, V Sivakumar
Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular (CVD) morbidity and mortality, mainly due to atherosclerosis. Decreased production or reduced bioavailability of nitric oxide (NO) can result in endothelial dysfunction (ED). Multiple mechanisms are known to cause a state of NO deficiency in patients with CKD. Patients in various stages of CKD grouped as group-1 (CKD stage 1 and 2), group-2 (CKD stage 3 and 4), group-3 (CKD stage 5) and healthy controls were included in the study...
September 2015: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/26560519/interrelationships-between-glutamine-and-citrulline-metabolism
#14
REVIEW
Juan C Marini
PURPOSE OF REVIEW: This article analyzes the contribution of glutamine to the synthesis of citrulline and reviews the evidence that glutamine supplementation increases citrulline production. RECENT FINDINGS: Glutamine supplementation has been proposed in the treatment of critically ill patients; however, a recent large multicenter randomized controlled trial resulted in increased mortality in the glutamine-supplemented group. Within this context, defining the contribution of glutamine to the production of citrulline, and thus to de-novo arginine synthesis, has become a pressing issue...
January 2016: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/26537926/lc-qtof-ms-based-targeted-metabolomics-of-arginine-creatine-metabolic-pathway-related-compounds-in-plasma-application-to-identify-potential-biomarkers-in-pediatric-chronic-kidney-disease
#15
Sandra Benito, Alicia Sánchez, Nora Unceta, Fernando Andrade, Luis Aldámiz-Echevarria, M Aránzazu Goicolea, Ramón J Barrio
Chronic kidney disease (CKD) is a major epidemiologic problem which causes several disturbances in adults and in pediatrics. Despite being a worldwide public health problem, information available for CKD in the pediatric population is scarce. For that reason, an ion-pair reversed-phase liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) method has been developed and validated in order to analyze 16 amino acids, amino acid derivatives, and analogous compounds related to the arginine-creatine metabolic pathway that are suspicious of being increased or decreased in plasma from patients with CKD...
January 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/26282875/phospholipase-d2-drives-mortality-in-sepsis-by-inhibiting-neutrophil-extracellular-trap-formation-and-down-regulating-cxcr2
#16
Sung Kyun Lee, Sang Doo Kim, Minsoo Kook, Ha Young Lee, Jaewang Ghim, Youngwoo Choi, Brian A Zabel, Sung Ho Ryu, Yoe-Sik Bae
We determined the function of phospholipase D2 (PLD2) in host defense in highly lethal mouse models of sepsis using PLD2(-/-) mice and a PLD2-specific inhibitor. PLD2 deficiency not only increases survival but also decreases vital organ damage during experimental sepsis. Production of several inflammatory cytokines (TNF, IL-1β, IL-17, and IL-23) and the chemokine CXCL1, as well as cellular apoptosis in immune tissues, kidney, and liver, are markedly decreased in PLD2(-/-) mice. Bactericidal activity is significantly increased in PLD2(-/-) mice, which is mediated by increased neutrophil extracellular trap formation and citrullination of histone 3 through peptidylarginine deiminase activation...
August 24, 2015: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/26122628/urine-beta2-microglobulin-is-an-early-marker-of-renal-involvement-in-lpi
#17
Mari Kärki, Kirsti Näntö-Salonen, Harri Niinikoski, Laura M Tanner
OBJECTIVE: Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder affecting the transport of cationic amino acids. It has previously been shown that approximately one third of the Finnish LPI patients have impaired renal function. The aim of this study was to analyse in detail urine beta2-microglobulin values, renal dysfunction, oral L-citrulline doses and plasma citrulline concentrations in Finnish LPI patients. METHODS AND RESULTS: Of the 41 Finnish LPI patients, 56% had proteinuria and 53% hematuria...
June 30, 2015: JIMD Reports
https://www.readbyqxmd.com/read/26064491/neutrophil-extracellular-trap-components-in-fibrinoid-necrosis-of-the-kidney-with-myeloperoxidase-anca-associated-vasculitis
#18
Masaharu Yoshida, Mariko Sasaki, Kentaro Sugisaki, Yutaka Yamaguchi, Michiyuki Yamada
In response to antineutrophil cytoplasmic antibody (ANCA), activated neutrophils release decondensed chromatin associated with cytoplasmic granular proteins composed of proteolytic enzymes and myeloperoxidase (MPO); these complexes are named neutrophil extracellular traps (NETs). NET formation requires peptidylarginine deiminase 4 (PAD4) to citrullinate chromatin histones and also MPO and neutrophil elastase to aid in decondensation and release of chromatin. Immunostaining of renal biopsy revealed that NET components of citrullinated histone, MPO and PAD4 were concurrently deposited both around fibrinoid necrosis in necrotizing glomerulonephritis in the early focal phase of ANCA-associated polyangiitis and along an interlobular arterial wall...
June 2013: Clinical Kidney Journal
https://www.readbyqxmd.com/read/25879155/adaptations-of-arginine-s-intestinal-renal-axis-in-cachectic-tumor-bearing-rats
#19
Nikki Buijs, Mechteld A R Vermeulen, Viola B Weeda, James R Bading, Alexander P J Houdijk, Paul A M van Leeuwen
Malignancies induce disposal of arginine, an important substrate for the immune system. To sustain immune function, the tumor-bearing host accelerates arginine's intestinal-renal axis by glutamine mobilization from skeletal muscle and this may promote cachexia. Glutamine supplementation stimulates argi-nine production in healthy subjects. Arginine's intestinal-renal axis and the effect of glutamine supplementation in cancer cach-exia have not been investigated. This study evaluated the long-term adaptations of the interorgan pathway for arginine production following the onset of cachexia and the metabolic effect of glutamine supplementation in the cachectic state...
2015: Nutrition and Cancer
https://www.readbyqxmd.com/read/25775142/arginine-depletion-by-arginine-deiminase-does-not-affect-whole-protein-metabolism-or-muscle-fractional-protein-synthesis-rate-in-mice
#20
Juan C Marini, Inka Cajo Didelija
Due to the absolute need for arginine that certain cancer cells have, arginine depletion is a therapy in clinical trials to treat several types of cancers. Arginine is an amino acids utilized not only as a precursor for other important molecules, but also for protein synthesis. Because arginine depletion can potentially exacerbate the progressive loss of body weight, and especially lean body mass, in cancer patients we determined the effect of arginine depletion by pegylated arginine deiminase (ADI-PEG 20) on whole body protein synthesis and fractional protein synthesis rate in multiple tissues of mice...
2015: PloS One
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