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Renal physiology

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https://www.readbyqxmd.com/read/28438781/transporter-mediated-disposition-clinical-pharmacokinetics-and-cholestatic-potential-of-glyburide-and-its-primary-active-metabolites
#1
Rui Li, Yi-An Bi, Anna Vildhede, Renato J Scialis, Sumathy Mathialagan, Xin Yang, Lisa D Marroquin, Jian Lin, Manthena V S Varma
Glyburide is widely used for the treatment of type 2 diabetes mellitus. We studied the mechanisms involved in the disposition of glyburide and its pharmacologically active hydroxy metabolites, M1 and M2b; and evaluated their clinical pharmacokinetics and the potential role in glyburide-induced cholestasis employing physiologically based pharmacokinetic (PBPK) modeling. Transport studies of parent and metabolites in human hepatocytes and transfected cell systems imply hepatic uptake mediated by organic anion transporting polypeptides...
April 24, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28438429/association-of-serum-magnesium-level-with-poor-glycemic-control-and-renal-functions-in-nepalese-patients-with-type-2-diabetes-mellitus
#2
Daya Ram Pokharel, Dipendra Khadka, Manoj Sigdel, Naval Kishor Yadav, Ramchandra Kafle, Ravindra Mohan Sapkota, Sanjay Kumar Jha
BACKGROUND: Hypomagnesaemia has been shown to be associated with type 2 diabetes mellitus (T2DM) and its complications. The present study investigated the association of hypomagnesaemia with T2DM and its complications in patients hailed mostly from the western hilly region of Nepal. METHODS: This study was conducted among 150 type 2 diabetic patients and 150 of non-diabetic controls between May to September 2016. Relevant demographic, anthropometric, physiological and biochemical variables were measured using standard protocols...
April 6, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28437467/mutant-uromodulin-expression-leads-to-altered-homeostasis-of-the-endoplasmic-reticulum-and-activates-the-unfolded-protein-response
#3
Céline Schaeffer, Stefania Merella, Elena Pasqualetto, Dejan Lazarevic, Luca Rampoldi
Uromodulin is the most abundant urinary protein in physiological conditions. It is exclusively produced by renal epithelial cells lining the thick ascending limb of Henle's loop (TAL) and it plays key roles in kidney function and disease. Mutations in UMOD, the gene encoding uromodulin, cause autosomal dominant tubulointerstitial kidney disease uromodulin-related (ADTKD-UMOD), characterised by hyperuricemia, gout and progressive loss of renal function. While the primary effect of UMOD mutations, retention in the endoplasmic reticulum (ER), is well established, its downstream effects are still largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28436367/bilateral-obstructing-ureteric-calculi-in-pregnancy-a-rare-cause-of-acute-renal-failure
#4
Todd G Manning, Daniel Christidis, David Wetherell, Ruth Cameron-Jeffs, Nathan Lawrentschuk
Bilateral obstructing ureteric calculi is a rare cause of acute renal failure. Although urolithiasis in later pregnancy is not uncommon, the development of bilateral obstruction secondary to ureteric calculi in the first trimester is rare and poses difficulty to diagnosis and management. Symptoms of diseases and physiological changes associated with pregnancy can obscure diagnosis of urolithiasis and obstructive uropathy. Advances in minimally invasive endourology afford intervention with reduced risk to fetal health...
April 2017: Canadian Journal of Urology
https://www.readbyqxmd.com/read/28433109/pathogenesis-of-wilson-disease
#5
Ivo Florin Scheiber, Radan Brůha, Petr Dušek
Wilson disease is an autosomal-recessive disorder originating from a genetic defect in the copper-transporting ATPase ATP7B that is required for biliary copper secretion and loading of ceruloplasmin with copper. Impaired ATP7B function in Wilson disease results in excessive accumulation of copper in liver, brain, and other tissues. Toxic copper deposits may induce oxidative stress, modify expression of genes, directly inhibit proteins, and impair mitochondrial function, leading to hepatic, neuropsychiatric, renal, musculoskeletal, and other symptoms...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28432788/structure-of-fam20a-reveals-a-pseudokinase-featuring-unique-disulfide-pattern-and-inverted-atp-binding
#6
Jixin Cui, Qinyu Zhu, Hui Zhang, Michael A Cianfrocco, Andres E Leschziner, Jack E Dixon, Junyu Xiao
Mutations in FAM20A cause tooth enamel defects known as Amelogenesis Imperfecta (AI) and renal calcification. We previously showed that Fam20A is a secretory pathway pseudokinase and allosterically activates the physiological casein kinase Fam20C to phosphorylate secreted proteins important for biomineralization (Cui et al., 2015). Here we report the nucleotide-free and ATP-bound structures of Fam20A. Fam20A exhibits a distinct disulfide bond pattern mediated by a unique insertion region. Loss of this insertion due to abnormal mRNA splicing interferes with the structure and function of Fam20A, resulting in AI...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28419353/the-effect-of-ramadan-fast-on-the-incidence-of-renal-colic-emergency-department-visits
#7
Iftach Sagy, Vladimir Zeldetz, Daniel Halperin, Muhammad Abu Tailakh, Victor Novack
Background: Renal colic (RC) is one of the most common reasons for emergency department (ED) visits. Although RC is associated with high ambient temperature and with physiological changes that occur during fast, the literature onbetween Ramadan and RC incidence is scarce. Methods: We obtained health data of patients visited the emergency department (ED) of a large tertiary center during the years 2004-2015, with a primary diagnosis of RC. To estimate the association of RC and Ramadan, we utilized bi-weekly RC incidence Poisson models adjusted for ambient temperature and seasonality in two ethnic groups residing in the region: Muslims and Jews...
April 13, 2017: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/28417963/loop-diuretics-affect-skeletal-myoblast-differentiation-and-exercise-induced-muscle-hypertrophy
#8
Shintaro Mandai, Susumu Furukawa, Manami Kodaka, Yutaka Hata, Takayasu Mori, Naohiro Nomura, Fumiaki Ando, Yutaro Mori, Daiei Takahashi, Yuki Yoshizaki, Yuri Kasagi, Yohei Arai, Emi Sasaki, Sayaka Yoshida, Yasuro Furuichi, Nobuharu L Fujii, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
Muscle wasting or sarcopenia contributes to morbidity and mortality in patients with cancer, renal failure, or heart failure, and in elderly individuals. Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) is highly expressed in mammalian skeletal muscle, where it contributes to the generation of membrane ion currents and potential. However, the physiologic function of NKCC1 in myogenesis is unclear. We investigated this issue using the NKCC1 inhibitors bumetanide and furosemide, which are commonly used loop diuretics...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28413968/hypertension-and-heart-failure-with-preserved-ejection-fraction-connecting-the-dots
#9
Costas Tsioufis, Georgios Georgiopoulos, Dimitrios Oikonomou, Costas Thomopoulos, Niki Katsiki, Alexandros Kasiakogias, Christina Chrysochoou, Dimitrios Konstantinidis, Theodoros Kalos, Dimitrios Tousoulis
Heart failure (HF) with preserved ejection fraction (EF) (HFpEF) accounts for approximately 50% of HF cases and its prevalence relative to HF with reduced EF is rising. Hypertension (HT) is the most common co-morbidity in HFpEF patients and it is implicated in both the pathogenesis and the prognosis of the disease. Therefore, HT is a modifiable risk factor of high yield in HFpEF. We reviewed the literature for epidemiologic data supporting the co-aggregation of the two entities as well as patho-physiologic mechanisms linking HT to HFpEF...
April 14, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28413960/circulating-ace2-in-cardiovascular-and-kidney-diseases
#10
Lidia Anguiano Gómez, Marta Riera Oliva, Julio Pascual Santos, María José Soler
Angiotensin converting enzyme(ACE) 2 is a homologue of ACE that catalyzes the conversion of Angiotensin(Ang) II into Ang1-7, which induces vasodilation, anti-fibrotic, anti-proliferative and anti-inflammatory effects. Given that ACE2 counterbalances the effects of Ang II, it has been proposed as a biomarker in kidney disease patients. Circulating ACE2 has been studied in human and experimental studies under physiological and pathological conditions and different techniques have been assessed to determine its enzymatic activity...
April 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28413520/prognosis-of-patients-with-acinetobacter-baumannii-infection-in-the-intensive-care-unit-a-retrospective-analysis
#11
Dong Xiao, Lu Wang, Daquan Zhang, Dongming Xiang, Qi Liu, Xuezhong Xing
The present retrospective study aimed to investigate the prognostic factors for critically ill patients with an Acinetobacter baumannii (A. baumannii) infection. A total of 37 patients from the intensive care unit (ICU) were enrolled in the study. Data was collected from patients, including age, gender, ethnicity, A. baumannii infection status, concurrent infection status, prescribed antibiotics, Acute Physiology and Chronic Health Evaluation II (APACHE II) and sepsis-related organ failure assessment (SOFA) scores, procalcitonin level, site of infection, shock, sepsis and renal replacement therapy status...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28412400/prediction-of-losartan-active-carboxylic-acid-metabolite-exposure-following-losartan-administration-using-static-and-physiologically-based-pharmacokinetic-models
#12
Hoa Q Nguyen, Jian Lin, Emi Kimoto, Ernesto Callegari, Susanna Tse, R Scott Obach
The aim of this study was to evaluate a strategy based on static and dynamic physiologically based pharmacokinetic (PBPK) modeling for the prediction of metabolite and parent drug area under the time-concentration curve ratio (AUCm/AUCp) and their PK profiles in humans using in vitro data when active transport processes are involved in disposition. The strategy was applied to losartan and its pharmacologically active metabolite carboxylosartan as test compounds. Hepatobiliary transport including transport-mediated uptake, canilicular and basolateral efflux, and metabolic clearance estimates were obtained from in vitro studies using human liver microsomes and sandwich cultured hepatocytes...
April 12, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28411279/characterization-and-interspecies-scaling-of-rhtnf-%C3%AE-pharmacokinetics-with-minimal-physiologically-based-pharmacokinetic-mpbpk-models
#13
Xi Chen, Debra C DuBois, Richard R Almon, William J Jusko
Tumor necrosis factor-α (TNF-α) is a soluble cytokine and target of specific monoclonal antibodies (mAbs) and other biological agents used for the treatment of inflammatory diseases. These biologics exert their pharmacological effects through binding and neutralizing TNF-α, and thus prevent TNF-α from interacting with its cell surface receptors. The magnitude of pharmacological effects is governed not only by the pharmacokinetics of mAbs, but also the kinetic fate of TNF-α. We have examined the pharmacokinetics of rhTNF-α in rats at low doses and quantitatively characterized its pharmacokinetic features with a minimal physiologically-based pharmacokinetic (mPBPK) model...
April 14, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28409342/zebrafish-as-a-model-of-kidney-disease
#14
Elvin E Morales, Rebecca A Wingert
Animal models have been an invaluable means to advance biomedical research as they provide experimental avenues for cellular and molecular investigations of disease pathology. The zebrafish (Danio rerio) is a good alternative to mammalian models that can be used to apply powerful genetic experimental methods normally used in invertebrates to answer questions about vertebrate development and disease. In the case of the kidney, the zebrafish has proven itself to be an applicable and versatile experimental system, mainly due to the simplicity of its pronephros, which contains two nephrons that possess conserved structural and physiological aspects with mammalian nephrons...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28409340/drosophila-malpighian-tubules-a-model-for-understanding-kidney-development-function-and-disease
#15
Naveen Kumar Gautam, Puja Verma, Madhu G Tapadia
The Malpighian tubules of insects are structurally simple but functionally important organs, and their integrity is important for the normal excretory process. They are functional analogs of human kidneys which are important physiological organs as they maintain water and electrolyte balance in the blood and simultaneously help the body to get rid of waste and toxic products after various metabolic activities. In addition, it receives early indications of insults to the body such as immune challenge and other toxic components and is essential for sustaining life...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28407811/saline-versus-balanced-crystalloids-for-intravenous-fluid-therapy-in-the-emergency-department-study-protocol-for-a-cluster-randomized-multiple-crossover-trial
#16
Wesley H Self, Matthew W Semler, Jonathan P Wanderer, Jesse M Ehrenfeld, Daniel W Byrne, Li Wang, Leanne Atchison, Matthew Felbinger, Ian D Jones, Stephan Russ, Andrew D Shaw, Gordon R Bernard, Todd W Rice
BACKGROUND: Prior studies in critically ill patients suggest the supra-physiologic chloride concentration of 0.9% ("normal") saline may be associated with higher risk of renal failure and death compared to physiologically balanced crystalloids. However, the comparative effects of 0.9% saline and balanced fluids are largely unexamined among patients outside the intensive care unit, who represent the vast majority of patients treated with intravenous fluids. METHODS/DESIGN: This study, entitled Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED), is a pragmatic, cluster, multiple-crossover trial at a single institution evaluating clinical outcomes of adults treated with 0...
April 13, 2017: Trials
https://www.readbyqxmd.com/read/28407045/novel-pathogenesis-regulation-of-apoptosis-by-apelin-apj-system
#17
Jiaqi Liu, Meiqing Liu, Linxi Chen
Apelin is the endogenous peptide APJ receptor, while APJ is a member of the G protein-coupled receptors family. Recent evidence strongly suggests that Apelin/APJ system influences apoptosis in various diseases through different signal pathways. In this review, we discuss the possible mechanisms by which the Apelin/APJ system inhibits apoptosis, including the phosphatidylinositol-3-kinase (PI3K)/Akt, ERK1/2, caspase signaling, and autophagy pathway. We also summarize the role of Apelin/APJ system in apoptosis in myocardial ischemia-reperfusion (I/R) injury, pulmonary artery hypertension, retinal neovascular disease, acute renal injury, skeletal homeostasis, and gastrointestinal diseases...
April 12, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28405625/resistance-to-hypertension-mediated-by-intercalated-cells-of-the-collecting-duct
#18
Johannes Stegbauer, Daian Chen, Marcela Herrera, Matthew A Sparks, Ting Yang, Eva Königshausen, Susan B Gurley, Thomas M Coffman
The renal collecting duct (CD), as the terminal segment of the nephron, is responsible for the final adjustments to the amount of sodium excreted in urine. While angiotensin II modulates reabsorptive functions of the CD, the contribution of these actions to physiological homeostasis is not clear. To examine this question, we generated mice with cell-specific deletion of AT1A receptors from the CD. Elimination of AT1A receptors from both principal and intercalated cells (CDKO mice) had no effect on blood pressures at baseline or during successive feeding of low- or high-salt diets...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28404591/intravital-imaging-of-the-kidney-in-a-rat-model-of-salt-sensitive-hypertension
#19
Bradley T Endres, Ruben M Sandoval, George J Rhodes, Silvia B Campos-Bilderback, Malgorzata M Kamocka, Christopher McDermott-Roe, Alexander Staruschenko, Bruce A Molitoris, Aron M Geurts, Oleg Palygin
Hypertension is one of the most prevalent diseases worldwide, and a major risk factor for renal failure and cardiovascular disease. The role of albuminuria, a common feature of hypertension and robust predictor of cardiorenal disorders, remains incompletely understood. The goal of this study was to investigate the mechanisms leading to albuminuria in the kidney of a rat model of hypertension, the Dahl salt-sensitive (SS) rat. To determine the relative contributions of the glomerulus and proximal tubule (PT) to albuminuria, we applied intravital two-photon-based imaging to investigate the complex renal physiological changes that occur during salt-induced hypertension...
April 12, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28403789/metaflammation-tissue-specific-alterations-of-the-nlrp3-inflammasome-platform
#20
Raffaella Mastrocola, Manuela Aragno, Giuseppe Alloatti, Massimo Collino, Claudia Penna, Pasquale Pagliaro
In the last decades, the extension of life expectancy and the increased consumption of foods rich in saturated fats and added sugars have exposed the general population to emerging health problems. The prevalence of metabolic syndrome (MS), composed of a cluster of factors as obesity, dyslipidemia, hyperglycemia, and hypertension, is rapidly increasing in industrialized and developing countries leading to precocious onset of age-related diseases. Indeed, oxidative stress, accumulation of advanced glycation endproducts, and a chronic low-grade inflammation are common features of MS and physiological ageing...
April 7, 2017: Current Medicinal Chemistry
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