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https://www.readbyqxmd.com/read/27901089/a-silac-based-method-for-quantitative-proteomic-analysis-of-intestinal-organoids
#1
Alexis Gonneaud, Christine Jones, Naomie Turgeon, Dominique Lévesque, Claude Asselin, François Boudreau, François-Michel Boisvert
Organoids have the potential to bridge 3D cell culture to tissue physiology by providing a model resembling in vivo organs. Long-term growing organoids were first isolated from intestinal crypt cells and recreated the renewing intestinal epithelial niche. Since then, this technical breakthrough was applied to many other organs, including prostate, liver, kidney and pancreas. We describe here how to apply a SILAC-based quantitative proteomic approach to measure protein expression changes in intestinal organoids under different experimental conditions...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900610/novel-sgc-stimulators-and-sgc-activators-for-the-treatment-of-heart-failure
#2
Stefanie Breitenstein, Lothar Roessig, Peter Sandner, Kelly S Lewis
The burden of heart failure (HF) increases worldwide with an aging population, and there is a high unmet medical need in both, heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). The nitric oxide (NO) pathway is a key regulator in the cardiovascular system and modulates vascular tone and myocardial performance. Disruption of the NO-cyclic guanosine monophosphate (cGMP) signaling axis and impaired cGMP formation by endothelial dysfunction could lead to vasotone dysregulation, vascular and ventricular stiffening, fibrosis, and hypertrophy resulting in a decline of heart as well as kidney function...
November 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27899683/validation-of-an-integrative-mathematical-model-of-dehydration-and-rehydration-in-virtual-humans
#3
W Andrew Pruett, John S Clemmer, Robert L Hester
Water homeostasis is one of the body's most critical tasks. Physical challenges to the body, including exercise and surgery, almost always coordinate with some change in water handling reflecting the changing needs of the body. Vasopressin is the most important hormone that contributes to short-term water homeostasis. By manipulating vascular tone and regulating water reabsorption in the collecting duct of the kidneys, vasopressin can mediate the retention or loss of fluids quickly. In this study, we validated HumMod, an integrative mathematical model of human physiology, against six different challenges to water homeostasis with special attention to the secretion of vasopressin and maintenance of electrolyte balance...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27899231/carvedilol-exacerbate-gentamicin-induced-kidney-mitochondrial-alterations-in-adult-rat
#4
Luís Félix, M M Oliveira, Romeu Videira, Elisabete Maciel, Nuno D Alves, Fernando M Nunes, Anabela Alves, José M Almeida, M Rosário M Domingues, Francisco P Peixoto
Gentamicin is an aminoglycoside antibiotic widely used to treat many types of bacterial infections. Although its properties, his clinical use is limited due to the occurrence of nephrotoxicity, which has been related to mitochondrial dysfunction. Carvedilol, an antihypertensive drug with strong antioxidant properties, has been tested in order to prevent gentamicin nephrotoxicity. This study aimed to test this hypothesis using a rat model of gentamicin-induced nephrotoxicity. Animals were treated subcutaneously with DMSO (control) (0...
November 26, 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/27898678/leukocyte-telomere-length-in-relation-to-17-biomarkers-of-cardiovascular-disease-risk-a-cross-sectional-study-of-us-adults
#5
David H Rehkopf, Belinda L Needham, Jue Lin, Elizabeth H Blackburn, Ami R Zota, Janet M Wojcicki, Elissa S Epel
BACKGROUND: Leukocyte telomere length (LTL) is a putative biological marker of immune system age, and there are demonstrated associations between LTL and cardiovascular disease. This may be due in part to the relationship of LTL with other biomarkers associated with cardiovascular disease risk. However, the strength of associations between LTL and adiposity, metabolic, proinflammatory, and cardiovascular biomarkers has not been systematically evaluated in a United States nationally representative population...
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27896974/learning-attributes-of-disease-progression-from-trajectories-of-sparse-lab-values
#6
Vibhu Agarwal, Nigam H Shah
There is heterogeneity in the manifestation of diseases, therefore it is essential to understand the patterns of progression of a disease in a given population for disease management as well as for clinical research. Disease status is often summarized by repeated recordings of one or more physiological measures. As a result, historical values of these physiological measures for a population sample can be used to characterize disease progression patterns. We use a method for clustering sparse functional data for identifying sub-groups within a cohort of patients with chronic kidney disease (CKD), based on the trajectories of their Creatinine measurements...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27896654/bowel-preparation-is-associated-with-reduced-morbidity-in-elderly-patients-undergoing-elective-colectomy
#7
Scott C Dolejs, Michael J Guzman, Alyssa D Fajardo, Bruce W Robb, Bryan K Holcomb, Ben L Zarzaur, Joshua A Waters
BACKGROUND: Bowel preparation in elderly patients is associated with physiologic derangements that may result in postoperative complications. The aim of this study is to determine the impact of bowel preparation on postoperative outcomes in elderly patients. METHODS: Patients age 75 years and older who underwent elective colectomy were identified from the 2012-2014 American College of National Surgical Quality Improvement Program (ACS-NSQIP database). Patients were grouped into no bowel preparation, mechanical bowel preparation (MBP), oral antibiotic preparation (OABP), or combined MBP + OABP...
November 28, 2016: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/27894883/incubation-relative-humidity-induces-renal-morphological-and-physiological-remodeling-in-the-embryo-of-the-chicken-gallus-gallus-domesticus
#8
Greta Bolin, Benjamin Dubansky, Warren W Burggren
The metanephric kidneys of the chicken embryo, along with the chorioallantoic membrane, process water and ions to maintain osmoregulatory homeostasis. We hypothesized that changes in relative humidity (RH) and thus osmotic conditions during embryogenesis would alter the developmental trajectory of embryonic kidney function. White leghorn chicken eggs were incubated at one of 25-30% relative humidity, 55-60% relative humidity, and 85-90% relative humidity. Embryos were sampled at days 10, 12, 14, 16, and 18 to examine embryo and kidney mass, glomerular characteristics, body fluid osmolalities, hematological properties, and whole embryo oxygen consumption...
November 25, 2016: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/27894421/nonoperative-management-of-blunt-solid-organ-injury-in-pediatric-surgery
#9
REVIEW
David M Notrica, Maria E Linnaus
In the last decade, higher rates of nonoperative management of liver, spleen, and kidney injuries have been achieved. An algorithmic approach may improve success on a national level. Factors for success include management strategy based on physiologic status of the child, early attempt at resuscitation using blood products, and appropriate use of adjuncts. Shorter hospitalizations are appropriate for children who have not bled significantly, and discharge instructions facilitate the safety of early discharge...
February 2017: Surgical Clinics of North America
https://www.readbyqxmd.com/read/27894247/aldose-reductase-as-a-drug-target-for-treatment-of-diabetic-nephropathy-promises-and-challenges
#10
Heba El Gamal, Shankar Munusamy
Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes mellitus and the leading cause of end stage renal disease. One of the key pathways activated in DN is the polyol pathway, in which glucose is converted to sorbitol (a relatively non-metabolizable sugar) by the enzyme aldose reductase (AR). Shunting of glucose into this pathway causes disruption to glucose metabolism and subsequently damages the tissues via increased oxidative stress, protein kinase c activation and production of advanced glycation end products (AGE) in the kidney...
November 28, 2016: Protein and Peptide Letters
https://www.readbyqxmd.com/read/27889508/physiological-responses-and-changes-in-gene-expression-in-the-large-yellow-croaker-larimichthys-crocea-following-exposure-to-hypoxia
#11
Qian-Feng Wang, Wei-Liang Shen, Cong-Cong Hou, Cheng Liu, Xiong-Fei Wu, Jun-Quan Zhu
Organisms at all levels of evolutionary complexity react to hypoxic stress. To clarify the effects of acute hypoxia on physiological and biochemical responses of Larimichthys crocea, we measured the activity levels of the antioxidant enzymes superoxide dismutase and catalase, hemoglobin concentration, functional indices of the liver (aspartate transaminase, alanine transaminase), heart (phosphocreatine kinase), and immune system (alkaline phosphatase), as well as mRNA expression levels of the immunity-related genes Hsp70 and HIF-1α at different time points of hypoxic...
November 24, 2016: Chemosphere
https://www.readbyqxmd.com/read/27885692/physiologically-based-pharmacokinetic-model-for-ethyl-tertiary-butyl-ether-and-tertiary-butyl-alcohol-in-rats-contribution-of-binding-to-%C3%AE-2u-globulin-in-male-rats-and-high-exposure-nonlinear-kinetics-to-toxicity-and-cancer-outcomes
#12
Susan J Borghoff, Caroline Ring, Marcy I Banton, Teresa L Leavens
In cancer bioassays, inhalation, but not drinking water exposure to ethyl tertiary-butyl ether (ETBE), caused liver tumors in male rats, while tertiary-butyl alcohol (TBA), an ETBE metabolite, caused kidney tumors in male rats following exposure via drinking water. To understand the contribution of ETBE and TBA kinetics under varying exposure scenarios to these tumor responses, a physiologically based pharmacokinetic model was developed based on a previously published model for methyl tertiary-butyl ether, a structurally similar chemical, and verified against the literature and study report data...
November 24, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27885585/the-conundrums-of-chronic-kidney-disease-and-aging
#13
REVIEW
Richard J Glassock, Aleksandar Denic, Andrew D Rule
Chronic kidney disease (CKD), as presently defined, is a common disorder. Aging is a nearly universal phenomenon that can affect renal anatomy and function, but at variable rates in individuals. Loss of nephrons and a decline in glomerular filtration rate (GFR) is a characteristic of normal aging, called renal senescence. Using fixed and absolute thresholds for defining CKD on the basis of GFR for all ages may lead to diagnostic uncertainty (a conundrum) in both young and older subjects. This brief review will consider the physiological and anatomical changes of the kidney occurring in the process of normal renal senescence focusing on GFR and will examine the relevance of these observation for the diagnosis of CKD using GFR as the distinguishing parameter...
November 25, 2016: Journal of Nephrology
https://www.readbyqxmd.com/read/27885372/treatment-planning-in-prrt-based-on-simulated-pet-data-and-a-pbpk-model-determination-of-accuracy-using-a-pet-noise-model
#14
Deni Hardiansyah, Wei Guo, Ali Asgar Attarwala, Peter Kletting, Felix M Mottaghy, Gerhard Glatting
AIM: To investigate the accuracy of treatment planning in peptide-receptor radionuclide therapy (PRRT) based on simulated PET data (using a PET noise model) and a physiologically based pharmacokinetic (PBPK) model. METHODS: The parameters of a PBPK model were fitted to the biokinetic data of 15 patients. True mathematical phantoms of patients (MPPs) were the PBPK model with the fitted parameters. PET measurements after bolus injection of 150 MBq (68)Ga-DOTATATE were simulated for the true MPPs...
November 25, 2016: Nuklearmedizin. Nuclear Medicine
https://www.readbyqxmd.com/read/27885332/2-3-5-4-tetrahydroxystilbene-2-o-%C3%AE-d-glucoside-promotes-expression-of-the-longevity-gene-klotho
#15
Shuang Ling, Ju Duan, Rongzhen Ni, Jin-Wen Xu
The longevity gene klotho has numerous physiological functions, such as regulating calcium and phosphorus levels, delaying senescence, improving cognition, reducing oxidative stress, and protecting vascular endothelial cells. This study tested whether 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG), a small molecule with antiaging effects, regulates the expression and physiological effects of klotho. Our results showed that THSG dose-dependently increased the luciferase reporter activity of the klotho gene, reversed the decrease in mRNA and protein expression of klotho which was induced by angiotensin II in NRK-52E renal tubular epithelial cells, and increased klotho mRNA expression in the cerebral cortex, hippocampus, testis, and kidney medulla of spontaneously hypertensive rats...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27881662/the-polycystins-are-modulated-by-cellular-oxygen-sensing-pathways-and-regulate-mitochondrial-function
#16
Valeria Padovano, Ivana Y Kuo, Lindsey K Stavola, Hans R Aerni, Benjamin J Flaherty, Hannah C Chapin, Ming Ma, Stefan Somlo, Alessandra Boletta, Barbara E Ehrlich, Jesse Rinehart, Michael J Caplan
Autosomal dominant polycystic kidney disease is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which form an ion channel complex that may mediate ciliary sensory processes and regulate endoplasmic reticulum Ca(2+) release. Loss of PC1 expression profoundly alters cellular energy metabolism. The mechanisms that control the trafficking of PC1 and PC2 as well as their broader physiological roles remain poorly understood. We found that O2 levels regulate the subcellular localization and the channel activity of the polycystin complex through its interaction with the O2-sensing prolyl hydroxylase domain containing protein EGLN3 (or PHD3), which hydroxylates PC1...
November 23, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27878608/claudins-in-barrier-and-transport-function-the-kidney
#17
REVIEW
Yongfeng Gong, Jianghui Hou
Claudins are discovered to be key players in renal epithelial physiology. They are involved in developmental, physiological, and pathophysiological differentiation. In the glomerular podocytes, claudin-1 is an important determinant of cell junction fate. In the proximal tubule, claudin-2 plays important roles in paracellular salt reabsorption. In the thick ascending limb, claudin-14, -16, and -19 regulate the paracellular reabsorption of calcium and magnesium. Recessive mutations in claudin-16 or -19 cause an inherited calcium and magnesium losing disease...
November 23, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27878313/targeting-renal-glucose-reabsorption-to-treat-hyperglycaemia-the-pleiotropic-effects-of-sglt2-inhibition
#18
REVIEW
Volker Vallon, Scott C Thomson
Healthy kidneys filter ∼160 g/day of glucose (∼30% of daily energy intake) under euglycaemic conditions. To prevent valuable energy from being lost in the urine, the proximal tubule avidly reabsorbs filtered glucose up to a limit of ∼450 g/day. When blood glucose levels increase to the point that the filtered load exceeds this limit, the surplus is excreted in the urine. Thus, the kidney provides a safety valve that can prevent extreme hyperglycaemia as long as glomerular filtration is maintained. Most of the capacity for renal glucose reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in the early proximal tubule...
November 22, 2016: Diabetologia
https://www.readbyqxmd.com/read/27878278/alteration-of-epoxyeicosatrienoic-acids-in-the-liver-and-kidney-of-cytochrome-p450-4f2-transgenic-mice
#19
Bijun Zhang, Guangrui Lai, Xiaoliang Liu, Yanyan Zhao
Arachidonic acid (AA) can be metabolized into 20-hydroxyeicosatetraenoic acid (20-HETE) by ω-hydroxylases, and epoxyeicosatrienoic acids (EETs) by epoxygenases. The effects of EETs in cardiovascular physiology are vasodilatory, anti-inflammatory and anti‑apoptotic, which are opposite to the function to 20‑HETE. However, EETs are not stable in vivo, and are rapidly degraded to the biologically less active metabolites, dihydroxyeicosatrienoic acids, via soluble epoxide hydrolase (sEH). Western blotting, reverse transcription‑quantitative polymerase chain reaction and liquid chromatography tandem mass spectrometry were performed in order to determine target RNA and protein expression levels...
November 23, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27875304/rapid-renal-regulation-of-peroxisome-proliferator-activated-receptor-gamma-coactivator-1%C3%AE-by-extracellular-regulated-kinase-1-2-in-physiological-and-pathological-conditions
#20
Justin B Collier, Ryan M Whitaker, Scott T Eblen, Rick G Schnellmann
Previous studies have shown that extracellular regulated kinase 1/2 (ERK1/2) directly inhibits mitochondrial function during cellular injury. We evaluated the role of ERK1/2 on the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) gene, a master regulator of mitochondrial function. The potent and specific MEK1/2 inhibitor trametinib rapidly blocked ERK1/2 phosphorylation, decreased cytosolic and nuclear FOXO3a/1 phosphorylation, and increased PGC-1α gene expression and its downstream mitochondrial biogenesis (MB) targets under physiological conditions in the kidney cortex and in primary renal cell cultures...
November 14, 2016: Journal of Biological Chemistry
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