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https://www.readbyqxmd.com/read/29150543/toxicokinetics-and-physiologically-based-pharmacokinetic-modeling-of-the-shellfish-toxin-domoic-acid-in-nonhuman-primates
#1
Jing Jing, Rebekah Petroff, Sara Shum, Brenda Crouthamel, Ariel R Topletz, Kimberly S Grant, Thomas M Burbacher, Nina Isoherranen
Domoic acid (DA), a neurotoxin, is produced by marine algae and has caused toxications worldwide in animals and humans. However, the toxicokinetics of DA has not been fully evaluated, and information is missing on the disposition of DA following oral exposures at doses that are considered safe for human consumption. In this study, toxicokinetics of DA were investigated in cynomolgus monkeys, following single doses of 5 µg/kg DA iv, 0.075 mg/kg DA po and 0.15 mg/kg DA po. Following iv dosing, DA had a systemic clearance of 124 ± 71 ml/hr/kg, volume of distribution at steady state of 131±71 ml/kg and elimination half-life of 1...
November 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29150416/-bicarbonate-from-physiology-to-treatment-for-all-clinicians
#2
Julie Beaume, Antoine Braconnier, Thibault Dolley-Hitze, Jean-Philippe Bertocchio
Acid-base regulation is essential to maintain homeostasis in humans. Carbonic acid/bicarbonate (H2CO3/HCO3(-)) couple is the most predominant extracellular buffer to keep plasma pH within a physiological range. The ability to (re)generate such a buffer is a key milestone that necessitates to understand a precise physiology of both renal tubule and digestive tract. Here, we first reviewed renal and digestive cycles of bicarbonate in physiology. We also reviewed pathological findings where acid-base disequilibrium is involved and nutritional and/or alkali therapy could be necessary...
November 14, 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/29149222/personalized-medicine-and-hispanic-health-improving-health-outcomes-and-reducing-health-disparities-a-national-heart-lung-and-blood-institute-workshop-report
#3
M Larissa Avilés-Santa, John Heintzman, Nangel M Lindberg, Rafael Guerrero-Preston, Kenneth Ramos, Ana L Abraído-Lanza, Jonca Bull, Adolph Falcón, Mary Ann McBurnie, Ernest Moy, George Papanicolaou, Ileana L Piña, Jennifer Popovic, Shakira F Suglia, Miguel A Vázquez
Persons of Hispanic/Latino descent may represent different ancestries, ethnic and cultural groups and countries of birth. In the U.S., the Hispanic/Latino population is projected to constitute 29% of the population by 2060. A personalized approach focusing on individual variability in genetics, environment, lifestyle and socioeconomic determinants of health may advance the understanding of some of the major factors contributing to the health disparities experienced by Hispanics/Latinos and other groups in the U...
2017: BMC Proceedings
https://www.readbyqxmd.com/read/29148702/influence-of-particle-geometry-on-gastrointestinal-transit-and-absorption-following-oral-administration
#4
Dong Li, Jie Zhuang, Haisheng He, Sifan Jiang, Amrita Banerjee, Yi Lu, Wei Wu, Samir Mitragotri, Li Gan, Jianping Qi
Geometry has been considered as one of the important parameters in nanoparticle design since it affects cellular uptake, transport across the physiological barriers and in vivo distribution. However, only a few studies have been conducted to elucidate the influence of nanoparticle geometry in their in vivo fate after oral administration. This paper discloses the effect of nanoparticle shape on transport and absorption in gastrointestinal tract (GIT). Nanorods and nanospheres were prepared, and labeled using fluorescence resonance energy transfer (FRET) molecules to track the in vivo fate of intact nanoparticles accurately...
November 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29144825/salt-hypertension-and-immunity
#5
A Justin Rucker, Nathan P Rudemiller, Steven D Crowley
The link between inappropriate salt retention in the kidney and hypertension is well recognized. However, growing evidence suggests that the immune system can play surprising roles in sodium homeostasis, such that the study of inflammatory cells and their secreted effectors has provided important insights into salt sensitivity. As part of the innate immune system, myeloid cells have diverse roles in blood pressure regulation, ranging from prohypertensive actions in the kidney, vasculature, and brain, to effects in the skin that attenuate blood pressure elevation...
November 16, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/29143759/the-role-of-food-antioxidants-benefits-of-functional-foods-and-influence-of-feeding-habits-on-the-health-of-the-older-person-an-overview
#6
REVIEW
Douglas W Wilson, Paul Nash, Harpal Singh Buttar, Keith Griffiths, Ram Singh, Fabien De Meester, Rie Horiuchi, Toru Takahashi
This overview was directed towards understanding the relationship of brain functions with dietary choices mainly by older humans. This included food color, flavor, and aroma, as they relate to dietary sufficiency or the association of antioxidants with neurodegenerative diseases such as dementia and Alzheimer's disease. Impairment of olfactory and gustatory function in relation to these diseases was also explored. The role of functional foods was considered as a potential treatment of dementia and Alzheimer's disease through inhibition of acetylcholinesterase as well as similar treatments based on herbs, spices and antioxidants therein...
October 28, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29142988/proximal-tubular-expression-patterns-of-megalin-and-cubilin-in-proteinuric-nephropathies
#7
Jia Sun, Kjell Hultenby, Jonas Axelsson, Johan Nordström, Bing He, Annika Wernerson, Karin Lindström
Introduction: Receptor-mediated endocytosis is responsible for protein reabsorption in the proximal tubules. For albumin this process involves at least 2 interacting receptors, megalin and cubilin. Albumin is not usually present in the urine, indicating a highly efficient tubular reuptake under physiological conditions. However, early appearance of albuminuria may mean that the tubular system is overwhelmed by large quantities of albumin or that the function is impaired. Methods: To better understand the physiological role of megalin and cubilin in human renal disease, renal biopsies from 15 patients with a range of albuminuria and 3 healthy living donors were analyzed for proximal tubular expression of megalin and cubilin using immunohistochemistry (IHC) and semiquantitative immune-electron microscopy...
July 2017: KI Reports
https://www.readbyqxmd.com/read/29142172/change-in-redox-state-and-heat-shock-protein-expression-in-an-indian-major-carp-cirrhinus-cirrhosus-exposed-to-zinc-and-lead
#8
Mahammed Moniruzzaman, Puja Midday, Anindita Dhara, Debjit Das, Indranath Ghosal, Debosree Mukherjee, Suman Bhusan Chakraborty
Fish are exposed to different heavy metals that may induce numerous physiological changes. In the present study, we examined the redox state in response to a severe stress resulting from two heavy metals (Zinc and Lead) contamination in carp Cirrhinus cirrhosus. Fish were exposed to 1/10th of LC50 of the respective metals [zinc chloride (2.72 mg/L) and lead acetate (2.53 mg/L)] for 30 days and allowed to recover for another 30 days without any metal exposure. Concentration of metals, different enzymatic and non-enzymatic antioxidant agents and expression levels of heat shock protein (HSP) 70 and 90 were measured in the liver and the kidney of fish...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29138470/obesity-promoting-and-anti-thermogenic-effects-of-neutrophil-gelatinase-associated-lipocalin-in-mice
#9
Akira Ishii, Goro Katsuura, Hirotaka Imamaki, Hiroyuki Kimura, Keita P Mori, Takashige Kuwabara, Masato Kasahara, Hideki Yokoi, Kousaku Ohinata, Tomoko Kawanishi, Junichi Tsuchida, Yuji Nakamoto, Kazuwa Nakao, Motoko Yanagita, Masashi Mukoyama, Kiyoshi Mori
Neutrophil gelatinase-associated lipocalin (NGAL, lipocalin 2 or LCN2) is an iron carrier protein whose circulating level is increased by kidney injury, bacterial infection and obesity, but its metabolic consequence remains elusive. To study physiological role of LCN2 in energy homeostasis, we challenged female Lcn2 knockout (KO) and wild-type (WT) mice with high fat diet (HFD) or cold exposure. Under normal diet, physical constitutions of Lcn2 KO and WT mice were indistinguishable. During HFD treatment, Lcn2 KO mice exhibited larger brown adipose tissues (BAT), consumed more oxygen, ate more food and gained less body weights as compared to WT mice...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138217/effectiveness-of-interprofessional-education-in-renal-physiology-curricula-for-health-sciences-graduate-students
#10
Lisa M Harrison-Bernard, Mihran V Naljayan, Jane M Eason, Donald E Mercante, Tina P Gunaldo
The primary purpose of conducting an interprofessional education (IPE) experience during the renal physiology block of a graduate-level course was to provide basic science, physical therapy, and physician assistant graduate students with an opportunity to work as a team in the diagnosis, treatment, and collaborative care of a patient with acute kidney injury. The secondary purpose was to enhance the understanding of basic renal physiology principles with a patient case presentation of renal pathophysiology...
December 1, 2017: Advances in Physiology Education
https://www.readbyqxmd.com/read/29136619/risk-factor-analysis-for-aki-including-laboratory-indicators-a-nationwide-multicenter-study-of-hospitalized-patients
#11
Sasa Nie, Zhe Feng, Li Tang, Xiaolong Wang, Yani He, Jingai Fang, Suhua Li, Yibin Yang, Huijuan Mao, Jundong Jiao, Wenhu Liu, Ning Cao, Wenge Wang, Jifeng Sun, Fengmin Shao, Wenge Li, Qiang He, Hongli Jiang, Hongli Lin, Ping Fu, Xinzhou Zhang, Yinghong Liu, Yonggui Wu, ChunSheng Xi, Meng Liang, Zhijie Qu, Jun Zhu, Guangli Wu, Yali Zheng, Yu Na, Ying Li, Wei Li, Guangyan Cai, Xiangmei Chen
BACKGROUND/AIMS: Risk factor studies for acute kidney injury (AKI) in China are lacking, especially those regarding non-traditional risk factors, such as laboratory indicators. METHODS: All adult patients admitted to 38 tertiary and 22 secondary hospitals in China in any one month between July and December 2014 were surveyed. AKI patients were screened according to the Kidney Disease: Improving Global Outcomes' definition of AKI. Logistic regression was used to analyze the risk factors for AKI, and Cox regression was used to analyze the risk of in-hospital mortality for AKI patients; additionally, a propensity score analysis was used to reconfirm the risk factors among laboratory indicators for mortality...
October 24, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29134616/zonulin-inflammation-and-iron-status-in-patients-with-early-stages-of-chronic-kidney-disease
#12
Ewelina Lukaszyk, Mateusz Lukaszyk, Ewa Koc-Zorawska, Anna Bodzenta-Lukaszyk, Jolanta Malyszko
BACKGROUND/AIMS: Zonulin is the only known regulator of intestinal permeability. It is also considered as a potential inflammatory marker in several conditions such as diabetes and inflammatory bowel syndrome. The aim of the study was to investigate zonulin levels in patients with early stages of CKD and its possible correlation with inflammation, anemia and iron status parameters. METHODS: Eighty-eight patients with early stages of CKD and 23 healthy volunteers were enrolled in the study...
November 13, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29133259/loss-of-pit-2-results-in-abnormal-bone-development-and-decreased-bone-mineral-density-and-length-in-mice
#13
Shunsuke Yamada, Mary C Wallingford, Suhaib Borgeia, Timothy C Cox, Cecilia M Giachelli
Normal bone mineralization requires phosphate oversaturation in bone matrix vesicles, as well as normal regulation of phosphate metabolism via the interplay among bone, intestine, and kidney. In turn, derangement of phosphate metabolism greatly affects bone function and structure. The type III sodium-dependent phosphate transporters, PiT-1 and PiT-2, are believed to be important in tissue phosphate metabolism and physiological bone formation, but their requirement and molecular roles in bone remain poorly investigated...
November 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29130363/antioxidant-role-of-autophagy-in-maintaining-the-integrity-of-glomerular-capillaries
#14
Jun Matsuda, Tomoko Namba, Yoshitsugu Takabatake, Tomonori Kimura, Atsushi Takahashi, Takeshi Yamamoto, Satoshi Minami, Shinsuke Sakai, Ryuta Fujimura, Jun-Ya Kaimori, Isao Matsui, Takayuki Hamano, Yoko Fukushima, Keiko Matsui, Tomoyoshi Soga, Yoshitaka Isaka
Autophagy is a lysosomal degradation system by which cytosolic materials and damaged organelles are broken down into basic components. To explore the physiological role of autophagy in glomerular endothelial cells (GEnCs), we compared the autophagic flux among cells in the kidney under starvation. Inhibition of autophagy by chloroquine administration significantly increased the number of autophagosomes or autolysosomes in GEnCs and proximal tubular cells, but not in podocytes, suggesting that the GEnCs exhibit substantial autophagic activity...
November 13, 2017: Autophagy
https://www.readbyqxmd.com/read/29130132/in-vivo-assessment-of-polydatin-a-natural-polyphenol-compound-on-arsenic-induced-free-radical-overproduction-gene-expression-and-genotoxicity
#15
Damla Arslan-Acaroz, Fahriye Zemheri, Hasan Huseyin Demirel, Ismail Kucukkurt, Sinan Ince, Abdullah Eryavuz
Arsenic (As) is a well-known contaminant of global groundwater. Its exposure causes several hazardous effects on animals and human via oxidative stress. The present study examined the effect of polydatin (PD) on free radical overproduction in rats exposed to As. Thirty-five male rats randomly allocated into five equal groups. To the control group, physiological saline was given orally and to the second group only 100 mg/L As was given by drinking water for 60 days. The other groups were treated with As (100 mg/L) and PD orally at 50, 100, and 200 mg/kg/day, respectively...
November 12, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29128526/functional-analysis-of-cullin-3-e3-ligases-in-tumorigenesis
#16
REVIEW
Ji Cheng, Jianping Guo, Zhiwei Wang, Brian J North, Kaixiong Tao, Xiangpeng Dai, Wenyi Wei
Cullin 3-RING ligases (CRL3) play pivotal roles in the regulation of various physiological and pathological processes, including neoplastic events. The substrate adaptors of CRL3 typically contain a BTB domain that mediates the interaction between Cullin 3 and target substrates to promote their ubiquitination and subsequent degradation. The biological implications of CRL3 adaptor proteins have been well described where they have been found to play a role as either an oncogene, tumor suppressor, or can mediate either of these effects in a context-dependent manner...
November 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29126725/conformationally-rigid-derivatives-of-way-267-464-synthesis-and-pharmacology-at-the-human-oxytocin-and-vasopressin-1a-receptors
#17
William T Jorgensen, Damien W Gulliver, Timothy A Katte, Eryn L Werry, Tristan A Reekie, Mark Connor, Michael Kassiou
WAY-267,464 (1) and twelve conformationally rigid analogues (3a-f-4a-f) were synthesised, characterised and evaluated in cellular assays with the aim of systematically exploring interactions with the oxytocin receptor (OTR). Each analogue was evaluated in radioligand binding displacement assays at both human OTR and arginine vasopressin 1a receptors (V1aR). Physiological characterisation was determined by whole cell IP1 accumulation assays on stably transfected human embryonic kidney (HEK) cells. Incorporation of the rigid, optionally substituted benzene ring abolished OTR activity and diminished V1aR pharmacology when compared to 1...
October 23, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29125546/hereditary-nephrogenic-diabetes-insipidus-pathophysiology-and-possible-treatment-an-update
#18
REVIEW
Serena Milano, Monica Carmosino, Andrea Gerbino, Maria Svelto, Giuseppe Procino
Under physiological conditions, excessive loss of water through the urine is prevented by the release of the antidiuretic hormone arginine-vasopressin (AVP) from the posterior pituitary. In the kidney, AVP elicits a number of cellular responses, which converge on increasing the osmotic reabsorption of water in the collecting duct. One of the key events triggered by the binding of AVP to its type-2 receptor (AVPR2) is the exocytosis of the water channel aquaporin 2 (AQP2) at the apical membrane the principal cells of the collecting duct...
November 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29123159/zinc-is-a-critical-regulator-of-placental-morphogenesis-and-maternal-hemodynamics-during-pregnancy-in-mice
#19
Rebecca L Wilson, Shalem Y Leemaqz, Zona Goh, Dale McAninch, Tanja Jankovic-Karasoulos, Gabriela E Leghi, Jessica A Phillips, Katrina Mirabito Colafella, Cuong Tran, Sean O'Leary, Sam Buckberry, Stephen Pederson, Sarah A Robertson, Tina Bianco-Miotto, Claire T Roberts
Zinc is an essential micronutrient in pregnancy and zinc deficiency impairs fetal growth. We used a mouse model of moderate zinc deficiency to investigate the physiological mechanisms by which zinc is important to placental morphogenesis and the maternal blood pressure changes during pregnancy. A 26% reduction in circulating zinc (P = 0.005) was exhibited in mice fed a moderately zinc-deficient diet. Zinc deficiency in pregnancy resulted in an 8% reduction in both near term fetal and placental weights (both P < 0...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29121774/sphingolipids-and-redox-signaling-in-renal-regulation-and-chronic-kidney-diseases
#20
Owais M Bhat, Xinxu Yuan, Guangbi Li, RaMi Lee, Pin Lan Li
SIGNIFICANCE: Sphingolipids play critical roles in the membrane biology and intracellular signaling events that influence cellular behavior and function. Our review focuses on the cellular mechanisms and functional relevance of the cross talk between sphingolipids and redox signaling, which may be critically implicated in the pathogenesis of different renal diseases. Recent Advances: Reactive oxygen species (ROS) and sphingolipids can regulate cellular redox homeostasis through the regulation of NADPH oxidase, mitochondrial integrity, nitric oxide synthase (NOS) and antioxidant enzymes...
November 9, 2017: Antioxidants & Redox Signaling
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