scholarly journals Pharmacokinetics of Hydrochlorothiazide in Children: A Potential Surrogate for Renal Secretion Maturation

2020 ◽  
Author(s):  
Sarah Jane Commander ◽  
Huali Wu ◽  
Felix Boakye‐Agyeman ◽  
Chiara Melloni ◽  
Chi Dang Hornik ◽  
...  
Keyword(s):  
Renal Secretion

scholarly journals Untargeted analysis of first trimester serum to reveal biomarkers of pregnancy complications: a case–control discovery phase study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
E. W. Harville ◽  
Y.-Y. Li ◽  
K. Pan ◽  
S. McRitchie ◽  
W. Pathmasiri ◽  
...  
Keyword(s):  
Pregnancy Complications ◽  
Predictive Power ◽  
Gestational Hypertension ◽  
Predictive Biomarkers ◽  
First Trimester ◽  
Resonance Spectroscopy ◽  
Renal Secretion ◽  
Global Alliance ◽  
Phase Study ◽  
High Resolution Mass Spectroscopy

AbstractUnderstanding of causal biology and predictive biomarkers are lacking for hypertensive disorders of pregnancy (HDP) and preterm birth (PTB). First-trimester serum specimens from 51 cases of HDP, including 18 cases of pre-eclampsia (PE) and 33 cases of gestational hypertension (GH); 53 cases of PTB; and 109 controls were obtained from the Global Alliance to Prevent Prematurity and Stillbirth repository. Metabotyping was conducted using liquid chromatography high resolution mass spectroscopy and nuclear magnetic resonance spectroscopy. Multivariable logistic regression was used to identify signals that differed between groups after controlling for confounders. Signals important to predicting HDP and PTB were matched to an in-house physical standards library and public databases. Pathway analysis was conducted using GeneGo MetaCore. Over 400 signals for endogenous and exogenous metabolites that differentiated cases and controls were identified or annotated, and models that included these signals produced substantial improvements in predictive power beyond models that only included known risk factors. Perturbations of the aminoacyl-tRNA biosynthesis, l-threonine, and renal secretion of organic electrolytes pathways were associated with both HDP and PTB, while pathways related to cholesterol transport and metabolism were associated with HDP. This untargeted metabolomics analysis identified signals and common pathways associated with pregnancy complications.

Adaptive responses of renal organic anion transporter 3 (OAT3) during cholestasis

2008 ◽  
Vol 295 (1) ◽  
pp. F247-F252 ◽  
Author(s):  
Jiarong Chen ◽  
Tomohiro Terada ◽  
Ken Ogasawara ◽  
Toshiya Katsura ◽  
Ken-ichi Inui
Keyword(s):  
Bile Acids ◽  
Cholic Acid ◽  
Molecular Mechanisms ◽  
Competitive Inhibition ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Specific Substrate ◽  
Renal Secretion ◽  
Sd Rats ◽  
Anion Transporter

During cholestasis, bile acids are mainly excreted into the urine, but adaptive renal responses to cholestasis, especially molecular mechanisms for renal secretion of bile acids, have not been well understood. Organic anion transporters (OAT1 and OAT3) are responsible for membrane transport of anionic compounds at the renal basolateral membranes. In the present study, we investigated the pathophysiological roles of OAT1 and OAT3 in terms of renal handling of bile acids. The Eisai hyperbilirubinemic rats (EHBR), mutant rats without multidrug resistance-associated protein 2, showed higher serum and urinary concentrations of bile acids, compared with Sprague-Dawley (SD) rats (wild type). The protein expression level of rat OAT3 was significantly increased in EHBR compared with SD rats, whereas the expression of rat OAT1 was unchanged. The transport activities of rat and human OAT3, but not OAT1, were markedly inhibited by various bile acids such as chenodeoxycholic acid and cholic acid. Cholic acid, glycocholic acid, and taurocholic acid, which mainly increased during cholestasis, are transported by OAT3. The plasma concentration of β-lactam antibiotic cefotiam, a specific substrate for OAT3, was more increased in EHBR than in SD rats despite upregulation of OAT3 protein. This may be due to the competitive inhibition of cefotiam transport by bile acids via OAT3. In conclusion, the present study clearly demonstrated that OAT3 is responsible for renal secretion of bile acids during cholestasis and that the pharmacokinetic profile of OAT3 substrates may be affected by cholestasis.

scholarly journals Faropenem Transport across the Renal Epithelial Luminal Membrane via Inorganic Phosphate Transporter Npt1

2000 ◽  
Vol 44 (3) ◽  
pp. 574-577 ◽  
Author(s):  
Hiroshi Uchino ◽  
Ikumi Tamai ◽  
Hikaru Yabuuchi ◽  
Kayoko China ◽  
Ken-ichi Miyamoto ◽  
...  
Keyword(s):  
Inorganic Phosphate ◽  
Expression System ◽  
Mevalonic Acid ◽  
Chloride Ion ◽  
Chloride Ions ◽  
Phosphate Transporter ◽  
Disulfonic Acid ◽  
Renal Secretion ◽  
Luminal Membrane ◽  
Anionic Drugs

ABSTRACT We previously showed that the mouse inorganic phosphate transporter Npt1 operates in the hepatic sinusoidal membrane transport of anionic drugs such as benzylpenicillin and mevalonic acid. In the present study, the mechanism of renal secretion of penem antibiotics was examined by using a Xenopus oocyte expression system. Faropenem (an oral penem antibiotic) was transported via Npt1 with a Michaelis-Menten constant of 0.77 ± 0.34 mM in a sodium-independent but chloride ion-sensitive manner. When the concentration of chloride ions was increased, the transport activity of faropenem by Npt1 was decreased. Since the concentration gradient of chloride ions is in the lumen-to-intracellular direction, faropenem is expected to be transported from inside proximal tubular cells to the lumen. So, we tested the release of faropenem from Xenopusoocytes. The rate of efflux of faropenem from Npt1-expressing oocytes was about 9.5 times faster than that from control water-injectedXenopus oocytes. Faropenem transport by Npt1 was significantly inhibited by β-lactam antibiotics such as benzylpenicillin, ampicillin, cephalexin, and cefazolin to 24.9, 40.5, 54.4, and 26.2% of that for the control, respectively. Zwitterionic β-lactam antibiotics showed lesser inhibitory effects on faropenem uptake than anionic derivatives, indicating that Npt1 preferentially transports anionic compounds. Other anionic compounds, such as indomethacin and furosemide, and the anion transport inhibitor 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid significantly inhibited faropenem uptake mediated by Npt1. In conclusion, our results suggest that Npt1 participates in the renal secretion of penem antibiotics.

Metabolism of zinc-65

1961 ◽  
Vol 200 (6) ◽  
pp. 1345-1348 ◽  
Author(s):  
M. E. Rubini ◽  
G. Montalvo ◽  
C. P. Lockhart ◽  
C. R. Johnson
Keyword(s):  
Plasma Concentration ◽  
Soft Tissue ◽  
Pancreatic Secretion ◽  
Half Life ◽  
Renal Excretion ◽  
Body Burden ◽  
Renal Secretion ◽  
Cadmium Ion ◽  
The Brain

The absorption, deposition, and excretion of zinc65 was studied in mice, rats, and dogs. When zinc65 was fed to the animals it was poorly absorbed, but its long biologic half-life made even the small portion absorbed physiologically significant. Absorption was obviated by feeding large quantities of nonradioactive carrier zinc. Injected zinc65 chloride first was deposited, preferably in the pancreas, liver, and spleen, with only minor deposition in muscle and in the brain. Subsequently, a large proportion was transferred to bone. The chief means of excretion was in feces, presumably via pancreatic secretion. Injected nonradioactive zinc or treatment with 2,3-dimercaptopropanol (BAL), Versene, or cadmium ion failed to alter body burden significantly. Cadmium, however, decreased soft tissue zinc65 deposition and increased accretion by the skeleton. Blood activity fell rapidly and less than .01% of the dose injected remained in the blood after 1 day. Renal excretion of zinc65 rose as plasma concentration fell and clearance ratios in excess of 1.0 were noted, indicating probable renal secretion.

scholarly journals Hyperfluorescence Imaging of Kidney Cancer Enabled by Renal Secretion Pathway Dependent Efflux Transport

2020 ◽  
Vol 133 (1) ◽  
pp. 355-363
Author(s):  
Bujie Du ◽  
Yue Chong ◽  
Xingya Jiang ◽  
Mengxiao Yu ◽  
U‐Gling Lo ◽  
...  
Keyword(s):  
Kidney Cancer ◽  
Renal Secretion ◽  
Efflux Transport ◽  
Secretion Pathway

scholarly journals Hyperfluorescence Imaging of Kidney Cancer Enabled by Renal Secretion Pathway Dependent Efflux Transport

2020 ◽  
Vol 60 (1) ◽  
pp. 351-359
Author(s):  
Bujie Du ◽  
Yue Chong ◽  
Xingya Jiang ◽  
Mengxiao Yu ◽  
U‐Gling Lo ◽  
...  
Keyword(s):  
Kidney Cancer ◽  
Renal Secretion ◽  
Efflux Transport ◽  
Secretion Pathway

Renal Secretion of Inactive Renin

2015 ◽  
pp. 160-163
Author(s):  
F. H. M. Derkx ◽  
R. P. Verhoeven ◽  
G. J. Wenting ◽  
A. J. Man in �t Veld ◽  
M. A. D. H. Schalekamp
Keyword(s):  
Renal Secretion ◽  
Inactive Renin
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