Accumulation kinetics of drugs with nonlinear plasma protein and tissue binding characteristics

1979 ◽  
Vol 7 (4) ◽  
pp. 397-405 ◽  
Author(s):  
Patrick J. McNamara ◽  
John T. Slattery ◽  
Milo Gibaldi ◽  
Gerhard Levy
Keyword(s):  
Plasma Protein ◽  
Tissue Binding ◽  
Nonlinear Plasma ◽  
Binding Characteristics ◽  
Accumulation Kinetics ◽  
Kinetics Of

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (03) ◽  
pp. 100-103 ◽  
Author(s):  
C. Schümichen ◽  
J. Waiden ◽  
G. Hoffmann
Keyword(s):  
Glomerular Filtration ◽  
Renal Clearance ◽  
Plasma Protein ◽  
Kinetic Data ◽  
Adult Rats ◽  
Compound A ◽  
Extravascular Space ◽  
Tubular Cells ◽  
Glomerular Filtrate ◽  
Kinetics Of

SummaryThe kinetic data of two different 99mTc-Sn-pyrophosphate compounds (compound A and B) were evaluated in non-adult rats. Only compound A concentrated in bone. Both compounds dispersed rapidly in the intravascular as well as the extravascular space. The plasma protein bond of both compounds increased with time after injection and impaired both the renal clearance of both compounds and the bone clearance of compound A. The renal clearance of both compounds was somewhat above that of 5 1Cr-EDTA. It is concluded that compound A and B is mainly excreted by glomerular filtration. About one fourth of the glomerular filtrate of compound B is reabsorbed and accumulated by the tubular cells.

scholarly journals Tbx21 and Foxp3 Are Epigenetically Stabilized in T-Bet+ Tregs That Transiently Accumulate in Influenza A Virus-Infected Lungs

2021 ◽  
Vol 22 (14) ◽  
pp. 7522
Author(s):  
Yassin Elfaki ◽  
Juhao Yang ◽  
Julia Boehme ◽  
Kristin Schultz ◽  
Dunja Bruder ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
T Cell Subsets ◽  
T Helper 1 ◽  
T Box ◽  
Cell Responses ◽  
Accumulation Kinetics ◽  
Kinetics Of

During influenza A virus (IAV) infections, CD4+ T cell responses within infected lungs mainly involve T helper 1 (Th1) and regulatory T cells (Tregs). Th1-mediated responses favor the co-expression of T-box transcription factor 21 (T-bet) in Foxp3+ Tregs, enabling the efficient Treg control of Th1 responses in infected tissues. So far, the exact accumulation kinetics of T cell subsets in the lungs and lung-draining lymph nodes (dLN) of IAV-infected mice is incompletely understood, and the epigenetic signature of Tregs accumulating in infected lungs has not been investigated. Here, we report that the total T cell and the two-step Treg accumulation in IAV-infected lungs is transient, whereas the change in the ratio of CD4+ to CD8+ T cells is more durable. Within lungs, the frequency of Tregs co-expressing T-bet is steadily, yet transiently, increasing with a peak at Day 7 post-infection. Interestingly, T-bet+ Tregs accumulating in IAV-infected lungs displayed a strongly demethylated Tbx21 locus, similarly as in T-bet+ conventional T cells, and a fully demethylated Treg-specific demethylated region (TSDR) within the Foxp3 locus. In summary, our data suggest that T-bet+ but not T-bet− Tregs are epigenetically stabilized during IAV-induced infection in the lung.

Kinetics of mercury accumulation by freshwater biofilms

2017 ◽  
Vol 14 (7) ◽  
pp. 458 ◽  
Author(s):  
Perrine Dranguet ◽  
Vera I. Slaveykova ◽  
Séverine Le Faucheur
Keyword(s):  
Food Webs ◽  
Food Chain ◽  
Microbial Composition ◽  
Biofilm Thickness ◽  
Aquatic Microorganisms ◽  
Uptake Rate Constant ◽  
The Difference ◽  
Accumulation Kinetics ◽  
Kinetics Of ◽  
Hg Accumulation

Environmental contextMercury (Hg) is a major environmental contaminant due to its toxicity, accumulation and biomagnification along the food chain. We demonstrate that Hg accumulation by biofilms, one possible entry point for Hg into food webs, is rapid and depends on biofilm structure and composition. These findings have important implications for the understanding of Hg bioavailability and effects towards aquatic microorganisms. AbstractMercury contamination is of high concern due to its bioaccumulation, toxicity and biomagnification along the food chain. Biofilms can accumulate Hg and contribute to its incorporation in freshwater food webs. Nevertheless, the accumulation kinetics of Hg by biofilms is not well described and understood. The aim of the present study was thus to gain mechanistic understanding of Hg accumulation by biofilms. Kinetics of Hg uptake by biofilms of different ages (e.g. different compositions) was characterised by determining Hg contents in biofilms with and without a cysteine-washing step. Hg accumulation was rapid in both biofilms, with the uptake rate constant of the younger biofilm 10 times higher than that of the older biofilm. Moreover, accumulated Hg reached a plateau at 24h exposure in the younger biofilm, whereas it increased linearly in the older biofilm. The observed difference in Hg uptake by the studied biofilms is likely a result of the difference in biofilm thickness (and thus Hg diffusion inside the biofilm matrix) and microbial composition. These findings have important implications for the understanding of Hg bioavailability and effects towards aquatic microorganisms.

Effects of IL-8, Gro-α, and LTB4on the adhesive kinetics of LFA-1 and Mac-1 on human neutrophils

2001 ◽  
Vol 281 (5) ◽  
pp. C1568-C1578 ◽  
Author(s):  
Scott M. Seo ◽  
Larry V. McIntire ◽  
C. Wayne Smith
Keyword(s):  
Chemokine Receptor ◽  
Time Window ◽  
Interleukin 8 ◽  
Intercellular Adhesion Molecule ◽  
Human Neutrophils ◽  
Binding Characteristics ◽  
Topographical Distribution ◽  
Cxc Chemokine ◽  
Kinetics Of ◽  
Regulate Firm

Firm adhesion of rolling neutrophils on inflamed endothelium is dependent on β2(CD18)-integrins and activating stimuli. LFA-1 (CD11a/CD18) appears to be more important than Mac-1 (CD11b/CD18) in neutrophil emigration at inflammatory sites, but little is known of the relative binding characteristics of these two integrins under conditions thought to regulate firm adhesion. The present study examined the effect of chemoattractants on the kinetics of LFA-1 and Mac-1 adhesion in human neutrophils. We found that subnanomolar concentrations of interleukin-8, Gro-α, and leukotriene B4(LTB4) induced rapid and optimal rates of LFA-1-dependent adhesion of neutrophils to intercellular adhesion molecule (ICAM)-1-coated beads. These optimal rates of LFA-1 adhesion were transient and decayed within 1 min after chemoattractant stimulation. Mac-1 adhesion was equally rapid initially but continued to rise for ≥6 min after stimulation. A fourfold higher density of ICAM-1 on beads markedly increased the rate of binding to LFA-1 but did not change the early and narrow time window for the optimal rate of adhesion. Using well-characterized monoclonal antibodies, we showed that activation of LFA-1 and Mac-1 by Gro-α was completely blocked by anti-CXC chemokine receptor R2, but activation of these integrins by interleukin-8 was most effectively blocked by anti-CXC chemokine receptor R1. The topographical distribution of beads also reflected significant differences between LFA-1 and Mac-1. Beads bound to Mac-1 translocated to the cell uropod within 4 min, but beads bound to LFA-1 remained bound to the lamellipodial regions at the same time. These kinetic and topographical differences may indicate distinct functional contributions of LFA-1 and Mac-1 on neutrophils.

Biphasic accumulation kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile in tumour cells and its modulation by lipophilic P-glycoprotein ligands

2005 ◽  
Vol 25 (2-3) ◽  
pp. 201-209 ◽  
Author(s):  
Teréz Márián ◽  
László Balkay ◽  
Gábor Szabó ◽  
Zoárd T. Krasznai ◽  
Zoltán Hernádi ◽  
...  
Keyword(s):  
Tumour Cells ◽  
P Glycoprotein ◽  
Accumulation Kinetics ◽  
Kinetics Of

scholarly journals Tissue Accumulation Kinetics of Ciclesonide‐active Metabolite and Budesonide in Mice

2013 ◽  
Vol 112 (6) ◽  
pp. 401-411 ◽  
Author(s):  
Ulla Mårs ◽  
Roland d'Argy ◽  
Karin Hallbeck ◽  
Anna Miller‐Larsson ◽  
Staffan Edsbäcker
Keyword(s):  
Active Metabolite ◽  
Tissue Accumulation ◽  
Accumulation Kinetics ◽  
Kinetics Of
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