An unsteady analysis of two-phase binding of drug in an asymmetric stenosed vessel

2021 ◽  
Author(s):  
Sayantan Biswas ◽  
Sarifuddin . ◽  
Prashanta Kumar Mandal
Keyword(s):  
Binding Sites ◽  
Patient Specific ◽  
Clear Understanding ◽  
Two Phase ◽  
Concentration Variance ◽  
Absorption Parameter ◽  
Luminal Side ◽  
Stenosed Vessel ◽  
Tissue Interface ◽  
Kinetics Of

Abstract In this paper, we investigate endovascular delivery to get a step ahead of the pharmacological limitations it has due to the complexity of dealing with a patient-specific vessel through a mathematical model. We divide the domain of computation into four sub-domains: the lumen, the lumen-tissue interface, the upper tissue and the lower tissue which are extracted from an asymmetric atherosclerotic image derived by the intravascular ultrasound (IVUS) technique. The injected drug at the luminal inlet is transported with the streaming blood which is considered Newtonian. An irreversible uptake kinetics of the injected drug at the lumen-tissue interface from the luminal side to the tissue domains is assumed. Subsequently, the drug is dispersed within the tissue followed by its retention in the extracellular matrix (ECM) and by receptor-mediated binding. The Marker and Cell (MAC) method has been leveraged to get a quantitative insight into the model considered. The effect of the wall absorption parameter on the concentration of all drug forms (free as well as two-phase bound) has been thoroughly investigated, and some other important factors, such as the averaged concentration, the tissue content, the fractional effect, the concentration variance and the effectiveness of drug have been graphically analyzed to gain a clear understanding of endovascular delivery. The simulated results predict that with increasing values of the absorption parameter, the averaged concentrations of all drug forms do decrease. An early saturation of binding sites takes place for smaller values of the absorption parameter, and also rapid saturation of ECM binding sites occurs as compared to receptor binding sites. Results also predict the influence of surface roughness as well as asymmetry of the domain about the centerline on the distribution and retention of drug. A thorough sensitivity analysis has been carried out to determine the influence of some parameters involved.

Protamine Neutralization of the Release of Tissue Factor Pathway Inhibitor Activity by Heparins

1993 ◽  
Vol 70 (06) ◽  
pp. 0942-0945 ◽  
Author(s):  
Job Harenberg ◽  
Marietta Siegele ◽  
Carl-Erik Dempfle ◽  
Gerd Stehle ◽  
Dieter L Heene
Keyword(s):  
Tissue Factor ◽  
Binding Sites ◽  
Tissue Factor Pathway Inhibitor ◽  
Factor Xa ◽  
Protamine Sulfate ◽  
Low Molecular Weight ◽  
Factor X ◽  
Rebound Phenomenon ◽  
Tissue Factor Pathway ◽  
Kinetics Of

SummaryThe present study was designed to investigate the action of protamine on the release of tissue factor pathway inhibitor (TFPI) activity by unfractionated (UF) and low molecular weight (LMW) heparin in healthy individuals. 5000 IU UF-heparin or 5000 IU LMW-heparin were given intravenously followed by saline, 5000 U protamine chloride or 5000 U protamine sulfate intravenously after the 10 min blood sample. Then serial blood samples for the measurement of TFPI activity and anti-factor Xa- activity were taken, in order to detect a possible relation between the remaining anti-factor X a activity after neutralization of LMW-heparin with protamine and TFPI activity and to establish whether or not a rebound phenomenon of plasmatic TFPI occurs.There was no difference in the release and in the kinetics of TFPI by UF- and LMW-heparin with subsequent administration of saline. After administration of protamine TFPI activity decreased immediately and irreversibly to pretreatment values. There were no differences between protamine chloride and protamine sulfate on the effect of TFPI induced by UF- or LMW-heparin. No rebound phenomenon of TFPI activity occurred. In contrast anti-factor Xa- activity, as measured by the chromogenic S2222-assay, issued the known differences between UF- and LMW-heparin. The half-life of the aXa-effect of LMW-heparin was twice as long as of UF-heparin. Protamine antagonized UF-heparin completely and about 60% of the anti-factor Xa activity of LMW-heparin, using chromogenic S2222-method. No differences could be detected for protamine chloride and sulfate form of protamineIt is assumed that protamine displaces heparins from the binding sites of TFPI. There were no differences between UF- and LMW-heparin. The data indicate that the sustained antifactor Xa activity after antagonization of LMW-heparins as well as heparin rebound phenomena are not mediated by TFPI activity.

Abnormal Platelet Serotonin Uptake and Binding Sites in Myeloproliferative Disorders

1984 ◽  
Vol 51 (03) ◽  
pp. 349-353 ◽  
Author(s):  
C Caranobe ◽  
P Sié ◽  
F Fernandez ◽  
J Pris ◽  
S Moatti ◽  
...  
Keyword(s):  
Binding Sites ◽  
High Capacity ◽  
Specific Inhibitor ◽  
Myeloproliferative Disorders ◽  
Normal Subjects ◽  
Binding Data ◽  
Full Explanation ◽  
Number Of Binding Sites ◽  
5 Ht Uptake ◽  
Kinetics Of

SummaryA simultaneous investigation of the kinetics of serotonin (5 HT) uptake and of binding sites was carried out in the platelets of normal subjects and of 10 patients affected with various types of myeloproliferative disorders (MD). The 5 HT uptake was analysed according to the Lineweaver-Burk and the Eadie-Hofstee methods. With the two methods, the patient’s platelets exhibited a dramatic reduction of the Vi max and of the Km; in some patients the Eadie-Hofstee analysis revealed that a passive diffusion phenomenon is superimposed on the active 5 HT uptake at least for the higher concentration used. The binding data were analysed with the Scatchard method. Two classes of binding sites (high affinity - low capacity, low affinity - high capacity) were found in normal subjects and patients. Pharmacological studies with imipramine, a specific inhibitor of 5 HT uptake, suggested that both the sites are involved in 5 HT uptake. The number of both binding sites was significantly decreased in patient’s platelets while the affinity constants of these binding sites were not significantly reduced in comparison with those of the control subjects. No correlations were found between Vi max, Km and the number of binding sites. These results suggest that a reduction in the number of platelet membrane acceptors for 5 HT commonly occurs in myeloproliferative disorders but does not provide a full explanation of the uptake defect.

m-[o-(2-Chloro-5-Fluorosulfonylphenylureido)Phenoxybutoxy]Benzamidine: Affinity Labeling Reagent Which Can Identify Secondary Binding Sites of Coagulation Complement and Fibrinolytic Serine Proteases

1979 ◽  
Author(s):  
D Bing ◽  
D Robison ◽  
J Andrews ◽  
R Laura
Keyword(s):  
Binding Sites ◽  
Serine Proteases ◽  
Enzyme Inhibitor ◽  
Molecular Model ◽  
Factor Xa ◽  
Affinity Labeling ◽  
Catalytic Center ◽  
Inhibitor Complex ◽  
Polypeptide Chains ◽  
Kinetics Of

We have determined that m-[o-(2-chloro-5-fluorosulfonylphenylureido)phenoxybutoxy]benza-midine [mCP(PBA)-F] is an affinity labeling reagent which labels both polypeptide chains of thrombin, factor Xa, complement component CIS and plasmin. As this means it is reacting outside of the catalytic center, we have called this reagent an exo-site affinity labeling reagent. Progressive irreversible inhibition of these enzymes by this reagent is rapid (k1st 2.5-4.6 x 10-3sec-1), the kinetics of inactivation are consistent with inhibition proceding via formation of a specific enzyme-inhibitor complex analogous to a Michaelis-Menton complex (KL - 115-26 μM), and diisopropylfluorophosphate or p-amidino-phenylmethanesulfonyfluoride Prevent labeling by [3H]mCP(PBA)-F. A molecular model of mCP(PBA)-F shows that the reactive SO2F group can be 17 A from the cationic amidine. The data are consistent with the hypothesis that both peptide chains are required for the specific proteolytic activity exhibited by these proteases and that the peptide chain which does not contain the active site serine is close to the catalytic center. (Supported by NIH and AHA grants

Interphase distribution of 2-furylethylenes

1985 ◽  
Vol 50 (8) ◽  
pp. 1642-1647 ◽  
Author(s):  
Štefan Baláž ◽  
Anton Kuchár ◽  
Ernest Šturdík ◽  
Michal Rosenberg ◽  
Ladislav Štibrányi ◽  
...  
Keyword(s):  
Partition Coefficient ◽  
Partition Coefficients ◽  
Transport Rate ◽  
Phase System ◽  
Two Phase ◽  
Interphase Distribution ◽  
Distribution Kinetics ◽  
System 1 ◽  
Kinetics Of

The distribution kinetics of 35 2-furylethylene derivatives in two-phase system 1-octanol-water was investigated. The transport rate parameters in direction water-1-octanol (l1) and backwards (l2) are partition coefficient P = l1/l2 dependent according to equations l1 = logP - log(βP + 1) + const., l2 = -log(βP + 1) + const., const. = -5.600, β = 0.261. Importance of this finding for assesment of distribution of compounds under investigation in biosystems and also the suitability of the presented method for determination of partition coefficients are discussed.

scholarly journals Kinetics of tau aggregation reveals patient specific tau characteristics among Alzheimer's cases

2021 ◽  
Author(s):  
Tarun V Kamath ◽  
Naomi Klickstein ◽  
Caitlin Commins ◽  
Analiese R Fernandes ◽  
Derek H Oakley ◽  
...  
Keyword(s):  
Growth Phase ◽  
Tau Proteins ◽  
Patient Specific ◽  
Lag Phase ◽  
Plateau Phase ◽  
Kinetic Assay ◽  
Cellular Processes ◽  
Morphological Differences ◽  
Tau Aggregation ◽  
Kinetics Of

Abstract The accumulation of tau aggregates throughout the human brain is the hallmark of a number of neurodegenerative conditions classified as tauopathies. Increasing evidence shows that tau aggregation occurs in a “prion-like” manner, in which a small amount of misfolded tau protein can induce other, naïve tau proteins to aggregate. Tau aggregates have been found to differ structurally among different tauopathies. Recently, however, we have suggested that tau oligomeric species may differ biochemically among individual patients with sporadic Alzheimer disease, and have also showed that the bioactivity of the tau species, measured using a cell-based bioassay, also varied among individuals. Here, we adopted a live-cell imaging approach to the standard cell-based bioassay to explore further whether the kinetics of aggregation also differentiated these patients. We found that aggregation can be observed to follow a consistent pattern in all cases, with a lag phase, a growth phase, and a plateau phase, which each provide quantitative parameters by which we characterize aggregation kinetics. The length of the lag phase and magnitude of the plateau phase are both dependent upon the concentration of seeding-competent tau, the relative enrichment of which differs among patients. The slope of the growth phase correlates with morphological differences in the tau aggregates, which may be reflective of underlying structural differences. This kinetic assay confirms and refines the concept of heterogeneity in the characteristics of tau proteopathic seeds among individuals with Alzheimer’s disease and is a method by which future studies may characterize longitudinal changes in tau aggregation and the cellular processes which may influence these changes.

Kinetics of Growth and Structure of Coatings Obtained on Sandelin Steels in the High-Temperature Galvanizing Process

2013 ◽  
Vol 212 ◽  
pp. 127-132 ◽  
Author(s):  
Henryk Kania
Keyword(s):  
High Temperature ◽  
Growth Kinetics ◽  
Structural Components ◽  
Compact Layer ◽  
Two Phase ◽  
Continuous Layer ◽  
Structure Of Coatings ◽  
Zinc Coatings ◽  
Kinetics Of ◽  
Diffuse Coating

In the paper the author presents the results of tests defining the characteristics of behaviour of Sandelin steel in the high-temperature galvanizing process. The growth kinetics of hot-dip zinc coatings on the substrate of 0.05% Si steel in the temperature range of 540-580°C has been established. The structure of the coatings and their phase composition have been developed and the chemical composition of structural components of the coating has be defined. It has been determined that the coating is composed of a compact layer δ1 and an area of a two-phase mixture of δ1 and Zn. The conducted tests confirmed the presence of phase Γ1 , which does not form a continuous layer but it forms individual precipitates which are irregular in shape. The growth kinetics of the coating indicates that an increase in temperature causes a decrease in the coating thickness, which might prove that dissolving processes prevailed over the processes of diffuse coating growth.

Studies of the uptake of macromolecules by cells. I. Uptake of proteins by cells of the Ehrlich–Lettré ascites carcinoma

1968 ◽  
Vol 46 (12) ◽  
pp. 1443-1450 ◽  
Author(s):  
Y. C. Choi ◽  
E. R. M. Kay
Keyword(s):  
Nucleic Acid ◽  
Cell Membrane ◽  
Binding Sites ◽  
Specific Binding ◽  
Protein Uptake ◽  
Specific Binding Sites ◽  
Model Protein ◽  
Uptake Process ◽  
Kinetics Of ◽  
Protein Treatment

The uptake of protein by cells of the Ehrlich–Lettré ascites carcinoma was characterized kinetically by using hemoglobin as a model protein. An attempt was made to show that the process is not an artefact due to nonspecific adsorption of protein to the cell membrane. The kinetics of the uptake process suggested that an interaction exists between the exogenous protein and specific binding sites on the membrane. Acetylation of hemoglobin enhanced the rate of uptake of this protein. Treatment of cells with neuraminidase, phospholipase A, and Pronase resulted in an inhibition of protein uptake. The experimental evidence for the uptake of hemoglobin was supported by evidence that L-serine-U-14C-labelled hemoglobin is transported into the cytoplasm and utilized subsequently, resulting in labelling of the nucleic acid nucleotides.

scholarly journals Connecting Structure with Kinetics of Single-Stranded DNA Fluctuations that Provide Potential Binding Sites for Replication Proteins

2021 ◽  
Vol 120 (3) ◽  
pp. 219a
Author(s):  
Claire Albrecht ◽  
Brett A. Israels ◽  
Chloe Chvatal ◽  
Peter H. von Hippel ◽  
Andrew H. Marcus
Keyword(s):  
Binding Sites ◽  
Replication Proteins ◽  
Single Stranded Dna ◽  
Potential Binding ◽  
Kinetics Of
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