scholarly journals MODELLING OF SEDIMENTATION FOR POLYDISPERSE MIXTURE

2017 ◽  
Author(s):  
EWELINA ŁUKASIEWICZ ◽  
MARIUSZ RZĄSA
Keyword(s):  
Polydisperse Mixture

Selectins, Heparins, and Cancer: Rationale for Clinical Trials.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. sci-20-sci-20
Author(s):  
Ajit P. Varki ◽  
Nissi M. Varki ◽  
Lubor Borsig
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Animal Studies ◽  
Vitamin K Antagonists ◽  
Major Effect ◽  
Heparin Therapy ◽  
Optimal Dosing ◽  
Polydisperse Mixture ◽  
Anticoagulant Function ◽  
Selectin Binding

Abstract Heparin has been in use as an anticoagulant for many decades, based on its ability to enhance antithrombin activity. However, heparin is a natural product, comprising a complex polydisperse mixture of highly sulfated glycosaminoglycan chains, only a fraction of which bind antithrombin. We reported that heparin has an unrelated biological effect in inhibiting P- and L-selectin binding to their natural ligands. Meanwhile, animal studies and analyses of human clinical data suggest that heparin therapy increases survival in various cancers. In contrast, clinical trials using Vitamin K antagonists showed no major effect on survival in most studies. Thus, the heparin effect on cancer may not be due primarily to its anticoagulant function, but rather to inhibition of P- and L-selectin. Indeed, we have demonstrated that the selectins play critical roles in animal models of the hematogeneous phase of carcinoma metastasis and of the platelet-rich microthromboses typical of classical Trousseau’s syndrome. This involves interactions of selectins with pathological ligands produced by carcinoma cells, particularly sialylated, fucosylated, and sulfated mucins. The critical selectin-mediated interactions blocked by heparin occur early in the metastatic cascade. Also, inhibition occurs at concentrations in the clinically acceptable range. Furthermore, there are many other salutary actions of heparin in cancer, including adsorption of cytokines and growth factors, inhibition of thrombin generation, and inhibition of heparanases. We, therefore, suggest that heparin therapy for metastasis prevention in humans be revisited, with these new paradigms in mind. Most of the above studies used unfractionated heparin. We found that selectin-inhibiting effects of low molecular weight heparins (LMWH) are varied and that the synthetic heparinoid pentasaccharide that specifically binds antithrombin does not block at clinically relevant levels. Optimal dosing to sustain clinically acceptable levels of all these drugs in mice gave congruent results. These data suggest a rational clinical trial comparing an optimal LMWH with the pentasaccharide in the pre-/peri- and immediate post-operative periods of newly diagnosed carcinomas. Notably, heparin can also attenuate inflammatory pathologies in animal models by blocking L- and P-selectin.

A pilot interlaboratory comparison of protocols that simulate aging of nanocomposites and detect released fragments

2014 ◽  
Vol 11 (4) ◽  
pp. 402 ◽  
Author(s):  
Wendel Wohlleben ◽  
Gemma Vilar ◽  
Elisabet Fernández-Rosas ◽  
David González-Gálvez ◽  
Claus Gabriel ◽  
...  
Keyword(s):  
Interlaboratory Comparison ◽  
Critical Parameters ◽  
Release Rates ◽  
Sampling Protocol ◽  
Unbound Fraction ◽  
Run Off ◽  
Validity Range ◽  
Aging Conditions ◽  
Essential Input ◽  
Polydisperse Mixture

Environmental context Nanoparticles are contained in many commercialised products, but the lack of validated methods to assess their potential release into the environment hampers our ability to perform a reliable risk assessment. Equipment to simulate aging is available, but the challenge is to sample released entities, and to analyse those fragments with suitable nano-analytics. We describe methods to characterise the degradation and surface accumulation of nanoparticles, and to quantify fragments released during UV irradiation of polymer nanocomposites. Abstract The safe use of nanoparticles as fillers in nanocomposite materials depends, in part, on a good understanding of what is released from aging nanocomposites, and at which rate. Here we investigated the critical parameters of the nanoparticle release phenomenon by a pilot inter-laboratory study of a polyamide containing 4mass% of silica nanoparticles (nanosilica). The main focus is on the validity range of the aging and release protocols. Both induced release by mechanical shear after dry weathering at different UV intensities and spontaneous release during wet weathering were investigated. We propose a combined protocol based on the finding that the characteristics of released fragments – which are the essential input for fate, transport and (eco-)toxicological testing – were reproducible between laboratories and between different aging, sampling and analysis protocols: the released fragments were a polydisperse mixture of predominantly composite fragments from the nanometre up to several micrometre diameter, and of clustered or individual nanosilica unbound to polymer. The unbound fraction was microscopically observed but could not be quantified. We found that aging conditions are very critical for the release rates, not for release characteristics. The sampling protocol tolerates some differences. Simplified aging + immersion protocols can at least partially replace, complement and extend dedicated weathering apparatus with run-off collection.

Towards the phase diagram of a polydisperse mixture of charged hard spheres

2005 ◽  
Vol 72 (1) ◽  
pp. 96-102 ◽  
Author(s):  
Yu. V Kalyuzhnyi ◽  
G Kahl ◽  
P. T Cummings
Keyword(s):  
Phase Diagram ◽  
Hard Spheres ◽  
Polydisperse Mixture ◽  
Charged Hard Spheres

Polydisperse mixture adsorption kinetics

AIChE Journal ◽  
1993 ◽  
Vol 39 (8) ◽  
pp. 1322-1329 ◽  
Author(s):  
Ramachandran Muralidhar ◽  
Julian Talbot
Keyword(s):  
Adsorption Kinetics ◽  
Mixture Adsorption ◽  
Polydisperse Mixture

AVE5026: A New Hemisynthetic Ultra Low Molecular Weight Heparin with Enriched Anti-Xa Activity and Enhanced Antithrombotic Activity for Management of Cancer Associated Thrombosis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4046-4046
Author(s):  
Debra Hoppensteadt ◽  
Walter Jeske ◽  
Jeanine M. Walenga ◽  
Jawed Fareed
Keyword(s):  
Molecular Weight ◽  
Animal Models ◽  
Tumor Growth ◽  
Bleeding Risk ◽  
Repeated Administration ◽  
Therapeutic Window ◽  
Bleeding Effect ◽  
Polydisperse Mixture ◽  
Antithrombotic Efficacy ◽  
Cancer Associated Thrombosis

Abstract AVE5026 is an ULMWH with a high anti-Xa activity associated with residual anti-IIa activity (ratio anti-Xa/IIa>30). This ratio may be favorable for use in cancer patients as it may have a higher therapeutic window. This agent is a polydisperse mixture of oligomeric heparin fragments (molecular weight 2000–3000 daltons) prepared by partial and controlled depolymerization of porcine mucosal heparin (UFH).. The anticoagulant profile of AVE5026 has been previously reported (Hoppensteadt, et al. Blood 2007). To validate the hypothesis that AVE5026 is an appropriate antithrombotic in cancer, studies were carried out to determine its antithrombotic, bleeding, tumor growth, angiogenesis and apoptosis effects in animal models. AVE5026 produced a dose-dependent antithrombotic response in the rat laser model of microvascular thrombosis (2.5 mg/kg IV, 9±1.7 laser shots; 5.0 mg/kg SC, 8±1.6 laser shots; control 3±0.8 laser shots). The relative bleeding effects of AVE5026 in a rat tail bleeding model were negligible in comparison to enoxaparin (E) and UFH (all 5 mg/kg IV; UFH >1000 sec; E 360±57 sec; AVE5026 209±29 sec; Control 215±32 seconds). Repeated administration of AVE5026 in dose ranges of 1–5 mg/kg od, SC for 14 days did not result in accumulation of the anti-Xa activity. Furthermore, in contrast to E, there was no enhancement of the hemorrhagic profile. Both E and AVE5026 inhibited tumor growth by regulating angiogenesis and apoptosis in a Lewis Lung carcinoma (14% vs. 22% decrease) rat model and in a Walker 256 carcinosarcoma model (21% vs. 30% decrease) Although comparable results to E were demonstrated in animal models of arterial thrombosis, the bleeding effect of AVE5026 were disproportionately lower. This superior safety-efficacy ratio may translate into improved antithrombotic efficacy with decreased bleeding risk, suggesting that AVE5026 may provide the optimal treatment strategy for the management of cancer associated thrombosis.

A kinetic study of the interaction of hydrous aluminum oxide colloids with a well-characterized soil fulvic acid

1982 ◽  
Vol 60 (15) ◽  
pp. 2023-2028 ◽  
Author(s):  
Mark K. S. Mak ◽  
Cooper H. Langford
Keyword(s):  
Aluminum Oxide ◽  
Kinetic Study ◽  
Fulvic Acid ◽  
Humic Substances ◽  
Ternary Complexes ◽  
Complex Stability ◽  
Polydisperse Mixture ◽  
Stock Solutions ◽  
Calcein Blue ◽  
Ion Species

Models of the species arising from the interaction of hydrous aluminum oxide colloids with humic substances have been prepared by neutralizing Al(III) stock solutions in the presence of a well-characterized fulvic acid and aging for 24 h. These samples have been examined kinetically using the fluorimetric Al(III) reagent calcein blue. The rates of formation of Al(III) calcein blue complexes allows recognition of five kinetically distinguishable components in the mixtures. Some are similar in lability to simple organic chelates of Al(III). Others are much less labile. Evidence for non-labile colloidal "ternary" complexes of Al(III) ion species complexed to fulvic acid, and bound to hydrous aluminum oxide colloid is presented. The polydisperse mixture character of fulvic acid is seen in patterns of complex lability much as it is seen in patterns of complex stability.

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