DIFFERENT LOW MOLECULAR WEIGHT HEPARINS (LMWHs) ARE NOT IDENTICAL IN THE IN VITRO SCREENING REGARDLESS OF POTENCY ADJUSTMENT

1987 ◽  
Author(s):  
D Hoppensteadt ◽  
J Fareed ◽  
J M Walenga ◽  
R M Emnuele ◽  
A Racanelli
Keyword(s):  
Molecular Weight ◽  
Test System ◽  
Low Molecular Weight ◽  
In Vitro Test ◽  
Low Molecular Weight Heparins ◽  
Relative Safety ◽  
Considerable Controversy ◽  
Vitro Test ◽  
Compositional Variations

There is considerable controversy in the standardization and potency evaluation of low molecular weight heparins (LMWHs).Since these agents are produced by fractionation or depolymerization procedures, the resulting material shows marked compositional variations regardless of the similarity in molecular weight. In order to address the question “are different LMWHs the same?”, we utilized a uniform multiparametric in vitro test battery. Seven commercial LMWHs Choay Fraxiparine (CY 216), Choay CY 222, Novo LHN, Kabi Fragmin, Opocrin 2123 (OP), Hepar RD 11885 (RD), Pharmuka Enoxaparine (PK) and an unfractionated porcine mucosal heparin (PMH) were studied at equigravimetric amounts in established assays. PMH and LMWHs were ranked acdording to the dose-dependent effects and the results are summarized in the following:As evident from the above data, each of the agents studied showed a distinct profile in the in vitro test system studied. This data suggests that LMWHs are individual drugs with marked differences in in vitro actions, which may not be the true determinants of the relative safety/efficacy in clinical settings.

An in vitro test system for compounds that modulate human inflammatory macrophage polarization

2018 ◽  
Vol 833 ◽  
pp. 328-338 ◽  
Author(s):  
Hiromi Shiratori ◽  
Carmen Feinweber ◽  
Sonja Luckhardt ◽  
Nadja Wallner ◽  
Gerd Geisslinger ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Test System ◽  
In Vitro Test ◽  
Vitro Test ◽  
Inflammatory Macrophage

Biomimetic in vitro test system for evaluation of dental implant materials

2020 ◽  
Vol 36 (8) ◽  
pp. 1059-1070
Author(s):  
Franziska Ehlicke ◽  
Jonathan Berndt ◽  
Nina Marichikj ◽  
Doris Steinmüller-Nethl ◽  
Heike Walles ◽  
...  
Keyword(s):  
Dental Implant ◽  
Test System ◽  
In Vitro Test ◽  
Implant Materials ◽  
Vitro Test

scholarly journals Prediction of in Vivo Cytotoxicity of Chemotherapeutic Agents by Their Effect on Malignant Leukocytes in Vitro

Blood ◽  
1967 ◽  
Vol 30 (2) ◽  
pp. 176-188 ◽  
Author(s):  
MARTIN J. CLINE
Keyword(s):  
Test System ◽  
Chemotherapeutic Agents ◽  
Response To Treatment ◽  
In Vitro Test ◽  
Malignant Cells ◽  
Vitro Test ◽  
In Vitro Effects ◽  
In Vivo Cytotoxicity

Abstract In order to develop a test system for predicting the response to chemotherapeutic agents, leukocytes from patients with leukemia and leukolymphosarcoma were cultured in vitro and the effect of several drugs on the incorporation of H3-uridine into ribonucleic acid was measured. Cortisol, vincristine and cytosine arabinoside at concentrations near the therapeutic range produced inhibition of H3-uridine incorporation in sensitive leukocytes. The in vitro effects of 6-mercaptopurine and methotrexate were variable. In 39 trials on 25 patients with leukemia or lymphosarcoma, the in vitro test was used successfully to predict the response to treatment with prednisone and vincristine. It was concluded that the in vitro test system can predict the in vivo cytotoxicity of certain drugs for malignant cells, although it cannot be used to predict the likelihood of the induction of remissions with these drugs.

In Vitro Characterization Of Low Molecular Weight Fractions Of Heparin

1981 ◽  
Author(s):  
Jawed Fareed ◽  
Harry L Messmore ◽  
Daniel A Walz ◽  
Jean Choay ◽  
J C Lormeau
Keyword(s):  
Molecular Weight ◽  
The Other ◽  
Low Molecular Weight ◽  
In Vitro Test ◽  
Thrombin Time ◽  
Specific Test ◽  
Platelet Factor ◽  
At Iii ◽  
Heparin Fractions

Numerous extraction, chromatographic (ion exchange, gel, and affinity), chemical and enzymatic degradation methods have been employed to obtain heparin fractions. The present assays to evaluate potency (e.g. pharmacopeial and coagulant) do not truly reflect the antithrombotic properties of these fractions. In addition, the synthetic peptide substrate based assays to measure the anti Xa activity do not correlate with the coagulant anti Xa assays. We have developed an in vitro test battery to evaluate low molecular weight heparin fractions. Porcine mucosal heparin fractions are assayed for anti Xa activity in coagulant and amidolytic assays and the results are expressed as a ratio. The effect of these fractions on coagulant assays such as prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), Stypven time (ST) on freshly prepared normal human plasma (NHP) is determined The retention characteristics of these fractions on platelet factor 4 and AT-III bound sepharose columns were also determined. We have compared the extracted and chemically depolymerized heparin fractions and found that the anti Xa activity doesn’t always correlate with the other parameters studied. The extracted fractions were slightly stronger in the USP assays and showed a biphasic retention on the PF-4 column whereas the chemically depolymerized product showed only one peak. On the other hand, on the AT-III column both fractions showed similar elution patterns. Our studies suggest that heparin and its fractions exhibit differential behavior on various assays and a specific test may not be used as an index of the potency of their antithrombotic effects. Furthermore, the potency of these fractions should be stated on a weight basis when evaluated in the in vivo animal models rather than in terms of a specific test (e.g. anti Xa activity and US Pharmacopeial assays).

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