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Low-dose polymyxin: an option for therapy of Gram-negative sepsis.

Harm S, Gabor F, Hartmann J - Innate Immun (2016)

Bottom Line: The formed LPS-PMB complex has lower inflammatory activity in blood, which results in highly reduced cytokine secretion.Furthermore, the combination of cytokine removal by adsorbent treatment with LPS inactivation by PMB dosage leads to strong suppression of inflammatory effects in blood in an in vitro model.Inactivation of endotoxins by low-dose intravenous PMB infusion or infusion into the extracorporeal circuit during blood purification can be applied to overcome the urgent need for endotoxin elimination not only in treatment of sepsis, but also in liver failure.

View Article: PubMed Central - PubMed

Affiliation: Department for Health Sciences and Biomedicine, Danube University Krems, Krems, Austria Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria stephan.harm@donau-uni.ac.at.

No MeSH data available.


Related in: MedlinePlus

Binding of PMB to plasma proteins determined by ultrafiltration through membranes with different MMCO. The filtration rate of PMB in plasma was compared with that in 0.9% NaCl solution. The data represent the percentage of PMB in the filtrate as referred to the positive control (mean ± SD; n = 3).
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fig7-1753425916639120: Binding of PMB to plasma proteins determined by ultrafiltration through membranes with different MMCO. The filtration rate of PMB in plasma was compared with that in 0.9% NaCl solution. The data represent the percentage of PMB in the filtrate as referred to the positive control (mean ± SD; n = 3).

Mentions: Most drugs bind to plasma proteins such as albumin, α1-acid glycoprotein, lipoproteins, α-, β- and γ-globulins, and to erythrocytes. Ultracentrifugation of PMB-spiked plasma through membranes with different MMCOs for separation of protein-bound PMB from free PMB revealed that this drug with a molecular weight of 1.3 kDa is mostly bound to plasma contents. Only the membrane with 100 kDa MMCO was permeable for higher amounts of PMB (25 ± 13%). The PMB-content of filtrates obtained from centrifugation through membranes with smaller pores was <10% compared with a PMB-solution without plasma (Figure 7). Thus, >90% of PMB is bound to plasma proteins and not even one-tenth exists in its free form in circulation.Figure 7.


Low-dose polymyxin: an option for therapy of Gram-negative sepsis.

Harm S, Gabor F, Hartmann J - Innate Immun (2016)

Binding of PMB to plasma proteins determined by ultrafiltration through membranes with different MMCO. The filtration rate of PMB in plasma was compared with that in 0.9% NaCl solution. The data represent the percentage of PMB in the filtrate as referred to the positive control (mean ± SD; n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2 - License 3
Show All Figures
getmorefigures.php?uid=PMC4834512&req=5

fig7-1753425916639120: Binding of PMB to plasma proteins determined by ultrafiltration through membranes with different MMCO. The filtration rate of PMB in plasma was compared with that in 0.9% NaCl solution. The data represent the percentage of PMB in the filtrate as referred to the positive control (mean ± SD; n = 3).
Mentions: Most drugs bind to plasma proteins such as albumin, α1-acid glycoprotein, lipoproteins, α-, β- and γ-globulins, and to erythrocytes. Ultracentrifugation of PMB-spiked plasma through membranes with different MMCOs for separation of protein-bound PMB from free PMB revealed that this drug with a molecular weight of 1.3 kDa is mostly bound to plasma contents. Only the membrane with 100 kDa MMCO was permeable for higher amounts of PMB (25 ± 13%). The PMB-content of filtrates obtained from centrifugation through membranes with smaller pores was <10% compared with a PMB-solution without plasma (Figure 7). Thus, >90% of PMB is bound to plasma proteins and not even one-tenth exists in its free form in circulation.Figure 7.

Bottom Line: The formed LPS-PMB complex has lower inflammatory activity in blood, which results in highly reduced cytokine secretion.Furthermore, the combination of cytokine removal by adsorbent treatment with LPS inactivation by PMB dosage leads to strong suppression of inflammatory effects in blood in an in vitro model.Inactivation of endotoxins by low-dose intravenous PMB infusion or infusion into the extracorporeal circuit during blood purification can be applied to overcome the urgent need for endotoxin elimination not only in treatment of sepsis, but also in liver failure.

View Article: PubMed Central - PubMed

Affiliation: Department for Health Sciences and Biomedicine, Danube University Krems, Krems, Austria Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria stephan.harm@donau-uni.ac.at.

No MeSH data available.


Related in: MedlinePlus