Progress in the development of RBC substitutes

Stowell, Christopher P.; Levin, Jack; Spiess, Bruce D.; Winslow, Robert M.

doi:10.1046/j.1537-2995.2001.41020287.x

Cited by 125 publications

(120 citation statements)

References 81 publications

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“…Hb solutions are potentially clinically useful for resuscitation, elective surgery, shock, cancer therapy, sickle cell anemia, coronary balloon angioplasty, stroke. and myocardial ischemia (8,9). In previous reports, it was found that the interaction of Hb with LPS results in a significant increase of the biological activity of LPS (8, 10 -12).…”

mentioning

confidence: 97%

Cross-linked Hemoglobin Converts Endotoxically Inactive Pentaacyl Endotoxins into a Physiologically Active Conformation

Brandenburg

Garidel

Andrä

et al. 2003

Journal of Biological Chemistry

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The interaction of purified ␣␣ cross-linked hemoglobin (␣␣Hb) with a pentaacylated mutant lipopolysaccharide (pLPS) and the corresponding lipid A (pLA) was studied biophysically and the effects correlated with data from biological assays, i.e. cytokine induction (tumor necrosis factor-␣) in human mononuclear cells and the Limulus amebocyte lysate assay. Fourier transform infrared spectroscopic and Zeta-Sizer experiments indicated an electrostatic as well as a non-electrostatic binding of ␣␣Hb to the hydrophilic and to the hydrophobic moieties of the endotoxins with an increase of the inclination angle of the pLA backbone, with respect to the membrane surface, from 25°to more than 50°. Small angle synchrotron radiation x-ray diffraction measurements indicated a reorientation of the lipid A aggregates from a multilamellar into a cubic structure as a result of ␣␣Hb interaction. Thus, in the absence of ␣␣Hb, the molecular shape of the pentaacyl samples was cylindrical with a moderate inclination of the diglucosamine backbone, whereas, in the presence of the protein, the shape was conical, and the inclination angle was high. The cytokine-inducing capability in human mononuclear cells, negligible for the pure pentaacylated compounds, increased markedly in the presence of ␣␣Hb in a concentration-dependent manner. In the Limulus assay, the pentaacylated samples were active a priori, and their activity was enhanced following binding to ␣␣Hb, at least at the highest protein concentrations. The data can be understood in the light of a reaggregation of the endotoxins because of ␣␣Hb binding, with the endotoxin backbones then readily accessible for serum and membrane proteins. By using fluorescence resonance energy transfer spectroscopy, an uptake of the endotoxin-Hb complex into phospholipid liposomes was observed, which provides a basis for cell activation.

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mentioning

confidence: 97%

Cross-linked Hemoglobin Converts Endotoxically Inactive Pentaacyl Endotoxins into a Physiologically Active Conformation

Brandenburg

Garidel

Andrä

et al. 2003

Journal of Biological Chemistry

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“…Third, it must be retained in plasma for a clinically relevant period of time. Finally, it must be costeffective and convenient in order to achieve widespread use [24].…”

Section: The Rationale For Hemoglobin Substitutesmentioning

confidence: 99%

“…This membrane protects the hemoglobin tetramers; without it, the tetramers would quickly dissociate into dimers and monomers, which subsequently get cleared by the kidney [24]. The average RBC carries its hemoglobin for an average of 120 days before being destroyed [8].…”

Section: The Rationale For Hemoglobin Substitutesmentioning

confidence: 99%

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Hemoglobin substitutes

2004

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“…10 O desenvolvimento desses produtos tem tido progresso considerável ultimamente. 11,12 zação da Hb para que viesse a ser usada como carreador de oxigênio livre de células. 20,21 Modificações estruturais da Hb incluem: ligação quí-mica cruzada a fim de estabilizar os tetrâmeros de Hb; polimerização da Hb produzindo moléculas de alto peso molecular, encapsulação de vários preparados de Hb e molé-culas de Hb recombinantes por engenharia genética.…”

Section: Introductionunclassified

Importância dos carreadores de oxigênio livre de células

Novaretti¹

2007

Rev. Bras. Hematol. Hemoter.

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IntroduçãoNo mundo todo, a necessidade de transfusões sangüíneas vem crescendo progressivamente. No Brasil, enquanto a demanda de sangue cresce à taxa de 1% ao ano, as expectativas de crescimento das doações de sangue variam de 0,5 a 0,7%/ano. 1 Conseqüentemente, a estimativa para o ano de 2030 é de um déficit de aproximadamente um milhão de unidades de sangue coletado, levando-se em conta o crescimento populacional projetado e as necessidades crescentes de transfusão, em especial para os que a necessitam cronicamente, para cirurgias de grande complexidade e no atendimento às emergências.2 Deve-se ressaltar que essa projeção não inclui situações de calamidade pública e desastres naturais.Se estimarmos as necessidades internacionais de transfusão de sangue e componentes, tendo por base a estimativa de 0,05 unidades per capita por ano, pode ser projetada uma demanda de assustadoras 300 milhões de unidades de sangue por ano.3 Quando são computados os números disponí-veis de transfusões de sangue em termos mundiais, temos cerca de 90 milhões de unidades transfundidas por ano. Caso esse número seja verdadeiro, há falta de 200 milhões de bolsas de sangue/ano. 4 Obviamente essas estimativas estão sujeitas a críticas, mas é evidente que não há suprimento total de sangue, particularmente de alguns tipos (como os Rhnegativo) em situações emergenciais, e a sazonalidade é importante fator que compromete o fornecimento de sangue. Deve-se ressaltar que, apesar de os progressos para o aumento da segurança transfusional e da diminuição vertigi-

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Progress in the development of RBC substitutes

Cited by 125 publications

References 81 publications

Cross-linked Hemoglobin Converts Endotoxically Inactive Pentaacyl Endotoxins into a Physiologically Active Conformation

Cross-linked Hemoglobin Converts Endotoxically Inactive Pentaacyl Endotoxins into a Physiologically Active Conformation

Hemoglobin substitutes

Importância dos carreadores de oxigênio livre de células

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