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Biomedical subjects

P Labrude

Publications and source records attributed to P Labrude.

At least 73 records · Page 4Linked to original sources
PubMed1989

[Hemoglobin niosomes. I. Preparation, functional and physico-chemical properties, and stability].

Hemoglobin niosomes. I, Preparation, functional and physical properties and stability. Hemoglobin niosomes (non ionic liposomes) obtained from L'Oréal synthetic lipids by solvents vaporization appear as unilamellar spherical red vesicles, isolated from each other and with heterogeneous size (0.5 to 4 microns). Their suspensions show a visible spectra superimposable to that of free hemoglobin which is incorporated at a rate of 0.3 to 0.5 g per lipid gram. Vesicles are permeable to oxygen and the hemoglobin dissociation curve can be modified similarly to non-encapsulated hemoglobin. Niosomes appear physically stable while hemoglobin undergoes a progressive oxidation to methemoglobin reaching 30% after 5 months at 4 degrees C. Even in the absence of dicetylphosphate (DCP), niosomes possess a negative charge confering to them an electrophoretic mobility. 5% DCP allows to obtain a zeta potential near to that of erythrocytes. The niosomes suspensions are more viscous than red blood cells but their rheological behavior is similar and the vesicles may have some deformability.

Chemical Phenomena↗
PubMed1988

[Not Available].

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Education, Pharmacy↗
PubMed1988

Hemoglobin solutions coupled with polyethylene glycol 1900: preparation, purification, quality control and pharmacological trials by hemorrhagic shock.

The usefulness of hemoglobin solutions as oxygen transporters is limited by their high affinity for oxygen and rapid elimination from the circulation. Various chemical modifications of hemoglobin aimed at overcoming these two handicaps have been suggested. We have developed a conjugate of pyridoxylated human hemoglobin with monomethoxypolyoxyethtylene 1900, whose preparation and properties are described. We present comparative results on short-term or definitive survival of Wistar rats which, during hemorrhagic shock due to the loss of 60 or 80% of their blood mass, were given a solution of native or modified hemoglobin, in some cases purified by ion-exchange chromatography to remove non-heme proteins, lipids, and some endotoxins. The more complex the treatment used to improve the properties and the purity of the hemoglobin solutions, the longer the animals survived. The loss of hemoglobin in the urine was greatly reduced after conjugation: after 20 h, less than 6% of the total infused.

Animals↗
PubMed1987

Problems of haemoglobin freeze-drying: evidence that water removal is the key to iron oxidation.

Formation of methaemoglobin during freeze-drying of oxyhaemoglobin raises the question of the cause and mechanism of the oxidation. Haemoglobin with or without lyoprotector (250 mM glucose or amino acid salt) has been subjected to freeze drying changes in either or both of two constraints--vacuum and rise in temperature. A rise in temperature from -40 to +10 degrees C had no substantial denaturing effect on haemoglobin whether protected or not. Maintenance of a vacuum over frozen haemoglobin for 18 h often produced subtotal desiccation. Unprotected haemoglobin was partially oxidized (39% MetHb) whereas protected haemoglobin was not (less than 4% MetHb). Haemoglobin was also dried by rapid dehydration of thin films in a stream of air at room temperature (20 degrees C). The methaemoglobin content was then 43% whereas the amino acid salt or glucose limited it at 4 and 7%, respectively. Haemoglobin is oxidized, therefore, only because of the removal of water. Protectors, not specific in structure and action, probably work by holding or reinforcing the critical number of hydration layers around haemoglobin.

Freeze Drying↗
PubMed1987

Synthetic carriers of oxygen.

During the last decade, construction of artificial carriers of oxygen for transfusion purposes has evolved in three main directions, which can be reviewed as follows. The first approach consists of modifying hemoglobin (Hb), the natural oxygen carrier, in order to lower its oxygen affinity and increase its intravascular persistence. To achieve this aim, two basic procedures have been used: molecular and environmental modification. In the first case, Hb is modified with chemical reagents; the second requires encapsulation of Hb to obtain artificial erythrocytes. The second approach is based on the use of synthetic oxygen-carrying chelates that mimic the oxygenation function of Hb. The main products in this class are metalloporphyrins, whose chemical environment is designed to render them efficient as reversible carriers of oxygen in vivo. Finally, the third approach deals with the perfluorochemicals used in emulsified form. Perfluorochemical liquids are excellent gas solvents, but some problems remain unsolved with regard to their development as oxygen carriers in vivo: low O2 dissolving capacity, toxicity, and excretion.

Animals↗
PubMed1986

[The place for using erythrocyte substitutes in hemodilution: fluosol-DA and polymerized pyridoxylated hemoglobin].

In conditions of limited haemodilution (haematocrit 0.25), an improvement in the rheological properties of blood and an increase in cardiac output allow increased perfusion of capillaries and maintenance of tissue oxygenation so long as normal circulating volume is maintained. However, some authors have suggested that blood substitutes enabling oxygen transport are necessary. The suitability of such substitutes depends on their physicochemical properties and, until now, only the use of haemoglobin solutions and fluorocarbon emulsions has been. The use of fluorocarbons requires respiration under hyperoxia or pure oxygen, which is a major limitation. Haemoglobin solutions suffer from inadequate concentration, short vascular persistence and too high an affinity for oxygen, but these deficiencies disappear with polymerized pyridoxylated haemoglobin. Though both types of preparation can keep animals alive with zero haematocrit for some time, their contribution to oxygenation goes down as the haematocrit goes up. According to Zander and Makowski [40]. the minimum acceptable amount of oxygen in the blood is reached with a haemoglobin concentration of 4.4 g X 100 ml-1 with a Po2 of 90 mmHg (12 kPa), and of 3.3 g X 100 ml-1 with a Po2 of 550 mmHg (73 kPa); these values correspond to a haematocrit close to 0.10. At this haematocrit and with a Po2 of 90 mmHg, a 70 g X l-1 haemoglobin solution contributes for 28% to the consumption of oxygen in baboons, while Fluosol DA 20, used at Po2 550 mmHg, takes care of 55% of this consumption. At higher haematocrits, it is not certain that these substitutions have a real advantage over the usual plasma expanders at normovolaemic haemodilution.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗
PubMed1985

Total exchange transfusion in rats with hemoglobin solutions: influence of hemoglobin concentration.

In most published studies of the oxygen transport capacity of hemoglobin solutions for total or partial replacement transfusions, the hemoglobin concentrations have been in the order of 70 g/l. In this study we tried to identify the hemoglobin concentration that would give the best survival in rats at zero hematocrit. The longest survival time, of more than 4 h, was obtained with a hemoglobin concentration of 125 g/l, despite an oncotic pressure much higher than that of plasma. This observation suggests the use of more highly concentrated solutions of modified or unmodified hemoglobin than are presently recommended, in order to increase their oxygen transport capacity.

Animals↗
PubMed1984

Freeze-drying of oxyhemoglobin: protection against oxidation in the presence of EDTA salts, sulfonic acid buffers, and pantothenic acid derivatives.

Hemoglobin was freeze-dried in the presence of salts of EDTA, sulfonic acids used as buffers, or derivatives of pantothenic acid. At 0.25 M most of the compounds effectively inhibited the formation of methemoglobin. The various model compounds used (sodium zinc EDTA, tris(hydroxymethyl) methylaminopropanesulfonic acid, and DL-pantothenol) produced similar decreases in methemoglobin formation as a function of the concentration of protective agent between 0.01 and 0.20 M. Experiments on the storage of the freeze-dried materials revealed substantial denaturation of oxyhemoglobin after 12 months at 4 degrees C. On the whole, these compounds were less effective than amino acid salts, during both desiccation and storage. The multiplicity of compounds that inhibit the denaturation of hemoglobin during freeze-drying indicates that their mode of action is nonspecific.

Buffers↗
PubMed1984

Influence of physical conditions on the oxidation of hemoglobin during freeze-drying.

The potential influence of some physical conditions--dialysis, crystallization, concentration, pH, and temperature--on the amount of methemoglobin obtained after freeze-drying of hemoglobin has been studied. Among these parameters, pH and crystallization influence the oxidation. In acid medium (pH 5), the oxygen saturation is better than that obtained for pH 8. Crystalline hemoglobin leads to a methemoglobin rate significantly lower (29% versus 49%) than untreated hemoglobin. Methemoglobin is continuously formed during desiccation even at the lowest temperature. Although it has been possible to lessen the denaturation of hemoglobin by the choice of a definite preliminary treatment of the samples, we were not able to reduce methemoglobin to low and physiological values. However, the results obtained with crystalline hemoglobin make it possible to propose mechanisms for the oxidation of the hemoprotein.

Crystallization↗
PubMed1983

Modification of human hemoglobin by covalent association with soluble dextran.

Stroma-free Hb solutions present some drawbacks when used as erythrocyte substitutes, mainly because the protein has a short in vivo half-life, due to its small hydrodynamic volume. Covalent coupling of oxyHb with dialdehyde-dextran (Mw congruent to 40 000; Mn congruent to 25 000) leads to adducts whose properties depend upon the pH of the condensations. At pH less than 9.6, many labile imine linkages are formed and the conjugates have a high molecular weight at the end of the reaction. In contrast, the final products obtained as pH increases from 9.6 to 10 contain a low-molecular-weight adduct in an increasing ratio; in this case the bond between dextran and Hb is stable and this stability is assumed to result from the rearrangement of a specific imine linkage formed at an NH2 site of Hb, into a ketoamine group (Amadori rearrangement). Dextran-Hb conjugates have oxygen-binding properties characterized by increased oxygen affinity, and decreased subunit cooperativity and alkaline Bohr effect, relative to unconjugated Hb. These differences become less as the time of condensation reaction decreases and seem to be due to modification of amine groups involved in the salt bridges that stabilize the deoxy form of the protein. Taking into account their oxygen-binding characteristics, the low-molecular-weight conjugates can be regarded as potential erythrocyte substitutes.

Chromatography, Gel↗
PubMed1983

Stability and functional properties of haemoglobin freeze-dried in the presence of four protective substances after prolonged storage: dose-effect relationships.

Freeze-dried haemoglobin samples protected during the desiccation by sucrose, arginine aspartate, lysine aspartate, sodium-zinc EDTA and Ficoll 70 have been stored under air at 4 degrees C for 15 months. The analysis showed that sufficient concentrations of sucrose and of the amino-acid salts prevent the oxidation of haemoglobin and maintain its functional properties. Relationships between the concentrations of these compounds and the methaemoglobin levels before and after storage were calculated. They define theoretical concentration points where methaemoglobin would not be found after storage. Sucrose is slightly more effective than the amino-acid, but oppositely, EDTA and Ficoll 70 do not allow prolonged storage of freeze-dried haemoglobin.

Amino Acids↗
PubMed1982

[Not Available].

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Biochemistry↗
PubMed1981

Freeze-drying of hemoglobin solutions without adjuvant and in presence of glucose, tris, and beta-alanine: a study by electron spin resonance of the oxidized compounds produced.

Hemoglobin cannot be freeze-dried without the presence of protective compounds. Carbohydrates are a well-known example of such compounds, but we have shown that some amine buffer and amino acids are also very effective. The mechanism of action of all these molecules is unknown. We report here experimental data showing that the protective effect is not the result of a direct bond between iron and the protective compound added.

Absorption↗
PubMed1981

Preparation and oxygen binding properties of soluble covalent hemoglobin-dextran conjugates.

Stroma-free hemoglobin solutions present some drawbacks when used as blood substitutes, essentially because the hemoprotein has a low vascular retention, due to its small hydrodynamic volume. Covalent coupling of the protein with dextran derivatives artificially increases its size and affords polymeric conjugates whose oxygen-binding properties (Barcroft's curve, Hill coefficient) depend on the molecular weight.

Chemical Phenomena↗