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P Labrude

Publications and source records attributed to P Labrude.

At least 37 records · Page 2Linked to original sources

[Pharmaceutical years of professor Pierre Donzelot (Besancon, Nancy, 1925-1947)].

Pierre Donzelot, born in Valentigney in 1901, was first charge de cours and assistant professor at the school of medicine and pharmacy in Besancon where he began to study pharmacy. After the first three years, he came to Nancy to become assistant of physics at the faculty of pharmacy and to obtain his diploma. He created a laboratory of research and began his PhD thesis on spectroscopy. After this thesis, Donzelot was nominated as a professor of physical chemistry at the Faculty of sciences but he remained in pharmacy for teaching. After 1947, he began a new activity, being nominated in high administrative functions in France and US. The note ends with Donzelot's activities for pharmacy after 1947 and memories of him in Valentigney, Besancon and Nancy.

Education, Pharmacy↗

In vitro study of the protective effect of trehalose and dextran during freezing of human red blood cells in liquid nitrogen.

Two nonpermeant cryoprotectants, the disaccharide trehalose and the polymeric carbohydrate (dextran, 40 kDa), were assessed as substitutes for glycerol in the cryopreservation of human red blood cells (RBC). The agents were evaluated by measuring the percentage of RBC recovery (total of free hemoglobin after freezing) and by evaluating the erythrocyte state after freezing. Ninety percent of the red cells were recovered after freezing in 30% (w/v) dextran in liquid nitrogen, which is very close to the recovery obtained in 35. 5% (w/v) glycerol (92%). The activities of pyruvate kinase and glucose-6-phosphate dehydrogenase of RBCs frozen and thawed with dextran were not modified, and the 2,3-diphosphoglycerate was reduced by 26%, but remained within normal values. ATP was reduced by 56%. The erythrocyte membrane integrity, evaluated by its osmotic fragility, was not altered, and the RBCs protected by dextran retained their normal discoid shape without the formation of microvesicles. The 24-h hemolysis of the washed red cells after storage at 4 degrees C was 7%. These results suggest that dextran protects red blood cells during freezing in liquid nitrogen, but that some effort is still needed to limit the drop of ATP concentration. One of the main advantages of dextran is that it does not penetrate the RBCs and requires less washing than glycerol.

Adenosine Triphosphate↗

Determination of the maximal tumor/normal skin ratio after HpD or m-THPC administration in hairless mouse (SKh-1) by fluorescence spectroscopy--a non-invasive method.

Two major steps in our study on the treatment of skin tumors by photochemotherapy (PCT) were the development of a skin tumor model in hairless mice by chemical carcinogenesis and by the use fluorescence spectroscopy, a semi-quantitative and non-invasive method, to determine the time after i.p. injection of photosensitizer when the tumor/normal skin ratio is the highest. Carcinogenesis provided mice bearing many benign papillomas and these were used to determine the tumor/normal skin ratios of two photosensitizers by fluorescence spectroscopy. Hematoporphyrin derivative (HpD) (5 mg/kg body weight) and m-tetra(hydroxyphenyl)-chlorin (m-THPC) (0.3 mg/kg body weight) were injected, and fluorescence measured at 4, 8, 24, 48, 72 and 96 h after injection. The tumor/normal skin ratio was 6.2 for HpD and 5.1 for m-THPC. The times required to reach these ratios were 48 h for HpD and 72 h for m-THPC. Published reports indicate that m-THPC gives a much higher tumor/normal skin ratio than HpD. These results must be confirmed by organic extraction. Photodynamic therapy with the same doses of HpD and m-THPC used in this pharmacokinetic study must also be carried out to compare the toxicities of the two photosensitizers and to determine which is best for this type of tumor.

Animals↗

Structure and stability of human hemoglobin microparticles prepared with a double emulsion technique.

Hemoglobin solutions can be used as blood substitutes but they present some disadvantages often due to their rapid removal from the bloodstream after injection. A possible way of overcoming this problem is to trap hemoglobin inside particles. This study deals with the preparation, structure and stability of poly(lactic acid) and ethylcellulose microparticles containing human hemoglobin obtained with a double emulsion technique. We investigated the manufacturing process of these particles in order to increase the encapsulation ratio of hemoglobin. For this purpose, some parameters involved in the procedure were optimized, such as hemoglobin concentration and duration of stirring: hemoglobin loading increases with its concentration in the preparation and well-defined stirring time avoids a leakage of hemoglobin. Hemoglobin concentration, surfactant concentration i.e. poly(vinylic alcohol), amounts of polymer and solvent (methylene chloride), duration and speed of stirring. The microparticles were prepared with satisfactory yields (60 to 73%). They were spherical and their mean size was lower than 200 microns. The functional properties of entrapped hemoglobin were studied. The encapsulation did not alter hemoglobin and the oxygen affinity of the hemoglobin remained unmodified (P50 about 13.9 mm Hg in a Bis-Tris buffer pH 7.4 at 37 degrees C). Moreover, only low levels of methemoglobin could be detected (less than 3%). Besides, about 90% of encapsulated hemoglobin could be released from microparticles, with a speed related to the internal structure of the particles. The prepared microparticles were stored during one month at +4 degrees C. No degradation of the particle structure occurred and the functional properties of hemoglobin were preserved. These particles could provide a potential source of oxygen in the field of biotechnologies but any application for a transfusional purpose would first require a drastic reduction in particle size.

Drug Compounding↗

[Théodore Guilloz, pharmacist and physician, pioneer and victim of radiology].

After the discovery of X rays, the first radiographies were obtained in France in January 1896. In Nancy, Guilloz obtained some of them on March 11. Pharmacist and physician, assistant professor and fellow at the Faculty of medicine, all his professional life was devoted to electrotherapy and radiology. This paper reports successively his studies in Besançon and his coming to Nancy, his career in hospital and university, his researchs and honours, his relations with the College of pharmacy, his illness consecutive to repeated irradiations, his activity during world War I and finally his death on March 26 1916.

France↗

[Nicolas and Camille Husson, chemists, archeologists, researchers ... in toul, during the second part of the 19th century].

Nicolas Husson (1814-1890) was chemist in Toul from 1843-1844 to 1875-1876. He was also a member of the town council and deputy of the mayor, in charge of questions interesting education and attendance. Collector, author of some 40 papers, he was very interested in archeology, geology and hygiene in the neighbourhood of Toul. He explored there holes such "Les Trous de Sainte-Reine" and "Le Trou des Celtes". His son Camille (1843-1886) was first a military chemist but he joined soon his father. He was essentially an independant researcher in chemical and alimentary analysis, toxicology and hygiene. Also the author of numerous papers and archeologist, he became national correspondent of the Academy of medicine and chairman of the "Société de pharmacie de Lorraine".

Archaeology↗

Hemoglobin-dialdehyde dextran conjugates: improvement of their oxygen-binding properties with anionic groups.

We studied the conjugates formed between hemoglobin and sulfated or unsulfated oxidized dextran. It appears that the presence of sulfated groups favors imino bond formation between the protein and the polymer, as the average molecular size of the conjugates is larger in this case. Under neutral conditions, the oxygen-binding properties of the conjugates depend on the presence or absence of oxygen during the coupling reaction. With unsulfated dextran, oxyhemoglobin leads to conjugates with increased oxygen affinity (P50/P50 native hemoglobin approximately 0.5) compared to that of free hemoglobin (P50 = 4 mm Hg), whereas deoxyhemoglobin leads to conjugates with decreased oxygen affinity (P50/P50 native hemoglobin approximately 3). The use of sulfated dextran reinforces this lowering in oxygen affinity, which indicates that sulfated dextran acts as a permanent macromolecular effector of hemoglobin (P50/P50 native hemoglobin approximately 4). Moreover, it can be assumed that some of the linkages involve the 2,3-diphosphoglycerate binding site, as the strong effector inositol hexaphosphate has only a slight effect on the oxygen-binding properties of the conjugate prepared in the deoxy state (P50/P50 native hemoglobin close to 4.4 and 6, respectively, for unsulfated and sulfated conjugates). Although dextran substituted with benzenehexacarboxylic acid (BHC) leads to a low-oxygen-affinity conjugate when linked to oxyhemoglobin through amide bonds (P50/P50 native hemoglobin approximately 5), oxidized dextran modified with BHC leads, with oxyhemoglobin, to a conjugate whose oxygen affinity is close to that of free hemoglobin (P50/P50 native hemoglobin approximately 1.2).

Aldehydes↗

[The gallery of portraits in the Faculty of Pharmacy in Nancy].

In homage to the Graduate School of Pharmacy in Strasburg, the School of Pharmacy of Nancy, who became its heir, instituted, beginning in 1914, a collection of portraits of former professors from these two cities. The portraits of several former Strasburgians are still exhibited in the Faculty at this time: those of L.-L. Oberlin, E.-T. Jacquemin, C.-F. Schlagdenhauffen, C.-E Schmitt and G.-M. Bleicher. The author reviews the activities of these professors in Nancy and reproduces three caricatures in which they are shown.

France↗

[Pulsed Doppler ultrasonography to measure the vasoactive effects of hemoglobin-dextran 10-benzene-tetracarboxylate, a potential erythrocyte substitute].

The effects of Dextran-Benzene-Tetracarboxylate-Hemoglobin (Dex-BTC-Hb), a chemically-modified hemoglobin-based oxygen carrier, on the vascular tone were compared to those of standard solutions, i.e. the animal's own blood and a 50 milligrams albumin solution, by measuring the carotid blood flow velocity, the mean arterial pressure, the heart rate and respiratory frequency, in anesthetized Hartley guinea pigs after a hemorragic shock. Stroma-free hemoglobin induced 40% hypertension and a 110% rise in blood flow velocity immediately after injection. The velocity was still increased 38%, 3 hours after injection. The calculations of the vascular resistances showed an increase in carotid vascular tone. Dex-BTC-Hb brought about 35% hypertension for two hours with no significant modifications of the vascular tone. These effects are similar to those of the albumin solution. These results indicate that, unlike stroma-free hemoglobin, Dex-BTC-Hb does not significantly affect the vascular tone, probably because of its slight interaction with the factors that regulate vascular tone.

Animals↗

In vitro effect of dextran-benzene-tetra-carboxylate hemoglobin on human blood rheological properties.

While conducting pharmacological investigations into oxygen carriers, it is important to study the in vitro and in vivo rheological behavior of blood cells in the presence of such preparations. With regard to the original nature of human hemoglobin bound to benzene tetracarboxylate substituted dextran (Dex-BTC-Hb), it seemed necessary to study its rheological effect in a simulated in vitro hemorrhagic shock compensated by a blood substitute. The viscosity of substitutes was determined as well as several rheological parameters after 0, 3 and 6 hours incubation periods of red blood cells with substitutes: viscosity of blood-substitute mixtures at different levels of plasma substitution erythrocyte aggregation of blood-substitute mixtures by determining the velocity of rouleau formation and the cohesion of rouleau network. This work yielded several observations: The viscosity of Dex-BTC-Hb was slightly higher than those of solutions of native Hb, Dex-BTC T10, Dextran 40 (Plasmacair, modified fluid gelatin (Plasmion and hydroxyethyl starch 200 (Elohes). The substitution of a blood volume with Dex-BTC-Hb, corresponding to a compensated 45% hemorrhagic shock, slightly increased the viscosity of hemodiluted blood as compared to other substitutes. In the presence of Dex-BTC-Hb, the aggregation of erythrocytes appears to be increased as compared to standard solutions. Yet, the effect was close to that of Plasmion or Elohes.

Blood Flow Velocity↗

Assessment of dextran 10-benzene-tetracarboxylate-hemoglobin, an oxygen carrier, using guinea pig isolated bowel model.

With the aim of assessing of dextran-benzene-tetracarboxylate hemoglobin as an oxygen carrier, we studied histological changes in the intestinal loop in anesthetized guinea pig. The intestinal tissue being very sensitive to hypoxia, an innervated loop was vascularly perfused with open-flow during one hour at zero hematocrit. To estimate the capacity of hemoglobin solution to oxygenate this tissue, we observed the mechanical and histological changes in the organ and the arterio-venous difference in PO2, oxyhemoglobin, deoxyhemoglobin and we compared them with human albumin, Tyrode and non-modified hemoglobin. The PO2 arteriovenous differences were 51.9 +/- 7.1 torr (m +/- SEM) for Tyrode, 40.2 +/- 6.4 torr for albumin solution, 113.7 +/- 6.5 torr for non-modified hemoglobin and 132.7 +/- 6.8 torr for dex-BTC-Hb. Compared to albumin and Tyrode solutions, hemoglobin solutions transferred more oxygen to tissues. The desaturation of dex-BTC-Hb was significantly superior (p < 0.05) to the one non-modified hemoglobin. With Hb solutions, this desaturation increased with time and it depended on the perfusion flow. The structure of jejunal villi when perfused with a hemoglobin solution, remained almost normal and the loop was still active. Nevertheless, non-modified hemoglobin leaked from the vessels to the lumen and caused edema and a rupture of overlapping epithelium at the tip of the villi. With dex-BTC-Hb, such histological modifications were less significant. With albumin and Tyrode, all villi were totally necrosed and the loop was completely inert. We have demonstrated that dextran-benzene-tetracarboxylate hemoglobin had the ability to maintain the tissue alive thanks to its good capacity to release oxygen and its satisfactory vascular persistence. Dex-BTC-Hb solution can answer to needs of tissue.

Animals↗

[Evaluation of hemoglobin dextran 10-benzene-tetracarboxylate, oxygen transporters, using a model of guinea pig intestine].

With the aim of assessing of dextran-benzene-tetracarboxylate hemoglobin as an oxygen carrier, we studied histological changes in the intestinal loop. The intestinal tissue being very sensitive to hypoxia, in the anesthetized guinea pig, an innervated loop was vascularly perfused with open-flow during one hour at zero hematocrit. To estimate the capacity of hemoglobin solution to oxygenate this tissue, we observed the mechanical and histological changes in the organ and the arterio-venous difference in PO2, oxyhemoglobin, deoxyhemoglobin and we compared them with human albumin, Tyrode and non-modified hemoglobin. The PO2 arterio-venous differences were 51.9 +/- 7.1 torr (m +/- SEM) for Tyrode, 40.2 +/- 6.4 torr for albumin solution, 113.7 +/- 6.5 torr for non-modified hemoglobin and 123.1 +/- 7.9 torr for dex-BTC-Hb. Compared to albumin and Tyrode solutions, hemoglobin solutions transferred more oxygen to tissues. The desaturation of dex-BTC-Hb was significantly superior (p < 0.05) to the one non-modified hemoglobin. The structure of jejunal villi when perfused with a hemoglobin solution, remained almost normal and the loop was still active. Nevertheless, non-modified hemoglobin leaked from the vessels to the lumen and caused oedema and a rupture of overlapping epithelium at the tip of the villi. With dex-BTC-Hb, such histological modifications were less significant. With albumin and Tyrode, all villi were totally necrosed and the loop was completely inert. We have demonstrated that dextran-benzene-tetracarboxylate hemoglobin had the ability to maintain the tissue alive thank to its good capacity to release oxygen and its satisfactory vascular persistence.

Animals↗

Human hemoglobin conjugated to carboxylate dextran as a potential red blood cell substitute. II--Pharmacotoxicological evaluation.

A solution of human hemoglobin bound to benzene tetracarboxylate substituted dextran, whose physicochemical characteristics are defined in part I, was evaluated in vivo as a potential red blood cell substitute. Further experiments show: - the confirmation of a lack of acute toxicity in mice and guinea pigs after injection of 12.5%, 25% and 50% of the blood mass and the absence of death in rabbits having undergone three successive 25% hemorrhagic shocks in three week intervals. A plasma half-life of 9.5 +/- 0.5 hours in 70-75% hemorrhagic shocks on guinea pigs and the absence of dex-BTC-Hb in thoracic and abdominal cavities. No tissue oedema was noticed. Total hemoglobinuria did not exceed 10% of the injected hemoglobin quantity and only involved free hemoglobin. A lack of death in 70-75% hemorrhagic shocks and survival times ranging from 10 hours to 3 days in total exchange transfusions in guinea pig experiments.

Animals↗

Methemoglobin formation after administration of hemoglobin conjugated to carboxylate dextran in guinea pigs. Attempts to prevent the oxidation of hemoglobin.

In 1990, McGown demonstrated in vitro a limitation of extracellular methemoglobin (metHb) formation by releasing and recycling of ascorbic acid by red blood cells. In order to investigate the autoxidation of free or modified hemoglobin in plasma and the possibility of reproducing McGown's phenomenon in vivo, we performed a 50% blood mass exchange in guinea-pigs with a 70 +/- 5 g/l dex-BTC-Hb solution (metHb < 5%). Methemoglobin was determined according to Evelyn-Malloy's method. We observed a clear but limited oxidation of plasmatic hemoglobin (MetHb approximately 30-40% at t = 12 hrs up to t = 24 hrs). A similar blood mass exchange was performed with the same hemoglobin solution which was previously totally oxidized into metHb. 40% of this methemoglobin was found to be reduced after 12 hrs. These results demonstrated a marked reducing activity by residual blood as shown by others. The addition of potentially protective compounds such as ascorbic acid (non enzymatic intraerythrocytar reduction pathway), methylene blue or riboflavin (enzymatic intraerythrocytar pathway), allowed a significant drop in the methemoglobin level. On the contrary, we didn't observe any reducing effect with reduced glutathione.

Animals↗

Preparation and characterisation of poly(lactic acid) hemoglobin microspheres.

For many years, a lot of research effort has been carried out with a view to preparing blood substitutes. Our group has developed a process of encapsulation of hemoglobin in polylactid microspheres. An aqueous solution of hemoglobin was emulsified into a solution of polymer in methylene chloride to form a W/O emulsion. This primary emulsion was then added to a external aqueous phase under stirring until the evaporation of methylene chloride. The microspheres were separated by filtration and washed with distilled water. Microspheres were spherical and their sizes vary between 10 and 500 microns. More than 80% of the hemoglobin was encapsulated. From the absorption spectra of hemoglobin from microspheres, we did not notice any alteration of the oxygen carrier. The dissociation curve of the hemoglobin demonstrated the permeability of the polymeric wall of these microspheres to oxygen. This curve was relatively sigmoidal and presented a P50 similar to that of free hemoglobin in the same experimental conditions. A cellulose's acetate gel electrophoresis of hemoglobin extracted from the microspheres showed one band that correlates with intact hemoglobin. These results suggest that hemoglobin does not interact chemically with the polymer matrix and that the process of microencapsulation does not alter the hemoglobin molecule.

Blood Substitutes↗