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Biomedical subjects

P Labrude

Publications and source records attributed to P Labrude.

At least 19 recordsLinked to original sources

[Pedology in pharmacy: stake, development, difficulties, constraints].

Pedology is a traditional activity of the pharmacist. To render this service to patients, the pharmacist must acquire a certain degree of professional proficiency to satisfy patients and comply with the quality regulations of the health authorities. Competition with other health care professionals must also be considered. To conserve this proficiency, a minimum number of soles would have to be sold each week. This requires time and training and thus raises the question of subsidiary activities of the pharmacy and its relative importance in the pharmacist's activity. The pharmacist who provides pedology services will be distinguished by the public, but the risk is the detriment to drug dispensing. A critical balance must be reached.

France↗

Involvement of neutrophilic granulocytes in the uptake of biodegradable non-stealth and stealth nanoparticles in guinea pig.

The in vivo behavior of monomethoxypoly(ethylene oxide)-poly(lactic acid) (MPEO20-PLA45/PLA (75/25)) nanoparticles in comparison with PLA ones was studied in guinea pig. Indeed, the aim of this study was to bring to the fore the in vivo stealth character of these copolymer nanoparticles and to identify the phagocytic circulating cells involved in their uptake. After the intravascular administration of fluorescent nanoparticles (rubrene), their phagocytosis by granulocytes and monocytes was assayed by flow cytometry. At the same time, the evolution of the number of these phagocytic cells was realized in order to identify their function in the nanoparticle uptake. Finally, a histological study of the spleen (30 h after the nanoparticle administration) was investigated to highlight the splenic trapping of these stealth nanoparticles. This study has shown that the phagocytic circulating cells involved in the nanoparticle uptake were mainly neutrophilic granulocytes and some of them were found in the spleen.

Animals↗

In vivo effects of Hb solutions on blood viscosity and rheologic behavior of RBCs: comparison with clinically used volume expanders.

BACKGROUND: Hb-based oxygen carriers (HbOCs) have vasoactive effects that are still poorly understood. Factors known to have vasoactive effects, such as plasma, whole-blood viscosity, and the rheologic behavior of RBCs, are modulated by HbOCs in vitro, but few in vivo studies have been performed. STUDY DESIGN AND METHODS: Rabbits were phlebotomized (30%) and resuscitated with unmodified stroma-free Hb (SFHb), dextran-tetracarboxylate-Hb (Dex-BTC-Hb), O-raffinose-polymerized Hb (OrpHb), HSA, or hydroxyethyl starch 200 (HES). Plasma viscosity was assessed with a capillary viscometer and whole-blood viscosity with a rotational viscosimeter. RBC aggregation kinetics were determined by analysis of back-scattered light in a rotating device. RESULTS: As compared to that in the control RBC suspension, resuscitation with SFHb, OrpHb, or HSA decreased plasma and whole-blood viscosity as well as RBC aggregation; resuscitation with Dex-BTC-Hb increased whole-blood viscosity at low shear rates as well as RBC aggregation, whereas that with HES decreased whole-blood viscosity but increased RBC aggregation. CONCLUSION: HbOCs have different rheologic effects in vitro and in vivo. There are marked differences among the Hb solutions in their in vivo effects on viscosity and RBC rheologic behavior (especially at low shear rates encountered in the venous circulation and the microcirculation), which may be related to the chemical modifications applied to hemoprotein. These results could contribute to an understanding of the vasoactive effects of HbOCs.

Adult↗

Systemic and renal hemodynamics after moderate hemodilution with HbOCs in anesthetized rabbits.

Hb-based O(2)-carrying solutions (HbOCs) have been developed as red blood cell substitutes for use in patients undergoing hemodilution. Variously modified Hb with diverse solution properties have been shown to produce variable hemodynamic responses. We examined, through pulsed-Doppler velocimetry, the systemic and renal hemodynamic effects of dextran-benzene-tetracarboxylate-conjugated (Hb-Dex-BTC), bis(3,5-dibromosalicyl)fumarate cross-linked (alphaalpha-Hb), and o-raffinose-polymerized (o-raffinose-Hb) Hb perfused in rabbits after moderate hemodilution (30% hematocrit), and we compared the effects of these Hb solutions with the effects elicited by plasma volume expanders. In addition, vascular hindrance (resistance/blood viscosity at 128.5 s(-1)) was calculated to determine whether a moderate decrease in the viscosity of blood mixed with HbOCs may impair vasoconstriction as a result of autoregulation after infusion of cell-free Hb. No changes were observed in renal hemodynamics after hemodilution with reference or Hb solutions. Increase in blood pressure and vascular resistance was found with Hb-Dex-BTC and alphaalpha-Hb (for 180 min) and, to a lesser extent, with o-raffinose-Hb (for 120 min). Furthermore, Hb-Dex-BTC (high viscosity) and o-raffinose-Hb (medium viscosity) induced comparable increases in vascular hindrance (from 0.091 to 0. 159 and from 0.092 to 0.162 cm(-1), respectively) but far less than that produced by alphaalpha-Hb (low viscosity, from 0.092 to 0.200 cm(-1)). These results suggest that maintaining the viscosity of blood by infusing solutions with high viscosity makes it possible to limit vasoconstriction due to autoregulation mechanisms and mainly caused by hemodilution per se.

Animals↗

[Validation of a method to inactivate fentanyl in the used devices of Durogesic].

A recent literature study has shown that after 3 days of use of a transdermic patch of fentanyl (Durogésic(R)), there was such an amount of drug remaining that may make its excessive use possible. First of all, we have developed a fentanyl assay by a spectrophotometric method and then, the remaining amount of fentanyl was determined in 29 used patches. This study has shown that a mean of 22% of fentanyl remained in the used patches, each original content astounded. Then, we have determined an easy and feasible method in a chemist's shop allowing inactivation of fentanyl in the used patches and so preventing its diversion.

Administration, Cutaneous↗

Rheological behaviour of red blood cells suspended in hemoglobin solutions. In vitro study comparing dextran-benzene-tetra-carboxylate hemoglobin, stroma free hemoglobin and plasma expanders.

Circulating volume expansion for intentional hemodilution and/or resuscitation of hemorrhagic shock can be performed with hemoglobin-based oxygen carriers (HBOC) which, in addition to oxygen transport, have vasoactive effects through poorly documented mechanisms. Among these, the effects of HBOC on red blood cell (RBC) rheology are relatively unknown. The aim of the present in vitro study was to measure the rheological effects of human hemoglobin bound to benzene-tetracarboxylate substituted dextran (Dex-BTC-Hb) as an example of chemically modified hemoglobin. The viscosity was assessed with a capillary and a rotational viscometer for shear rates of 0.5-128 s-1. Erythrocyte aggregation was determined by analysis of the red light backscattered in a RBC suspension and with a rheoscope. The deformability was determined by the pressure-flow relationship of the RBC suspensions passed through polycarbonate filters. At hematocrit of 0.35 l/l and at low shear rates, the viscosity of RBC was higher in the presence of Dex-BTC-Hb as compared to free Hb, Dex-BTC, Dextran 40 (Plasmacair), modified fluid gelatin (MFG-Plasmion) or hydroxyethyl starch (HEA-Elohes). The effect on erythrocyte aggregation of Dex-BTC-Hb was greater than that of standard solutions, but close to that of MFG or HEA. There was no apparent change in RBC deformability. Dex-BTC-Hb, unlike free Hb, has a hyperaggregating effect on RBC, similar to that of some clinically used volume expanders. This hyperaggregating effect could influence the in vivo rheological behavior of substituted Hb by increasing shear stress.

Blood Substitutes↗

Presence of hemoglobin inside aortic endothelial cells after cell-free hemoglobin administration in guinea pigs.

The endothelium is the production site of several potent vasoactive factors that contribute to the modulation of the vascular tone. Because hemoglobin-based oxygen carriers (HBOC) have been demonstrated to cause vasoconstriction and thereby increase arterial pressure by interacting with endothelium-derived factors such as nitric oxide and endothelin-1, we hypothesized that hemoglobin could penetrate into the endothelial cells. Therefore, we investigated the presence of hemoglobin into guinea pig aortic endothelial cells by immunohistochemical staining after exchange transfusion with a hemoglobin-based oxygen carrier. Despite the large molecular size of HBOC due to chemical modifications designed to prevent hemoglobin subunit dissociation and extravascular leakage, hemoglobin was detectable by immunohistochemical staining into the endothelial cells. These findings suggest that the vascular endothelial cells could uptake hemoglobin by endocytosis mechanisms or could help hemoglobin to cross the endothelial barrier toward media by transcytosis mechanisms. These findings are very important to lead future investigations to the mechanisms by which HBOC cause vasoconstriction.

Animals↗

Cardiovascular and hemorheological effects of three modified human hemoglobin solutions in hemodiluted rabbits.

The cardiovascular effects of human albumin (Alb) and three human hemoglobin (Hb) solutions, dextran-benzene-tetracarboxylate Hb, alphaalpha-crosslinked Hb, and o-raffinose-polymerized Hb were compared in anesthetized rabbits undergoing acute isovolemic hemodilution with Hct reduction from 41.4 +/- 2.7 to 28.8 +/- 1.6%. The impact of the vasoconstricting properties of Hb was examined by measuring heart rate (HR), mean arterial pressure (MAP), abdominal aortic, and femoral arterial blood flow, vascular resistance (VR), and aortic distension during the first 3 h after hemodilution. The impact of the hemorheological parameters was assessed by measurements of hemodiluted blood viscosity. In contrast to Alb, the Hb solutions elicited an immediate increase in MAP (20-38%). The effects of Alb and Hb solutions on HR, as well as on aortic and femoral arterial blood flow, were similar. VR decreased with Alb (20-28%) and increased with all three Hb solutions (30-90%), but the MAP and VR rising trends were different with each Hb solution. Aortic distension decreased in Hb groups compared with the Alb group for the first 60 min. The viscosity of hemodiluted blood was similar for all groups at high shear rates but was dependent on the viscosity of the solutions at low shear rates. We conclude that the vasoconstriction elicited by the Hb solutions overrides the vasodilation associated with viscosity changes due to hemodilution and would be the major factor responsible to the cardiovascular changes.

Albumins↗

The effects of stroma-free and dextran-conjugated hemoglobin on hemodynamics and carotid blood flow in hemorrhaged guinea pigs.

Hemoglobin solutions are potential resuscitative fluids with volume expanding and oxygen delivery abilities developed to reduce the use of blood transfusion. Most hemoglobin solutions in clinical trials increase transiently arterial pressure by inhibiting nitric oxide-dependent vasodilation. Our objective was to compare the effects on central hemodynamics and carotid blood flow of two hemoglobin solutions after resuscitation from hemorrhage in anesthetized guinea pigs. After anesthesia and instrumentation, severe hemorrhage was induced by withdrawing 50% of the blood volume. Resuscitation was performed after 15 min of hypovolemia with 5% albumin, stroma-free hemoglobin, or hemoglobin conjugated to dextran-benzenetetracarboxylate (Dex-BTC-Hb). The mean arterial pressure (MAP), carotid blood flow (CBF), vascular resistance index and heart rate (HR) were monitored for 3 hours after resuscitation. After hemorrhage, MAP and CBF dropped to 57.6 +/- 4.4% and 58.9 +/- 3.7% of control values respectively. Albumin failed to maintain hemodynamics in the decompensatory phase of shock. Both hemoglobin solutions gave rise to a transient increase in MAP (35%); stroma-free hemoglobin increased the CBF (150%) and resistance index (24%) whereas Dex-BTC-Hb had no effect on CBF and vascular resistances. None of the solutions affected the HR. Modified hemoglobin has attenuated effects on CBF and resistance index compared to stroma-free hemoglobin. This may be due to a balance between the stimulation of nitric oxide synthesis by shear-stress and the inhibition of vasodilation by nitric oxide trapping.

Animals↗

Induction of superficial bladder tumors in the female Fischer 344 rats with AY-27 tumor cells for the study of diffusion and localization of hemoglobin derived components (hematoporphyrin derivative) in view of photochemotherapy.

Photochemotherapy (PCT) consists in administration of a photosensitizer and subsequent irradiation of the tumor with visible light. Routinely, the photosensitizer is given intravenously (i.v.), but the major drawback of this procedure is the resulting skin photosensitivity. The goal of our study is to examine whether intravesical (i.b.) instillation of the photosensitizer for PDT of bladder cancer might be feasible in order to target the tumors and to avoid the photosensitization phenomenon. After first studying the biodistribution of hematoporphyrin derivative (HpD) in vivo in the rat bladder, two and four hours after intravesical administration, by fluorescence microscopy, we compared two different methods for the induction of superficial bladder tumors in rats with AY-27 tumor cell line in order to perform the same study on bladder tumors. The best results for the penetration depth of HpD in the normal bladder wall were obtained two hours after the bladder instillation where the photosensitizer was detected only in the bladder surface (urothelium and small part of the chorion). That's why we must choose the most appropriate bladder tumor model in order to obtain superficial bladder tumors that mimic the clinical behavior of superficial bladder cancer in man. Both techniques used in this study gave a high tumor take rate in a short time (> 90%). But we really obtained superficial bladder tumors directly attached to the bladder surface with one of the two methods of tumor induction consisting in the abrasion of the bladder surface prior to the administration of the tumoral cells in the bladder cavity.

Animals↗

[The Pharmacopee de Nancy from Francois Mandel].

Expected by the apothecaries since 1624, this pharmacopoeia, written in Latin in 1790, is published in 1795 with french translation face to face. New chemical nomenclature and partly new names for preparations give it new look, simpler than Codex of Paris 1758. Nevertheless, its impact on pharmaceutical practice was insignificant.

France↗

[The pharmacist, painter and engraver Adrien Recouvreur and the chemistry of painting].

Adrian Recouvreur was born in Commercy, in the department of Meuse, on January 27, 1858. He was a student in pharmacy in Nancy and Reims where he obtained his diploma in 1885. He bought then a pharmacy in his native town. During his student years, he studied also painting and drawing in Commercy and Nancy. It seems also that he belonged to the Ecole de Nancy and he coasted some of the founders of this society. In 1896 or 1897, he renounced to pharmaceutical activity to devote all his time to painting, engraving and art criticism. He left then Lorraine to settle himself in Angers where he became soon the preserver of Musee Turpin de Criosse. He died in this town on March 18, 1944, after having handed down to posterity a great number of art works to his native and his reception towns. His knowledges in chemistry gave him the idea to be useful to his artist friends by realizing studies and experiments on colours whose alterability seemed to him alarming for the future of many art works. Some books gather the results of his work in this field.

Engraving and Engravings↗

[Marcel Petitmengin (1881-1908), pharmacist botanist: his life, his work].

Marcel Petitmengin was born in Nancy in January 1881. Student at the school of pharmacy and preparator in its laboratory for natural history, he received his diploma in 1904. He had already published some papers on botany and belonged to the International Academy for Geographical botany. He choose the flora of Mount Viso, in Italy, for his philosophical thesis. In the same time, he worked on greek flora with Maire, then on Primulaceae from Asia. Having published about fifty papers on botany, he died from tuberculosis in October 1908, being twenty-seven years old. Very faithful, he took part actively in protestantism in Nancy.

Botany↗

[Pierre Bayen (Chalons-sur-Marne 1725-Paris 1798), organizer of military pharmacy, chemist].

Pierre Bayen was born in Chalons in 1725. Pupil in pharmacy in Reims and in Paris, he begun his military career during the "Expedition de Minorque". After the "Guerre de Sept-Ans", named major apothecary, he had to organize the military pharmacy. At the end of his life, he was named general inspector of the medical corps. Member of the College de pharmacie, he devoted a great deal of his time to chemical research and he was named as a member of the Institut national de France when it was created. Bayen is one of the founders of analytical chemistry and of mineralogy. His results on the toxicology of pewter plates were famous. He is one of the precursors of the discovery of oxygen and one of the creators of modern chemistry. Bayen died in Paris in 1798.

Chemistry, Analytic↗

Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method.

Nanoparticles were prepared by the double emulsion method (w/o/w), using methylene chloride as an organic solvent and polyvinyl alcohol (PVA) or human serum albumin (HSA) as a surfactant. Experimental parameters such as the preparation temperature, the solvent evaporation methods, the internal aqueous phase volume, the surfactant concentration and the polymer molecular weight were investigated for particle size, the zeta potential, the residual surfactant percentage and the polydispersity index. Preparation parameters leading to particles with well-defined characteristics such as an average size around 200 nm and a polydispersity index lower than 0.1 were identified. The conditions were optimized to ensure protein encapsulation: a cool temperature, a short processing time, a sufficient internal aqueous phase and careful washing. It appeared that the higher the surfactant concentration in the external aqueous phase was, the smaller the particles, the lower the polydispersity index and the higher the residual amount of surfactant were. For PVA or HSA, the agreement between the convenient surfactant concentration and its critical aggregation concentration could be emphasized. Otherwise, an increased polymer molecular weight led both to a slightly decreased particle size and to a lower polydispersity index. Moreover, multilayer absorption of PVA which does not depend on Poly(lactic-acid) molecular weight was exhibited. Finally, the zeta potential resulted from the polymer molecular weight and the residual PVA.

Drug Delivery Systems↗

Proposition of a technique to assess the vasoactive effects of hemoglobin-based oxygen carrying solutions in vivo: preliminary results in the rabbit aorta.

Most of hemoglobin-based oxygen carriers (HBOCs) increase the blood pressure after injection in the blood stream by a mechanism involving one or more factors that contribute to the regulation of the vascular tone. Many techniques make it possible to study the vascular effects of HBOCs both in vivo and in vitro. The in vivo methods assess the blood pressure and some estimated regional blood flows (use of radioactive or colored microspheres). Measurements of the real vessel diameter and blood flow would be useful to understand hemoglobin-mediated vasoconstriction mechanism. Our purpose was to elaborate an experimental model in anesthetized rabbits to monitor the diameter and the blood flow velocity in the same vessel in order to calculate the absolute blood flow. The blood flow velocity (in cm/s) was assessed by pulsed Doppler velocimetry and the diameter (in mm) was assessed by a technique of Wall Tracking. The first results indicate that the method is well adapted to study the effects of resuscitative fluids (plasma and blood substitutes) on the aorta vascular tone after hemodilution or resuscitation from severe hemorrhage.

Animals↗

Hemoglobin autooxidation/oxidation mechanisms and methemoglobin prevention or reduction processes in the bloodstream. Literature review and outline of autooxidation reaction.

The amount of circulating methemoglobin in healthy humans is the result of a balance between methemoglobin production (from autooxidation and oxidation) and hemoglobin reduction. Hemoglobin autooxidation and oxidation are very complex and are not well understood. This article analyses the literature on hemoglobin autooxidation, oxidation and reduction and sets out a sequence of reactions for the oxidation of hemoglobin and the ways in which the percentage of methemoglobin is regulated or methemoglobin production prevented. Most of the information concerns erythrocyte hemoglobin, but plasma extracellular hemoglobin (from hemolysis or hemoglobin-based blood substitutes) is also considered where possible.

Hemoglobin A↗