RESUMEN
Early in the morning of Wednesday 5th February 1766, Stanislaw Leszcziynski (Leczinski), Duke of Lorraine and Bar, fell to the ground, very close to the fireplace in his room. He remained in this position for a long time, exposed to the flames, and suffered serious burns. During the first nine days, physicians used topical agents and dressings, associated with internal drugs, particularly quinine. But septicemia occurred after about two weeks. By February 20th, Stanislaw was in a very poor condition. Some stimulating drugs were administered, but he died three days later. He was 88 years old.
RESUMEN
Nitric oxide is implicated in the target action of Nebivolol, a selective ß1 adrenoceptor blocker used in hypertension treatment. As the Nitric Oxide (NO) production and the actin cytoskeleton are linked, the aim of this work was to study the involvement of actin cytoskeleton on mechanism of action of Nebivolol in cultured endothelial cells. We studied the effect of Nebivolol (200 µM) on actin filaments remodeling and its impact on NO production and eNOS activation. Results showed that Nebivolol perturbs actin filaments polymerization, increases NO production and eNOS activity between 30 minutes and 1 h. Stabilization of actin filaments with phalloïdine (50 µM) abolishes Nebivolol effects on eNOS activation and NO production. Furthermore, Rho-kinase activity decreased during the first hour of Nebivolol treatment, then increased after 3 h, while actin filaments repolymerized, eNOS activation and NO production decreased. In SMCs, Nebivolol induced a decrease in the Rho-kinase activity from 1 h until 24 h of incubation. In conclusion, we suggest that Nebivolol induced NO production in Endothelial Cells (ECs) via complementary actions between actin cytoskeleton remodeling inducing eNOS activation and Rho-kinase implication. The effect of Nebivolol on ECs occurs during the first hour, this effect on SMCs seems to be maintained until 24 h, explaining persisted action of Nebivolol observed in vivo.
Asunto(s)
Citoesqueleto de Actina/metabolismo , Benzopiranos/metabolismo , Etanolaminas/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Quinasas Asociadas a rho/metabolismo , Células Endoteliales , Humanos , Nebivolol , Óxido Nítrico/farmacología , PolimerizacionRESUMEN
BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate into several lineages with valuable applications in regenerative medicine. MSCs differentiation is highly dependent on physicochemical properties of the culture substrate, cell density and on culture medium composition. OBJECTIVE: In this study, we assessed the influence of fetal bovine serum (FBS) level on Wharton's jelly (WJ)-MSCs behavior seeded on polyelectrolyte multilayer films (PEMF) made of four bilayers of poly-allylamine hydrochloride (PAH) as polycation and poly-styrene sulfonate (PSS) as polyanion. METHODS: MSCs isolated from WJ by explants method were amplified until the third passage. Their phenotypic characterization was performed by flow cytometry analyses. MSCs were seeded on PEMF, in Endothelial growth medium-2 (EGM-2) supplemented by either 5% or 2% FBS. Cell's behavior was monitored for 20 days by optical microscopy and immunofluorescence. RESULTS: Until 2 weeks on glass slides, no difference was observed whatever the FBS percentage. Then with 5% FBS, MSCs formed three-dimensional spheroids on PSS/PAH after 20 days of culture with a nuclear aggregate. Whereas, with 2% FBS, these spheroids did not appear and cells grown in 2D conserved the fibroblast-like morphology. CONCLUSIONS: The decrease of FBS percentage from 5% to 2% avoids 3D cell spheroids formation on PAH/PSS. Such results could guide bioengineering towards building 2D structures like cell layers or 3D structures by increasing the osteogenic or chondrogenic differentiation potential of MSCs.
Asunto(s)
Sangre , Técnicas de Cultivo de Célula/métodos , Medios de Cultivo , Células Madre Mesenquimatosas/fisiología , Materiales Biocompatibles/química , Cationes/química , Agregación Celular/fisiología , Recuento de Células , Forma de la Célula , Materiales Biocompatibles Revestidos/química , Medios de Cultivo/análisis , Factor de Crecimiento Epidérmico/administración & dosificación , Factor 2 de Crecimiento de Fibroblastos/administración & dosificación , Fibroblastos/citología , Citometría de Flujo , Humanos , Factor I del Crecimiento Similar a la Insulina/administración & dosificación , Fenotipo , Poliaminas/química , Polielectrolitos , Polímeros/química , Poliestirenos/química , Esferoides Celulares/citología , Ingeniería de Tejidos/métodos , Factor A de Crecimiento Endotelial Vascular/administración & dosificaciónRESUMEN
BACKGROUND: Polyelectrolyte multilayer (PEMs) films made of poly(allylamine hydrochloride) (PAH) as polycation and poly(styrene sulfonate) (PSS) as polyanion, with a PAH ending layer, can be used as a coating in order to improve the anti-thrombogenicity and patency of vascular grafts in vascular engineering field. They induce strong adhesion of mature endothelial cells on glass, expanded polytetrafluoroethylene and cryopreserved arteries. Despite their outstanding effect on mature and progenitor endothelial cells, PEMs ending with PAH showed a poor outcome on Wharton's jelly mesenchymal stem cells (WJ-MSCs) culture. OBJECTIVE: The aim of this work was to examine the influence of the ending charge of PEMs on WJ-MSCs behavior. METHODS: WJ-MSCs amplified until the 3rd passage were seeded and cultured on (PAH-PSS)3-PAH and on (PAH-PSS)4 coated glass for 10 days. Stem cell phenotype was checked by flow cytometry and cell morphology was followed by bright field microscopy. RESULTS: Flow cytometry analysis showed that WJ-MSCs were positive for MSC's markers CD73, CD90 and CD105 and negative for hematopoietic markers CD34 and CD45. Light microscopy showed development of nodule-like structures after 10 days of culture on (PAH-PSS)3-PAH, which resulted in a disturbance of cell monolayer. Whereas WJ-MSCs cultured on (PAH-PSS)4 ending with PSS showed a normal cell growth like on collagen and reached confluence after 10 days. CONCLUSION: The culture surface seems to have a determining role in WJ-MSC's "spatial" behavior, which could be considered in the field of tissue engineering.
Asunto(s)
Materiales Biocompatibles/química , Técnicas de Cultivo de Célula , Células Madre Mesenquimatosas/fisiología , Poliaminas/química , Poliestirenos/química , 5'-Nucleotidasa/análisis , Antígenos CD/análisis , Antígenos CD34/análisis , Cationes/química , Adhesión Celular , Proliferación Celular , Forma de la Célula , Materiales Biocompatibles Revestidos/química , Electroquímica , Endoglina , Citometría de Flujo , Proteínas Ligadas a GPI/análisis , Vidrio/química , Humanos , Antígenos Comunes de Leucocito/análisis , Fenotipo , Polielectrolitos , Polímeros/química , Receptores de Superficie Celular/análisis , Propiedades de Superficie , Antígenos Thy-1/análisisRESUMEN
Mesenchymal stem cells (MSCs) have tremendous potential as a cell source for regenerative medicine due to their capacity for differentiation into endothelial-like cells when seeded on nonmodified cover glasses. This absence of removable surface, preventing recovery of cell sheet, constitutes a critical obstacle to predict an application in tissue engineering. It remains unknown whether MSCs differentiation could be realized when the cells are cultivated on a scaffold that could be used in vascular engineering. In this study, we propose to differentiate human MSCs into endothelial-like cells on surfaces coated with polyelectrolyte multilayer film (PMF) and fibronectin (control surfaces). We quantified Platelet Endothelial Cell Adhesion Molecule (PECAM) and von Willebrand Factor (vWF) expressions (endothelial cell specific markers) and nitric oxide (NO) production, which is representative of the cell functionality. After only two weeks of differentiation, we showed, on PMF, that MSCs expressed PECAM and vWF, exhibiting a differentiation into endothelial-like cells, which functionality was explored by a significant production of nitrites. These results highlight the importance of PMF to get human MSCs differentiation and suggest that this film of nanometer thickness opens a new route for vascular bioengineering by pre-seeding hMSCs directly into a vascular graft functionalized by a removable coating.
Asunto(s)
Electrólitos/farmacología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Poliaminas/farmacología , Polímeros/farmacología , Ácidos Sulfónicos/farmacología , Ingeniería de Tejidos/métodos , Injerto Vascular/métodos , Adulto , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Fibronectinas/farmacología , Técnica del Anticuerpo Fluorescente , Humanos , Inmunofenotipificación , Células Madre Mesenquimatosas/metabolismo , Nitritos/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Factor de von Willebrand/metabolismoRESUMEN
Elixirs were formerly very used drugs or drinks. They are alcoholized and sugared, often offered as liquors, pleasant to drink, and contain drugs or not. Many are uncommon now, but Garrus elixir has passed through the centuries. Digestive stimulative, tonic, flavour of potions, aperitive and liquor, it is obtained by maceration of aloes, saffron, myrrh, clove, cinnamon and nutmeg in alcohol before distillation, then addition of vanilla, maiden-hair, orangeflower water and sugar. It seems to have been discovered at the end of the 17th century or the beginning of 18th century by Joseph Garrus, medicine doctor, living in Paris. When he died, in 1722, the elixir was already well known. During the Regency, it was administered to Duchess of Berry, who died nevertheless, and to some important members of the royal Court. During all the 18th century, it was considered as a panacea with many useful properties, inscribed in some pharmacopoeias and disposable in the drugstores. However, Garrus was acused of having simply improved the formula of the "élixir de propriété" of Paracelsius, also called tincture of aloes, myrrh and saffron. Taking in account the great number of formulas containing these same drugs and plants, it is difficult today to elucidate their origins and to discover who was imitated by another. The elixir of Doctor Garrus is also known in literature since its name is used in Madame Bovary and Tartarin sur les Alpes. At the beginning of our 21st century, some of us consider it as one of the best aperitive liquors.
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Bebidas Alcohólicas , Enfermedades del Sistema Digestivo/tratamiento farmacológico , Etanol/uso terapéutico , Enfermedades del Sistema Digestivo/historia , Francia , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: recent studies in bio-engineering have showed the influence of Polyelectrolyte Multilayer (PEM) films on endothelial cells (ECs), especially poly(sodium-4-styrene-sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH). They were tested either with human mature ECs or rabbit immature endothelial progenitor cells (EPCs), but never on human EPCs. In view to obtain an EC covered surface, human cord blood (HCB) EPCs were cultivated on PSS/PAH films. MATERIAL AND METHODS: PEMs were obtained by 7 alternate depositions of cationic PAH and anionic PSS layers. HCB mononuclear cells were isolated by centrifugation through density gradient. 7 days after seeding on PEM, unattached cells were removed and adherent EPCs were cultivated in endothelial specific medium until P6. Appearance of CD31 and vWF was evaluated by confocal microscopy. RESULTS: EPCs not only successfully adhered on PEM, but also spread and proliferated. Moreover, cells differentiated into a typical endothelial cobblestone monolayer within 2 weeks. Immunostaining of CD31 and vWF confirmed the formation of an EC-like confluent monolayer. Furthermore, these cells showed after 6 passages a good phenotypic stability while reseeded on the PEM film. CONCLUSION: these results show an easy way to obtain mature ECs from human stem cells, which may open new applications for a scaffold cellularization in tissue bio-engineering.
Asunto(s)
Electrólitos/química , Células Endoteliales/citología , Sangre Fetal/citología , Membranas Artificiales , Células Madre Mesenquimatosas/citología , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/química , Técnicas de Cultivo de Célula/métodos , Diferenciación Celular , Aumento de la Célula , Proliferación Celular , Células Cultivadas , Células Endoteliales/fisiología , Sangre Fetal/fisiología , Humanos , Ensayo de Materiales , Células Madre Mesenquimatosas/fisiologíaRESUMEN
Hypoxia is a diminution of oxygen quantity delivered to tissue for cellular need to product energy. Hypoxia derives from two major conditions in health diseases: anemia and ischemia. Anemic hypoxia comes from damage to O(2) transport like red blood cells diminution or disease. Ischemic hypoxia is a diminution of blood flow following a diminution of blood volume after a hemorrhagic shock. After hypoxia, vessels dilate to increase blood flow allowing a better oxygenation of peripheral tissues. This vasodilation appears immediately after the beginning of hypoxia and can be maintained during several hours. Today, the molecular mechanisms of this vasodilation stay unclear. But it seems that potassic channels, ATP concentration and medium acidification in addition to vasodilator/vasoconstrictor balance play a great role to facilitate the oxygenation of the ischemic areas.As endothelial cells (EC) are lining the vasculature, they are always in contact with blood, which carries, amongst other compounds, oxygen. In this way, they are the first target for an oxygen partial pressure (PO(2)) diminution. EC, through different mechanosensors, can sense a variation in PO(2) and adapt their metabolism to maintain ATP production. Under hypoxia, EC switch into hypoxic metabolism, leading to the production of reactive oxygen species (ROS). Indeed, when PO(2) is low, the respiratory chain in the mitochondria runs slower. Furthermore, cytochrome C capacity to trap O(2) is reduced; this phenomenon alters the cellular redox potential and leads to the accumulation of electrons that induce the formation of ROS.This review presents an overview of the behaviour of endothelial cells face to hypoxia. We propose to focus on nitric oxide, hypoxia inducible factor (HIF), lactate and ROS productions. Then we present the different mode of culture of EC under hypoxia. Finally, we conclude on the difficulty to study hypoxia because of the various types of system developed to reproduce this phenomenon and the different signalling ways that can be activated.
Asunto(s)
Células Endoteliales/metabolismo , Factor 1 Inducible por Hipoxia/metabolismo , Ácido Láctico/metabolismo , Modelos Cardiovasculares , Óxido Nítrico/metabolismo , Oxígeno/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Hipoxia de la Célula/fisiología , Células Endoteliales/citología , HumanosRESUMEN
This review begins with an examination of the notion of quality in the industrial setting, its definition and the steps taken to achieve quality assurance. The review then considers what is meant by quality in the field of health, and in particular for orthopedic devices dispensed in a community pharmacy. Special attention is given to dispensing standard orthopedic devices; five aspects are considered: organization, personal competence, products, services, and relationship with the patient. The first aspect, organization, involves the selling area, stocks, different sizes and sale prices, and the introduction of new devices. Dispensing involves, reception and physical examination of the patient, information delivery, decision-making on the choice of an orthesis, measurement, trial and application, as well as complementary advice and completion of the patient's file. Quality is measured in terms of patient needs.
Asunto(s)
Dispositivos de Fijación Ortopédica/normas , Farmacias/normas , Francia , Humanos , Industrias/normas , Garantía de la Calidad de Atención de SaludRESUMEN
The idea to develop a blood substitute was stimulated by the need of military in the last two world wars and by transmission of pathogenic germs (Hepatitis B in 1960, HIV in 1980 and Hepatitis C in 1990) during blood transfusion that limited the donor blood transfusion. There are two main groups of blood substitutes: perfluorocarbon emulsions and hemoglobin-based oxygen carriers (HBOC). These latter are of natural origin: human, bovine or recombinant and undergo three modifications types: chemicals (intramolecular cross-linking, polymerisation, conjugation to macromolecules and combination of several chemical modifications), genetics or technological by microencapsulation. HBOCs are in different phases of clinical trials and some of them present side effects (hemodynamic and oxidative). The understanding of these effects and the possibility of correcting them, condition their use on a large scale and the economic consequences, which they can generate.
Asunto(s)
Sustitutos Sanguíneos/uso terapéutico , Hemoglobinas/uso terapéutico , Animales , Biopolímeros , Sustitutos Sanguíneos/administración & dosificación , Sustitutos Sanguíneos/efectos adversos , Sustitutos Sanguíneos/química , Bovinos , Ensayos Clínicos como Asunto , Reactivos de Enlaces Cruzados/farmacología , Dextranos/uso terapéutico , Composición de Medicamentos , Hemoglobinas/administración & dosificación , Hemoglobinas/química , Hemoglobinas/efectos de los fármacos , Hemoglobinas/genética , Humanos , Maleimidas/uso terapéutico , Oxígeno/sangre , Oxígeno/farmacocinética , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes/uso terapéuticoRESUMEN
Several reports indicated that cell-free hemoglobin induced vasoconstriction. This phenomenon was due to different pharmacological (NO trapping, vasoactive agents release and endothelial uptake...) and physical (viscosity and oxidative process of cell-free hemoglobin...) factors. We have previously showed that the blood pressure increase would be due to the presence of Dex-BTC-Hb inside arterial wall. However, we do not know how hemoglobin penetrate inside arterial wall. The objective of this study was to examine the new hypothesis of hemoglobin penetration inside arterial wall dependent of endocytosis. For this reason, an endocytosis inhibitor, cytochalasin D, was tested. We measured in anesthetized guinea pigs, the evolution of mean arterial pressure (MAP) and plasma hemoglobin concentration in presence or absence of cytochalasin D (1.6 x 10(-4) M). These measurements were carried out before and after 50% isovolemic exchange transfusion (IET) with two cell-free hemoglobins: Dex-BTC-Hb (300 kDa) and stroma-free hemoglobin (64.5 kDa). The administration of Dex-BTC-Hb or stroma-free hemoglobin induced an immediate increase in MAP that peaked within 17 min after IET and returned to baseline after 120 min. cytochalasin D attenuated the elevation of MAP when administrated before Dex-BTC-Hb but not when administrated before stroma-free hemoglobin. Furthermore, without cytochalasin D, plasma hemoglobin concentration after Dex-BTC-Hb or stroma-free hemoglobin administration decreased significantly 120 min after IET. In presence of cytochalasin D, plasma hemoglobin concentration stayed constant in Dex-BTC-Hb-treated animals but not in stroma-free hemoglobin-treated animals. cytochalasin D inhibits the endocytosis in case of Dex-BTC-Hb but not in case of stroma-free hemoglobin. This would be due to the molecular weight of cell-free hemoglobin. Based on these data, we suggest that endocytosis is one of the mechanisms by which cell-free hemoglobin with high molecular weight penetrated inside vascular endothelial cells. This endocytosis would have an impact on induced hypertension.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Dextranos/farmacología , Hemoglobinas/farmacología , Animales , Citocalasina D/farmacología , Endocitosis/efectos de los fármacos , Cobayas , Hemoglobinas/análisis , Masculino , Inhibidores de la Síntesis del Ácido Nucleico/farmacologíaRESUMEN
Free hemoglobin (Hb) present at high concentration in plasma--in case of hemolysis, hemoglobin based oxygen carrier (HBOC) administration or in case of subarachnoid hemorrhage--induce hypertension as result of vasoconstriction. In this context, we studied on an exchange transfusion (ET) model at 50% of hematocrit with a HBOC, the distribution of this Hb inside abdominal aortic wall in guinea pigs in relation with mean arterial pressure (MAP) evolution. MAP was monitored during 180 min after ET and rings of abdominal aorta were taken at different times, when modifications of MAP were important, and analyzed by immunohistochemistry and confocal microscopy. Gelofusine 4%, used as control, did not modify MAP while free Hb increased MAP that reached its maximum (53% of hypertension) at t=17 min after the end of ET. MAP started to decrease (45% of hypertension) at t =60 min after ET, and recovered its baseline value at t=180 min. Confocal analysis of the vessel showed that: at 17 min (when hypertension was maximal), free Hb was present in endothelial cells (EC) and in vasa vasorum; at t=60 min (when hypertension decreased) and at t =10 min (when hypertension disappeared), free Hb was detected still in EC, but inside all abdominal aorta wall too. These results suggest in the first time that free Hb could induce a hypertension by direct interaction with EC but would also be unable to maintain this hypertension in spite of its massive tissue distribution.
Asunto(s)
Presión Sanguínea/fisiología , Hemoglobinas/análisis , Hemoglobinas/fisiología , Hipertensión/fisiopatología , Animales , Aorta Abdominal/química , Cobayas , Hematócrito , Hipertensión/veterinaria , Inmunohistoquímica , Masculino , Microscopía ConfocalRESUMEN
Better medical practice begins with personal evaluation. A group of Lorraine medical practitioners too part in an evaluation of their prescription practices and their compliance with existing regulations. The prescription servers as a link between the physician, the pharmacists and the patient. Three broad topics were studies in this audit: patient identification, regulation per se, and general criteria such as legibility and computerization. Among the different mandatory inscriptions, the only item which was often missing was the patient's age. The results listed here present the average performance observed in a group of medical practitioners and the highest and lowest performances.
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Prescripciones de Medicamentos/normas , Medicina Familiar y Comunitaria/normas , Médicos de Familia , Factores de Edad , Recolección de Datos , Medicina Familiar y Comunitaria/legislación & jurisprudencia , Francia , Legislación de Medicamentos , FarmacéuticosRESUMEN
The hemoglobin-based oxygen carriers (HBOC), like dextran-benzene-tetracarboxylate-hemoglobin (Dex-BTC-Hb), which are present at high concentrations in plasma disturb arterial pressure and induce hypertension. To study if the increase of mean arterial pressure (MAP) is due to the presence of cell-free hemoglobin (Hb) inside abdominal aortic wall, we followed on a model of 50% isovolemic exchange transfusion (IET) in anesthetized guinea pigs, the kinetic of Dex-BTC-Hb distribution inside abdominal aortic wall and we investigated the relationship between arterial pressure modifications and modified Hb distribution. The administration of Dex-BTC-Hb induced instantaneously an increase of MAP that reached its maximum (53% of hypertension from baseline) at 17 min after the end of the IET and was maintained maximally up to 30 min. A significantly decrease of MAP (45% of hypertension from baseline) was observed after 60 min and the baseline level was recovered at 180 min. The investigation of tissue at 17 min by confocal microscopy showed the presence of free Hb in or upon endothelial cells (EC) in intima and in vasa vasorum. At 180 min, the free Hb was found in or upon EC and inside all abdominal aortic wall meanwhile MAP recovered its basal value. These results suggest for the first time that Hb in intima seems to induce the hypertension observed upon IET but can not sustain it even if Hb stayed present in intima and in abdominal aortic wall.
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Aorta Abdominal/fisiología , Presión Sanguínea/efectos de los fármacos , Sustitutos Sanguíneos/farmacología , Sustitutos Sanguíneos/farmacocinética , Dextranos/farmacología , Dextranos/farmacocinética , Hemoglobinas/farmacología , Hemoglobinas/farmacocinética , Animales , Aorta Abdominal/metabolismo , Células Endoteliales/metabolismo , Cobayas , Hematócrito , Cinética , Masculino , Microscopía Confocal , Factores de Tiempo , Distribución Tisular , Túnica Íntima/metabolismo , Vasa Vasorum/metabolismoRESUMEN
During the last ten Years, major reforms have been implemented in the French armies due to discontinuation of mandatory enlistment. For the medical corps, recruitment and training for reservists has ceased since the national school for reserve officers in Libourne was closed. During this same time, the number of foreign engagements of the French armies has revealed the need for available young reserve officers in the medical corps. Reserve training of students in medicine, pharmacy, odontology, or nursing has been considered and different possibilities considered. One option is to develop a teaching unit during the third Year of the curriculum allowing volunteer students to become junior officers. For pharmacy students, specific training on drug supply, nuclear, biological and chemical weapons and terrorism as well as clinical chemistry, toxicology, and hygiene are also organized.
Asunto(s)
Medicina Militar/economía , Farmacéuticos , Francia , Humanos , Selección de Personal , Recursos HumanosRESUMEN
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.
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Farmacéuticos , Podiatría/economía , Francia , Farmacias/economía , Podiatría/educaciónRESUMEN
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.
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Viscosidad Sanguínea/efectos de los fármacos , Eritrocitos/fisiología , Hemoglobinas/farmacología , Adulto , Animales , Agregación Eritrocitaria/fisiología , Hemorreología/efectos de los fármacos , Humanos , Masculino , Fragilidad Osmótica/efectos de los fármacos , Conejos , Resucitación , Soluciones/farmacologíaRESUMEN
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.
Asunto(s)
Analgésicos Opioides/análisis , Fentanilo/análisis , Administración Cutánea , Analgésicos Opioides/administración & dosificación , Fentanilo/administración & dosificación , Trastornos Relacionados con Sustancias/prevención & controlRESUMEN
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.
Asunto(s)
Hemodilución , Hemodinámica/efectos de los fármacos , Oxihemoglobinas/farmacología , Circulación Renal/efectos de los fármacos , Animales , Aorta/efectos de los fármacos , Aorta/fisiología , Presión Sanguínea/efectos de los fármacos , Viscosidad Sanguínea/efectos de los fármacos , Gases/sangre , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Conejos , Flujo Sanguíneo Regional/efectos de los fármacos , Soluciones , Resistencia Vascular/efectos de los fármacosRESUMEN
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.