Plasma 5-hydroxyindoleacetic acid as an endogenous index of renal plasma flow

Plasma 5-hydroxyindoleacetic acid as an endogenous index of renal plasma flow. 5-Hydroxyindoleacetic acid (5-HIAA), the major serotonin metabolite, was measured in human plasma and urine using liquid chromatography and electrochemical detection. The renal extraction of 5-HIAA was 78%, a value compatible with an almost complete extraction during a single passage of the blood through the kidney. In addition, plasma levels of 5-HIAA measured in patients with a wide range of renal function was inversely correlated (r = 0.85) with the clearance of para-aminohippuric acid (PAH). The results indicate that 5-HIAA determinations can be used as an alternative procedure to the PAH clearance method for the estimation of renal plasma flow in clinical practice

Pharmacokinetic aspects of retinal drug delivery

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.Peer reviewe

Modelisation differentielle directe des robots manipulateurs

INIST T 72089 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

Tuning of the sequence technique.: Baroreflex in mice

International audienceThe sequence method was first described by Di Rienzo in cats and applied in different species including humans. Until now, no systematic study of spontaneous baroreflex sensitivity (BRS) has been performed by the sequence method in mice. This study aimed to characterize the best estimates of BRS using the sequence method by tuning all the possible parameters, specifically, the number of beats involved in a sequence, the minimal changes in blood-pressure (BP) ramps, and the minimal changes in pulse-interval (PI) ramps. Also, the relevance to set a minimal correlation coefficient in the regression line between BP and PI was tested. An important point was the delay to be applied between BP and PI. This delay represents the physiological time for the baroreflex loop to efficiently correct the BP variations

Communication de l'Académie d'agriculture de France Section des Sciences de la vie | Covid-19 : des vaccins et des traitements issus des biotechnologies végétales sont à l'étude

International audienceL’intensité de la pandémie de Covid-19 causée par le SARS-CoV-2 et la rapidité de sa diffusion exigent de ne négliger aucune piste, notamment en tirant partie des atouts indéniables qu'apportent les biotechnologies végétales. C’est pourquoi l’Académie d’agriculture de France souhaite encourager l’usage des plantes pour développer de nouveaux programmes de recherche en biotechnologie. Dans une note récente des membres de cette Académie attirent l’attention sur des travaux actuels dans ce domaine. C’est ainsi qu’en avril 2020, deux sociétés biopharmaceutiques, Kentucky BioProcessing (Owensboro, Etats-Unis) et Medicago (Québec, Canada) ont fait état de leurs travaux sur l’expression de protéines recombinantes, qui pourraient déboucher sur des vaccins potentiels contre la Covid-19. Ces sociétés utilisent la plante Nicotiana benthamiana, une espèce indigène d'Australie, modèle en biotechnologie pour sa croissance rapide et sa capacité naturelle à exprimer des séquences de gènes d’autres espèces, caractéristiques la rendant bien adaptée à la production de produits biopharmaceutiques. D’autres travaux de biotechnologie végétale sont également menés dans des laboratoires publics et privés, en Chine, Espagne, Etats-Unis, France, Grande-Bretagne et Mexique

Sympathetic baroreceptor regulation during hypoxic hypotension in humans: New insights

Background: Baroreceptor activation by a continuous infusion of phenylephrine selectively abolishes the muscle sympathetic nerve activity (MSNA) response to hypoxia in humans. Baroreceptor deactivation enhances the MSNA rise during hypoxia in animals. Whether this is true in humans is unknown and was tested in the present study. Methods: We assessed MSNA responses elicited by isocapnic hypoxia (10% O 2 in N 2) during baroreflex loading and unloading with phenylephrine and nitroprusside, respectively, in 19 healthy volunteers. The study was randomized and placebo-controlled. Results: Phenylephrine and nitroprusside increased and decreased, respectively, blood pressure during normoxia and hypoxia, whereas the reverse occurred for heart rate and MSNA (all P < 0.001 vs. placebo). As compared with normoxia, cardiac barosensitivity decreased during the infusion of placebo and nitroprusside in the presence of hypoxia, as well as sympathetic barosensitivity during the infusion of nitroprusside (all P < 0.05). Three patients even disclosed a reduction in arterial pressure, which became apparent at the third minute of hypoxia and worsened steadily thereafter (SBP: 91 ± 7 mmHg; DBP 47 ± 9 mmHg), in spite of a gradual rise in heart rate of 20 ± 4 bpm. Changes in baroreceptor loading conditions did not affect ventilation during normoxia and hypoxia. Conclusion: Cardiac and sympathetic baroreceptor sensitivity decrease during baroreceptor unloading in the presence of peripheral chemoreceptor activation. Normal humans have limited reflex capabilities to sustain simultaneous reductions in oxygen and pressure, and may experience hemodynamic instability episodes in such condition.SCOPUS: ar.jinfo:eu-repo/semantics/publishe