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Étude de la biodistribution de nanoparticules de poly(acide lactique) chez le poisson-zèbre après administration muqueuse et intraveineuse / Poly(lactic acid) nanoparticles biodistribution study in the zebrafish aftermucous and intravenous administrationRességuier, Julien 31 January 2017 (has links)
L'utilisation des nanobiotechnologies dans le domaine de la santé est en plein essor. Les nanoparticules de poly(acide lactique) (PLA) représentent un nanosystème biocompatible capable d'accroître la spécificité et l'efficacité de traitements thérapeutiques et vaccinaux administrables par voie muqueuse et intraveineuse. Toutefois, l'optimisation de ces nanosystèmes se heurte à une caractérisation incomplète de leur biodistribution in vivo, en particulier à l'échelle cellulaire.L'objectif de ce travail de thèse est d'enrichir les connaissances sur la biodistribution des nanoparticules de PLA in vivo après administration muqueuse ou intraveineuse, dans le but d'élargir les perspectives d'optimisation et d'utilisation. Animal complexe et adapté pour les études sur organisme-entier, le modèle du poisson-zèbre (Danio rerio) a été utilisé. Pour mener à bien ce projet, une méthodologie rigoureuse d'analyse de la biodistribution des nanoparticules de PLA a été développée. Ce qui permit, après administration par balnéation, d'en révéler le fort tropisme inné envers les cellules dendritiques muqueuses. Ces données ont servi à élaborer une stratégie de ciblage, utilisant la lectine agglutinine de cacahuète, capable d'augmenter la prise en charge des nanoparticules de PLA par les branchies et la peau. Enfin, l'étude du devenir de ces nanoparticules après injection intraveineuse, a révélé de nombreuses interactions avec le système circulatoire. Ce travail a permis d'approfondir la connaissance des interactions des nanoparticules de PLA avec le vivant, soulignant le potentiel prometteur de ces nanoparticules pour la vaccination muqueuse / Medecine shows a growing interest regarding nanobiotechnologies. Among them are poly(lactic acid) (PLA) nanoparticles, which represent a biocompatible and competent nanosystem to heighten the specificity and efficacy of diverse therapeutic and vaccine treatments, following mucosal and intravenous administration. However, the further optimization of such nanosystem is poised by the lack of informations regarding their in vivo biodistribution, especially at the cellular level.The main objective of this PhD is to increment the knowledge about PLA nanoparticles biodistribution in vivo, after muquous and intravenous administration, to further expand their optimisation and use perspectives. The zebrafish model has been utilized to perform this research because of his conserved complexity as well as his suitability for whole-organism studies.To fulfill this project, a precise methodology has been developed to analyze the PLA nanoparticles biodistribution. Which allowed, after bathing administriation, to unveil their robust innate tropism toward mucous dendritic cells. From these data has been established a targeting strategy, utilizing the peanut agglutinin lectin, which has been proved to enhance nanoparticle uptakes by both gills and skin mucosae. Finally, the study of PLA nanoparticles behavior and destiny after intravenous injection, revealed numerous elaborated interactions with the circulatory system.Overall, this work has been able to strengthen our understandings of PLA nanoparticles among living organisms, furthermore highlighting their promizing potential as nanovehicles for mucosal vaccines
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Central city youth and HIV/AIDS an emerging community construct: Finding the best fit ofprovention and intervention serviceBlack, Michael David 01 January 1998 (has links)
No description available.
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Vliv inhalačních a intravenózních anestetik na odolnost srdečního svalu k nedostatku kyslíku / Cardiac tolerance to oxygen deprivation: the effects of inhalational and intravenous anestheticsŘíha, Hynek January 2012 (has links)
Background: Surgical procedures are invariably accompanied by the use of inhalational and intravenous anesthetics. Both groups have strong influence on cardiovascular system by the interaction with myocardial oxygen supply/demand ratio and cardiomyocyte functions at the level of cell membranes, ion channels and regulatory enzymes. Aims: 1. To examine the effects of different isoflurane concentrations on the left ventricular (LV) dimensions and systolic function in the rat. 2. To examine the effects of isoflurane-induced myocardial preconditioning (APC) on the cardiac tolerance to ischemia- reperfusion (I-R) injury. 3. To compare the influence of anesthesia, based on ketamine- dexmedetomidine (KET-DEX), on the release of biochemical markers of myocardial injury and the early postoperative course with the anesthesia, based on sevoflurane-sufentanil (SEVO), in the patients undergoing coronary artery bypass grafting (CABG). Methods: 1. We carried out transthoracic echocardiographic examination in the rats immobilized by 1.5-3% concentration of isoflurane. 2. After inducing APC by isoflurane (0.5 and 1 MAC), we evaluated ventricular arrhythmias during regional ischemia (45 min), induced by the occlusion of the left anterior descending artery, and subsequent reperfusion (60 min), using the model of...
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Effective Treatment with Abciximab for Consecutive Bilateral Middle Cerebral Artery OcclusionPütz, Volker, Weise, Matthias, Kummer, Rüdiger von, Gahn, Georg January 2006 (has links)
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Vliv inhalačních a intravenózních anestetik na odolnost srdečního svalu k nedostatku kyslíku / Cardiac tolerance to oxygen deprivation: the effects of inhalational and intravenous anestheticsŘíha, Hynek January 2012 (has links)
Background: Surgical procedures are invariably accompanied by the use of inhalational and intravenous anesthetics. Both groups have strong influence on cardiovascular system by the interaction with myocardial oxygen supply/demand ratio and cardiomyocyte functions at the level of cell membranes, ion channels and regulatory enzymes. Aims: 1. To examine the effects of different isoflurane concentrations on the left ventricular (LV) dimensions and systolic function in the rat. 2. To examine the effects of isoflurane-induced myocardial preconditioning (APC) on the cardiac tolerance to ischemia- reperfusion (I-R) injury. 3. To compare the influence of anesthesia, based on ketamine- dexmedetomidine (KET-DEX), on the release of biochemical markers of myocardial injury and the early postoperative course with the anesthesia, based on sevoflurane-sufentanil (SEVO), in the patients undergoing coronary artery bypass grafting (CABG). Methods: 1. We carried out transthoracic echocardiographic examination in the rats immobilized by 1.5-3% concentration of isoflurane. 2. After inducing APC by isoflurane (0.5 and 1 MAC), we evaluated ventricular arrhythmias during regional ischemia (45 min), induced by the occlusion of the left anterior descending artery, and subsequent reperfusion (60 min), using the model of...
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The Use of Synthetic Platelets to Augment HemostasisShoffstall, Andrew J. 19 August 2013 (has links)
No description available.
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Bioaccumulation and Neuroinflammation of GoldNanoparticles in the Central Nervous SystemFallahi, Fahimeh 29 May 2013 (has links)
No description available.
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Efficacy and Safety of Intravenous and Oral Nadolol for Supraventricular Tachycardia in ChildrenMehta, A V., Chidambaram, B 01 March 1992 (has links)
The efficacy and safety of oral nadolol in supraventricular tachycardia were evaluated prospectively in 27 children (median age 5.5 years). Fifteen patients had an unsuccessful trial of digoxin therapy. Intravenous nadolol was given to seven patients during electrophysiologic study; five of these had an excellent response and two had a partial response (25% decrease in tachycardia rate). Six of these patients had a similar response to oral nadolol. Twelve patients received both propranolol and nadolol. Among six patients, intravenous propranolol was successful in four and unsuccessful in two; all six had a similar response to oral nadolol. With oral propranolol, tachycardia was well controlled in four patients and persistent in two; five of five patients had a similar response to oral nadolol. Twenty-six patients were treated with oral nadolol; the arrhythmia was well controlled in 23, 2 had recurrent tachycardia and 1 patient had tachycardia at a 25% slower rate. The effective dose of nadolol ranged between 0.5 and 2.5 mg/kg body weight once daily (median dose 1 mg/kg per day). During follow-up (3 to 36 months), compliance and tolerance were excellent; excluding 2 patients with reactive airway disease who developed wheezing, only 3 (12%) of 24 had side effects necessitating a change in drug therapy. Once a day nadolol is a safe and effective agent in the management of supraventricular tachycardia in children. Its long-term efficacy can be predicted by the short-term response to intravenous nadolol or propranolol during programmed electrophysiologic study.
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Exploring the experiences of women injecting nyaope residing in the City of Tshwane Municipality, GautengLefoka, Moganki Hendrick 06 1900 (has links)
The purpose of the study was to explore the experiences of female nyaope injectors residing in City of Tshwane Municipality, Gauteng. The study was conducted at COSUP sites namely; Soshanguve, Pretoria CBD, Sunnyside, Mamelodi, Eersterust, and Attridgeville. The study focused on females who have a history of injecting nyaope, accessing substance use related services at a registered service provider within City of Tshwane Municipality, Gauteng.
Research design of the study was exploratory, which is basically used to explore a new topic or learn more about phenomenon where little is known. The research approach was purely qualitative methodology. This permitted the researcher to deeply explore the lived experiences of female nyaope injectors residing in City of Tshwane Municipality, Gauteng. A qualitative in-depth interview method was used to collect data from 24 participants who took part in the study.
Questions of the interview were semi-structured, in-depth one-on-one interviews and were used to explore the lived experiences of female nyaope injectors residing in City of Tshwane Municipality, Gauteng.
The findings of the study revealed that females who are injecting nyaope, are at risk of contracting HIV and other blood-borne infections. The stigma that is perpetuated by families, intimate partners, communities, health care professionals, and police officers is creating a hostile environment for female nyaope injectors; which increases the risk of contracting HIV and other blood-borne infections. Harm reduction services have the potential to address the needs of female nyaope injectors if fully implemented.
It can be concluded that there is a need for substance abuse service providers to implement comprehensive harm reduction services to curb HIV prevalence amongst female nyaope injectors. / Health Studies / M.A. (Social Behavioural Studies in HIV/AIDS)
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The anti-inflammatory properties of intravenous immunoglobulin in a murine model of allergic airway disease ; effects on the development of regulatory T-cellsMassoud, Amir Hossein 04 1900 (has links)
Les immunoglobulines intraveineuses (IVIg) constituent une préparation polyclonale d’IgG
isolée et regroupée à partir du plasma sanguin de multiples donneurs. Initialement utilisé comme
traitement de remplacement chez les patients souffrant d’immunodéficience primaire ou
secondaire, les IVIg sont maintenant largement utilisées dans le traitement de plusieurs
conditions auto-immunes, allergiques ou inflammatoires à une dose élevée, dite immunomodulatrice.
Différents mécanismes d’action ont été postulés au fil des années pour expliquer
l’effet thérapeutique des IVIg dans les maladies auto-immunes et inflammatoires. Entre autre, un
nombre grandissant de données issues de modèles expérimentaux chez l’animal et l’humain
suggère que les IVIg induisent l’expansion et augmentent l’action suppressive des cellules T
régulatrices (Tregs), par un mécanisme qui demeure encore inconnu. Également, les patients
atteints de maladies auto-immunes ou inflammatoires présentent souvent un nombre abaissé de
Tregs par rapport aux individus sains. Ainsi, une meilleure compréhension des mécanismes par
lesquels les IVIg modulent les cellules T régulatrices est requise afin de permettre un usage plus
rationnel de ce produit sanguin en tant qu’alternative thérapeutique dans le traitement des
maladies auto-immunes et inflammatoires.
Par le biais d’un modèle expérimental d’allergie respiratoire induite par un allergène, nous avons
démontré que les IVIg diminuaient significativement l’inflammation au niveau des voies
aériennes ce, en association avec une différenciation des Tregs à partir des cellules T non
régulatrices du tissu pulmonaire. Nous avons également démontré qu’au sein de notre modèle
expérimental, l’effet anti-inflammatoire des IVIg était dépendant des cellules dendritiques
CD11c+ (CDs) pulmonaires, puisque cet effet pouvait être complètement reproduit par le transfert adoptif de CDs provenant de souris préalablement traitées par les IVIg. À cet effet, il est
déjà établi que les IVIg peuvent moduler l’activation et les propriétés des CDs pour favoriser la
tolérance immunitaire et que ces cellules seraient cruciales pour l’induction périphérique des
Tregs. C’est pourquoi, nous avons cherché à mieux comprendre comment les IVIg exercent leur
effet sur ces cellules. Pour la première fois, nous avons démontré que la fraction d’IgG riche en
acide sialique (SA-IVIg) (constituant 2-5% de l’ensemble des IgG des donneurs) interagit avec
un récepteur dendritique inhibiteur de type lectine C (DCIR) et active une cascade de
signalement intracellulaire initiée par la phosphorylation du motif ITIM qui est responsable des
changements observés en faveur de la tolérance immunitaire auprès des cellules dendritiques et
des Tregs. L’activité anti-inflammatoire de la composante SA-IVIg a déjà été décrite dans des
études antérieures, mais encore une fois le mécanisme par lequel ce traitement modifie la
fonction des CDs n’a pas été établi. Nous avons finalement démontré que le récepteur DCIR
facilite l’internalisation des molécules d’IgG liées au récepteur et que cette étape est cruciale
pour permettre l’induction périphérique des Tregs.
En tant que produit sanguin, les IVIg constitue un traitement précieux qui existe en quantité
limitée. La caractérisation des mécanismes d’action des IVIg permettra une meilleure utilisation
de ce traitement dans un vaste éventail de pathologies auto-immunes et inflammatoires. / Intravenous immunoglobulin (IVIg) is a therapeutic preparation of normal human polyclonal IgG
derived from pooled plasma from a large number of healthy donors. Initially used as replacement
therapy for patients with primary and secondary immune deficiencies, IVIg is now also widely
used for the treatment of a variety of autoimmune, allergic and systemic inflammatory disorders,
at high immunomodulatory doses. The beneficial effect of IVIg in autoimmune and
inflammatory diseases has been attributed to different mechanisms. Increasing evidence shows
that IVIg induces expansion and enhances the suppressive function of regulatory T cells (Tregs)
in different experimental animal models and human subjects, through an unknown mechanism.
Human inflammatory and autoimmune diseases are known to be associated with Treg deficiency.
Therefore, a more precise understanding of the mechanisms by which IVIg modulate Treg
populations seems to be needed for more rational use of this compound as an alternative therapy
in context of various inflammatory and autoimmune disorders.
Using a robust antigen-driven model of allergic airway disease, we have demonstrated that IVIg
markedly attenuates airway inflammation and this effect is associated with the induction of Tregs
from non-regulatory T cells in pulmonary tissues. We have also demonstrated that the antiinflammatory
actions of IVIg, in our model are dependent on a population of pulmonary CD11c+
dendritic cells (DCs), as the action of IVIg could be completely replicated by adoptive transfer of
CD11c+ DCs from IVIg-treated mice. we have shown that tolerogenic DCs involve in the
peripheral induction of Tregs. Given the requirement of DCs in the induction of Tregs, we
explored the mechanism by which IVIg interacts and modulate these cells and for the first time
demonstrated that the purified sialylated fraction of human IgG (SA-IVIg) (that consists 2-5% of whole IgG) interacts with an inhibitory C-type lectin receptor on dendritic (DCIR) and this
interaction triggers an ITIM intracellular signaling cascade. This subsequently results in
rendering tolerogenic activities to DCs and peripheral induction of Tregs. The anti-inflammatory
activity of SA-IVIg has been shown in previous studies, but the mechanism by which it
modulates DCs functions is not well understood. We also demonstrated that DCIR facilitates the
internalization of IgG molecules into DC and this internalization appears to be a crucial step for
induction of Tregs.
IVIg is a costly therapeutic compound. Characterization of the mechanism of action of IVIg can
lead to a better application of this plasma based therapy in a wide range of autoimmune and
inflammatory diseases.
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