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Stabilität und laterale Mobilität von porenüberspannenden Membranen auf porösen Siliziumsubstraten / Stability and lateral mobility of pore-suspending membranes on porous silicon substratesWeiskopf, Daniela 30 April 2009 (has links)
No description available.
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Antioxidant properties of Lippia javanica (Burm.f.) Spreng. / C. PretoriusPretorius, Corlea January 2010 (has links)
The evolution of aerobic metabolic processes unavoidably led to the production of reactive
oxygen species (ROS). ROS have the ability to cause harmful oxidative damage to
biomolecules. Increased ROS generation and subsequent oxidative stress have been
associated with aging and neurodegenerative disorders such as Parkinson’s and Alzheimer’s
diseases as a result of the extreme sensitivity of the central nervous system to damage from
ROS. Antioxidant defence systems have co–evolved with aerobic metabolic processes to
counteract oxidative damage inflicted by ROS. The impact of neurodegenerative disorders
on society is increasing rapidly as the life expectancy of the global population increases. In
this day and age, a much younger group of the population is also experiencing
neurodegenerative symptoms as a result of the harmful effect of the human
immunodeficiency virus (HIV) on the central nervous system.
Plants are an invaluable source of medicinal compounds. The use of plants for their healing
properties is rooted in ancient times. The aim of this study was to select from twenty one
plants, the plant with the most promising antioxidant activity and to determine whether
extracts of this plant could act as free radical scavengers, comparing the results to Trolox, a
known free radical scavenger. The next step was to isolate and characterize a compound
from an extract exhibiting promising antioxidant activity. Bioassay–guided fractionation was
followed to achieve this.
During screening trials, twenty one plants, namely Berula erecta, Heteromorpha
arborescens, Tarchonanthus camphoratus, Vernonia oligocephala, Gymnosporia buxifolia,
Acacia karroo, Elephantorrhiza elephantina, Erythrina zeyheri, Leonotis leonurus,
Plectranthus ecklonii, P. rehmanii, P. venteri, Salvia auretia, S. runcinata, Solenostemon
latifolius, S. rotundifolius, Plumbago auriculata, Clematis brachiata, Vangueria infausta,
Physalis peruviana and Lippia javanica were selected from literature, based on reported
antioxidant activity within the plant families, for screening of their antioxidant activity. One
hundred and ten extracts were prepared from the leaves, using Soxhlet extraction and the
solvents petroleum ether (PE), dichloromethane (DCM), ethyl acetate (EtOAc) and ethanol
(EtOH), consecutively.
The focus during initial screening trials was on chemistry–based assays. The oxygen radical
absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays were
employed for the primary screening of the one hundred and ten leaf extracts. The ORAC
assay was used to determine whether the plant extracts were able to scavenge peroxyl
radicals and the FRAP assay was used to determine the reducing abilities of the extracts.
Quantification of the peroxyl radical scavenging activity by the ORAC assay revealed that
activity was observed for most of the extracts, with the ethyl acetate and ethanol extracts of
L. javanica exhibiting the most promising activity. This pattern of activity was also found with the reducing capacity evaluated by the FRAP assay in which the EtOAc and EtOH extracts of
L. javanica also exhibited the most promising activity.
L. javanica was selected for further study by screening for biological activity, employing the
nitro–blue tetrazolium (NBT) assay and thiobarbituric acid reactive substances (TBARS)
assay. Using a cyanide model to induce neurotoxic effects in rat brain homogenate, the
neuroprotective properties of the extracts of L. javanica leaves were examined using the NBT
assay and compared to that of Trolox. The NBT assay determines the level of superoxide
anions. All the extracts of L. javanica significantly reduced superoxide anion generation at all
concentrations used. The petroleum ether and ethyl acetate extracts, at all concentrations,
reduced superoxide anion generation to values lower than that of the control, suggesting that
these extracts may be able to attenuate normal free radical processes in the brain. The
petroleum ether extract exhibited the most promising activity at a concentration of 1.25 and
2.5 mg/ml and also exhibited similar results as the ethyl acetate extract at a lower
concentration than the ethyl acetate extract (2.5 mg/ml compared to 5 mg/ml).
A toxin–solution consisting of hydrogen peroxide (H2O2), iron(III)chloride (FeCl3) and ascorbic
acid was used to induce lipid peroxidation and the ability of the extracts of the leaves of
L. javanica to attenuate lipid peroxidation was investigated in rat brain homogenate and
compared to that of Trolox. All of the extracts of L. javanica significantly attenuated toxininduced
lipid peroxidation at all concentrations used. All of the extracts were also able to
significantly attenuate toxin–induced lipid peroxidation to values lower than that of the control.
These results suggest that all of the extracts of L. javanica possess the ability to attenuate
not only toxin–induced lipid peroxidation, but also lipid peroxidation that occurs during normal
processes in the brain.
The petroleum ether extract was subjected to bioassay–guided fractionation using column
and thin–layer chromatography and the NBT and TBARS assays. Fraction DD1 was
investigated by means of nuclear magnetic resonance, infrared and mass spectrometry. The
exact structure of fraction DD1 was not elucidated.
Considering all the results, it is clear that L. javanica shows great potential as a medicinal
plant with antioxidant activity and may therefore be beneficial in diminishing the destructive
oxidative effects inflicted by free radicals. There are however still many compounds to be
isolated from L. javanica.
Key words: Verbenaceae, Lippia javanica, antioxidant, neurodegeneration, oxygen radical
absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), nitro–blue
tetrazolium assay (NBT), thiobarbituric acid reactive substances assay (TBARS). / Thesis (M.Sc. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2011.
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Antioxidant properties of Lippia javanica (Burm.f.) Spreng. / C. PretoriusPretorius, Corlea January 2010 (has links)
The evolution of aerobic metabolic processes unavoidably led to the production of reactive
oxygen species (ROS). ROS have the ability to cause harmful oxidative damage to
biomolecules. Increased ROS generation and subsequent oxidative stress have been
associated with aging and neurodegenerative disorders such as Parkinson’s and Alzheimer’s
diseases as a result of the extreme sensitivity of the central nervous system to damage from
ROS. Antioxidant defence systems have co–evolved with aerobic metabolic processes to
counteract oxidative damage inflicted by ROS. The impact of neurodegenerative disorders
on society is increasing rapidly as the life expectancy of the global population increases. In
this day and age, a much younger group of the population is also experiencing
neurodegenerative symptoms as a result of the harmful effect of the human
immunodeficiency virus (HIV) on the central nervous system.
Plants are an invaluable source of medicinal compounds. The use of plants for their healing
properties is rooted in ancient times. The aim of this study was to select from twenty one
plants, the plant with the most promising antioxidant activity and to determine whether
extracts of this plant could act as free radical scavengers, comparing the results to Trolox, a
known free radical scavenger. The next step was to isolate and characterize a compound
from an extract exhibiting promising antioxidant activity. Bioassay–guided fractionation was
followed to achieve this.
During screening trials, twenty one plants, namely Berula erecta, Heteromorpha
arborescens, Tarchonanthus camphoratus, Vernonia oligocephala, Gymnosporia buxifolia,
Acacia karroo, Elephantorrhiza elephantina, Erythrina zeyheri, Leonotis leonurus,
Plectranthus ecklonii, P. rehmanii, P. venteri, Salvia auretia, S. runcinata, Solenostemon
latifolius, S. rotundifolius, Plumbago auriculata, Clematis brachiata, Vangueria infausta,
Physalis peruviana and Lippia javanica were selected from literature, based on reported
antioxidant activity within the plant families, for screening of their antioxidant activity. One
hundred and ten extracts were prepared from the leaves, using Soxhlet extraction and the
solvents petroleum ether (PE), dichloromethane (DCM), ethyl acetate (EtOAc) and ethanol
(EtOH), consecutively.
The focus during initial screening trials was on chemistry–based assays. The oxygen radical
absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays were
employed for the primary screening of the one hundred and ten leaf extracts. The ORAC
assay was used to determine whether the plant extracts were able to scavenge peroxyl
radicals and the FRAP assay was used to determine the reducing abilities of the extracts.
Quantification of the peroxyl radical scavenging activity by the ORAC assay revealed that
activity was observed for most of the extracts, with the ethyl acetate and ethanol extracts of
L. javanica exhibiting the most promising activity. This pattern of activity was also found with the reducing capacity evaluated by the FRAP assay in which the EtOAc and EtOH extracts of
L. javanica also exhibited the most promising activity.
L. javanica was selected for further study by screening for biological activity, employing the
nitro–blue tetrazolium (NBT) assay and thiobarbituric acid reactive substances (TBARS)
assay. Using a cyanide model to induce neurotoxic effects in rat brain homogenate, the
neuroprotective properties of the extracts of L. javanica leaves were examined using the NBT
assay and compared to that of Trolox. The NBT assay determines the level of superoxide
anions. All the extracts of L. javanica significantly reduced superoxide anion generation at all
concentrations used. The petroleum ether and ethyl acetate extracts, at all concentrations,
reduced superoxide anion generation to values lower than that of the control, suggesting that
these extracts may be able to attenuate normal free radical processes in the brain. The
petroleum ether extract exhibited the most promising activity at a concentration of 1.25 and
2.5 mg/ml and also exhibited similar results as the ethyl acetate extract at a lower
concentration than the ethyl acetate extract (2.5 mg/ml compared to 5 mg/ml).
A toxin–solution consisting of hydrogen peroxide (H2O2), iron(III)chloride (FeCl3) and ascorbic
acid was used to induce lipid peroxidation and the ability of the extracts of the leaves of
L. javanica to attenuate lipid peroxidation was investigated in rat brain homogenate and
compared to that of Trolox. All of the extracts of L. javanica significantly attenuated toxininduced
lipid peroxidation at all concentrations used. All of the extracts were also able to
significantly attenuate toxin–induced lipid peroxidation to values lower than that of the control.
These results suggest that all of the extracts of L. javanica possess the ability to attenuate
not only toxin–induced lipid peroxidation, but also lipid peroxidation that occurs during normal
processes in the brain.
The petroleum ether extract was subjected to bioassay–guided fractionation using column
and thin–layer chromatography and the NBT and TBARS assays. Fraction DD1 was
investigated by means of nuclear magnetic resonance, infrared and mass spectrometry. The
exact structure of fraction DD1 was not elucidated.
Considering all the results, it is clear that L. javanica shows great potential as a medicinal
plant with antioxidant activity and may therefore be beneficial in diminishing the destructive
oxidative effects inflicted by free radicals. There are however still many compounds to be
isolated from L. javanica.
Key words: Verbenaceae, Lippia javanica, antioxidant, neurodegeneration, oxygen radical
absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), nitro–blue
tetrazolium assay (NBT), thiobarbituric acid reactive substances assay (TBARS). / Thesis (M.Sc. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2011.
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Nanoscale imaging of synapse morphology in the mouse neocortex in vivo by two-photon STED microscopy / Imagerie nanométrique de la morphologie synaptique dans le néocortex de souris in vivo par microscopie deux-photon STEDTer Veer, Mirelle Jamilla Tamara 25 November 2016 (has links)
Le cerveau est un organe complexe composé de neurones et des cellules non-neuronales. La communication entre les neurones a lieu via les synapses, dont le remodelage morphologique est considéré essentiel pour le traitement et le stockage des informations dans le cerveau des mammifères. Récemment, ce point de vue neuro-centré de la fonction synaptique a évolué, en prenant également en compte les processus gliaux à proximité immédiate de la synapse. Cependant, comme leur structure est bien en deçà de la résolution spatiale de la microscopie optique conventionnelle, les progrès dans les enquêtes dans leur environnement physiologique, le cerveau intact, ont été entravés. En effet, on sait peu sur les variations nanométriques de la morphologie des épines dendritiques et l'interaction avec les processus gliaux, et, finalement, comment elles affectent la transmission synaptique in vivo. Dans cette thèse, nous cherchons à visualiser la dynamique de la nano-morphologie des épines dendritiques et les processus gliaux dans le cortex à tonneaux de souris in vivo. Nous avons donc mis en place l’imagerie super-résolution 2P-STED en temps réel, ce qui permet une haute résolution spatiale et la pénétration profonde des tissus, chez la souris anesthésiée in vivo. Nous montrons que la nano-morphologie des épines est diversifiée, variable, mais globalement stable, et que les différences dans la morphologie des épines peut avoir un effet sur leur compartimentation in vivo. En outre, la mise en œuvre de l’imagerie super-résolution en double couleur in vivo et le développement d'une approche de marquage astrocytaire, nous ont permis de fournir la caractérisation à l'échelle nanométrique des interactions neurone-glie. Ces résultats apportent un aperçu sans précédent dans la dynamique de la synapse à l'échelle nanométrique in vivo, et ouvrent la voie à une meilleure compréhension de la façon dont les réarrangements morphologiques des synapses contribuent à la physiologie du cerveau. / The brain is a complex organ consisting of neurons and non-neuronal cells. Communication between neurons takes place via synapses, whose morphological remodeling is thought to be crucial for information processing and storage in the mammalian brain. Recently, this neuro-centric view of synaptic function has evolved, also taking into account the glial processes in close vicinity of the synapse. However, as their structure is well below the spatial resolution of conventional light microscopy, progress in investigating them in a physiological environment, the intact brain, has been impeded. Indeed, little is known on the nanoscale morphological variations of dendritic spines, the interaction with glial processes, and how these affect synaptic transmission in vivo. Here, we aim to visualize the dynamic nano-morphology of dendritic spines in mouse somatosensory cortex in vivo. We implemented super-resolution 2P-STED time-lapse imaging, which allows for high spatial resolution and deep tissue penetration, in anesthetized mice, and show that the nano-morphology of spines is diverse, variable, but on average stable, and that differences in spine morphology can have an effect on spine biochemical compartmentalization in vivo. Moreover, implementation of dual color in vivo super-resolution imaging and a novel astrocytic labeling approach provided the first steps towards nanoscale characterization of neuron-glia interactions in vivo. These findings bring new insights in synapse dynamics at the nanoscale in vivo, and our methodological endeavors help pave the way for a better understanding of how nanoscale aspects of spine morphology and their dynamics might contribute to brain physiology and animal behavior.
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Étude du trafic cellulaire de la convertase de proprotéine PCSK9 responsable de la dégradation du récepteur des lipoprotéines de faible densité (LDLR)Ait Hamouda, Hocine 06 1900 (has links)
Les maladies cardiovasculaires (MCV) sont la principale cause de mortalité dans
les pays industrialisés. L'hypercholestérolémie constitue un facteur de risque majeur pour
les MCV. Elle est caractérisée par des niveaux élevés de lipoprotéines de faible densité
(LDL, aussi appelé “mauvais cholestérol”). La présence prolongée de haut niveaux de
LDL dans la circulation augmente le risque de formation de plaques athérosclérotiques,
ce qui peut conduire à l'obstruction des artères et l'infarctus du myocarde. Le LDL est
normalement extrait du sang par sa liaison au récepteur du LDL (LDLR) qui est
responsable de son endocytose dans les hépatocytes. Des études génétiques humaines ont
identifié PCSK9 (proprotein convertase subtilisin/kexin type 9) comme le troisième locus
responsable de l'hypercholestérolémie autosomique dominante après le LDLR et son
ligand l’apolipoprotéine B-100. PCSK9 interagit avec le LDLR et induit sa dégradation,
augmentant ainsi les niveaux plasmatiques de LDL. Les mutations gain de fonction (GF)
de PCSK9 sont associées à des niveaux plasmatiques élevés de LDL et à l'apparition
précoce des MCV, alors que les mutations perte de fonction (PF) de PCSK9 diminuent le
risque de MCV jusqu’à ~ 88% grâce à une réduction du LDL circulant. De ce fait,
PCSK9 constitue une cible pharmacologique importante pour réduire le risque de MCV.
PCSK9 lie le LDLR à la surface cellulaire et/ou dans l'appareil de Golgi des hépatocytes
et provoque sa dégradation dans les lysosomes par un mécanisme encore mal compris. Le
but de cette étude est de déterminer pourquoi certaines mutations humaines de PCSK9
sont incapables de dégrader le LDLR tandis que d'autres augmentent sa dégradation dans
les lysosomes. Plusieurs mutations GF et PF de PCSK9 ont été fusionnées à la protéine
fluorecente mCherry dans le but d'étudier leur mobilité moléculaire dans les cellules
hépatiques vivantes. Nos analyses quantitatives de recouvrement de fluorescence après
photoblanchiment (FRAP) ont montré que les mutations GF (S127R et D129G) avaient
une mobilité protéique plus élevée (> 35% par rapport au WT) dans le réseau trans-
Golgien. En outre, nos analyses quantitatives de recouvrement de fluorescence inverse
après photoblanchiment (iFRAP) ont montré que les mutations PF de PCSK9 (R46L)
avaient une mobilité protéique plus lente (<22% par rapport au WT) et une fraction
mobile beaucoup plus petite (<40% par rapport au WT). Par ailleurs, nos analyses de
microscopie confocale et électronique démontrent pour la toute première fois que PCSK9
est localisée et concentrée dans le TGN des hépatocytes humains via son domaine Cterminal
(CHRD) qui est essentiel à la dégradation du LDLR. De plus, nos analyses sur
des cellules vivantes démontrent pour la première fois que le CHRD n'est pas nécessaire à
l'internalisation de PCSK9. Ces résultats apportent de nouveaux éléments importants sur
le mécanisme d'action de PCSK9 et pourront contribuer ultimement au développement
d'inhibiteurs de la dégradation du LDLR induite par PCSK9. / Coronary heart diseases (CHD) are a leading cause of death in Western societies.
Hypercholesterolemia is a major risk factor for CHD. It is characterized by high levels of
circulating low-density lipoprotein cholesterol (LDL, also called "bad cholesterol"). The
prolonged presence of elevated levels of LDL in the circulation increases the risk of
formation of atherosclerotic plaques, which can lead to obstruction of arteries and
myocardial infarction. LDL is normally cleared from the blood through the binding of its
sole protein constituent apolipoprotein B100 to hepatic LDL receptor (LDLR), which
mediates its endocytosis in the liver. Human genetic studies have identified PCSK9 as the
third gene responsible of autosomal dominant hypercholesterolemia after LDLR and its
ligand apolipoprotein B100. PCSK9 interacts with the LDLR and induces its degradation
thereby causing plasma LDL levels to rise. PCSK9 gain-of-function (GOF) mutations are
associated with elevated plasma LDL levels and premature CHD while PCSK9 loss-offunction
(LOF) mutations reduce the risk of CHD up to ~88% owing to reduction of
circulating LDL. Accordingly, PCSK9 is recognized as a major pharmacological target to
lower the risk of CHD. PCSK9 binds the LDLR at the cell surface and/or in the Golgi
apparatus of hepatocytes and causes its degradation in lysosomes by a mechanism not yet
clearly understood. The goal of this study was to determine why some human PCSK9
mutations fail to induce LDLR degradation while others increase it in lysosomes. Several
PCSK9 LOF and GOF mutations were fused to the fluorescent protein mCherry to study
their molecular mobility in living human liver cells. Our quantitative analysis of
fluorescence recovery after photobleaching (FRAP) showed that PCSK9 GOF mutations
S127R and D129G have a higher protein mobility (>35% compared to WT) at the trans-
Golgi network (TGN). Our quantitative analysis of inverse fluorescence recovery after
photobleaching (iFRAP) showed that PCSK9 LOF mutation R46L presented a much
slower protein mobility (<22% compared to WT) and a much slower mobile fraction
(<40% compared to WT). In addition, our confocal and electron microscopy analyses
demonstrate for the first time that PCSK9 is localized and concentrated at the TGN of
human hepatocytes. Furthermore, our results demonstrate that PCSK9 localization in the
TGN is mediated through its C-terminal cysteine and histidine-rich domain (CHRD),
which is essential for LDLR degradation. Also, our live-cell analyses demonstrate for the
first time that the CHRD is not required for internalization of PCSK9. These results
provide important new information on the mechanism of action of PCSK9 and may
ultimately help in the development of inhibitors of the PCSK9-induced LDLR
degradation.
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Regulatory Effects of the Actin-binding Proteins Moesin and MyosinII on Synaptic Activity at the Drosophila Neuromuscular JunctionSeabrooke, Sara 23 February 2011 (has links)
The nervous system is made up of specialized cells which receive and respond to environmental stimuli. Intercellular communication in the nervous system is achieved predominantly through chemical synaptic transmission. Within the chemical synapse, the actin cytoskeleton plays a major role in regulating synaptic activities, although the extent and clarity in our understanding of these processes is still limited. Using the genetically pliable model, Drosophila melanogaster, this thesis begins to unravel contributions of actin binding proteins to synaptic development and physiology at the larval neuromuscular junction (NMJ). Two actin binding proteins, Moesin and Nonmuscle Myosin II (NMMII) were selected for study based on previous studies implicating them in synaptic development. Combining genetics, fluorescent imaging and electrophysiological recordings this thesis unveils previously unidentified functions for Moesin and NMMII in morphology and physiology of the Drosophila NMJ. Moesin was found to help restrain synaptic growth but did not affect synaptic physiology. By correlating morphological and electrophysiological measurements in Moesin mutants, it was determined that physiology and morphology can be independently regulated at the NMJ. NMMII was used to investigate a role for actin binding proteins in physiology at the Drosophila NMJ. By using the fluorescent imaging technique, FRAP, this becomes the first research to implicate NMMII in unstimulated synaptic vesicle mobility. FRAP indicated that vesicle mobility was highly dependent on the expression level of NMMII. Electrophysiological analysis of NMMII indicated distinct mechanisms for spontaneous and evoked vesicle release. NMMII expression exhibited a positive correlation with basal synaptic transmission and was important in mobilizing vesicles for synaptic potentiation. In addition, NMMII was found to be involved in a high frequency dependent low frequency depression. This work begins to identify how vesicles traverse within boutons and suggests differential mechanisms of synaptic release, both of which are partially dependent of NMMII expression. Studying Moesin and NMMII have revealed a complex interplay between the actin cytoskeleton and synaptic function and together this research furthers our understanding of how the actin cytoskeleton regulates synaptic activity.
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Regulatory Effects of the Actin-binding Proteins Moesin and MyosinII on Synaptic Activity at the Drosophila Neuromuscular JunctionSeabrooke, Sara 23 February 2011 (has links)
The nervous system is made up of specialized cells which receive and respond to environmental stimuli. Intercellular communication in the nervous system is achieved predominantly through chemical synaptic transmission. Within the chemical synapse, the actin cytoskeleton plays a major role in regulating synaptic activities, although the extent and clarity in our understanding of these processes is still limited. Using the genetically pliable model, Drosophila melanogaster, this thesis begins to unravel contributions of actin binding proteins to synaptic development and physiology at the larval neuromuscular junction (NMJ). Two actin binding proteins, Moesin and Nonmuscle Myosin II (NMMII) were selected for study based on previous studies implicating them in synaptic development. Combining genetics, fluorescent imaging and electrophysiological recordings this thesis unveils previously unidentified functions for Moesin and NMMII in morphology and physiology of the Drosophila NMJ. Moesin was found to help restrain synaptic growth but did not affect synaptic physiology. By correlating morphological and electrophysiological measurements in Moesin mutants, it was determined that physiology and morphology can be independently regulated at the NMJ. NMMII was used to investigate a role for actin binding proteins in physiology at the Drosophila NMJ. By using the fluorescent imaging technique, FRAP, this becomes the first research to implicate NMMII in unstimulated synaptic vesicle mobility. FRAP indicated that vesicle mobility was highly dependent on the expression level of NMMII. Electrophysiological analysis of NMMII indicated distinct mechanisms for spontaneous and evoked vesicle release. NMMII expression exhibited a positive correlation with basal synaptic transmission and was important in mobilizing vesicles for synaptic potentiation. In addition, NMMII was found to be involved in a high frequency dependent low frequency depression. This work begins to identify how vesicles traverse within boutons and suggests differential mechanisms of synaptic release, both of which are partially dependent of NMMII expression. Studying Moesin and NMMII have revealed a complex interplay between the actin cytoskeleton and synaptic function and together this research furthers our understanding of how the actin cytoskeleton regulates synaptic activity.
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Associação entre metabolismo do ferro e estresse oxidativo em pacientes com doeça de ParkinsonMedeiros, Márcio Schneider January 2014 (has links)
Introdução: A fisiopatologia da doença de Parkinson está associada a lesões por estresse oxidativo/nitrosativo. O ferro encontra-se acumulado na substância negra (SN) de pacientes com DP e está relacionado com esse dano através das espécies reagentes de oxigênio (EROs) e de nitrogênio (ERNs) na reação de Fenton. EROs e ERNs são produzidas normalmente em processos celulares e inflamatórios, e controladas por sistemas antioxidantes. Objetivo: Avaliar níveis periféricos de ferro em pacientes com DP para determinar se acúmulo na SN está relacionado com níveis elevados no sangue. Determinar biomarcadores periféricos confiáveis de estresse oxidativo/nitrosativo Métodos: Selecionados 40 pacientes com DP e 46 indivíduos controles para comparar níveis séricos de ferro, ferritina e transferrina, e de biomarcadores de estresse oxidativo/nitrosativo: superóxido dismutase (SOD), catalase, óxido nítrico (NOx), substâncias reativas ao ácido tiobarbitúrico (TBARS), tióis não-proteicos, “advanced oxidation protein products” (AOPP), “ferric reducing ability of plasma” (FRAP), NTPDases, ecto-5’-nucleotidase, adenosina deaminase (ADA), mieloperoxidase, albumina modificada pela isquemia (IMA) e vitamina C. Resultados: Níveis de ferro estavam diminuídos em pacientes com DP, enquanto ferritina e transferrina não mostraram diferença. Os biomarcadores de estresse oxidativo como TBARS, AOPP, NTPDases, IMA, mieloperoxidase, FRAP, vitamina C e tiois não-proteicos encontraram-se significativamente aumentados na DP. SOD, catalase, ecto-5’-nucleotidase não foram diferentes entre os grupos e os marcadores NOx e ADA foram significativamente aumentados nos controles. Nenhuma correlação foi encontrada entre os biomarcadores e dados sociodemográficos e de características da doença. Conclusão: Níveis plasmáticos de ferro encontram-se diminuídos em pacientes com DP comparados com controles saudáveis. Os biomarcadores TBARS, AOPP, NTPDases, IMA e mieloperoxidase mostraram-se confiáveis para lesão oxidativa, enquanto tióis não-proteicos, FRAP e vitamina C demonstram diminuição da capacidade antioxidante na DP. / Background: Parkinson’s disease (PD) pathophysiology is associated with oxidative/nitrosative stress damage. Iron accumulates in the substantia nigra (SN) of PD patients and is related to this damage along with oxygen and nitrogen reactive species (ROS, RNS) through Fenton reaction. ROS and RNS are normally produced in cell and inflammatory processes, controlled by antioxidant systems. Objective: To determine peripheral levels of iron, ferritin and transferrin in PD patients to evaluate whether iron accumulation in the SN could be related to serum levels. To determine reliable peripheral biomarkers of oxidative/nitrative stress. Methods: Forty PD patients and 46 controls were selected to compared serum levels of iron, ferritin, transferrin and oxidative/nitrative stress biomarkers: superoxide dismutase (SOD), catalase, nitric oxide (NOx), thiobarbituric acid reactive substances (TBARS), non-protein thiols, advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP), NTPDases, ecto-5’-nucleotidase, adenosine deaminase (ADA), myeloperoxidase, ischemic-modified albumin (IMA) and vitamin C. Results: Iron levels were decreased in patients with PD, while ferritin and transferrin were not different. Oxidative stress biomarkers, TBARS, AOPP, NTPDases, IMA, myeloperoxidase, FRAP, vitamin C and non-proteic thiols were significantly higher in PD. SOD, catalase, ecto-5’-nucleotidase were not different between the groups and biomarkers NOx and ADA were significantly increased in the controls. No correlation was found between biomarkers and sociodemographic and disease data. Conclusion: Plasmatic levels of iron are decreased in patients with PD compared to healthy controls. Biomarkers TBARS, AOPP, NTPDases, IMA and myeloperoxidase presented as reliable to measure oxidative/nitrative damage, while non-proteic thiols, FRAP and vitamin C show a decrease in the antioxidant capacity in PD.
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Associação entre metabolismo do ferro e estresse oxidativo em pacientes com doeça de ParkinsonMedeiros, Márcio Schneider January 2014 (has links)
Introdução: A fisiopatologia da doença de Parkinson está associada a lesões por estresse oxidativo/nitrosativo. O ferro encontra-se acumulado na substância negra (SN) de pacientes com DP e está relacionado com esse dano através das espécies reagentes de oxigênio (EROs) e de nitrogênio (ERNs) na reação de Fenton. EROs e ERNs são produzidas normalmente em processos celulares e inflamatórios, e controladas por sistemas antioxidantes. Objetivo: Avaliar níveis periféricos de ferro em pacientes com DP para determinar se acúmulo na SN está relacionado com níveis elevados no sangue. Determinar biomarcadores periféricos confiáveis de estresse oxidativo/nitrosativo Métodos: Selecionados 40 pacientes com DP e 46 indivíduos controles para comparar níveis séricos de ferro, ferritina e transferrina, e de biomarcadores de estresse oxidativo/nitrosativo: superóxido dismutase (SOD), catalase, óxido nítrico (NOx), substâncias reativas ao ácido tiobarbitúrico (TBARS), tióis não-proteicos, “advanced oxidation protein products” (AOPP), “ferric reducing ability of plasma” (FRAP), NTPDases, ecto-5’-nucleotidase, adenosina deaminase (ADA), mieloperoxidase, albumina modificada pela isquemia (IMA) e vitamina C. Resultados: Níveis de ferro estavam diminuídos em pacientes com DP, enquanto ferritina e transferrina não mostraram diferença. Os biomarcadores de estresse oxidativo como TBARS, AOPP, NTPDases, IMA, mieloperoxidase, FRAP, vitamina C e tiois não-proteicos encontraram-se significativamente aumentados na DP. SOD, catalase, ecto-5’-nucleotidase não foram diferentes entre os grupos e os marcadores NOx e ADA foram significativamente aumentados nos controles. Nenhuma correlação foi encontrada entre os biomarcadores e dados sociodemográficos e de características da doença. Conclusão: Níveis plasmáticos de ferro encontram-se diminuídos em pacientes com DP comparados com controles saudáveis. Os biomarcadores TBARS, AOPP, NTPDases, IMA e mieloperoxidase mostraram-se confiáveis para lesão oxidativa, enquanto tióis não-proteicos, FRAP e vitamina C demonstram diminuição da capacidade antioxidante na DP. / Background: Parkinson’s disease (PD) pathophysiology is associated with oxidative/nitrosative stress damage. Iron accumulates in the substantia nigra (SN) of PD patients and is related to this damage along with oxygen and nitrogen reactive species (ROS, RNS) through Fenton reaction. ROS and RNS are normally produced in cell and inflammatory processes, controlled by antioxidant systems. Objective: To determine peripheral levels of iron, ferritin and transferrin in PD patients to evaluate whether iron accumulation in the SN could be related to serum levels. To determine reliable peripheral biomarkers of oxidative/nitrative stress. Methods: Forty PD patients and 46 controls were selected to compared serum levels of iron, ferritin, transferrin and oxidative/nitrative stress biomarkers: superoxide dismutase (SOD), catalase, nitric oxide (NOx), thiobarbituric acid reactive substances (TBARS), non-protein thiols, advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP), NTPDases, ecto-5’-nucleotidase, adenosine deaminase (ADA), myeloperoxidase, ischemic-modified albumin (IMA) and vitamin C. Results: Iron levels were decreased in patients with PD, while ferritin and transferrin were not different. Oxidative stress biomarkers, TBARS, AOPP, NTPDases, IMA, myeloperoxidase, FRAP, vitamin C and non-proteic thiols were significantly higher in PD. SOD, catalase, ecto-5’-nucleotidase were not different between the groups and biomarkers NOx and ADA were significantly increased in the controls. No correlation was found between biomarkers and sociodemographic and disease data. Conclusion: Plasmatic levels of iron are decreased in patients with PD compared to healthy controls. Biomarkers TBARS, AOPP, NTPDases, IMA and myeloperoxidase presented as reliable to measure oxidative/nitrative damage, while non-proteic thiols, FRAP and vitamin C show a decrease in the antioxidant capacity in PD.
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Associação entre metabolismo do ferro e estresse oxidativo em pacientes com doeça de ParkinsonMedeiros, Márcio Schneider January 2014 (has links)
Introdução: A fisiopatologia da doença de Parkinson está associada a lesões por estresse oxidativo/nitrosativo. O ferro encontra-se acumulado na substância negra (SN) de pacientes com DP e está relacionado com esse dano através das espécies reagentes de oxigênio (EROs) e de nitrogênio (ERNs) na reação de Fenton. EROs e ERNs são produzidas normalmente em processos celulares e inflamatórios, e controladas por sistemas antioxidantes. Objetivo: Avaliar níveis periféricos de ferro em pacientes com DP para determinar se acúmulo na SN está relacionado com níveis elevados no sangue. Determinar biomarcadores periféricos confiáveis de estresse oxidativo/nitrosativo Métodos: Selecionados 40 pacientes com DP e 46 indivíduos controles para comparar níveis séricos de ferro, ferritina e transferrina, e de biomarcadores de estresse oxidativo/nitrosativo: superóxido dismutase (SOD), catalase, óxido nítrico (NOx), substâncias reativas ao ácido tiobarbitúrico (TBARS), tióis não-proteicos, “advanced oxidation protein products” (AOPP), “ferric reducing ability of plasma” (FRAP), NTPDases, ecto-5’-nucleotidase, adenosina deaminase (ADA), mieloperoxidase, albumina modificada pela isquemia (IMA) e vitamina C. Resultados: Níveis de ferro estavam diminuídos em pacientes com DP, enquanto ferritina e transferrina não mostraram diferença. Os biomarcadores de estresse oxidativo como TBARS, AOPP, NTPDases, IMA, mieloperoxidase, FRAP, vitamina C e tiois não-proteicos encontraram-se significativamente aumentados na DP. SOD, catalase, ecto-5’-nucleotidase não foram diferentes entre os grupos e os marcadores NOx e ADA foram significativamente aumentados nos controles. Nenhuma correlação foi encontrada entre os biomarcadores e dados sociodemográficos e de características da doença. Conclusão: Níveis plasmáticos de ferro encontram-se diminuídos em pacientes com DP comparados com controles saudáveis. Os biomarcadores TBARS, AOPP, NTPDases, IMA e mieloperoxidase mostraram-se confiáveis para lesão oxidativa, enquanto tióis não-proteicos, FRAP e vitamina C demonstram diminuição da capacidade antioxidante na DP. / Background: Parkinson’s disease (PD) pathophysiology is associated with oxidative/nitrosative stress damage. Iron accumulates in the substantia nigra (SN) of PD patients and is related to this damage along with oxygen and nitrogen reactive species (ROS, RNS) through Fenton reaction. ROS and RNS are normally produced in cell and inflammatory processes, controlled by antioxidant systems. Objective: To determine peripheral levels of iron, ferritin and transferrin in PD patients to evaluate whether iron accumulation in the SN could be related to serum levels. To determine reliable peripheral biomarkers of oxidative/nitrative stress. Methods: Forty PD patients and 46 controls were selected to compared serum levels of iron, ferritin, transferrin and oxidative/nitrative stress biomarkers: superoxide dismutase (SOD), catalase, nitric oxide (NOx), thiobarbituric acid reactive substances (TBARS), non-protein thiols, advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP), NTPDases, ecto-5’-nucleotidase, adenosine deaminase (ADA), myeloperoxidase, ischemic-modified albumin (IMA) and vitamin C. Results: Iron levels were decreased in patients with PD, while ferritin and transferrin were not different. Oxidative stress biomarkers, TBARS, AOPP, NTPDases, IMA, myeloperoxidase, FRAP, vitamin C and non-proteic thiols were significantly higher in PD. SOD, catalase, ecto-5’-nucleotidase were not different between the groups and biomarkers NOx and ADA were significantly increased in the controls. No correlation was found between biomarkers and sociodemographic and disease data. Conclusion: Plasmatic levels of iron are decreased in patients with PD compared to healthy controls. Biomarkers TBARS, AOPP, NTPDases, IMA and myeloperoxidase presented as reliable to measure oxidative/nitrative damage, while non-proteic thiols, FRAP and vitamin C show a decrease in the antioxidant capacity in PD.
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