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Find video protocols related to scientific articles indexed in Pubmed.
Intranasal delivery of influenza rNP adjuvanted with c-di-AMP induces strong humoral and cellular immune responses and provides protection against virus challenge.
PLoS ONE
PUBLISHED: 08-20-2014
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There is a critical need for new influenza vaccines able to protect against constantly emerging divergent virus strains. This will be sustained by the induction of vigorous cellular responses and humoral immunity capable of acting at the portal of entry of this pathogen. In this study we evaluate the protective efficacy of intranasal vaccination with recombinant influenza nucleoprotein (rNP) co-administrated with bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) as adjuvant. Immunization of BALB/c mice with two doses of the formulation stimulates high titers of NP-specific IgG in serum and secretory IgA at mucosal sites. This formulation also promotes a strong Th1 response characterized by high secretion of INF-? and IL-2. The immune response elicited promotes efficient protection against virus challenge. These results suggest that c-di-AMP is a potent mucosal adjuvant which may significantly contribute towards the development of innovative mucosal vaccines against influenza.
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Blockade of monoacylglycerol lipase inhibits oligodendrocyte excitotoxicity and prevents demyelination in vivo.
Glia
PUBLISHED: 08-08-2014
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The endocannabinoids 2-araquidonoylglycerol (2-AG) and anandamide (AEA) are bioactive lipids crucially involved in the regulation of brain function in basal and pathological conditions. Blockade of endocannabinoid metabolism has emerged as a promising therapeutic strategy for inflammatory diseases of the central nervous system, including myelin disorders such as multiple sclerosis. Nevertheless, the biological actions of endocannabinoid degradation inhibitors in oligodendrocytes and white matter tracts are still ill defined. Here we show that the selective monoacylglycerol lipase (MAGL) inhibitor JZL184 suppressed cell death by mild activation of AMPA receptors in oligodendrocytes in vitro, an effect that was mimicked by MAGL substrate 2-AG and by the second major endocannabinoid AEA, in a concentration-dependent manner, whereas inhibition of the AEA metabolizing enzyme fatty acid amide hydrolase with URB597 was devoid of effect. Pharmacological experiments suggested that oligodendrocyte protection from excitotoxicity resulting from MAGL blockade involved the activation of cannabinoid CB1 receptors and the reduction of AMPA-induced cytosolic calcium overload, mitochondrial membrane depolarization, and production of reactive oxygen species. Administration of JZL184 under a therapeutic regimen decreased clinical severity, prevented demyelination, and reduced inflammation in chronic experimental autoimmune encephalomyelitis. Furthermore, MAGL inactivation robustly preserved myelin integrity and suppressed microglial activation in the cuprizone-induced model of T-cell-independent demyelination. These findings suggest that MAGL blockade may be a useful strategy for the treatment of immune-dependent and -independent damage to the white matter. GLIA 2015;63:163-176.
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Contrast-enhanced harmonic endoscopic ultrasound imaging: Basic principles, present situation and future perspectives.
World J. Gastroenterol.
PUBLISHED: 04-23-2014
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Over the last decade, the development of stabilised microbubble contrast agents and improvements in available ultrasonic equipment, such as harmonic imaging, have enabled us to display microbubble enhancements on a greyscale with optimal contrast and spatial resolution. Recent technological advances made contrast harmonic technology available for endoscopic ultrasound (EUS) for the first time in 2008. Thus, the evaluation of microcirculation is now feasible with EUS, prompting the evolution of contrast-enhanced EUS from vascular imaging to images of the perfused tissue. Although the relevant experience is still preliminary, several reports have highlighted contrast-enhanced harmonic EUS (CH-EUS) as a promising noninvasive method to visualise and characterise lesions and to differentiate benign from malignant focal lesions. Even if histology remains the gold standard, the combination of CH-EUS and EUS fine needle aspiration (EUS-FNA) can not only render EUS more accurate but may also assist physicians in making decisions when EUS-FNA is inconclusive, increasing the yield of EUS-FNA by guiding the puncture with simultaneous imaging of the vascularity. The development of CH-EUS has also opened up exciting possibilities in other research areas, including monitoring responses to anticancer chemotherapy or to ethanol-induced pancreatic tissue ablation, anticancer therapies based on ultrasound-triggered drug and gene delivery, and therapeutic adjuvants by contrast ultrasound-induced apoptosis. Contrast harmonic imaging is gaining popularity because of its efficacy, simplicity and non-invasive nature, and many expectations are currently resting on this technique. If its potential is confirmed in the near future, contrast harmonic imaging will become a standard practice in EUS.
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Differential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine.
PLoS ONE
PUBLISHED: 01-01-2014
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5'-deoxy-5'-methylthioadenosine (MTA) is an endogenous compound produced through the metabolism of polyamines. The therapeutic potential of MTA has been assayed mainly in liver diseases and, more recently, in animal models of multiple sclerosis. The aim of this study was to determine the neuroprotective effect of this molecule in vitro and to assess whether MTA can cross the blood brain barrier (BBB) in order to also analyze its potential neuroprotective efficacy in vivo.
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Interventional endoscopic ultrasonography: an overview of safety and complications.
Surg Endosc
PUBLISHED: 07-06-2013
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In recent years, endoscopic ultrasonography (EUS)-guided techniques have been developed as alternatives to surgical, radiologic, or conventional endoscopic approaches for the treatment or palliation of several digestive diseases. The use of EUS guidance allows the therapeutic area to be targeting more precisely, with a possible clinical benefit and less morbidity. Nevertheless, the risks persist and must be taken into consideration. This review gives an overview of the complications observed with the most established procedures of therapeutic EUS.
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A3 Adenosine receptors mediate oligodendrocyte death and ischemic damage to optic nerve.
Glia
PUBLISHED: 06-13-2013
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Adenosine receptor activation is involved in myelination and in apoptotic pathways linked to neurodegenerative diseases. In this study, we investigated the effects of adenosine receptor activation in the viability of oligodendrocytes of the rat optic nerve. Selective activation of A3 receptors in pure cultures of oligodendrocytes caused concentration-dependent apoptotic and necrotic death which was preceded by oxidative stress and mitochondrial membrane depolarization. Oligodendrocyte apoptosis induced by A3 receptor activation was caspase-dependent and caspase-independent. In addition to dissociated cultures, incubation of optic nerves ex vivo with adenosine and the A3 receptor agonist 2-CI-IB-MECA(1-[2-Chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-b-D-ribofuranuronamide)-induced caspase-3 activation, oligodendrocyte damage, and myelin loss, effects which were prevented by the presence of caffeine and the A3 receptor antagonist MRS 1220 (N-[9-Chloro-2-(2-furanyl)[1,2,4]-triazolo [1,5-c]quinazolin-5-yl]benzene acetamide). Finally, ischemia-induced injury and functional loss to the optic nerve was attenuated by blocking A3 receptors. Together, these results indicate that adenosine may trigger oligodendrocyte death via activation of A3 receptors and suggest that this mechanism contributes to optic nerve and white matter ischemic damage. GLIA 2014;62:199-216.
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Cytosolic zinc accumulation contributes to excitotoxic oligodendroglial death.
Glia
PUBLISHED: 02-26-2013
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Dyshomeostasis of cytosolic Zn(2+) is a critical mediator of neuronal damage during excitotoxicity. However, the role of this cation in oligodendrocyte pathophysiology is not well understood. The current study examined the contribution of Zn(2+) deregulation to oligodendrocyte injury mediated by AMPA receptors. Oligodendrocytes loaded with the Zn(2+)-selective indicator FluoZin-3 responded to mild stimulation of AMPA receptors with fast cytosolic Zn(2+) rises that resulted from intracellular release, as they were not blocked by the extracellular Zn(2+) chelator Ca-EDTA. Pharmacological experiments suggested that AMPA-induced Zn(2+) mobilization depends on cytosolic Ca(2+) accumulation, arises from mitochondria and protein-bound pools, and is triggered by mechanisms that do not involve the generation of reactive oxygen species. Moreover, intracellular Zn(2+) rises resulting from AMPA receptor activation seem to be promoted by Ca(2+)-dependent cytosolic acidification. Addition of the cell-permeable Zn(2+) chelator TPEN significantly reduced mitochondrial membrane depolarization, reactive oxygen species production, and cell death by sub-maximal activation of AMPA receptors both in vitro and in situ, suggesting that Zn(2+) deregulation is an important mediator of oligodendrocyte excitotoxicity. These data provide evidence that strategies aimed at maintaining Zn(2+) homeostasis may be useful for the treatment of disorders in which excitotoxicity is an important trigger of oligodendroglial death.
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Development of a universal CTL-based vaccine for influenza.
Bioengineered
PUBLISHED: 01-21-2013
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In pursuit of better influenza vaccines, many strategies are being studied worldwide. An attractive alternative is the generation of a broadly cross-reactive vaccine based on the induction of cytotoxic T-lymphocytes (CTL) directed against conserved internal antigens of influenza A virus. The feasibility of this approach using recombinant viral vectors has recently been demonstrated in mice and humans by several research groups. However, similar results might also be achieved through immunization with viral proteins expressed in a prokaryotic system formulated with the appropriate adjuvants and delivery systems. This approach would be much simpler and less expensive. Recent results from several laboratories seem to confirm this is as a valid option to be considered.
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[Cost of therapy for neurodegenerative diseases. Applying an activity-based costing system].
Gac Sanit
PUBLISHED: 01-17-2013
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To apply the activity based costing (ABC) model to calculate the cost of therapy for neurodegenerative disorders in order to improve hospital management and allocate resources more efficiently.
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Bax and calpain mediate excitotoxic oligodendrocyte death induced by activation of both AMPA and kainate receptors.
J. Neurosci.
PUBLISHED: 03-19-2011
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Sustained activation of AMPA and kainate receptors in rat oligodendrocytes induces cytosolic calcium overload, mitochondrial depolarization, and an increase of reactive oxygen species, resulting in cell death. Here, we provide evidence that Bax, a proapoptotic member of the Bcl-2 protein family, is involved in excitotoxic apoptotic death of oligodendrocytes and that calpain mediates Bax activation. Cultured Bax(-/-) oligodendrocytes, obtained from the optic nerve of Bax knock-out mice, were resistant to AMPA and kainate receptor-mediated insults. In turn, both mitochondrial calcium uptake and mitochondrial alterations after excitotoxic insults were diminished in Bax-null oligodendrocytes. Moreover, pretreatment with furosemide, a blocker of Bax translocation to mitochondria, significantly protected rat and mouse oligodendrocytes from AMPA- and kainate-induced damage; in contrast, bongkrekic acid, a blocker of the mitochondrial permeability transition pore, had no effect. Finally, we analyzed the participation of calpain, which cleaves Bax and is activated by AMPA and kainate, in oligodendrocyte death. Pretreatment with 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606), a broad cell-permeable calpain inhibitor, and two additional calpain inhibitors diminished Bax activation, inhibited its translocation to mitochondria, and attenuated all apoptotic events resulting from excitotoxic insults to rat oligodendrocytes. Together, these results indicate that Bax and calpain are essential intermediaries of the mitochondria-dependent death pathway, triggered by AMPA and kainate receptor activation in oligodendrocytes.
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Dual-specific phosphatase-6 (Dusp6) and ERK mediate AMPA receptor-induced oligodendrocyte death.
J. Biol. Chem.
PUBLISHED: 02-07-2011
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Oligodendrocytes, the myelinating cells of the CNS, are highly vulnerable to glutamate excitotoxicity, a mechanism involved in tissue damage in multiple sclerosis. Thus, understanding oligodendrocyte death at the molecular level is important to develop new therapeutic approaches to treat the disease. Here, using microarray analysis and quantitative PCR, we observed that dual-specific phosphatase-6 (Dusp6), an extracellular regulated kinase-specific phosphatase, is up-regulated in oligodendrocyte cultures as well as in optic nerves after AMPA receptor activation. In turn, Dusp6 is overexpressed in optic nerves from multiple sclerosis patients before the appearance of evident damage in this structure. We further analyzed the role of Dusp6 and ERK signaling in excitotoxic oligodendrocyte death and observed that AMPA receptor activation induces a rapid increase in ERK1/2 phosphorylation. Blocking Dusp6 expression, which enhances ERK1/2 phosphorylation, significantly diminished AMPA receptor-induced oligodendrocyte death. In contrast, MAPK/ERK pathway inhibition with UO126 significantly potentiates excitotoxic oligodendrocyte death and increases cytochrome c release, mitochondrial depolarization, and mitochondrial calcium overload produced by AMPA receptor stimulation. Upstream analysis demonstrated that MAPK/ERK signaling alters AMPA receptor properties. Indeed, Dusp6 overexpression as well as incubation with UO126 produced an increase in AMPA receptor-induced inward currents and cytosolic calcium overload. Together, these data suggest that levels of phosphorylated ERK, controlled by Dusp6 phosphatase, regulate glutamate receptor permeability and oligodendroglial excitotoxicity. Therefore, targeting Dusp6 may be a useful strategy to prevent oligodendrocyte death in multiple sclerosis and other diseases involving CNS white matter.
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Cannabidiol induces intracellular calcium elevation and cytotoxicity in oligodendrocytes.
Glia
PUBLISHED: 07-21-2010
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Heavy marijuana use has been linked to white matter histological alterations. However, the impact of cannabis constituents on oligodendroglial pathophysiology remains poorly understood. Here, we investigated the in vitro effects of cannabidiol, the main nonpsychoactive marijuana component, on oligodendrocytes. Exposure to cannabidiol induced an intracellular Ca(2+) rise in optic nerve oligodendrocytes that was not primarily mediated by entry from the extracellular space, nor by interactions with ryanodine or IP(3) receptors. Application of the mitochondrial protonophore carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP; 1 ?M) completely prevented subsequent cannabidiol-induced Ca(2+) responses. Conversely, the increase in cytosolic Ca(2+) levels elicited by FCCP was reduced after previous exposure to cannabidiol, further suggesting that the mitochondria acts as the source of cannabidiol-evoked Ca(2+) rise in oligodendrocytes. n addition, brief exposure to cannabidiol (100 nM-10 ?M) led to a concentration-dependent decrease of oligodendroglial viability that was not prevented by antagonists of CB(1), CB(2), vanilloid, A(2A) or PPAR? receptors, but was instead reduced in the absence of extracellular Ca(2+). The oligodendrotoxic effect of cannabidiol was partially blocked by inhibitors of caspase-3, -8 and -9, PARP-1 and calpains, suggesting the activation of caspase-dependent and -independent death pathways. Cannabidiol also elicited a concentration-dependent alteration of mitochondrial membrane potential, and an increase in reactive oxygen species (ROS) that was reduced in the absence of extracellular Ca(2+). Finally, cannabidiol-induced cytotoxicity was partially prevented by the ROS scavenger trolox. Together, these results suggest that cannabidiol causes intracellular Ca(2+) dysregulation which can lead to oligodendrocytes demise.
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Mangifera indica L. extract attenuates glutamate-induced neurotoxicity on rat cortical neurons.
Neurotoxicology
PUBLISHED: 04-08-2009
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Overstimulation of ionotropic glutamate receptors causes excitotoxic neuronal death contributing to neurodegenerative disorders. Massive influx of calcium in excitotoxicity provokes alterations in the membrane potential of mitochondria and increases the production of reactive oxygen species. Here we report that Mangifera indica L. extracts (MiE) prevent glutamate-induced excitotoxicity in primary cultured neurons of the rat cerebral cortex. To evaluate the effects of MiE on excitotoxicity, cells were stimulated with L-glutamic acid (50 microM; 10 min) alone or in the presence of MiE. Maximal protection (56%) was obtained with 2.5 microg/mL of MiE. In turn, we measured the effects of MiE on excitotoxic-induced oxidative stress and mitochondrial depolarization by fluorimetry using 5,6-chloromethyl-2,7-dichlorodihydrofluorescein diacetate and tetramethylrhodamine, respectively. Both parameters were effectively reduced by MiE at concentrations which showed neuroprotection. Mangiferin, an antioxidant polyphenol which is a major component of MiE, was also effective in preventing neuronal death, oxidative stress and mitochondrial depolarization. Maximal protection (64%) was obtained at 12.5 microg/mL of mangiferin which also attenuated oxidative stress and mitochondrial depolarization at the neuroprotective concentrations. Together, these results indicate that MiE is an efficient neuroprotector of excitotoxic neuronal death, indicates that mangiferin carries a substantial part of the antioxidant and neuroprotective activity of MiE, and that this natural extract has therapeutic potential to treat neurodegenerative disorders.
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Molecular mechanisms of neuroprotection by two natural antioxidant polyphenols.
Cell Calcium
PUBLISHED: 02-07-2009
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Excessive activation of glutamate receptors, or excitotoxicity, contributes to acute and chronic neurological disorders including stroke. We previously showed that two natural polyphenol antioxidants, mangiferin and morin, are neuroprotective in a model of ischemic brain damage. In this study, we analyzed the molecular mechanisms underlying neuroprotection by mangiferin and morin in an in vitro model of excitotoxic neuronal death involving NMDA receptor overactivation. We observed that both polyphenols reduce the formation of reactive oxygen species, activate the enzymatic antioxidant system, and restore the mitochondrial membrane potential. Moreover, both antioxidants inhibit glutamate-induced activation of calpains, normalize the levels of phosphorylated Akt kinase and Erk1/2, as well as of cytosolic Bax, inhibit AIF release from mitochondria, and regulate the nuclear translocation of NF-kappaB. Each of these effects contributes to the substantial reduction of apoptotic neuronal death induced by glutamate. These results demonstrate that mangiferin and morin exhibit excellent antioxidant and antiapoptotic properties, supporting their clinical application as trial neuroprotectors in pathologies involving excitotoxic neuronal death.
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Diagnostic endoscopic ultrasonography: assessment of safety and prevention of complications.
World J. Gastroenterol.
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Endoscopic ultrasonography (EUS) has gained wide acceptance as an important, minimally invasive diagnostic tool in gastroenterology, pulmonology, visceral surgery and oncology. This review focuses on data regarding risks and complications of non-interventional diagnostic EUS and EUS-guided fine-needle biopsy (EUS-FNB). Measures to improve the safety of EUS und EUS-FNB will be discussed. Due to the specific mechanical properties of echoendoscopes in EUS, there is a low but noteworthy risk of perforation. To minimize this risk, endoscopists should be familiar with the specific features of their equipment and their patients specific anatomical situations (e.g., tumor stenosis, diverticula). Most diagnostic EUS complications occur during EUS-FNB. Pain, acute pancreatitis, infection and bleeding are the primary adverse effects, occurring in 1% to 2% of patients. Only a few cases of needle tract seeding and peritoneal dissemination have been reported. The mortality associated with EUS and EUS-FNB is 0.02%. The risks associated with EUS-FNB are affected by endoscopist experience and target lesion. EUS-FNB of cystic lesions is associated with an increased risk of infection and hemorrhage. Peri-interventional antibiotics are recommended to prevent cyst infection. Adequate education and training, as well consideration of contraindications, are essential to minimize the risks of EUS and EUS-FNB. Restricting EUS-FNB only to patients in whom the cytopathological results may be expected to change the course of management is the best way of reducing the number of complications.
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An automatic wash method for dimethyl sulfoxide removal in autologous hematopoietic stem cell transplantation decreases the adverse effects related to infusion.
Transfusion
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Products cryopreserved with dimethyl sulfoxide (DMSO) in stem cell transplant (SCT) often cause many adverse effects during their infusion (major cardiovascular events, dyspnea … even death). These are especially frequent in pediatric patients. We tested if a fully automated and closed wash procedure (Sepax S-100, Biosafe) allowed us to maintain the absolute CD34+ cell number, cell viability, and engraftment potential, decreasing the untoward reactions.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.