45 results on '"Miranda, Aline S."'
Search Results
2. Stress-inducible phosphoprotein 1 (HOP/STI1/STIP1) regulates the accumulation and toxicity of α-synuclein in vivo
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Lackie, Rachel E., de Miranda, Aline S., Lim, Mei Peng, Novikov, Vladislav, Madrer, Nimrod, Karunatilleke, Nadun C., Rutledge, Benjamin S., Tullo, Stephanie, Brickenden, Anne, Maitland, Matthew E. R., Greenberg, David, Gallino, Daniel, Luo, Wen, Attaran, Anoosha, Shlaifer, Irina, Del Cid Pellitero, Esther, Schild-Poulter, Caroline, Durcan, Thomas M., Fon, Edward A., Duennwald, Martin, Beraldo, Flavio H., Chakravarty, M. Mallar, Bussey, Timothy J., Saksida, Lisa M., Soreq, Hermona, Choy, Wing-Yiu, Prado, Vania F., and Prado, Marco A. M.
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- 2022
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3. TRPV1 modulation of contextual fear memory depends on stimulus intensity and endocannabinoid signalling in the dorsal hippocampus
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Iglesias, Lia P., Fernandes, Heliana B., de Miranda, Aline S., Perez, Malena M., Faccioli, Lucia H., Sorgi, Carlos A., Bertoglio, Leandro J., Aguiar, Daniele C., Wotjak, Carsten T., and Moreira, Fabrício A.
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- 2023
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4. Neuromuscular defects after infection with a beta coronavirus in mice
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Rossi, Leonardo, Santos, KiviaB.S., Mota, Bárbara I., Pimenta, Jordane, Oliveira, Bruna, Machado, Caroline A., Fernandes, Heliana B., Barbosa, Leticia A., Rodrigues, Hermann A., Marques, Gabriel, Gomes-Martins, Gabriel A., Chaimowicz, Gabriel F., Queiroz-Junior, Celso Martins, Chaves, Ian, Tapia, Juan C., Teixeira, Mauro M., Costa, Vivian V., Miranda, Aline S., and Guatimosim, Cristina
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- 2023
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5. Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington’s disease
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Santos, Rebeca P. M., Ribeiro, Roberta, Ferreira-Vieira, Talita H., Aires, Rosaria D., de Souza, Jessica M., Oliveira, Bruna S., Lima, Anna Luiza D., de Oliveira, Antônio Carlos P., Reis, Helton J., de Miranda, Aline S., Vieira, Erica M. L., Ribeiro, Fabiola M., and Vieira, Luciene B.
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- 2022
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6. Neuroanatomical and cognitive biomarkers of alpha‐synuclein propagation in a mouse model of synucleinopathy prior to onset of motor symptoms.
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Tullo, Stephanie, Miranda, Aline S., del Cid‐Pellitero, Esther, Lim, Mei Peng, Gallino, Daniel, Attaran, Anoosha, Patel, Raihaan, Novikov, Vladislav, Park, Megan, Beraldo, Flavio H., Luo, Wen, Shlaifer, Irina, Durcan, Thomas M., Bussey, Timothy J., Saksida, Lisa M., Fon, Edward A., Prado, Vania F., Prado, Marco A. M., and Chakravarty, M. Mallar
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PARKINSON'S disease , *MAGNETIC resonance imaging , *CELLULAR pathology , *LABORATORY mice , *ANIMAL disease models - Abstract
Significant evidence suggests that misfolded alpha‐synuclein (aSyn), a major component of Lewy bodies, propagates in a prion‐like manner contributing to disease progression in Parkinson's disease (PD) and other synucleinopathies. In fact, timed inoculation of M83 hemizygous mice with recombinant human aSyn preformed fibrils (PFF) has shown symptomatic deficits after substantial spreading of pathogenic alpha‐synuclein, as detected by markers for the phosphorylation of S129 of aSyn. However, whether accumulated toxicity impact human‐relevant cognitive and structural neuroanatomical measures is not fully understood. Here we performed a single unilateral striatal PFF injection in M83 hemizygous mice, and using two assays with translational potential, ex vivo magnetic resonance imaging (MRI) and touchscreen testing, we examined the combined neuroanatomical and behavioral impact of aSyn propagation. In PFF‐injected mice, we observed widespread atrophy in bilateral regions that project to or receive input from the injection site using MRI. We also identified early deficits in reversal learning prior to the emergence of motor symptoms. Our findings highlight a network of regions with related cellular correlates of pathology that follow the progression of aSyn spreading, and that affect brain areas relevant for reversal learning. Our experiments suggest that M83 hemizygous mice injected with human PFF provides a model to understand how misfolded aSyn affects human‐relevant pre‐clinical measures and suggest that these pre‐clinical biomarkers could be used to detect early toxicity of aSyn and provide better translational measures between mice and human disease. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Protective effect of a spider recombinant toxin in a murine model of Huntington's disease
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Joviano-Santos, Julliane V., Valadão, Priscila A.C., Magalhães-Gomes, Matheus P.S., Fernandes, Lorena F., Diniz, Danuza M., Machado, Thatiane C.G., Soares, Kivia B., Ladeira, Marina S., Miranda, Aline S., Massensini, Andre R., Gomez, Marcus V., and Guatimosim, Cristina
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- 2021
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8. Metabotropic glutamate receptor 5 ablation accelerates age-related neurodegeneration and neuroinflammation
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Carvalho, Toniana G., Alves-Silva, Juliana, de Souza, Jessica M., Real, Ana L.C.V., Doria, Juliana G., Vieira, Erica L.M., Gomes, Giovanni F., de Oliveira, Antonio C., Miranda, Aline S., and Ribeiro, Fabiola M.
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- 2019
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9. Inhibition of the dopamine transporter as an animal model of bipolar disorder mania: Locomotor response, neuroimmunological profile and pharmacological modulation
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Bastos, Juliana R., Perico, Katherinne M., Marciano Vieira, Érica L., Teixeira, Antônio L., Machado, Fabiana S., de Miranda, Aline S., and Moreira, Fabrício A.
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- 2018
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10. Blockade of mGluR5 in astrocytes derived from human iPSCs modulates astrocytic function and increases phagocytosis.
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de Lima, Izabella B. Q., Cardozo, Pablo L., Fahel, Julia S., Lacerda, Juliana P. S., Miranda, Aline S., Teixeira, Antônio L., and Ribeiro, Fabiola M.
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ASTROCYTES ,PHAGOCYTOSIS ,BLOCKADE ,CENTRAL nervous system ,GLUTAMATE receptors - Abstract
TNF-α is essential for induction and maintenance of inflammatory responses and its dysregulation is associated with susceptibility to various pathogens that infect the central nervous system. Activation of both microglia and astrocytes leads to TNF-α production, which in turn triggers further activation of these cells. Astrocytes have been implicated in the pathophysiology of a wide range of neurodegenerative diseases with either harmful or protective roles, as these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including the metabotropic glutamate receptor 5 (mGluR5). Under neuroinflammatory conditions, mGluR5 activation in astrocytes can be neuroprotective or have the opposite effect. In the current study, we investigated the role of mGluR5 in hiPSC-derived astrocytes subjected to pro-inflammatory stimulation by recombinant TNF-α (rTNF-α). Our results show that mGluR5 blockade by CTEP decreases the secreted levels of pro-inflammatory cytokines (IL-6 and IL-8) following short rTNF-α stimulation, although this effect subsides with time. Additionally, CTEP enhances synaptoneurosome phagocytosis by astrocytes in both non-stimulated and rTNF-α-stimulated conditions, indicating that mGluR5 blockade alone is enough to drive synaptic material engulfment. Finally, mGluR5 antagonism as well as rTNF-α stimulation augment the expression of the reactivity marker SERPINA3 and reduces the expression of synaptogenic molecules. Altogether, these data suggest a complex role for mGluR5 in human astrocytes, since its blockade may have beneficial and detrimental effects under inflammatory conditions. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Suppressor of cytokine signaling 2 modulates the immune response profile and development of experimental cerebral malaria
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Brant, Fatima, Miranda, Aline S., Esper, Lisia, Gualdrón-López, Melisa, Cisalpino, Daniel, de Souza, Danielle da Gloria, Rachid, Milene Alvarenga, Tanowitz, Herbert B., Teixeira, Mauro Martins, Teixeira, Antônio Lucio, and Machado, Fabiana Simão
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- 2016
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12. Effects of Physical Exercise on Plasma Levels of Brain-Derived Neurotrophic Factor and Depressive Symptoms in Elderly Women—A Randomized Clinical Trial
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Pereira, Daniele S., de Queiroz, Bárbara Z., Miranda, Aline S., Rocha, Natália P., Felício, Diogo C., Mateo, Elvis C., Favero, Michelle, Coelho, Fernanda M., Jesus-Moraleida, Fabianna, Gomes Pereira, Danielle A., Teixeira, Antonio L., and Máximo Pereira, Leani S.
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- 2013
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13. Functional Performance and Inflammatory Cytokines After Squat Exercises and Whole-Body Vibration in Elderly Individuals With Knee Osteoarthritis
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Simão, Adriano P., Avelar, Núbia C., Tossige-Gomes, Rosalina, Neves, Camila D., Mendonça, Vanessa A., Miranda, Aline S., Teixeira, Mauro M., Teixeira, Antônio L., Andrade, André P., Coimbra, Cândido C., and Lacerda, Ana Cristina
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- 2012
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14. Reduced serum levels of adiponectin in elderly patients with major depression
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Diniz, Breno S., Teixeira, Antonio L., Campos, Alline C., Miranda, Aline S., Rocha, Natalia P., Talib, Leda L., Gattaz, Wagner F., and Forlenza, Orestes V.
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- 2012
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15. Circulating Glial-derived neurotrophic factor is reduced in late-life depression
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Diniz, Breno S., Teixeira, Antonio L., Miranda, Aline S., Talib, Leda L., Gattaz, Wagner F., and Forlenza, Orestes V.
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- 2012
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16. Effect of exercise on the plasma BDNF levels in elderly women with knee osteoarthritis
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Gomes, Wellington F., Lacerda, Ana Cristina R., Mendonça, Vanessa A., Arrieiro, Arthur N., Fonseca, Sueli F., Amorim, Mateus R., Teixeira, Antônio L., Teixeira, Mauro M., Miranda, Aline S., Coimbra, Cândido C., and Brito-Melo, Gustavo E. A.
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- 2014
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17. Neuroprotective effect of CTK 01512-2 recombinant toxin at the spinal cord in a model of Huntington's disease.
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Joviano-Santos, Julliane V., Valadão, Priscila A. C., Magalhães-Gomes, Matheus P. S., Fernandes, Lorena F., Diniz, Danuza M., Machado, Thatiane C. G., Soares, Kivia B., Ladeira, Marina S., Massensini, Andre R., Gomez, Marcus V., Miranda, Aline S., Tápia, Juan C., and Guatimosim, Cristina
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HUNTINGTON disease ,SPIDER venom ,NEUROTOXIC agents ,SPINAL cord ,MOVEMENT disorders ,INTRATHECAL injections ,NERVOUS system ,SPINAL cord injuries ,MUSCULAR atrophy - Abstract
Pha1ß is a neurotoxin from the venom of the Phoneutria nigriventer spider, available as CTK 01512-2, a recombinant peptide. Owing to its antinociceptive and analgesic properties, CTK 01512-2 has been described to alleviate neuroinflammatory responses. Despite the diverse actions of CTK 01512-2 on the nervous system, little is known regarding its neuroprotective effect, especially in neurodegenerative conditions such as Huntington's disease (HD), a genetic movement disorder without cure. Here, we investigated whether CTK 01512-2 has a neuroprotective effect in a mouse model of HD. We hypothesized that spinal cord neurons might represent a therapeutic target, because the spinal cord seems to be involved in the motor symptoms ofHD(BACHD)mice. We treated BACHDmice with CTK 01512-2 by intrathecal injection and performed in vivo motor behavioural and morphological analyses in the CNS (brain and spinal cord) and muscles. Our data showed that intrathecal injection of CTK 01512-2 significantly improved motor performance in the open field task. CTK 01512-2 protected neurons in the spinal cord (but not in the brain) from death, suggesting a local effect. CTK 01512-2 exerted its neuroprotective effect by inhibiting BACHD neuronal apoptosis, as revealed by a reduction in caspase-3 in the spinal cord. CTK 01512-2 was also able to revert BACHD muscle atrophy. In conclusion, our data suggest a novel role for CTK 01512-2 acting directly in the spinal cord to ameliorate morphofunctional aspects of spinal cord neurons and muscles and improve the performance of BACHD mice in motor behavioural tests. Given that HD shares similar symptoms with many neurodegenerative conditions, the findings presented herein might also be applicable to other disorders. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Late Anxiety-Like Behavior and Neuroinflammation in Mice Subjected to Sublethal Polymicrobial Sepsis
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Calsavara, Allan C., Rodrigues, David H., Miranda, Aline S., Costa, Priscila A., Lima, Cristiano X., Vilela, Márcia C., Rachid, Milene A., and Teixeira, Antônio L.
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- 2013
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19. Decreased Levels of Circulating Adiponectin in Mild Cognitive Impairment and Alzheimer’s Disease
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Teixeira, Antonio L., Diniz, Breno S., Campos, Alline C., Miranda, Aline S., Rocha, Natalia P., Talib, Leda L., Gattaz, Wagner F., and Forlenza, Orestes V.
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- 2013
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20. Effect Of Exercise In Plasma Cytokines And Soluble Receptors Levels In Elderly Women With Osteoarthritis: 3063: Board #26 June 4 9:30 AM - 11:00 AM
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Gomes, Wellington F., Mendonça, Vanessa A., Arrieiro, Arthur N., Fonseca, Sueli F., Amorim, Mateus R., Rocha-Vieira, Etel, Brito-Melo, Gustavo E. A., Teixeira, Antônio L., Teixeira, Mauro M., Miranda, Aline S., Coimbra, Cândido C., and Lacerda, Ana Cristina R.
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- 2011
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21. Lower circulating levels of angiotensin-converting enzyme (ACE) in patients with schizophrenia
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Mohite, Satyajit, de Campos-Carli, Salvina M., Rocha, Natalia P., Sharma, Shiva, Miranda, Aline S., Barbosa, Izabela G., Salgado, Joao V., Simoes-e-Silva, Ana Cristina, and Teixeira, Antonio L.
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- 2018
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22. Interaction between cytokine gene polymorphisms and the effect of physical exercise on clinical and inflammatory parameters in older women: study protocol for a randomized controlled trial
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Pereira Daniele S, Queiroz Bárbara Z, Mateo Elvis CC, Assumpção Alexandra M, Felício Diogo C, Miranda Aline S, Anjos Daniela MC, Jesus-Moraleida Fabianna, Dias Rosângela C, Pereira Danielle AG, Teixeira Antônio L, and Pereira Leani SM
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Polymorphism ,Cytokines ,Older adult ,Exercise ,Physical performance ,BDNF ,Medicine (General) ,R5-920 - Abstract
Abstract Background Aging is associated with chronic low-grade inflammatory activity with an elevation of cytokine levels. An association between regular physical activity and reduction of blood levels of anti-inflammatory cytokines is demonstrated in the literature pointing to an anti-inflammatory effect related to exercise. However, there is no consensus regarding which type of exercise and which parameters are the most appropriate to influence inflammatory markers. Evidence indicates that the single nucleotide polymorphism (SNP) can influence the synthesis of those cytokines affecting their production. Methods/Design The design of this study is a randomized controlled trial. The aim of this study is to investigate the interaction between the cytokine genes SNP and the effect of physical activity on older women. The main outcomes are: serum levels of sTNFR-1, sTNFR-2, interleukin (IL)-6, IL-10, measured by the ELISA method; genotyping of tumor necrosis factor- (TNF)-alpha (rs1800629), IL6 (rs1800795), IL10 (rs1800896) by the TaqMan Method (Applied Biosystems, Foster City, CA, USA); and physical performance assessed by Timed Up and Go and 10-Meter Walk Tests. Secondary outcomes include: Geriatric Depression Scale, Perceived Stress Scaleand aerobic capacity, assessed by the six-minute walk; and lower limb muscle strength, using an isokinetic dinamometer (Biodex Medical Systems, Inc., Shirley, NY,USA). Both exercise protocols will be performed three times a week for 10 weeks, 30 sessions in total. Discussion Investigating the interaction between genetic factors and exercise effects of both protocols of exercise on the levels of inflammatory cytokine levels can contribute to guide clinical practice related to treatment and prevention of functional changes due to chronic inflammatory activity in older adults. This approach could develop new perspectives on preventive and treatment proposals in physical therapy and in the management of the older patient. Trial registration (ReBEC) RBR9v9cwf
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- 2012
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23. Intracerebral infection with dengue-3 virus induces meningoencephalitis and behavioral changes that precede lethality in mice
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Campos Marco A, Kroon Erna G, Costa Vivian V, Miranda Aline S, Lacerda-Queiroz Norinne, Rodrigues David H, Ferreira Gustavo P, Campos Roberta DL, Vilela Marcia C, Rachid Milene A, Amaral Debora CG, Teixeira Mauro M, and Teixeira Antonio L
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Dengue, one of the most important arboviral diseases of humans, may cause severe systemic disease. Although dengue virus (DENV) has been considered to be a non-neurotropic virus, dengue infection has been associated recently with a series of neurological syndromes, including encephalitis. In this work, we evaluated behavioral changes and inflammatory parameters in C57BL/6 mice infected with non-adapted dengue virus 3 (DENV-3) genotype I. Methods C57BL/6 mice received 4 × 103 PFU of DENV-3 by an intracranial route. We evaluated the trafficking of leukocytes in brain microvasculature using intravital microscopy, and evaluated chemokine and cytokine profiling by an ELISA test at 3 and 6 days post infection (p.i.). Furthermore, we determined myeloperoxidase activity and immune cell populations, and also performed histopathological analysis and immunostaining for the virus in brain tissue. Results All animals developed signs of encephalitis and died by day 8 p.i. Motor behavior and muscle tone and strength parameters declined at day 7 p.i. We observed increased leukocyte rolling and adhesion in brain microvasculature of infected mice at days 3 and 6 p.i. The infection was followed by significant increases in IFN-γ, TNF-α, CCL2, CCL5, CXCL1, and CXCL2. Histological analysis showed evidence of meningoencephalitis and reactive gliosis. Increased numbers of neutrophils, CD4+ and CD8+ T cells were detected in brain of infected animals, notably at day 6 p.i. Cells immunoreactive for anti-NS-3 were visualized throughout the brain. Conclusion Intracerebral infection with non-adapted DENV-3 induces encephalitis and behavioral changes that precede lethality in mice.
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- 2011
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24. Negative Modulation of the Metabotropic Glutamate Receptor Type 5 as a Potential Therapeutic Strategy in Obesity and Binge-Like Eating Behavior.
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Oliveira, Tadeu P. D., Gonçalves, Bruno D. C., Oliveira, Bruna S., de Oliveira, Antonio Carlos P., Reis, Helton J., Ferreira, Claudia N., Aguiar, Daniele C., de Miranda, Aline S., Ribeiro, Fabiola M., Vieira, Erica M. L., Palotás, András, and Vieira, Luciene B.
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FOOD habits ,GLUTAMATE receptors ,WEIGHT loss ,ADIPOSE tissue diseases ,LABORATORY mice ,REWARD (Psychology) - Abstract
Obesity is a multifactorial disease, which in turn contributes to the onset of comorbidities, such as diabetes and atherosclerosis. Moreover, there are only few options available for treating obesity, and most current pharmacotherapy causes severe adverse effects, while offering minimal weight loss. Literature shows that metabotropic glutamate receptor 5 (mGluR5) modulates central reward pathways. Herein, we evaluated the effect of VU0409106, a negative allosteric modulator (NAM) of mGluR5 in regulating feeding and obesity parameters. Diet-induced obese C57BL/6 mice were treated for 14 days with VU0409106, and food intake, body weight, inflammatory/hormonal levels, and behavioral tests were performed. Our data suggest reduction of feeding, body weight, and adipose tissue inflammation in mice treated with high-fat diet (HFD) after chronic treatment with VU0409106. Furthermore, a negative modulation of mGluR5 also reduces binge-like eating, the most common type of eating disorder. Altogether, our results pointed out mGluR5 as a potential target for treating obesity, as well as related disorders. Diet-induced obese (DIO) C57BL/6 mice were treated for 14 days with VU0409106, a negative allosteric modulator of mGluR5. Food intake, body weight, inflammatory/hormonal levels, and behavioral tests were performed. Our data suggest reduction of feeding, body weight, and adipose tissue inflammation in DIO mice after chronic treatment with VU0409106. [ABSTRACT FROM AUTHOR]
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- 2021
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25. Potential Role of Nutrient Intake and Malnutrition as Predictors of Uremic Oxidative Toxicity in Patients with End-Stage Renal Disease.
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Silva, Robson E., Simões-e-Silva, Ana C., Miranda, Aline S., Justino, Patrícia B. I., Brigagão, Maísa R. P. L., Moraes, Gabriel O. I., Gonçalves, Reggiani V., and Novaes, Rômulo D.
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- 2019
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26. Low urinary levels of angiotensin‐converting enzyme 2 may contribute to albuminuria in children with sickle cell anaemia.
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Belisário, André R., Vieira, Érica L. M., Almeida, Jéssica A., Mendes, Fabíola G., Miranda, Aline S., Rezende, Paulo V., Viana, Marcos B., and Simões e Silva, Ana C.
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SICKLE cell anemia treatment ,ANGIOTENSIN converting enzyme ,URINALYSIS ,ALBUMINURIA ,ENZYME inhibitors - Published
- 2019
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27. Laquinimod attenuates inflammation by modulating macrophage functions in traumatic brain injury mouse model.
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Katsumoto, Atsuko, Miranda, Aline S., Butovsky, Oleg, Teixeira, Antônio L., Ransohoff, Richard M., and Lamb, Bruce T.
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INFLAMMATION , *BRAIN injuries , *PUBLIC health , *CENTRAL nervous system , *MESSENGER RNA - Abstract
Background: Traumatic brain injury (TBI) is a critical public health and socio-economic problem worldwide. A growing body of evidence supports the involvement of inflammatory events in TBI. It has been reported that resident microglia and infiltrating monocytes promote an inflammatory reaction that leads to neuronal death and eventually behavioral and cognitive impairment. Currently, there is no effective treatment for TBI and the development of new therapeutic strategies is a scientific goal of highest priority. Laquinimod, an orally administered neuroimmunomodulator initially developed for the treatment of multiple sclerosis, might be a promising neuroprotective therapy for TBI. Herein, we aim to investigate the hypothesis that laquinimod will reduce the central nervous system (CNS) damage caused by TBI.Methods: To test our hypothesis, Ccr2rfp/+ Cx3cr1 gfp/+ mice were submitted to a moderate TBI induced by fluid percussion. Sham controls were submitted only to craniotomy. Mice were treated daily by oral gavage with laquinimod (25 mg/kg) 7 days before and 3 days after TBI. The brains of mice treated or not treated with laquinimod were collected at 3 and 120 days post injury, and brain morphological changes, axonal injury, and neurogenesis were evaluated by microscopy analysis. We also isolated microglia from infiltrating monocytes, and the expression of immune gene mRNAs were analyzed by employing a quantitative NanoString nCounter technique.Results: Laquinimod prevented ventricle enlargement caused by TBI in the long term. Immunohistochemical analyses revealed decreased axonal damage and restored neurogenesis in the laquinimod-treated TBI group at early stage (3 days post injury). Notably, laquinimod inhibited the monocytes infiltration to the brain. Hierarchial clustering demonstrated that the microglial gene expression from the TBI group treated with laquinimod resembles the sham group more than the TBI-water control group.Conclusions: Administration of laquinimod reduced lesion volume and axonal damage and restored neurogenesis after TBI. Laquinimod might be a potential therapy strategy to improve TBI long-term prognosis. [ABSTRACT FROM AUTHOR]- Published
- 2018
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28. Effect of mushroom Agaricus blazei on immune response and development of experimental cerebral malaria.
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Val, Cynthia H., Brant, Fátima, Miranda, Aline S., Rodrigues, Flávia G., Oliveira, Bruno C. L., Santos, Elândia A., Assis, Diego R. R., Esper, Lísia, Silva, Bruno C., Rachid, Milene A., Tanowitz, Herbert B., Teixeira, Antônio L., Teixeira, Mauro M., Régis, Wiliam C. B., and Machado, Fabiana S.
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CEREBRAL malaria ,AGARICUS ,PLASMODIUM berghei ,ALTERNATIVE medicine ,DRUG resistance ,CYTOKINES - Abstract
Background: Cerebral malaria (CM) is debilitating and sometimes fatal. Disease severity has been associated with poor treatment access, therapeutic complexity and drug resistance and, thus, alternative therapies are increasingly necessary. In this study, the effect of the administration of Agaricus blazei, a mushroom of Brazilian origin in a model of CM caused by Plasmodium berghei, strain ANKA, was investigated in mice. Methods: C57BL/6 mice were pre-treated with aqueous extract or fractions of A. blazei, or chloroquine, infected with P. berghei ANKA and then followed by daily administration of A. blazei or chloroquine. Parasitaemia, body weight, survival and clinical signs of the disease were evaluated periodically. The concentration of pro-and anti-inflammatory cytokines, histopathology and in vitro analyses were performed. Results: Mice treated with A. blazei aqueous extract or fraction C, that shows antioxidant activity, displayed lower parasitaemia, increased survival, reduced weight loss and protection against the development of CM. The administration of A. blazei resulted in reduced levels of TNF, IL-1β and IL-6 production when compared to untreated P. berghei-infected mice. Agaricus blazei (aqueous extract or fraction C) treated infected mice displayed reduction of brain lesions. Although chloroquine treatment reduced parasitaemia, there was increased production of proinflammatory cytokines and damage in the CNS not observed with A. blazei treatment. Moreover, the in vitro pretreatment of infected erythrocytes followed by in vivo infection resulted in lower parasitaemia, increased survival, and little evidence of clinical signs of disease. Conclusions: This study strongly suggests that the administration of A. blazei (aqueous extract or fraction C) was effective in improving the consequences of CM in mice and may provide novel therapeutic strategies. [ABSTRACT FROM AUTHOR]
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- 2015
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29. Up-regulation of brain cytokines and chemokines mediates neurotoxicity in early acute liver failure by a mechanism independent of microglial activation.
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Faleiros, Bruno E., Miranda, Aline S., Campos, Alline C., Gomides, Lindisley F., Kangussu, Lucas M., Guatimosim, Cristina, Camargos, Elizabeth R. S., Menezes, Gustavo B., Rachid, Milene A., and Teixeira, Antônio L.
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CYTOKINES , *CHEMOKINES , *NEUROTOXICOLOGY , *MICROGLIA , *NEUROLOGY , *DISEASE progression - Abstract
The neurological involvement in acute liver failure (ALF) is characterized by arousal impairment with progression to coma. There is a growing body of evidence that neuroinflammatory mechanisms play a role in this process, including production of inflammatory cytokines and microglial activation. However, it is still uncertain whether brain-derived cytokines and glial cells are crucial to the pathophysiology of ALF at the early stage, before coma development. Here, we investigated the influence of cytokines and microglia in ALF-induced encephalopathy in mice as soon as neurological symptoms were identifiable. Behavior was assessed at 12, 24, 36 and 48 h post-injection of thioacetamide, a hepatotoxic drug, through locomotor activity by an open field test. Brain concentration of cytokines (TNF-α and IL-1β) and chemokines (CXCL1, CCL2, CCL3 and CCL5) were assessed by ELISA. Microglial activation in brain sections was investigated through immunohistochemistry, and cellular ultrastructural changes were observed by transmission electron microscopy. We found that ALF-induced animals presented a significant decrease in locomotor activity at 24 h, which was accompanied by an increase in IL-1β, CXCL1, CCL2, CCL3 and CCL5 in the brain. TNF-α level was significantly increased only at 36 h. Despite marked morphological changes in astrocytes and brain endothelial cells, no microglial activation was observed. These findings suggest an involvement of brain-derived chemokines and IL-1β in early pathophysiology of ALF by a mechanism independent of microglial activation. [ABSTRACT FROM AUTHOR]
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- 2014
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30. Inflammation biomarkers and delirium in critically ill patients.
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Ritter, Cristiane, Tomasi, Cristiane D., Dal-Pizzol, Felipe, Pinto, Bernardo Bollen, Dyson, Alex, de Miranda, Aline S., Comim, Clarissa M., Soares, Márcio, Teixeira, Antonio L., Quevedo, João, and Singer, Mervyn
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- 2014
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31. Soluble Endoglin, Transforming Growth Factor-Beta 1 and Soluble Tumor Necrosis Factor Alpha Receptors in Different Clinical Manifestations of Preeclampsia.
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Perucci, Luiza O., Gomes, Karina B., Freitas, Letícia G., Godoi, Lara C., Alpoim, Patrícia N., Pinheiro, Melina B., Miranda, Aline S., Teixeira, Antônio L., Dusse, Luci M., and Sousa, Lirlândia P.
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ENDOGLIN ,TRANSFORMING growth factors-beta ,TUMOR necrosis factors ,PREECLAMPSIA ,PREGNANCY ,BLOOD circulation - Abstract
Background: Despite intensive research, the etiopathogenesis of preeclampsia (PE) remains uncertain. Inflammatory and angiogenic factors are thought to play considerable roles in this disease. The objective of this study was to investigate the association between soluble endoglin (sEng), transforming growth factor beta-1 (TGF-β1) and tumor necrosis factor alpha soluble receptors (sTNF-Rs) and the clinical manifestations of PE. Methods: Plasma levels of sEng, TGF-β1 and sTNF-Rs were determined by ELISA in 23 non-pregnant, 21 normotensive pregnant and 43 PE women. PE women were stratified into subgroups according to the severity [mild (n = 12) and severe (n = 31)] and onset-time of the disease [early (n = 19) and late (n = 24)]. Results: Pregnancy was associated with higher levels of sEng, sTNF-R1 and sTNF-R2 than the non-pregnant state. Moreover, PE women had higher levels of sEng and sTNF-R1 than normotensive pregnant women. No difference was found in TGF-β1 levels, comparing the three study groups. Late PE had higher levels of sTNF-R1 and sTNF-R2 than early PE. No significant differences were found in sEng and TGF-β1 comparing early and late PE. sEng levels were higher in severe PE than in mild PE and no difference was found for TGF-β1, sTNF-R1 and sTNF-R2 levels. There was a positive correlation among sEng, TNF-R1 and sTNF-2 levels. Logistic regression analysis revealed that primiparity and sEng levels are independently associated with the development of PE. Furthermore, sEng levels are independently associated with the disease severity. Conclusions: These results suggest that pregnancy is a condition associated with higher levels of anti-angiogenic and pro-inflammatory factors than the non-pregnant state and that PE is associated with an imbalance of these factors in the maternal circulation. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
32. Further evidence for an anti-inflammatory role of artesunate in experimental cerebral malaria.
- Author
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Miranda, Aline S., Brant, Fátima, Rocha, Natália P ., Cisalpino, Daniel, Rodrigues, David H., Souza, Danielle G., Machado, Fabiana S., Rachid, Milene A., Teixeira Jr., Antônio L., and Campos, Alline C.
- Subjects
- *
CEREBRAL malaria , *PLASMODIUM falciparum , *MALARIA treatment , *PLASMODIUM berghei , *INFLAMMATION , *HIPPOCAMPUS (Brain) proteins , *THERAPEUTICS , *DISEASE risk factors - Abstract
Background Cerebral malaria (CM) is a clinical syndrome resulting from Plasmodium falciparum infection. A wide range of clinical manifestations follow the disease including cognitive dysfunction, seizures and coma. CM pathogenesis remains incompletely understood and without treatment this condition is invariably fatal. Artesunate has been accepted as the most effective drug for treating severe malaria. Besides its antiparasitic activity, an antiinflammatory property has also been reported. In the current study, the immunomodulatory role of artesunate was investigated using a Plasmodium berghei ANKA model of CM, trough evaluation of behavioural changes and cytokines expression in hippocampus and in frontal cortex. Methods C57Bl/6 mice were infected with P. berghei by intraperitoneal route, using a standardized inoculation of 106 parasitized erythrocytes. Memory function was evaluated using the stepdown inhibitory avoidance test. The mRNA expression of IFN-γ, IL-1β, IL-6 and TNF in the frontal cortex and hippocampus of control and infected mice on day 5 post-infection were estimated by quantitative real time PCR. Plasmodium berghei -infected mice also received intraperitoneally a single dose of artesunate (32 mg/kg) on day 4 post-infection, and 24 hours after treatment behavioural and immunological analysis were performed. The protein levels of cytokines IL-2, IL-6, IL-10, IL-17, IFN-γ, TNF in the serum, frontal cortex and hippocampus of controls and P. berghei -infected mice treated or not treated with artesunate were determined using a cytometric bead array (CBA) kit. The survival and neurological symptoms of CM were also registered. Results CM mice presented a significant impairment of aversive memory compared to controls on day 5 post-infection. A higher mRNA expression of pro-inflammatory cytokines was found in the hippocampus and frontal cortex of infected mice. A single dose of artesunate was also able to decrease the expression of inflammatory cytokines in the hippocampus and frontal cortex of P. berghei-infected mice. In parallel, a significant improvement in neurological symptoms and survival were observed in artesunate treated mice. Conclusions In summary, the current study provided further evidence that CM affects key brain areas related to cognition process. In addition, different patterns of cytokine expression during the course of CM could be modulated by a single administration of the anti-malarial artesunate. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
33. Brain-derived neurotrophic factor plasma levels are associated with mortality in critically ill patients even in the absence of brain injury.
- Author
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Ritter, Cristiane, Miranda, Aline S., Renˆ Giombelli, Vin¡cius, Tomasi, Cristiane D., Comim, Clarissa M., Lucio Teixeira, Antonio, Quevedo, JoÆo, and Dal-Pizzol, Felipe
- Subjects
BRAIN-derived neurotrophic factor ,NEUROBEHAVIORAL disorders ,BRAIN injuries ,PATIENTS ,MORTALITY ,ETIOLOGY of diseases - Abstract
Introduction: Because of its relevance to the functioning of the central nervous system, brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of different neuropsychiatric diseases. Whether the BDNF level can be a marker of brain dysfunction and thus predict mortality in critically ill patients is not known. Thus we aimed to determine whether the plasma levels of BDNF are associated with morbidity and mortality in critically ill patients. Methods: Healthy volunteers (n = 40) and consecutive patients older than 18 years (n = 76) admitted for more than 24 hours in an Intensive Care Unit (ICU) in a University hospital between July and October 2010 were included in the present study. First blood samples were collected within 12 hours of enrollment (D0), and a second sample, 48 hours after (D2) for determination of plasma BDNF levels. The relation between BDNF levels and mortality was the primary outcome. The secondary outcomes were the relation between BDNF levels and delirium and coma-free days (DCFD) and ICU and hospital length of stay (LOS). Results: Admission plasma levels of BDNF were higher in ICU patients when compared with healthy volunteers (1,536 (962) versus 6,565 (2,838) pg/ml). The mean BDNF D2 was significantly lower in nonsurvivor patients (5,865 (2,662) versus 6,741 (2,356) pg/ml). After adjusting for covariates, BDNF levels, the need for mechanical ventilation, and sepsis were associated with mortality. Even in patients without clinically detectable brain dysfunction, lower BDNF D2 levels were associated with mortality. BDNF D2 had a mild correlation to DCFD (r = 0.44), but not to ICU and hospital LOS. In addition, plasma BDNF did not correlate to different plasma cytokines and platelets levels. Conclusions: The plasma levels of BDNF were independently associated with mortality, even in the absence of clinically detectable brain dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
34. Interaction between cytokine gene polymorphisms and the effect of physical exercise on clinical and inflammatory parameters in older women: study protocol for a randomized controlled trial.
- Author
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Oereira, Daniele S, Queiroz, Bárbara Z, Mateo, Elvis CC, Assumpção, Alexandra M, Felício, Diogo C, Miranda, Aline S, Anjos, Daniela MC, Jesus-Moraleida, Fabianna, Dias, Rosângela C, Pereira, Danielle AG, Teixeira, Antônio L, and Pereira, Leani SM
- Subjects
CYTOKINES ,GENETIC polymorphisms ,POPULATION genetics ,RANDOMIZED controlled trials ,OLDER women ,PHYSICAL fitness - Abstract
Background: Aging is associated with chronic low-grade inflammatory activity with an elevation of cytokine levels. An association between regular physical activity and reduction of blood levels of anti-inflammatory cytokines is demonstrated in the literature pointing to an anti-inflammatory effect related to exercise. However, there is no consensus regarding which type of exercise and which parameters are the most appropriate to influence inflammatory markers. Evidence indicates that the single nucleotide polymorphism (SNP) can influence the synthesis of those cytokines affecting their production. Methods/Design: The design of this study is a randomized controlled trial. The aim of this study is to investigate the interaction between the cytokine genes SNP and the effect of physical activity on older women. The main outcomes are: serum levels of sTNFR-1, sTNFR-2, interleukin (IL)-6, IL-10, measured by the ELISA method; genotyping of tumor necrosis factor- (TNF)-alpha (rs1800629), IL6 (rs1800795), IL10 (rs1800896) by the TaqMan Method (Applied Biosystems, Foster City, CA, USA); and physical performance assessed by Timed Up and Go and 10-Meter Walk Tests. Secondary outcomes include: Geriatric Depression Scale, Perceived Stress Scaleand aerobic capacity, assessed by the six-minute walk; and lower limb muscle strength, using an isokinetic dinamometer (Biodex Medical Systems, Inc., Shirley, NY,USA). Both exercise protocols will be performed three times a week for 10 weeks, 30 sessions in total. Discussion: Investigating the interaction between genetic factors and exercise effects of both protocols of exercise on the levels of inflammatory cytokine levels can contribute to guide clinical practice related to treatment and prevention of functional changes due to chronic inflammatory activity in older adults. This approach could develop new perspectives on preventive and treatment proposals in physical therapy and in the management of the older patient. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
35. Usual gait speed assessment in middle-aged and elderly Brazilian subjects.
- Author
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Novaes, Rômulo D., Miranda, Aline S., and Dourado, Victor Z.
- Abstract
Objectives: To evaluate the usual gait speed of asymptomatic adult and elderly Brazilians with a 10-meter walk test and to compare the results with foreign reference values. Methods: Seventy-nine asymptomatic volunteers ≥40 years old of both genders were assessed. After anamnesis, anthropometry and the application of a habitual physical activity questionnaire, the volunteers were submitted to a 10-meter walk test at usual speed by means of which gait speed, the number of steps and length of stride were calculated. Results: Except for age, all study variables were significantly lower in women. Subjects ≥70 years old presented a significantly lower gait speed than subjects between 40 and 49 years old and between 50 and 59 in both men (1.09±0.18 m/s, 1.35±0.11 m/s and 1.34±0.22 m/s, respectively) and women (1.02±0,10 m/s, 1.27±0.20 m/s and 1.27±0,15 m/s), respectively). Gait speed showed moderate correlations with age (r=-0.41, p<0.001) and height (r=0.35, p=0.001). After multiple regression analysis, age and gender were selected as relevant attributes of gait speed in that they explained 24.6% of this variable. The gait speed values in this study were significantly lower than foreign reference values (p<0.05). Conclusions: The gait speed presented age-related decline and values significantly lower than those described for foreign populations. This finding indicates the need for comprehensive investigation of gait speed reference values for the Brazilian population. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
36. Intracerebral infection with dengue-3 virus induces meningoencephalitis and behavioral changes that precede lethality in mice.
- Author
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Amaral, Debora C.G., Rachid, Milene A., Vilela, Marcia C., Campos, Roberta D.L., Ferreira, Gustavo P., Rodrigues, David H., Lacerda-Queiroz, Norinne, Miranda, Aline S., Costa, Vivian V., Campos, Marco A., Kroon, Erna G., Teixeira, Mauro M., and Teixeira, Antonio L.
- Subjects
MENINGOENCEPHALITIS ,DENGUE ,ARBOVIRUS diseases ,ENZYME-linked immunosorbent assay ,GENETIC research - Abstract
Background: Dengue, one of the most important arboviral diseases of humans, may cause severe systemic disease. Although dengue virus (DENV) has been considered to be a non-neurotropic virus, dengue infection has been associated recently with a series of neurological syndromes, including encephalitis. In this work, we evaluated behavioral changes and inflammatory parameters in C57BL/6 mice infected with non-adapted dengue virus 3 (DENV-3) genotype I. Methods: C57BL/6 mice received 4 x 10
3 PFU of DENV-3 by an intracranial route. We evaluated the trafficking of leukocytes in brain microvasculature using intravital microscopy, and evaluated chemokine and cytokine profiling by an ELISA test at 3 and 6 days post infection (p.i.). Furthermore, we determined myeloperoxidase activity and immune cell populations, and also performed histopathological analysis and immunostaining for the virus in brain tissue. Results: All animals developed signs of encephalitis and died by day 8 p.i. Motor behavior and muscle tone and strength parameters declined at day 7 p.i. We observed increased leukocyte rolling and adhesion in brain microvasculature of infected mice at days 3 and 6 p.i. The infection was followed by significant increases in IFN- γ, TNF- α, CCL2, CCL5, CXCL1, and CXCL2. Histological analysis showed evidence of meningoencephalitis and reactive gliosis. Increased numbers of neutrophils, CD4+ and CD8+ T cells were detected in brain of infected animals, notably at day 6 p.i. Cells immunoreactive for anti-NS-3 were visualized throughout the brain. Conclusion: Intracerebral infection with non-adapted DENV-3 induces encephalitis and behavioral changes that precede lethality in mice. [ABSTRACT FROM AUTHOR]- Published
- 2011
- Full Text
- View/download PDF
37. Ontogeny and Functions of Central Nervous System Macrophages.
- Author
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Katsumoto, Atsuko, Haiyan Lu, Miranda, Aline S., and Ransohoff, Richard M.
- Subjects
- *
MICROGLIA , *EPITHELIAL cells , *STEM cells , *MACROPHAGES , *CONNECTIVE tissue cells - Abstract
Microglia, the only nonneuroepithelial cells found in the parenchyma of the CNS, originate during embryogenesis from the yolk sac and enter the CNS quite early (embryonic day 9.5-10 in mice). Thereafter, microglia are maintained independently of any input from the blood and, in particular, do not require hematopoietic stem cells as a source of replacement for senescent cells. Monocytes are hematopoietic cells, derived from bone marrow. The ontogeny of microglia and monocytes is important for understanding CNS pathologies. Microglial functions are distinct from those of blood-derived monocytes, which invade the CNS only under pathological conditions. Recent data reveal that microglia play an important role in managing neuronal cell death, neurogenesis, and synaptic interactions. In this article, we discuss the physiology of microglia and the functions of monocytes in CNS pathology. We address the roles of microglia and monocytes in neurodegenerative diseases as an example of CNS pathology. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
38. Anticonvulsant effect of cannabidiol in the pentylenetetrazole model: Pharmacological mechanisms, electroencephalographic profile, and brain cytokine levels.
- Author
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Vilela, Luciano R., Lima, Isabel V., Kunsch, Érica B., Pinto, Hyorrana Priscila P., de Miranda, Aline S., Vieira, Érica Leandro M., de Oliveira, Antônio Carlos P., Moraes, Marcio Flávio D., Teixeira, Antônio L., and Moreira, Fabricio A.
- Subjects
- *
CANNABACEAE , *ANTICONVULSANTS , *ELECTROENCEPHALOGRAPHY , *TRPV cation channels , *SEIZURES (Medicine) , *EPILEPSY - Abstract
Cannabidiol (CBD), the main nonpsychotomimetic compound from Cannabis sativa , inhibits experimental seizures in animal models and alleviates certain types of intractable epilepsies in patients. Its pharmacological profile, however, is still uncertain. Here we tested the hypothesis that CBD anticonvulsant mechanisms are prevented by cannabinoid (CB 1 and CB 2 ) and vanilloid (TRPV1) receptor blockers. We also investigated its effects on electroencephalographic (EEG) activity and hippocampal cytokines in the pentylenetetrazole (PTZ) model. Pretreatment with CBD (60 mg/kg) attenuated seizures induced by intraperitoneal, subcutaneous, and intravenous PTZ administration in mice. The effects were reversed by CB 1 , CB 2 , and TRPV1 selective antagonists (AM251, AM630, and SB366791, respectively). Additionally, CBD delayed seizure sensitization resulting from repeated PTZ administration (kindling). This cannabinoid also prevented PTZ-induced EEG activity and interleukin-6 increase in prefrontal cortex. In conclusion, the robust anticonvulsant effects of CBD may result from multiple pharmacological mechanisms, including facilitation of endocannabinoid signaling and TRPV1 mechanisms. These findings advance our understanding on CBD inhibition of seizures, EEG activity, and cytokine actions, with potential implications for the development of new treatments for certain epileptic syndromes. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
39. A three-compartment apparatus alters the brain concentration of cytokines and neurotrophic factors in cocaine-induced CPP in mice.
- Author
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Rosa, Magda L.P., Machado, Caroline A., Asth, Laila, Toscano, Eliana C.B., da Silva Oliveira, Bruna, Marzano, Lucas A.S., Ferreira, Rodrigo N., Teixeira, Antônio L., Moreira, Fabrício A., and Miranda, Aline S.
- Subjects
- *
COCAINE abuse , *PSYCHONEUROIMMUNOLOGY , *PREFRONTAL cortex , *CYTOKINES , *CONDITIONED response , *MICE - Abstract
Cocaine-induced neuroinflammation plays an important role in the pathophysiology of drug addiction. Evidence suggests that the immune response contributes for memory consolidation related to place preference behavior underlying cocaine administration in mice. Conditioned place preference (CPP) is a protocol extensively used to study the rewarding and/or aversive motivational effects of drug abuse in rodents, reproducing cocaine-seeking behavior in humans. Besides the variety of apparatus used in the CPP protocol, whether different types of apparatus are able to induce the same conditioned behavior response and neurobiological changes remains to be fully explored. We hypothesize that the immune response is involved in the cocaine-induced CPP and that the type of apparatus might influence this response. Herein, two- and three-compartment apparatuses were tested using the behavioral model of CPP. Cocaine-induced CPP was demonstrated in both apparatuses. However, mice injected with cocaine had decreased levels of IL-1β, IL-6, IL-10, and GDNF in the pre-frontal cortex, and decreased CX3CL1 in the striatum, in the CPP protocol using three compartments compared to controls. While similar levels were seen in the CPP protocol using two compartments. In conclusion, the current study demonstrated that the type of apparatus might influence the investigation of neurobiological mechanisms associated with cocaine-induced CPP. Our data also suggest that the three compartment-apparatus seems to be a more appropriate model to investigate the neuroinflammatory response related to cocaine addiction. • Peripheral administration of cocaine induces CPP behavior in mice. • The three-compartment apparatus alters brain levels of cytokines. • The three-compartment apparatus alters brain levels of neurotrophic factors. • Cytokines and Neurotrophic Factors play a role in Cocaine-induced CPP behavior. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
40. Early Post-stroke Depressive Symptoms are Associated with Low Peripheral Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) and Glial Cell-derived Neurotrophic Factor (GDNF).
- Author
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Pedroso VSP, Vieira ÉLM, de Miranda AS, Venna VR, McCullough LD, and Teixeira AL
- Subjects
- Aged, Biomarkers blood, Cross-Sectional Studies, Depression etiology, Female, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Stroke complications, Depression blood, Depression diagnosis, Glial Cell Line-Derived Neurotrophic Factor blood, Stroke blood, Stroke diagnosis, Triggering Receptor Expressed on Myeloid Cells-1 blood
- Abstract
Background: Stroke is a major cause of death and disability worldwide. Among its complications, post-stroke depression (PSD) leads to a significant burden. The diagnosis of PSD is complex, and there are no biomarkers that can assist in its early identification and adequate management., Objective: The aim of the present study is to investigate peripheral biomarkers in the acute phase of stroke and their potential association with depressive symptoms., Methods: We evaluated 60 patients in the acute phase of stroke by using standardized instruments of psychiatric and neurological assessment (Mini International Neuropsychiatric Interview-Plus- MINI-Plus, Hospital Anxiety and Depression Scale-HADS, and National Institutes of Health Stroke Scale-NIHSS) and measured peripheral biomarkers., Results: In multivariate analysis, low peripheral levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and higher NIHSS scores were associated with PSD. The severity of depressive symptoms was inversely correlated with sTREM-1 and glial cell-derived neurotrophic factor (GDNF) levels., Conclusion: This is the first study indicating an association between sTREM-1 and PSD. Our results may point to the involvement of glial mechanisms in the manifestation of depressive symptoms after stroke., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2020
- Full Text
- View/download PDF
41. Low urinary levels of angiotensin-converting enzyme 2 may contribute to albuminuria in children with sickle cell anaemia.
- Author
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Belisário AR, Vieira ÉLM, de Almeida JA, Mendes FG, Miranda AS, Rezende PV, Viana MB, and Simões E Silva AC
- Subjects
- Age Factors, Albuminuria diagnosis, Anemia, Sickle Cell diagnosis, Angiotensin-Converting Enzyme 2, Biomarkers, Child, Disease Susceptibility, Humans, Renin-Angiotensin System, Albuminuria etiology, Albuminuria urine, Anemia, Sickle Cell complications, Peptidyl-Dipeptidase A urine
- Published
- 2019
- Full Text
- View/download PDF
42. Neurotrophic Factors in Parkinson's Disease: What Have we Learned from Pre-Clinical and Clinical Studies?
- Author
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Ferreira RN, de Miranda AS, Rocha NP, Simoes E Silva AC, Teixeira AL, and da Silva Camargos ER
- Subjects
- Animals, Clinical Studies as Topic, Drug Evaluation, Preclinical, Exercise, Humans, Nerve Growth Factors chemistry, Nerve Growth Factors metabolism, Parkinson Disease therapy, Nerve Growth Factors pharmacology, Parkinson Disease drug therapy
- Abstract
Background: Parkinson´s Disease (PD) is a chronic, progressive condition, being the second most common neurodegenerative disorder worldwide. The classical features include: bradykinesia, resting tremor, rigidity and festination. These neurological alterations are probably due to the death of dopaminergic neurons in the Substantia Nigra pars compacta and consequent reduction of dopamine input into the striatum. The decrease of dopamine levels may also be involved in the emergence of non-motor symptoms, including cognitive impairment, anxiety and depression symptoms. Neurotrophic Factors (NF) are proteins that modulate neuronal function, development, and survival. It has been reported that NF might exert a protective role in PD., Objective: We aim to discuss the emerging evidence from pre-clinical and clinical studies regarding the role of NF in PD as well as their potential as promising therapeutic strategies., Methods: We carried out an extensive literature search in PubMed central., Results: Pre-clinical studies using NF to treat PD are divergent probably due to several methodological differences, thus precluding any conclusion. Clinical studies findings obtained with the administration of NF in patients with PD were even more disappointed. On the other hand, pre-clinical and clinical studies generally support that physical activity is a low-cost, non-pharmacologic strategy with good results to treat PD., Conclusion: The use of NF as a treatment for PD is still a promise not incorporated in clinical practice. Methods to deliver NFs, doses and compounds administered, side effects, population characteristics and duration of disease may probably contribute to the unsuccessful results., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2018
- Full Text
- View/download PDF
43. Renin angiotensin system in liver diseases: Friend or foe?
- Author
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Simões E Silva AC, Miranda AS, Rocha NP, and Teixeira AL
- Subjects
- Animals, Cell Proliferation, Fibrosis physiopathology, Hemodynamics, Hepatorenal Syndrome metabolism, Humans, Inflammation, Liver pathology, Liver Cirrhosis metabolism, Mice, Peptidyl-Dipeptidase A metabolism, Angiotensin II metabolism, Liver Diseases metabolism, Renin-Angiotensin System
- Abstract
In the last three decades, the understanding of the renin angiotensin system (RAS) has been changed by the discoveries of functional local systems, novel biologically active peptides, additional specific receptors, alternative pathways of angiotensin (Ang) II generation, and new roles for enzymes and precursor components other than those in Ang II synthesis. In this regard, the discovery that Ang-(1-7) opposes the pressor, proliferative, pro-fibrotic, and pro-inflammatory effects mediated by Ang II has contributed to the realization that the RAS is composed of two axes. The first axis consists of the angiotensin-converting enzyme (ACE), with Ang II as the end product, and the angiotensin type 1 (AT
1 ) receptor as the main effector mediating the biological actions of Ang II. The second axis results from ACE2-mediated hydrolysis of Ang II, leading to the production of Ang-(1-7), with the Mas receptor as the main effector conveying the vasodilatory, anti-proliferative, anti-fibrotic, and anti-inflammatory effects of Ang-(1-7). Experimental and clinical studies have shown that both axes of the RAS may take part in the pathogenesis of liver diseases. In this manuscript, we summarize the current evidence regarding the role of RAS in hepatic cirrhosis and its complications, including hemodynamic changes and hepatorenal syndrome. The therapeutic potential of the modulation of RAS molecules in liver diseases is also discussed., Competing Interests: Conflict-of-interest statement: Simões e Silva AC, Miranda AS, Rocha NP and Teixeira AL declare no conflict of interest related to this publication.- Published
- 2017
- Full Text
- View/download PDF
44. Role of the aryl hydrocarbon receptor in the immune response profile and development of pathology during Plasmodium berghei Anka infection.
- Author
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Brant F, Miranda AS, Esper L, Rodrigues DH, Kangussu LM, Bonaventura D, Soriani FM, Pinho V, Souza DG, Rachid MA, Weiss LM, Tanowitz HB, Teixeira MM, Teixeira AL, and Machado FS
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Brain immunology, Brain pathology, Cytokines immunology, Cytokines metabolism, Gene Deletion, Humans, Liver immunology, Liver pathology, Malaria parasitology, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Aryl Hydrocarbon genetics, Spleen immunology, Suppressor of Cytokine Signaling 3 Protein, Basic Helix-Loop-Helix Transcription Factors immunology, Basic Helix-Loop-Helix Transcription Factors metabolism, Malaria immunology, Malaria pathology, Plasmodium berghei immunology, Receptors, Aryl Hydrocarbon immunology, Receptors, Aryl Hydrocarbon metabolism, Suppressor of Cytokine Signaling Proteins immunology, Suppressor of Cytokine Signaling Proteins metabolism
- Abstract
Infection with Plasmodium falciparum may result in severe disease affecting various organs, including liver, spleen, and brain, resulting in high morbidity and mortality. Plasmodium berghei Anka infection of mice recapitulates many features of severe human malaria. The aryl hydrocarbon receptor (AhR) is an intracellular receptor activated by ligands important in the modulation of the inflammatory response. We found that AhR-knockout (KO) mice infected with P. berghei Anka displayed increased parasitemia, earlier mortality, enhanced leukocyte-endothelial cell interactions in the brain microvasculature, and increased inflammation in brain (interleukin-17 [IL-17] and IL-6) and liver (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]) compared to infected wild-type (WT) mice. Infected AhR-KO mice also displayed a reduction in cytokines required for host resistance, including TNF-α, IL-1β, and IFN-γ, in the brain and spleen. Infection of AhR-KO mice resulted in an increase in T regulatory cells and transforming growth factor β, IL-6, and IL-17 in the brain. AhR modulated the basal expression of SOCS3 in spleen and brain, and P. berghei Anka infection resulted in enhanced expression of SOCS3 in brain, which was absent in infected AhR-KO mice. These data suggest that AhR-mediated control of SOCS3 expression is probably involved in the phenotype seen in infected AhR-KO mice. This is, to our knowledge, the first demonstration of a role for AhR in the pathogenesis of malaria., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Published
- 2014
- Full Text
- View/download PDF
45. Usual gait speed assessment in middle-aged and elderly Brazilian subjects.
- Author
-
Novaes RD, Miranda AS, and Dourado VZ
- Subjects
- Adult, Age Factors, Aged, Brazil, Female, Humans, Male, Middle Aged, Time Factors, Walking physiology
- Abstract
Objectives: To evaluate the usual gait speed of asymptomatic adult and elderly Brazilians with a 10-meter walk test and to compare the results with foreign reference values., Methods: Seventy-nine asymptomatic volunteers ≥40 years old of both genders were assessed. After anamnesis, anthropometry and the application of a habitual physical activity questionnaire, the volunteers were submitted to a 10-meter walk test at usual speed by means of which gait speed, the number of steps and length of stride were calculated., Results: Except for age, all study variables were significantly lower in women. Subjects ≥70 years old presented a significantly lower gait speed than subjects between 40 and 49 years old and between 50 and 59 in both men (1.09±0.18 m/s, 1.35±0.11 m/s and 1.34±0.22 m/s, respectively) and women (1.02±0,10 m/s, 1.27±0.20 m/s and 1.27±0,15 m/s), respectively). Gait speed showed moderate correlations with age (r=-0.41, p<0.001) and height (r=0.35, p=0.001). After multiple regression analysis, age and gender were selected as relevant attributes of gait speed in that they explained 24.6% of this variable. The gait speed values in this study were significantly lower than foreign reference values (p<0.05)., Conclusions: The gait speed presented age-related decline and values significantly lower than those described for foreign populations. This finding indicates the need for comprehensive investigation of gait speed reference values for the Brazilian population.
- Published
- 2011
- Full Text
- View/download PDF
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