Lucas Gazarini

Association of genetic markers with ischemic stroke in pediatric patients with sickle cell anemia

Introduction: Sickle cell anemia (SCA) is characterized by complex clinical heterogeneity. Amongs... more Introduction: Sickle cell anemia (SCA) is characterized by complex clinical heterogeneity. Amongst them, ischemic stroke (IS) stands out because it affects 8% to 12% of patients up to the age of 20, with a mortality rate of 20% in untreated cases. Objectives: To evaluate the association of SNPs -786T/C NOS3 and C667T MTHFR in the occurrence of IS in SCA pediatric patients undergoing regular blood transfusion. Methods: Ninety SCA pediatric patients 12.1±3.3 years old being followed-up at HEMORIO/RJ, divided into Patients with IS in hypertransfusion (n=20) and Patients without IS not transfused (n=70). Results: IS Group: genotypic frequencies: -786T/C NOS3, 4 (20%) CC, 4 (20%) CT and 22 (60%) TT; C667T MTHFR, 3 (15%) TT, 2 (10%) CT and 15 (75%) CC. Group without IS: genotypic frequencies: -786T/C NOS3, 1 (1.4%) CC, 25 (35.7%) CT and 44 (62.8%) TT; C667T MTHFR, 1 (1.4%) TT, 18 (25.7%) CT and 51 (72.8%) CC. Chisquare test revealed association of SNPs -786T/C NOS3 (p = 0,017) and C667T MTHFR (p = 0,004) with the occurrence of stroke in SCA patients, in which the frequency of homozygous mutants is higher in the IS group than in the control group (-786T/C NOS3 20% vs. 1.4% and C667T MTHFR 15% vs. 1.4%). Conclusions: The polymorphisms evaluated influenced the occurrence of IS in SCA pediatric patients especially when carrying recessive alleles. Studies with larger sample sizes and similar inclusion/exclusion criteria is needed.

Activity in prelimbic cortex is required for adjusting the anxiety response level during the elevated plus-maze retest

Neuroscience, Sep 1, 2010

The prelimbic (PL) subregion of medial prefrontal cortex has been implicated in anxiety regulatio... more The prelimbic (PL) subregion of medial prefrontal cortex has been implicated in anxiety regulation. It is unknown, however, whether PL cortex also serves to fine-tuning the level of anxiety-related behavior exhibited on the next exposure to the same potentially threatening situation. To address this, we infused cobalt (1.0 mM) to temporarily inactivate the PL cortex during testing, post-testing or retesting

Educação Em Saúde Na Escola Sobre Depressão e Suicídio: Um Relato De Experiência

Todo o conteúdo deste livro está licenciado sob uma Licença de Atribuição Creative Commons. Atrib... more Todo o conteúdo deste livro está licenciado sob uma Licença de Atribuição Creative Commons. Atribuição 4.0 Internacional (CC BY 4.0). O conteúdo dos artigos e seus dados em sua forma, correção e confiabilidade são de responsabilidade exclusiva dos autores. Permitido o download da obra e o compartilhamento desde que sejam atribuídos créditos aos autores, mas sem a possibilidade de alterá-la de nenhuma forma ou utilizá-la para fins comerciais.

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On making (and turning adaptive to) maladaptive aversive memories in laboratory rodents

Neuroscience & Biobehavioral Reviews, Apr 1, 2023

P.4.b.016 Ventromedial prefrontal cortex activity is required for anxiety expression: distinct neurochemical mechanisms evidence

European Neuropsychopharmacology, Aug 1, 2010

Protein synthesis in dorsal hippocampus supports the drug tolerance induced by prior elevated plus-maze experience

Neuroscience, Apr 1, 2011

ABSTRACT Tolerance to the anxiolytic-like effect of drugs may develop because of a memory derived... more ABSTRACT Tolerance to the anxiolytic-like effect of drugs may develop because of a memory derived from prior experience in certain apparatuses such as the elevated plus-maze (EPM). Activity in basolateral amygdala was shown to be required for consolidating this knowledge. The dorsal hippocampus (DH) is also implicated in long-term memory consolidation, a process relying on new protein synthesis. It is unknown, however, whether the DH protein synthesis disruption would prevent the phenomenon rendering animals unresponsive to benzodiazepines in the EPM retest. To address this, we bilaterally infused the protein synthesis inhibitor anisomycin (ANI) into the rat DH 0, 3 or 6 h after, or 15 min before, the EPM test. DH infusion of ANI (80 μg) around the time of EPM testing preserved the anxiolysis of the midazolam (MDZ; 0.5 mg/kg, i.p.) in rats retested in the EPM 24 h later, suggesting that information consolidated by DH protein synthesis impacts on the subsequent animal&#39;s responsiveness to this drug. To examine whether impaired memory acquisition could also contribute to the prevention of MDZ tolerance seen in EPM-experienced animals infused with ANI before testing, the EPM retest was performed 3 h after testing to coincide with the temporal window in which short-term memory remains, for the reason that this process does not require protein synthesis for its formation. The pretest DH anisomycin infusion&#39;s ability to prevent the MDZ tolerance on retesting was now missing. This result confirms a specific action of the ANI on memory consolidation. We also found that rats express further avoidance to open-arms in the EPM retest. However, neither pretest nor posttest DH ANI infusion interfered with this pattern of results exhibited by EPM-experienced rats.

P.1.g.008 Vitamin E ameliorates memory and changes the expression of nitric oxide-producing neurons in the brains of diabetic rats

European Neuropsychopharmacology, Sep 1, 2009

P.1.j.001 Combined pharmacological intervention targeting the glucocorticoid–adrenergic–endocannabinoid circuitry induces a traumatic memory

European Neuropsychopharmacology, Oct 1, 2014

Efficacy and security of ivermectin given orally to rats naturally infected withSyphaciaspp.,Giardiaspp. andHymenolepis nana

Laboratory Animals, Dec 5, 2014

The results of this study show that the oral administration of ivermectin (48 mg/L) repeatedly fo... more The results of this study show that the oral administration of ivermectin (48 mg/L) repeatedly for 72 h used in accordance with the present protocol is a safe and highly effective treatment for Giardia spp. and Hymenolepis nana in laboratory rat colonies. The drug can be easily and safely administered using drinking water. This simple regimen should control pinworm infection ( Syphacia muris), a problem that can be endemic in laboratory colonies. Experiments using healthy animals are likely to generate more consistent results, thereby requiring a reduced number of animals per group.

On the interplay among endocannabinoid, noradrenergic, and glucocorticoid systems: Evidence from aversive memory studies

Elsevier eBooks, 2023

A Inibição da síntese proteica no hipocampo dorsal de ratos impede a tolerância ao midazolam induzida pela experiência prévia no labirinto em cruz elevado

Ao professor Leandro José Bertoglio, pela confiança depositada e disposição em me acompanhar e or... more Ao professor Leandro José Bertoglio, pela confiança depositada e disposição em me acompanhar e orientar na realização desse trabalho, bem como pelo crescimento pessoal proporcionado. Aos professores Antônio de Pádua Carobrez e Thereza Christina Monteiro de Lima por disponibilizarem seus laboratórios quando precisei. Aos demais professores da Pós-Graduação em Farmacologia pela contribuição na minha formação. Aos professores Dr. Roberto Andreatini, Dr. Rui Daniel Schröder Prediger e Dr. André de Ávila Ramos, por aceitarem o convite para compor a banca e pela colaboração no aperfeiçoamento desse trabalho. Aos meus pais, Vanderlei e Ivanir, pelo esforço e apoio constantes para que eu pudesse ter uma formação concreta, bem como pelas influências positivas para a construção do meu caráter e educação. À minha irmã, Janaina, pela companhia desde sempre, conselhos e inspiração. À professora Dra. Rúbia Weffort de Oliveira, pelos ensinamentos, apoio constante, confiança e amizade. Os meus grandes amigos, Camila, Kássia, Monica, Tiago e Jeanne, sempre presentes. Aos meus amigos de departamento Thaize, Filipe, Evelyn, Ana Paula, Andressa, Claudini, Ju Kroon, Grasi, Eloisa e Cris Mochny, pelos momentos bons, diversão, ideias e sugestões. Aos companheiros de laboratório Ana, Cris Stern, Rafael, Shirlley e Thaís, pela amizade, paciência, disposição, trabalho em conjunto e por tudo que me ensinaram. Aos funcionários do departamento e demais colegas da pósgraduação e a todos os que, de alguma maneira, colaboraram no andamento desse trabalho. À CAPES, CNPq e FAPESC, pelo apoio financeiro.

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Medial prefrontal cortex mechanisms of cannabidiol-induced aversive memory reconsolidation impairments

Neuropharmacology, Mar 1, 2022

Growing evidence indicates that cannabidiol (CBD), a substance present in the Cannabis sativa pla... more Growing evidence indicates that cannabidiol (CBD), a substance present in the Cannabis sativa plant, has potential therapeutic value to regulate abnormal emotional memories associated with post-traumatic stress and drug use disorders. CBD can attenuate their valence after retrieval (i.e., during reconsolidation) or potentiate their suppression by extinction. Pharmacological research has now focused on elucidating how it acts. Systemic antagonism of cannabinoid type-1 (CB1) receptors has often prevented the abovementioned effects of CBD. However, it is unknown which brain regions CBD stimulates CB1 receptors and how it interferes with local activity-related plasticity to produce these effects. The present study addressed these questions considering the reconsolidation of contextual fear memories in rats. We focused on the medial prefrontal cortex (mPFC), which comprises the anterior cingulate (AC), prelimbic (PL), and infralimbic (IL) subregions, as local activity or plasticity has been associated with the process to-be-investigated. Animals that received post-retrieval systemic CBD treatment presented relatively fewer cells expressing Zif268/Egr1 protein, a proxy for synaptic plasticity related to reconsolidation, in the AC and PL. At the same time, there were no significant differences in the IL. Pretreatment with the CB1 receptor antagonist AM251 into the AC, PL, or IL prevented the impairing effects of systemic CBD treatment on reconsolidation. CBD also caused reconsolidation impairments when injected directly into the AC or PL but not the IL. Together, these findings show complementary mechanisms through which CBD may hinder the reconsolidation of destabilized aversive memories along the dorsoventral axis of the mPFC.

Associating Aversive Task Exposure with Pharmacological Intervention to Model Traumatic Memories in Laboratory Rodents

Springer eBooks, 2023

Revisitando os mecanismos de modulação noradrenérgica sobre as memórias de medo: do fisiológico ao disfuncional

Tese apresentada como requisito parcial para a obtenção do título de Doutor em Farmacologia, pelo

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research article PTSD-Like Memory Generated Through Enhanced Noradrenergic Activity is Mitigated by a Dual Step Pharmacological Intervention Targeting its

This is an Open Access article distributed under the terms of the Creative Commons Attribution No... more

Association of genetic markers with ischemic stroke in pediatric patients with sickle cell anemia

São Paulo Medical Journal, 2021

Introduction: Sickle cell anemia (SCA) is characterized by complex clinical heterogeneity. Amongs... more Introduction: Sickle cell anemia (SCA) is characterized by complex clinical heterogeneity. Amongst them, ischemic stroke (IS) stands out because it affects 8% to 12% of patients up to the age of 20, with a mortality rate of 20% in untreated cases. Objectives: To evaluate the association of SNPs -786T/C NOS3 and C667T MTHFR in the occurrence of IS in SCA pediatric patients undergoing regular blood transfusion. Methods: Ninety SCA pediatric patients 12.1±3.3 years old being followed-up at HEMORIO/RJ, divided into Patients with IS in hypertransfusion (n=20) and Patients without IS not transfused (n=70). Results: IS Group: genotypic frequencies: -786T/C NOS3, 4 (20%) CC, 4 (20%) CT and 22 (60%) TT; C667T MTHFR, 3 (15%) TT, 2 (10%) CT and 15 (75%) CC. Group without IS: genotypic frequencies: -786T/C NOS3, 1 (1.4%) CC, 25 (35.7%) CT and 44 (62.8%) TT; C667T MTHFR, 1 (1.4%) TT, 18 (25.7%) CT and 51 (72.8%) CC. Chisquare test revealed association of SNPs -786T/C NOS3 (p = 0,017) and C667T M...

adrenergic receptors β and 1-α consolidation and reconsolidation by differentially recruiting Enhanced noradrenergic activity potentiates fear memory

Medial prefrontal cortex mechanisms of cannabidiol-induced aversive memory reconsolidation impairments

Neuropharmacology, 2022

Growing evidence indicates that cannabidiol (CBD), a substance present in the Cannabis sativa pla... more Growing evidence indicates that cannabidiol (CBD), a substance present in the Cannabis sativa plant, has potential therapeutic value to regulate abnormal emotional memories associated with post-traumatic stress and drug use disorders. CBD can attenuate their valence after retrieval (i.e., during reconsolidation) or potentiate their suppression by extinction. Pharmacological research has now focused on elucidating how it acts. Systemic antagonism of cannabinoid type-1 (CB1) receptors has often prevented the abovementioned effects of CBD. However, it is unknown which brain regions CBD stimulates CB1 receptors and how it interferes with local activity-related plasticity to produce these effects. The present study addressed these questions considering the reconsolidation of contextual fear memories in rats. We focused on the medial prefrontal cortex (mPFC), which comprises the anterior cingulate (AC), prelimbic (PL), and infralimbic (IL) subregions, as local activity or plasticity has been associated with the process to-be-investigated. Animals that received post-retrieval systemic CBD treatment presented relatively fewer cells expressing Zif268/Egr1 protein, a proxy for synaptic plasticity related to reconsolidation, in the AC and PL. At the same time, there were no significant differences in the IL. Pretreatment with the CB1 receptor antagonist AM251 into the AC, PL, or IL prevented the impairing effects of systemic CBD treatment on reconsolidation. CBD also caused reconsolidation impairments when injected directly into the AC or PL but not the IL. Together, these findings show complementary mechanisms through which CBD may hinder the reconsolidation of destabilized aversive memories along the dorsoventral axis of the mPFC.

A Inibição da síntese proteica no hipocampo dorsal de ratos impede a tolerância ao midazolam induzida pela experiência prévia no labirinto em cruz elevado

Ao professor Leandro José Bertoglio, pela confiança depositada e disposição em me acompanhar e or... more Ao professor Leandro José Bertoglio, pela confiança depositada e disposição em me acompanhar e orientar na realização desse trabalho, bem como pelo crescimento pessoal proporcionado. Aos professores Antônio de Pádua Carobrez e Thereza Christina Monteiro de Lima por disponibilizarem seus laboratórios quando precisei. Aos demais professores da Pós-Graduação em Farmacologia pela contribuição na minha formação. Aos professores Dr. Roberto Andreatini, Dr. Rui Daniel Schröder Prediger e Dr. André de Ávila Ramos, por aceitarem o convite para compor a banca e pela colaboração no aperfeiçoamento desse trabalho. Aos meus pais, Vanderlei e Ivanir, pelo esforço e apoio constantes para que eu pudesse ter uma formação concreta, bem como pelas influências positivas para a construção do meu caráter e educação. À minha irmã, Janaina, pela companhia desde sempre, conselhos e inspiração. À professora Dra. Rúbia Weffort de Oliveira, pelos ensinamentos, apoio constante, confiança e amizade. Os meus grandes amigos, Camila, Kássia, Monica, Tiago e Jeanne, sempre presentes. Aos meus amigos de departamento Thaize, Filipe, Evelyn, Ana Paula, Andressa, Claudini, Ju Kroon, Grasi, Eloisa e Cris Mochny, pelos momentos bons, diversão, ideias e sugestões. Aos companheiros de laboratório Ana, Cris Stern, Rafael, Shirlley e Thaís, pela amizade, paciência, disposição, trabalho em conjunto e por tudo que me ensinaram. Aos funcionários do departamento e demais colegas da pósgraduação e a todos os que, de alguma maneira, colaboraram no andamento desse trabalho. À CAPES, CNPq e FAPESC, pelo apoio financeiro.

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Educação Em Saúde Sobre Gravidez Na Adolescência: Um Relato De Experiência

Educação em Saúde na Escola: Relatos de Experiência, 2019

Todo o conteúdo deste livro está licenciado sob uma Licença de Atribuição Creative Commons. Atrib... more Todo o conteúdo deste livro está licenciado sob uma Licença de Atribuição Creative Commons. Atribuição 4.0 Internacional (CC BY 4.0). O conteúdo dos artigos e seus dados em sua forma, correção e confiabilidade são de responsabilidade exclusiva dos autores. Permitido o download da obra e o compartilhamento desde que sejam atribuídos créditos aos autores, mas sem a possibilidade de alterá-la de nenhuma forma ou utilizá-la para fins comerciais.

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