Mestrado em Bioquímica

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http://repositorio.ufes.br/handle/10/17562

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Alterações comportamentais, bioquímicas e moleculares em modelo animal de inalação crônica de "crack" : papel dos sistemas dopaminérgico e endocanabinóide no córtex pré-frontal
(Universidade Federal do Espírito Santo, 2014-07-17) Azevedo, Lorena Bianchine Areal de; Martins e Silva, Cristina; Pires, Rita Gomes Wanderley; Bittencourt, Ana Paula Santana de Vasconcellos; Ribeiro, Fabiola Mara
abstract
Análise da expressão de potenciais inflamassomas envolvidos na quimiorresistência adquirida à cisplatina em modelo in vitro de carcinoma de ovário seroso de alto grau
(Universidade Federal do Espírito Santo, 2018-10-08) Silva, Ana Maria Rodrigues da; Rangel, Letícia Batista Azevedo; Salgado, Breno Souza; Lyra Junior, Paulo Cilas Morais
High-grade serous ovarian cancer (HGS-OC) is the most frequent cause of deaths among gynecological malignancies. Due to their asymptomatic development as well as the lack of sensitive and specific screening methods, the disease is diagnosed in advanced and incurable stages. Although tumors usually respond to first line taxanes and platinum-based chemotherapy, most patients develop relapse and chemoresistance. Inflammation has been involved in the initiation and development of many types of cancer, including HGS-OC. Recently, the protein components of the innate immune system, known as inflammassome, have been associated with the mechanisms of progression and metastasis of neoplasias, however, it’s role in drugresistance is little explored. In this study, through RT-PCR and western blot analysis we investigated the clinical significance of inflammassomas in modulating the chemoresistant phenotype in cisplatin-resistant cells (ACRP) obtained from the parental line of HGS-OC (A2780). Our results have shown that, even though mRNA expression levels of NLRP3 remained unaltered in the ACRP, the NLRP3 protein expression appears to vary in a dose-dependent way with cisplatin treatment, although it does not configure the main event in chemoresistance. An increase in mRNA expression levels of the NLRP1, but not of NLRC4, in resistant cell line ACRP was also obtained. In conclusion, our study was the first to show the involvement of NLRP1 inflammassome in the development and regulation of cisplatin-resistance in HGS-OC cells, making it an attractive target with great therapeutic potential against the disease.
Avaliação da expressão dos genes DNAHC6, DYNLT1, Pcdh21, SIGMAR1, Lingo1 e Gabra2 como marcadores moleculares na Doença de Huntington
(Universidade Federal do Espírito Santo, 2018-09-27) Mendonça, Suellen Rosseto; Pires, Rita Gomes Wanderley; Bem, Daniela Amorim Melgaço Guimarães do; Silva, Cristina Martins e; Muniz, Marcelo Ramos; Errera, Flavia Imbroisi Valle
abstract
Avaliação dos efeitos tóxicos da exposição ao inseticida clorpirifós sobre as respostas cardiovasculares e comportamentais em animais experimentais
(Universidade Federal do Espírito Santo, 2014-07-23) Cunha, Alexandre Frinhani; Sampaio, Karla Nívea; Andrade, Tadeu Uggere de; Moraes, Leonardo Resstel Barbosa
abstract
Avaliação dos parâmetros comportamentais e de estresse oxidativo em animais submetidos à separação maternal e ao consumo de etanol em binge durante a adolescência
(Universidade Federal do Espírito Santo, 2016-09-16) Telles, Vanessa Ghidetti Alvarenga; Rodrigues, Lívia Carla de Melo; Bittencourt, Ana Paula Santana de Vasconcellos; Dalmaz, Carla; Gonçalves, Juliana Barbosa Coitinho
Early life stress can generate long-lasting effects on brain and behavior during adulthood. Furthermore, stressful experiences stimulate abusive consumption of ethanol, which induces neuronal damages and contributes to increases on parameters of oxidative stress on Central Nervous System. The aim of this research was to evaluate the effects of Maternal Separation (MS) and of intermittent ethanol binge drinking in adolescent rats on behavioral and oxidative stress parameters. Pregnant Wistar rats were used. After birth of litters, the animals were divided into control group (NS) or maternal separation group (MS). Maternal separation was performed from 2 to 15 postnatal day, 3 hours daily. At postnatal day 35, animals were divided again into 3 groups: animals which received intragastric saline (vehicle group) or ethanol in doses of 3.0 or 6.0 g/kg. Ethanol was administered once a day, in a regimen of two consecutive days interspersed by two days without ethanol, totalizing 10 doses for chronic binge treatments. Acute binge exposure happened at postnatal day 35 until 37 postnatal day.
Avaliação físico-química de nanopartículas de ouro reduzidas com citrato de sódio e capeadas com Virola oleifera
(Universidade Federal do Espírito Santo, 2017-06-30) Corrêa, Andressa dos Santos; Oliveira, Jairo Pinto de; Guimarães, Marco Cesar Cunegundes; Nogueira, Breno Valentim; Silva, André Romero da
The capping of gold nanocrystals using sodium citrate with Virola oleifera was the focus of this thesis, which aim/aiming at synthesize and characterize evaluate the final extract concentration and pH influence in surface particle adsorption. Furthermore, was analysed antioxidant activity and citotoxicity of AuNPs, for investigate your potential biological application. For this goal, the best capping time, and subsequently the optimum pH range and final extract concentration was determined and was realizes a 32 factorial design with 3 levels and 2 variables (pH and extract concentration) to verify the optimal capping conditions. In this way, it has been proved the adsorption was most intense between pH 3 and 5 and the most stable was the lower final extract concentration. The x-ray diffraction and the transmission electron microscopy confirmed the face-centered cubic structure of citrate AuNPs and the quasi spherical aspect, respectively. The adsorption of aromatic molecules was confirmed by spectroscopy techniques: Fourier-Transform Infrared (FTIR) and Raman. The DPPH and FRAP analyzes shows enhancement of antioxidant activity with capping of citrate gold nanoparticles. Furthermore, the citotoxicity assay shows low citotoxicity of capped gold nanoparticles.
Bases moleculares envolvidas na neuroproteção causada pela exposição a um ambiente enriquecido em modelo animal de isquemia cerebral
(Universidade Federal do Espírito Santo, 2017-07-07) Gonçalves, Lara Vezula; Pires, Rita Gomes Wanderley; Silva, Cristina Martins e; Massensini, Andre Ricardo; Nogueira, Breno Valentim
abstract
Caracterização físico-química da isoforma γ-tripsina bovina
(Universidade Federal do Espírito Santo, 2014-06-26) Lacerda, Caroline Dutra; Santos, Alexandre Martins Costa; Santana, Marcos Aurélio de Santana; Ribeiro, Joselito Nardy; Pires, Rita Gomes Wanderley
A novel bovine trypsin isoform was purified from commercial sample by ion exchange chromatography by Sephadex SP C50®. New isoform contain in addition of loss of N- terminus hexapeptide (as found in parent molecule β-trypsin) an intra-chain split between Lys-155 and Ser-156. The novel enzyme denominate gamma-trypsin showed similar properties with α-trypsin isoform in: polypeptide number chain (two chain), molecular masses (23,312 Da), secondary structure, hydrodynamic radius and others. In spite of enzymatic and structural similarities of both isoforms, -trypsin preferably has a lower rate formation from β-trypsin, a lower surface charge, but the gamma-trypsin has a higher thermal stability than α-trypsin. Due to obtaining facility of purification of bovine trypsin isoforms from commercial font, and properties described above, become this enzyme an interesting alternative for the food industry, detergent and biocatalysis research.
Caracterizações bioquímica e hemostática de pacientes com diabetes Mellitus Tipo 2 em insulinização
(Universidade Federal do Espírito Santo, 2014-07-15) Gonçalves, Nadmy Arrivabene Zavaris; Bem, Daniela Amorim Melgaço Guimarães do; Vassalo, Breno Valentim; Gomes, Isabele Beserra Santos
The study aims to characterize biochemically and hemostatic mellitos patients with diabetes mellitus type 2 (DM2) who developed insulin regimen. Composed group under analysis, 40 patients attended the Basic Health Unit of Consolation, Vitória / ES, aged 25 to 80 years, diagnosed with DM2 and that were already evoluted to insulinization. As controls, 40 patients were selected in the same age group without laboratory and / or clinical diagnosis of DM. Markers of inflammation, hypercoagulability and fibrinolysis were measured: Fibrinogen, D-dimer (D-Di) and plasminogen activator type 1 inhibitor (PAI-1). The polymorphism (-675 4G/5G) in the promoter region of the PAI-1 gene was correlated with their serum levels. Biochemical parameters were measured: plasma glucose (PG), glycated hemoglobin (A1C), total cholesterol (TC), HDL cholesterol (HDL-C), LDL (LDLc) cholesterol, triglycerides (TGC), ultrasensitive C reactive protein (hsCRP), urea and serum creatinine. There was still checking BMI, obesity, smoking, hypothyroidism, hypertension, dyslipidemia and insulin resistance. Statistical analysis showed significant differences (p <0.05) between groups with regard to mean values of HDLC, VLDL-C, TGC, urea, hsCRP and fibrinogen. There was significant difference between groups for VLDLc, TGC, creatinine and fibrinogen. Controls present correlations between: fibrinogen and glucose, hsCRP and fibrinogen, PAI-1 and glucose, PAI-1 and BMI. In insulinization DM2 group correlation was observed correlation between: fibrinogen and D-di, hsCRP and fibrinogen, D-Di and glucose (negative), PAI-1 and triglycerides, PAI-1 and BMI. PAI-1 levels were higher in the control group in subjects with genotype 5G5G, 4G5G and 4G4G followed. Binary Logistic Regression confirmed that the variables hypertension and fibrinogen were significant at p-value (0.009) and (0.049) and adjusted odds ratio (4.184, 1.426 to 12.276) and (3.293, 1.006 to 10.775), respectively, showing that hypertensive patients have a risk 4.18 times more likely to have insulinization type 2 diabetes and that individuals with hyperfibrinogenemia have a 3.29 times greater risk. With this study we hope to contribute to better understanding of the complex changes that accompany the user insulinization type 2 diabetic patients in expectation of seeking appropriate treatment and prevention for the macrovascular complications of diabetes.
Coloração de espécimes anatômicos para aplicação no processo de plastinação por meio de corantes histológicos : floxina b, safranina, fucsina fenicada e tricrômico de masson
(Universidade Federal do Espírito Santo, 2018-09-17) Siqueira, Bruno Magela de Melo; Bittencourt, Ana Paula Santana de Vasconcellos; Bittencourt, Athelson Stefanon; Silva, André Romero da; Ribeiro, Joselito Nardy
The Study of Anatomy has been known for several centuries and before this, every moment has generated several repercussions in this area of biomedical sciences. Even with advancement in the technological sectors, the teaching of anatomical concepts through corpses in health courses is still essential. A more common way of preserving anatomical parts for studies is through a substance that was discovered in 1867 by German Hoffman by accident: formaldehyde, but such substance has an unpleasant odor and irritates the nasal passages and the eye region. Plastination is the newest in terms of technology for the preservation of anatomical specimens. This technique was developed by the German Dr. von Hagens in 1977 and its principles reflect in the idea of impregnating polymers (silicone, epoxy or polyester) in biological tissues, removing the fat and water present, thus increasing their durability and with aspects close to the original object. Plastination is free from toxic conservative substances, thus facilitating its role for didactic and scientific purposes. The dye is used for a better visualization of the structures in the anatomical part and thus ending with that aspect of worn, emphasizing the true color of the object. In view of the above, has developed a staining protocol in skeletal muscle tissue, applied to the Plastination technique with the following dyes: Phloxine B, Safranin, Phenicated Fuchsin and Masson's Trichrome. The interaction of the dye with the muscle tissue, fat and epithelial tissue of the samples that were used for the research was evaluated. All the dyes used in the macroscopic staining were able to show certain structures such as tendon, fascia and connective tissue inside the muscle. It was also evaluated the photodegradation of these dyes in solution. It was noticed that the dyes that obtained more satisfactory results in relation to the dyeing of the specimens were those of anionic character: Phloxine B and Masson's Trichrome, but in relation to the resistance of the dyes in light exposure, it was not possible to choose the one that obtained the best because the solutions exhibited different behaviors when exposed to light. The final protocol for the staining muscle tissues will be applied in the collection of the Life Sciences Museum of the Federal University of Espírito Santo and in the Department of Morphology of the same University.
Determinação da atividade e da estabilidade termodinâmica da isoforma α-tripsina bovina em meios aquo-orgânicos
(Universidade Federal do Espírito Santo, 2015-02-24) Pereira, Evaldo Vitor; Gonçalves, Juliana Barbosa Coitinho; Santos, Alexandre Martins Costa; Pires, Rita Gomes Wanderley; Fernandes, Patrícia Machado Bueno; Bemquerer, Marcelo Porto
abstract
Determinação de parâmetros estruturais e termodinâmicos da isoforma a-tripsina bovina em solventes aquo-orgânicos
(Universidade Federal do Espírito Santo, 2017-02-23) Rosa, Dayanne Pinho; Gonçalves, Juliana Barbosa Coitinho; Santos, Alexandre Martins Costa; Fernandes, Patrícia Machado Bueno; Cicilini, Maria Aparecida; Bem, Daniela Amorim Melgaço Guimaraes do
Organic solvents are common in industrial processes that use enzymes but, at the same time, it is known that they change the properties thereof, thus the effects of aqueous-organic solvent (ethanol) in different concentration on the α-trypsin structure have been investigated by spectroscopic techniques and thermodynamic data analysis. The results from spectroscopic measurements, including far-UV Circular Dichroism, UV-Vis absorption spectroscopy, intrinsic tryptophan fluorescence and dynamic light scattering (DLS) suggest the formation of partially folded states, instead of aggregates states, at high ethanol concentration (> 60% v/v ethanol), with little loss of secondary structure, but with significant tertiary structure changes. The thermodynamic data (Tm and ∆H) suggest a loosen of intramolecular weak interactions, which reflects in a flexibility increase such that the catalytic capacity can be increased or decreased according to the ethanol concentration into the system. Overall results we suggest that in range of 0-60% v/v ethanol/buffer, α-trypsin undergoes reversible multimerization phenomena maintaining its catalytic activity. However from 60% v/v ethanol/buffer, population of folded partially states with less catalytic activity are predominant.
Efeito da separação maternal sobre a impulsividade, consumo voluntário de etanol e expressão de componentes do sistema endocanabinóide e dopaminérgico em córtex pré-frontal e hipocampo : influência do consumo de etanol em binge na adolescência
(Universidade Federal do Espírito Santo, 2016-09-16) Mata, Martielo Januário da; Bittencourt, Ana Paula Santana de Vasconcellos; Dalmaz, Carla; Pires, Rita Gomes Wanderley
Maternal separation is an animal model used to mimic stressful events in the neonatal period, which may lead to the development of cognitive impairments and substances abuse, such as ethanol. This substance is a potential risk to health due to its high consumption by young people, and its consumption alters behavior and neurotransmitter systems function, such as dopaminergic and endocannabinoid systems. In this study, we evaluate the influence of ethanol binge drinking in adolescent rats subjected to maternal separation on learning, impulsivity and voluntary ethanol consumption in adulthood, as well as (the effects of these treatments) on the endocannabinoid and dopaminergic systems. For this, male Wistar rats were separated from their mothers or not (control group) during the postnatal days (DPN) 2-15, for 3 hours daily. Animals not separated were kept on animal facility reared conditions. At DPN 35, the animals were divided in acute or chronic treatment. Both groups were again divided into 3 subgroups, which receive vehicle (saline) or ethanol in doses of 3.0 or 6.0 g/kg by intragastric administration. Ethanol was administered during three consecutive days (acute treatment) or once a day, two consecutive days, interspersed by two days without ethanol, totalizing 10 doses (chronic treatment). At the end of this procedure, the animals were subjected to behavioral tests (learning and impulsivity tests), both using a T-maze, and to the voluntary ethanol consumption test, or euthanized for prefrontal cortex and hippocampus removal. The mRNA expression of the components of the endocannabinoid system: CB1, monoacylglycerol lipase, fatty acid amide hydrolase, N-acylphosphatidylethanolamine phospholipase D and diacylglycerol lipase were evaluated in both structures, and the dopaminergic receptors D1, D2 and tyrosine hydroxylase enzyme were evaluated only in the prefrontal cortex. We observed that maternal separation increased impulsivity behavior and voluntary consumption of ethanol, and ethanol in adolescence impaired short-term memory and appears to reverse other behavioral changes due to maternal separation. In the prefrontal cortex, maternal separation and ethanol altered dopaminergic system with reduction of D1 mRNA expression and increased tyrosine hydroxylase, and appears to increase the enzymes for endocannabinoid synthesis, N-acyl-phosphatidylethanolamine phospholipase D e diacylglycerol 17 lipase. In the hippocampus, the group submitted to both treatments presented a reduction of CB1 mRNA expression and the enzyme N-acylphosphatidylethanolamine phospholipase D, and an increased expression of diacylglycerol lipase. In conclusion, maternal separation and ethanol were able to cause behavioral changes and modifications in endocannabinoid and dopaminergic systems, and maternal separation modifies ethanol effects response.
Efeito de diferentes agonistas de receptores galaninérgicos no núcleo dorsal da rafe de ratos expostos a modelos animais de ansiedade e pânico
(Universidade Federal do Espírito Santo, 2015-02-26) Morais, Juliana da Silva; Harres, Vanessa Beijamini; Bittencourt, Athelson Stefanon; Andreatini, Roberto
Galanin (GAL) is a peptide present in the CNS of various mammals, including human being. Three different receptors have been cloned for the GAL, GALR1 and GALR3, inhibitory, and GALR2, excitatory. The distribution of GAL in structures involved in the control of emotions, and behavior studies suggest that GAL may be involved in the neurobiology of anxiety. The effect seems to depend on both the GAL administration site as involved receptor subtype. The dorsal raphe nucleus (DRN) is distinguished by the presence of serotonergic neurons, important to mediate the antidepressant effect of several drugs. About 40% of the neurons of the DRN co-expressing serotonin and GAL. The activation of GALR1 in this structure decreases the firing rate of serotonergic neurons in the DRN. Previous results from our laboratory showed anxiolytic effect of GAL intra-DRN in rats exposed to the elevated T maze (ETM), but no effect on the escape, related to panic. One of the limitations of this model is that the escape (latency to leave the open arm) usually occurs within a few seconds, so that detect panicogenic effect (low latency escape) can be difficult. Thus, one aim of this study was to investigate the effect of intra-DRN rat GAL in another experimental model of panic, electrical stimulation of the dorsal periaqueductal gray matter (DPAG), more sensitive to detect panicogenic effect. Furthermore, given the existence of different subtypes of galaninergic receptors (GALR1 and GALR2) in the DRN with opposite transduction mechanisms, inhibitory and excitatory, respectively, it is possible that activation of GALR1 receptors is responsible for mediating the anxiolytic/panicogenic effect while activation of GALR2 receptors induces anxiogenic/panicolytic effect. Accordingly, we tested this hypothesis using a selective agonist for GALR1 (M617) and a selective agonist for GALR2 (AR-M1896) in the DRN in rats exposed to ETM. The administration of M617 1.0 and 3.0 nmol in the DRN facilitated inhibitory avoidance, suggesting an anxiogenic-like effect., while administration of AR-M1896 3,0nmoles in the DRN impaired the inhibitory avoidance, suggesting an anxiolytic-like effect, both without changing locomotor activity of animals tested in the open field. Also there was no effect of these drugs on the ETM escape behavior. Later, the pre-treatment with WAY100635 was tested in order to verify that administration of a 5-HT1A antagonist would be able to block the effects seen with GALR2 agonist in animals exposed to ETM. The anxiolytic effect of AR-M1896 was attenuated by the prior administration of WAY100635 at a dose of 0,18nmol. Therefore these results suggest a relationship between the observed effect with the AR-M1896, the release of 5-HT and activation of 5-HT1A receptors. And finally, the GAL 0,3nmol intra-DRN increased significantly the jumpping and trotting thresholds of animals submitted to electrical stimulation of the DPAG, suggesting a panicolytic effect. Together, the results show that the GAL in the DRN participates in the mediation of behavioral responses related to anxiety and, less clearly, to Panic Disorder. The results also shows that effect of GAL on anxiety depends galaninergic subtype receptor activated.
Efeito de diferentes tempos de exposição a um ambiente enriquecido na memória de camundongos : uma abordagem comportamental e molecular
(Universidade Federal do Espírito Santo, 2015-12-11) Rohor, Bruna Zanetti; Martins e Silva, Cristina; Pires, Rita Gomes Wanderley; Bittencourt, Ana Paula Santana de Vasconcellos; Rodrigues, Lívia Carla de Melo
The environment is formed by a set of situations around the individual and has influence on all organisms. A stressor environment has negative influences in a subject, but an enriched environment (EE) has positive influences. In animals, the AE is defined as a combination of inanimate and social complex stimuli that can improve motor, cognitive and sensory functions. The EE is composed of different objects of different shapes, sizes, colors, textures, among others. Environmental novelty, voluntary physical activity and social interaction are also part of EE. The EE is capable of promoting increased visual, sensory, cognitive and motor functions. Cognitive improvement, increased synaptic plasticity, adult hippocampal neurogenesis, modulation of gene expression and changes in levels of neurotransmitters and neurotrophic factors are EE-induced alterations already described. However, several EE paradigms are found in the literature, and this variety of protocols produces a range of controversial results on the effects induced by EE.
Efeitos comportamentais da cetamina em ratos expostos ao labirinto em T elevado : possível envolvimento da via de sinalização de BDNF/TrkB na matéria cinzenta periaquedutal (MCP)
(Universidade Federal do Espírito Santo, 2016-04-06) Silote, Gabriela Pandini; Joca, Sâmia Regiane Lourenço; Harres, Vanessa Beijamini; Hott, Sara Cristina; Schenberg, Luiz Carlos
abstract
Efeitos da exposição a um ambiente enriquecido sobre parâmetros comportamentais, bioquímicos e moleculares em um modelo murino da doença de Parkinson
(Universidade Federal do Espírito Santo, 2015-08-05) Hilário, Willyan Franco; Silva, Cristina Martins e; Pires, Rita Gomes Wanderley; Nakamura-Palacios, Ester Miyuki; Rodrigues, Lívia Carla de Melo
abstract
Efeitos de inibidores da DNA metiltransferase na modulação de comportamentos aversivos relacionados à ansiedade
(Universidade Federal do Espírito Santo, 2017-12-15) Oliveira, Mayana Cardoso de; Harres, Vanessa Beijamini; Bortoli, Valquíria Camin de; Rodrigues, Lívia Carla de Melo; Bem, Daniela Amorim Melgaço Guimarães do
Anxiety disorders such as generalized anxiety disorder (GAD) and panic disorder (PT), cause significant impacts on the lives of patients affected by them. Pharmacological treatment of GAD and PT presents problems of efficacy and safety. In this sense, new pharmacological targets have been studied in order to develop more effective treatment options. The pathogenesis of anxiety disorders is complex in nature and interacts with environmental and biological factors, particularly genetic factors. Recently, it has been shown that epigenetic processes can influence gene regulation and mediate adaptation to environmental factors in mental disorders, characterized by a stable hereditary phenotype resulting from changes in the chromosome without changes in the DNA sequence. Epigenetic modifications include changes in DNA, such as methylation, which consists of the addition of a methyl (CH3) catalyzed enzyme by DNA methyltransferases (DNMTs).
Efeitos do isolamento social neonatal, da fluoxetina e do lactato de sódio sobre o pânico experimental induzido por cianeto de potássio ou estimulação da matéria cinzenta periaquedutal em ratos
(Universidade Federal do Espírito Santo, 2015-08-31) Moraes, Erich Antonio; Schenberg, Luiz Carlos; Harres, Vanessa Beijamini; Sampaio, Karla Nivea
Panic attacks (PAs) can be precipitated either by the inhalation of 5% carbon dioxide (CO2) or by the infusion of 0.5 mol/L sodium lactate (LAC) in predisposed patients, but not in healthy subjects or patients with other psychiatric disorders. These and other observations suggested that PAs are "suffocation false alarms". The panic disorder is likewise characterized by the high comorbidity with childhood separation anxiety (CSA). Consequently, the CSA has been considered both as a predisposing factor of panic and as an important factor of the resistance to panicolitics. Preclinical studies of our laboratory showed, on the other hand, that panicolitics attenuate experimental panic attacks to both the electrical stimulation of the dorsal periaqueductal gray matter (DPAG) and the intravenous injection of potassium cyanide (KCN) in doses and regimenssimilar to those used in the clinics. These studies also showed that neonatal social isolation, a model of CSA, supress the panicolitic effect of fluoxetine (FLX, 1-2 mg.kg-1.dia-1, 21 days) on panic-like responses to electrical stimulation of DPAG. Therefore, the present study evaluated the effects of a higher dose of FLX (Experiment-1) as well as of the infusion of LAC (Experiment-2) on PAs to electrical stimulations of DPAG or to intravenous injections of KCN, respectively, in rats subjected to social isolation as neonates. In Experiment-1, adult male Wistar rats subjected either to 3-h daily neonatal social isolation (NSI) or brief-handling fictive social isolation (FSI) throughout the lactation period, were implanted with electrodes into the DPAG and treated with saline (0.9%, SAL) or fluoxetine (4 mg.kg-1.dia-1, FLX4) over 21 days. Although the panic thresholds remained virtually unchanged in SAL-treated FSI rats, they were progressively increased in SAL-treated NSI rats. Moreover, FLX4-treated rats showed higher thresholds that those treated with SAL. However, comparison to baseline thresholds showed that FLX4 had differential effects on FSI and NSI groups, increasing or reducing thresholds, respectively. Although there were no significant differences between ISF and FSI at the end of the treatment with FLX4, the threshold percent changes relative to baseline suggest that FLX4 had effects even facilitatory on panic responses. The resistance of neonatally-isolated rats to FLX4 extended previous studies with smaller doses of FLX. In turn, the results of Experiment-2 showed that intravenous infusion of a clinically effective concentration of LAC (0.5 mol/L) does not have any effect on the escape responses to KCN in rats either virgin or submitted to the FSI or NSI. Although the latter results suggest that panics to both KCN (experimental) and LAC (clinical) are mediated by different systems, conclusions require further experiments with higher concentrations of LAC.
Efeitos do tratamento com ácido rosmarínico em parâmetros bioquímicos e motores em modelo pré clínico da doença de Parkinson
(Universidade Federal do Espírito Santo, 2018-03-23) Silva, Sarah Martins Presti da; Silva, Cristina Martins e; Pires, Rita Gomes Wanderley; Figueiredo, Suely Gomes de; Harres, Vanessa Beijamini
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Currently, the main therapeutic approach relieves only motor symptoms, however, it does not prevent or stop the neurodegeneration. Rosmarinic Acid (RA) is an ester of caffeic and 3,4-dihydroxyphenylacetic acids obtained from many plant species such as Salvia officinalis L. (sage) and Rosmarinus officinalis (rosemary). This compound has a wide collection of biological activities, antioxidant and free radical scavenging being key factors in the in vivo outcomes reported for RA, howerer, the literature is scarce in studies showing the effects of RA on healthy animals and MPTP treated animals.

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