Doutorado em Ciências Biológicas (ICB)

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    Efeitos cardiometabólicos e renais de peptídeos bioativos do feijão comum (phaseolus vulgaris)
    (Universidade Federal de Goiás, 2022-08-18) Ribeiro, Juliana Vila Verde; Batista, Karla de Aleluia; http://lattes.cnpq.br/9859814532588957; Custódio, Carlos Henrique Xavier; http://lattes.cnpq.br/0207928273284808; Custodio, Carlos Henrique Xavier; Batista, Karla de Aleluia; Torsoni , Marcio Alberto; Sant'Ana, Anderson de Souza; Gomes, Rodrigo Mello
    The common bean is susceptible to the hardening process and once hardened, it is not commercialized, being considered an agroindustry residue. However, it is possible to use it as a source of proteins and bioactive peptides. The bean bioactive peptides may have antihypertensive, antihyperglycemic, hypoglycemic, antioxidant and hypocholesterolemic activity. Thus, this work sought to study the bioactivity of the low molecular weight peptide fraction extracted from hardened common bean (Phaseolus vulgaris) grains on renal, cardiovascular and metabolic functions. To evaluate the effect of the common bean peptide, the following methodologies were used: I) Obtaining the extract and peptide fraction – from the hardened beans, flour was made using a knife mill. This flour was used to extract the peptides and proteins, using a combined solution of acetonitrile, water and formic acid (25: 24: 1), this extract was subjected to the fractionation process, using a 3 kDa filtration membrane, this extract was named as PV3. II) Comparison of PV3 amino acid sequences with other amino acid sequences reported by other authors. III) Evaluation of osmolarity and sodium and potassium ions in the PV3 extract. IV) Evaluation of the vasorelaxant effect and physiological mechanisms involved in vasorelaxation in renal artery rings from normotensive (Wistar) and hypertensive (SHR) animals. V) Evaluation of renal parameters in WT and SHR animals. VI) Evaluation of hemodynamic parameters in WT and SHR. VII) Evaluation of body mass gains and food consumption in C57BL6/6J mice submitted to a high-fat diet and administration of PV3 by pseudogavem. VIII) Assessment of glycemic levels, pyruvate, insulin and pyruvate tolerance test. IX) Evaluation of the mechanisms involved in PV3 in the insulin pathway by Western Blotting and qPCR. X) evaluation of the energy metabolism of PV3 by q PCR. The main results of this study are: I) homology of amino acid sequences of PV3 with several amino acid sequences described in the literature that show antihypertensive activity, II) PV3 causes a relaxing effect dependent on the endothelium and oxidonitrergic pathways; III) PV3 caused a natriuretic effect and decreased the glomerular filtration rate; IV) PV3 caused a hypotensive effect that was concomitant to a reduction in vascular resistance in the aortic and renal vascular beds; V) PV3 prevented the damage caused by the hyperlipidic diet, such as reduction of adiposity and glycemic levels.; VI) PV3 acts on the IRS/PI3K and AMPK pathway to reduce glycemic levels; 22 VII) PV3 acts in the regulation of energy balance. Such findings are relevant for the molecular and physiological study of bioactive peptides of food origin; and these results contribute to the use of hardened beans in the formulation of nutraceutical foods to treat hypertension, type 2 diabetes and obesity.
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    Análise metabólica em ratos Wistar submetidos à dessincronização circadiana forçada e alimentação em tempo restrito
    (Universidade Federal de Goiás, 2023-01-26) Oliveira, Isis Gabrielli Barbieri de; Rosa, Daniel Alves; http://lattes.cnpq.br/5848020104921718; Rosa, Daniel Alves; Pansani, Aline Priscila; Araújo, John Fontenele; Torsoni, Marcio Alberto; Iglesia, Horacio de la
    The suprachiasmatic nucleus is part of a multi-oscillatory timing system in mammals, regulating various physiological rhythms and under modulation by internal or environmental synchronizers, among them: the light-dark cycle (LD), the most important photic synchronizer of this system. However, non-photic synchronizers such as food availability remain more unclear. Here, we use Wistar rats (250-300g) randomly distributed into four groups: control CTR AL under a symmetrical cycle of 12:12h LD and ad libitum food availability or CTR RF with time-restricted feeding (TRF); DSC AL submitted to the forced circadian desynchronization protocol under a symmetrical cycle of 11:11h LD with ad libitum food availability and DSC RF with TRF, during eight weeks to evaluate the impact of DSC and TRF on locomotor activity, hepatic metabolism and on the antioxidant system. During the eighth week, all animals were submitted to the insulin and glucose tolerance test – ipITT and oGTT. After 48h of recovery, they were euthanized. Plasma, liver and hypothalamus samples were removed and stored for biochemical analyses, Western blotting and RT-qPCR. Results: As expected, all DSC animals showed dissociation of the locomotor activity rhythm. TRF increased the rate of dyssynchrony in the DSC RF group, indicating dominance of the light-entrained component (LEC). DSC or TRF separately did not alter total food intake or body mass, but the association of both included total food intake, reflecting on the evolution of body mass. However, the separate analysis of food intake in the LD phases demonstrates that in the light phase intake is higher in the DSC group when compared to the CTR AL.TRF promotes simultaneous increase of NPY and CART only in animals under LD cycle 12:12h. DSC increased DSC increased the gene expression of PTEN, PTPN1 and G6Pase, the PI3K protein, the activity of SOD-1 and catalase enzymes and the oxidative stress biomarkers TBARS and protein carbonyl in the liver, but TRF attenuated only the effects on G6Pase and PI3K. Conclusion: In summary, these findings show that forced desynchronization increases considerable oxidative stress and promotes changes in insulin signaling in liver, which were not attenuated by the association with TRF
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    Efeito tipo-antidepressivo do derivado piperazínico 2,6-di-terc-butil-4-((4-(2-hidroxietil)piperazina-1-il)metil)fenol (LQFM212) e possíveis mecanismos de ação envolvidos
    (Universidade Federal de Goiás, 2023-02-27) Moreira, Lorrane Kelle da Silva; Costa, Elson Alves; http://lattes.cnpq.br/2607893423583912; Costa, Elson Alves; Fajemiroye, James Oluwagbamigbe; Ghedini, Paulo César; Rocha, Fábio Fagundes da; Carvalho, Pablinny Moreira Galdino de
    Depressive disorders affect individuals worldwide and may also be associated with other mental disorders such as anxiety disorders. Despite advances to improve understanding of the neurobiology of depressive disorders, no single established mechanism per se can explain all facets of these disorders and the available drugs often show therapeutic delay for clinical effectiveness. A plethora of results show the effects of piperazine derivatives on the central nervous system and are indicators of its therapeutic potential for treating mental disorders. Previously, it was shown that the piperazine derivative 2,6-di-tert-butyl-4-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)phenol (LQFM212) has anxiolytic-like activity which involves serotonergic pathway, nicotinic receptors and BZD-site of GABAA receptor, without cognitive impairments. In this regard, since the same compound can have anxiolytic as well as antidepressant effects, the aim of this research was to evaluate the possible antidepressant-like activity of the compound LQFM212. Swiss albino male mice orally treated with LQFM212 (54 μmol/kg) showed behavioral effects related to antidepressant-like activity, in the forced swimming test (FST), after treatment with a single dose or with repeated doses for 15 consecutive days. Pretreatment with WAY-100635 (0.7 μmol/kg), p-chlorophenylalanine (500 μmol/kg), prazosin (2.6 μmol/kg), SCH-23390 (15 μg/kg), sulpiride (146 μmol/kg) ou α-methyl-p-tyrosine (512 μmol/kg) reversed the antidepressant-like effect of LQFM212 in the FST. Furthermore, repeated treatment with LQFM212 increased hippocampal brain-derived neurotrophic factor (BDNF) levels. Regarding the monitoring of body weight and the evaluation of possible biochemical changes the treatment with repeated doses with LQFM212 (54 μmol/kg) did not change: animals' body weight, liver glutathione (GSH) levels, and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine. A possible action of the compound LQFM212 on inflammatory parameters, in mice, was evaluated by systemic inflammation by the lipopolysaccharide (LPS)-induced neuroinflammation model and by local inflammation by the carrageenan- or LPS-induced pleurisy model. In the LPS-induced neuroinflammation model, oral treatment with LQFM212 (54 μmol/kg) reversed the anxiety-like and depression-like behaviors, in the open field, forced swimming and tail suspension tests, the increase of pro-inflammatory cytokines (TNF-α and IL-1β) and the decrease of anti-inflammatory cytokines (IL-4 and IL-10), into animals’ serum, caused by intraperitoneal administration of LPS (1 mg/kg). In this same model, treatment with LQFM212 (54 μmol/kg) also attenuated oxidative stress-related changes, demonstrated by reduced nitrite levels and myeloperoxidase (MPO) activity, and increased glutathione levels in the prefrontal cortex and hippocampus, and also reduced cholinesterase activity in the whole brain, of animals that received intraperitoneal administration of LPS (1 mg/kg). On the other hand, oral treatment with LQFM212 (54 μmol/kg) failed to reduce the increase in cell migration and pro-inflammatory cytokines (TNF-α and IL-1β) in pleural exudate caused by intrapleural administration of 1% carrageenan or LPS (250 ng/mL) in the pleurisy model. In addition to the reduction in MPO activity seen in the LPS-induced neuroinflammation model, treatment with LQFM212 (54 μmol/kg) also reduced the activity of this enzyme in the pleural exudate of animals subjected to the carrageenan- or LPS-induced pleurisy model. Taken together, the results showed that treatment with LQFM212 promotes behavioral changes suggestive of antidepressant-like activity in mice, which probably involve the monoaminergic pathways, in addition to increased hippocampal levels of BDNF, suggesting changes in synaptic neuroplasticity possibly as a mechanism underlying the antidepressant-like effect of the compound. The effects found in the LPS-induced neuroinflammation model did not seem to be secondary to a peripheral anti-inflammatory action of LQFM212, since this compound failed to reduce the changes caused by carrageenan or LPS in the pleurisy model. On the other hand, treatment with LQFM212 reduced MPO enzyme activity in pleural exudate, prefrontal cortex, and hippocampus, and increased per se GSH levels in both brain regions mentioned above, thus suggesting a possible antioxidant activity in vivo that may contribute to the effects observed in the neuroinflammation and pleurisy model.
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    Avaliação das atividades genotóxica, antigenotóxica, angiogênica e potencial de cicatrização do látex da Synadenium umbellatum Pax
    (Universidade Federal de Goiás, 2009-11-27) Reis, Paulo Roberto de Melo; Lee, Chen Chen; http://lattes.cnpq.br/4621907105842007
    Synadenium umbellatum Pax (1894) is a vegetable species from Euphorbiaceae‟s family. The species of this family produce latex. The latex extracted from S. umbellatum has been used by the Brazilian people as anti-tumoral, anti-inflammatory and wound healing agents. However, this latex presents toxic substances and proteolic enzymes. The aim of this work was to evaluate the possible genotoxic, antigenotoxic, cytotoxic, angiogenic and wound healing activities of S. umbellatum latex (SuL) in rats. The genotoxic and antigenotoxic activities were evaluated by mouse bone marrow micronucleus test. An alkylant agent mitomycin C (4 mg.kg-1 body weight) was used as a positive control. For all doses, micronucleated polychromatic erythrocytes (MNPCE) frequency was evaluated after 24 hours of treatment. To evaluate the antimutagenic activity, animals were treated with 10, 30, 50 and 100 mg.kg-1 and 4 mg. kg-1 of mitomycin C (MMC) simultaneously. The frequency of MNPCE was evaluated 24 hours after exposure. Cytotoxicity was evaluated by the polychromatic and normochromatic erythrocytes ratio (PCE/NCE). Angiogenic activity of the SuL was evaluated in chorioallantoic membrane (CAM) of fertilized chicken eggs. The concentrations of the SuL were of 10 and 20 mg/mL. Wound healing activity was evaluated in skin of rats. The skin fragment was removed with area 3 x 2,5 cm and submitted to topic application with 5 mL of SuL (concentration 10 mg/mL) and positive and negative controls. The results showed that the SuL was strongly mutagenic, cytotoxic, and antimutagenic, and a moderate activity of anticytotoxicity. In the evaluation of the angiogenesis, the SuL has promoted the increase of the proliferation of blood vessels in the chorioallantoic xvii membrane of fertilized chicken eggs and it also induced the increase of velocity of wound healing in rat skin lesion.
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    O-GlcNAcilação de proteínas como um sensor de nutrientes sinalizando disfunção placentária na gestação hipertensiva
    (Universidade Federal de Goiás, 2022-11-30) Passos Junior, Rinaldo Rodrigues dos; Vitorino, Fernanda Regina Casagrande Giachini; http://lattes.cnpq.br/3100345884689140; Vitorino, Fernanda Regina Casagrande Giachini; Martín, Sebastián San; Fagundes, Danny Laura; Biancardi, Manoel Francisco; Gomes, Rodrigo Mello
    The protein O-GlcNAcylation is essential for a proper placental development and this post-translational modification is found to be disrupted in hypertensive disorders of pregnancy. The present study aimed to investigate the impact of hypertension on the protein O-GlcNAcylation and fetal-placental development throughout pregnancy. First, a non-systematic literature review was carried out, based on analyzes and interpretations of the existing scientific production to understand the involvement of OGlcNAc in the establishment of hypertension. Subsequently, we sought to characterize how O-GlcNAcylation of proteins affects placental function and fetal growth throughout pregnancy under hypertensive conditions. To achieve this, spontaneously hypertensive rats (SHR) and Wistar were divided into 14, 17, and 20 days of pregnancy (DOP) groups. On the 14th, 17th, and 20th DOP, placentas were collected and submitted to western blot, immunohistochemistry, and morphological analysis. OGlcNAc protein expression was lower in placentas from SHR compared to Wistar at 14 (p=0.003) and 20 DOP (p<0.0001). Reduced OGT (p=0.01) and OGA (p=0.002) enzymes expression was found on 14 DOP in SHR. Increased pre-implantation losses were found in SHR at 14, 17, and 20 DOP. SHR presented reduced fetal weight and increased small for gestational age fetuses on all DOP analyzed. Placental weight was increased in near-term SHR (p=0.006) whereas placental efficiency was decreased in SHR at 17 (p=0.01) and 20 DOP (p<0.0001). Morphological analysis showed reduced junctional zone area and labyrinth vasculature alterations on placentas from SHR in all DOP analyzed. Reduced placental O-GlcNAc content was found in both the junctional zone and labyrinth of the placentas from SHR. Decreased glycogen cell content in placental tissue from SHR at 14, 17, and 20 DOP. Moreover, GLUT1 expression was found to be decreased in placentas from SHR in all DOP. Collectively, these findings suggest that reduced protein O-GlcNAcylation, resulting from decreased placental nutritional apport, contributes to placental structural and functional derangement during hypertensive pregnancy, impairing fetal growth.
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    Contribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN)
    (Universidade Federal de Goiás, 2022-10-31) Naves, Lara Marques; Pedrino, Gustavo Rodrigues; http://lattes.cnpq.br/1155446449250341; Pedrino, Gustavo Rodrigues; Custódio, Carlos Henrique Xavier; Fajemiroye, James Oluwagbamigbe; Mourão, Aline Andrade; Oliveira, André Henrique Freiria de
    Neurogenic hypertension is characterized by a chronic elevation of blood pressure (BP) associated with exacerbation of sympathetic nerve activity (SNA). In this sense, the neuroinflammation, marked by the presence of pro-inflammatory cytokines (PIC) in the central nervous system (CNS), can be related to increased sympathetic drive and arterial hypertension (AH) development. Furthermore, the presence of tumor necrosis factor alpha (TNF-α) in sympathetic premotor neurons that compose the rostral ventrolateral medulla (RVLM) and hypothalamic paraventricular nucleus (PVN) is associated with hypertensive phenotype. However, the pathways and mechanisms by which TNF-α act in the CNS remain under investigation. Thus, the present study investigated the cardiovascular and autonomic effects promoted by TNF-α administration in the PVN and the participation of glutamatergic neurotransmission and N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the RVLM in these responses. For this, Wistar and spontaneously hypertensive rats (SHR) (270 - 300g) were anesthetized with urethane (400 mg/mL, intravenous - i.v.) associated with α-chloralose (40 mg/mL, i.v.) and instrumented to mean arterial pressure (MAP), heart rate (HR) and splanchnic sympathetic nervous activity (SSNA) recordings. The animals were organized into five groups and subjected to unilateral nanoinjections (50 nL) in the RVLM as follows: I. Wistar subjected to vehicle nanoinjections (Ringer's solution, normotensive SHAM group, n=5); II. SHR subjected to vehicle nanoinjections (Ringer's solution, hypertensive SHAM group, n=7); III. SHR subjected to kynurenic acid nanoinjections (KYN, 50 mM, glutamate receptor antagonist, hypertensive GLU group, n=6); IV. SHR subjected to 2-amino-5-phosphonovaleric acid nanoinjections (AP5, 24 nmol/50 nL, NMDA receptor antagonist, hypertensive NMDA group, n=7) and V. SHR subjected to 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f] quinoxaline nanoinjections (NBQX, 5.2 nmol/50 nL, AMPA receptor antagonist, hypertensive AMPA group, n=6). Then, all groups were subjected to ipsilateral TNF-α nanoinjections (0.6 pmol/50 nL, 50 nL) in the PVN. Nanoinjections of vehicle, KYN, AP5 or NBQX in RVLM did not change baseline values of MAP, HR and SSNA. In the normotensive SHAM group, TNF-α nanoinjections into the PVN induced an ANSE increase after 50 min of TNF-α nanoinjections, without modifying the MAP and HR. In contrast, in the hypertensive SHAM group, TNF-α nanoinjections in the PVN promoted a progressive splanchnic sympathoexcitation initiated 20 min after the TNF-α nanoinjections. After 50 min of TNF-α nanoinjections, a pressor response was observed, without changing HR, in the hypertensive SHAM group. Previous inhibition of RVLM glutamatergic neurotransmission did not alter the pressor response induced by TNF-α in hypertensive animals and did not change the HR. However, abolished the splanchnic sympathoexcitation observed after TNF-α. Additionally, NMDA or AMPA receptors previous inhibition in RVLM was not able to change the TNF-α-induced late increase in MAP and the HR in hypertensive animals. However, attenuated the splanchnic sympatoexcitation generated after the TNF-α nanoinjections. These results suggest that cardiovascular and autonomic changes promoted by TNF-α in the PVN are exacerbated in hypertensive animals and that the integrity of glutamatergic neurotransmission and NMDA and AMPA receptors in the RVLM are essential for the sympathoexcitatory response induced by TNF-α in the PVN in SHR.
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    Efeito neuroprotetor e antiepiléptico da infusão intracerebroventricular crônica de angiotensina-(1-7) em ratos com epilepsia do lobo temporal
    (Universidade Federal de Goiás, 2020-03-02) Gomes, Karina Pereira; Castro, Carlos Henrique de; http://lattes.cnpq.br/6354834854727314; Colugnati, Diego Basile; http://lattes.cnpq.br/3875833705952056; Colugnati, Diego Basile; Torres, Bruno Benetti Junta; Pedrino, Gustavo Rodrigues; Blanch, Graziela Torres; Menegatti, Ricardo
    Epilepsy is a severe neurological disorder characterized by permanent predisposition of the brain to generate spontaneous and recurrent seizures. Temporal Lobe Epilepsy (TLE) is the most frequent type of epilepsy in adults and is often refractory to pharmacological treatments available. Recently, several neuropeptides and their receptors have been suggested as promising therapeutic targets for the treatment of epilepsy, including neuropeptides and receptors of the Renin Angiotensin System (RAS). The aim of this study was to evaluate the effects of chronic treatment with Angiotensin-(1-7) (Ang-(1-7)) in male Wistar rats with TLE. The Pilocarpine (PILO) model was used for TLE induction and after the first spontaneous seizure, the animals were submitted to stereotactic surgery for implant of a guide cannula attached to an osmotic minipump. Rats of control group (CT) underwent the same procedures as the rats of groups with epilepsy, but were resistant to PILO model, not developing ELT. Intracerebroventricular infusion of Ang-(1-7) (200ng/kg/h) or sterile saline solution (NaCl 0.9%) was performed for 30 days and body weight, feed intake and spontaneous seizures were evaluated. At the end of the treatment, behavioral tests were performed in Elevated Plus Maze (EPM) and Open Field (OF) for evaluation of anxiety-like behavior and locomotor/exploratory activity. In the next day after behavioral tests, the animals were euthanized and the hippocampus were dissected, stored and later processed for protein analysis using Western Blot technique. For RAS components investigation, protein levels of Angiotensin Converting Enzyme 2 (ACE2) and Neutral Endopeptidase (NEP), as well as AT1, AT2 and Mas receptors were evaluated. In addition, hippocampal levels of Interleukin-6 (IL-6), Superoxide Dismutase (SOD), Catalase (CAT), B-Cell Lymphoma 2 (Bcl-2) and the phosphorylation of Mammalian Target of Rapamycin (mTOR) were quantified. Chronic intracerebroventricular treatment with Ang-(1-7) significantly reduced the frequency of spontaneous epileptic seizures, mainly at light photoperiod of the light-dark cycle, without changing its duration. Saline treated TLE rats (EP) showed significantly lower body weight gain than control rats without epilepsy (CT), which was attenuated in the last two weeks by Ang- (1-7) treatment (EP + Ang-(1-7)). However, the feed intake did not differ among evaluated groups. The time spent in EPM open arms by EP group was significantly higher than CT group, an effect attenuated by Ang-(1-7) treatment. In addition, the total number of entries in EPM arms was higher in EP group, which was reversed in EP + Ang-(1-7) group. The number of crossings in OF was significantly higher in EP group, which was reversed by Ang-(1-7) treatment. However, the immobility time and the numbers of rearing, also increased in the EP group, were only attenuated by Ang-(1- 7) treatment. Our results, revealed that Ang-(1-7) positively regulated the antioxidant protein CAT, the anti-apoptotic protein Bcl-2 and also increased the phosphorylation of anti-apoptotic protein mTOR, all reduced by epilepsy in hippocampus. In addition, the upregulation of AT1 receptor induced by TLE in hippocampus was also attenuated by treatment with Ang-(1-7). The protein levels of ACE2, NEP and SOD enzymes, as well as AT2 receptor and IL-6 were not statistically different between the groups. Mas receptor was downregulated in hippocampus of EP + Ang-(1-7) group. Our data suggest that Ang-(1-7) has direct modifying effects on chronic TLE by reducing oxidative stress and hippocampal neuronal death. From these results we can conclude that chronic intracerebroventricular treatment with Ang-(1-7) in rats with PILO induced- TLE reduces hippocampal neuronal damage and the frequency of spontaneous seizures, attenuating the damage in body weight gain and behavioral abnormalities. This study provides evidence that Ang-(1-7) and its receptor are promising targets for the treatment of TLE and its comorbidities.
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    Contribuição das neurotransmissões excitatórias nos núcleos pré-óptico mediano e paraventricular do hipotálamo na modulação da atividade nervosa simpática renal e esplâncnica
    (Universidade Federal de Goiás, 2018-09-20) Mourão, Aline Andrade; Toney, Glenn M.; Pedrino, Gustavo Rodrigues; http://lattes.cnpq.br/1155446449250341; Pedrino, Gustavo Rodrigues; Cavasin, Gláucia Maria; Mendes, Elizabeth Pereira; Rosa, Daniel Alves; Rebelo, Ana Cristina Silva
    The increase of sympathetic nervous activity (SNA) stands out as the main aggravating factor for diseases related to the cardiovascular system, as well arterial hypertension (AH). In fact, several research groups have directed their studies to the understanding of how alterations of regions and nuclei located in the central nervous system (CNS) could result in sympathetic hyperactivity and, consequently, the development and maintenance of AH. Cardiovascular control regions such as the median preoptic nucleus (MnPO) and the paraventricular nucleus (PVN) of the hypothalamus have been the focus of important investigations on the involvement of the CNS in the physiopathology of AH. However, signaling pathways that can modulate the neurons of these nuclei still need to be clarified. Therefore, the first part of this study aimed to investigate the involvement of angiotensinergic and glutamatergic neurotransmissions in the MnPO on the sympathetic activity and blood pressure increases observed in hypertensive rats. Spontaneously hypertensive rats (SHR) and rats submitted previously to the Goldblatt protocol (two kidneys; one clip; 2K1C) were used. Rats of both groups (250 to 350g, n=6) were anesthetized with urethane (1.2g/kg,i.v.) and instrumented to record mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA). Nanoinjection (100nl) of saline (NaCl, 150 mM), Losartan (AT1 receptor antagonist; 10mM) and kynurenic acid (glutamate receptor antagonist; 50mM) into the MnPO were performed. In 2K1C rats, glutamatergic blockade promoted decreases in MAP and RSNA (-19.1 ± 0.9 mmHg, -21.6 ± 2.8 %, p< 0.05) when compared to saline (-0.4 ± 0.6 mmHg, 0.2 ± 0.7 %, p < 0.05). Angiotensinergic inhibition also reduced these parameters (-11.5 ± 1.2 mmHg, -10.5 ± 1.0 %, p < 0.05) in 2K1C. In SHR, Kynurenic acid nanoinjections produced hypotension and sympathoinhibition (-21.0 ± 2.5 mmHg, -24.7 ± 2.4 %, p < 0.05), as well Losartan nanoinjections (-9.7 ± 1.2 mmHg; p < 0.05) and RSNA (-12.0 ± 2.4 %, p < 0.05). These findings support the conclusion that a tonic excitatory neurotransmission exerted by angiotensin II, and mostly by glutamate in the MnPO are involved in the elevation of blood pressure and RSNA observed in models of genetic hypertension or secondary to renal artery stenosis. In the second part of this study, we tested the hypothesis that the pro-inflammatory cytokine (PIC) tumor necrosis factor alpha (TNFα) could acutely activate the PVN neurons to promote SNA increased. For that purpose, Sprague-Dawley rats (350-550g) were anesthetized with a mixture of α-chloralose (80 mg / kg) and urethane (800 mg / kg) and instrumented for MAP, HR, splanchnic SNA (SSNA) recordings and unilateral nanoinjections in PVN. The animals were submitted to series of experiments with the following pretreatments in the PVN: vehicle (PBS, 0.5 nmol / 50 nl, n = 5), NBQX (AMPA receptor antagonist; 5.2 nmol / 50 nl n = 5) and AP5 (NMDA receptor antagonist; 24 nmol / 50 nl, n = 5). After each pretreatment, nanoinjection of TNFα (0.6 pmol / 50 nl) was performed and cardiovascular and sympathetic variables, evaluated for 60 min. TNFα nanoinjections in the PVN promoted progressive ramp-like increase of SSNA (55 ± 5.5 %) when pretreated with vehicle (3 ± 3 %, p < 0.05). However, no changes were observed in MAP (95 ± 8 mmHg vs. 94.5 ± 6.2 mmHg) and HR (400.2 bpm ± 13.5 vs. 377 ± 9 bpm) in this group. On the other hand, the blockade of ionotropic glutamate receptors AMPAR and NMDAR promoted reduction in the sympathoexcitatory response (24 ± 5% and 32 ± 6.5%, respectively) induced by the TNFα in the PVN. No changes in cardiovascular parameters were observed in these groups (NBQX: 93 ± 9 mmHg and 429 ± 10 bpm, AP5: 104 ± 3 mmHg and 439 ± 29 bpm). The following experiments sought to investigate the role of NMDA and AMPA in the maintenance of splanchnic sympathoexcitation caused by TNFα nanoinjections in the PVN. Thus, vehicle nanoinjections (PBS, 0.5 nmol / 50 nl, n = 3), NBQX (5.2 nmol / 50 nl, n = 5) and AP5 (24 nmol / 50 nl, n = 4) after 60 min of the TNFα nanoinjection in the PVN. The evaluated parameters were then recorded for additional 60 min. Post treatments did not promote significant alterations in any of the evaluated variables, suggesting that these receptors are not important in maintaining the sympathoexcitation triggered by the administration of TNFα in PVN. Finally, we evaluated whether the PVN inhibition could influence the maintenance of the sympathoexcitation induced by the TNFα. Thus, unilateral nanoinjections of the GABAA receptor agonist, muscimol (1 nmol / 50 nl, n = 5) were performed after 60 min of the TNFα nanoinjections in the PVN. Activation of GABAA receptors in PVN reversed TNFα-induced splanchnic sympathoexcitation from 173 ± 11% to 106 ± 5%, (p < 0.05). The results found in the present study indicate that the development of SSNA increase promoted by TNFα in the PVN is dependent of the ionotropic glutamate receptors AMPAR and NMDAR in this nucleus. Together these findings indicate the importance of glutamatergic neurotransmission in PVN for the generation of the sympathoexcitatory response triggered by neuroinflammation induced by (TNFα) in this nucleus. the MnPO are involved in the elevation of blood pressure and RSNA observed in models of genetic hypertension or secondary to renal artery stenosis. In the second part of this study, we tested the hypothesis that the pro-inflammatory cytokine (PIC) tumor necrosis factor alpha (TNFα) could acutely activate the PVN neurons to promote SNA increased. For that purpose, Sprague-Dawley rats (350-550g) were anesthetized with a mixture of α-chloralose (80 mg / kg) and urethane (800 mg / kg) and instrumented for MAP, HR, splanchnic SNA (SSNA) recordings and unilateral nanoinjections in PVN. The animals were submitted to series of experiments with the following pretreatments in the PVN: vehicle (PBS, 0.5 nmol / 50 nl, n = 5), NBQX (AMPA receptor antagonist; 5.2 nmol / 50 nl n = 5) and AP5 (NMDA receptor antagonist; 24 nmol / 50 nl, n = 5). After each pretreatment, nanoinjection of TNFα (0.6 pmol / 50 nl) was performed and cardiovascular and sympathetic variables, evaluated for 60 min. TNFα nanoinjections in the PVN promoted progressive ramp-like increase of SSNA (55 ± 5.5 %) when pretreated with vehicle (3 ± 3 %, p < 0.05). However, no changes were observed in MAP (95 ± 8 mmHg vs. 94.5 ± 6.2 mmHg) and HR (400.2 bpm ± 13.5 vs. 377 ± 9 bpm) in this group. On the other hand, the blockade of ionotropic glutamate receptors AMPAR and NMDAR promoted reduction in the sympathoexcitatory response (24 ± 5% and 32 ± 6.5%, respectively) induced by the TNFα in the PVN. No changes in cardiovascular parameters were observed in these groups (NBQX: 93 ± 9 mmHg and 429 ± 10 bpm, AP5: 104 ± 3 mmHg and 439 ± 29 bpm). The following experiments sought to investigate the role of NMDA and AMPA in the maintenance of splanchnic sympathoexcitation caused by TNFα nanoinjections in the PVN. Thus, vehicle nanoinjections (PBS, 0.5 nmol / 50 nl, n = 3), NBQX (5.2 nmol / 50 nl, n = 5) and AP5 (24 nmol / 50 nl, n = 4) after 60 min of the TNFα nanoinjection in the PVN. The evaluated parameters were then recorded for additional 60 min. Post treatments did not promote significant alterations in any of the evaluated variables, suggesting that these receptors are not important in maintaining the sympathoexcitation triggered by the administration of TNFα in PVN. Finally, we evaluated whether the PVN inhibition could influence the maintenance of the sympathoexcitation induced by the TNFα. Thus, unilateral nanoinjections of the GABAA receptor agonist, muscimol (1 nmol / 50 nl, n = 5) were performed after 60 min of the TNFα nanoinjections in the PVN. Activation of GABAA receptors in PVN reversed TNFα-induced splanchnic sympathoexcitation from 173 ± 11% to 106 ± 5%, (p < 0.05). The results found in the present study indicate that the development of SSNA increase promoted by TNFα in the PVN is dependent of the ionotropic glutamate receptors AMPAR and NMDAR in this nucleus. Together these findings indicate the importance of glutamatergic neurotransmission in PVN for the generation of the sympathoexcitatory response triggered by neuroinflammation induced by (TNFα) in this nucleus.
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    Atividade tóxica e genotóxica induzida por combinações de antirretrovirais em Drosophila melanogaster e camundongos Mus musculus
    (Universidade Federal de Goiás, 2016-11-07) Moraes Filho, Aroldo Vieira de; Lee, Chen Chen; http://lattes.cnpq.br/4621907105842007; Lee, Chen Chen; Spanó, Mário Antônio; Pires, Débora de Jesus; Morais, Simone Maria Teixeira de Sabóia; Silva, Carolina Ribeiro e
    As result of several mutations of HIV and failures resulting in treatments with only one medicine, it became critical to use a combination of two or more antiretrovirals in AIDS treatment protocols. So, the investigations that were carried out in this research were concentrated in the evaluation of the effects related with cytotoxicity and genotoxicity of Efavirenz (EFV) e Tenofovir (TDF) as isolated and in combination with Combivir® (AZT+3TC) and Lamivudina (3TC). For this, three test systems were used: (i) the Comet assay in Drosophila and mouse bone marrow in order to determine the genotoxic effects of the drugs tested by the DNA strand breaks; (ii) the Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster, that evaluates the toxic, mutagenic and recombinogenic activity of the compounds and (iii) the Micronucleus Test (MN) in mouse bone marrow, that detects aneugenic and clastogenic effects of agents. The results demonstrated that EFV was toxic at high concentrations and did not show induction of mutagenic and/or recombinogenic events. Inversely, Combivir and Combivir+EFV showed no lethal dose 70 (LD 70) in the concentrations used for genotoxic analysis, but induced mutagenic and/or recombinogenic effects in all tested concentrations, with prevalence of recombinogenic events. The antiretrovirals TDF, 3TC and TDF + 3TC were not toxic, but were gentoxic in all tested concentrations, with a prevalence of recombinogenicity. All of the isolated and combined compounds were positive in the Comet-assay with D. melanogaster. However, the two combinations were negative in the Comet-assay with mouse bone marrow. Combivir+EFV induced micronuclei (MN) in 24 and 48 hours. TDF+3TC induced MN only in 24 hours. Based on these results, we expect to expand the knowledge about the toxic and genotoxic activities of these combinations and to provide support for the development of new studies in AIDS treatment protocols.
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    Análise da dinâmica do glicoproteoma de trichoderma asperelloides durante o micoparasitismo
    (Universidade Federal de Goiás, 2022-01-21) Naoum, Stéphanie; Monteiro, Valdirene Neves; http://lattes.cnpq.br/8264822485508916; Ulhoa, Cirano José; http://lattes.cnpq.br/8368469162867277; Ulhoa, Cirano José; Bailão, Alexandre Melo; Georg, Raphaela de Castro; Paula, Renato Graciano de
    Glycosylation is a post-translational modification that occurs in most cells and is an important mechanism for several cellular processes such as protein secretion, cell signaling, protein translocation and stability, maintenance of cell structure and receptor-ligand interactions. In fungi there is a set of enzymes specialized in glycosylation of proteins, exerting functions related to the structure of the cell wall and the cell as a whole, assisting in integrity, growth, differentiation and signaling. Fungi of the genus Trichoderma are known for their ability to biocontrol through mycoparasitism mechanisms involving the production of cell wall degrading hydrolytic enzymes. Therefore, the objective of this work was to identify the N-glycosylated proteins produced by T. asperelloides (TR356) during mycoparasitism. The Concanavalin A (ConA) affinity chromatography technique was used to enrich the samples and select N-glycated glycoproteins with oligomannosidic structure. In the interaction between the fungi, the contact condition showed a difference in the protein content when compared to the control samples. The specific activities of the enzymes β-1,3-exoglycanase, β-1,3-endoglycanase, chitinase, N-acetyl-glucosaminidase, β-glucosidase, acid phosphatase, α-mannosidase, α-arabinofuranosidase and demonstrated a significant increase in activities in conditions before contact and contact. Several proteins were identified in the samples using the mass spectrometry technique. A total of 253 proteins were identified in the control sample. In samples referring to before contact and contact between T. asperelloides (TR 356) and S. sclerotiorum the number of identified proteins was higher, 582 and 524 proteins, respectively. We can infer that the presence of the pathogen S. sclerotiorum in the same environment as T. asperelloides stimulates the production of specific proteins for this situation, necessary for mycoparasitism. Glycoproteins with different amounts of N-glycosylation sites involved in mycoparasitism were identified, and the number of glycoproteins and N-glycosylation sites increased in pre-contact and in-contact situations. Most secreted proteins are involved in carbohydrate metabolism and transport, cell signaling, and post-translational modifications and folding. The identified proteins of the intracellular environment are involved in post-translational modification and protein folding, in carbohydrate metabolism and transport, and in cellular metabolism in general. Finally, we observed that a significant number of identified proteins still do not have a defined function, which can be considered an important source of new studies and new knowledge in relation to mycoparasitism.
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    Marcadores bioquímicos e inflamatórios em ratos submetidos ao modelo de sobrecarga de sódio pós-natal
    (Universidade Federal de Goiás, 2021-09-17) Barros, Laiza Alencar Santos; Oliveira, André Henrique Freiria; http://lattes.cnpq.br/0152151142555605; Oliveira, André Henrique Freiria; Gomes, Clayson Moura; Rosa, Daniel Alves; Colugnati, Diego Basile; Almeida, Roberto Lopes de
    WHO data shows that the consumption of salt by the population exceeds what is indicated, which can become a public health concern, because although the ingestion of high salt levels is classically associated with the installation of hypertension, saline environment leads to an osmotic disorder which results in multiple physiological changes in the renal, central nervous and immune systems. Even studies have linked salt overload to metabolic disorders, little is known about the consequences of a hypersodium diet in the early stages of life. Experimental groups (E) of Wistar and Holtzman male rats were treated with 0.3M saline, while the control group (C) had access to water, for 60 days. During the treatment, plethysmografhy was performed for blood pressure (BP) and heart rate (HR) measurements. After a recover period, when both groups received water, biological samples were taken for analysis of hematological parameters, in blood, ad biochemical and immunological parameters, in serum and plasma. Contrary to expectations, the Holtzman rats showed no increase in BP or HR, after hypertonic saline treatment. In addition, they do not increased inflammatory cytokines, and were normal for all biochemical parameters surveyed, except for serum creatinine, with was decreased (E: 0.27 ± 0.07 vs C:0.46 ± 0.04 mg/dl, p<0.05). On the other hand, Wistar rats developed hypertension (E: 159.9 ± 5.2 mmHg vs. C: 149.7 ± 3.2 mmHg, p<0.05) and increased HR (E: 412.9 ± 7.7 bpm vs. C: 375.7 ± 12.9 bpm, p<0.05). In addition, we found differences in biochemical parameters for renal function, with elevated urea (C: 44.39 ± 0.32 mg/dl and E: 49.5 ± 0.69 mg/dl), and low creatinine (C: 0.96 ± 0.02 mg/dl and E: 068 ± 0.004 mg/dl); also differences for liver function, with increased ALT (C: 16.26 ± 0.43 mg/dl and E: 32.63 ± 0,6 mg/dl) and total and indirect bilirubin. Furthermore, components of lipidogram and serum glucose (C: 83.63 ± 0.42 mg/dl and E: 124.2 mg/dl) were elevated. Therefore, we can reinforce that there are metabolic variations between animal strains, explaining why the Holtzman rats were not sensitive to the saline protocol. In addition, changes in the biochemical parameters of Wistar rats allow us to state that sodium overload causes several metabolic diseases, with involvement of renal and liver function, besides to alterations in the metabolism of lipids and carbohydrates.
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    Estudo genético em casais com histórico de perdas fetais recorrentes
    (Universidade Federal de Goiás, 2021-09-28) Sestari, Sheila Janaina; Bérgamo, Nádia Aparecida; http://lattes.cnpq.br/2282798263482973; Bicudo, Lucilene Arilho Ribeiro; http://lattes.cnpq.br/6837561883041187; Bicudo, Lucilene Arilho Ribeiro; Gamba, Bruno Faulin; Castro, Eduardo Camelo de; Lacerda, Elisangela de Paula Silveira; Bicudo, Lucilene Arilho Ribeiro
    Recurrent miscarriage is defined as the loss of two or more consecutive pregnancies at a gestational age of less than 20-22 weeks. It is a problem of extensive research in reproductive health and affects about 5% of couples who want pregnancy. Its etiology is complex and associated with several factors, such as genetic, endocrine, anatomical, immunological, thrombophilic, viral and bacterial infections, environmental, among others. Parental genetic causes account for a considerable proportion, especially in first trimester pregnancy losses. The aim of this study was to perform genetic analysis in couples with recurrent miscarriage in search of an association with pregnancy losses. In the cytogenetic analysis, we identified a frequency of 2.5% of structural chromosomal abnormalities (inversion and translocation) and about 17.5% of heteromorphisms. In the analysis of the C677T and A1298C polymorphisms of the MTHFR gene and I/D of the ACE gene, no significant association was identified regarding the increased risk of recurrent miscarriage in any of the evaluated polymorphisms. Regarding copy number variants (CNVs), the literature review identified 16 CNVS in 10 different chromosomes, all with potential risk for pregnancy maintenance. Thus, the positive findings for genetic alterations in this study support its association with recurrent miscarriage, as well as the importance of these analyzes for an assertive medical conduct and carrying out genetic counseling.
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    O papel da O-glicosilação com N-acetilglucosamina na gestação
    (Universidade Federal de Goiás, 2021-06-14) Dela Justina, Vanessa; Vitorino, Fernanda Regina Casagrande Giachini; http://lattes.cnpq.br/3100345884689140; Vitorino, Fernanda Regina Casagrande Giachini; Priviero, Fernanda Bruschi Marinho; Passaglia, Rita de Cassia Aleixo Tostes; Filgueira, Fernando Paranaiba; Castro, Carlos Henrique de
    O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification that modulates several proteins. The increase in O-Glycosylation is observed during hyperglycemia, favoring endothelial dysfunction as well as placental modifications. The hypothesis of this work was that the increase in O-Glycosylation during pregnancy, generates vascular and placental dys- function, resulting in inadequate nutritional support between the maternal -fetal interface. For this, the work was divided in two parts. PART I: To characterize how different glycemic levels affect O-GlcNAcylation of cells in different placental regions. Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n= 5); mild hyperglycemia (> 140 mg/dL, at least two moments in the oral glucose tolerance test; n= 7) or normoglycemia (<120 mg/dL; n= 5). Cells in the labyrinth and junctional zones are targeted by the accumu- lation of O-GlcNAc in response to severe hyperglycemia, possibly due to reduced O-GlcNAcase (OGA) expression. O-GlcNAc is not seen during mild hyperglycemia, possibly due to OGA compensatory expression/activity. In addition, morphometric changes, occurring simultane- ously with increased accumulation of O-GlcNAc in placental tissue, can contribute to placental dysfunction during hyperglycemia. PART II:) To assess whether the increase in O-GlcNAc impairs the endothelial function of the uterine artery. Pregnant (P) or non-pregnant (NP) rats were treated with glucosamine (300mg/kg) or vehicle for 21 days, i.p. Glucosamine treatment increased the expression of O-GlcNAc in UA in NP rats. A decrease in endothelium-dependent relaxation was observed in UA of treated NP rats, compared to the vehicle, which was abo- lished by incubation of the nitric oxide synthase inhibitor (eNOS). eNOS activity as well as total Akt expression are reduced after treatment with glucosamine in NP rats. In addition, UAs from NP rats treated with glucosamine showed an increase in the activation of glycogen sy n- thase kinase 3 beta (GSK3β), as well as an increase in the expression of OGT. Interestingly, during pregnancy, treatment with glucosamine decreases the expression of O-GlcNAc in UA, accompanied by an improvement in relaxation for acetylcholine, while the activities of eNOS and GSK3β and the total expressions of Akt and OGT remained unchanged. Endothelium- independent relaxation was not altered in the groups studied. Therefore, the underlying me- chanism that occurs between P and NP is, at least in part, dependent on Akt/GSK3β/OGT mo- dification. We believe that, during pregnancy, hormonal changes play a vascular protective role, preventing endothelial dysfunction induced by O-glycosylation. In the future, it will be interesting to assess whether strategies that normalize O-GlcNAcylation levels in placental proteins will result in gestational success in pathological conditions, including hyperglycemia.
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    Efeitos celulares e comportamentais de peptídeos bioativos de baixo peso molecular extraídos de Phaseolus vulgaris
    (Universidade Federal de Goiás, 2020-11-18) Graziani, Daniel; Fernandes, Kátia Flávia; http://lattes.cnpq.br/9737543228759171; Custódio, Carlos Henrique Xavier; http://lattes.cnpq.br/0207928273284808; Custódio, Carlos Henrique Xavier; Cruz, Vanessa de Sousa; Araújo, Eugênio Gonçalves de; Fajemiroye, James Oluwagbamigbe; Silva, Elder Sales da
    INTRODUCTION: Approximately 3.000 tons of beans are not used in human consumption due to their hardening, which makes them a product of low commercial value. Several studies with bioactive peptides derived from beans have therapeutic potential to treat various diseases. OBJECTIVES: to evaluate the effects of a low molecular weight bean extract (Phaseolus vulgaris) hardened on: i) cytotoxic and cytoprotective effects on endothelial cells; ii) production of reactive oxygen species (ROS) and nitric oxide (NO) in endothelial cells; iii) oxidonitrergic-dependent vasodilator effects; iv) anxiety and depression behavior in rats; v) the antioxidant effect on rat brain. METHODS: The extract was composed of a peptide fraction less than 3 KDa (PV3) of the hardened bean residue. The PV3 sequences were corrected by mass spectrometry coupled to liquid chromatography and were analyzed with computational tools. Human umbilical vein endothelial cells (HUVEC) were treated with PV3 in the following procedures: 10 μg/ml, 20 μg/ml, 30 μg/ml and 250 μg/ml. Cellular oxidative stress was caused by 3% H2O2. Cytotoxicity and cytoprotective effects were obtained by the MTT assay, while ROS and NO were quantified by fluorescent probes (DHE and DAF-FM) by Confocal Microscopy. The vasodilator effects of NO3 and endothelium-dependent PV3 were obtained in the supplied aortic rings. The behavioral effects of acute and chronic PV3 treatments were adopted by three protocols: i) elevated plus maze test (EPM) to assess the effect of the anxiolytic type. ii) open field (OF) to assess locomotion and exploration; iii) forced swimming (NS) to test the behavior of the depressive type. The involvement of catecholaminergic pathways in the effects evoked by PV3 was tested using the enzyme tyrosine hydroxylase inhibitor, AMPT (200mg / kg). RESULTS: 35 peptides with an average mass of 1.14 KDa were identified. There was no cell death from treatment with PV3 10μg/mL and 20 μg/mL. PV3 30μg/mL increased cell viability, whereas cytotoxicity was observed only with PV3 250 μg/mL. Only PV3 at 10 μg/mL was able to protect cells from oxidative stress. PV3 also increased the release of NO without causing cell death. It was also able to reduce the relative production of cell ROS induced by H2O2. The vasodilator effects of PV3 were based on the release of NO dependent on the endothelium. In the EPM test, the acute injection of PV3 (50μg / kg) increased the frequency and the time spent in the open arms, suggesting an anxiolytic effect. In the OF test, PV3 (50μg / kg) increased the frequency of crossings and immobility time, showing that PV3 does not impair locomotion, which corroborates the anxiolytic effect found in the ECL. In the FS test, PV3 (50μg / kg) reduced the immobility time, suggesting an effect similar to the antidepressant. The anxiolytic-type effect found after acute injections was absent in chronic treatment with PV3 (50μg/kg). AMPT was able to reverse the effect of the anxiolytic type and the antidepressant type evoked by acute PV3 (50μg/kg). CONCLUSION: PV3 has low cytotoxicity, the ability to reduce ROS and increase NO in the endothelium, in addition to promoting anxiolytic and antidepressant effects with catecholaminergic involvement.
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    Extração e caracterização físico-química do amido nos cormos de Trimezia juncifolia (KLATT) Benth & Hook
    (Universidade Federal de Goiás, 2019-08-30) Cruz, Viviane Ovidio de Almeida; Fernandes, Kátia Flávia; http://lattes.cnpq.br/9737543228759171; Fernandes, Kátia Flávia; Batista, Karla de Aleluia; Moraes, Moemy Gomes de; Leal, Maria Carolina Bezerra Di Medeiros; Cruz, Maurício Vicente
    The members of Iridaceae family have the storage of carbohydrates in underground organs as main characteristic. Some Iridaceae species might store more than one type of carbohydrate, being starch the main reserve compound. Trimezia juncifolia belongs to the Iridaceae family and has a corm as an underground reserve organ and has fibrosis cataphylls, which presents a large amount of starch. This starch reserve is used to provide energy during the onset of vegetative growth and to maintain metabolism during periods of stress, such as the seasonal drought, when the plant is under the phenological stage of dormancy, interrupting its growth and reducing its metabolism. Starch is a semi-crystalline polysaccharide composed of two types of polymers: amylose and amylopectin. The starch is stored as granules and may present differences in morphology, crystalline structure, amylose and amylopectin ratio and chain size, depending on the botanical origin. In this sense, the objective of this work was to extract and characterize the starch from corms of T. juncifolia collected in the dry and wet season. Results evidenced a yield of starch extraction in the range of 57.2% in the wet season and 69.2% in the dry season. The starch granules presented a bimodal size distribution. The size of starch extracted in the dry season was higher (3.69-33.75 μm) than extracted in the wet season (2.78-14.4 μm) and both presented shape similar to wheat starch. The content of amylose was 44 % and 41 % for starch from corms collected in dry season and wet season, respectively. The birefringence of starch granules was higher in wet season. The degree of polymerization of amylopectin analyzed through chromatography showed a slight difference between starch from wet (DP 81) and dry (DP 80) season. Amylose branches showed higher difference in the degree of polymerization between wet (DP 51) and dry (DP 41) season. X-ray analysis revealed differences in starch stored in the corms. Starch from dry season presented similarity with type-A polymorph more compact whereas a C-type polymorph a mixture of type-A and type-B was observed in the wet season. The crystallinity values were 27% and 25.9% for wet and dry season starches, respectively. The endothermic transition temperature were: wet season To= 39.7 ºC, Tp= 84.1ºC, Tc= 157.4 ºC and ΔT = 117.7 ºC; dry season: To= 27.6 ºC, Tp= 73 ºC, Tc= 116.6 ºC and ΔT = 89 ºC. Furthermore, the enthalpy changes (wet season: ΔH = 84.9 J g−1 / dry season: ΔH = 54.9kJ g−1) were accessed by DCS analysis. In conclusion, the results of this study indicate that the water availability in the environment results in biochemical changes in the characteristics of the starch stored in the cataphylls from T. juncifolia.
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    Efeitos de peptídeos derivados da beta globina LVV-H6 e LVV-H7 sobre os comportamentos tipo-ansiedade e tipo-depressão, função cardíaca e vascular de ratos
    (Universidade Federal de Goiás, 2019-10-11) Cruz, Kellen Rosa da; Ianzer, Danielle Alves; http://lattes.cnpq.br/7609262674053858; Custódio, Carlos Henrique Xavier; http://lattes.cnpq.br/3868498714495781; Custódio, Carlos Henrique Xavier; Ferreira, Patrícia Maria; Ghedini, Paulo Cesar; Silva, Elder Sales da; Parreira, Ricardo Cambraia
    Hemorphins are peptides derived from the hemoglobin β-globin chain. LVV- hemorphine-6 and LVV-hemorphine-7 (LVVs) are bioactive hemorphins, which exhibit similar amino acid residue sequence, differing only by the amino acid Phenylalanine at the N-terminus of LVV-hemorphine-7. Both hemorphins reduce anxiety-like and depression-like behavior, the latter being promoted by LVV-h7, is oxytocin receptors dependent, but not the effect evoked by LVV-h6. In addition, the data in the literature about the cardiovascular effects evoked by LVV-h7 are controversial and there are no studies on the effects of LVV-h6 on this physiological system. Therefore, the objective of this study was to identify the mechanisms involved in behavioral effects and also to verify the effects on vasomotricity and cardiac function in the aorta artery and isolated heart of Wistar rats. The experimental protocols were carried out according to the norms of use of animals, under project approval by the committee of ethics and animal use of the UFG (Protocol of approval nº 090/14). The Elevated Pluz Maze (EPM) was used to evaluate the anxiety-like behavior and were then placed in the Open Field (OF) to evaluate locomotion. To evaluate the depression-like behavior, the Forced Swim test (FST) was used. The isolated vessel technique was used to evaluate vascular reactivity in thoracic aorta rings isolated and the Langendorff technique to evaluate heart function in heart i solated from Wistar rats. The anxiolytic-like effect of both hemorphins does not depend on the route of biosynthesis of catecholamines or the activation of opioid receptors. However, the antidepressant-like effect of LVVs was reversed by blockade of opioid receptors, indicating the activation of these receptors as a potential mechanism. Both LVVs similarly reduce perfusion pressure, maximal and minimum dP/dt and systolic and diastolic intraventricular pressure in heart isolated from rats, without promoting contraction or relaxation of aorta rings isolated from rats. Thus, although LVVs cause the same effects on anxiety-like and depression-like behavior, the underlying mechanisms are partially different, even with a substantial similarity in the primary structure of these hemorphins. In addition, LVVs act by decreasing cardiac function, in the evaluated parameters, in isolated heart of normotensive rats without affecting the vasomotricity of aorta rings isolated of normotensive rats.
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    Efeitos cardiovasculares do tratamento com aceturato de diminazeno sobre a insuficiência cardíaca induzida por infarto do miocárdio em ratos normotensos e hipertensos
    (Universidade Federal de Goiás, 2020-07-15) Lopes, Paulo Ricardo; Colugnati, Diego Basile; http://lattes.cnpq.br/3875833705952056; Pedrino, Gustavo Rodrigues; http://lattes.cnpq.br/1155446449250341; Rebelo, Ana Cristina Silva; Castro, Carlos Henrique de; Colugnati, Diego Basile; Pedrino, Gustavo Rodrigues; Biancardi, Manoel Francisco
    Diminazene aceturate (Dize) is a broad spectrum antiparasitic that promotes, among other effects, the activation of the angio tensin II converting enzyme (ACE II). However, there are few studies that relate the use of Dize in the treatment of myocar dial infarction (MI) and very few that relate the treatment of heart failure (HF). Due to its activation effect of the counter regulatory axis of the Renin Angiotensin System (RAS), it is possible that chronic treatment with Dize can improve cardiocirculat ory function i n animals with HF MI induced . Thus, this work sought to evaluate the performance of Dize on the cardiac and circulatory function of normotensive (WT) and hypertensive (SHR) animals after MI. For that, males WT and SHR of 250 300g with 12 week s of life were used. HF was induced by MI through ligation of the left descending coronary artery. Fictitious surgeries (Sham) were also performed to mimic the surgical stress of infarction induction. After the MI, the period of 30 days to install the HF p icture, diagnosed by echocardiography, was waited. Then the animals were divided into 4 groups of WT animals and 4 was waited. Then the animals were divided into 4 groups of WT animals and 4 groups of SHR animals in the respective treatments: Sham + Vehicle, Sham + groups of SHR animals in the respective treatments: Sham + Vehicle, Sham + DizeDize, , HF + Vehicle and HF + HF + Vehicle and HF + DizeDize. The treatment with . The treatment with DizeDize (10 mg /(10 mg / Kg / day; i.g.) or Kg / day; i.g.) or vehicle (water) by gavage lasted 21 days. After treatment, the animals were vehicle (water) by gavage lasted 21 days. After treatment, the animals were anesthetized and catheterized for recording and analysis of hemodynamic and anesthetized and catheterized for recording and analysis of hemodynamic and autonomic parameters in all groups. Subsequently, the animals were autonomic parameters in all groups. Subsequently, the animals were euthanized;euthanized; theirtheir hearts and thoracic aortic segments were removed for tests in isolated organ hearts and thoracic aortic segments were removed for tests in isolated organ baths. baths. Evidence showing hypertension, in the 17Evidence showing hypertension, in the 17--weekweek--old SHR model, promoting an old SHR model, promoting an increase in fibrotic cardiac content (interstitial and perivascular), hypertrophy of increase in fibrotic cardiac content (interstitial and perivascular), hypertrophy of cardiomyocytcardiomyocytes and economic and vascular activity. It reduced the contraction and es and economic and vascular activity. It reduced the contraction and effective relaxation of the heart ex vivo, vascular reactivity, parasympathetic effective relaxation of the heart ex vivo, vascular reactivity, parasympathetic cardiac activity, sensitivity and effectivcardiac activity, sensitivity and effectiveness of the baroreflex system. eness of the baroreflex system. In In normotensive animals with HF normotensive animals with HF induced by coronary ligation after 17 weeks, cardiac induced by coronary ligation after 17 weeks, cardiac remodeling with increased heart size and cardiomyocytes, fibrosis in the heart remodeling with increased heart size and cardiomyocytes, fibrosis in the heart (interstitial and perivascular) and vascular contractile capacity. He has cardiac (interstitial and perivascular) and vascular contractile capacity. He has cardiac dysfunction of the systolic type in vivo, dysfunction of the systolic type in vivo, impaired diastolic capacity ex vivo, reduced impaired diastolic capacity ex vivo, reduced vascular capacity, spontaneous baroreflex effectiveness and PAS.vascular capacity, spontaneous baroreflex effectiveness and PAS. Hypertension Hypertension associated with HF 17 weeks after coronary ligation promotes hypertrophy of the associated with HF 17 weeks after coronary ligation promotes hypertrophy of the heart and cardiomyocytes, perivascular and interstitiheart and cardiomyocytes, perivascular and interstitial fibrosis, cardiac dysfunction al fibrosis, cardiac dysfunction in vivo and ex vivo, increased contractile vascular capacity and reduced relaxing in vivo and ex vivo, increased contractile vascular capacity and reduced relaxing capacity, friendly autonomic predominance, reduced blood pressure and capacity, friendly autonomic predominance, reduced blood pressure and effectiveness of the baroreflex system and maintenance of high BP.effectiveness of the baroreflex system and maintenance of high BP. TreaTreatment with tment with the hypertension model reduces cardiac fibrosis, reduces sympathetic activity and the hypertension model reduces cardiac fibrosis, reduces sympathetic activity and improves the reflex baroreceptor. In HF, it reduces cardiac remodeling (myocyte improves the reflex baroreceptor. In HF, it reduces cardiac remodeling (myocyte and fibrosis), facilitates vascular relaxation and improves the reflex baroreceptorand fibrosis), facilitates vascular relaxation and improves the reflex baroreceptor. . In hypertension associated with HF, it is possible to reduce or remodel (myocytes In hypertension associated with HF, it is possible to reduce or remodel (myocytes and and fifibbroserosess), improve cardiac functions in the isolated organ, facilitate vascular ), improve cardiac functions in the isolated organ, facilitate vascular relaxation and improve the reflex baroreceptor.relaxation and improve the reflex baroreceptor. Together, our results demonstrate Together, our results demonstrate that tthat treatment with size can be a tool explored in cardiovascular pathologies, but it reatment with size can be a tool explored in cardiovascular pathologies, but it seems to act differently in each pathology. Finally, further studies are needed to seems to act differently in each pathology. Finally, further studies are needed to elucidate how the treatment with Dize acts on HF and hypertension, which occur elucidate how the treatment with Dize acts on HF and hypertension, which occur isolated or coisolated or concomitant.ncomitant.
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    Caracterização clínica e análise genética em pacientes com deficiência intelectual indeterminada, de uma instituição de internação crônica em Trindade-Goiás
    (Universidade Federal de Goiás, 2019-01-29) Torres, Vinicius Montenegro; Bérgamo, Nádia Aparecida; http://lattes.cnpq.br/2282798263482973; Bicudo, Lucilene Arilho Ribeiro; http://lattes.cnpq.br/6837561883041187; Bicudo, Lucilene Arilho Ribeiro; Saddi, Vera Aparecida; Mazzeu, Juliana Forte; Gamba, Bruno Faulin; Silva, Daniela de Melo e
    ID is a clinical manifestation that has heterogeneous and complex aetiology and 50% of it have no definite cause. In 48 patients institutionalized with Intellectual Disability (ID) and under 25 years of age, a detailed clinical, laboratory and radiological evaluation was performed. After this investigation, 27 individuals were classified as having undetermined ID and submitted to karyotype, MLPA of ID implicated subtelomeric regions, chromosomal microarray analysis and, when justified, PCR for screening of X Fragile Syndrome. In the clinical evaluation, these individuals with undetermined ID presented syndromic characteristics, family recurrence, severe intensity and association with short stature and weight. When greater severity of undetermined ID was observed, a greater frequency of male patients, low BMI, Epilepsy and Physical Deficiency was identified. Hearing Deficiency, Visual Impairment and short stature showed a tendency to exhibit the same behavior. Microcephaly and Autism Spectrum Disorder, contrary to previous studies, did not present this behavior. The karyotype and MLPA exams presented normal results in all cases. Clinical evaluation and molecular examination of relatives suggested that a patient had Spinocerebellar Ataxia Type 7. PCR screening for X Fragile Syndrome detected an affected individual. Twenty-three cases underwent chromosomal microarray analysis and seven pathogenic CNVs (30.43%) were detected. Microdeletions, microduplications and complex rearrangements were observed in different chromosomes and variable sizes. Rare genetic aberrations were detected and corroborated to define the phenotype associated with the subjects. Thus, obtained data indicated a strong genetic component in indeterminate ID. The current and previous studies corroborate to define chromosomal microarray analysis, the gold standard genetic test for initial evaluation in patients with undetermined ID. This technique is becoming more accessible and presents high sensitivity.
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    Efeito da alantoína sobre a úlcera gástrica: estudo do mecanismo gastroprotetor
    (Universidade Federal de Goiás, 2019-02-01) Silva, Dayane Moreira da; Costa, Elson Alves; http://lattes.cnpq.br/2607893423583912; Costa, Elson Alves; Carvalho, João Ernesto de; Paula, Joelma Abadia Marciano de; Biancardi, Manoel Francisco; Santos, Fernanda Cristina Alcântara dos
    Gastric ulcer affects people worldwide and the recurrence have fueled for new therapeutic strategies. Despite the well-known use of allantoin in cosmetic products, it effect has never been studied in gastric ulcer. In this way, the presente work aimed explore the pharmacological pathways associated with the allantoin efficacy against commonly harmful agents that cause injuries to the stomach. The gastroprotective activity of this compound was evaluate in diferent experimental models induced by ethanol, ethanol acidity and pylorus ligature. All the experimental protocols were approved by CEUA/UFG, protocol n. 064/15. Female albino Swiss mice (30-35g) were used in the experiments. They were maintained at 23  2C and 12 h light/dark cycle, with free access to food and water. Animals were fasted 16 h before the experimental sessions with free access to glucose water (5%). The stomach of mice were used to quantification of reduced gluthatione (GSH), gastric vascular permeability, pro-inflammatory cytokines (TNF- e IL-1), gastric mucus, PGE2 levels and the myeloperoxidase (MPO) activity. The gastric lesions were examined macroscopically and histopatological analysis in light microscopy and eletronic microscopic transmission were carried out. The results showed that allantoin at dose of 60 mg/kg (p.o.) decreased the formation of gastric lesion in all the experimental models and the intraduodenal treatment revealed the antisecretory action. The treatment with allantoin preserved the GSH levels and decreased the gastric vascular permeability, MPO activity and pro-inflammatory cytokines levels. The treatment with allantoin preserved the gastric adhered mucus as well as the PGE2 levels. Microscopic and ultrastructural analysis revealed that allantoin maintained tissue integrity and prevented morphological changes in cells caused by ethanol. Altogether, the results of present work brings evidences that allantoin possesses gastroprotective activity through anti-oxidative, antisecretory, and cytoprotective mechanisms.
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    Efeitos da Angiotensina-(1-7) e Angiotensina II no inotropismo cardíaco e vasomotricidade coronariana: um complexo envolvimento entre os receptores angiotensinérgicos
    (Universidade Federal de Goiás, 2018-04-26) Nunes, Allancer Divino de Carvalho; Castro, Carlos Henrique de; http://lattes.cnpq.br/6354834854727314; Castro, Carlos Henrique de; Pedrino, Gustavo Rodrigues; Pansani, Aline; Bendhack, Lusiane Maria; Ferreira, Anderson José
    Despite Angiotensin-(1-7) [Ang-(1-7)] and Angiotensin II (Ang II) be considered important regulators of the cardiovascular system, its direct effects on cardiac contractility remain unclear and even controversial. Several studies, using different preparations, have showed that Ang-(1-7) or Ang II produce positive, negative or no inotropic effects. Thus, the aim of this study was to increase the knowledge about the effect of the low concentration of Ang-(1-7) and Ang II on cardiac contractility, coronary vascular function and the possible receptors and mechanisms of action involved in these effects. The in vivo effects of Ang-(1-7) and Ang II on cardiac contractility were evaluated in anesthetized rats. The Ang-(1-7) 4 nmol/L and Ang II 40 nmol/L caused negative inotropism in anesthetized rats. None of the peptides were able to change heart rate or arterial blood pressure in anesthetized rats. The direct effects of the Ang-(1-7) and Ang II on cardiac contractility were evaluated in isolated perfused rat hearts. After a basal period (30-40 minutes), the hearts were perfused for an additional 15 min with Ang-(1-7) and Ang II (20 pmol/L) in presence or absence of Mas receptor antagonist A-779 (2 nmol/L), AT2 receptor antagonist PD1233190 (2 nmol/L), AT1 receptor antagonist Losartan (1μmol/L), MrgD receptor antagonist D-PRO (2 nmol/L), ACE2 inhibitor DX600 (2nmol/L), Nitric Oxide synthase (NOS) inhibitor L-Name (10 nmol/L), Guanylyl cyclase (GC) inhibitor ODQ (200 nmol/L) and Adenylyl cyclase (AC) inhibitor MDL 12,330A (1μmol/L). Low concentrations of Ang-(1-7) and Ang II reduced the left ventricular end-systolic pressure (LVESP). The A-779 did not blocked the effect of Ang-(1-7) or Ang II. PD123319 and Losartan inhibited the Ang-(1-7) but not Ang II-induced negative inotropic effects. On the other hand, D-PRO was able to block the negative inotropic effect of the Ang II and Ang-(1-7). Furthermore, L-Name, ODQ and MDL 12,330A inhibited the Ang-(1-7) but not Ang II-induced negative inotropic effects. Similarly, low concentrations of Ang- (1-7) and Ang II-induced coronary vasodilatation. The A-779, D-PRO, L-Name, MDL 12,330A blocked the effect of Ang-(1-7) or Ang II. The DX600 blocked the vasodilatation induced by Ang II. PD123319, Losartan and ODQ inhibited the Ang-(1-7) but not Ang II-induced coronary vasodilatation. In addiction, the pharmacological blocked and gene silencing of AT1 receptor in endothelial human cells stimulated with Ang-(1-7) decreased AKT phosphorilation induced by Ang-(1-7). These data demonstrate that Ang-(1-7) and Ang II, at picomolar concentrations, induce significant and similar negative inotropic and coronary vasodilatation effects involving complex interaction mechanisms between many different receptors, altering intracellular signaling and their constitutive activity.