Browsing by Author "Binda, Nancy Scardua"

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    Analgesic effects of Phα1β toxin : a review of mechanisms of action involving pain pathways.
    (2021) Silva, Juliana Figueira da; Binda, Nancy Scardua; Pereira, Elizete Maria Rita; Lavor, Mário Sérgio Lima de; Vieira, Luciene Bruno; Souza, Alessandra Hubner de; Rigo, Flávia Karine; Ferrer, Hèlia Tenza; Castro Júnior, Célio José de; Ferreira, Juliano; Gomez, Marcus Vinicius
    Phα1β is a neurotoxin purified from spider venom that acts as a high-voltage-activated (HVA) calcium channel blocker. This spider peptide has shown a high selectivity for N-type HVA calcium channels (NVACC) and an analgesic effect in several animal models of pain. Its activity was associated with a reduction in calcium transients, glutamate release, and reactive oxygen species production from the spinal cord tissue and dorsal ganglia root (DRG) in rats and mice. It has been reported that intrathecal (i.t.) administration of Phα1β to treat chronic pain reverted opioid tolerance with a safer profile than ω-conotoxin MVIIA, a highly selective NVACC blocker. Following a recent development of recombinant Phα1β (CTK 01512-2), a new molecular target, TRPA1, the structural arrangement of disulphide bridges, and an effect on glial plasticity have been identified. CTK 01512-2 reproduced the antinociceptive effects of the native toxin not only after the intrathecal but also after the intravenous administration. Herein, we review the Phα1β antinociceptive activity in the most relevant pain models and its mechanisms of action, highlighting the impact of CTK 01512-2 synthesis and its potential for multimodal analgesia.
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    Análise da associação entre diuréticos tiazídicos e o desenvolvimento do diabetes mellitus do tipo 2.
    (2021) Andrade, Ana Eliza Almeida de; Binda, Nancy Scardua; Silva, Juliana Figueira da
    A hipertensão arterial e o diabetes mellitus tipo 2 (DM2) são enfermidades importantes do ponto de vista da saúde em escala mundial. As alterações na pressão arterial (PA) e glicemia podem contribuir para eventos cardiovasculares graves, além do quadro tornar- se mais preocupante quando o mesmo paciente apresenta ambas as doenças. Diuréticos tiazídicos (DT) são fármacos anti-hipertensivos utilizados para reduzir a PA, e prevenir eventos cardiovasculares. Entretanto, podem causar efeitos adversos,sendo a hipocalemia e a hiperglicemia os mais relevantes para esse estudo, cujo objetivo é analisar dados que associem o uso de DT com o possível desenvolvimento de DM2. Essa revisão integrativa de literatura internacional selecionou oito estudos, dentre os quais observou-se possível relação entre o uso de DT, principalmente em altas doses, e a elevação da glicemia, que pode ocorrer com poucas semanas de uso contínuo. A partir desse estudo foi possível identificar como fatores que influenciam o desenvolvimento da hiperglicemia: a dose administrada; a duração do tratamento; o desenvolvimento da hipocalemia, e a variabilidade genética populacional. O principal mecanismo relacionado ao aumento dos níveis de glicose sanguínea é a hipocalemia ocasionada pela classe farmacológica, devido a essencial participação do potássio na exocitose de insulina. A elevação da glicose gerada pelos DT é pouco discutida até o momento, e ainda não é um fator preponderante para a interrupção do tratamento. No entanto, a atuação do farmacêutico e equipe multiprofissional é necessária para acompanhamento da adequada indicação clínica de DT e observação das contraindicações, como a presença prévia de hiperglicemia.
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    Antioxidant activity, sensory analysis and acceptability of red fruit juice supplemented with Brazilian green propolis.
    (2022) Lopes, Géssica Aparecida; Fidelis, Priscila Cardoso; Almeida, Bruno de Moura; Almeida, Jane José; Ientz, Gislaine de Almeida Santana; Binda, Nancy Scardua; Teixeira, Arthur Ferrari; Vieira Filho, Sidney Augusto; Caligiorne, Rachel Basques; Guimarães, Dênia Antunes Saúde; Brumano, Maria Helena Nasser; Figueiredo, Sônia Maria de
    In this work were determining the total phenolic content, total flavonoids and antioxidant capacity in formulations of red fruit juice supplemented with different concentrations of aqueous extract of Brazilian green propolis. And, also was investigate the formulation sensory acceptance by volunteers’ consumers. The addition of propolis to red fruit juice increased the content of total phenolic compounds and flavonoids, enhanced the antioxidant activity of the final product as assessed by radical scavenging DPPH and ABTS and FRAP methods, and no negative effect on consumer taste. All red fruit juice formulations containing propolis presented significant results through overall acceptability test and were approved in relation to purchase intent by the volunteer consumers. Formulation F3 (6.1 mg.mL-1) showed the best results. The antioxidant activity increment was proportional to the concentration of aqueous green propolis extracts added to the juice. The positive purchase intention reached up 64.75% of participants’ acceptance. A new, sugar-free drink with pleasurable sensory and functional properties, combined with health benefits, has been obtained.
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    Aspectos farmacológicos da ivermectina e seu potencial uso no tratamento da COVID-19.
    (2020) Pedroso, Luana Amaral; Binda, Nancy Scardua; Teixeira, Mônica Cristina; Guimarães, Andrea Grabe
    A ivermectina é um fármaco antiparasitário de amplo espectro largamente utilizado em medicina humana e veterinária. É o medicamento de escolha para tratamento da oncocercose, além de ser aprovada para o tratamento de filariose linfática, estrongiloidíase, ascaridíase, escabiose e pediculose. Estudos avaliam a capacidade antitumoral, antibacteriana e antiviral da ivermectina, além de seus benefícios no tratamento de doenças metabólicas. Atualmente o grande interesse global em relação à ivermectina recai sobre o seu potencial no tratamento da COVID-19. Neste estudo foram descritos os aspectos gerais sobre a farmacologia, as características físico-químicas, os protocolos de tratamento, os aspectos de segurança e a toxicologia da ivermectina, bem como as propriedades que poderiam corroborar ou não com seu uso no tratamento da COVID-19. Foi realizada uma revisão narrativa baseada em publicações da base de dados Pubmed utilizando descritores como ivermectin, pharmacology, therapeutic use, saffety, toxicity e Covid-19. Observou-se que além da ampla indicação terapêutica, a ivermectina possui um extenso uso off-label. De modo geral, considera-se que a atividade antiviral da ivermectina seja devido à sua capacidade em estimular a resposta imune do paciente e em inibir a replicação viral. Todavia, a sua segurança terapêutica para a prevenção e tratamento da COVID-19 ainda não foi determinada, visto que as concentrações efetivas encontradas nos estudos in vitro indicam o uso de concentrações superiores àquelas aprovadas para humanos e os efeitos adversos podem ser potencializados. Até o momento não existem protocolos de tratamento com esse medicamento para a COVID-19 e a ANVISA apoia o uso da ivermectina apenas para indicações terapêuticas previamente registradas.
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    Calcium channels blockers toxins attenuate abdominal hyperalgesia and inflammatory response associated with the cerulein-induced acute pancreatitis in rats.
    (2021) Carvalho, Vanice Paula Ricardo; Silva, Juliana Figueira da; Buzelin, Marcelo Araújo; Silva Júnior, Cláudio Antônio da; Santos, Duana Carvalho dos; Diniz, Danuza Montijo; Binda, Nancy Scardua; Borges, Marcia Helena; Guimarães, André Luiz Senna; Pereira, Elizete Maria Rita; Gomez, Marcus Vinicius
    Agents that modulate the activity of high-voltage gated calcium channels (HVCCs) exhibit experimentally and clinically significant effect by relieving visceral pain. Among these agents, the toxins Phα1β and ω-conotoxin MVIIA effectively reduce chronic pain in rodent models. The molecular mechanisms underlying the chronic pain associated with acute pancreatitis (AP) are poorly understood. Hypercalcemia is a risk factor; the role of cytosolic calcium is considered to be a modulator of pancreatitis. Blockade of Ca2+ signals may be useful as a prophylactic treatment of pancreatitis. We explored the pathophysiological roles of three peptide toxins: Phα1β and its re- combinant form CTK 01512-2—blockers of TRPA1 receptor and HVCCs and ω-conotoxin MVIIA, a specific blocker of N-type calcium channels in cerulein-induced AP. Cerulein injection elicits AP in rats, evidenced by an increase in hyperalgesic pain, inflammatory infiltration, amylase and lipase secretion, and reactive oxygen species, TNF-α, and p65 NF-κB levels. These effects of cerulein-induced AP were abolished by Phα1β and its recombinant form CTK 01512-2, whereas ω-conotoxin MVIIA had no effect on the induced increase in pancreatic enzyme secretion. Our results demonstrate that Phα1β and CTK 01512-2 toxins—antagonists of HVCCs and TRPA1 receptor presented an effective response profile, in the control of nociception and inflammatory process in the AP model in rats, without causing changes in spontaneous locomotion of the rats.
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    Conotoxin MVIIA improves cell viability and antioxidant system after spinal cord injury in rats.
    (2018) Oliveira, Karen Maciel de; Binda, Nancy Scardua; Lavor, Mário Sérgio Lima de; Silva, Carla Maria Osório; Rosado, Isabel Rodrigues; Alves, Endrigo Gabellini Leonel; Silva, Juliana Figueira da; Oliveira, Camila M.; Melo, Marilia Martins; Gomez, Marcus Vinicius; Melo, Eliane Gonçalves de
    This study evaluates whether intrathecal MVIIA injection after spinal cord injury (SCI) elicits neuroprotective effects. The test rats were randomly distributed into six groups— sham, placebo, MVIIA 2.5 μM, MVIIA 5 μM, MVIIA 10 μM, and MVIIA 20 μM—and were administered the treatment four hours after SCI. After the optimal MVIIA dose (MVIIA 10 μM) was defined, the best time for application, one or four hours, was analyzed. Locomotor hind limb function and side effects were assessed. Forty-eight hours after the injury and immediately after euthanasia, spinal cord segments were removed from the test rats. Cell viability, reactive oxygen species, lipid peroxidation, and glutamate release were investigated. To examine the MVIIA mechanism of action, the gene expressions of pro-apoptotic (Bax, nNOS, and caspase-3, -8, -9, -12) and anti-apoptotic (Bcl-xl) factors in the spinal cord tissue samples were determined by real-time PCR, and the activities of antioxidant enzymes were also investigated. Application of intrathecal MVIIA 10 μM four hours after SCI prompted a neuroprotective effect: neuronal death decreased (22.46%), oxidative stress diminished, pro-apoptotic factors (Bax, nNOS, and caspase-3, -8) were expressed to a lesser extent, and mitochondrial viability as well as anti-apoptotic factor (Bcl-xl) expression increased. These results suggested that MVIIA provided neuroprotection through antioxidant effects. Indeed, superoxide dismutase (188.41%), and glutathione peroxidase (199.96%), reductase (193.86%), and transferase (175.93%) expressions increased. Therefore, intrathecal MVIIA (MVIIA 10 μM, 4 h) application has neuroprotective potential, and the possible mechanisms are related to antioxidant agent modulation and to intrinsic and extrinsic apoptotic pathways.
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    Oficinas culinárias aumentam a ingestão de fibras e melhoram o estado emocional e a qualidade de vida de pacientes diabéticos?
    (2020) Lopes, Géssica Aparecida; Guimarães, Nathalia Sernizon; Santos, Vanessa Fortes da Silva; Carvalho, Flávia Garcia; Souza, Anelise Andrade de; Vieira Filho, Sidney Augusto; Binda, Nancy Scardua; Caligiorne, Rachel Basques; Figueiredo, Sônia Maria de
    Introdução: Diabetes mellitus é uma doença metabólica de evolução crônica que pode resultar em complicações clínicas e prejuízos multidimensionais no estado emocional e na qualidade de vida dos pacientes. Objetivo: Comparar a ingestão de fibras dietéticas, o estado emocional e a qualidade de vida de diabéticos participantes e não participantes de oficinas culinárias. Métodos: Estudo observacional descritivo realizado em Ambulatório pertencente a uma universidade pública da Região dos Inconfidentes, Minas Gerais, com pacientes com diabetes mellitus do tipo 2, de ambos os sexos. As avaliações da ingestão dietética de fibras, estado emocional e qualidade de vida foram realizadas através da aplicação do recordatório de 24 horas, escala B-PAID e WHOQOL-BREF, respectivamente. Dados foram analisados pelo software Stata®, versão 13.0. Resultados: Ao total, 22 diabéticos tipo 2 participaram deste estudo, alocados em dois grupos: grupo 1 (G1) participantes de oficinas culinárias (n=11) e grupo 2 (G2) não participantes das oficinas culinárias (n=11). A média do consumo de fibras dietéticas foi de 24,6 g para o G1 e 19,7g para o G2 (p<0.01). Quanto ao escore de avaliação do estado emocional, observou-se que os participantes de oficinas culinárias obtiveram 11,7 pontos e não participantes 30,7 pontos (p<0.01). Participantes de oficinas culinárias relataram qualidade de vida “boa” em 81,8% dos casos em detrimento de 18,2% dos não participantes das oficinas culinárias (p=0.013). Conclusão: Os diabéticos participantes das oficinas culinárias relataram maior ingestão de fibras, melhores estado emocional e qualidade de vida de pacientes diabéticos.
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    Phoneutria toxin PnTx3-5 inhibits TRPV1 channel with antinociceptive action in an orofacial pain model.
    (2020) Pereira, Elizete Maria Rita; Souza, Jéssica Mabelle; Carobin, Natália Virtude; Silva, Juliana Figueira da; Astoni, Duana Carvalho dos Santos; Silva Júnior, Cláudio Antônio da; Binda, Nancy Scardua; Borges, Marcia Helena; Nagem, Ronaldo Alves Pinto; Kushmerick, Christopher; Ferreira, Juliano; Castro Junior, Célio José de; Ribeiro, Fabiola Mara; Gomez, Marcus Vinicius
    Capsaicin, an agonist of TRPV1, evokes intracellular [Ca2+] transients and glutamate release from perfused trigeminal ganglion. The spider toxin PnTx3-5, native or recombinant is more potent than the selective TRPV1 blocker SB-366791 with IC50 of 47 ± 0.18 nM, 45 ± 1.18 nM and 390 ± 5.1 nM in the same experimental conditions. PnTx3-5 is thus more potent than the selective TRPV1 blocker SB-366791. PnTx3-5 (40 nM) and SB-366791 (3 μM) also inhibited the capsaicin-induced increase in intracellular Ca2+ in HEK293 cells transfected with TRPV1 by 75 ± 16% and 84 ± 3.2%, respectively. In HEK293 cells transfected with TRPA1, cinnamaldehyde (30 μM) generated an increase in intracellular Ca2+ that was blocked by the TRPA1 antagonist HC-030031 (10 μM, 89% inhibition), but not by PnTx3-5 (40 nM), indicating selectivity of the toxin for TRPV1. In whole-cell patch-clamp experiments on HEK293 cells transfected with TRPV1, capsaicin (10 μM) generated inward currents that were blocked by SB-366791 and by both native and recombinant PnTx3-5 by 47 ± 1.4%; 54 ± 7.8% and 56 ± 9.0%, respectively. Intradermal injection of capsaicin into the rat left vibrissa induced nociceptive behavior that was blocked by pre-injection with either SB-366791 (3 nmol/site i.d., 83.3 ± 7.2% inhibition) or PnTx3-5 (100 fmol/site, 89 ± 8.4% inhibition). We conclude that both native and recombinant PnTx3-5 are potent TRPV1 receptor antagonists with antinociceptive action on pain behavior evoked by capsaicin.
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    Physicochemical characteristics of Brazilian green propolis evaluated during a six-year period.
    (2017) Figueiredo, Sônia Maria de; Binda, Nancy Scardua; Vieira Filho, Sidney Augusto; Almeida, Bruno de Moura; Abreu, Sheila Rago Lemos; Paulino, Niraldo; Pastore, Gláucia Maria; Sato, Hélia Harumi; Theodoropoulos, Viviane Cristina Toreti; Tapia, Eulália Vargas; Park, Yong Kun; Caligiorne, Rachel Basques
    Background: Propolis has been used as a natural health product mainly due to the presence of polyphenols, flavonoids, phenolic aldehydes, amino acids, vitamins and others bioactive constituents. To this natural substance are attributed different biological and pharmacological properties which are influenced by its chemical composition and organoleptic properties. The aim of this work was to evaluate the physicochemical properties and parameters of green propolis collected during a period of six years (2008-2013) in the state of Minas Gerais, located at the southeastern region of Brazil. Methods: The methodology were in accordance with Brazilian legislation on the identity and quality standards of propolis. The evaluated parameters of hydroalcoholic from green propolis were total flavonoids, antioxidant activity - DPPH method, oxidation index, wax content, humidity and insoluble impurities. Results: Propolis samples collected in different seasons during the years 2008 to 2013 presented mean values of total flavonoids (3.4 ± 0.11 mg/g), antioxidant activity DPPH (4.76 ± 0.16 μg/mL), oxidation index (3, 4 ± 0.33 seconds) and wax (15.14 ± 0.78% m/m), which are in accordance with Brazilian legislation. Conclusion: Green propolis did not show abrupt seasonal changes during the six years of investigation, and may be considered as an adequate functional ingredient.
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    The inhibitory efect of Phα1β toxin on diabetic neuropathic pain involves the CXCR4 chemokine receptor.
    (2020) Silva Júnior, Cláudio Antônio da; Castro Junior, Célio José de; Pereira, Elizete Maria Rita; Binda, Nancy Scardua; Silva, Juliana Figueira da; Cordeiro, Marta do Nascimento; Diniz, Danuza Montijo; Santa Cecília, Flávia Viana; Ferreira, Juliano; Gomez, Marcus Vinicius
    Background: Diabetic neuropathy is a common cause of painful diabetic neuropathy (PDN). C-X-C chemokine receptor type 4 (CXCR4) expression is increased in peripheral nerve samples from diabetes patients, suggesting a role for CXCR4 in PDN. Therefore, we evaluated the effects of Phα1β, ω-conotoxin MVIIA, and AMD3100 in a model of streptozotocin (STZ)-induced PDN in rodents and naïve model of rats with the activation of the CXCR4/stromal cell-derived factor 1 (SDF-1) signal. Methods: Diabetic neuropathy was induced by intraperitoneal (ip) injection of STZ in Wistar rats. Naïve rats were intrathecally injected with SDF-1 to test the CXCR4/SDF-1 signal. The effects of Phα1β intrathecal (it), ω-conotoxin MVIIA intrathecal (it), and AMD3100 intraperitoneal (ip) on rat hypersensitivity, IL-6, and the intracellular calcium [Ca2+]i content of diabetic synaptosomes were studied. Results: The drugs reduced the hypersensitivity in diabetic rats. SDF-1 (1.0 µg/it) administration in naïve rats induced hypersensitivity. Phα1β (100 pmol/it) or AMD3100 (2.5 µg/ip) reduced this hypersensitivity after 2 h treatments, while ω-conotoxin MVIIA did not have an effect. IL-6 and [Ca2+]i content increased in the spinal cord synaptosomes in diabetic rats. The drug treatments reduced IL-6 and the calcium influx in diabetic synaptosomes. Conclusions: Phα1β, ω-conotoxin MVIIA, and AMD3100, after 2 h of treatment of STZ-induced PDN, reduced hypersensitivity in diabetic rats. In naïve rats with CXCR4/SDF-1 activation, the induced hypersensitivity decreased after 2 h treatments with Phα1β or AMD-3100, while ω-conotoxin MVIIA did not affect. The inhibitory effects of Phα1β on PDN may involve voltage-dependent calcium channels.