EFAR - Escola de Farmácia

URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/451

Notícias

O curso de Farmácia em Ouro Preto foi criado em 1839, sendo a mais antiga Escola de Farmácia da América Latina.

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3'UTR polymorphism of Thymidylate Synthase gene increased the risk of persistence of pre-neoplastic cervical lesions.
(2020) Silva, Nayara Nascimento Toledo; Santos, Ana Carolina da Silva; Nogueira, Verlândia Mendes; Carneiro, Cláudia Martins; Lima, Angélica Alves
Background: Cervical cancer is caused by high-risk Human Papillomavirus (hr-HPV) infection associated with cofactors that has been analyzed as predictors of the remission or persistence of cytological abnormalities remission or persistence. These cofactors can be either environmental, epigenetic, or genetic. Polymorphism in genes of enzymes that act on one-carbon metabolism alter their activity and also may be associated with cervical carcinogenesis because they affect DNA synthesis and repair, and gene expression. Therefore, this study aimed to analyze the risk of persistence of pre-neoplastic cervical lesions according to genetic polymorphisms involved in one-carbon metabolism. Methods: Our sample consisted of 106 women, divided into two groups – Remission (n = 60), i.e., with the presence of pre-neoplastic lesions at first meeting (T1) and normal cytology after 6 months of follow-up (T2), and Persistence (n = 46), i.e., with the presence of pre-neoplastic lesions at T1 and T2. We obtained cervical samples for cytological analysis (T1 and T2), HPV detection (T1), and evaluation of polymorphism C667T of Methylenetetrahydrofolate Reductase (MTHFR C677T), A2756G of Methionine Synthase (MS A2756G), A66G of Methionine Synthase Reductase (MTRR A66G), double or triple 28 bp tandem repeat in 5′-untranslated enhanced region of Thymidylate Synthase (TSER), and 6 bp deletion at nucleotide 1494 in TS 3′-untranslated region (TS3’UTR). To analyze all genetic polymorphisms simultaneously, we calculated the Genetic Risk Score (GRS). Results: We observed no differences between the Remission and Persistence groups regarding the GRS. Also, there were no differences in the genotypic and allelic distribution of MTHFR C677T and MS A2756G polymorphisms. However, the risk of persistence was higher among women with the heterozygote genotype - ins/del [OR (IC95%): 3.22 (1.19–8.69), p = 0.021], or the polymorphic genotype – del/del [OR (IC95%): 6.50 (1.71–24.70), p = 0.006] of TS3’UTR. Conclusions: The presence of the TS3’UTR polymorphism increased the risk of persistence of cervical abnormalities. This genetic variant could be a potential marker of cervical carcinogenesis and therefore assist the follow-up of women with persistent pre-neoplastic cervical lesions.
3-beta-(Stearyloxy)olean-12-ene from Austroplenckia populnea : structure elucidation by 2D-NMR and quantitative 13C-NMR spectroscopy.
(2003) Vieira Filho, Sidney Augusto; Duarte, Lucienir Pains; Silva, Grácia Divina de Fátima; Howarth, O. W.; Lula, Ivana Silva
3 -(Stearyloxy)olean-12-ene was isolated from a hexane extract of Austroplenckia populnea Reiss (Celastraceae) leaves. The structure was solved by means of quantitative 13C-NMR, HMBC, HMQC, COSY, NOESY, and NOE difference spectra. The mass spectrum showed an [M 1] ion peak at m/z 693, and the molecular formula C48H84O2 was confirmed by combustion analysis.
7-Chloroquinolinotriazoles : synthesis by the azide-alkyne cycloaddition click chemistry, antimalarial activity, cytotoxicity and SAR studies.
(2014) Pereira, Guilherme Rocha; Brandão, Geraldo Célio; Arantes, Lucas Micquéias; Oliveira Junior, Haliton Alves de; Paula, Renata Cristina de; Nascimento, Maria Fernanda Alves do; Santos, Fábio Mendes dos; Rocha, Ramon Kleber da; Lopes, Júlio César Dias; Oliveira, Alaíde Braga de
Twenty-seven 7-chloroquinolinotriazole derivatives with different substituents in the triazole moiety were synthesized via copper-catalyzed cycloaddition (CuAAC) click chemistry between 4-azido-7- chloroquinoline and several alkynes. All the synthetic compounds were evaluated for their in vitro activity against Plasmodium falciparum (W2) and cytotoxicity to Hep G2A16 cells. All the products disclosed low cytotoxicity (CC50 > 100 mM) and five of them have shown moderate antimalarial activity (IC50 from 9.6 to 40.9 mM). As chloroquine analogs it was expected that these compounds might inhibit the heme polymerization and SAR studies were performed aiming to explain their antimalarial profile. New structural variations can be designed on the basis of the results obtained.
Abordagem epidemiológica e epigenética para estudo da esquistossomose mansônica.
(2019) Assenço, Regina Aparecida Gomes; Cota, Renata Guerra de Sá; Borges, William de Castro; Gomes, Maria Aparecida; Babá, Élio Hideo; Lana, Marta de; Veloso, Vanja Maria; Cota, Renata Guerra de Sá
Inicialmente foi realizado um estudo descritivo da positividade da esquistossomose mansônica, por meio de exames parasitológicos de fezes, realizados utilizando o método de Kato-Katz, no período de 2011 a 2015 no município de Mariana, Minas Gerais, Brasil. As áreas endêmicas foram localizadas por meio de mapas de distribuição. Concluiu-se que a maioria dos indivíduos infectados tinha entre 16 e 30 anos de idade; e crianças e adolescentes de 0 a 15 anos representam uma parte importante desse cenário. A maioria das pessoas infectadas apresentou uma baixa carga parasitária refletida pelo número predominante, de 0 e 4 ovos, encontrados nos exames realizados utilizando a técnica de Kato-Katz. Paralelamente, padronizou-se a metodologia de extração de miRNAs a partir de sangue, soro ou plasma de camundongos experimentalmente infectados com 100 cercárias de S. mansoni. Posteriormente o sangue total e o soro de 30 indivíduos infectados com S. mansoni e 30 não infectados, pertencentes a distritos do Município de Mariana, Minas Gerais, foram utilizados para a extração de miRNAs. Apesar de até o momento não temos uma visão consolidada do perfil de miRNA em indivíduos infectados, na esquistosomose murina detectou-se um enriquecimento dos seguintes miRNAs: Bantan, miR-2c-3p e miR190 nas amostras sequenciadas, independente do tempo e tratamento da infecção nas amostras. Nesse trabalho foi investigado se a metilação do DNA hepático, no modelo de esquistossome murina seria alterado em resposta à infecção por S. mansoni. Para investigar essa hipótese, foi avaliado: (i) a expressão dos genes DNMT1, DNMT3A, DNMT3B, TET1, TET2 e TET3 (ii) o conteúdo global de metilação e (iii) se haveria correlação entre número de ovos presente no fígado e a expressão dos genes que codificam as enzimas que metilam e desmetilam o DNA. Foi observado um aumento de expressão das enzimas TET1, TET2 e TET3 em resposta à infecção por S. mansoni e na expressão das enzimas envolvidas na metilação de novo do DNA, que não apresentou correlação direta com o conteúdo global de metilação do DNA hepático. Verificou-se que a interferência epigenética ocorreu e tem particular relevância no contexto da expressão gênica e da manifestação fenotípica. Investigações adicionais explorando como as interações modulam os mecanismos de de regulação da expressão gênica ao nível epigenético no parasita, podem revelar novas estratégias dirigidas para o controle da esquistossomose.
Ação do resveratrol e das tinturas das cascas e das folhas de Vitis labrusca L. var. Isabel na hiperlipidemia induzida em coelhos.
(2010) Fonseca, Karina Zanoti; Oliveira, Tânia Toledo de; Nagem, Tanus Jorge; Souza, Gustavo Henrique Bianco de; Pedrosa, Maria Lúcia; Oliveira, Tânia Toledo de; Mosqueira, Vanessa Carla Furtado
As doenças crônicas não transmissíveis acometem milhões de pessoas em todo o mundo e seu principal fator de risco é a hiperlipidemia. A terapia medicamentosa para a hiperlipidemia pode envolver efeitos colaterais que dificultam a adesão ao tratamento. Assim, somando-se ao grande potencial fitoterápico que algumas plantas do território brasileiro possuem e o incentivo da fitoterapia no Sistema Único de Saúde, é necessário investigar novas formas de tratamento. Neste trabalho investigou-se o efeito do resveratrol e das tinturas das cascas e das folhas da uva Vitis labrusca L. var. Isabel em coelhos com hiperlipidemia induzida. Os animais utilizados foram fornecidos pelo setor de Cunicultura do Departamento de Zootecnia da Universidade Federal de Viçosa, sendo 72 coelhos da raça Nova Zelândia, machos, albinos, com idade de 55 dias e peso de 2000 g, divididos em 12 grupos, sendo um doente sem tratamento, um controle, atorvastatina (medicamento utilizado como padrão) e outros 9 grupos que receberam três doses crescentes de resveratrol, tintura das cascas e das folhas. Os animais foram tratados diariamente durante 60 dias, juntamente com a dieta acrescida de 1% de colesterol. Os parâmetros sanguíneos: colesterol total; HDL; triglicérides; Gama GT; creatinina; ácido úrico; uréia; TGO; TGP, lipase foram analisados. A análise histológica das artérias e do fígado foi realizada para complementar as análises. Os dados foram analisados pelo teste de ANOVA seguido pelo teste de Tukey. Para a identificação do resveratrol em todas as partes aéreas da uva pesquisada, foi utilizado o cromatógrafo a líquido Waters Corporation, USA, 2695. Para separação dos compostos utilizou-se uma coluna de fase reversa Symnethy C18 (4,6 x 75 mm, 3,5 μm) com detector de arranjo diodo UV/VIS. No tempo 30, o resveratrol e a tintura das cascas nas maiores doses produziram a maior redução de colesterol total. Para HDL o grupo resveratrol 37,5 mg foi o melhor e para a atividade da lipase foi o grupo que recebeu a tintura das folhas 1,5 mL. Resveratrol na 22,5 mg e tintura das cascas na 2,0 mL foram os tratamentos que mais reduziram os níveis de triglicérides. No tempo 60, o tratamento com tintura das cascas 2,0 mL produziu o melhor resultado para colesterol total, HDL, o grupo resveratrol 37,5 mg, triglicérides e atividade da lipase, o grupo que recebeu tintura das folhas 2,0 mL. A análise histológica revelou que os grupos tintura da casca, tintura da folha e resveratrol nas maiores doses tiveram os melhores efeitos na aterosclerose produzida pela hiperlipidemia, sendo comparados à estatina, enquanto os outros grupos não diferiram do grupo doente sem tratamento.a análise do fígado mostrou que o grupo resveratrol 56,5 mg não diferiu do grupo controle, enquanto a atorvastatina foi o tratamento que produziu maior toxicidade e esteatose. Todos os outros grupos foram melhores que o medicamento de mercado. O trans resveratrol não foi identificado em nenhuma das partes aéreas, enquanto o cis foi detectado em todas.
Accelerated Blood Clearance (ABC) phenomenon favors the accumulation of tartar emetic in pegylated liposomes in BALB/c mice liver.
(2018) Lopes, Tamara Cristina Moreira; Silva, Débora Faria; Costa, Walyson Coelho; Frezard, Frederic Jean Georges; Barichello, José Mario; Barcellos, Neila Marcia Silva; Lima, Wanderson Geraldo de; Rezende, Simone Aparecida
Tartar emetic (TE) was the first drug used to treat leishmaniasis.However, its use was discontinued due to high toxicity. Association of TE with liposomes is a strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower rates of uptake by macrophages and prolonged circulation compared to their nonpegylated counterparts. However, repeated administration of Lpeg can cause an Accelerated Blood Clearance (ABC) phenomenon, whereby recognition of liposomes by antibodies results in faster phagocytosis. Thiswork evaluated the effect of TE administration on histopathological aspects and the effect of the ABC phenomenon on targeting and toxicity in mice. Our results show that treatment with free or liposomal TE had no effect on the erythrocyte count, on liver and spleen weight, and on hepatic, splenic, and cardiac histology in mice. Severe lesions were observed on the kidneys of animals treated with a single dose of free TE. Treatment with TE in Lpeg after induction of ABC phenomenon caused a significant increase in Sb level in the liver without toxicity. Furthermore, mice treated with TE in liposomes showed normal renal histopathology. These results suggest site-specific targeting of Sb to the liver after induction of ABC phenomenon with no toxicity to other organs.
Accomplishing the genotype-specific serodiagnosis of single and dual Trypanosoma cruzi infections by flow cytometry Chagas- Flow ATE-IgG2a.
(2018) Alessio, Glaucia Diniz; Araújo, Fernanda Fortes de; Sales Júnior, Policarpo Ademar; Gomes, Matheus de Souza; Amaral, Laurence Rodrigues do; Xavier, Marcelo Antônio Pascoal; Carvalho, Andréa Teixeira de; Lana, Marta de; Martins Filho, Olindo Assis
The methods currently available for genotype-specific diagnosis of T. cruzi infection still present relevant limitations, especially to identify mixed infection. In the present investigation, we have evaluated the performance of Chagas-Flow ATE-IgG2a test for early and late differential diagnosis of single and dual genotype-specific T. cruzi infections. Serum samples from Swiss mice at early and late stages of T. cruzi infection were assayed in parallel batches for genotype-specific diagnosis of single (TcI, TcVI or TcII) and dual (TcI+TcVI, TcVI+TcII or TcII+TcI) infections. The intrinsic reactivity to TcI, TcVI and TcII target antigens, including amastigote (AI/AVI/AII), trypomastigote-(TI/TVI/TII) and epimastigote (EI/ EVI/EII), at specific reverse of serum dilutions (500 to 64,000), was employed to provide reliable decision-trees for ªearlyº vs ªlateº, ªsingle vs ªdualº and ªgenotype-specificº serology. The results demonstrated that selective set of attributes ªEII 500/EI 2,000/AII 500º were able to provide high-quality accuracy (81%) to segregate early and late stages of T. cruzi infection. The sets ªTI 2,000/AI 1,000/EII 1,000º and ªTI 8,000/AII 32,000º presented expressive scores to discriminate single from dual T. cruzi infections at early (85%) and late stages (84%), respectively. Moreover, the attributes ªTI 4,000/TVI 500/TII 1,000º, ªTI 16,000/EI 2,000/EII 2,000/AI 500/TVI 500º showed good performance for genotype-specific diagnosis at early stage of single (72%) and dual (80%) T. cruzi infections, respectively. In addition, the attributes ªTI 4,000/AII 1,000/EVI 1,000º, ªTI 64,000/AVI 500/AI 2,000/AII 1,000/EII 4,000º showed moderate performance for genotype-specific diagnosis at late stage of single (69%) and dual (76%) T. cruzi infections, respectively. The sets of decision-trees were assembled to construct a sequential algorithm with expressive accuracy (81%) for serological diagnosis of T. cruzi infection. These findings engender new perspectives for the application of Chagas-Flow ATE-IgG2a method for genotype-specific diagnosis in humans, with relevant contributions for epidemiological surveys as well as clinical and post-therapeutic monitoring of Chagas disease.
ACE inhibition by astilbin isolated from Erythroxylum gonocladum (Mart.) O.E. Schulz.
(2010) Lucas Filho, Milton Dayrell; Silva, Grazielle Caroline da; Côrtes, Steyner de França; Guia, Thiago Rennó dos Mares; Ferraz, Vany Perpetua; Serra, Carla Penido; Braga, Fernão Castro
Erythroxylum species have several traditional uses in different countries, including the treatment of hypertension. The ethanol extract from E. gonocladum aerial parts, a species endemic to the Brazilian cerrado, elicited a concentration-dependent inhibition of angiotensin converting enzyme (ACE) (pIC50=4.53±0.05). Extract fractionation led to the isolation of two compounds, whose structures were assigned by spectrometric data as astilbin and β-sitosterol, along with a mixture of palmitic, stearic and linolenic acids. This is the first report on the occurrence of these compounds on E. gonocladum. Astilbin promoted significant ACE inhibition in vitro (pIC50=5.86±0.33) and its activity did not differ from captopril, when both compounds were assayed at 10 μM concentration.
Ações de saúde e económicas como resposta à pandemia do SARS-CoV-2 no Brasil.
(2020) Santi, Valmir de; Campesatto, Eliane Aparecida; Nascimento, Renata Cristina Rezende Macedo do; Uehara, Wilson Hiroshi de Oliveira
Activation of the ET-1/ETA pathway contributes to erectile dysfunction associated with mineralocorticoid hypertension.
(2008) Carneiro, Fernando Silva; Nunes, Kenia Pedrosa; Vitorino, Fernanda Regina Casagrande Giachini; Lima, Victor Vitorino; Carneiro, Zidonia N.; Nogueira, Edson F.; Leite, Romulo; Ergul, Adviye; Rainey, William E.; Webb, Robert Clinton; Passaglia, Rita de Cassia Aleixo Tostes
Introduction. The cavernosal tissue is highly responsive to endothelin-1 (ET-1), and penile smooth muscle cells not only respond to but also synthesize ET-1. Aim. Considering that ET-1 is directly involved in end-organ damage in salt-sensitive forms of hypertension, we hypothesized that activation of the ET-1/ETA receptor pathway contributes to erectile dysfunction (ED) associated with mineralocorticoid hypertension. Methods. Wistar rats were uninephrectomized and submitted to deoxycorticosterone acetate (DOCA)-salt treatment for 5 weeks. Control (Uni [uninephrectomized control]) animals were uninephrectomized and given tap water. Uni and DOCA-salt rats were simultaneously treated with vehicle or atrasentan (ETA receptor antagonist, 5 mg/ Kg/day). Cavernosal reactivity to ET-1, phenylephrine (PE), ETB receptor agonist (IRL-1620) and electric field stimulation (EFS) were evaluated in vitro. Expression of ROCKa, ROCKb, myosin phosphatase target subunit 1 (MYPT-1), and extracellular signal-regulated kinase 1/2 (ERK 1/2) were evaluated by western blot analysis. ET-1 and ETA receptor mRNA expression was evaluated by real-time reverse-transcriptase polymerase chain reaction. Voltage-dependent increase in intracavernosal pressure/mean arterial pressure (ICP/MAP) was used to evaluate erectile function in vivo. Main Outcome Measure. ETA receptor blockade prevents DOCA-salt-associated ED. Results. Cavernosal strips from DOCA-salt rats displayed augmented preproET-1 expression, increased contractile responses to ET-1 and decreased relaxation to IRL-1620. Contractile responses induced by EFS and PE were enhanced in cavernosal tissues from DOCA-salt hypertensive rats. These functional changes were associated with increased activation of the RhoA/Rho-kinase and ERK 1/2 pathways. Treatment of rats with atrasentan completely prevented changes in cavernosal reactivity in DOCA-salt rats and restored the decreased ICP/MAP, completely preventing ED in DOCA-salt rats. Conclusion. Activation of the ET-1/ETA pathway contributes to mineralocorticoid hypertension-associated ED. ETA receptor blockade may represent an alternative therapeutic approach for ED associated with salt-sensitive hypertension and in pathological conditions where increased levels of ET-1 are present.
Activation ofGPR40 induces hypothalamic neurogenesis through p38‐ and BDNF‐dependent mechanisms.
(2020) Engel, Daiane Fátima; Bobbo, Vanessa Cristina Dias; Solon, Carina Silva; Nogueira, Guilherme Augusto Silva; Assis, Alexandre Moura; Mendes, Natália Ferreira; Zanesco, Ariane Maria; Papangelis, Athanasios; Ulven, Trond; Velloso, Licio Augusto
Hypothalamic adult neurogenesis provides the basis for renewal of neurons involved in the regulation of whole-body energy status. In addition to hormones, cytokines and growth factors, components of the diet, particularly fatty acids, have been shown to stimulate hypothalamic neurogenesis; however, the mechanisms behind this action are unknown. Here, we hypothesized that GPR40 (FFAR1), the receptor for medium and long chain unsaturated fatty acids, could mediate at least part of the neurogenic activity in the hypothalamus. We show that a GPR40 ligand increased hypothalamic cell proliferation and survival in adult mice. In postnatal generated neurospheres, acting in synergy with brain-derived neurotrophic factor (BDNF) and interleukin 6, GPR40 activation increased the expression of doublecortin during the early diferentiation phase and of the mature neuronal marker, microtubule-associated protein 2 (MAP2), during the late diferentiation phase. In Neuro-2a proliferative cell-line GPR40 activation increased BDNF expression and p38 activation. The chemical inhibition of p38 abolished GPR40 efect in inducing neurogenesis markers in neurospheres, whereas BDNF immunoneutralization inhibited GPR40-induced cell proliferation in the hypothalamus of adult mice. Thus, GPR40 acts through p38 and BDNF to induce hypothalamic neurogenesis. This study provides mechanistic advance in the understating of how a fatty acid receptor regulates adult hypothalamic neurogenesis.
Activity of alkaloids from Aspidosperma nitidum against Leishmania (Leishmania) amazonensis.
(2022) Veiga, Andreza do Socorro Silva da; Silveira, Fernando Tobias; Silva, Edilene Oliveira da; Diniz Júnior, José Antônio Picanço; Araújo, Sanderson Corrêa; Campos, Marliane Batista; Marinho, Andrey Moacir do Rosário; Brandão, Geraldo Célio; Vale, Valdicley Vieira; Percário, Sandro; Dolabela, Maria Fâni
This study evaluated the morphological changes caused by fractions and subfractions, obtained from barks of Aspidosperna nitidum, against L. (L.) amazonensis promastigotes. The ethanolic extract (EE) obtained through the maceration of trunk barks was subjected to an acid–base partition, resulting the neutral (FN) and the alkaloid (FA) fractions, and fractionation under refux, yielded hexane (FrHEX), dichloromethane (FrDCL), ethyl acetate (FrACoET), and methanol (FrMEOH) fractions. The FA was fractionated and three subfractions (SF5-6, SF8, and SF9) were obtained and analyzed by HPLC–DAD and 1 H NMR. The antipromastigote activity of all samples was evaluated by MTT, after that, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for the active fractions were performed. Chromatographic analyzes suggest the presence of alkaloids in EE, FN, FA, and FrDCL. The fractionation of FA led to the isolation of the indole alkaloid dihydrocorynantheol (SF8 fractions). The SF5-6, dihydrocorynantheol and SF-9 samples were active against promastigotes, while FrDCL was moderately active. The SEM analysis revealed cell rounding and changes in the fagellum of the parasites. In the TEM analysis, the treated promastigotes showed changes in fagellar pocket and kinetoplast, and presence of lipid inclusions. These results suggest that alkaloids isolated from A. nitidum are promising as leishmanicidal.
Activity of the new triazole derivative albaconazole against Trypanosoma (Schizotrypanum) cruzi in dog hosts.
(2004) Guedes, Paulo Marcos da Matta; Urbina, Julio Alberto; Lana, Marta de; Afonso, Luís Carlos Crocco; Veloso, Vanja Maria; Tafuri, Washington Luiz; Coelho, George Luiz Lins Machado; Chiari, Egler; Bahia, Maria Terezinha
Albaconazole is an experimental triazole derivative with potent and broad-spectrum antifungal activity and a remarkably long half-life in dogs, monkeys, and humans. In the present work, we investigated the in vivo activity of this compound against two strains of the protozoan parasite Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas’ disease, using dogs as hosts. The T. cruzi strains used in the study were previously characterized (murine model) as susceptible (strain Berenice-78) and partially resistant (strain Y) to the drugs currently in clinical use, nifurtimox and benznidazole. Our results demonstrated that albaconazole is very effective in suppressing the proliferation of the parasite and preventing the death of infected animals. Furthermore, the parasitological, PCR, serological, and proliferative assay results indicated parasitological cure indices of 25 and 100% among animals inoculated with T. cruzi strain Y when they were treated with albaconazole at 1.5 mg/kg of body weight/day for 60 and 90 days, respectively. On the other hand, although albaconazole given at 1.5 mg/kg/day was very effective in suppressing the proliferation of the parasite in animals infected with the Berenice-78 T. cruzi strain, no parasitological cure was observed among them, even when a longer treatment period (150 doses) was used. In conclusion, our results demonstrate that albaconazole has trypanocidal activity in vivo and is capable of inducing radical parasitological cure, although natural resistance to this compound was also indicated. Furthermore, the compound can be used in long-term treatment schemes (60 to 150 days) with minimal toxicity and thus represents a potentially useful candidate for the treatment of human Chagas’ disease.
Activity of the sesquiterpene lactone goyazensolide against Trypanosoma cruzi in vitro and in vivo.
(2020) Milagre, Matheus Marques; Branquinho, Renata Tupinambá; Gonçalves, Maíra Fonseca; Assis, Gabriela Maíra Pereira de; Oliveira, Maykon Tavares de; Reis, Levi Eduardo Soares; Guimarães, Dênia Antunes Saúde; Lana, Marta de
Background: The current drugs for Chagas disease treatment present several limitations Methods: The sesquiterpene lactone goyazensolide (GZL) was evaluated regarding to cytotoxicity and trypanocidal activity against amastigotes, selectivity index (SI) in vitro, acute toxicity and anti-Trypanosoma cruzi activity in vivo. Results: The in vitro cytotoxicity in H9c2 cells was observed at doses >250 ng mL−1 of GZL and the SI were of 52.82 and 4.85 (24 h) and of 915.00 and 41.00 (48 h) for GZL and BZ, respectively. Nephrotoxicity and hepatotoxicity were not verified. Treatment with GZL of mice infected with CL strain led to a significant decrease of parasitaemia and total survival at doses of 1 and 3 mg kg−1 day−1 by oral and IV, respectively. This last group cured 12.5% of the animals (negativation of HC, PCR, qPCR and ELISA). Animals infected with Y strain showed significant decrease of parasitaemia and higher negativation in all parasitological tests in comparison to BZ and control groups, but were ELISA reactive, as well as the BZ group, but mice treated with 5.0 mg kg−1 day−1 by oral were negative in parasitological tests and survived. Conclusion: GZL was more active against T. cruzi than benznidazole in vitro and presented important therapeutic activity in vivo in both T. cruzi strains.
Additive effects of resveratrol and doxorubicin on bladder cancer cells.
(2022) Soares, Luciana Bicalho Moreira; Lima, Ana Paula Braga; Melo, André Sacramento; Almeida, Tamires Cunha; Teixeira, Luiz Fernando de Medeiros; Silva, Glenda Nicioli da
The treatment of bladder cancer remains a challenge in clinical practice. Different chemotherapeutic protocols can be used; however, it is common to observe tumor recurrence and secondary effects that result in toxicity. Doxorubicin (DOX), one of the most effective anticancer agents used to treat bladder cancer, can cause chronic cardiotoxicity, limiting its use in clinical practice. Resveratrol (RES), a natural product with potential antitumor activity against bladder cancer, is associated with rapid metabolism and low bioavailability and needs to be combined with chemotherapeutic drugs to improve its use. Our study aimed to assess the therapeutic effect of a low concentration of DOX (2µM) in combination with RES (150, 200 and 250µM) on two bladder cancer cell lines. We investigated the mechanism of interaction between the drugs by performing cytotoxicity, clonogenic, oxidative stress, cell migration, cell morphology and nuclear division index (NDI) assays. Cytotoxicity evaluation revealed an additive interaction between RES and DOX for both cell lines. Additionally, the results of cell colony formation, oxidative stress, cell migration, cell morphology and NDI assays showed that a combination of DOX and RES was more effective than RES or DOX alone. In conclusion, a low concentration of DOX combined with RES could potentiate the antitumor effects of the drugs on bladder cancer cells, thus overcoming the secondary effects caused by DOX and the low bioavailability of resveratrol.
Adenosine actions are preserved in corpus cavernosum from obese and type II diabetic db/db mouse.
(2008) Carneiro, Fernando Silva; Vitorino, Fernanda Regina Casagrande Giachini; Lima, Victor Vitorino; Neotzold, Zidonia Nunes; Leite, Romulo; Inscho, Edward W.; Passaglia, Rita de Cassia Aleixo Tostes; Webb, Robert Clinton
Introduction—Erectile dysfunction (ED) in diabetes is associated with autonomic neuropathy and endothelial dysfunction. Whereas the nonadrenergic-noncholinergic (NANC)/neurogenic nitric oxide pathway has received great attention in diabetes-associated ED, few studies have addressed sympathetic overactivity. Aim—To test the hypothesis that adenosine-induced inhibition of adrenergic-mediated contractile responses in mouse corpus cavernosum is impaired in the presence of diabetes. Methods—The db/db (obesity and type II diabetes caused by a leptin receptor mutation) mouse strain was used as a model of obesity and type II diabetes, and standard procedures were performed to evaluate functional cavernosal responses. Main Outcome Measures—Increased cavernosal responses to sympathetic stimulation in db/ db mice are not associated with impaired prejunctional actions of adenosine. Results—Electrical field stimulation (EFS)-, but not phenylephrine (PE)-, induced contractions are enhanced in cavernosal strips from db/db mice in comparison with those from lean littermates. Direct effects of adenosine, 2-chloro-adenosine, A1 receptor agonist C-8031 (N6 cyclopentyladenosine), and sodium nitroprusside are similar between the strips from lean and db/ db mice, whereas relaxant responses to acetylcholine and NANC stimulation are significantly impaired in the cavernosal strips from db/db mice. 5′-Iodotubercidin (adenosine kinase inhibitor) and dipyridamole (inhibitor of adenosine transport), as well as the A1 agonist C-8031, significantly and similarly inhibit contractions induced by stimulation of adrenergic nerves in the cavernosal strips from lean and db/db mice. Conclusions—Results from this study suggest that corpora cavernosa from obese and diabetic db/db mice display altered neural-mediated responses that would favor penile detumescence, i.e., increased contractile response to adrenergic nerve stimulation and decreased relaxant responses upon activation of NANC nerves. However, increased cavernosal responses to adrenergic nerve stimulation are not due to impaired negative modulation of sympathetic neurotransmission by adenosine in this diabetic model.
Adhesion on yeast cell surface as a trapping mechanism of pathogenic bacteria by Saccharomyces probiotics.
(2012) Tiago, Fabiana da Conceição Pereira; Martins, Flaviano dos Santos; Souza, Éricka Lorenna de Sales e; Pimenta, Paulo Filemon Paolucci; Araújo, Helena Rocha Corrêa de; Castro, Ieso de Miranda; Brandão, Rogélio Lopes; Nicoli, Jacques Robert
Recently, much attention has been given to the use of probiotics as an adjuvant for the prevention or treatment of gastrointestinal pathology. The great advantage of therapy with probiotics is that they have few side effects such as selection of resistant bacteria or disturbance of the intestinal microbiota, which occur when antibiotics are used. Adhesion of pathogenic bacteria onto the surface of probiotics instead of onto intestinal receptors could explain part of the probiotic effect. Thus, this study evaluated the adhesion of pathogenic bacteria onto the cell wall of Saccharomyces boulardii and Saccharomyces cerevisiae strains UFMG 905, W303 and BY4741. To understand the mechanism of adhesion of pathogens to yeast, cell-wall mutants of the parental strain of Saccharomyces cerevisiae BY4741 were used because of the difficulty of mutating polyploid yeast, as is the case for Saccharomyces cerevisiae and Saccharomyces boulardii. The tests of adhesion showed that, among 11 enteropathogenic bacteria tested, only Escherichia coli, Salmonella Typhimurium and Salmonella Typhi adhered to the surface of Saccharomyces boulardii, Saccharomyces cerevisiae UFMG 905 and Saccharomyces cerevisiae BY4741. The presence of mannose, and to some extent bile salts, inhibited this adhesion, which was not dependent on yeast viability. Among 44 cell-wall mutants of Saccharomyces cerevisiae BY4741, five lost the ability to fix the bacteria. Electron microscopy showed that the phenomenon of yeast–bacteria adhesion occurred both in vitro and in vivo (in the digestive tract of dixenic mice). In conclusion, some pathogenic bacteria were captured on the surface of Saccharomyces boulardii, Saccharomyces cerevisiae UFMG 905 and Saccharomyces cerevisiae BY4741, thus preventing their adhesion to specific receptors on the intestinal epithelium and their subsequent invasion of the host.
Adsorption of starch, amylose, amylopectin and glucose monomer and their effect on the flotation of hematite and quartz.
(2003) Pavlovic, Suzana; Brandão, Paulo Roberto Gomes
The depressant effect of corn starch, its polysaccharide components (amylose and amylopectin), the monomer glucose and the dimer maltose were studied on hematite and quartz, by means of infrared spectrometry, adsorption isotherms determination and microflotation tests. All the carbohydrates tested have been effective in maintaining hematite hydrophilic, including glucose and maltose; as for quartz, only a flocculation action (mainly by amylopectin) had a mild effect in decreasing its floatability by the amine collector. FTIR studies confirmed that the carbohydrates adsorbed intensively onto hematite and the spectra of the adsorbed polymers and monomer were very similar, even though the non-adsorbed monomer spectrum was markedly different. The common adsorption mechanism indicated is a surface reaction involving the iron ion.
Advances in Chagas disease chemotherapy.
(2006) Guedes, Paulo Marcos da Matta; Fietto, Juliana Lopes Rangel; Lana, Marta de; Bahia, Maria Terezinha
Chagas disease is endemic from Mexico to Argentina, where it is estimated that 16 to 18 million people are infected with its causative agent, Trypanosoma cruzi, and 100 million remain at risk of infection, emphasizing the necessity to sustain and extend control measures and strategies to combat this disease. Specific chemotherapy with benznidazole or nifurtimox has been recommended for treatment of recent and congenital infection. However, clinical trials with nifurtimox and benznidazole have shown that these compounds have very low activity in preventing the development of chronic Chagas disease. Moreover, the drugs induce a number of toxic side effects. The discovery of new active, non-toxic compounds would probably expand treatment, including those patients in which clinical manifestations are absent or can only be disclosed by more elaborate medical procedures. Recent developments in the study of basic biochemical aspects of T. cruzi have allowed for the identification of new targets for chemotherapy. Like many fungi, T. cruzi has a strict requirement for specific endogenous sterol synthesis for cell viability and growth and is extremely susceptible to sterol biosynthesis inhibitors (SBI). An intensive investigation of the potential trypanocidal effect of specific SBI has been performed, and it was demonstrated that some of these compounds exhibited suppressive and curative activity in murine and dog models of acute and chronic Chagas disease. Other potential targets for anti-T. cruzi chemotherapy that include the antiproliferative lysophospholipid analogs (evaluated in clinical trials as the first oral treatment for visceral leishmaniasis), cysteine protease inhibitors and compounds that interfere with purine salvage and inositol metabolism are also discussed.
Ageing down-modulates liver inflammatory immune responses to schistosome infection in mice.
(2010) Faria, Elaine Speziali de; Aranha, Claudio Henrique Magalhães; Carvalho, Andréa Teixeira de; Santiago, Andrezza Fernanda; Oliveira, Rafael Pires de; Rezende, Michelle Carvalho de; Carneiro, Cláudia Martins; Corrêa, Deborah Aparecida Negrão; Coelho, Paulo Marcos Zech; Faria, Ana Maria Caetano de
Ageing is associated with several alterations in the immune system. Our aim in this study was to compare the development of immunity to Schistosoma mansoni infection in young versus aged C57Bl ⁄ 6 mice using the liver as the main organ to evaluate pathological alterations and immune responses. In the acute phase, young mice had large liver granulomas with fibrosis and inflammatory cells. Chronic phase in young animals was associated with immunomodulation of granulomas that became reduced in size and cellular infiltrate. On the other hand, aged animals presented granulomas of smaller sizes already in the acute phase. Chronic infection in these mice was followed by no alteration in any of the inflammatory parameters in the liver. In concert with this finding, there was an increase in activated CD4+ T, CD19+ B and NK liver cells in young mice after infection whereas old mice had already higher frequencies of activated B, NK and CD4+ T liver cells and infection does not change these frequencies. After infection, liver production of inflammatory and regulatory cytokines such as IFN-c, IL-4 and IL-10 increased in young but not in old mice that had high levels of IL-4 and IL-10 regardless of their infection status. Our data suggest that the unspecific activation status of the immune system in aged mice impairs inflammatory as well as regulatory immune responses to S. mansoni infection in the liver, where major pathological alterations and immunity are at stage. This poor immune reactivity may have a beneficial impact on disease development.