Mestrado em Ciências Farmacêuticas

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A dispensação de medicamentos influencia o conhecimento e a adesão do paciente sobre sua farmacoterapia? Uma revisão sistemática e metanálise
(Universidade Federal do Espírito Santo, 2024-08-28) Santana, Elizabete Priscila Costa; Santos Júnior, Genival Araújo dos; Rocha, Kérilin Stancine Santos; https://orcid.org/0000-0002-2313-2140; Santos, Sabrina Cerqueira; Santana, Rafael Santos
Background: Patient's inadequate medication knowledge and non-medication adherence are considered an issue in healthcare, as they can lead to negative outcomes, such as therapeutic failures and hospitalization. Even though drug dispensing is a service traditionally performed by pharmacists, there is still no evidence about the influence of this service in these health outcomes. Objective. To evaluate the influence of drug dispensing on the patient's medication knowledge and medication adherence. Methods: A systematic review was conducted in which search was performed in PubMed/Medline, Biblioteca Virtual da Saúde, Web of Science, Embase, Open Thesis and Google Scholar databases. Two reviewers read the titles, abstracts and complete texts according to the eligibility criteria and extracted the data from the included articles. The methodological quality was assessed through the tools provided by JBI Institute. The data was analyzed through qualitative synthesis and meta-analysis was conducted for randomized controlled trials that used the outcome of medication adherence using RStudio software version 4.3.3. Results: A total of 7.590 studies were identified on the initial search, from which 11 articles met the eligibility criteria and were included in this systematic review. The studies were published in Africa, Latin America, Asia, Europe and Australia. Most of the studies were interventional (n=7). Five of the studies evaluated the influence of drug dispensing on the patient’s medication knowledge, from which four showed that knowledge increased after dispensing. Eight studies evaluated the influence of dispensing on medication adherence and the meta-analysis showed that patients who received the dispensing were 1.19 times more likely to adhere to medications compared to those who did not receive the service. Six studies met more than 70% of the quality assessment criteria. Conclusion: This systematic review showed that dispensing increases patient’s medication knowledge and patients are more likely to adhere to their medications when they receive this service.
Análise de tolerância e persitência de Staphylococcus aureus induzidos por vancomicina
(Universidade Federal do Espírito Santo, 2019-08-26) Birro, Jessica de Cassia Teixeira; Santos, Kenia Valeria dos; https://orcid.org/0000-0001-6871-3128; http://lattes.cnpq.br/9074173162086323; https://orcid.org/0000-0003-3848-5827; http://lattes.cnpq.br/9772676460303864; Resende, Juliana Alves; https://orcid.org/0000000254763754; http://lattes.cnpq.br/8223821041049149; Ferreira, Gabriella Freitas; https://orcid.org/; http://lattes.cnpq.br/
Introduction: Staphylococcus aureus lineages with reduced susceptibility to vancomycin (VAN) gained attention researchers due to it relation between therapeutic fails and recalcitrance. Microbial survival strategies are denominated tolerance and persistence, they are able to change transiently the metabolism of a sub population exposes to bactericidal antibiotics. So, in this study we investigated if different concentrations of vancomycin are able to induced tolerance or persistence in S. aureus. Materials and methods: Five lineages of S. aureus were intermittently exposed to 10 µg/mL of VAN by 6 h. They were selected derivative lineages of ATCC 29213 (parental), E10.6 and E100, to continue the assays. They were confirmed the purity of derivative lineages by MALDI-TOF MS and similarity genetic by PFGE. After, they were characterized tolerance/persistence from susceptibility by minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) for VAN and modified disk difusion test with VAN, oxacillin (OXA) and ciprofloxacin (CIP). Those assays were confirmed by time-kill curve with 50 µg/mL of VAN and, in the end, they analysed the phenotypic changes in growth taxa, autolysis percentual in Triton X-100, TBARS levels and Zeta potential. Results: All lineages did not change the viable cells quantitative when exposes to 10 µg/mL of VAN. For ATCC 29213, even though 100 µg/mL of VAN were sufficient to erradicate the population. No one derivative lineage changes in the susceptibility, but MBC/MIC ratio was smaller than 32 for all lineages. The parental lineage and it derivatives E10.6 and E100 showed high level to tolerance/persistence for OXA and CIP (p > 0,05), although this assay was not viable to VAN. In 6 h, E10.6 lineage showed the same MDK99 than parental lineage, being equal to 3 h in exponential phase and to 6 h in stacionary phase. In contrast, for both lineages the MDK99,99 was 6 h in exponential phase and bigger than 6 h in stacionary phase. Little changes in adpatative phase were observed only in 0,25 µg/mL and 0,5 µg/mL of VAN. From of 1 µg/mL of VAN it was not observed growth. TBARS levels were increased for the treated group with VAN, as well as the autolysis percentuals, while the membrane superficial charge has became more negative (p > 0,05 for all). Conclusions: The treatment with diferentes concentrations of VAN do not change viable counting, as well as do not change the tolerance/persistence levels for VAN, OXA and CIP. Although, it is able to increase the lipidic peroxidation levels and autolysis percentual, while reduce the surface charge in parental and derivative lineages.
ANÁLISE DO PERFIL DE CITOCINAS EM PESSOAS VIVENDO COM HIV
(Universidade Federal do Espírito Santo, 2020-08-11) Souza, Nayana de Oliveira; Pancoto, Joao Alexandre Tres; https://orcid.org/0000000319861452; http://lattes.cnpq.br/4056599319097766; https://orcid.org/; http://lattes.cnpq.br/; Batitucci, Maria do Carmo Pimentel; https://orcid.org/; http://lattes.cnpq.br/0010148251489155; Freitas, Janaina Cristiana de Oliveira Crispim; https://orcid.org/; http://lattes.cnpq.br/
Infection with the human immunodeficiency virus (HIV) causes progressive deterioration of the immune system. Nevertheless, despite the increase in life expectancy of these individuals, it has been observed that chronic diseases affect the people living wi
Avaliação antitumoral de chalconas sintéticas em sistema nanoestruturado
(Universidade Federal do Espírito Santo, 2024-02-28) Sampaio, Guilherme José Schwarzt; Andrade, Gracielle Ferreira; Kitagawa, Rodrigo Rezende; https://orcid.org/0000-0002-2208-6699; Oliveira, Marcelo Antônio de; Beltrame, Flávio Luís
The difficulty faced in treating cancer has led to several researches aimed at developing systems that perform targeted drug delivery, with the aim of increasing the effectiveness of treatment and reducing adverse effects. In the present study, a series of substituted chalcones were evaluated for their cytotoxic action on gastric adenocarcinoma cells (AGS) and breast cancer cells (MCF-7) using the MTT tetrazolium method, highlighting 3-methoxychalcone, 3-chlorochalcone and 3 hydroxychalcone. Considering the physicochemical characteristics of these compounds, 3-hydroxychalcone was chosen for incorporation into mesoporous silica nanoparticles due to the presence of the hydroxyl group, which could favor the incorporation process through hydrogen interactions. The synthesis of mesoporous silica nanoparticles (MSN) and their surface modification with 3 aminopropyltriethoxylane (APTES) were carried out and, subsequently, 3 hydroxychalcone was incorporated into these materials. The mesoporous silica nanoparticles were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), elemental analysis (CHN), scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta potential and nitrogen adsorption. Furthermore, in vitro release tests were carried out to verify the release profile of 3-hydroxychalcone from mesoporous silica samples. The results obtained demonstrated that the mesoporous silica nanoparticles exhibited a gradual and prolonged release profile. In the cytotoxicity test with silica samples incorporated with 3-hydroxychalcone, important cytotoxic activity was observed (IC50 = 12.93 to 106.67 μM) against AGS and MCF-7 cells, with the MSN-CHO sample (IC50 = 12.93 to 22.30 μM) exhibited a cytotoxic effect superior to free 3-hydroxychalcone (IC50 = 47.58 to 47.97 μM). The results indicate that the nanoparticles positively influence the interaction of chalcone with tumor cells. Despite numerous published studies reporting the pharmacological potential of chalcones, few studies report the application of these compounds in drug delivery systems and the results obtained in this work indicate the great potential that these materials have for application in cancer treatment.
Avaliação da atividade anti-Acanthamoeba castellanii de frações alcaloídicas de diferentes espécies da família Amaryllidaceae e da licorina
(Universidade Federal do Espírito Santo, 2017-04-04) Rosa, Maressa Dietrich; Borges, Warley de Souza; Bueloni, Cinthia Furst Leroy Gomes; Rott, Marilise Brittes; Kitagawa, Rodrigo Rezende
Free-living amoebae (FLA) are protozoa of wide environmental dispersion. Acanthamoeba is classified as one of the genres of FLA and can behave as an elective parasite in humans, causing two diseases: Amebic Granulomatous Encephalitis (AGE), a cronic disease of the central nervous system, difficult to treat; and Amebic Keratitis (AK), a very painful ocular cornea disease that can lead to Blindness and loss of the eyeball in more critical cases. The treatment for CA is very difficult, long, toxic and does not present complete effectiveness against existing cases. The great challenge of the treatment is the high toxicity and the resistance to the medicines. The use of plants as research sources for new amebicidal bioactive compounds has shown a good alternative; since these have high amoebicidal power and low toxicity. The objective of this study was to investigate the in vitro antiAcanthamoeba castellanii activity of 22 alkaloid enriched fractions of 12 species of Amaryllidaceae and the alkaloid lycorine on Acanthamoeba castellanii trophozoites using 3- (4,5-dimethyl) 5-diphenyltetrazolium (MTT). Chlorhexidine 0.02% was used as a positive control. The species Hippeastrum canastrense, Hippeastrum dinizcruziae, Crinum giganteum Hippeastum puniceum and lycorine showed a concentration-dependent effect, with H. canastrense and H. diniz-cruziae at the concentration of 2000 μg.mL-1, with a high amebicide (100% Inhibition) greater than chlorhexidine (86% inhibition). The cytotoxicity of these fractions and the lycopene were also evaluated on MDCK mammalian cells by the use of the MTT dye and showed a concentration-dependent effect, and H. diniz-cruziae at concentrations of 250, 500 and 1000 μg.mL-1 showed low cytotoxicity (5 to 7% inhibition) less than chlorhexidine (97% inhibition). The IC50 value calculated for H. canastrense, H. dinizcruziae, Crinum giganteum, H. puniceum and lycorine was from 285.61 to 962.75 μg.mL-1 and the selectivity index (SI) was 1, 27 to 7.0. The H. diniz-cruziae species presented promising results, with high amebicidal power (100% inhibition), low cytotoxicity (5 to 7% inhibition), lower IC50 value of 285.61 μg.mL-1 and higher IS value (7,0), being a promising target for the discovery of new drugs with antiAcanthamoeba castellanii activity.
Avaliação da eficácia de atropina e pralidoxima na intoxicação aguda por clorpirifós e desenvolvimento de metodologia analítica para identificação e quantificação de organofosforados e seus antídotos por HPLC-MS/MS
(Universidade Federal do Espírito Santo, 2016-03-22) Marques, Graziany Leite Moreira; Pelição, Fabrício Souza; Sampaio, Karla Nívea; Pires, Rita Gomes Wanderley; Martinis, Bruno Spinosa de
Organophosphorus insecticides (OP) are probably the most widely used pesticides in the world. In Brazil, these compounds are considered one of the main responsible for poisoning. Chlorpyrifos (CPF), an OP compound highly used, promotes, similarly to other OP, inhibition of the cholinesterases (ChEs) leading to the accumulation of acetylcholine in the central and peripheral cholinergic synapses. The treatment for OP poisoning involves a combination of muscarinic antagonists, such as atropine (ATR); oximes for reactivating the ChEs, mainly represented by the pralidoxime (2-PAM) and benzodiazepines, generally diazepam, for treatment of occasional seizures. However, the effectiveness of oximes in humans is still doubtful, mainly due to the polarity of these compounds, which leads to poor penetration of these drugs into the central nervous system (CNS). Therefore, this study aims to investigate the efficacy of the antidotes adopted in the OP poisoning, over the clinical signs and on the reactivation of the ChEs inhibition induced by the acute poisoning with CPF, as well as validate analytical method for identifying and quantifying various OPs, ATR and 2-PAM, using high-performance liquid chromatography coupled to mass spectrometry (HPLCMS/MS). Adult male rats (n=280) were divided into 8 groups: saline (SAL), CPF, SAL+ATR, CPF+ATR, SAL+2-PAM, CPF+2-PAM, SAL+ATR+2-PAM and CPF+ATR+2-PAM. The antidotes treatment with ATR (10 mg/kg); 2-PAM (40 mg/kg) or ATR (10mg/kg) +2-PAM (40 mg/kg) was delivered by intraperitoneal injections (i.p.) one hour after the administration of CPF (30 mg/kg, i.p.) or SAL (0.9%, i.p.) and the animals were observed for acute toxicity signs for up to 5 hours. In periods of 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours and 24 hours after the antidotes treatment administration, the animals were decapitated for collecting blood and brain (except cerebellum) samples for measurements of ChEs activity, as well as for CPF and CPF-oxon analysis by HPLC-MS/MS. The method developed for the OPs and antidotes analysis proved to be efficient and fast, attending the validation criteria stated in the RDC nº 27 of ANVISA (BRASIL, 2012). The analysis demonstrates that the CPF blood concentration significantly decreased over the first 24 hours after administration. The CPF caused inhibition of plasma ChE and treatment with 2-PAM was capable of reversing this inhibition for up to 1 hour after administration. However, when considering the brain AChE the 2-PAM only induced a small reactivation of the enzyme from the second hour of the treatment administration. Although not fully effective, the treatments with ATR, 2-PAM or ATR+2-PAM employed prevented or reverted, at different levels, the typical cholinergic symptoms of the OP poisoning.
Avaliação da estabilidade da Finasterida, estudos de compatibilidade fármaco-excipientes e controle de qualidade das formulações farmacêuticas sólidas do mercado
(Universidade Federal do Espírito Santo, 2020-05-29) Sousa, Igo Pinheiro Lopes e; Oliveira, Marcelo Antonio de; https://orcid.org/0000-0002-7842-807X; http://lattes.cnpq.br/5918727154250383; https://orcid.org/0000-0001-8307-6841; http://lattes.cnpq.br/2462426162523377 ; Bruno, Cristina Helena; https://orcid.org/0000-0001-7027-9068; http://lattes.cnpq.br/7690269357195395; Lima, Fabiana Vieira; https://orcid.org/0000-0002-3563-4105; http://lattes.cnpq.br/2087921184058843
Finasteride is a specific competitive inhibitor of the enzyme 5-alfarreductase, an intracellular enzyme responsible for the conversion of testosterone to dihydrotestosterone, used in the treatment of benign prostatic hyperplasia, prostate cancer and androgenetic alopecia. There are reports of crystalline polymorphism for the drug, but there are no studies of forced degradation or compatibility of commercial pharmaceutical formulations. The drug belongs to class II of the Biopharmaceutical Classification System and dissolution is the limiting step of bioavailability, this fact being an indication of the importance of further studies in relation to compatibility with excipients, degradation mechanisms, and kinetics of these possible chemical reactions, as that any changes directly influence absorption. The efficacy and safety of drugs containing finasteride depends directly on the assessment of its intrinsic stability and on compatible and stable formulations. Initially, the methodology for determining the drug was developed and optimized by High Performance Liquid Chromatography and subsequently subjected to validation tests as described in RDC 166/2017. The mobile phase was composed of acetonitrile, methanol and water, in the proportion of 26:39:35, in a flow of 1.2 mL.min-1 , under a temperature of 30 ºC, and octadecylsilane column (RP-18) of 250 x 4.6 mm, 5 µm, and detection at 210 nm. Then, forced degradation studies were conducted to assess the stability of finasteride, and it was evaluated by chromatography; study of degradation kinetics; studies of drug-excipient compatibility, using thermoanalytical techniques, thermogravimetry and differential thermal analysis; in addition to the quality control of market formulations. The analytical method optimized by High Performance Liquid Chromatography was subjected to the tests required in the legislation for validation, which pointed out that the method was approved in terms of the required parameters. Therefore, considered selective in relation to degradation products and placebo, linear in the working range of 0.07 to 0.13 mg.mL-1, precise, exact with an average recovery percentage of 99.97% and robust, with its detection limit of 4.46 µg.mL-1 and quantification limit of 13.52 µg.mL-1, acceptable and consistent for the present work. Finasteride has been shown to be stable under different stress conditions evaluated, except in the condition of basic hydrolysis, at extreme pH above 12.7. Thus, the degradation kinetics in liquid medium was calculated from this point, with the t90 obtained being 32.64 hours, at pH 12.7. Drug-excipient compatibility studies were performed by thermal analysis and demonstrated that the excipients starch, pregelatinized starch, stearic acid, croscarmellose sodium, microcrystalline cellulose, crospovidone, silicon dioxide, sodium starch glycolate, polyethylene glycol 6000, iron oxides red and yellow, and talc are compatible with finasteride. Among these, the excipients ethylcellulose, hydroxypropylmethylcellulose, sodium lauryl sulfate, Opadry YS-1-7006, polyvinylpyrrolidone K30 and titanium dioxide showed some interaction with the drug, which after complementary studies by X-Ray Diffraction it was possible to confirm compatibility in drug-excipient relationship, with an interaction with crystalline drug change. In addition to these, lactose and magnesium stearate proved to be incompatible, according to the TGA and DTA curves and, to ensure the safety of the formulation, it is suggested to replace these excipients with others of the same property, respectively mannitol and stearic acid. Among the market formulations submitted to quality control, only the two formulations manipulated did not reach the minimum quality requirements established by the pharmacopoeial specifications, respectively regarding dissolution and content uniformity tests. Still, in relation to the dissolution profile, only Lab 4 was considered a pharmaceutical equivalent to the reference laboratory. But even so, it was possible to notice some similarity in the dissolution curve of the other laboratories of the pharmaceutical specialties. Among the objectives achieved, considering the relevance of the tests and results obtained, this work provides bases for the development of safer formulations, containing finasteride, making it possible to devise drugs that can achieve the legal and clinical expectations imposed on them, especially from the point of view technological
AVALIAÇÃO DA ESTABILIDADE FÍSICO-QUÍMICA DE SUSPENSÃO OFTÁLMICA DE CETOCONAZOL
(Universidade Federal do Espírito Santo, 2022-04-29) Cardozo, Ramon de Oliveira; Giuberti, Cristiane dos Santos; https://orcid.org/0000000205608731; http://lattes.cnpq.br/3644255863698492; https://orcid.org/; http://lattes.cnpq.br/; Tavares, Guilherme Diniz; https://orcid.org/; http://lattes.cnpq.br/; Nunes, Kariane Mendes; https://orcid.org/; http://lattes.cnpq.br/
abstract
Avaliação da influência do acompanhamento farmacoterapêutico e da terapia insulínica sobre a qualidade de vida, adesão ao tratamento e estresse oxidativo em pacientes com diabetes mellitus tipo 2
(Universidade Federal do Espírito Santo, 2018-06-29) Meriguete, Angélica Marchesi Lira; Guimarães do Bem, Daniela Amorim Melgaço; Gonçalves, Rita de Cássia Ribeiro; Zandonade, Eliana
The practices of Pharmaceutical Care in Brazil are structured to promote medication adherence and quality of life, especially relevant in the context of type 2 diabetes mellitus (T2DM), which represents a growing problem of global health. It is a chronic metabolic disorder characterized by an increase in oxidative stress, which is related to the appearance of its main complications. T2DM is related to long and complex treatments, presence of comorbidities and complications which, together interfere negatively in the adherence to therapy. There are reports in the literature that the application of pharmaceutical care services has brought benefits on metabolic control and improved medication adherence of individuals with type 2 diabetes. In this study, it was evaluated if the pharmacotherapeutic follow-up performed for six months in patients with type 2 diabetes mellitus interferes in metabolic control, treatment adherence, quality of life and levels of pro and antioxidant species, besides the influence of insulin therapy on these parameters. Data collection was conducted before and after the six months of follow-up. 75 patients completed the study, 44 in the non-insulin therapy group and 31 in the insulin therapy group. After follow-up, an improvement in medication adherence was observed in the two groups. Similarly, there was a significant increase in the quality of life scores (p<0.0001) for the total sample. The physical domain of the insulin therapy group showed no change between the period (p = 0.052). In the oxidative stress parameters evaluated, there was a decrease in nitric oxide levels in both groups (p<0.0001) and an increase in superoxide dismutase concentration for the group with insulin therapy (p=0.0048). These results show that the proposed pharmacotherapeutic followup positively influenced on the medication adherence, quality of life and oxidative stress levels, and therefore, may contribute to delay the onset of the main chronic complications of the disease
Avaliação da qualidade e da compatibilidade fármaco-excipientes das formulações farmacêuticas sólidas do mercado contendo meloxicam
(Universidade Federal do Espírito Santo, 2017-03-15) Silveira, Lucas Melo da; Oliveira, Marcelo Antônio de; Jamal, Claudia Masrouah; França, Hildegardo Seibert
Meloxicam (MLX) is a non-steroidal anti-inflammatory, cyclooxygenase (COX) inhibitor, used to relieve inflammation and pain. MLX have a preferential affinity for COX-2, which is associated with a lower incidence of gastrointestinal side effects. The drug belongs to Class II of the Biopharmaceutical Classification System (BCS) where dissolution is the bioavailability limiting step. In view of this classification, it is a fundamental to carry out further studies regarding the compatibility between drug and excipients, mechanisms and kinetics of degradation reactions, since any changes directly influence the quality of the product. The aim of the present work is to evaluate the solid pharmaceutical formulations containing MLX found on the market defining more suitable excipients to improve the stability of pharmaceutical formulations. Thermal analysis techniques were used to characterize and evaluate the compatibility between the drug and the excipients present in the market formulations. Method by high performance liquid chromatography was developed and validated for quantification of MLX and possible degradation products. Alternative method by UV spectrophotometry was validated for quantification of MLX in the formulations. In the study of compatibility between drug-excipient was found incompatibility with magnesium stearate, red iron oxide, povidone, sodium starch glycolate and mannitol. In the study of intrinsic stability, the drug was subjected to conditions of forced degradation where it was unstable in alkaline medium. In the evaluation of the solid state kinetics, the MLX degraded according to AvramiErofeyev A4 model, presenting a shelf life of about 6 years for the raw material under inert condition. In the evaluation of the quality control of the products of the market, it was observed that the Lab10 and Lab11 were disapproved in the dissolution test. As for the evaluation of the dissolution profile only two products have been shown to be pharmaceutical equivalents
Avaliação das atividades gastroprotetora, anti-Helicobacter pylori, imunomoduladora e antioxidante dos "boldos" de interesse ao SUS : Plectranthus barbatus Andrews (Lamiaceae) e Vernonia condensata Baker (Asteraceae)
(Universidade Federal do Espírito Santo, 2017-02-02) Borges, Augusto Santos; Kitagawa, Rodrigo Rezende; Beltrame, Flávio Luís; Fronza, Marcio
Helicobacter pylori is a Gram-negative bacteria capable to survive the gastric environment and has a great influence in the development of many gastric diseases, like gastritis, peptic ulcers and even the gastric cancer. Plectranthus barbatus (Falso-boldo) and Vernonia condensata (Boldo-baiano) are species of medicinal plants with a wide traditional use in Brazil for the treatment of gastric injuries, however, none scientific reports have been described about the activity against H. pylori. Thus, this study aimed to determine the anti-H. pylori activity, gastroprotection activity, immunomodulation activity, antioxidant activity and phytochemical profile of extracts and fractions of these species. The phytochemical profile was evaluated through preliminary phytochemical assay, polyphenols and flavonoid content assays and mass spectrometry. The gastroprotective was measured by in vivo ulcer model induced by ethanol. The anti-H. pylori activity was made by minimal inhibitory and bactericidal concentration (MIC and MBC) and urease inhibition activity. The immunomodulatory activity was measured by detection of nitric oxide and cytokines (TNF-α, IL-1β and IL-6) released from LPS stimulated macrophages. Furthermore, was made the inhibitory potential against the artificial radicals (DPPH and ABTS•+) and oxygen and nitrogen reactive species (O2 - , HOCl, H2O2 and NO). The oral treatment with the extracts from both species shows gastroprotection ranging 58 – 78%. The anti-H. pylori results was significant only for the P. barbatus species, which showed an MIC of 256 µg/mL for the ethyl acetate fraction (AcOEt) and 512 µg/mL for the aqueous extract. Furthermore, the AcOEt fraction showed MBC of 1024 µg/mL. The results of the antioxidant capacity were significant for both species against the artificial radicals as well to the reactive oxygen species: O2 - (IC50: 32 – 72 µg/mL) and HOCl (IC50: 53 – 85 µg/mL). For the results of immunomodulatory activity, was possible to realize anti-inflammatory capacity in both species, but, the V. condensata showed greater potential and managed to decrease the productions of NO and cytokines, in a dose-response way, in the LPS stimulated macrophages (28 – 88 % of inhibition). Both species showed significant amounts of flavonoids and polyphenols. In addition, P. barbatus presented different diterpenes such as plectrin, hydrolyzed abietane, barbatusin, 3β- hydroxy-3deoxybarbatusin and cyclobutatusin as well the polyphenols coleoside B and rosmarinic acid. Altogether, the P. barbatus species, in special your AcOEt fraction, proved to be promising for future use in the prevention and treatment of H. pylori infections, because in addition to the inhibition of growth of H. pylori capacity, it also showed promising gastroprotective, immunomodulatory and antioxidant activity.
Avaliação das técnicas de VDRL e teste rápido como triagem para sífilis em gestantes de um município da região norte do Espírito Santo, Brasil
(Universidade Federal do Espírito Santo, 2019-07-02) Maciel, Janaina dos Santos; Souza, Marco Antonio Andrade de; https://orcid.org/0000-0003-1190-8834; http://lattes.cnpq.br/4683031081739485; https://orcid.org/0000-0002-5251-3866; http://lattes.cnpq.br/4927605851322125; Marinato, Luciana Barbosa Firmes; https://orcid.org/0000-0003-4029-6611; http://lattes.cnpq.br/2921679871709008; Gradella, Debora Barreto Teresa; https://orcid.org/0000-0003-1512-675X; http://lattes.cnpq.br/8752877408344935
Syphilis is a systemic disease caused by Treponema pallidum. Known since the fifteenth century, it is an infectious disease sexually transmitted, of chronic evolution, subject to crises of exacerbation and periods of latency. Its diagnosis can be made through treponemic and non-treponemic tests. In order to verify the concordance of the rapid test for syphilis in pregnant women, when compared to VDRL and the need for confirmatory tests, in both pregnant and newborn infants born to pregnant women infected with T. pallidum, a study was performed in a hospital of a medium-sized municipality in northern Espírito Santo. For the analysis in the pregnant women the rapid tests, the VDRL test were applied, and in the case of positivity for one or both tests, the confirmatory examination was applied TPHA. The results indicated that 93 (33.7%) of the 276 samples were positive for one or both methods, but only 89 (32.2%) remained positive when the confirmatory test was performed, and that 35 (39.3%) pregnant women, with the diagnosis for syphilis confirmed through the TPHA, were positive only for rapid test. The VDRL and TPHA tests were applied in the newborns and the study detected a 61.0% (25) positivity rate in infants born to syphilis mothers using the VDRL nontreponemal test, while using the treponemic test (TPHA) was detected 97.6% (40). A demographic characterization of the pregnant women was carried out using a questionnaire and a prevalence profile of syphilic women of fertile age of 47.4%, married and with up to 11 years of schooling of 68.4% and 94.8%, respectively, corroborating the results found in other studies. The results indicated that there is a need for adjustment in the diagnostic procedure for neonates, considering the use of a treponemal test and that the implementation of the rapid test in prenatal care can provide early access to the diagnosis and treatment of syphilis in pregnant women and their sexual partners, reduction of acquired syphilis transmission and reinfection and reduction of congenital syphilis cases.
Avaliação do efeito gastroprotetor das sementes de Persea americana Mill
(Universidade Federal do Espírito Santo, 2018-03-28) Athaydes, Brena Ramos; Kitagawa, Rodrigo Rezende; Gonçalves, Rita de Cássia Ribeiro; Borges, Warley de Souza; Fronza, Marcio
Peptic ulcer is one of the most common diseases affecting the world's population. It is characterized by an imbalance between protective (mucus and bicarbonate production, antioxidants and prostaglandins) and aggressor factors (oxidative stress, non-steroidal anti-inflammatory drugs and Helicobacter pylori) of the gastric mucosa. The inflammatory ulcer process induces the release of pro-inflammatory cytokines and oxidative stress, which can chronically lead to gastric cancer. In Brazil, there are reports of the use of Persea americana Mill. seeds (avocado) for the treatment of gastric diseases, however, without scientific evidence. Some research also highlights its antioxidant and antimicrobial effects. In this context, we evaluated the antioxidant and anti-H. pylori activity, the immunomodulatory effect and the antitumor effect in gastric adenocarcinoma cells of the hydroalcoholic extract (SCE) and ethyl acetate (SEAP) and hexane (SHP) partitions from avocado seeds. SEAP obtained better results; therefore, we also performed its chemical profile and the study of its gastroprotective effects in the acute indomethacin-induced gastric ulcer model, through histological analysis and quantification of the biochemical parameters of the inflammation. SEAP and SHP efficiently inhibited gastric tumor cells and H. pylori growth, confirmed by bacterial morphology changes. SEAP presented better results in the capture of ABTS•+, DPPH• , O2 •- , H2O2, HOCl and inhibition of HRP enzyme, besides modulating inflammation by inhibiting IL-6 production significantly. SEAP chromatographic study by ESI FT-ICR MS showed the presence of flavonoids, phenylpropanoids and tannins, such as caffeioylquinic acid, catechin and epicatechin (confirmed by HPLC-DAD) and quercetin and kaempferol derivatives. SEAP reduced gastric lesions characteristics in macroscopic and histological analysis, besides increasing mucus production. In oxidative stress parameters, there was a significant reduction of AOPP and MDA levels with increase of SOD activity. These results show that P. americana Mill. seeds are capable to inhibit the pathways involved in the formation of ulcer and gastric cancer due to the presence of phenolic compounds, being a strategic alternative in the treatment of gastric diseases.
Avaliação do perfil químico e atividades biológicas de Myrcíaria Strigipes O. Berg (Myrtaceae)
(Universidade Federal do Espírito Santo, 2016-03-17) Faitanin, Rafael Destefani; Kitagawa, Rodrigo Rezende; Jamal, Claudia Masrouah; Gonçalves, Rita de Cássia Ribeiro; Silveira, Dâmaris
Brazil is the owner of the largest and richest genetic diversity of plant species, however, most of them don’t have chemical-biologial studies. Myrciaria strigipes O. Berg (Myrtaceae) is a native species known popularly as "cambucá da praia" and "cabeludinha da praia" and it’s used in traditional medicine for cramps, edema and abdominal pain. The aim of this study was to evaluate the chemical profile, the toxicity and the antimicrobial, antioxidant, thrombolytic activities and α-amylase, α- glucosidase and tyrosinase enzymes inhibition activities of M. strigipes. The chemical profile was characterized from phytochemical screening, High Performance Liquid Chromatography analysis and the fractionation/purification techniques. The toxicity was determined against larvae of Artemia salina Leach. and the antimicrobial activity against Staphylococcus aureus, Escherichia coli and Candida albicans. The antioxidant activity was measured using the synthetic radicals DPPH and ABTS. The in vitro thrombolytic activity was evaluated through the extracts capacity to cause lysis in human blood clot. The inhibitory activities of α-amylase, α-glucosidase and tyrosinase enzymes were determined using in vitro spectrophotometric methods. Preliminary phytochemical analysis of ethanolic extracts of leaves (EEF) and branches (EEG) indicated the presence of flavonoids, coumarins, alkaloids, saponins, tannins, triterpenes, steroids and anthraquinones, yet this was only found in the EEF. They were isolated and/or identified of the EEF five compounds of terpenes class, four pentacyclic triterpenes (friedelin, 28-hydroxyfriedelin, glutinol and ursolic acid) and a tetracyclic steroid (β-sitosterol), and three phenolic compounds (isoquercitrin, hyperoside and ellagic acid). The EEF showed a little toxicity (LD50 = 648.17 µg/mL) and only the EEG showed antimicrobial activity, inhibiting the growth of S. aureus. The EEF and EEG showed antioxidant capacity and promising inhibitory activity on α-glucosidase, EC50 of 40,66 e 18,52 µg/mL, respectively, while the positive control showed EC50 of 37,30 µg/mL. This study reported, for the first time, chemical aspects and biological activities of M. strigipes species, and the results demonstrate the need for more studies to further chemical knowledge and understanding about the mechanism(s) and substance(s) responsible for activities shown by this species.
Avaliação do potencial antifúngico e da citotoxicidade de derivados semissintéticos do eugenol
(Universidade Federal do Espírito Santo, 2019-06-24) Dutra, Jessyca Aparecida Paes; Kitagawa, Rodrigo Rezende; Schuenck, Ricardo Pinto; Fronza, Marcio; Jamal, Claudia Masrouah
The increase of resistant fungal infections directed the search for alternative strategies in order to identify new therapeutic approaches. Among these strategies is the molecular modification, which aims to obtain derivatives from synthetic or natural compounds. In the essential oil of clove is present eugenol, a phenolic with ample antifungal activity and structural patterns that favor the obtaining of analogues. In this context, the present study evaluated the antifungal and cytotoxic activity of eugenol analogues. The antifungal action was evaluated in vitro on Candida albicans and C. parapsilosis through minimal inhibitory (MIC) and minimal fungicide (CFM) concentration, and in silico on CYP51 by molecular docking. The evaluation of the morphological damage to the yeasts was performed through SEM. Basal and post-metabolic cytotoxicity were evaluated in vitro on cell lines by the MTT-tetrazolium test. In this study the derivatives 2 and 4, allyl chain present, presented greater antifungal action. However, derivatives 5 and 6 that undergo changes in the side chain showed activity similar to or less than eugenol. The evaluation of modes of interaction at the CYP51 site demonstrated that derivatives 2 and 4 have structural patterns essential for the interaction when compared to fluconazole. Both derivatives showed similar morphological changes to fluconazole, reinforcing the hypothesis of interaction with the active site of CYP51. These derivatives had baseline IC50 values of 34.57 and 14.60 μg/mL, respectively. Whereas 2 was less cytotoxic than amphotericin B, and more cytotoxic than fluconazole from 50μg/mL. Derivative 4 was more cytotoxic than both standards from 25μg/mL. However, after exposure to the S9 system, derivative 4 maintained cytotoxicity while 2 was more cytotoxic. Regarding the selectivity, derivative 2 showed higher SI for fungal cells when compared to 4 and eugenol. It was found that none of the analogs attended all desirable aspects. Some were more active while others presented reasonable cytotoxicity and varied profiles of selectivity and liver metabolism. In this way, it is concluded that derivatives 2 and 4 are attractive as prototypes for future antifungal drugs. However, directed changes should be based on the results obtained, in order to contribute to the expansion of the limited therapeutic arsenal with more active and less cytotoxic drugs
Avaliação do potencial gastroprotetor da silimarina e silibina frente a infecção por Helicobacter pylori e em células tumorais gástricas
(Universidade Federal do Espírito Santo, 2019-09-30) Bittencourt, Milena Lopes Francisco ; Goncalves, Rita de Cassia Ribeiro; https://orcid.org/0000000193522454; http://lattes.cnpq.br/6525693905417002; https://orcid.org/0000-0002-9797-9512; http://lattes.cnpq.br/8581970808798897; Batitucci, Maria do Carmo Pimentel; https://orcid.org/0000-0002-3485-4448; http://lattes.cnpq.br/0010148251489155; Amorim, Fernanda Gobbi; https://orcid.org/0000-0003-1453-3185; http://lattes.cnpq.br/2251298775197322
Phytotherapy is an important therapeutic option in the prevention and treatment of health problems. Silybum marianum (L.) Gaertn is a plant popularly known as "cardo mariano". From the plant it is possible to obtain silymarin, a complex mixture of flavolignans used in Brazil as a phytotherapeutic medicine as a hepatoprotective, which has silibinin as its major component. Despite having many studies with silymarin, little is known about its effects on the gastric system. Diseases related to the stomach are common conditions that most often lead to chronicity and can progress to cancer. One of the contributing factors for its development is the presence of Helicobacter pylori bacteria. The bacterium can colonize and infect the stomach producing a series of changes that in the long run can culminate in the development of gastric cancer. In this sense, we sought to evaluate the effect of silymarin and silibinin on H. pylori, macrophage imonumodulatory response and cytotoxic activity on gastric tumor cell line. The broth microdilution technique was used to determine the minimum inhibitory concentration (MIC) and then to verify the synergistic activity with metronidazole by the checkerboard method. Evaluation of morphological changes in the bacterial cell was performed by scanning electron microscopy after exposure of the bacteria to sub-MICs. It was also performed the evaluation of the interaction with subunit of PBP by in silico method. Evaluation of urease inhibition was performed in vitro. Immunomodulatory activity was assessed by the detection of nitric oxide and cytokines (TNF-α, IL-6 and IL-10) released by macrophages. Finally, cytotoxic activity in gastric adenocarcinoma cells (AGS) was assessed by the MTT method. Cytotoxicity after metabolization was also evaluated. Silymarin and silibinin showed a discrete activity on H. pylori, showing no synergistic effect with metronidazole. Regarding urease, no significant inhibitory activity was observed. A potential immunomodulatory was observed at 50 μg/mL with inhibition of cytokines produced by H. pylori stimulated macrophages (TNF-ɑ: 84.54 ± 2.24% and 100.00 ± 3.47%, IL-6: 88.66 ± 1.56% and 56.83 ± 6.69%, IL-10: 73.88 ± 3.86% and 70.29 ± 8.41% for silymarin and silibinin respectively) and NO (95.05 ± 7.76% and 73.33 ± 7.14% for silymarin and silibinin). At the same concentration, it presented a mild inhibitory action on superoxide production (35.85 ± 10.98% and 27.09 ± 7.47% for silymarin and silibinin). In addition, they demonstrated significant cytotoxic activity on AGS (IC50: 46.27 ± 1.99 and 55.70 ± 2.14 μg/mL for silymarin and silibinin) with good selectivity index (IS: 2.12 and 1.52 for silymarin and silibinin) when compared to standard chemotherapy. And increased cytotoxicity after metabolization, with decreased IC50. Thus, silymarin and silibinin have been shown to possess important characteristics for potential use in the prevention and treatment of H. pylori infection and its complications, such as gastric cancer.
Avaliação do potencial quimioprotetor de nanodispersão e extrato etanólico de Mikania glomerata Sprengel (asteraceae)
(Universidade Federal do Espírito Santo, 2016-02-04) Santana, Esdras Andrade; Batitucci, Maria do Carmo Pimentel; Matsumoto, Silvia Tamie; Giuberti, Cristiane dos Santos
Mikania glomerata is a medicinal plant having the coumarin as a chemical tracer, and due to bronchodilatory properties is widely used in traditional medicine in Brazil. The main objective of this study was to evaluate the potential of ethanol extract (EE) and nanodispersion (ND) of M. glomerata against cytotoxic and mutagenic effects induced by chemotherapy cyclophosphamide (CPA). This assessment was performed using micronucleus assay in bone marrow erythrocytes of Swiss albino mice (Mus musculus) in vivo through the simultaneous treatment protocol. The treatments using EE were performed with the 1.0; 0.5; 0.25; 0.008 e 0.004 mg.kg-1 concentrations of coumarin and ND in 0.008 e 0.004 mg.kg-1 concentrations of coumarin. The results showed that most of treatments reduced the cytotoxic damage caused by CPA. Only the treatment with EE 0.004 mg.kg-1 of coumarin did not show this effect. In the evaluation of antimutagenicity, the treatments with 1.0; 0.5; 0.25 mg.kg-1 concentrations of coumarin and ND (0.008 e 0.004 mg.kg-1 of coumarin), demonstrated to be effective in reducing the micronucleus frequency, which means they are antimutagenic agents. The treatment using ND (0.008 mg.kg-1 of coumarin) showed a 60.38% damage reduction, indicating greater effectiveness among the treated groups. Overall, treatments with nanodispersions were more efficient in chemoprotective action, although its low coumarin content in the experimental conditions. The results reinforce the importance of using nanotechnology to transport of natural compounds and the potential of compounds extraction technology through nanodispersions.
AVALIAÇÃO DO USO DE MEDICAMENTOS POTENCIALMENTE INAPROPRIADOS E DA ADESÃO À FARMACOTERAPIA EM IDOSOS ATENDIDOS POR UM PLANO DE SAÚDE SUPLEMENTAR
(Universidade Federal do Espírito Santo, 2020-08-26) Tranhago, Camilla da Penha; Bem, Daniela Amorim Melgaco Guimaraes Do; https://orcid.org/; http://lattes.cnpq.br/8710745257083012; https://orcid.org/; http://lattes.cnpq.br/; Pereira, Mariana Linhares; https://orcid.org/; http://lattes.cnpq.br/; Junior, Genival Araujo dos Santos; https://orcid.org/0000000256181846; http://lattes.cnpq.br/5917097187533724
The association between polypharmacy, the presence of multiple comorbidities and physiological changes related to aging increases the complexity of pharmacotherapy in the elderly. In this context, some medications may be considered inappropriate for these
Avaliação in vitro da atividade anti-Helicobacter pylori e potencial antioxidante de extratos e frações de Baccharis trimera (Less.) DC
(Universidade Federal do Espírito Santo, 2016-03-22) Nunes, Otalibio Castiglioni; Gonçalves, Rita de Cássia Ribeiro; Vellosa, José Carlos Rebuglio; Borges, Warley de Souza
One of the major risk factors for the development of ulcers and gastric cancer is the infection by Helicobacter pylori, in which there is a considerable oxidative stress. In Brazil, the plant Baccharis trimera (Less) DC, known as "Carqueja", is commonly used to treat gastrointestinal and liver disorders. Tannins, flavonoids, saponins, diterpene lactones, sesquiterpenes, phenolic compounds and volatile oils were identified in this specie. Thus, the goal of this study was to evaluate the antiHelicobacter pylori activity of the aqueous (AqE), ethanolic (EE), and hydroalcoholic (HE) extracts of B. trimera, as well as the aqueous (AqF), hexane (HxF), and acetonitrile / chloroform (ACF) fractions obtained from the HE. In addition, it aims to analyze the phytochemical composition and its effects on free radicals and biological oxidants. For all extracts and fractions, it was performed a phytochemical screening and the determination of the content of polyphenol, flavonoid and total tannins. The anti- Helicobacter pylori activity was evaluated by microdilution broth assay and urease inhibitory capacity. Bacterial morphology, after sample exposure, was evaluated by scanning electron microscope (SEM) using the extracts and fractions that reached the minimum inhibitory concentration (CIM90). Screening of antioxidant activity for all samples was determined by DPPH and ABTS radical scavenging activities. Assays using the oxidizing biological agents, hydrogen peroxide (H2O2), superoxide anion (O2 •- ), hypochlorous acid (HOCl), hydroxyl radical (HO• ), and nitric oxide (NO• ) were performed with HE and its fractions due the best results in the antiH. pylori and initial screening antioxidant assays, except for the HxF because of its poor performance in the antioxidant screening. The highest concentration of polyphenols was observed in the HE, flavonoids in the ACF, and tannins in the AqF. Anti-H pylori assay presented a CIM90 of 512 μg/mL for HE, and 1024 μg/mL for ACF, the latter being bactericidal. SEM showed morphological changes such as stretching and cell lysis in the samples tested, and may suggest some modifications in the wall, such as alterations in the peptidoglycan synthesis. In the enzyme urease inhibition assay, the most significant result was obtained by the ACF, which inhibited 36.24% in the highest concentration tested. The best result among the extracts in the initial antioxidant screening was achieved by the HE, which obtained the following EC50: DPPH, 17.40 ± 0.52 and ABTS, 9.99 ± 1.21. The best EC50 for the fractions were: DPPH, AqF, 27.41 ± 1.65, and ABTS, AqF, 10.80 ± 1.90. In the O2 •- scavenging activity, AqF showed EC50 of 5.85 ± 0.86 μg/mL. In the inhibition assay of HOCl, all samples tested were able to inhibit greater than 50%, except AqF. In the inhibition assay of HO• , NO• e H2O2, the results were better for ACF and its EC50 was 2.90 ± 0.48, 132.13 ± 7.38 e 66.70 ± 2.30 μg/mL, respectively. The analyzes indicate that B. trimera, in particular the HE and its fractions, AqF and ACF, may exhibit promising compounds for the prevention and treatment of diseases caused by H. pylori. These results were based on the relationship between the presence of phenolic compounds and the inhibition of oxidants, as well as changes in the bacterial membrane.
Avaliação in vitro e in silico do potencial anti-paracoccidioides brasiliensis de chalconas sintéticas
(Universidade Federal do Espírito Santo, 2024-02-29) Pereira, Giuliano da Conceição; Gonçalves, Rita de Cássia Ribeiro; https://orcid.org/0000-0001-9352-2454; Federico, Leonardo Bruno; Coitinho, Juliana Barbosa
The search for new therapeutic compounds is crucial to enhance the patient's clinical condition and provide treatments with minimal adverse effects. Chalcones, substances obtained from natural or synthetic sources and classified as flavonoids, share a common central structure and have garnered increasing interest due to their broad biological activity, including antitumor, antioxidant, anti-inflammatory, antiviral, antibacterial, and antifungal properties. The fungus species Paracoccidioides brasiliensis causes paracoccidioidomycosis (PCM), a systemic fungal infection with the potential to cause severe sequelae and even lead to death. Current therapeutic strategies for systemic fungal infections are time-consuming, costly, and associated with side effects. A database containing 21 chalcones was created and tested in silico for pharmacokinetic attributes, revealing high lipophilicity, gastrointestinal absorption, and permeabilization of the blood-brain barrier. The chalcones showed low Tanimoto similarity with drugs used for PCM. Prediction of chalcones' activities regarding relevant molecular targets in fungal metabolism, along with molecular docking, highlighted significant interactions, especially with fumarate reductase. In silico results were analyzed, and five compounds were selected for in vitro testing. The selected compounds exhibited moderate antifungal activity with MIC values ranging from 32 to >128 µg/mL, all surpassing the standard amphotericin B. In cytotoxicity assays, the five compounds exhibited reduced IC50 values, indicating high cytotoxicity with different values before and after metabolization. Despite promising characteristics, the study suggests that using chalcones as drugs against PCM requires additional studies with the aim to optimize the structure-activity relationship.

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