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Ars pharm ; 62(1): 89-95, ene.-mar. 2021.
Artigo em Inglês | IBECS-Express | IBECS | ID: ibc-ET6-1764


INTRODUCTION: The coronavirus disease 2019 (COVID-19) is a viral disease that affects several human organs and sys¬tems. Preventive or prophylactic treatments are specifically useful in emerging infectious diseases such as COVID-19 because they reduce the need for hospitalization and public health spending. Although the SARS-CoV-2 preventive effect of several therapeutic agents (e.g., hydroxychloroquine/chloroquine, remdesivir, lopinavir, and ritonavir) has been extensively evaluated, none of them have demonstrated significant clinical efficacy. METHOD: We aim to address and discuss the recently published studies on the chemoprophylactic potential of quer¬cetin against SARS-CoV-2. A literature search was carried out on different databases, such as PubMed/MEDLINE, Scielo, Scopus, Web of Science, Cochrane Library, and Clinical Studies that report the effect of quercetin against SARS-CoV-2 or other types of coronaviruses were included and critically evaluated. RESULTS: Studies have shown that quercetin, an FDA-approved flavonoid used as an antioxidant and anti-inflamma¬tory agent, inhibits the entry of coronavirus (SARS-CoV) into the host cell. Moreover, an in silico study showed that quercetin is a potent inhibitor of the SARS-CoV-2 main protease (Mpro), suggesting that this flavonoid is also active against COVID-19. CONCLUSIONS: Because quercetin might prevent and lessen the duration of SARS-CoV-2 infections, it is plausible to assume that the prophylactic use of this flavonoid produces several clinical benefits. However, this preliminary evidence needs to be confirmed by in vitro assays and, posteriorly, in randomized clinical trials

INTRODUCCIÓN: La enfermedad del coronavirus 2019 (COVID-19) es una enfermedad viral que afecta a varios órganosy sistemas. Los tratamientos preventivos o profilácticos son especialmente útiles en enfermedades infecciosas emergentes como COVID-19 porque reducen la necesidad de hospitalización y el gasto en salud pública. Aunque el efecto preventivo del SARS-CoV-2 de varios agentes terapéuticos (e.g., hidroxicloroquina/cloroquina, remdesivir,lopinavir y ritonavir) se ha evaluado ampliamente, ninguno de ellos ha demostrado una gran eficacia clínica. MÉTODO: Por lo tanto, aquí nuestro objetivo es abordar y discutir los estudios publicados recientemente sobre el potencial quimioprofilático de la quercetina contra el SARS-CoV-2. METODOLOGÍA: Se realizó una búsqueda de la literaturaen bases como PubMed/MEDLINE, Scielo, Scorpus, Web of Science, Cochrane Library y Clinical Se incluyeron y evaluaron críticamente estudios que abordan la quercetina contra el SARS-CoV-2 u otros tipos decoronavirus. RESULTADOS: Algunos estudios han demostrado que la quercetina, un flavonoide aprobado por la FDA que se utiliza como agente antioxidante y antiinflamatorio, inhibe la entrada del coronavirus (SARS-CoV) en la célula huésped.Además, un estudio in silico mostró que la quercetina es un potente inhibidor de la proteasa principal del SARSCoV-2 (Mpro), lo que sugiere que este flavonoide también es activo contra COVID-19. CONCLUSIONES: Debido a que la quercetina podría prevenir y disminuir la duración de las infecciones por SARSCoV-2, es plausible suponer que el uso profiláctico de este flavonoide produce varios beneficios clínicos. Pero, estas pruebas preliminares deben ser confirmadas mediante ensayos in vitro y, posteriormente, en un ensayo clínico aleatorizado

Arch Virol ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33410995


Mayaro fever is an infection caused by Mayaro virus (MAYV) that stands out among the neglected diseases transmitted by arthropods. Brazil is the country with the highest number of confirmed cases of MAYV infection. However, epidemiological surveillance studies conducted in Brazil are decentralized and focus on small outbreaks and unconfirmed cases. Thus, the aim of this review was to determine the general epidemiological profile of MAYV infections in Brazil. Several medical databases (i.e., PUBMED/MEDLINE, Scopus, Cochrane Library, LILACS, SciELO, and Biblioteca Virtual em Saúde) were searched for studies reporting cases of MAYV infections in Brazilian patients. Then, the rate of exposure to MAYV in Brazil was analyzed using RStudio® Software. We identified 37 studies published from 1957 to 2019, containing data of 12,374 patients from 1955 to 2018. The general rate of exposure to MAYV in Brazil was 10% (95% CI; 0.04-0.22), with 1,304 reported cases. The highest incidence of MAYV infection was found in the northern region (13%; 95% CI; 0.05-0.29), with 1,142 cases (88% of all cases). Furthermore, autochthonous MAYV cases have also been reported in the Central West (8%; 95% CI; 0.03-0.18) and Southeast (0.4%; 95% CI; 0.00-0.28). The states with the highest number of cases are Amazonas (490 cases), Pará (276 cases), and Goiás (87 cases). In conclusion, the general rate of exposure to MAYV in Brazil between 1955 and 2018 was considerable, especially in the Legal Amazon, in which 93% of cases were reported.

J Ethnopharmacol ; 266: 113423, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33007390


ETHNOPHARMACOLOGICAL RELEVANCE: Pristimerin is a triterpenoid considered the main component of Salacia crassifolia extracts. This terpene has shown promising antitumor, anti-inflammatory, and antimicrobial effects. Likewise, S. crassifolia has been used in traditional medicine to treat cancer and as an antimicrobial and anti-inflammatory agent. AIM OF THE STUDY: This study aimed to evaluate the antibacterial activity of the hexane extract of Salacia crassifolia roots (HER) and its isolate, pristimerin, against pathogenic bacteria. MATERIALS AND METHODS: First, we evaluated the spectrum of action of HER and pristimerin by the determination of the minimum inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC). Subsequently, we analyzed the time-kill curve of these plant-derived compounds against Staphylococcus aureus. Then, we examined their mode of action by three different assays: the crystal violet methodology, the release of intracellular material, and transmission electron microscopy methods (TEM). Finally, we evaluated the effect of HER and pristimerin on the pre-formed biofilm of S. aureus by the crystal violet assay, the synergistic effect by the checkerboard method, the cytotoxicity against Vero cells, and the in silico activity using the online software PASS. RESULTS: HER and pristimerin presented a narrow spectrum of action against Gram-positive bacteria (MIC 0.195-25 µg/mL), and their primary mode of action is the alteration of membrane permeability of S. aureus. Our results show that the compounds disrupted the pre-formed biofilm of S. aureus in a dose-dependent manner. Furthermore, HER and pristimerin presented a significant synergic effect after the combination with well-known antibiotics, which was associated with the ability of these phytomedicines to change membrane permeability. Regarding the cytotoxic effect, the selective index (SI) of HER ranged from 0.37 to 11.86, and the SI of pristimerin varied from 0.24 to 30.87, according to the bacteria tested. CONCLUSIONS: Overall, HER and pristimerin showed a promising antibacterial effect in vitro through the alteration of membrane permeability of S. aureus.

Eur J Med Chem ; 210: 113048, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33316690


Invasive candidiasis, such as intra-abdominal candidiasis (IAC), is a significant cause of morbidity and mortality worldwide. IAC is still poorly understood, and its treatment represents a challenge for public health. In this study, we showed the in vitro anti-Candida activity of four alkaloid synthetic derivatives and their antifungal potential in a murine model of IAC. The biological effects of alkaloids were evaluated against Candida spp. through the determination of the minimum inhibitory concentration (MIC). For the alkaloids that showed antifungal activity, the fungicidal concentration, time-kill curve, synergism with azoles and polyenes, phenotypic effects, and the effect against virulence factors were also determined. The most active alkaloids were selected for in vivo assays. The compounds 6a and 6b were active against C. albicans, C. glabrata, and C. tropicalis (MIC 7.8 µg/mL) and showed promising antifungal activity against C. krusei (MIC 3.9 µg/mL). The compound 6a presented a potent fungicidal effect in vitro, eliminating the yeast C. albicans after 8 h of incubation at MIC. An important in vitro synergistic effect with ketoconazole was observed for these two alkaloids. They also induced the lysis of fungal cells by binding to the ergosterol of the membrane. Besides that, 6a and 6b were able to reduce yeast-to-hyphal transition in C. albicans, as well as inhibit the biofilm formation of this pathogen. In the in vivo assay, the compound 6a did not show acute toxicity and was mainly absorbed by the liver, spleen, and lung after a parenteral administration. Also, this analogue significantly reduced the fungal load of C. albicans on the kidney and spleen of animals with IAC. Therefore, these results showed that the compound 6a is a potent anti-Candida agent in vitro and in vivo.

Meat Sci ; 173: 108394, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33316706


We conducted a systematic review and meta-analysis to determine the rate of contamination in bovine meat and meat products with Shiga toxin-producing Escherichia coli (STEC) in Brazil over the last fifteen years. Data were obtained from online databases in February 2020, and 25 papers were selected from 1036 articles identified in the literature search and 13 articles from gray literature, totaling 4286 samples analyzed. The overall rate of STEC was estimated to be 1% in Brazil. The highest rate (9%) was observed in Mato Grosso, followed by Rio Grande do Sul (1%), Goiás (1%), and São Paulo (1%). Regarding the sample type analyzed, hot carcasses had the highest rate (8%) of positive samples for STEC, followed by cold carcasses (2%) and beef samples (1%). As the available data were concentrated in the São Paulo state, the findings of this meta-analysis reveal the need for further studies in Brazil to allow better risk assessment and prevention of human STEC infections.

Inflamm Bowel Dis ; 27(2): 169-181, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-32095814


BACKGROUND: The differential diagnosis of inflammatory bowel diseases (IBDs) between Crohn's disease (CD) and ulcerative colitis (UC) is important for designing an effective therapeutic regimen. However, without any adequate gold standard method for differential diagnosis currently, therapeutic design remains a major challenge in clinical practice. In this context, recent studies have showed that circulating leptin stands out as a potential biomarker for the categorization of IBDs. Thus, we aimed to summarize the current understanding of the prognostic and diagnostic value of serum leptin in patients with IBDs. METHODS: A systematic search was performed in PubMed/MEDLINE, Scopus, Cochrane Library, and Web of Science databases. Articles that aimed to study the relationship between circulating levels of leptin and IBDs were included. Finally, the meta-analysis was performed with the mean serum leptin levels in patients with IBDs and healthy controls using RevMan 5.3 software, with I2 > 50% as a criterion for substantial heterogeneity. RESULTS: Nineteen studies were included. Serum leptin levels among patients with IBDs and healthy controls did not show a significant difference (95% CI, -2.15 to 0.57; I2, 86%, P ≤ 0.00001). Similarly, there was no association of leptin levels with the activity of IBDs (95% CI, -0.24 to 0.06; I2, 50%; P = 0.13). However, serum leptin levels were significantly higher in patients with CD than those in patients with UC (95% CI, -2.09 to -0.37; I2, 7%; P ≤ 0.36). CONCLUSION: This review suggested that serum leptin levels might be a promising biomarker to help in the differentiation between CD and UC.

Eur J Pharm Sci ; 156: 105592, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33049305


Skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) require the development of new and effective topical antibiotics. In this context, melittin, the main component of apitoxin, has a potent antibacterial effect. However, little is known regarding the anti-inflammatory potential this peptide in infection models, or its ability to induce clinically important resistance. Here, we aimed to conduct an in-depth characterization of the antibacterial potential of melittin in vitro and evaluate the pharmaceutical potential of an ointment containing melittin for the treatment of non-surgical infections induced by MRSA. The minimum inhibitory concentration of melittin varied from 0.12 to 4 µM. The antibacterial effect was mainly bactericidal and fast (approximately 0.5 h after incubation) and was maintained even in stationary cells and mature MRSA biofilms. Melittin interacts synergistically with beta-lactams and aminoglycosides, and its ability to form pores in the membrane reverses the resistance of vancomycin-intermediate Staphylococcus aureus (VISA) to amoxicillin, and vancomycin. Its ability to induce resistance in vitro was absent, and melittin was stable in several conditions often associated with infected wounds. In vivo, aointment containing melittin reduced bacterial load and the content of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6 (IL-6), and IL-1 beta. Collectively, these data point to melittin as a potential candidate for topical formulations aimed at the treatment of non-surgical infections caused by MRSA.

Rev. colomb. ciencias quim. farm ; 49(2): 267-279, May-Aug. 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1144351


SUMMARY Staphylococcus aureus is one of the main bacteria that affect human health. Its reduced susceptibility to beta-lactam antibiotics has driven the clinical use of macrolides and lincosamides. However, the presence of macrolide-lincosamide-streptogramin B (MLSB)-resistant S. aureus strains is increasingly common. Wastewater treatment plants (WWTPs) are the main anthropogenic source of resistance determinants. However, few studies have assessed the importance of this environment on the dissemination of MLSB-resistant S. aureus strains. Thus, we aimed to evaluate the impact of a domestic WWTP on the resistance to MLSB and penicillin in S. aureus in southeast Brazil. Of the 35 isolates tested, 40.6% were resistant to penicillin. Resistance to erythromycin (8.6%) and quinolones (2.8%) was less common. Despite the low rate of resistance to clindamycin (2.8%), many isolates showed reduced susceptibility to this antibiotic (57.1%). Regarding the resistance phenotypes of staphylococci isolates, inducible MLSB resistance (D-test positive) was found in two isolates. In addition, 27 S. aureus isolates showed the ability to produce penicillinase. In this article, we report for the first time the importance of WWTPs in the dissemination of MSLB resistance among S. aureus from southeast Brazil.

RESUMEN Staphylococcus aureus es una de las principales bacterias que afectan la salud humana. Su susceptibilidad reducida a los antibióticos betalactámicos ha impulsado el uso clínico de macrólidos y lincosamidas. Sin embargo, la presencia de cepas resistentes a macrólido-lincosamida-estreptogramina B (MLSB) de S. aureus es cada vez más común. Las plantas de tratamiento de aguas residuales (PTAR) son la principal fuente antropogénica de determinantes de resistencia. Sin embargo, pocos estudios han evaluado la importancia de este entorno en la diseminación de cepas de S. aureus resistentes a MLSB. Nuestro objetivo fue evaluar el impacto de una PTAR doméstica en MLSB y la resistencia a la penicilina en S. aureus en el sureste de Brasil. De los 35 aislamientos analizados, el 40,6% eran resistentes a la penicilina. La resistencia a la eritromicina (8,6%) y quinolonas (2,8%) fue menos común. A pesar de la baja tasa de resistencia a la clindamicina (2,8%), muchos aislamientos mostraron sensibilidad reducida a este antibiótico (57,1%). Con respecto a los fenotipos de resistencia de los aislamientos de estafilococos, la resistencia inducible a MLSB (prueba D positiva) se encontró en dos aislamientos. Además, 27 aislamientos de S. aureus mostraron la capacidad de producir penicilinasa. En este artículo informamos, por primera vez, la importancia de las PTAR en la difusión de la resistencia a MSLB entre S. aureus del sureste de Brasil.

RESUMO O Staphylococcus aureus é uma das principais bactérias que afetam a saúde humana. Sua reduzida suscetibilidade aos antibióticos beta-lactâmicos tem impulsionado o uso clínico de macrolídeos e lincosamidas. No entanto, a presença de cepas de S. aureus resistentes a macrolídeo-lincosamida-estreptogramina B (MLSB) é cada vez mais comum. As estações de tratamento de esgoto (ETEs) são a principal fonte antropogênica de determinantes de resistência. No entanto, poucos estudos avaliaram a importância desse ambiente na disseminação de cepas de S. aureus resistentes ao MLSB. Assim, nosso objetivo foi avaliar o impacto de uma ETE doméstico na resistência ao MLSB e à penicilina em S. aureus no sudeste do Brasil. Dos 35 isolados testados, 40,6% eram resistentes à penicilina. Resistência à eritromicina (8,6%) e quinolonas (2,8%) foi menos comum. Apesar da baixa taxa de resistência à clindamicina (2,8%), muitos isolados apresentaram sensibilidade reduzida a esse antibiótico (57,1%). Em relação aos fenótipos de resistência dos isolados de estafilococos, a resistência induzível ao MLSB (D-teste positivo) foi encontrada em dois isolados. Além disso, 27 isolados de S. aureus mostraram a capacidade de produzir penicilinase. Neste artigo relatamos pela primeira vez a importância das ETEs na disseminação da resistência do MSLB entre S. aureus do sudeste do Brasil.

Arch Virol ; 165(8): 1729-1737, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32514689


The novel human coronavirus (SARS-CoV-2), the causative agent of COVID-19, has quickly become a threat to the public health and economy worldwide. Despite the severity of some cases, there are no current pathogen-specific antivirals available to treat the disease. Therefore, many studies have focused on the evaluation of the anti-SARS-CoV-2 activity of clinically available drugs. Here, we conducted a systematic review to describe the drug repositioning strategy against SARS-CoV-2 and to discuss the clinical impact of this approach in the current pandemic context. The systematic review was performed on March 23, 2020, using PubMed/MEDLINE, Scopus, Cochrane Library, and Biblioteca Virtual de Saúde (BVS). The data were summarized in tables and critically analyzed. After the database search, 12 relevant studies were identified as eligible for the review. Among the drugs reported in these studies, 57 showed some evidence of antiviral activity. Antivirals, especially antiretrovirals, are the main class of therapeutic agents evaluated against COVID-19. Moreover, studies have reported the anti-SARS-CoV-2 activity of antitumor (16%; 9/57), antimalarial (7%, 4/57), and antibacterial (5%; 3/57) agents. Additionally, seven pharmacological agents (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, damageprevir, lopinavir/ritonavir) are in phase IV of clinical trials. Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus.

Antibacterianos/farmacologia , Antirretrovirais/farmacologia , Antimaláricos/farmacologia , Antineoplásicos/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Pneumonia Viral/tratamento farmacológico , Antivirais/farmacologia , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle
Eur J Clin Microbiol Infect Dis ; 39(8): 1427-1438, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32533271


We conducted a systematic review and meta-analysis to determine the rate of polymyxin resistance among Acinetobacter baumannii isolates causing infection in hospitalized patients around the world during the period of 2010-2019. The systematic review was performed on September 1, 2019, using PubMed/MEDLINE, Scopus, and Web of Science; studies published after January 1, 2010, were selected. The data were summarized in tables, critically analyzed, and treated statistically using the RStudio® Software with Meta package and Metaprop Command. After applying exclusion factors, 41 relevant studies were selected from 969 articles identified on literature search. The overall rate of polymyxin-resistant A. baumannii (PRAB) related to hospitalized patients was estimated to be 13% (95% CI, 0.06-0.27), where a higher rate was observed in America (29%; 95% CI, 0.12-0.55), followed by Europe (13%; 95% CI, 0.02-0.52), and Asia (10%; 95% CI, 0.02-0.32). The extensive use of polymyxins on veterinary to control bacterial infection and growth promotion, as well as the resurgence in prescription and use of polymyxins in the clinics against carbapenem-resistant gram-negative bacteria, may have contributed to the increased incidence of PRAB. The findings of this meta-analysis revealed that the rate of PRAB recovered from hospitalized patients is distinctively high. Thus, action needs to be taken to develop strategies to combat the clinical incidence of PRAB-induced hospital infections.

Rev. colomb. ciencias quim. farm ; 49(1): 218-233, Jan.-Apr. 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1144348


SUMMARY Chalcones highlights as an important structure in medicinal chemistry and thus has been widely used as a template in the development of new drugs. In this study, we aim to determine the antibacterial, anti-Candida, and anti-Dengue potential of new chalcone-bearing 2,4-dihydroxyl and tetrahydropyranyl moieties. Antimicrobial activity assays showed that microorganism of the Staphylococcus genus (including methicillin-resistant strains) were susceptible to 2,4-dihydroxychalcones, with minimum inhibitory concentrations (MICs) ranging of 19.5 to 125 µg.mL-1. Compound 4e, which showed the highest bacteriostatic effect, also has bactericidal activity from of 80 µg.mL-1. The growth of oral isolates of Candida albicans was also efficiently inhibited with compound 4e (MIC: 15.6-32.3 µg.mL-1), which was fungicidal at 15.6 µg.mL-1. However, the presence of the tetrahydropyranyl moiety impaired both the antibacterial and antifungal effects. None of the chalcones tested were actives against Dengue virus serotype 2. In conclusion, the compound 4e showed good anti-Staphylococci and anti-Candida activity and may be a promising prototype for the development of new antimicrobial agents.

RESUMEN Las chalconas se destacan como una estructura importante en la química médica y, por lo tanto, se ha empleado como prototipo para el desarrollo de nuevos fármacos. En este estudio, nuestro objetivo fue determinar el potencial antibacteriano, anti Candida y anti-Dengue de las nuevas chalconas que poseen los grupos 2,4-dihidroxilo y tetrahidropiranilo. El ensayo de actividad antimicrobiana mostró que las bacterias del género Staphylococcus (incluidas las cepas resistentes a la meticilina) fueron sensibles a las 2,4-dihidroxicalconas estudiadas, con concentraciones inhibitorias mínimas (CIM) que oscilan entre 19,5 y 125 µg.mL-1. El compuesto 4e, que tuvo el mejor efecto bacteriostático, también mostró un efecto bactericida a partir de la concentración de 80 µg.mL-1. El crecimiento de los aislamientos orales de Candida albicans también se inhibió eficientemente con el compuesto 4e (CIM: 15.6-32.3 µg.mL-1), que fue fungicida a una concentración de 15.6 µg.mL-1. Sin embargo, la presencia del grupo tetrahidropiranilo perjudicó la actividad antibacteriana y anti-fúngica de los análogos de la chalcona. Además, ninguno de los compuestos evaluados mostró un efecto contra el virus del dengue serotipo 2. En conclusión, el compuesto 4e muestra una buena actividad anti-estafilocócica y anti-Candida y puede ser un prototipo prometedor para el desarrollo de nuevos agentes antimicrobianos.

RESUMO As chalconas se destacam como uma importante estrutura na química medicinal e dessa forma tem sido empregada como um protótipo para o desenvolvimento de novos fármacos. Nesse estudo, nós objetivamos determinar o potencial antibacteriano, anti-Candida, e anti-Dengue de novas chalconas que possuem os grupos 2,4-dihidroxil e tetrahidropiranil. O ensaio de atividade antimicrobiana mostrou que bactérias do gênero Staphylococcus (incluindo linhagens resistentes a meticilina) foram sensíveis para as 2,4-dihidroxichalconas estudadas, com concentrações inibitórias mínimas (CIM) variando de 19,5 para 125 Dengue potential of new chalcone µg.mL-1. O composto 4e, o qual apresentou o melhor efeito bacteriostático, também mostrou efeito bactericida a partir da concentração de 80 µg.mL-1. O crescimento de isolados orais de Candida albicans foi também eficientemente inibido com o composto 4e (CIM: 15.6-32.3 µg.mL-1), o qual foi fungicida a concentração de 15,6 µg.mL-1. Entretanto, a presença do grupo tetrahidropiranil prejudicou a atividade antibacteriana e antifúngica dos análogos de chalcona. Adicionalmente, nenhum dos compostos avaliados mostrou efeito contra o vírus da dengue sorotipo 2. Em conclusão, o composto 4e apresenta boa atividade anti-estafilocóccica e anti-Candida, e pode ser um promissor protótipo para o desenvolvimento de novos agentes antimicrobianos.

Nutr Metab Cardiovasc Dis ; 30(6): 1023-1031, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32249140


BACKGROUND AND AIMS: Consumption of a high caloric diet induces autonomic imbalance, which can lead to cardiovascular disease. Impaired arterial baroreflex control is suggested to play an important role in cardiovascular autonomic imbalance, often seen in obesity. We previously demonstrated that cafeteria diets increase the sympathetic drive to white and brown adipose tissue. METHODS AND RESULTS: After feeding a cafeteria diet to rats for 26 days, we evaluated: (i)heart rate (HR) and arterial pressure (AP); (ii)baroreflex and chemoreflex function; and (iii) autonomic modulation of the heart and vessels, measured through pulse interval (PI) and systolic arterial pressure (SAP) variability analyses and following administration of autonomic blockers. The cafeteria diet increased body fat mass and serum insulin, leptin, triacylglycerol and cholesterol levels. Baseline HR (15%) was also increased, accompanied by increased power in the low frequency band (60%) and in the low frequency/high frequency ratio (104%) in the PI spectra. Nonlinear analysis revealed an increased occurrence of 0V (39%) and decreased occurrence of 2UV (18%) patterns. Following administration of autonomic blockers, we observed an increase in cardiac sympathetic tone (425%) in cafeteria diet-fed rats. The cafeteria diet had no effect on AP, SAP variability, baroreflex and chemoreflex control. CONCLUSION: Our findings suggest that consumption of a cafeteria diet increases sympathetic drive to the heart but not to the blood vessels, independent of impairment in baroreflex and chemoreflex functions. Other mechanisms may be involved in the increased cardiac sympathetic drive, and compensatory vascular mechanisms may prevent the development of hypertension in this model of obesity.

Barorreflexo , Células Quimiorreceptoras/metabolismo , Dieta , Ingestão de Energia , Coração/inervação , Obesidade/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Animais , Pressão Arterial , Modelos Animais de Doenças , Frequência Cardíaca , Masculino , Obesidade/etiologia , Obesidade/metabolismo , Ratos Wistar , Fatores de Tempo
Adv Pharm Bull ; 10(1): 119-124, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32002370


Purpose: Here, we aim to evaluate the antileishmanial activity of compounds with a benzoxazinoid (BX) skeleton, previously synthesized by our group, against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum promastigotes. Methods: Anti-promastigote activity, as well as cytotoxicity, were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assays. The selectivity index (SI) for each compound was calculated using a ratio of the cytotoxicity of compounds and the geometric mean (GM) of antileishmanial concentrations to each species tested. The comparisons between groups were carried out using a t test or analysis of variance (one-way ANOVA). A P value of less than 0.05 was considered significant. Results: All the compounds tested were active, with IC50 falling between 92±6.19 µg/mL and 238±6.57 µg/mL for L. braziliensis, and 89±6.43 µg/mL and 188±3.58 µg/mL against L. infantum. Bex2, Bex3, Pyr1, Pyr2, and Pyr4 were compounds that showed activity similar to the drug Glucantime®, exhibited low cytotoxicity against splenic hamster cells (CC50 raging between >400 and 105.7±2.26 µg/mL) and had favorable selectivity indices (SI 1.12 to 3.96). Conclusion: The analogs in question are promising prototypes for the pharmaceutical development of novel, safer and more effective leishmanicidal agents.

Folia Microbiol (Praha) ; 65(2): 393-405, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31401762


Nosocomial infections are an important cause of morbi-mortality worldwide. The increase in the rate of resistance to conventional drugs in these microorganisms has stimulated the search for new therapeutic options. The nitro moiety (NO2) is an important pharmacophore of molecules with high anti-infective activity. We aimed to synthesize new nitro-derivates and to evaluate their antibacterial and anti-Candida potential in vitro. Five compounds [3-nitro-2-phenylchroman-4-ol (3); 3-nitro-2-phenyl-2H-chromene (4a); 3-nitro-2-(4-chlorophenyl)-2H-chromene (4b); 3-nitro-2-(4-fluorophenyl)-2H-chromene (4c), and 3-Nitro-2-(2,3-dichlorophenyl)-2H-chromene (4d)] were efficiently synthesized by Michael-aldol reaction of 2-hydroxybenzaldehyde with nitrostyrene, resulting in one ß-nitro-alcohol (3) and four nitro-olefins (4a-4d). The antibacterial and anti-Candida potentials were evaluated by assaying minimal inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and minimum bactericidal concentration (MBC). Mono-halogenated nitro-compounds (4b and 4c) showed anti-staphylococcal activity with MIC values of 15.6-62.5 µg/mL and MBC of 62.5 µg/mL. However, the activity against Gram-negative strains was showed to be considerably lower and our data suggests that this effect was associated with the outer membrane. Furthermore, nitro-compounds 4c and 4d presented activity against Candida spp. with MIC values ranging from 7.8-31.25 µg/mL and MFC of 15.6-500 µg/mL. In addition, these compounds were able to induce damage in fungal cells increasing the release of intracellular material, which was associated with actions on the cell wall independent of quantitative changes in chitin and ß-glucan. Together, these findings show that nitro-compounds can be exploited as anti-staphylococcal and anti-Candida prototypes.

Anti-Infecciosos/farmacologia , Nitrocompostos/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Desenho de Fármacos , Humanos , Testes de Sensibilidade Microbiana , Nitrocompostos/síntese química , Nitrocompostos/química
Mol Biol Rep ; 47(2): 1471-1483, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31813128


The plasmid-mediated quinolone resistance (PMQR) genes have changed the resistance pattern to quinolones, especially among Enterobacteriales. The dissemination of these genes in Latin American countries, where the prescription of fluoroquinolones is high, has been described in several studies; however, no review of the impact of PMQR in this continent has been conducted. This review summarized current knowledge about the circulation of PMQR among Enterobacteriales in Latin American. After the search and selection, 61 articles were included in the study. Most of studies reported PMQR genes among Enterobacteriales from human (47/61, 77%) and animal (18/61, 29.5%) samples, recovered mainly in Brazil (23/61, 37.7%), Mexico (11/61, 18%), and Uruguay (7/61, 11.5%). Nine different PMQR genes (qnrA, qnrB, qnrS, qnrD, qnrE, aac-(6')-Ib-cr, oqxA, oqxB, and qepA) were found in Latin America, with aac (6')-Ib-cr (37/61, 60.6%) and qnrB (26/61, 42.6%) being the most frequently reported. Escherichia coli (40/61, 65.6%) was the species most frequently reported to carry a PMQR gene, followed by Klebsiella pneumoniae (24/61, 39.3%), Enterobacter cloacae (15/61, 24.6%), and Salmonella spp. (14/61, 22.9%). Thus, this review provides important information which might help in designing measures to control the spread of quinolone resistance determinants on this continent.

Farmacorresistência Bacteriana/genética , Enterobacteriaceae/efeitos dos fármacos , Plasmídeos/metabolismo , Quinolonas/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Geografia , Humanos , América Latina
Nat Prod Res ; : 1-6, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31554433


Dengue virus (DENV) is the most prevalent mosquito-borne viral pathogen and made the disease a major health concern worldwide. However, specific antiviral drugs against this arbovirose or vaccines are not yet available for treatment or prevention. Thus, here we aimed to study the antiviral activity of hydroethanolic extract, fraction ethyl acetate and subfractions of the leaves of Bauhinia holophylla (Fabaceae:Cercideae), a native plant of the Brazilian Cerrado, against DENV-2 by methylthiazolyldiphenyl-tetrazolium bromide (MTT) method in mammalian cells culture. As results, the hydroethanolic extract showed the most potent effect, with an inhibitory concentration (IC50) of 3.2 µg mL-1 and selectivity index (SI) of 27.6, approximately 16-times higher anti-DENV-2 activity than of the ribavirin (IC50 52.8 µg mL-1). Our results showed in this study appointed that B. holophylla has a promising anti-dengue activity, which was associated mainly with the presence of flavonoids.

Burns ; 45(7): 1495-1508, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31351820


PURPOSE: In this study, we aimed reviewed the data about the patterns of antimicrobial susceptibility and resistance determinants among carbapenem-resistant Acinetobacter baumannii (CRAB) from patients with burn injury. METHODS: A systematic review was conducted using the PRISMA statement in PUBMED/MEDLINE, Scopus, Scientific Electronic Library Online (SciELO), Biblioteca Virtual de Saúde (BVS) and Cochrane Library. The data referring to enzymatic resistance mechanisms were evaluated by meta-analyses according to random effect. RESULTS: 17 articles that evaluated 1226 CRAB recovered from patients with burn injury were included in study. The majority of studies are from Iran (12/17; 70.6%), published in 2016 (6/17; 35.3%) and showed prospective design (15/17; 88.2%). The samples were obtained mainly from burn wounds (14/17; 82.3%) and more than half of the studies did not identify if the isolates originated from infected or colonized patients (10/17; 58.8%). Second the meta-analyses, OXA-type carbapenemase was the main mechanism involved in low susceptibility to carbapenems (53.2%; 95% CI = 60, 80.0%, I2 = 86.0%), followed by metallo-ß-lactamases (MBL) (30.2%; 95% CI = 11, 42.0%, I2 = 93.0%), and Klebsiella pneumoniae carbapenemase (KPC) (16.6%; 95% CI = 5, 63.0%, I2 = 88.0%). The majority of strains harbored blaOXA-23-like (12/17; 70.6%) or blaOXA-24/40-like (12/17; 35.3%) genes. The studies included showed that minocycline (69.5%) and colistin (99.9%) susceptibility remains high and is not impacted by carbapenem resistance in these isolates. CONCLUSIONS: The results summarized in this review indicate the importance of a high-quality surveillance program to design suitable and effective interventions to control CRAB infection in burn units worldwide.

Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/metabolismo , Proteínas de Bactérias/metabolismo , Queimaduras/epidemiologia , Farmacorresistência Bacteriana , beta-Lactamases/metabolismo , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/fisiologia , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Colistina/uso terapêutico , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Humanos , Minociclina/uso terapêutico
Travel Med Infect Dis ; 31: 101459, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336179


A systematic review was performed in order to integrate and synthesize available information on mcr genes dissemination in Latin America. Four databases were searched for articles reporting plasmid-mediated colistin resistance between bacteria isolated from countries of Latin America and the Caribbean. Abstract books of scientific events realized in each region were also examined. After search and selection, 48 studies that included 18,705 isolates recovered between 2000 and 2018 were evaluated. The overall frequency of mcr genes in Latin America was 2.9% (550/18,705), with IncX4 plasmids shown to be the key vectors responsible for the dissemination of genes within the continent. Brazil, Bolivia and Argentina were the countries with the highest number of mcr-positive isolates, and only Colombia (mcr-5) and Brazil (mcr-3) presented mcr genes other than type 1. Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica serovar Typhimurium were mainly found to carry the gene within the continent and these microorganisms showed high susceptibility to ertapenem, meropenem, piperacillin/tazobactam, fosfomycin and tigecycline. This review showed that the mcr gene is circulating in several countries of Latin America. Thus, it is important to encourage microbiological and molecular surveillance programs to avoid the spread of these genes within and outside the continent.

Colistina , Farmacorresistência Bacteriana/genética , Plasmídeos/genética , Bactérias/efeitos dos fármacos , Região do Caribe/epidemiologia , Colistina/farmacologia , Genes Bacterianos/genética , América Latina/epidemiologia
Rev Med Virol ; 29(5): e2056, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31172625


Dengue virus is known to modulate host cell lipid metabolism in order to promote efficient viral replication. Recent studies have focused on circulating lipids as potential biomarkers of dengue severity; however, the results obtained so far lack the consistency to establish a definite relationship between the two. Therefore, in the present study, we investigated serum lipids as potential biomarkers of dengue severity by conducting a meta-analysis of the currently available clinical data. Nine studies that evaluated 1,953 patients were included in the review, many of which were cross-sectional (44.4%) and conducted in Asian countries (55.5%). These studies observed the presence of lipids in serum samples (77%) of patients in the acute phase of the disease (88.8%). Circulating total-cholesterol (P = .001) and LDL (P = .001) levels, but not HDL (P = .07), VLDL (P = .9) and triglyceride (P = .57) levels, were inversely and significantly correlated with dengue severity. Total cholesterol (P ≤ .001) and LDL (P = .001) were also useful in determining the risk of hypovolemic shock in patients with severe dengue. Subgroup analysis showed that factors, such as design (cross-sectional vs cohort), racial-ethnic differences (Asian vs Latin Americans), and age range (children vs adult) influenced the correlation and also contributed to the high level of heterogeneity in the studies. Our meta-analysis demonstrates that total-cholesterol and LDL-cholesterol levels should be explored as routine laboratory markers for dengue severity, as they will help in employing an appropriate patient therapy, and thus optimize the use of available resources.

Biomarcadores , Dengue/sangue , Dengue/diagnóstico , Lipídeos/sangue , Humanos , Prognóstico , Viés de Publicação , Dengue Grave/sangue , Dengue Grave/diagnóstico , Índice de Gravidade de Doença