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1.
Metabolites ; 13(2)2023 Feb 03.
Article in English | MEDLINE | ID: mdl-36837841

ABSTRACT

Trichoderma is recognized as a prolific producer of nonribosomal peptides (NRPs) known as peptaibols, which have remarkable biological properties, such as antimicrobial and anticancer activities, as well as the ability to promote systemic resistance in plants against pathogens. In this study, the sequencing of 11-, 14- and 15-res peptaibols produced by a marine strain of Trichoderma isolated from the ascidian Botrylloides giganteus was performed via liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS). Identification, based on multilocus phylogeny, revealed that our isolate belongs to the species T. endophyticum, which has never been reported in marine environments. Through genome sequencing and genome mining, 53 biosynthetic gene clusters (BGCs) were identified as being related to bioactive natural products, including two NRP-synthetases: one responsible for the biosynthesis of 11- and 14-res peptaibols, and another for the biosynthesis of 15-res. Substrate prediction, based on phylogeny of the adenylation domains in combination with molecular networking, permitted extensive annotation of the mass spectra related to two new series of 15-res peptaibols, which are referred to herein as "endophytins". The analyses of synteny revealed that the origin of the 15-module peptaibol synthetase is related to 18, 19 and 20-module peptaibol synthetases, and suggests that the loss of modules may be a mechanism used by Trichoderma species for peptaibol diversification. This study demonstrates the importance of combining genome mining techniques, mass spectrometry analysis and molecular networks for the discovery of new natural products.

2.
Sci Rep ; 12(1): 18500, 2022 11 02.
Article in English | MEDLINE | ID: mdl-36323732

ABSTRACT

The nucleocapsid (N) protein plays critical roles in coronavirus genome transcription and packaging, representing a key target for the development of novel antivirals, and for which structural information on ligand binding is scarce. We used a novel fluorescence polarization assay to identify small molecules that disrupt the binding of the N protein to a target RNA derived from the SARS-CoV-2 genome packaging signal. Several phenolic compounds, including L-chicoric acid (CA), were identified as high-affinity N-protein ligands. The binding of CA to the N protein was confirmed by isothermal titration calorimetry, 1H-STD and 15N-HSQC NMR, and by the crystal structure of CA bound to the N protein C-terminal domain (CTD), further revealing a new modulatory site in the SARS-CoV-2 N protein. Moreover, CA reduced SARS-CoV-2 replication in cell cultures. These data thus open venues for the development of new antivirals targeting the N protein, an essential and yet underexplored coronavirus target.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Ligands , Nucleocapsid Proteins/genetics , RNA/metabolism , Antiviral Agents/pharmacology , Protein Binding
3.
Med Chem ; 18(6): 701-709, 2022.
Article in English | MEDLINE | ID: mdl-34784878

ABSTRACT

BACKGROUND: Tuberculosis (TB) is one of the top ten causes of death worldwide, while Chagas disease (CD) is the parasitic disease that kills the largest number of people in the Americas. TB is the leading cause of death for patients with AIDS; it kills 1.5 million people and causes 10 million new cases every year. The lack of newly developed chemotherapeutic agents and insufficient access to health care services for a diagnosis increase the incidence of multidrug-resistant TB (MDRTB) cases. Although CD was identified in 1909, the chronic stages of the disease still lack adequate treatment. OBJECTIVE: The purpose of this work was to design and synthesize two new series of 2-nitroimidazole 5a-e and imidazooxazoles 6a-e with 1H-1,2,3-triazolil nucleus and evaluate their activities against Tc and Mycobacterium tuberculosis (Mtb). METHODS: Two series of five compounds were synthesized in a 3 or 4-step route in moderated yields, and their structures were confirmed by NMR spectral data analyses. The in vitro antitrypanosomal evaluation of products was carried out in an intracellular model using L929 cell line infected with trypomastigotes and amastigote forms of Tc of ß-galactosidase-transfected Tulahuen strain. Their antimycobacterial activity was evaluated against Mtb strain H37Rv. RESULTS: In general, 2-nitroimidazolic derivatives proved to be more potent in regard to antitrypanocidal and antimycobacterial activity. The non-cytotoxic 2-nitroimidazole derivative 5b was the most promising with a half maximum inhibitory concentration of 3.2 µM against Tc and a minimum inhibitory concentration of 65.3 µM against Mtb. CONCLUSION: Our study reinforced the importance of 2-nitroimidazole and 1H-1,2,3-triazole nuclei in antimicrobial activity. In addition, derivative 5b proved to be the most promising, presenting important activity against Tc and Mtb and could be used as a starting point for the development of new agents against these diseases.


Subject(s)
Mycobacterium tuberculosis , Nitroimidazoles , Trypanosoma cruzi , Tuberculosis, Multidrug-Resistant , Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Humans , Microbial Sensitivity Tests , Nitroimidazoles/pharmacology
4.
ACS Infect Dis ; 7(8): 2455-2471, 2021 08 13.
Article in English | MEDLINE | ID: mdl-34279922

ABSTRACT

Chagas disease, an infectious condition caused by Trypanosoma cruzi, lacks treatment with drugs with desired efficacy and safety profiles. To address this unmet medical need, a set of trypanocidal compounds were identified through a large multicenter phenotypic-screening initiative and assembled in the GSK Chagas Box. In the present work, we report the screening of the Chagas Box against T. cruzi malic enzymes (MEs) and the identification of three potent inhibitors of its cytosolic isoform (TcMEc). One of these compounds, TCMDC-143108 (1), came out as a nanomolar inhibitor of TcMEc, and 14 new derivatives were synthesized and tested for target inhibition and efficacy against the parasite. Moreover, we determined the crystallographic structures of TcMEc in complex with TCMDC-143108 (1) and six derivatives, revealing the allosteric inhibition site and the determinants of specificity. Our findings connect phenotypic hits from the Chagas Box to a relevant metabolic target in the parasite, providing data to foster new structure-activity guided hit optimization initiatives.


Subject(s)
Chagas Disease , Trypanocidal Agents , Trypanosoma cruzi , Chagas Disease/drug therapy , Humans , Sulfonamides , Trypanocidal Agents/pharmacology
5.
J Membr Biol ; 254(2): 189-199, 2021 04.
Article in English | MEDLINE | ID: mdl-33598793

ABSTRACT

Our study aimed to investigate the effects of the new cardiotonic steroid BD-15 (γ-benzylidene derivatives) in the behavioral parameters, oxidative stress and the Na, K-ATPase activity in the hippocampus, prefrontal cortex and heart from rats to verify the safety and possible utilization in brain disorders. For this study, groups of male Wistar rats were used after intraperitoneal injection of 20, 100 and 200 µg/Kg with BD-15. The groups were treated for three consecutive days and the control group received 0.9% saline. BD-15 did not alter behavior of rats treated with different doses. An increase in the specific α2,3-Na, K-ATPase activity was observed for all doses of BD-15 tested in the hippocampus. However, in the prefrontal cortex, only the dose of 100 µg/Kg increased the activity of all Na, K-ATPase isoforms. BD-15 did not cause alteration in the lipid peroxidation levels in the hippocampus, but in the prefrontal cortex, a decrease of lipid peroxidation (~ 25%) was observed. In the hippocampus, GSH levels increased with all doses tested, while in the prefrontal cortex no changes were found. Subsequently, when the effect of BD-15 on cardiac tissue was analyzed, no changes were observed in the tested parameters. BD-15 at a dosage of 100 µg/Kg proved to be promising because it is considered therapeutic for brain disorders, since it increases the activity of the α3-Na, K-ATPase in the hippocampus and prefrontal cortex, as well as decreasing the oxidative stress in these brain regions. In addition, this drug did not cause changes in the tissues of the heart and kidneys, preferentially demonstrating specificity for the brain.


Subject(s)
Benzylidene Compounds/pharmacology , Digoxin/pharmacology , Hippocampus/enzymology , Prefrontal Cortex/enzymology , Sodium-Potassium-Exchanging ATPase/metabolism , Animals , Brain Diseases , Heart/drug effects , Hippocampus/drug effects , Male , Prefrontal Cortex/drug effects , Rats , Rats, Wistar
6.
Food Res Int ; 139: 109836, 2021 01.
Article in English | MEDLINE | ID: mdl-33509461

ABSTRACT

Fruits are widely recognized as sources of biologically active metabolites, such as antioxidant compounds. In this context, fruits commonly consumed in the central Amazonia, especially in its biggest metropolis (Manaus - AM/Brazil), are attractive as potential sources of antioxidant compounds related to biological activities. Most of such fruits are still poorly studied and/or remain unknown outside the Amazon region. Therefore, this study aims to investigate nine fruits (abiu, cubiu, biribá, breadfruit, genipap, peach palm, murici, soursop, and umari) regarding their chemical composition (fixed and volatile), reducing capacity, antioxidant activity, enzyme inhibition, and cytotoxicity. Determination of small organic acids, hydroxycinnamic acids, flavan-3-ols and flavonoid aglycones was done by HPLC-MS/MS, whereas determination of volatile organic compounds (VOCs) was done by HS-SPME/GC-MS. Reducing capacity was determined by the Folin-Ciocalteu method, and antioxidant activities were evaluated by DPPH, ABTS, and H-ORACFL assays. In vitro activities regarding inhibition of enzymes were tested for α-glucosidase, lipase, and α-amylase, and anti-glycation activities were evaluated for methylglyoxal and fructose. Cytotoxicity of fruit extracts was evaluated by cell viability of human fibroblast cell line (MRC-5). A total of 16 antioxidant compounds and 139 VOCs were determined, whose profiles were unique for each studied fruit. Total phenolic contents as well as antioxidant activities found herein were similar or even higher than those reported for several traditional fruits. Some of fruit extracts were able to inhibit α-glucosidase and glycation in methylglyoxal and fructose models, whereas none of them was active for lipase and α-amylase. All of the fruit extracts showed to be non-cytotoxic to MRC-5 cell line.


Subject(s)
Fruit , Malpighiaceae , Antioxidants/pharmacology , Brazil , Humans , Tandem Mass Spectrometry
7.
ACS Med Chem Lett ; 11(6): 1250-1256, 2020 Jun 11.
Article in English | MEDLINE | ID: mdl-32551008

ABSTRACT

Chagas disease is a parasitic infection affecting millions of people across Latin America, imposing a dramatic socioeconomic burden. Despite the availability of drugs, nifurtimox and benznidazole, lack of efficacy and incidence of side-effects prompt the identification of novel, efficient, and affordable drug candidates. To address this issue, one strategy could be probing the susceptibility of Trypanosoma parasites toward NADP-dependent enzyme inhibitors. Recently, steroids of the androstane group have been described as highly potent but nonselective inhibitors of parasitic glucose-6-phosphate dehydrogenase (G6PDH). In order to promote selectivity, we have synthesized and evaluated 26 steroid derivatives of epiandrosterone in enzymatic assays, whereby 17 compounds were shown to display moderate to high selectivity for T. cruzi over the human G6PDH. In addition, three compounds were effective in killing intracellular T. cruzi forms infecting rat cardiomyocytes. Altogether, this study provides new SAR data around G6PDH and further supports this target for treating Chagas disease.

8.
Mol Genet Genomics ; 295(3): 717-739, 2020 May.
Article in English | MEDLINE | ID: mdl-32124034

ABSTRACT

The phenylpropanoid pathway is an important route of secondary metabolism involved in the synthesis of different phenolic compounds such as phenylpropenes, anthocyanins, stilbenoids, flavonoids, and monolignols. The flux toward monolignol biosynthesis through the phenylpropanoid pathway is controlled by specific genes from at least ten families. Lignin polymer is one of the major components of the plant cell wall and is mainly responsible for recalcitrance to saccharification in ethanol production from lignocellulosic biomass. Here, we identified and characterized sugarcane candidate genes from the general phenylpropanoid and monolignol-specific metabolism through a search of the sugarcane EST databases, phylogenetic analysis, a search for conserved amino acid residues important for enzymatic function, and analysis of expression patterns during culm development in two lignin-contrasting genotypes. Of these genes, 15 were cloned and, when available, their loci were identified using the recently released sugarcane genomes from Saccharum hybrid R570 and Saccharum spontaneum cultivars. Our analysis points out that ShPAL1, ShPAL2, ShC4H4, Sh4CL1, ShHCT1, ShC3H1, ShC3H2, ShCCoAOMT1, ShCOMT1, ShF5H1, ShCCR1, ShCAD2, and ShCAD7 are strong candidates to be bona fide lignin biosynthesis genes. Together, the results provide information about the candidate genes involved in monolignol biosynthesis in sugarcane and may provide useful information for further molecular genetic studies in sugarcane.


Subject(s)
Biosynthetic Pathways/genetics , Lignin/biosynthesis , Plant Proteins/genetics , Propanols/metabolism , Saccharum/genetics , Saccharum/metabolism , Gene Expression Regulation, Plant , Genotype , Lignin/genetics , Propanols/chemistry , Saccharum/classification , Saccharum/growth & development
10.
Rev. Salusvita (Online) ; 38(4): 939-958, 2019.
Article in Portuguese | LILACS | ID: biblio-1102962

ABSTRACT

Introdução: O uso de plantas na medicina fitoterápica é uma alternativa à medicina tradicional, por cota de seus efeitos anti inflamatórios, antimicrobianos e antioxidantes, potencialmente eficazes no auxílio do processo cicatricial. Objetivo: O estudo avaliou, por análise histológica, o potencial dos extratos aquosos da Psidium guajava e da Myrciaria cauliflora no reparo de feridas de segunda intenção. Método: Foram utilizadas 20 ratas Wistar adultas, distribuídas aleatoriamente em quatro grupos de 5 animais, com tratamento tópico diário das lesões de 6 mm de diâmetro: Controle Positivo (CP) - solução aquosa de Bepantol® 5%; Controle Negativo (CN) - água bidestilada estéril; e Grupos Experimentais (GO) - extrato aquoso da casca do caule da goiabeira 10% e (JU) - extrato aquoso da folha da jabuticabeira 1 g/mL. Cinco e dez dias após a lesão, os fragmentos de tecido contendo a ferida foram coletados e fixados em formalina tamponada. Foram realizados cortes histológicos de 5 mm e as lâminas foram coradas com Hematoxilina-Eosina para serem analisadas por microscopia de luz. Por uma análise qualitativa, percebe-se que há diferenças na cinética de fechamento das feridas, pois o uso dos extratos e do Bepantol®, possibilitaram reepitelização mais rápida e menor quantidade de células inflamatórias agudas. Aos 10 dias, nos animais JU sugere-se processo de reparo avançado, com boa vascularização e pouca inflamação, e no grupo GO sugere-se formação de cicatriz menor em comprimento que a dos demais grupos, com deposição de fibras de colágeno mais próximas topograficamnete da pele intacta. Conclusão: Considerando-se os resultados obtidos no presente estudo, com 5 e 10 dias não há evidências de que qualquer tratamento foi de fato impactante e mudou de forma expressiva a cicatrização das feridas.


Introduction: The use of plants in herbal medicine is an alternative to traditional medicine due to its anti-inflammatory, antimicrobial and antioxidant effects, potentially effective in the healing process. Objective: The study evaluated, by histological analysis, the potential of aqueous extracts of Psidium guajava and Myrciaria cauliflora in the repair of second intention wounds. Method: Twenty adult female Wistar rats were randomly assigned to four groups of five animals each. The animals received daily topical treatment in 6 mm diameter lesions. The groups were: Positive Control (CP) - aqueous solution of Bepantol® 5%; Negative Control (CN) - sterile bidistilled water; Experimental Groups (GO) - aqueous extract of guava stem bark at 10% and (JU) - aqueous extract of jabuticaba leaf at 1 g/mL. Five and ten days after injury, tissue fragments containing the wound were collected and fixed in formalin. Sections of 5 µm thickness were performed and stained with HematoxylinEosin for analysis by microscopy. From a qualitative analysis there are no differences in the kinetics of wound closure, since the use aqueous extract and Bepantol®, allowed faster reepithelization and fewer acute inflammatory cells. At 10 days, in JU group, an advanced repair process was observed, with good vascularization and low inflammation, and in the GO group, scar formation is suggested to be smaller than that of the other groups, with deposition of collagen fibers closer to the intact skin. Conclusion: Considering the results obtained in the present study, at day 5 and day10, there is no evidence that any treatment was in fact impacting and significantly altering the woud healing.


Subject(s)
Wound Healing , Phytotherapy
11.
Pesqui. prát. psicossociais ; 12(3): 1-19, set.-dez. 2017. tab
Article in Portuguese | LILACS | ID: biblio-895287

ABSTRACT

Este trabalho investigou a elaboração do objeto social 'ciganos' entre não ciganos da Grande Vitória/ES, a partir da dimensão afetiva e dos níveis de contato em relação ao grupo cigano. Participaram do estudo 56 pessoas, com idades entre 18 e 45 anos, que apresentaram tanto sentimentos positivos quanto negativos em relação aos ciganos. Para o tratamento dos dados, coletados por meio da aplicação de questionário, utilizou-se o software EVOC e a Análise de Conteúdo Categorial. Os resultados informam que o posicionamento afetivo se organiza, principalmente, a partir das dimensões positiva 'curiosidade' e 'respeito', e negativa 'insegurança' e 'desconfiança'. Associado a esse campo de ambiguidades, entre os elementos centrais das representações de ciganos encontram-se significados como 'nomadismo' e 'cultura diferente', além de estereótipos negativos e termos que descrevem a dimensão figurativa do objeto social. Discute-se a função das representações encontradas na manutenção do preconceito e da discriminação social contra esse grupo.


This study investigated the construction of the social object 'gypsies' among non-gypsies in the metropolitan region of Vitória/ES, based on the affective dimension and the levels of contact towards the gypsy group. Fifty-six (56) individuals aged between 18 and 45 participated in the study. They presented both positive and negative feelings towards gypsies. The data were gathered through questionnaires, and then treated using the software EVOC and Categorical Content Analysis approach. The results showed that the affective field is organized mainly based on the positive dimensions 'curiosity' and 'respect', and the negative ones 'insecurity' and 'suspicion'. Associated to this field of ambiguity, among the central elements of the representations of gypsies, we found meanings such as 'nomadism' and 'different culture', as well as negative stereotypes and terms that describe the figurative dimension of the social object. This study discusses the function of these representations in the maintenance of prejudice and social discrimination against this group.


Este trabajo investigó la elaboración del objeto social 'gitanos' entre los no gitanos de la Gran Vitória/ES, a partir de la dimensión afectiva y de los niveles de contacto con relación al grupo gitano. Participaron en el estudio 56 personas de 18 a 45 años de edad que presentaron tanto sentimientos positivos como negativos con relación a los gitanos. Para el análisis de los datos, recogidos por medio de cuestionarios, se utilizó el software EVOC y el Análisis de Contenido Categorial. Los resultados informan que la posición afectiva se organiza, principalmente, a partir de las dimensiones positivas 'curiosidad' y 'respeto'; y negativas 'inseguridad' y 'desconfianza'. Asociado a este campo de ambigüedades, entre los elementos centrales de las representaciones de gitanos, se encuentran significados como 'nomadismo' y 'cultura diferente', además de estereotipos negativos y términos que describen la dimensión figurativa del objeto social. Se discute la función de las representaciones encontradas en el mantenimiento del prejuicio y de la discriminación social contra este grupo.


Subject(s)
Social Desirability , Rome , Psychology, Social , Race Relations , Stereotyping , Population Groups , Interpersonal Relations
12.
Bioorg Med Chem ; 25(21): 5891-5903, 2017 11 01.
Article in English | MEDLINE | ID: mdl-28988624

ABSTRACT

The pyrazole nucleus is an aromatic azole heterocycle with two adjacent nitrogen atoms. Pyrazole derivatives have exhibited a broad spectrum of biological activities, and approved pyrazole-containing drugs include celecoxib, antipyrine, phenylbutazone, rimonabant, and dipyrone. Many research groups have synthesized and evaluated pyrazoles against several biological agents. This review examines recent publications relating the structures of pyrazoles with their corresponding biological activities.


Subject(s)
Pyrazoles/pharmacology , Analgesics/chemistry , Analgesics/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Humans , Pyrazoles/chemistry
13.
Mol Plant Microbe Interact ; 30(7): 578-588, 2017 07.
Article in English | MEDLINE | ID: mdl-28562158

ABSTRACT

The uptake and transport of sulfate in bacteria is mediated by an ATP-binding cassette transporter (ABC transporter) encoded by sbpcysUWA genes, whose importance has been widely demonstrated due to their relevance in cysteine synthesis and bacterial growth. In Xanthomonas citri, the causative agent of canker disease, the expression of components from this ABC transporter and others related to uptake of organic sulfur sources has been shown during in vitro growth cultures. In this work, based on gene reporter and proteomics analyses, we showed the activation of the promoter that controls the sbpcysUWA operon in vitro and in vivo and the expression of sulfate-binding protein (Sbp), a periplasmic-binding protein, indicating that this protein plays an important function during growth and that the transport system is active during Citrus sinensis infection. To characterize Sbp, we solved its three-dimensional structure bound to sulfate at 1.14 Å resolution and performed biochemical and functional characterization. The results revealed that Sbp interacts with sulfate without structural changes, but the interaction induces a significant increasing of protein thermal stability. Altogether, the results presented in this study show the evidence of the functionality of the ABC transporter for sulfate in X. citri and its relevance during infection.


Subject(s)
Periplasmic Binding Proteins/metabolism , Proteomics/methods , Sulfates/metabolism , Xanthomonas/metabolism , Amino Acid Sequence , Base Sequence , Biological Transport , Citrus sinensis/microbiology , Gene Expression Regulation, Bacterial , Models, Molecular , Periplasmic Binding Proteins/chemistry , Periplasmic Binding Proteins/genetics , Plant Diseases/microbiology , Protein Binding , Protein Domains , Sequence Homology, Amino Acid , Sulfates/chemistry , Xanthomonas/genetics , Xanthomonas/physiology
14.
Ribeirão Preto; s.n; 2015. tab, ilus.
Thesis in Portuguese | Sec. Est. Saúde SP, SESSP-CTDPROD, Sec. Est. Saúde SP, SESSP-ACVSES, SESSP-PAPSESSP, Sec. Est. Saúde SP | ID: biblio-1082505

ABSTRACT

O presente trabalho descreve os resultados obtidos da determinação da concentração inibitória mínima (CIM) dos antibióticos polimixina B, amicacina, imipenem e tigeciclina para cepas de Klebsiella pneumoniae.O método utilizado foi a microdiluição em caldo, tendo como referência o documento M7 - A6 do Clinical and Laboratory Standards nstitute (CLSI). Foram avaliadas 56 bactérias KPC isoladas de diversos sítios de pacientes do Hospital das Clínicas da FMRP-USP, no período de janeiro à dezembro de 2014. A identificação das KPC baseou-se no sistema de automação Vitek2 e algumas confirmações do perfil de resistência por disco difusão.Para a realização da técnica de microdiluição em caldo, foram feitos repiques de 48 horas das bactérias. A técnica foi realizada em duplicata e em cada placa havia controles positivos e negativos.A CIM da polimixina B variou de 1μg/ml à 64μg/ml sendo a CIM50 igual à 8 μg/ml, CIM90 igual à 64 μg/ml e a MG foi de 17,08 μg/ml. A CIM da amicacina variou ≤1μg/ml à 128 μg/ml, com CIM50 de 4 μg/ml e CIM90 de 32 μg/ml e uma MG correspondente à 9,14 μg/ml. O imipenem obteve uma variação de CIM de ≤ 2 μg/ml à 512 μg/ml, CIM50 de 32 μg/ml e CIM90 de 256 μg/ml e MG de 78,39 μg/ml. E a tigeciclina apresentou uma variação de CIM de 0,25 μg/ml à 4 μg/ml, CIM50 de 1 μg/ml e CIM90 de 2 μg/ml e MG de 1,21 μg/ml.A resistência a polimixina B foi confirmada pelo método de microdiluição em caldo, revelando um maior percentual de isolados resistentes à polimixina comparando com os resultados de disco-difusão e Vitek2. A grande maioria das cepas mostraram sensíveis à amicacina, entretanto, as reistentes à polimixina tendem a ser menos sensíveis à amicacina. Independente da sensibilidade à polimixina B, 98,22% apresentaram sensibilidade à amicacina...


Subject(s)
Amikacin , Imipenem , Klebsiella pneumoniae , Polymyxin B , Microbial Sensitivity Tests
15.
Bioorg Med Chem Lett ; 23(23): 6310-2, 2013 Dec 01.
Article in English | MEDLINE | ID: mdl-24125880

ABSTRACT

A new series of 5-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1H-tetrazole derivatives (4a-m) and their precursor 1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (3a-m) were synthesized and evaluated as antileishmanials against Leishmania braziliensis and Leishmania amazonensis promastigotes in vitro. In parallel, the cytotoxicity of these compounds was evaluated on the RAW 264.7 cell line. The results showed that among the assayed compounds the substituted 3-chlorophenyl (4a) (IC50/24h=15±0.14 µM) and 3,4-dichlorophenyl tetrazoles (4d) (IC50/24h=26±0.09 µM) were the most potent against L. braziliensis promastigotes, as compared the reference drug pentamidine, which presented IC50=13±0.04 µM. In addition, 4a and 4d derivatives were less cytotoxic than pentamidine. However, these tetrazole derivatives (4) and pyrazole-4-carbonitriles precursors (3) differ against each of the tested species and were more effective against L.braziliensis than on L. amazonensis.


Subject(s)
Leishmania/drug effects , Nitriles/chemistry , Pyrazoles/chemistry , Tetrazoles/chemical synthesis , Tetrazoles/pharmacology , Animals , Antiprotozoal Agents , Cell Line , Dose-Response Relationship, Drug , Mice , Stereoisomerism , Structure-Activity Relationship , Tetrazoles/chemistry
16.
Psicol. saber soc ; 1(2): 245-264, jul.-dez. 2012. ilus, tab
Article in Portuguese | Index Psychology - journals | ID: psi-65222

ABSTRACT

Referenciado na Teoria das Representações Sociais, este trabalho objetivou investigar as representações sociais de ciganos entre não ciganos, bem como a dimensão afetiva a elasassociada. Participaram do estudo, desenvolvido em duas etapas, universitários de instituições públicas e privadas da Grande Vitória-ES. No primeiro estudo (E1), os participantes responderam a um questionário estruturado (n=108), composto pelos seguintes núcleos de informação:evocações livres referentes ao termo ‘ciganos’, campo afetivo relacionado ao objeto de representação, níveis de contato com ciganos e dados socioeconômicos; e no segundo estudo(E2) foram realizadas entrevistas (n=09) com questões exploratórias acerca do conhecimento dos participantes sobre os ciganos, dos sentimentos a eles associados e das experiências de contato com este grupo étnico. Os dados de E1 foram tratados por meio do software SPAD-T, cuja análise indicou a formação de três clusters de sujeitos a partir da dimensão afetiva investigada: ‘sentimentos positivos’ (n=18), ‘sentimentos negativos’ (n=27) e ‘ambíguos’ (n=63). Na segunda etapa, foram entrevistados os sujeitos do cluster ‘sentimentos positivos’, e o tratamento dos dados foi realizado através do software ALCESTE e da Análise de Conteúdo. Os resultadospermitem discutir que os indivíduos apresentaram variações nas representações acerca do objeto social ‘ciganos’. A formação do campo representacional e de sua dimensão afetiva estiveram apoiados na imagem dos ciganos (a) como povo alegre, da dança e de roupas coloridas, que desperta sentimentos de curiosidade, encantamento e admiração, mas também (b) de um grupo que rouba e trapaceia, provocando insegurança, medo e mal-estar entre os nãociganos. (AU)


Referenced in the Social Representations Theory, this research aimed at investigating the social representations of gypsies among non-gypsies and the affective dimension associated with these representations. Participated in this study, carried out in two stages, students from the metropolitan region of Vitória-ES. In a first study (E1) they answered to a structured questionnaire (n=108), consisted of the following information sets: free evocations bind to the term 'gypsy', affective field related to the object of representation, contact experiences with gypsies and socioeconomic data; and in a second study (E2) there were conducted interviews (n=09) with exploratory questions about the participants' knowledge regarding the gypsies,feelings directed to them and levels of contact with this ethnic group. Data from E1 were processed by using the SPAD-T software, whose analysis indicated the formation of three clustersof subjects considering the affective dimension: positive feelings (n=18), negative feelings (n=27) and ambiguous (n=63). In the second stage, subjects from the 'positive feelings' cluster were interviewed, and data processing was performed by using ALCESTE software and Content Analysis. The results allow discussing that individuals had variations in the representations about the social object 'gypsies'. The formation of the representational field and its affective dimension were supported by the image of gypsies (a) as happy people, who dance and wear colorful clothes, which arouses feelings of curiosity, dazzlement and admiration, but also (b) of a group who steals and cheats, causing insecurity, fear and malaise among non-gypsies. (AU)


Subject(s)
Humans , Male , Female , Psychology, Social , Ethnicity/psychology , Affect
17.
Psicol. saber soc ; 1(2): 245-264, jul.-dez. 2012. ilus, tab
Article in Portuguese | LILACS | ID: lil-776079

ABSTRACT

Referenciado na Teoria das Representações Sociais, este trabalho objetivou investigar as representações sociais de ciganos entre não ciganos, bem como a dimensão afetiva a elasassociada. Participaram do estudo, desenvolvido em duas etapas, universitários de instituições públicas e privadas da Grande Vitória-ES. No primeiro estudo (E1), os participantes responderam a um questionário estruturado (n=108), composto pelos seguintes núcleos de informação:evocações livres referentes ao termo ‘ciganos’, campo afetivo relacionado ao objeto de representação, níveis de contato com ciganos e dados socioeconômicos; e no segundo estudo(E2) foram realizadas entrevistas (n=09) com questões exploratórias acerca do conhecimento dos participantes sobre os ciganos, dos sentimentos a eles associados e das experiências de contato com este grupo étnico. Os dados de E1 foram tratados por meio do software SPAD-T, cuja análise indicou a formação de três clusters de sujeitos a partir da dimensão afetiva investigada: ‘sentimentos positivos’ (n=18), ‘sentimentos negativos’ (n=27) e ‘ambíguos’ (n=63). Na segunda etapa, foram entrevistados os sujeitos do cluster ‘sentimentos positivos’, e o tratamento dos dados foi realizado através do software ALCESTE e da Análise de Conteúdo. Os resultadospermitem discutir que os indivíduos apresentaram variações nas representações acerca do objeto social ‘ciganos’. A formação do campo representacional e de sua dimensão afetiva estiveram apoiados na imagem dos ciganos (a) como povo alegre, da dança e de roupas coloridas, que desperta sentimentos de curiosidade, encantamento e admiração, mas também (b) de um grupo que rouba e trapaceia, provocando insegurança, medo e mal-estar entre os nãociganos.


Referenced in the Social Representations Theory, this research aimed at investigating the social representations of gypsies among non-gypsies and the affective dimension associated with these representations. Participated in this study, carried out in two stages, students from the metropolitan region of Vitória-ES. In a first study (E1) they answered to a structured questionnaire (n=108), consisted of the following information sets: free evocations bind to the term 'gypsy', affective field related to the object of representation, contact experiences with gypsies and socioeconomic data; and in a second study (E2) there were conducted interviews (n=09) with exploratory questions about the participants' knowledge regarding the gypsies,feelings directed to them and levels of contact with this ethnic group. Data from E1 were processed by using the SPAD-T software, whose analysis indicated the formation of three clustersof subjects considering the affective dimension: positive feelings (n=18), negative feelings (n=27) and ambiguous (n=63). In the second stage, subjects from the 'positive feelings' cluster were interviewed, and data processing was performed by using ALCESTE software and Content Analysis. The results allow discussing that individuals had variations in the representations about the social object 'gypsies'. The formation of the representational field and its affective dimension were supported by the image of gypsies (a) as happy people, who dance and wear colorful clothes, which arouses feelings of curiosity, dazzlement and admiration, but also (b) of a group who steals and cheats, causing insecurity, fear and malaise among non-gypsies.


Subject(s)
Humans , Male , Female , Affect , Ethnicity/psychology , Psychology, Social
18.
Rev. gaúch. enferm ; 23(2): 81-107, jul. 2002.
Article in Portuguese | LILACS, BDENF - Nursing | ID: lil-347890

ABSTRACT

Trata-se de um estudo fenomenológico-hermenêutico, com base no referencial de Van Manen, que teve como objetivo distinguir os significados das experiências vividas no estado de coma e seu impacto no processo de ser e viver...


Subject(s)
Humans , Coma , Existentialism
19.
Rev Gaucha Enferm ; 23(2): 81-107, 2002 Jul.
Article in Portuguese | MEDLINE | ID: mdl-12593114

ABSTRACT

This is a hermeneutic phenomenological study based on the Van Manen's framework, that aimed to distinguish the meanings of the experiences lived in the state of coma and its impact on the being and living process. It was developed with four participants, three males and one female. Based on the analysis of the information three themes were identified: the unexpected as reality; the singularity of the modified states of consciousness, and the transformation of the being and living process. The coma emerged as an unexpected and unique process, permeated by different and modified states of consciousness; and possibly the unconsciousness as a state of inner life; and having a great impact on the life process of the participants. Finally we addressed some implications for the nursing care.


Subject(s)
Coma/nursing , Coma/psychology , Humans
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