RESUMO
Melanosomes have been considered crucial targets in melanoma treatments. In this study we explored the role of melanosomes in photodynamic therapy (PDT), employing the synthetic Zn(II) phthalocyanine Pc13, a potent photosensitizer that promotes melanoma cell death after irradiation. Phototoxic action is mediated by reactive oxygen species increase. The internalization mechanism of Pc13 and its consequent subcellular localization were evaluated in melanotic B16-F0 cells. Pharmacological inhibitors of dynamin or caveolae, but not of clathrin, decreased Pc13 cellular uptake and phototoxicity. Similar results were obtained when cells over-expressed dominant negative mutants of dynamin-2 and caveolin-1, indicating that Pc13 is internalized by caveolae-mediated endocytosis. Confocal microscopy analysis revealed that Pc13 targets melanosomes and damage of these structures after irradiation was demonstrated by transmission electron microscopy. Treatment of pigmented B16-F0 and WM35 melanoma cells with the melanin synthesis inhibitor phenylthiourea for 48 h led to cell depigmentation and enhanced cell death after irradiation, whereas a 3-h period of inhibition did not modify melanin content but produced a marked reduction of Pc13 phototoxicity, together with a decrease of oxidative melanin synthesis intermediates. In contrast, the effect of Pc13 in amelanotic A375 cells was not altered by phenylthiourea treatment. These results provide evidence that melanosomes have a dual role in the efficacy of PDT. While melanin antagonizes the phototoxic action of Pc13, the release of cytotoxic synthetic intermediates to cytosol after irradiation and melanosome damage is conducive to the phototoxic response. Based on these findings, we demonstrate that melanosome-targeted PDT could be an effective approach for melanoma treatment.
Assuntos
Dermatite Fototóxica , Melanoma , Caveolina 1/metabolismo , Caveolina 1/farmacologia , Caveolina 1/uso terapêutico , Endocitose , Humanos , Indóis/química , Isoindóis , Melaninas/metabolismo , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Melanossomas/metabolismo , Melanossomas/ultraestrutura , Feniltioureia/metabolismo , Feniltioureia/farmacologia , Feniltioureia/uso terapêuticoRESUMO
Dengue, yellow fever, Zika, and chikungunya arboviruses are endemic in tropical countries and are transmitted by Aedes aegypti. Resistant populations of this mosquito against chemical insecticides are spreading worldwide. This study aimed to evaluate the biological effects of exposure of pesticide-sensitive Ae. aegypti larvae (Rockefeller) to conidia of the entomopathogen, Metarhizium brunneum, laboratory strains ARSEF 4556 and V275, and any synergistic activity of phenylthiourea (PTU). In addition, to investigate the nature of any cross-resistance mechanisms, these M. brunneum strains were tested against the Rockefeller larvae and two temephos- and deltamethrin-resistant wild mosquito populations from Rio de Janeiro. Treatment of Rockefeller larvae with 106 conidia/ml of ARSEF 4556 and V275 fungal strains resulted in significant decreased survival rates to 40 and 53.33%, respectively (P < 0.0001), compared with untreated controls. In contrast, exposure to 104 or 105 conidia/ml showed no such significant survival differences. However, the addition of PTU to the conidia in the bioassays significantly increased mortalities in all groups and induced a molt block. Experiments also showed no differences in Ae. aegypti mortalities between the fungal treated, wild pesticide-resistant populations and the Rockefeller sensitive strain. The results show the efficacy of M. brunneum in controlling Ae. aegypti larvae and the synergistic role of PTU in this process. Importantly, there was no indication of any cross-resistance mechanisms between Ae. aegypti sensitive or resistant to pesticides following treatment with the fungi. These results further support using M. brunneum as an alternative biological control agent against mosquito populations resistant to chemical insecticides.
Assuntos
Aedes/microbiologia , Agentes de Controle Biológico/farmacologia , Controle de Insetos , Resistência a Inseticidas , Inseticidas/farmacologia , Metarhizium/fisiologia , Controle Biológico de Vetores , Aedes/efeitos dos fármacos , Animais , Larva/efeitos dos fármacos , Larva/microbiologia , Organofosfatos/farmacologia , Feniltioureia/farmacologia , Piretrinas/farmacologiaRESUMO
Avaliar a sensibilidade gustativa a proteína PTC nos docentes de uma faculdade privada de Goiás, associando esta sensibilidade gustativa à ingestão de alimentos que contém essa substância, hábitos socioculturais e alimentares. Método: A avaliação da sensibilidade ao composto PTC (Feniltiocarbamida) ocorreu junto a 40 docentes de uma faculdade privada do estado de Goiás após administração oral de uma gota da solução de concentração 0,01% do composto, seguida pela aplicação do questionário para avaliar à substância testada. Os dados foram analisados no programa EpiInfo versão 7.2.3.0. Para se verificar a associação entre a sensibilidade gustativa ao PTC e as variáveis dependentes. utilizou-se os testes do qui-quadrado ou o teste exato de Fisher. Resultados: Observou-se que 65% dos docentes recrutados apresentam sensibilidade ao PTC. De 40 participantes, 47,5% eram do sexo feminino e 52,5% do sexo masculino. A população era da faixa etária entre 24 e 62 anos. Após a administração da solução do composto PTC (0,01%), a sensibilidade ao sabor amargo foi a mais relatada. Não houve associação entre a sensibilidade gustativa ao PTC e as variáveis estudadas. Conclusão: A inclusão na dieta de alimentos considerados saudáveis, associados ao sabor amargo, pode também ser influenciada pelo grau de sensibilidade e tolerância à esses alimentos.
To evaluate the taste sensitivity to PTC protein in the teachers of a private college in Goiás, associating this taste sensitivity to the ingestion of foods that contain this substance, sociocultural and eating habits. Method: The sensitivity assessment to the compound PTC (Phenylthiocarbamide) occurred with 40 teachers from a private college in the state of Goiás after oral administration of a drop of the 0.01% concentration solution of the compound, followed by the application of the questionnaire to evaluate the tested substance. The data were fulfilled using the EpiInfo program version 7.2.3.0. To verify an association between taste sensitivity to PTC and as dependent dependents. chi-square tests or Fisher's exact test are used. Results: It was observed that 65% of the recruited professors are sensitive to PTC. Of the 40 participants, 47.5% were female and 52.5% male. The population was between 24 and 62 years old. After administration of the PTC compound solution (0.01%), sensitivity to bitter taste was the most reported. There was no association between taste sensitivity to PTC and the variables studied. Conclusion: The inclusion in the diet of foods considered considered, associated with the bitter taste, can also be influenced by the degree of sensitivity and tolerance to these foods.
Evaluar la sensibilidad gustativa a la proteína PTC en los profesores de un colegio privado de Goiás, asociando esta sensibilidad gustativa a la ingestión de alimentos que contienen esta sustancia, hábitos socioculturales y alimentarios. Método: La evaluación de sensibilidad al compuesto PTC (Feniltiocarbamida) se realizó con 40 profesores de un colegio privado en el estado de Goiás luego de la administración oral de una gota de la solución de concentración al 0.01% del compuesto, seguida de la aplicación del cuestionario para evaluar la sustancia probada. Los datos se cumplieron utilizando el programa EpiInfo versión 7.2.3.0. Verificar una asociación entre la sensibilidad gustativa a PTC y como dependientes dependientes. Se utilizan pruebas de chicuadrado o la prueba exacta de Fisher. Resultados: Se observó que el 65% de los profesores reclutados son sensibles al PTC. De los 40 participantes, el 47,5% eran mujeres y el 52,5% hombres. La población tenía entre 24 y 62 años. Después de la administración de la solución del compuesto PTC (0,01%), la sensibilidad al sabor amargo fue la más notificada. No hubo asociación entre la sensibilidad gustativa al PTC y las variables estudiadas. Conclusión: La inclusión en la dieta de los alimentos considerados considerados, asociados al sabor amargo, también puede estar influenciada por el grado de sensibilidad y tolerancia a estos alimentos.
Assuntos
Animais , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Feniltioureia , Paladar , Consumo de Bebidas Alcoólicas , Docentes , Alimentos , Dieta Saudável , Fumar TabacoRESUMO
Anti-nutritional factors, including hemagglutinins, are natural substances that reduce nutritional bioavailability and/or generate adverse physiological effects. Most are bitter toxic compounds, but present chemo-protective properties at low concentrations. Responses to phenylthiocarbamide (PTC) allow for an evaluation of humans' perception of bitter taste, a perception that has evolutionary advantages. Therefore, we hypothesized that relationships between food preference, dietary exposures and disease risk could reflect possible associations not only with the recognition threshold for the bitter taste of PTC, but also with ABO/Rh blood group phenotypes. To test this hypothesis, 375 volunteers of both genders, aged 16-49 years, were recruited. Data were obtained from laboratory tests and questionnaires. PTC test followed literature; blood typing used commercially available sera. Allele frequencies calculated from phenotypes were: T=0.51, t=0.49 (PTC); IA=0.22, IB=0.08, i=0.70 (ABO); D=0.57, d=0.43 (Rh). Associations with the recognition threshold for bitter taste were found for blood group B, females, and risk of developing food allergy for bitter taste at PTC dilution 1 (the highest concentration) (OR=3.862; 95%CI=1.387-10.756; p=0.016); for each more diluted PTC solution, the chance of food allergy fell 25.2% (95%CI = 0.764-0.836), while for each more concentrated solution the chance of food allergy increased 20.1% (p=0.000). There were also nominally significant differences among PTC tasting, ABO/Rh, genders and age-groups in relation to food preferences. Results demonstrated that the ability to recognize PTC in taste test is related to blood group B, females, and risk of developing food allergy, thus confirming the research hypothesis, and presenting original and important associations.
Assuntos
Antígenos de Grupos Sanguíneos/sangue , Hipersensibilidade Alimentar/etiologia , Preferências Alimentares , Frequência do Gene , Feniltioureia , Percepção Gustatória/genética , Paladar , Sistema ABO de Grupos Sanguíneos , Adolescente , Adulto , Tipagem e Reações Cruzadas Sanguíneas , Brasil , Estudos Transversais , Dieta , Feminino , Hipersensibilidade Alimentar/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Sistema do Grupo Sanguíneo Rh-Hr , Inquéritos e Questionários , Adulto JovemRESUMO
This study aimed to evaluate the effects of thyroid hormone on the decidua and metrial gland of rats and to examine the expression of angiogenic factors. 72 adult, female rats were divided into hypothyroid, T4-treated2, and control groups. At 10, 14 and 19 days of gestation (DG), the decidua and metrial gland were collected for histomorphometric and immunohistochemical evaluation of the expression of VEGF, Flk-1 and Tie-2. Hypothyroidism reduced the area of the decidua at 10 and 19 DG. Furthermore, VEGF was increased at 10 and 14 DG, and Flk-1 only at 14 DG, but both was reduced at 19 DG in the metrial gland without significantly changing the area occupied by blood vessels. Rats treated with T4 showed an increase in the decidua blood vessels at 10 and 19 DG. However, at 10 DG, excess T4 resulted in increased of Flk-1 in the decidua and metrial gland. Hypothyroidism increased the Tie-2 at 10 and 19 DG in the decidua and metrial gland. In conclusion, hypothyroidism reduces the area of the decidua and increases the expression of VEGF, Tie-2 and Flk-1. The excess of T4 promotes tissue angiogenesis by increasing the number of vessels in the decidua because of the increased expression of Flk-1.(AU)
Este estudo teve como objetivo avaliar os efeitos dos hormônios tireoidianos sobre a decídua e a glândula metrial pela análise da expressão de fatores angiogênicos em ratas. 72 ratas adultas, fêmeas foram distribuídas nos grupos hipotiroideo, tratado com T4 e controle. Aos 10, 14 e 19 dias de gestação (DG), a decídua e a glândula metrial foram coletadas para avaliação histomorfométrica e imunoistoquímica da expressão de VEGF, Flk-1 e Tie-2. O hipotireoidismo reduziu a área da decídua aos 10 e 19 DG. Além disso, o VEGF aumentou aos 10 e 14 DG e o Flk-1 apenas aos 14 DG, mas ambos foram reduzidos aos 19 DG na glândula metrial sem alterar significativamente a área ocupada pelos vasos sanguíneos. As ratas tratadas com T4 apresentaram aumento do número de vasos sanguíneos na decídua aos 10 e 19 DG. Além disso, aos 10 DG, o excesso de T4 resultou no aumento de Flk-1 na decídua e na glândula metrial. O hipotireoidismo aumentou o Tie-2 em 10 e 19 DG na decídua e na glândula metrial. Desta forma, pode-se concluir que o hipotireoidismo reduz a área da decídua e aumenta a expressão de VEGF, Tie-2 e Flk-1. O excesso de T4 promove a angiogênese tecidual ao aumentar o número de vasos na decídua devido ao aumento da expressão de Flk-1.(AU)
Assuntos
Animais , Feminino , Ratos , Feniltioureia/análise , Hormônios Tireóideos/análise , Decídua , Indutores da Angiogênese/análise , Glândula MetrialRESUMO
This study aimed to evaluate the effects of thyroid hormone on the decidua and metrial gland of rats and to examine the expression of angiogenic factors. 72 adult, female rats were divided into hypothyroid, T4-treated2, and control groups. At 10, 14 and 19 days of gestation (DG), the decidua and metrial gland were collected for histomorphometric and immunohistochemical evaluation of the expression of VEGF, Flk-1 and Tie-2. Hypothyroidism reduced the area of the decidua at 10 and 19 DG. Furthermore, VEGF was increased at 10 and 14 DG, and Flk-1 only at 14 DG, but both was reduced at 19 DG in the metrial gland without significantly changing the area occupied by blood vessels. Rats treated with T4 showed an increase in the decidua blood vessels at 10 and 19 DG. However, at 10 DG, excess T4 resulted in increased of Flk-1 in the decidua and metrial gland. Hypothyroidism increased the Tie-2 at 10 and 19 DG in the decidua and metrial gland. In conclusion, hypothyroidism reduces the area of the decidua and increases the expression of VEGF, Tie-2 and Flk-1. The excess of T4 promotes tissue angiogenesis by increasing the number of vessels in the decidua because of the increased expression of Flk-1.(AU)
Este estudo teve como objetivo avaliar os efeitos dos hormônios tireoidianos sobre a decídua e a glândula metrial pela análise da expressão de fatores angiogênicos em ratas. 72 ratas adultas, fêmeas foram distribuídas nos grupos hipotiroideo, tratado com T4 e controle. Aos 10, 14 e 19 dias de gestação (DG), a decídua e a glândula metrial foram coletadas para avaliação histomorfométrica e imunoistoquímica da expressão de VEGF, Flk-1 e Tie-2. O hipotireoidismo reduziu a área da decídua aos 10 e 19 DG. Além disso, o VEGF aumentou aos 10 e 14 DG e o Flk-1 apenas aos 14 DG, mas ambos foram reduzidos aos 19 DG na glândula metrial sem alterar significativamente a área ocupada pelos vasos sanguíneos. As ratas tratadas com T4 apresentaram aumento do número de vasos sanguíneos na decídua aos 10 e 19 DG. Além disso, aos 10 DG, o excesso de T4 resultou no aumento de Flk-1 na decídua e na glândula metrial. O hipotireoidismo aumentou o Tie-2 em 10 e 19 DG na decídua e na glândula metrial. Desta forma, pode-se concluir que o hipotireoidismo reduz a área da decídua e aumenta a expressão de VEGF, Tie-2 e Flk-1. O excesso de T4 promove a angiogênese tecidual ao aumentar o número de vasos na decídua devido ao aumento da expressão de Flk-1.(AU)
Assuntos
Animais , Feminino , Ratos , Feniltioureia/análise , Hormônios Tireóideos/análise , Decídua , Indutores da Angiogênese/análise , Glândula MetrialRESUMO
BACKGROUND: Sinonasal biofilms have been demonstrated in specimens collected from chronic rhinosinusitis (CRS) patients. Mounting evidence suggests that biofilms contribute to therapeutically recalcitrant CRS. Recently, the bitter taste receptor T2R38 has been implicated in the regulation of the sinonasal mucosal innate immune response. TAS2R38 gene polymorphisms affect receptor functionality and contribute to variations seen in sinonasal innate defense as well as taste perception reflected in gustatory sensitivity to the bitter compound phenylthiocarbamide (PTC). In a population of CRS patients with active infection or inflammation, we sought to determine if a correlation between T2R38 phenotype and in vitro biofilm formation existed. METHODS: Endoscopically guided sinonasal swabs were obtained prospectively from CRS (±polyp) patients with evidence of persistent inflammation or mucopurulence. In vitro biofilm formation was assessed with a modified Calgary Biofilm Detection Assay. Patients' phenotypic (functional) expression of the bitter taste receptor T2R38 was evaluated with a taste test including the compound PTC. Linear regression was used to determine the level of significance between mean in vitro biofilm formation levels and mean PTC taste test intensity ratings across CRS patients. RESULTS: Sinonasal swabs were obtained from 59 patients, with 42 of the 59 samples demonstrating in vitro biofilm formation. Analysis revealed an inverse linear association between in vitro biofilm formation and PTC taste intensity ratings (p = 0.019) for all patients. This association was exclusively driven by nonpolypoid CRS patients (p = 0.0026). CONCLUSION: In vitro biofilm formation from sinonasal clinical isolates is inversely correlated with PTC taste sensitivity in nonpolypoid CRS patients.
Assuntos
Biofilmes , Pseudomonas/fisiologia , Receptores Acoplados a Proteínas G/fisiologia , Rinite/fisiopatologia , Sinusite/fisiopatologia , Paladar , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Feniltioureia , Receptores Acoplados a Proteínas G/genética , Adulto JovemRESUMO
BACKGROUND: The bitter taste receptor T2R38, expressed in the tongue and nasal epithelium, has been shown to trigger sinonasal innate immunity contributing to the prevention of gram-negative upper airway bacterial infections. Common polymorphisms of the T2R38 gene, correlating with bitter taste sensitivity to phenylthiocarbamide (PTC), have been linked to differences in sinonasal innate immune response, with specific genotypes significantly more common in medically recalcitrant chronic rhinosinusitis patients. The purpose of this study was to examine this association between T2R38 function and sinonasal infection or symptoms in a healthy population. METHODS: A survey of the frequency of sinus infections, as well as other nasal symptoms such as colds, allergies, and overall nasal quality of life (nQOL), was administered to healthy adult participants. nQOL was measured using a 0 to 3 scale of worsening symptoms. A PTC compound taste strip was administered with T2R38 taste sensitivity classified as extremely, somewhat, or not sensitive. RESULTS: Among 217 participants (55% female, 70% Caucasian, 42% age 21 to 25 years), 30% did not detect bitterness (nontasters), 34% were moderate tasters, and 36% were "supertasters," experiencing a strong, unpalatable bitterness. Supertasters were associated with less frequent sinus infections (p = 0.04), and PTC sensitivity was predictive of nasal symptoms: Supertasters had the best nQOL scores, followed by moderate tasters and nontasters (means: 0.65, 0.81, 1.00, respectively; p = 0.014 for trend). There were no significant associations with other variables. CONCLUSION: This study provides evidence that T2R38 functionality in the tongue correlates with nasal symptoms in healthy individuals.
Assuntos
Feniltioureia , Rinite/diagnóstico , Sinusite/diagnóstico , Paladar/fisiologia , Adolescente , Adulto , Idoso , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Receptores Acoplados a Proteínas G/metabolismo , Infecções Respiratórias/diagnóstico , Adulto JovemRESUMO
One of the first approaches undertaken in the quest for antitubercular compounds was that of understanding the mechanism of action of old drugs and proposing chemical modifications or other strategies to improve their activity, generally lost to the mechanisms of resistance developed by Mycobacterium tuberculosis. A leading case was the work carried out on a set of compounds with proven activity on the essential pathway of the synthesis of mycolic acids. As a result, different solutions were presented, improving the activity of those inhibitors or producing novel compounds acting on the same molecular target(s), but avoiding the most common resistance strategies developed by the tubercle bacilli. This review focuses on the activity of those compounds, developed following the completion of the studies on several of the classic antitubercular drugs.
Assuntos
Antituberculosos/síntese química , Mycobacterium tuberculosis/efeitos dos fármacos , Ácidos Micólicos/antagonistas & inibidores , Antituberculosos/farmacologia , Desenho de Fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Etionamida/análogos & derivados , Etionamida/síntese química , Etionamida/farmacologia , Humanos , Isoniazida/análogos & derivados , Isoniazida/síntese química , Isoniazida/farmacologia , Mycobacterium tuberculosis/metabolismo , Ácidos Micólicos/metabolismo , Feniltioureia/análogos & derivados , Feniltioureia/síntese química , Feniltioureia/farmacologia , Relação Estrutura-Atividade , Tioacetazona/análogos & derivados , Tioacetazona/síntese química , Tioacetazona/farmacologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologiaRESUMO
Tyrosinase is an enzyme of industrial interest. The production and characterization of tyrosinase from P. sanguineus CCT-4518 were investigated. The selection of inductors, luminosity influence, inoculum size and type of culture medium on the production of tyrosinase and the effect of inhibitors on enzyme activity were performed. Optimum conditions for intracellular tyrosinase production was observed after 2 days using 0.15% L-tyrosine as inducer, in the presence of light, with inoculum size of 10 mycelium discs, using 2% malt extract broth medium, incubated at 30°C, and constant agitation of 150 rpm. Tyrosinase activity was completely inhibited by the addition of 6 mM salicylhydroxamic acid or phenylthiourea, however an inhibition of 4.15% was recorded by the addition of 0.1 mM sodium azide. No inhibition could be detected in case of 0.1 mM phenyl methanesulfonyl fluoride addition. Optimal conditions for intracellular tyrosinase activity using L-dopa as substrate were observed at pH 6.6 and 45°C. Thermal stability studies indicated that the enzyme is stable at 45°C for 15 minutes. Higher temperatures decreased tyrosinase activity. Enzyme production was confirmed by non-denaturing polyacrylamide gel electrophoresis and the protein profile was investigated by denaturing polyacrylamide gel electrophoresis.
Assuntos
Feniltioureia/análise , Feniltioureia/isolamento & purificação , Inibidores Enzimáticos/análise , Monofenol Mono-Oxigenase/análise , Monofenol Mono-Oxigenase/isolamento & purificação , Eletroforese , Ativação EnzimáticaRESUMO
Trypanosoma brucei, the etiologic agent of sleeping sickness, is exposed to important changes in nutrients and temperature during its life cycle. To adapt to these changes, the fluidity of its membranes plays a crucial role. This fluidity, mediated by the fatty-acid composition, is regulated by enzymes named desaturases. We have previously shown that the oleoyl desaturase is essential for Trypanosoma cruzi and T. brucei. In this work, we present experimental support for the relevance of stearoyl-CoA desaturase (SCD) for T. brucei's survival, in both its insect or procyclic-form (PCF) and bloodstream-form (BSF) stages. We evaluated this essentiality in two different ways: by generating a SCD knocked-down parasite line using RNA interference, and by chemical inhibition of the enzyme with two compounds, Isoxyl and a thiastearate with the sulfur atom at position 10 (10-TS). The effective concentration for 50% growth inhibition (EC(50)) of PCF was 1.0 ± 0.2 µM for Isoxyl and 5 ± 2 µM for 10-TS, whereas BSF appeared more susceptible with EC(50) values 0.10 ± 0.03 µM (Isoxyl) and 1.0 ± 0.6 µM (10-TS). RNA interference showed to be deleterious for both stages of the parasite. In addition, T. brucei-infected mice were fed with Isoxyl, causing a reduction of the parasitemia and an increase of the rodents' survival.
Assuntos
Parasitemia/microbiologia , Estearoil-CoA Dessaturase/metabolismo , Trypanosoma brucei brucei/enzimologia , Tripanossomíase Africana/microbiologia , Animais , Feminino , Técnicas de Silenciamento de Genes , Camundongos , Parasitemia/tratamento farmacológico , Feniltioureia/análogos & derivados , Feniltioureia/uso terapêutico , Interferência de RNA , Estearoil-CoA Dessaturase/genética , Trypanosoma brucei brucei/efeitos dos fármacos , Trypanosoma brucei brucei/genética , Tripanossomíase Africana/tratamento farmacológicoRESUMO
Edman degradation in the gas phase has been observed by collision activated dissociation of N-terminal phenylthiocarbamoyl (PTC) protonated peptide to yield abundant complementary b1 and y(n-1) ion pairs. Here, we demonstrated the relation between the observed losses of aniline and/or the entire PTC derivatizing group with the availability of mobile protons using electrospray ionization mass spectrometry. In order to select the peptides with more efficient fragmentation, while simplifying the mixture of peptides, we extend the phenylisotiocyanate (PITC) derivatization of amino groups to the selective isolation of multiply charged peptides (those having the number of arginines and histidines residues higher than one) using a procedure previously developed in our group. Thus, it was possible to identify in the filtered protein database the sequence of the isolated multiply charged peptides derived from a single protein and a complex mixture of proteins extracted from Escherichia coli using only the molecular mass and the N-terminal amino acid information. For this purpose, we developed a novel bioinformatic tool for automatic identification of peptides from liquid chromatography-tandem mass spectrometry (LC-MS/MS) experiments, which potentially can be used in high-throughput proteomics.
Assuntos
Cromatografia Líquida/métodos , Peptídeos/análise , Feniltioureia/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Algoritmos , Sequência de Aminoácidos , Animais , Bovinos , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/isolamento & purificação , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Estreptoquinase/química , Estreptoquinase/metabolismoRESUMO
PURPOSE: The objective of the present study was to evaluate whether sensitivity to bitter taste and perception of sweet taste have an influence on dental caries in urban and rural areas. MATERIALS AND METHODS: The caries experience in 181 children, aged 12 years, from rural and urban areas of southern Brazil, was assessed according to World Health Organization guidelines. Sensitivity to the bitterness of phenylthiocarbamide was determined using the HarrisKalmus procedure, and the sweet taste thresholds of sucrose were measured by Nilsson and Holm's method. RESULTS: The caries index (DMFT > 0) was 3.73 (SD = 2.26) in the rural area and 3.51 (SD = 2.14) in the urban area. The sensitivity to bitter taste and sweet taste perception showed significant association with the gender of schoolchildren (P = 0.04). Girls were predominant in the high sweet perception taster group (62.3%) and the bitter taster group (59.4%). No significant difference in sweet perception status could be observed between the groups of low and high caries severity. The genetic ability to taste bitterness significantly influenced the levels of caries only in children from the urban area (P = 0.005). Bitter non-tasters presented higher severity of caries. A positive correlation was observed between sensitivity to bitter taste and sweet taste perception among children in the rural (r = 0.42, P = 0.002) and urban areas (r = 0.36, P = 0.001). CONCLUSIONS: These findings suggest that the bitter non-tasters are more susceptible to dental caries than the tasters in the urban area.
Assuntos
Suscetibilidade à Cárie Dentária , Cárie Dentária/genética , Percepção Gustatória/genética , Paladar/genética , Brasil , Distribuição de Qui-Quadrado , Criança , Estudos Transversais , Índice CPO , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Feniltioureia , População Rural , Estatísticas não Paramétricas , Sacarose , Limiar Gustativo , População UrbanaRESUMO
Drug trial with CIBA 1906 was conducted in 50 cases of lepromatous leprosy who were intolerant to dapsone therapy. Drug was tolerated well and lepra reactions were infrequent and mild. Clinical improvement was seen in 72% cases whereas no appreciable change was detected in 28% cases. An average reduction of 0.4 in BI was detected in 62% cases, while remaining cases did not show any reduction in BI. No significant side effects were encountered during the study. Antibacterial activity of CIBA 1906 was not found superior to dapsone.
Assuntos
Masculino , Humanos , Adulto , Ensaios Clínicos como Assunto , Feniltioureia/análogos & derivados , Feniltioureia/efeitos adversos , Feniltioureia/uso terapêutico , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológicoAssuntos
Feniltioureia , Paladar , Tuberculose/fisiopatologia , Brasil , Feminino , Humanos , Masculino , Fatores Socioeconômicos , SuéciaRESUMO
Over 100 patients with lepromatous leprosy were treated with rifampicin in a series of pilot, uncontrolled, and controlled trials in 1968-77. The rapid bactericidal effect of rifampicin on Mycobacterium leprae was confirmed. Clinical improvement became apparent sometimes as early as 14 days after the start of treatment. Nevertheless, a few persisting viable M leprae were detected as long as five years after the start of treatment with rifampicin either by itself or in combination with the bacteriostatic drug thiambutosine. Treatment with rifampicin and dapsone for six months reduced the number of persisting leprosy bacteria more than treatment with dapsone alone. Although rifampicin proved more effective than dapsone, it is unlikely that used by itself if can significantly shorten the length of treatment in lepromatous leprosy. Therefore initial intensive combined treatment with two or more bactericidal drugs (including rifampicin) warrants further investigation in both untreated leprosy and lepromatous leprosy resistant to dapsone.
Assuntos
Humanos , Animais , Camundongos , Combinação de Medicamentos , Dapsona/uso terapêutico , Ensaios Clínicos como Assunto , Feniltioureia/análogos & derivados , Feniltioureia/uso terapêutico , Hanseníase/tratamento farmacológico , Mycobacterium leprae , Rifampina/administração & dosagem , Rifampina/farmacologia , Rifampina/uso terapêuticoAssuntos
Frequência do Gene , Mãos/fisiologia , Indígenas Sul-Americanos , Feniltioureia , Limiar Gustativo/fisiologia , Paladar/fisiologia , Língua/fisiologia , Adolescente , Adulto , Comportamento/fisiologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Movimento , PeruRESUMO
Ninety-six Miskito, 85 Sumo and 79 Rama Indians were tested for P.T.C. taste ability according to a modification of Harris and Kalmus' sorting technique. Miskito's "non-taster" high frequency approach values reported for some highly inbred Central and South American Indian populations, while Rama's and Sumo's figures appear in aggrement with values reported for other relatively pure Amerindians.