RESUMO
In this study, the molluscicidal and antiparasitic activities of divaricatic acid was evaluated, targeting the mollusc Biomphalaria glabrata and cercariae of the helminth Schistosoma mansoni. Divaricatic acid showed high toxicity against both adult snails (5.5⯵g/mL) and embryos (20⯵g/mL after 6â¯h of exposure). Similar activity was observed in S. mansoni cercariae after only a short exposure time. The divaricatic acid proved to be a promising substance for the control of the snail B. glabrata, an intermediate host of schistosomiasis, as well as the cercariae of the pathogen.
RESUMO
PURPOSE: Some phytochemicals have shown the potential of being radiomodifiers, especially phenolic compounds, such as lichenic secondary metabolites. To evaluate the phytochemical usnic acid as a radiomodifier, embryonic cells of molluscs have been used due to their ease of collection, high sensitivity to physical and chemical agents, well-known embryology and low cost for analysis. MATERIALS AND METHODS: This study aimed to assess the radiosensitizing action of usnic acid on Biomphalaria glabrata embryos. Samples were irradiated with 4 Gy of gamma rays from a 60Co source (dose rate 2.906 Gy/h). An acute toxicity test was performed using B. glabrata embryos in the blastula stage, in order to determine the toxicity of usnic acid and to establish the lethal Concentration for 50% (LC50). Subsequently, the radiomodifing capacity of usnic acid was estimated using assays with B. glabrata embryos. RESULTS: Irradiation increased the number of non-viable embryos compared to unirradiated controls. Additionally, it was observed that embryos exposed to a non-toxic concentration of usnic acid (0.6 µg/mL) before irradiation showed a further enhancement in non-viable embryos when compared with exposure to ionizing radiation alone. CONCLUSION: The results presented here indicate that usnic acid makes cells more sensitive to the damaging effects of radiation.
Assuntos
Benzofuranos/farmacologia , Biomphalaria/embriologia , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/efeitos da radiação , Radiossensibilizantes/farmacologia , Animais , Benzofuranos/toxicidade , Radioisótopos de Cobalto , Raios gama , Dose Letal Mediana , Radiossensibilizantes/toxicidadeRESUMO
In this study, the molluscicidal and antiparasitic activities of divaricatic acid was evaluated, targeting the mollusc Biomphalaria glabrata and cercariae of the helminth Schistosoma mansoni. In addition, the environmental toxicity of divaricatic acid was assessed by bioassay using the microcrustacean Artemia salina. Divaricatic acid showed high toxicity against both adult snails (5µg/mL) and embryos (20µg/mL after 6h of exposure). Similar activity was observed in Schistosoma mansoni cercariae after only a short exposure time (10µg/mL after 30min of exposure). The divaricatic acid did not show toxicity in the acute test using Artemia salina at concentrations equal to or below 200µg/mL. The divaricatic acid proved to be a promising substance for the elimination of the snail Biomphalaria glabrata, an intermediate host of schistosomiasis, as well as the cercariae of the pathogen, while being non-toxic to the Artemia salina at the same concentrations. This is the first experimental observation of the molluscicidal and cercaricide activity of divaricatic acid.
Assuntos
Antiparasitários/farmacologia , Biomphalaria/efeitos dos fármacos , Depsídeos/farmacologia , Moluscocidas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Animais , Artemia , Cercárias/efeitos dos fármacosRESUMO
ABSTRACTIn this study, ethanol-water extracts of pequi fruit peel were fractionated in order to identify and quantify the major antioxidant present in it. The fractions were subjected to liquid-liquid phase extraction and silica-gel column chromatography, and antioxidant activity was monitored using the 2,2-diphenyl-1-picrylhydrazyl radical-scavenging assay. The purity of the fractions was evaluated using thin-layer chromatography and high-performance liquid chromatography (HPLC). The substance with antioxidant property was identified through the analysis in a liquid chromatography-mass spectroscopy fragmentation and was quantified using HPLC. After the Silica-gel fractionation, it was identified a fraction with high antioxidant activity and purity, which contained gallic acid as the main compound. The gallic acid was found at the amount of 26.54 ± 1.13 mg/g of the dry mass of the pequi fruit peel. Because the quantifications were performed using crude ethanol-water extract, it was suspected that gallic acid was present in a free form. Thus, pequi fruit peel may serve as an attractive alternative of feedstock for natural antioxidant production. Moreover, the results obtained in this study emphasize the value of the pequi plant, and suggests improved opportunities for families that use this fruit`s products.
RESUMOExtratos hidroetanólicos da casca do fruto do pequi foram fracionados a fim de identificar e quantificar o principal antioxidante presente. Frações do extrato foram submetidas ao particionamento líquido-líquido e fracionamento em coluna de sílica gel. As atividades antioxidantes das frações foram monitoradas usando ensaio de redução do radical 2,2-difenil-1-picrilhidrazila e a pureza das frações foi avaliada em cromatografia de camada delgada e cromatografia líquida de alta eficiência (CLAE). A substância com propriedades antioxidantes foi identificada através da análise em sistema de cromatografia líquida associada à espectrometria de massas e foi quantificada em HPLC. Após o fracionamento identificou-se uma fração com alta atividade antioxidante e pureza, contendo ácido gálico como o composto principal. Ácido gálico foi encontrado em concentrações de 26,54 ± 1,13 mg/g de massa seca. Devido às quantificações terem sido realizadas no extrato hidroetanólico bruto, acredita-se que o ácido gálico esteja presente na forma livre. Assim, a casca do fruto pequi pode servir como interessante alternativa de matéria prima para a produção desse antioxidante natural. Além disso, esse resultado enfatiza o valor da planta do pequi e sugere oportunidades para as famílias que utilizam produtos de pequi.
Assuntos
Ericales/metabolismo , Antioxidantes/farmacologia , Produtos Biológicos/classificação , Extratos Vegetais/análise , Cromatografia Líquida de Alta Pressão/instrumentaçãoRESUMO
Maternal consumption of a high-fat diet (HFD) during pregnancy and lactation is closely related to hepatic lipid accumulation, insulin resistance and increased serum cytokine levels in offspring and into their adulthood. MicroRNA (miRNA) have been implicated in cholesterol biosynthesis and fatty acid metabolism. We evaluated the modulation of hepatic fatty acid synthesis (de novo), ß-oxidation pathways, and miRNA-122 (miR-122) and miRNA-370 (miR-370) expression in recently weaned offspring (day 28) of mouse dams fed a HFD (HFD-O) or a standard chow (SC-O) during pregnancy and lactation. Compared with SC-O mice, HFD-O mice weighed more, had a larger adipose tissue mass and were more intolerant to glucose and insulin (P< 0·05). HFD-O mice also presented more levels of serum cholesterol, TAG, NEFA and hepatic IκB kinase and c-Jun N-terminal kinase phosphorylation compared with SC-O mice (P< 0·05). Protein levels of fatty acid synthase, acetyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase were similar in HFD-O and SC-O mice, whereas expression levels of SCD1 mRNA and protein were more abundant in HFD-O mice than in SC-O mice (P< 0·05). Interestingly, mRNA expression levels of the ß-oxidation-related genes ACADVL and CPT1 were decreased in HFD-O mice (P< 0·05). Furthermore, the expression of miR-122 was reduced but that of miR-370 was increased in HFD-O mice compared with that in SC-O mice (P< 0·05). Changes in hepatic lipid metabolism were accompanied by increased mRNA content of AGPAT1 and TAG deposition in HFD-O mice (P< 0·05). Taken together, the present results strongly suggest that maternal consumption of a HFD affects the early lipid metabolism of offspring by modulating the expression of hepatic ß-oxidation-related genes and miRNA that can contribute to metabolic disturbances in adult life.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Lactação , Metabolismo dos Lipídeos , Fígado/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , MicroRNAs/biossíntese , Adiposidade , Animais , Feminino , Desenvolvimento Fetal , Regulação da Expressão Gênica no Desenvolvimento , Intolerância à Glucose/etiologia , Intolerância à Glucose/imunologia , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Fígado/enzimologia , Fígado/imunologia , Fígado/patologia , Masculino , Camundongos , Obesidade/fisiopatologia , Gravidez , Complicações na Gravidez/fisiopatologia , Distribuição Aleatória , Organismos Livres de Patógenos Específicos , Desmame , Aumento de PesoRESUMO
Few chronic food protein models have described the relationship between allergenicity and the molecular structure of food protein after physical processing. The effect of γ-radiation on the structure of food protein was measured by fluorescence, circular dichroism and microcalorimetry. BALB/c mice were intraperitoneally sensitized and then given non-irradiated and irradiated Con-A by daily gavage for 28days. The tendency to form insoluble amorphous aggregates and partially unfolded species was observed after irradiation. The administration of non-irradiated and irradiated samples at low-dose significantly increased weight loss as well as plasma levels of eotaxin in animals repeatedly exposed to Con-A. Significant lymphocytic infiltrate filling completely the stroma of microvilli and tubular glands was observed in the small intestinal of the group given Con-A irradiated at a low dose. This phenotype was not observed in animals treated with Con-A irradiated at a high dose.
Assuntos
Concanavalina A/química , Concanavalina A/imunologia , Concanavalina A/efeitos da radiação , Hipersensibilidade Alimentar/etiologia , Administração Oral , Animais , Varredura Diferencial de Calorimetria , Dicroísmo Circular , Concanavalina A/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Feminino , Hipersensibilidade Alimentar/patologia , Raios gama , Intestino Delgado/imunologia , Intestino Delgado/patologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Microvilosidades/imunologia , Microvilosidades/patologia , Conformação Proteica , Redução de PesoRESUMO
Autism spectrum disorders (ASD) is a group of behaviorally defined neurodevelopmental disabilities characterized by multiple genetic etiologies and a complex presentation. Several studies suggest the involvement of the serotonin system in the development of ASD, but only few have investigated serotonin receptors. We have performed a case-control and a family-based study with 9 polymorphisms mapped to two serotonin receptor genes (HTR1B and HTR2C) in 252 Brazilian male ASD patients of European ancestry. These analyses showed evidence of undertransmission of the HTR1B haplotypes containing alleles -161G and -261A at HTR1B gene to ASD (P=0.003), but no involvement of HTR2C to the predisposition to this disease. Considering the relatively low level of statistical significance and the power of our sample, further studies are required to confirm the association of these serotonin-related genes and ASD.
Assuntos
Transtorno Autístico/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptor 5-HT1B de Serotonina/genética , Receptor 5-HT2C de Serotonina/genética , Alelos , Brasil , Estudos de Casos e Controles , Família , Genótipo , Haplótipos , Humanos , Masculino , Análise de Sequência de DNARESUMO
OBJECTIVE: The aim of this study was to determine pharmacokinetic parameters after subcutaneous administration of a single dose (400 IU/kg) of lyophilized recombinant human erythropoietin-alpha (rhEPOalpha) to preterm newborns. The parameters determined were: maximum concentration (C(max)), time to reach maximum concentration (T(max)), absorption half-life (t(l/2abs)), volume of distribution (Vd), elimination half-life (t(l/2el)), clearance (C(L)), constant of elimination (k(el)) and area under the 0-72 h curve (AUC(0-72). METHODS: The study group comprised 20 premature newborns (eight males and 12 females) delivered in the Teaching Hospital, University of São Paulo. The inclusion criteria were birth weight < 1500 g or gestational age < or = 34 weeks, and clinical and hemodynamic stability. Serum erythropoietin (EPO) concentration was determined before and 1, 4, 6, 12, 24,48 and 72 h after subcutaneous administration of 400 IU/kg rhEPOalpha, and the pharmacokinetic parameters were calculated. RESULTS: There was a significant difference in serum EPO concentration between t72 and t0 (p = 0.001). Mean values (range) of the pharmacokinetic parameters were as follows: C(max), 739.8 (188.0-1390.0) mIU/ml; T(max), 7.7 (4.0-12.0) h; t(l/2abs), 2.9 (0.8-4.8) h, V(d), 0.705 (0.23-1.73) 1/kg; t(l/2e1), 14.9 (8.7-36.1) h; C(L), 0.032 (0.014-0.066) 1/h; k(el), 0.0475 (0.0200-0.0700); and AUC(0-72), 19058.2 (7648.0-34701.5) mIU/ml per h. The Spearman test showed no correlation between the pharmacokinetic parameters analyzed and the characteristics of the population studied. CONCLUSIONS: Studies evaluating the effectiveness of therapy with recombinant human erythropoietin in premature newborns have used various doses, administered at intervals between 24 and 48 h. The kinetics of absorption measured in our study supports the use of 400 IU/kg within an interval of no less than 72 h, together with therapeutic control of the drug and evaluation of the erythropoietic response.
Assuntos
Eritropoetina/administração & dosagem , Eritropoetina/farmacocinética , Recém-Nascido/metabolismo , Recém-Nascido Prematuro/metabolismo , Absorção , Área Sob a Curva , Relação Dose-Resposta a Droga , Eritropoetina/sangue , Feminino , Liofilização , Meia-Vida , Humanos , Injeções Subcutâneas , Masculino , Concentração Osmolar , Proteínas Recombinantes , Fatores de TempoRESUMO
In order to evaluate the association between serum vitamin A levels and ocular lesions attributable to non-complicated malaria, 200 patients seen consecutively at the Malaria Outpatient Clinic of FUNASA, Manaus, Amazonas, Brazil were included in this study. Ophthalmologic examination consisted of indirect binocular ophthalmoscopy under medicamentous mydriasis, biomicroscopy with a portable slit lamp and measurement of central visual acuity. Vitamin A serum concentration was determined by HPLC, and deficiency was defined as serum values equal to or lower than 0.35 micromol/l. Serum vitamin A values between 0.36 and 0.70 micromol/l were considered as marginal levels. Hypovitaminosis A (
Assuntos
Infecções Oculares Parasitárias/etiologia , Malária/etiologia , Deficiência de Vitamina A/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Ensaio de Imunoadsorção Enzimática , Infecções Oculares Parasitárias/sangue , Feminino , Humanos , Malária/sangue , Masculino , Pessoa de Meia-Idade , Vitamina A/sangue , Deficiência de Vitamina A/sangueRESUMO
The hydro-alcohol extract of the dry leaves of Peumus boldus and boldine, showed abortive and teratogenic action and changes in the blood levels of bilirubin, cholesterol, glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and urea in rats. The long term administration of the extract and boldine did not cause histological modification during a period of 90 days.