RESUMO
Introduction: Neurotrophin-3 (NT-3) is thought to play a role in the neurobiological processes implicated in mood and anxiety disorders. NT-3 is a potential pharmacological target for mood disorders because of its effects on monoamine neurotransmitters, regulation of synaptic plasticity and neurogenesis, brain-derived neurotrophic factor (BDNF) signaling boosting, and modulation of the hypothalamic-pituitary-adrenal (HPA) axis. The mechanisms underlying NT-3 anxiolytic properties are less clear and require further exploration and definition. Areas covered: The evidence that supports NT-3 as a pharmacological target for anxiety and mood disorders is presented and this is followed by a reflection on the quandaries, stumbling blocks, and future perspectives for this novel target. Expert opinion: There is evidence for miRNAs being key post-transcriptional regulators of neurotrophin-3 receptor gene (NTRK3) in anxiety disorders; however, the anxiolytic properties of NT-3 need further examination and delineation. Moreover, NT-3 expression by non-neuronal cells and its role in brain circuits that participate in anxiety and mood disorders require further scrutiny. Further work is vital before progression into clinical trials can be realized.
Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Neurotrofina 3/metabolismo , Animais , Transtornos de Ansiedade/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Humanos , MicroRNAs/genética , Terapia de Alvo Molecular , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/fisiopatologia , Receptor trkC/genéticaRESUMO
OBJECTIVES: To analyze the association of adipokines and tumor necrosis factor α (TNFα) and its receptors with characteristics of systemic lupus erythematosus (SLE) and to investigate the correlation between adipokines and the TNF system. METHODS: One hundred and thirty-six SLE women, aged ≥18 years old, were assessed. TNFα, soluble TNFα receptors 1 (sTNFR1) and 2 (sTNFR2) and adipokines were analyzed by ELISA kits. RESULTS: The median (IQR) of age was 41.5 (33.0-49.7) years old and of disease duration 11.3 (7.8-15.8) years. The median (IQR) of disease activity was 0 (0-4) and of damage index was 2 (1-3). Higher levels of sTNFR1 and sTNFR2 were associated with nephritis (p < 0.001 for both), and sTNFR1 (p = 0.025) and TNFα (p = 0.014) were positively associated with arthritis. Higher sTNFR1 levels were found in participants that were not using antimalarial drugs (p = 0.04). Independent correlation was found between sTNFR1 (ß = 0.253; p = 0.003) and sTNFR2 (ß = 0.297; p < 0.001) levels and disease activity and damage index (sTNFR1: ß = 0.367; p < 0.001; sTNFR2: ß = 0.335; p < 0.001). Higher adiponectin levels were independently associated with nephritis (p = 0.009) and antimalarial drugs use (p = 0.015). There was a positive correlation between leptin and sTNFR2 levels (p = 0.002) and between resistin levels and sTNFR1 (p < 0.001) and sTNFR2 (p < 0.001). CONCLUSION: The correlation between adipokines and TNF system allows a better understanding of the role of adipokines in the inflammatory response in SLE patients.
Assuntos
Adipocinas/metabolismo , Lúpus Eritematoso Sistêmico/fisiopatologia , Nefrite Lúpica/fisiopatologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Antimaláricos/administração & dosagem , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Leptina/metabolismo , Pessoa de Meia-Idade , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Resistina/metabolismo , Índice de Gravidade de DoençaRESUMO
This study aimed to evaluated the resistance and susceptibility of 10 cowpea cultivars to Meloidogyne incognita in field studies and to analyze the kinetics of the enzymes superoxide dismutase, catalase, peroxidase, chitinase, ß-1,3-glucanases and cystein proteinase inhibitors in the root system of two contrasting cowpea cultivars after inoculation with M. incognita. The cultivars CE-31 and Frade Preto were highly resistant; CE-28, CE-01, CE-315, CE-237, were very resistant; CE-70 and CE-216 were moderately resistant, whereas Vita-3 and CE-109 were slightly resistant. In the roots of the highly resistant cultivar CE-31 the activity of the antioxidant enzyme superoxide dismutase increased and catalase decreased and those of the pathogenesis-related proteins chitinase, ß-1,3-glucanase, peroxidase and cystein proteinase inhibitor increased in comparison with the root system of the slightly resistant CE-109, during the course of M. incognita infestation. Thus the changes in the activities of these enzymes might be related to the smaller final population of M. incognita in CE-31 and may contribute to the high resistance of this cowpea cultivar against infection and colonization by this nematode species.
Assuntos
Antioxidantes/metabolismo , Fabaceae/enzimologia , Interações Hospedeiro-Parasita , Proteínas de Plantas/metabolismo , Raízes de Plantas/parasitologia , Tylenchoidea/patogenicidade , Animais , Inibidores de Cisteína Proteinase/metabolismo , Resistência à Doença , Ativação Enzimática , Fabaceae/imunologia , Fabaceae/parasitologia , Feminino , Glucana 1,3-beta-Glucosidase/metabolismo , Infecções por Nematoides/imunologia , Infecções por Nematoides/parasitologia , Peroxidase/metabolismo , Doenças das Plantas/imunologia , Doenças das Plantas/parasitologia , Raízes de Plantas/enzimologia , Raízes de Plantas/imunologia , Especificidade da Espécie , Superóxido Dismutase/metabolismo , Tylenchoidea/imunologiaRESUMO
Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. This condition has been associated with cognitive, behavioral and motor dysfunctions, seizures and coma. The underlying mechanisms of CM are incompletely understood. Glutamate and other metabolites such as lactate have been implicated in its pathogenesis. In the present study, we investigated the involvement of glutamate in the behavioral symptoms of CM. Seventeen female C57BL/6 mice (20-25 g) aged 6-8 weeks were infected with P. berghei ANKA by the intraperitoneal route using a standardized inoculation of 10(6) parasitized red blood cells suspended in 0.2 mL PBS. Control animals (N = 17) received the same volume of PBS. Behavioral and neurological symptoms were analyzed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. Glutamate release was measured in the cerebral cortex and cerebrospinal fluid of infected and control mice by fluorimetric assay. All functional categories of the SHIRPA battery were significantly altered in the infected mice at 6 days post-infection (dpi) (P ≤ 0.05). In parallel to CM symptoms, we found a significant increase in glutamate levels in the cerebral cortex (mean ± SEM; control: 11.62 ± 0.90 nmol/mg protein; infected at 3 dpi: 10.36 ± 1.17 nmol/mg protein; infected at 6 dpi: 26.65 ± 0.73 nmol/mg protein; with EGTA, control: 5.60 ± 1.92 nmol/mg protein; infected at 3 dpi: 6.24 ± 1.87 nmol/mg protein; infected at 6 dpi: 14.14 ± 0.84 nmol/mg protein) and in the cerebrospinal fluid (control: 128 ± 51.23 pmol/mg protein; infected: 301.4 ± 22.52 pmol/mg protein) of infected mice (P ≤ 0.05). These findings suggest a role of glutamate in the central nervous system dysfunction found in CM.
Assuntos
Animais , Feminino , Camundongos , Sintomas Comportamentais/fisiopatologia , Córtex Cerebral/química , Líquido Cefalorraquidiano/química , Ácido Glutâmico/metabolismo , Malária Cerebral/metabolismo , Plasmodium berghei , Malária Cerebral/líquido cefalorraquidiano , Malária Cerebral/fisiopatologiaRESUMO
Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. This condition has been associated with cognitive, behavioral and motor dysfunctions, seizures and coma. The underlying mechanisms of CM are incompletely understood. Glutamate and other metabolites such as lactate have been implicated in its pathogenesis. In the present study, we investigated the involvement of glutamate in the behavioral symptoms of CM. Seventeen female C57BL/6 mice (20-25 g) aged 6-8 weeks were infected with P. berghei ANKA by the intraperitoneal route using a standardized inoculation of 106 parasitized red blood cells suspended in 0.2 mL PBS. Control animals (N = 17) received the same volume of PBS. Behavioral and neurological symptoms were analyzed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. Glutamate release was measured in the cerebral cortex and cerebrospinal fluid of infected and control mice by fluorimetric assay. All functional categories of the SHIRPA battery were significantly altered in the infected mice at 6 days post-infection (dpi) (P ≤ 0.05). In parallel to CM symptoms, we found a significant increase in glutamate levels in the cerebral cortex (mean ± SEM; control: 11.62 ± 0.90 nmol/mg protein; infected at 3 dpi: 10.36 ± 1.17 nmol/mg protein; infected at 6 dpi: 26.65 ± 0.73 nmol/mg protein; with EGTA, control: 5.60 ± 1.92 nmol/mg protein; infected at 3 dpi: 6.24 ± 1.87 nmol/mg protein; infected at 6 dpi: 14.14 ± 0.84 nmol/mg protein) and in the cerebrospinal fluid (control: 128 ± 51.23 pmol/mg protein; infected: 301.4 ± 22.52 pmol/mg protein) of infected mice (P ≤ 0.05). These findings suggest a role of glutamate in the central nervous system dysfunction found in CM.
Assuntos
Sintomas Comportamentais/fisiopatologia , Córtex Cerebral/química , Líquido Cefalorraquidiano/química , Ácido Glutâmico/metabolismo , Malária Cerebral/metabolismo , Plasmodium berghei , Animais , Feminino , Malária Cerebral/líquido cefalorraquidiano , Malária Cerebral/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Chitin-binding vicilin from Enterolobium contortisiliquum seeds was purified by ammonium sulfate followed by gel filtration on Sephacryl 300-SH and on Sephacryl 200-SH. The vicilin, called EcV, is a dimeric glycoprotein composed of 1.03% carbohydrates and a Mr of 151 kDa, consisting of two subunits of Mr of 66.2 and 63.8 kDa. The EcV homogeneity was confirmed in a PAGE where it was observed to be a unique acid protein band with slow mobility in this native gel. E. contortisiliquum vicilin (EcV) was tested for anti-insect activity against C. maculatus and Zabrotes subfasciatus larvae and for phytopathogenic fungi, F. solani and C. lindemuntianum. EcV was very effective against both bruchids, producing 50% mortality for Z. subfasciatus at an LD50 of 0.43% and affected 50% of the larvae mass with an ED50 of 0.65%. In artificial diets given to C. maculatus, 50% of the larvae mass was affected with an ED50 of 1.03%, and larva mortality was 50% at LD50 of 1.11%. EcV was not digested by midgut homogenates of C. maculatus and Z. Subfasciatus until 12 h of incubation, and at 24 h EcV was more resistant to Z. subfasciatus larval proteases. The binding to chitin present in larvae gut associated to low EcV digestibility could explain its lethal effects. EcV also exerted an inhibitory effect on the germination of F. solani at concentrations of 10 and 20 microg mL-1. The effect of EcV on fungi is possibly due to binding to chitin-containing structures of the fungal cell wall.
Assuntos
Quitina/metabolismo , Fabaceae/química , Fungicidas Industriais/farmacologia , Inseticidas , Proteínas de Plantas/farmacologia , Sementes/química , Animais , Besouros , Fungicidas Industriais/isolamento & purificação , Inseticidas/isolamento & purificação , Proteínas de Plantas/isolamento & purificação , Proteínas de Armazenamento de SementesRESUMO
Immunization coverage was evaluated in all 12-23 month-old children living in the area were five years before a Primary Care Practice had been set up. All children were investigated through home visits, checking of the immunization chart and relying on mothers' information. In 1986, a baseline study had identified an immunization coverage of under 60% for each of the scheduled vaccines. The current study confirmed that coverage was of 87% for three doses of DTP, 89% for Sabin, 88% for one dose of measles vaccine and 79% for BCG. Despite the high coverage achieved for each specific vaccine, when the basic schedule for the first year was verified, it was observed that only 75% of the children had received the full scheme. Immunization coverage is uneven in different census tracts, being higher in the poorest and more remote areas, where seam the health was given extra attention. A comparison with the routine administrative evaluation of the immunization coverage showed that this underestimated the real coverage. Maternal immunization uptake was also evaluated (antitetanus vaccine during pregnancy) and only 49% of the women were found to be adequately protected. The information collected led to a reorganization of the whole immunization program in a 100% coverage.