RESUMO
BACKGROUND: The deficiency in 1α, 25-dihydroxyvitamin D3 (VD3) seems to increase the risk for neurodegenerative pathologies, including Parkinson's disease (PD). The majority of its actions are mediated by the transcription factor, VD3 receptor (VD3R). METHODS: The neuroprotective effects of VD3 were investigated on a PD model. Male Wistar rats were divided into the following groups: sham-operated (SO), 6-OHDA-lesioned (non-treated), and 6-OHDA-lesioned and treated with VD3 (7 days before the lesion, pre-treatment or for 14 days after the 6-OHDA striatal lesion, post-treatment). Afterwards, the animals were subjected to behavioral tests and euthanized for striatal neurochemical and immunohistochemical assays. The data were analyzed by ANOVA and the Tukey test and considered significant for p < 0.05. RESULTS: We showed that pre- or post-treatments with VD3 reversed behavioral changes and improved the decreased DA contents of the 6-OHDA group. In addition, VD3 reduced the oxidative stress, increased (TH and DAT), and reduced (TNF-alpha) immunostainings in the lesioned striata. While significant decreases in VD3R immunoreactivity were observed after the 6-OHDA lesion, these changes were blocked after VD3 pre- or post-treatments. We showed that VD3 offers neuroprotection, decreasing behavioral changes, DA depletion, and oxidative stress. In addition, it reverses partially or completely TH, DAT, TNF-alpha, and VD3R decreases of immunoreactivities in the non-treated 6-OHDA group. CONCLUSIONS: Taken together, VD3 effects could result from its anti-inflammatory and antioxidant actions and from its actions on VD3R. These findings should stimulate translational research towards the VD3 potential for prevention or treatment of neurodegenerative diseases, as PD.
Assuntos
Neurônios Dopaminérgicos/efeitos dos fármacos , Encefalite/etiologia , Encefalite/patologia , Estresse Oxidativo/efeitos dos fármacos , Transtornos Parkinsonianos/complicações , Vitamina D/farmacologia , Animais , Apomorfina/farmacologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Comportamento Exploratório/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Oxidopamina/toxicidade , Transtornos Parkinsonianos/induzido quimicamente , Ratos , Ratos Wistar , Comportamento Estereotipado/efeitos dos fármacos , Natação/fisiologia , Simpatolíticos/toxicidade , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
OBJECTIVES: Aspidosperma species are used for several diseases, especially for malaria in Brazil. Although the genus is object of pharmacological studies, almost none are found on Aspidosperma pyrifolium. We investigate neuroprotective, antioxidant and anti-inflammatory properties of the APSE-Aq fraction (benzoic acid glycosylated derivative) on Parkinson's disease model. METHODS: Male Wistar rats were subjected to a 6-hydroxydopamine injection into the right striatum and treated or not with APSE-Aq (100 or 200 mg/kg, p.o.). The sham-operated group was injected with saline. Two weeks later, animals were subjected to behavioural, neurochemical and immunohistochemical evaluation. The data were analysed by ANOVA and Tukey test. KEY FINDINGS: The APSE-Aq-treated group shows a partial recovery of behavioural changes as compared with the untreated-6-hydroxydopamine group. A partial recovery was also observed in nitrite contents and lipid peroxidation. APSE-Aq treatments significantly reversed decreases in striatal dopamine and metabolites in the untreated 6-hydroxydopamine group. Immunostainings for markers as tyrosine hydroxylase and dopamine transporter decreased in the untreated 6-hydroxydopamine group and values recovered after APSE-Aq treatments. Similar data were seen for TNF-alpha. CONCLUSION: APSE-Aq presents neuroprotective, antioxidant and anti-inflammatory activities. Considering that APSE-Aq is chemically related to salicylic acid, it may act on similar targets.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Aspidosperma/química , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Nitritos/metabolismo , Oxidopamina/metabolismo , Extratos Vegetais/química , Ratos , Sementes/química , Fator de Necrose Tumoral alfa/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
The aim of the study was to evaluate the performance of the HPV-HR test to detect high-risk human papillomavirus (HPV) in urine samples in comparison with a commercial molecular HPV test. MATERIALS AND METHODS: This is a prospective study, in which 350 patients diagnosed previously with cervical intraepithelial neoplasia (CIN) grade 2 or higher were enrolled. Urine and cervical specimens were collected. Urine was tested with the HPV-HR test and cervical specimens were tested with the Cobas. RESULTS: Of the 336 evaluable patients, there were 271 cases of CIN 2+, of which 202 were CIN 3+ and the remaining 65 patients were less than CIN 2. Positivity was 77.1% (95% confidence interval [CI] = 72.5-81.5) for the urine samples and 83.6% (95% CI = 79.6-87.6) for the cervical samples. Agreement between cervical and urine samples for HPV detection was 79.8% (κ = 0.363; 95% CI = 0.243-0.484). Sensitivity for CIN 2+ was 83.4% (95% CI = 78.4-87.6) for urine and 90.8% (95% CI = 86.7-92.9) for cervical samples. The sensitivity for CIN 3+ was 85.6% (95% CI = 80.0-90.2) for urine and 92.6% (95% CI = 88.0-95.8) for cervical samples. Specificity for worse than CIN 2 was 50.8% (95% CI = 33.7-59.0) and 46.2% (95% CI = 33.7-59.0) for urine and cervical samples, respectively. CONCLUSIONS: Although these results demonstrated slightly higher detection rates for HR-HPV and clinical sensitivity in cervical samples than in urine, when compared with histological diagnoses, urine sampling is a viable alternative to access women who do not participate in routine screening programs.
Assuntos
Papillomaviridae/isolamento & purificação , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/virologia , Urina/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colo do Útero/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Estudos Prospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
Inflammation plays a pivotal role in the development of ischemic brain damage. Astrocyte activation promotes the production of several proinflammatory mediators, such as TNF-α and iNOS. Eventually, neuronal death occurs, leading to the development of motor and memory deficits in patients. Boldine is the main alkaloid in the leaves and bark of the Peumus boldus Molina, and has anti-inflammatory and antioxidant properties. The aim of this work was to investigate the neuroprotective effect of boldine on neuroinflammation and memory deficits induced by permanent middle cerebral artery occlusion (pMCAO) in mice. Thirty minutes before pMCAO and during the next 5 days, animals received vehicle (0.025 µmol/l HCl) or boldine (8, 16 and 25 mg/kg, intraperitoneally). The extension of the infarct area, neurological scores, and myeloperoxidase activity were evaluated 24 h after pMCAO. Locomotor activity, working, and aversive memory were evaluated 72 h after pMCAO, object recognition memory was tested 96 h after pMCAO, and spatial memory was tested 120 h after pMCAO. Cresyl violet, Fluoro-Jade C staining, and immunohistochemical for GFAP, TNF-α, and iNOS were also carried out. The treatment with boldine significantly decreased the infarct area, improved the neurological scores, and increased cell viability. The vertical exploratory activity and aversive, spatial, object recognition, and working memory deficits induced by pMCAO were prevented by boldine. Moreover, myeloperoxidase activity and GFAP, TNF-α, and iNOS immunoreactivity were decreased significantly by boldine. Although various mechanisms such as its antioxidant activity should be considered, these results suggest that the neuroprotective effect of boldine might be related in part to its anti-inflammatory properties.
Assuntos
Aporfinas/farmacologia , Inflamação/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Aporfinas/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inflamação/patologia , Injeções Intraperitoneais , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/prevenção & controle , Camundongos , Fármacos Neuroprotetores/administração & dosagem , Peumus/química , Acidente Vascular Cerebral/complicaçõesRESUMO
Vicilins (7S storage proteins) found in various legume seeds have been previously shown to interfere with the germination of spores or conidia of phytopathogenic fungi and inhibit yeast growth and glucose stimulated acidification of the medium by yeast cells. In the present work vicilins from cowpea (Vigna unguiculata) seeds were added to the growth medium of Saccharomyces cerevisiae cells and Fusarium oxysporum conidia. Helix pomatia lectin, wheat germ agglutinin and Ulex europaeus lectin were used to identify differences in the binding of the vicilins to the surface of cells of S. cerevisiae and F. oxysporum treated with this protein. After the growth period, the material in suspension (yeast cells) was centrifuged and the final pellet was also treated with different sugar (glucose, sucrose, glucosamine, N-acetyl-glucosamine) concentrations and 0.1 M HCl for extraction of vicilins associated to chitinous structures present in yeast cells. Our results showed that vicilin sub-units were present in the different sugar extracts of yeast cells pretreated with the vicilins and these proteins were eluted by 0.5 M solutions of sugars in the following order of efficiency of elution: N-acetyl-glucosamine, sucrose/glucose and glucosamine.
Assuntos
Ligação Competitiva/efeitos dos fármacos , Carboidratos/farmacologia , Membrana Celular/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Proteínas de Plantas/farmacologia , Acetilglucosamina/farmacologia , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/fisiologia , Ligação Competitiva/fisiologia , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Parede Celular/metabolismo , Parede Celular/ultraestrutura , Fungos/efeitos dos fármacos , Fungos/crescimento & desenvolvimento , Fungos/ultraestrutura , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Fusarium/ultraestrutura , Glucosamina/farmacologia , Glucose/farmacologia , Microscopia Eletrônica , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/ultraestrutura , Proteínas de Armazenamento de Sementes , Sacarose/farmacologiaRESUMO
Vicilins (7S storage proteins) found in various legume seeds have been previously shown to interfere with the germination of spores or conidia of phytopathogenic fungi and inhibit yeast growth and glucose stimulated acidification of the medium by yeast cells. In the present work vicilins from cowpea (Vigna unguiculata) seeds were added to the growth medium of Saccharomyces cerevisiae cells and Fusarium oxysporum conidia. Helix pomatia lectin, wheat germ agglutinin and Ulex europaeus lectin were used to identify differences in the binding of the vicilins to the surface of cells of S. cerevisiae and F. oxysporum treated with this protein. After the growth period, the material in suspension (yeast cells) was centrifuged and the final pellet was also treated with different sugar (glucose, sucrose, glucosamine, N-acetyl-glucosamine) concentrations and 0.1 M HCl for extraction of vicilins associated to chitinous structures present in yeast cells. Our results showed that vicilin sub-units were present in the different sugar extracts of yeast cells pretreated with the vicilins and these proteins were eluted by 0.5 M solutions of sugars in the following order of efficiency of elution: N-acetyl-glucosamine, sucrose/glucose and glucosamine. (AU)
Assuntos
RESEARCH SUPPORT, NON-U.S. GOVT , Ligação Competitiva/efeitos dos fármacos , Carboidratos/farmacologia , Membrana Celular/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Proteínas de Plantas/farmacologia , Acetilglucosamina/farmacologia , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/fisiologia , Ligação Competitiva/fisiologia , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Parede Celular/metabolismo , Parede Celular/ultraestrutura , Fungos/efeitos dos fármacos , Fungos/crescimento & desenvolvimento , Fungos/ultraestrutura , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Fusarium/ultraestrutura , Glucosamina/farmacologia , Glucose/farmacologia , Microscopia Eletrônica , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/ultraestrutura , Sacarose/farmacologiaRESUMO
Vicilins (7S storage proteins) found in various legume seeds have been previously shown to interfere with the germination of spores or conidia of phytopathogenic fungi and inhibit yeast growth and glucose stimulated acidification of the medium by yeast cells. In the present work vicilins from cowpea (Vigna unguiculata) seeds were added to the growth medium of Saccharomyces cerevisiae cells and Fusarium oxysporum conidia. Helix pomatia lectin, wheat germ agglutinin and Ulex europaeus lectin were used to identify differences in the binding of the vicilins to the surface of cells of S. cerevisiae and F. oxysporum treated with this protein. After the growth period, the material in suspension (yeast cells) was centrifuged and the final pellet was also treated with different sugar (glucose, sucrose, glucosamine, N-acetyl-glucosamine) concentrations and 0.1 M HCl for extraction of vicilins associated to chitinous structures present in yeast cells. Our results showed that vicilin sub-units were present in the different sugar extracts of yeast cells pretreated with the vicilins and these proteins were eluted by 0.5 M solutions of sugars in the following order of efficiency of elution: N-acetyl-glucosamine, sucrose/glucose and glucosamine.
Assuntos
Carboidratos/farmacologia , Ligação Competitiva/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Proteínas de Plantas/farmacologia , Acetilglucosamina/farmacologia , Fungos/efeitos dos fármacos , Fungos/crescimento & desenvolvimento , Fungos/ultraestrutura , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Fusarium/ultraestrutura , Glucosamina/farmacologia , Glucose/farmacologia , Ligação Competitiva/fisiologia , Microscopia Eletrônica , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Parede Celular/metabolismo , Parede Celular/ultraestrutura , Sacarose/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/ultraestrutura , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/fisiologiaRESUMO
Vicilins (7S storage proteins) found in various legume seeds have been previously shown to interfere with the germination of spores or conidia of phytopathogenic fungi and inhibit yeast growth and glucose stimulated acidification of the medium by yeast cells. In the present work vicilins from cowpea (Vigna unguiculata) seeds were added to the growth medium of Saccharomyces cerevisiae cells and Fusarium oxysporum conidia. Helix pomatia lectin, wheat germ agglutinin and Ulex europaeus lectin were used to identify differences in the binding of the vicilins to the surface of cells of S. cerevisiae and F. oxysporum treated with this protein. After the growth period, the material in suspension (yeast cells) was centrifuged and the final pellet was also treated with different sugar (glucose, sucrose, glucosamine, N-acetyl-glucosamine) concentrations and 0.1 M HCl for extraction of vicilins associated to chitinous structures present in yeast cells. Our results showed that vicilin sub-units were present in the different sugar extracts of yeast cells pretreated with the vicilins and these proteins were eluted by 0.5 M solutions of sugars in the following order of efficiency of elution: N-acetyl-glucosamine, sucrose/glucose and glucosamine.
RESUMO
Vicilin (7S storage proteins) isolated from different legume seeds were shown to inhibit yeast growth and glucose stimulated acidification of the medium by yeast cells. The degree of growth inhibition varied with the origin of vicilins. It was more than 90% for vicilins from cowpea (Vigna unguiculata, cultivar pitiuba) and equal to 65% for vicilins from Vigna radiata, in the case of Saccharomyces cerevisae. Vicilins from cowpea seeds inhibited the glucose stimulated acidification of the medium by S. cerevisae up to 60%. We have also observed that vicilins bind to yeast cells. We suggest that vicilins bind to chitin-containing structures of yeast cells and that such association could result in inhibition of H+ pumping, cell growth and spore formation. A final consequence of the yeast growth inhibition by vicilins is (probably) the formation of spores.