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1.
J Helminthol ; 92(6): 674-680, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29067895

RESUMO

This study describes the effects of extracts and fractions of Persea willdenovii leaves against goat gastrointestinal nematodes and their cytotoxicity on Vero cells. The in vitro ovicidal and larvicidal activities of the crude ethanolic, hexane, ethyl acetate (EAE), butanolic and residual hydroethanolic extracts were assessed through the inhibition of egg hatching and larval motility assays. The most active extract (EAE) was then fractionated by chromatography in an open column containing silica gel, to furnish six fractions (Fr1-Fr6), which were also tested. The cytotoxicity of active extracts and fractions was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue exclusion assay. The EAE and two fractions (Fr1 and Fr2) showed inhibitory activity in the egg hatching of gastrointestinal nematodes of goats in a concentration-dependent manner. The effective concentrations for 50% inhibition (EC50) of egg hatching were 2.3, 0.12 and 2.94 mg/ml for EAE, Fr1 and Fr2, respectively. All extracts and fractions were not effective in inhibiting 50% of motility of infective larvae. EAE and Fr2 had IC50 values (50% inhibitory concentration) of 4.95 and 2.66 mg/ml, respectively. Fr1 showed a slight cytotoxic effect (cellular inviability <30%) only after 48 h of treatment (MTT test). Gas chromatography-mass spectrometry (GC-MS) analysis showed the presence of six fatty acid ethyl esters, a fatty acid methyl ester and a long-chain ketone in the most active fraction. These constituents identified in P. willdenovii can be related to the high ovicidal activity and relatively non-toxic effect of the extracts.


Assuntos
Anti-Helmínticos/farmacologia , Anti-Helmínticos/toxicidade , Nematoides/efeitos dos fármacos , Persea/química , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Animais , Anti-Helmínticos/química , Anti-Helmínticos/isolamento & purificação , Bioensaio , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Cromatografia Gasosa-Espectrometria de Massas , Cabras , Concentração Inibidora 50 , Larva/efeitos dos fármacos , Larva/fisiologia , Locomoção/efeitos dos fármacos , Nematoides/fisiologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Células Vero
2.
Genet Mol Res ; 16(2)2017 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-28510252

RESUMO

Understanding non-additive effects in the expression of quantitative traits is very important in genotype selection, especially in species where the commercial products are clones or hybrids. The use of molecular markers has allowed the study of non-additive genetic effects on a genomic level, in addition to a better understanding of its importance in quantitative traits. Thus, the purpose of this study was to evaluate the behavior of the GBLUP model in different genetic models and relationship matrices and their influence on the estimates of genetic parameters. We used real data of the circumference at breast height in Eucalyptus spp and simulated data from a population of F2. Three commonly reported kinship structures in the literature were adopted. The simulation results showed that the inclusion of epistatic kinship improved prediction estimates of genomic breeding values. However, the non-additive effects were not accurately recovered. The Fisher information matrix for real dataset showed high collinearity in estimates of additive, dominant, and epistatic variance, causing no gain in the prediction of the unobserved data and convergence problems. Estimates presented differences of genetic parameters and correlations considering the different kinship structures. Our results show that the inclusion of non-additive effects can improve the predictive ability or even the prediction of additive effects. However, the high distortions observed in the variance estimates when the Hardy-Weinberg equilibrium assumption is violated due to the presence of selection or inbreeding can converge at zero gains in models that consider epistasis in genomic kinship.


Assuntos
Eucalyptus/genética , Modelos Genéticos , Característica Quantitativa Herdável , Epistasia Genética , Eucalyptus/crescimento & desenvolvimento , Genótipo
3.
Haemophilia ; 19(5): 773-81, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23711237

RESUMO

A total of 76 unrelated male patients with mild (n = 55) or moderate (n = 21) haemophilia A living in the southern Brazilian state of Rio Grande do Sul were studied by direct sequencing of all F8 26 exons, the 5' UTR and 3' UTR, intron-exon junctions and the promoter region. When no mutation was found, a multiplex ligation-dependent probe amplification analysis was performed. We identified the disease-causing mutations in 69 patients, who showed 33 different mutations: 27 missense, one small deletion, two small duplications and three splice site mutations. Seven missense and two splice site mutations were not previously reported in HAMSTeRS and were not identified in any current literature search. Nine recurrent mutations were found, one of them never described before (p.Tyr1786Phe). Haplotype analysis indicated that this mutation had originated in the Brazilian population as a single event in a common ancestor. The possible influence of these mutations in the determination of the disease was carefully considered, including bioinformatic tools. These data add to the general knowledge of the disease and can also be useful for HA diagnosis and detection of carriers in the southern Brazilian population.


Assuntos
Fator VIII/genética , Hemofilia A/genética , Hemofilia A/patologia , Mutação , Regiões 3' não Traduzidas , Regiões 5' não Traduzidas , Adolescente , Adulto , Idoso , Brasil , Criança , Pré-Escolar , Éxons , Genótipo , Haplótipos , Hemofilia A/tratamento farmacológico , Humanos , Lactente , Íntrons , Masculino , Pessoa de Meia-Idade , Patologia Molecular , Fenótipo , Adulto Jovem
4.
Rev Esp Anestesiol Reanim (Engl Ed) ; 70(4): 224-230, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36842688

RESUMO

BACKGROUND: Pregnancy in spinal cord injured patients has specific issues that must be carefully addressed. However, guidelines for their management are scarce. METHODS: A systematic review of the literature regarding the anaesthetic management during delivery of pregnant patients with cervical spinal cord injury was performed on the electronic databases of PubMed (Medline) and Cochrane. RESULTS: Twenty-two papers were included. A higher incidence of preterm birth and caesarean delivery were seen. Anaesthetic management was diverse, although most pregnant patients received epidural analgesia. Autonomic dysreflexia symptoms were present in 51% of pregnancies. CONCLUSION: Timely management of these patients could possibly reduce caesarean and preterm delivery rates, avoid or minimize common complications, as well as reduce costs. An early reference to anaesthesiology consultation and a multidisciplinary approach is recommended.


Assuntos
Anestésicos , Disreflexia Autonômica , Nascimento Prematuro , Traumatismos da Medula Espinal , Gravidez , Feminino , Humanos , Recém-Nascido , Criança , Traumatismos da Medula Espinal/complicações , Cesárea , Disreflexia Autonômica/etiologia
5.
Braz J Biol ; 84: e253599, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35019099

RESUMO

The antioxidant activity of Tetragonisca angustula honey (TAH) and its ethanolic extract (TAEE) were investigated. The total levels of phenolic (TPC) and flavonoids (TFC) were also evaluated. The results for TPC were 19.91 ± 0.38 and 29.37 ± 1.82 mg GAE g-1 and for TFC 0.20 ± 0.02 and 0.14 ± 0.01 mg QE g-1 of TAH and TAEE, respectively. Antioxidant activities were 73.29 ± 0.49% and 93.36 ± 0.27% in the DPPH● assay and 71.73 ± 4.07% and 97.86 ± 0.35% in ABTS●+ for TAH and TAEE, respectively. The total reducing activity was determined by the method of reducing power (PR) and iron ion (Fe III) and the results varied in PR from 151.7 ± 25.7 and 230.7 ± 25.2 mg GAE L-1, for TAH and TAEE respectively and for (Fe III) in EC50 0.284 in TAEE and 0.687 in TAH. Chemical analysis by HPLC-DAD of the ethanolic extract (TAEE) revealed the presence of ferulic acid as majority phenolic component in the extract. The 1H NMR analysis confirmed this structure and showed the also presence of glucose, citric acid, succinic acid, proline and hydrocarbon derivatives. In addition, the botanical origin was also investigated and showed a multifloral characteristic, having found 19 pollen types with a botanical predominance of the Anacardiaceae family, with Tapirira pollen occurring as predominant (42.6%) and Schinus as secondary (25.7%). The results showed that T. angustula honey is an interesting source of antioxidant phenolic compounds due to its floral origin and can act as a protector of human health when consumed.


Assuntos
Antioxidantes , Mel , Animais , Brasil , Ácidos Cumáricos , Mel/análise , Humanos , Fenóis/análise
7.
Genet Mol Res ; 10(1): 16-24, 2011 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-21218382

RESUMO

Luehea divaricata is a native plant of the Brazilian Cerrado, known as "açoita-cavalo". It is used as a popular herbal medicine in the treatment of dysentery, bleeding, arthritis, tumors, ulcers, and gangrenous wounds. Considering that herbal medicines sometimes provoke tumors and/or may prevent mutational events, it is important to study the action of these natural drugs on DNA. Aqueous extract of the bark of L. divaricata was evaluated at three different concentrations (0.10, 0.30, 0.50 mg/mL), individually and in combination with the neoplastic drug doxorubicin (DXR), by the somatic mutation and recombination test (SMART/wing) in Drosophila melanogaster. Distilled water was included as a negative control. The mutation frequency in the treatments with L. divaricata extract alone was not significantly higher than in the negative control for standard (ST) and high bioactivation (HB) crosses. When L. divaricata extract was combined with DXR, there was a significant reduction in the frequency of spots when compared to DXR alone, in both crosses. Further studies with other experimental models would be useful to confirm that L. divaricata extract is not harmful and that it could be used in the prevention of cancer.


Assuntos
Drosophila melanogaster/efeitos dos fármacos , Malvaceae/química , Mutagênicos/toxicidade , Extratos Vegetais/toxicidade , Plantas Medicinais/toxicidade , Animais , Doxorrubicina/farmacologia , Drosophila melanogaster/genética , Testes de Mutagenicidade , Mutação/efeitos dos fármacos , Análise de Sobrevida , Asas de Animais/efeitos dos fármacos
8.
Genet Mol Res ; 9(2): 1153-62, 2010 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-20568060

RESUMO

Palicourea coriacea, popularly known as "douradinha", is a medicinal plant from the Brazilian Cerrado region used in folk medicine to treat kidney and urethral stones and kidney inflammation. We evaluated the cytotoxic, genotoxic, and possible antigenotoxic activities of an aqueous extract of P. coriacea on somatic cells of Drosophila melanogaster, using the somatic mutation and recombination test. We used third-stage larvae of D. melanogaster from a standard cross and a high bioactivation cross and tested 10 different doses of P. coriacea aqueous extract (5, 15, 25, 35, 50, 65, 80, 95, 110, and 125 mg/mL). Doxorubicin (0.125 mg/mL) was used as a positive control and distilled water as a negative control. None of the doses was lethal to the larvae.There was no genotoxic effect at 5, 10, or 15 mg extract/mL. However, a significant decrease in the frequency of spots induced by doxorubicin was observed when administered with P. coriacea aqueous extract at these same doses. We conclude that P. coriacea aqueous extract is not cytotoxic or genotoxic at these doses, but it does protect against the genotoxic action of doxorubicin.


Assuntos
Doxorrubicina/farmacologia , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Rubiaceae/genética , Rubiaceae/metabolismo , Animais , Relação Dose-Resposta a Droga , Genes de Plantas , Técnicas Genéticas , Heterozigoto , Larva/efeitos dos fármacos , Testes de Mutagenicidade , Mutação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plantas Medicinais , Recombinação Genética/efeitos dos fármacos , Asas de Animais/efeitos dos fármacos
9.
Braz J Med Biol Res ; 53(3): e8876, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32077463

RESUMO

The immune stimulatory and anti-neoplastic functions of type I interferon have long been applied for the treatment of melanoma. However, the systemic application of high levels of this recombinant protein is often met with toxicity. An approach that provides localized, yet transient, production of type I interferon may overcome this limitation. We propose that the use of mesenchymal stem cells (MSCs) as delivery vehicles for the production of interferon-ß (IFNß) may be beneficial when applied together with our cancer gene therapy approach. In our previous studies, we have shown that adenovirus-mediated gene therapy with IFNß was especially effective in combination with p19Arf gene transfer, resulting in immunogenic cell death. Here we showed that MSCs derived from mouse adipose tissue were susceptible to transduction with adenovirus, expressed the transgene reliably, and yet were not especially sensitive to IFNß production. MSCs used to produce IFNß inhibited B16 mouse melanoma cells in a co-culture assay. Moreover, the presence of p19Arf in the B16 cells sensitizes them to the IFNß produced by the MSCs. These data represent a critical demonstration of the use of MSCs as carriers of adenovirus encoding IFNß and applied as an anti-cancer strategy in combination with p19Arf gene therapy.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/administração & dosagem , Interferon beta/metabolismo , Melanoma Experimental/terapia , Células-Tronco Mesenquimais/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Terapia Genética , Masculino , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Transdução Genética
10.
Braz. j. biol ; 84: e253599, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355891

RESUMO

Abstract The antioxidant activity of Tetragonisca angustula honey (TAH) and its ethanolic extract (TAEE) were investigated. The total levels of phenolic (TPC) and flavonoids (TFC) were also evaluated. The results for TPC were 19.91 ± 0.38 and 29.37 ± 1.82 mg GAE g-1 and for TFC 0.20 ± 0.02 and 0.14 ± 0.01 mg QE g-1 of TAH and TAEE, respectively. Antioxidant activities were 73.29 ± 0.49% and 93.36 ± 0.27% in the DPPH● assay and 71.73 ± 4.07% and 97.86 ± 0.35% in ABTS●+ for TAH and TAEE, respectively. The total reducing activity was determined by the method of reducing power (PR) and iron ion (Fe III) and the results varied in PR from 151.7 ± 25.7 and 230.7 ± 25.2 mg GAE L-1, for TAH and TAEE respectively and for (Fe III) in EC50 0.284 in TAEE and 0.687 in TAH. Chemical analysis by HPLC-DAD of the ethanolic extract (TAEE) revealed the presence of ferulic acid as majority phenolic component in the extract. The 1H NMR analysis confirmed this structure and showed the also presence of glucose, citric acid, succinic acid, proline and hydrocarbon derivatives. In addition, the botanical origin was also investigated and showed a multifloral characteristic, having found 19 pollen types with a botanical predominance of the Anacardiaceae family, with Tapirira pollen occurring as predominant (42.6%) and Schinus as secondary (25.7%). The results showed that T. angustula honey is an interesting source of antioxidant phenolic compounds due to its floral origin and can act as a protector of human health when consumed.


Resumo A atividade antioxidante do mel de Tetragonisca angustula (TAH) e seu extrato etanólico (TAEE) foram investigados. Os níveis totais de fenólicos (TPC) e flavonóides (TFC) também foram avaliados. Os resultados para TPC foram 19,91 ± 0,38 e 29,37 ± 1,82 mg GAE g-1 e para TFC 0,20 ± 0,02 e 0,14 ± 0,01 mg QE g-1 de TAH e TAEE, respectivamente. As atividades antioxidantes foram 73,29 ± 0,49% e 93,36 ± 0,27% no ensaio DPPH● e 71,73 ± 4,07% e 97,86 ± 0,35% no ABTS●+ para TAH e TAEE, respectivamente. A atividade redutora total foi determinada pelo método de poder redutor (PR) e íon ferrico (Fe III) e os resultados variaram em PR de 151,7 ± 25,7 e 230,7 ± 25,2 mg GAE L-1, para TAH e TAEE respectivamente e para (Fe III) em EC50 0,284 em TAEE e 0,687 em TAH. A análise química por HPLC-DAD do extrato etanólico (TAEE) revelou a presença de ácido ferúlico como componente majoritário no extrato. A análise de RMN 1H confirmou esta estrutura e mostrou a presença de glicose, ácido cítrico, ácido succínico, prolina e derivados de hidrocarbonetos no TAEE. Além disso, a origem botânica também foi investigada e apresentou característica multifloral, tendo encontrado 19 tipos polínicos com predomínio botânico da família Anacardiaceae, sendo o pólen Tapirira predominante (42,6%) e o Schinus secundário (25,7%). Os resultados mostraram que o mel de T. angustula é uma interessante fonte de compostos fenólicos antioxidantes devido à sua origem floral e pode atuar como protetor da saúde humana quando consumido.


Assuntos
Humanos , Animais , Mel/análise , Antioxidantes , Fenóis/análise , Brasil , Ácidos Cumáricos
11.
Braz. j. biol ; 842024.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469316

RESUMO

Abstract The antioxidant activity of Tetragonisca angustula honey (TAH) and its ethanolic extract (TAEE) were investigated. The total levels of phenolic (TPC) and flavonoids (TFC) were also evaluated. The results for TPC were 19.91 ± 0.38 and 29.37 ± 1.82 mg GAE g-1 and for TFC 0.20 ± 0.02 and 0.14 ± 0.01 mg QE g-1 of TAH and TAEE, respectively. Antioxidant activities were 73.29 ± 0.49% and 93.36 ± 0.27% in the DPPH assay and 71.73 ± 4.07% and 97.86 ± 0.35% in ABTS+ for TAH and TAEE, respectively. The total reducing activity was determined by the method of reducing power (PR) and iron ion (Fe III) and the results varied in PR from 151.7 ± 25.7 and 230.7 ± 25.2 mg GAE L-1, for TAH and TAEE respectively and for (Fe III) in EC50 0.284 in TAEE and 0.687 in TAH. Chemical analysis by HPLC-DAD of the ethanolic extract (TAEE) revealed the presence of ferulic acid as majority phenolic component in the extract. The 1H NMR analysis confirmed this structure and showed the also presence of glucose, citric acid, succinic acid, proline and hydrocarbon derivatives. In addition, the botanical origin was also investigated and showed a multifloral characteristic, having found 19 pollen types with a botanical predominance of the Anacardiaceae family, with Tapirira pollen occurring as predominant (42.6%) and Schinus as secondary (25.7%). The results showed that T. angustula honey is an interesting source of antioxidant phenolic compounds due to its floral origin and can act as a protector of human health when consumed.


Resumo A atividade antioxidante do mel de Tetragonisca angustula (TAH) e seu extrato etanólico (TAEE) foram investigados. Os níveis totais de fenólicos (TPC) e flavonóides (TFC) também foram avaliados. Os resultados para TPC foram 19,91 ± 0,38 e 29,37 ± 1,82 mg GAE g-1 e para TFC 0,20 ± 0,02 e 0,14 ± 0,01 mg QE g-1 de TAH e TAEE, respectivamente. As atividades antioxidantes foram 73,29 ± 0,49% e 93,36 ± 0,27% no ensaio DPPH e 71,73 ± 4,07% e 97,86 ± 0,35% no ABTS+ para TAH e TAEE, respectivamente. A atividade redutora total foi determinada pelo método de poder redutor (PR) e íon ferrico (Fe III) e os resultados variaram em PR de 151,7 ± 25,7 e 230,7 ± 25,2 mg GAE L-1, para TAH e TAEE respectivamente e para (Fe III) em EC50 0,284 em TAEE e 0,687 em TAH. A análise química por HPLC-DAD do extrato etanólico (TAEE) revelou a presença de ácido ferúlico como componente majoritário no extrato. A análise de RMN 1H confirmou esta estrutura e mostrou a presença de glicose, ácido cítrico, ácido succínico, prolina e derivados de hidrocarbonetos no TAEE. Além disso, a origem botânica também foi investigada e apresentou característica multifloral, tendo encontrado 19 tipos polínicos com predomínio botânico da família Anacardiaceae, sendo o pólen Tapirira predominante (42,6%) e o Schinus secundário (25,7%). Os resultados mostraram que o mel de T. angustula é uma interessante fonte de compostos fenólicos antioxidantes devido à sua origem floral e pode atuar como protetor da saúde humana quando consumido.

13.
Sci Rep ; 7(1): 17337, 2017 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-29230035

RESUMO

A new approach for non-isothermal tempering analysis utilizing dilatometry is proposed and was carried out on a medium carbon steel with high silicon and additions of Mo and V for secondary hardening. The method includes a second non-isothermal step performed with the same heating rate (2 °C/min) used for the first step in order to create a baseline for analysis. The results were correlated with several other characterization techniques. Mössbauer spectroscopy confirmed the formation of transition carbides by auto-tempering as well as the presence of retained austenite decomposition (stage II) and cementite precipitation (stage III), which demonstrated significant overlap. Electrical resistivity measurements were correlated with dislocation densities obtained through X-ray diffraction analysis. Transmission electron microscopy dark field images confirmed the secondary hardening assessment from dilatometry.

14.
Environ Toxicol Pharmacol ; 56: 198-203, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28961514

RESUMO

Carnauba wax is extracted from the leaves of the Copernicia prunífera and contains approximately 80% of esters in its composition. The purpose of the present study was evaluate the hypolipidemic effect of p-methoxycinnamic diesters (PCO-C) extracted from Copernicia prunífera in a model of acute and chronic dyslipidemia in mice. The levels of total cholesterol and triglycerides were significantly reduced plasma levels in PCO-C at the dose of 100mg/kg in a model of acute and chronic dyslipidemia. Histological studies showed that PCO-C has no hepatotoxic effect and reduces hepatic steatosis in animals that consumed hyperlipidemic ration. Thus, it was concluded that PCO-C isolated from Copernicia Prunifera was effective in reducing total cholesterol and triglyceride levels in both dyslipidemia induction models. The finding indicates that PCO-C might be beneficial in treatment of hyperlipidemia and atherosclerosis.


Assuntos
Arecaceae/química , Dislipidemias/tratamento farmacológico , Ésteres/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Dislipidemias/induzido quimicamente , Ésteres/química , Ésteres/farmacologia , Masculino , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Triglicerídeos/sangue , Ceras/química , Ceras/farmacologia
15.
Science ; 355(6328): 925-931, 2017 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-28254935

RESUMO

The extent to which pre-Columbian societies altered Amazonian landscapes is hotly debated. We performed a basin-wide analysis of pre-Columbian impacts on Amazonian forests by overlaying known archaeological sites in Amazonia with the distributions and abundances of 85 woody species domesticated by pre-Columbian peoples. Domesticated species are five times more likely than nondomesticated species to be hyperdominant. Across the basin, the relative abundance and richness of domesticated species increase in forests on and around archaeological sites. In southwestern and eastern Amazonia, distance to archaeological sites strongly influences the relative abundance and richness of domesticated species. Our analyses indicate that modern tree communities in Amazonia are structured to an important extent by a long history of plant domestication by Amazonian peoples.


Assuntos
Domesticação , Florestas , Árvores , Brasil , História Antiga , Humanos
16.
Cancer Res ; 54(2): 386-92, 1994 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-7903909

RESUMO

The biotransformation of taxol by human liver was investigated in vitro with microsomes isolated from adult and developing human tissues. In vitro, no metabolism was detected with kidney microsomes, whereas two metabolites were generated by liver microsomes. The most prominent metabolite, termed M5, corresponded to an hydroxylation at the C6 position on the taxane ring, while the other metabolite, termed M4, corresponded to an hydroxylation at the para-position on the phenyl ring at the C3'-position of the C13 side chain. These two taxol derivatives have been shown to be the major metabolites recovered in bile from a patient infused with taxol. Several approaches have been used to identify the cytochrome P450 (CYP) isozymes involved in these reactions. No positive correlation was observed between the in vitro synthesis of these two metabolites, suggesting that two cytochrome P450 isozymes could be involved, although they could not be distinguished by their apparent affinities (Km approximately 15 microM). The formation of metabolite M4 was substantially reduced both by antibody directed against CYP3A and by the addition of CYP3A substrates such as orphenadrine, erythromycin, troleandomycin, and testosterone. Conversely, the formation of metabolite M5 remained unaffected by antibodies against CYP3A and by CYP3A substrates but was sensitive to diazepam inhibition, a preferential substrate of CYP2C. Correlation between CYP2C content or diazepam demethylation and the synthesis of metabolite M5 was highly positive. The formation of metabolite M4 developed during the early postnatal period. In contrast, the synthesis of metabolite M5 rose only after 3 months of age. These data clearly implicate CYP3A in the formation of metabolite M4 and CYP2C in the synthesis of metabolite M5. Microsomes from patients treated with barbiturates and benzodiazepines increased the formation of metabolite M4 to the level of metabolite M5, demonstrating that drug interactions could modify the human metabolism of taxol.


Assuntos
Microssomos Hepáticos/metabolismo , Paclitaxel/farmacocinética , Fatores Etários , Biotransformação , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos
17.
Braz J Biol ; 76(4): 912-927, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27191459

RESUMO

The goal of this study is to analyze the floristic patterns and the structure of disturbed and undisturbed upland forests, in Permanent Preservation Areas (PPAs) along the Moju river, in the Brazilian state of Pará. Trees with a diameter equal to or larger than 10cm at 1.30m from the ground (DBH) ≥10cm were analyzed for the upper stratum. For the middle stratum, individuals with DBH between 4.99 and 9.99cm were sampled. Forty-five families and 221 species were found in disturbed forests, and 43 families and 208 species in undisturbed forests. Floristic similarity was high between strata and between forest types, with values above 50%. Similarity was highest between middle strata. The most species-abundant families in undisturbed forests were Fabaceae, Sapotaceae, Chrysobalanaceae and Myrtaceae; the species with the highest density there were Eschweilera grandiflora, Licania sclerophylla and Zygia cauliflora. In disturbed forests, the dominant families were Fabaceae, Sapotaceae, Lecythidaceae and Melastomataceae. The Shannon-Wiener diversity index was 3.21 for undisturbed forests and 2.85 for disturbed forests. Non-metric multidimensional scaling (MDS) analysis did not group the forests by their floristic composition in both upper and middle strata. Overall, the PPA forests along the Moju river, even if disturbed, did not show major floristic changes but substantially change their structural characteristics.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais , Florestas , Árvores , Brasil , Rios
18.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;53(3): e8876, 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1089338

RESUMO

The immune stimulatory and anti-neoplastic functions of type I interferon have long been applied for the treatment of melanoma. However, the systemic application of high levels of this recombinant protein is often met with toxicity. An approach that provides localized, yet transient, production of type I interferon may overcome this limitation. We propose that the use of mesenchymal stem cells (MSCs) as delivery vehicles for the production of interferon-β (IFNβ) may be beneficial when applied together with our cancer gene therapy approach. In our previous studies, we have shown that adenovirus-mediated gene therapy with IFNβ was especially effective in combination with p19Arf gene transfer, resulting in immunogenic cell death. Here we showed that MSCs derived from mouse adipose tissue were susceptible to transduction with adenovirus, expressed the transgene reliably, and yet were not especially sensitive to IFNβ production. MSCs used to produce IFNβ inhibited B16 mouse melanoma cells in a co-culture assay. Moreover, the presence of p19Arf in the B16 cells sensitizes them to the IFNβ produced by the MSCs. These data represent a critical demonstration of the use of MSCs as carriers of adenovirus encoding IFNβ and applied as an anti-cancer strategy in combination with p19Arf gene therapy.


Assuntos
Animais , Masculino , Coelhos , Melanoma Experimental/terapia , Interferon beta/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/administração & dosagem , Células-Tronco Mesenquimais/metabolismo , Transdução Genética , Melanoma Experimental/metabolismo , Terapia Genética , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
19.
Am J Med Genet ; 98(3): 230-4, 2001 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-11169560

RESUMO

We report on a family with typical clinical findings of Noonan syndrome associated with giant cell lesions in maxilla and mandible. We discuss the obvious clinical overlap between Noonan syndrome and Noonan-like/multiple giant cell lesion syndrome, and we give further clinical and molecular support that these two entities could be allelic conditions.


Assuntos
Granuloma de Células Gigantes/patologia , Síndrome de Noonan/patologia , Adolescente , Adulto , Cromossomos Humanos Par 12/genética , DNA/genética , Diagnóstico Diferencial , Saúde da Família , Feminino , Granuloma de Células Gigantes/genética , Haplótipos , Humanos , Masculino , Repetições de Microssatélites , Síndrome de Noonan/genética , Linhagem , Síndrome
20.
J Periodontol ; 71(6): 1009-14, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10914805

RESUMO

BACKGROUND: Prostaglandins are implicated in periodontal bone destruction. We investigated the effect of a non-selective cyclooxygenase (COX) inhibitor (indomethacin-IND) or a type 2 COX inhibitor (meloxicam-MLX) in an experimental periodontal disease (EPD) model. METHODS: Wistar rats were subjected to placement of a nylon thread ligature around the maxillary molars and sacrificed after 7 days. Alveolar bone loss (ABL) was measured in one quadrant as the distance between the cemento-enamel junction and the alveolar bone. The other quadrant was processed for histopathologic analysis. Daily weight and white blood cell count were recorded. Groups were treated subcutaneously for 7 days with either IND (0.5, 1, or 2 mg/kg) or MLX (0.75, 1.5, or 3 mg/kg). Controls received no treatment. Macroscopic analysis of the gastric mucosa was done. The control group did not receive any manipulation, and a non-treated group consisted of rats subjected to periodontitis that received no pharmacological treatment. RESULTS: In the non-treated (NT) group, there was significant ABL, severe mononuclear influx, and an increase in osteoclast numbers. Significant neutrophilia and lymphomonocytosis occurred at 6 hours and at 7 days, respectively, as compared to controls. Significant weight loss persisted until the seventh day in the NT group. Both IND and MLX reduced ABL and histopathologic changes. Neutrophilia and lymphomonocytosis were also significantly reversed. Both IND and MLX induced earlier weight recovery. The stomachs of the IND (1 and 2 mg/kg) groups presented hemorrhage and ulcers, whereas in the MLX-treated groups, there were mild petechiae just in the 3 mg/kg group. CONCLUSIONS: COX inhibition prevented ABL in this experimental periodontal disease model. MLX displays similar efficacy and less gastric damage than IND. MLX may provide a better risk/benefit ratio in the treatment of human periodontitis than non-selective COX inhibitors.


Assuntos
Perda do Osso Alveolar/prevenção & controle , Inibidores de Ciclo-Oxigenase/uso terapêutico , Isoenzimas/antagonistas & inibidores , Periodontite/prevenção & controle , Peroxidases/antagonistas & inibidores , Processo Alveolar/patologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Peso Corporal , Contagem de Células , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/efeitos adversos , Modelos Animais de Doenças , Indometacina/administração & dosagem , Indometacina/efeitos adversos , Indometacina/uso terapêutico , Injeções Subcutâneas , Contagem de Leucócitos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/patologia , Leucocitose/patologia , Leucocitose/prevenção & controle , Masculino , Meloxicam , Dente Molar , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Osteoclastos/patologia , Prostaglandina-Endoperóxido Sintases , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos , Tiazinas/administração & dosagem , Tiazinas/efeitos adversos , Tiazinas/uso terapêutico , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos , Tiazóis/uso terapêutico , Colo do Dente/patologia
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