RESUMO
O objetivo do presente trabalho foi avaliar a cinética de secagem das folhas de erva baleeira (Cordia verbenacea DC.) bem como ajustar diferentes modelos matemáticos aos valores experimentais de razão de umidade. As folhas de erva baleeira foram colhidas com teor de água inicial de 75% b.u., sendo submetidas à secagem sob condições controladas de temperatura (40, 50, 60 e 70°C), até o teor de água aproximado de 10% b.u.. Aos dados experimentais foram ajustados oito modelos matemáticos citados na literatura específica e utilizados para a representação do processo de secagem de produtos agrícolas. Com base nos resultados obtidos pôde-se concluir que o modelo de Midilli é o que melhor representa a cinética de secagem das folhas de erva baleeira. O aumento da temperatura do ar de secagem promoveu maior taxa de remoção de água do produto. O coeficiente de difusão efetivo aumenta com a elevação da temperatura, sendo que sua relação com a temperatura de secagem pode ser descrita pela equação de Arrhenius. A energia de ativação para a difusão líquida durante a secagem das folhas de erva baleeira foi de 62,89 kJ mol-1 .
The objective of the present work was to evaluate the drying kinetics of Cordia verbanacea DC. leaves, as well to fit different mathematical models to the experimental data of the moisture ratio. The Cordia verbanacea Dc. leaves wers harvested with initial moisture content of approximately 75% w.b. and submitted to the drying process under controlled conditions of temperature (40, 50 60 and 70ºC), until the approximate moisture content of 10% w.b. Eight mathematical models mentioned or the specific literature were fitted to the experimental data and used to predict the drying process of the agricultural products. Based on the results obtained,swe have concluded that the Midilli model was the one that best represents the drying kinetics of Cordia verbanacea leaves. The temperature increase of the drying air promotes higher removal rate of water from the product. The effective diffusion coefficient increases with temperature elevation,tand its relationship with the drying temperature can be described through the Arrhenius equation, which presents activation energy of 62.89 kJ mol-1 for the liquid diffusion during the drying of the Cordia verbanacea DC. leaves.
Assuntos
Folhas de Planta , Cordia/classificação , Plantas Medicinais/classificação , Componentes Aéreos da Planta/crescimento & desenvolvimento , Umidade/prevenção & controleRESUMO
Interferon (IFN)-based combination therapy with ribavirin has become the gold standard for the treatment of chronic hepatitis C virus infection. Haematologic toxicities, such as neutropenia, thrombocytopenia, and anaemia, however, frequently cause poor treatment tolerance, resulting in poor therapeutic efficacy. The aim of this study was to identify host genetic polymorphisms associated with the efficacy or haematologic toxicity of IFN-based combination therapy in chronic hepatitis C patients. We performed comprehensive single nucleotide polymorphism detection in all exonic regions of the 12 genes involved in the IFN signalling pathway in 32 healthy Japanese volunteers. Of 167 identified polymorphisms, 35 were genotyped and tested for an association with the efficacy or toxicity of IFN plus ribavirin therapy in 240 chronic hepatitis C patients. Multiple logistic regression analysis revealed that low viral load, viral genotypes 2 and 3, and a lower degree of liver fibrosis, but none of the genetic polymorphisms, were significantly associated with a sustained virologic response. In contrast to efficacy, multiple linear regression analyses demonstrated that two polymorphisms (IFNAR1 10848-A/G and STAT2 4757-G/T) were significantly associated with IFN-induced neutropenia (P = 0.013 and P = 0.011, respectively). Thrombocytopenia was associated with the IRF7 789-G/A (P = 0.031). In conclusion, genetic polymorphisms in IFN signalling pathway-related genes were associated with IFN-induced neutropenia and thrombocytopenia in chronic hepatitis C patients. In contrast to toxicity, the efficacy of IFN-based therapy was largely dependent on viral factors and degree of liver fibrosis.
Assuntos
Hepatite C Crônica/tratamento farmacológico , Interferons/efeitos adversos , Interferons/uso terapêutico , Polimorfismo Genético , Adulto , Idoso , Feminino , Genótipo , Humanos , Fator Regulador 7 de Interferon/genética , Japão , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Mutação Puntual , RNA Viral/genética , Receptor de Interferon alfa e beta/genética , Fator de Transcrição STAT2/genética , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The effect of the prostaglandin E2 (PGE2) signal through prostaglandin E receptor 2 (EP2) receptors on the repair of injured articular cartilage was investigated using a selective agonist for EP2. METHODS: Chondral and osteochondral defects were prepared on the rabbit femoral concave in both knee joints, and gelatin containing polylactic-co-glycolic acid microspheres conjugated with or without the EP2 agonist was placed nearby. Animals were sacrificed at 4 or 12 weeks post-operation, and regenerated cartilage tissues and subchondral structure remodeling were evaluated by histological scoring. The quality of regenerated tissues was also evaluated by the immunohistochemical staining of EP2, type II collagen, and proliferating cell nuclear antigen (PCNA). As an evaluation of side effects, the inflammatory reaction of the synovial membrane was analyzed based on histology and the mRNA expression of matrix metalloproteinase3 (MMP3), tissue inhibitor of metalloproteinase 3 (TIMP3), and interleukin-1 beta (IL-1 beta). Also, the activity of MMP3 and the amount of tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein in joint fluid were measured. RESULTS: In both models, the EP2 agonist enhanced the regeneration of the type II collagen-positive tissues containing EP2- and PCNA-positive chondrocytes, and the histological scale of regenerated tissue and subchondral bone was better than that of on the control side, particularly at 12 weeks post-operation. No inflammatory reaction in the synovial membrane was observed, and no induction of pro-inflammatory cytokines was found in joint fluid. CONCLUSION: Selective stimulation of the PGE2 signal through EP2 receptors by a specific agonist promoted regeneration of cartilage tissues with a physiological osteochondral boundary, suggesting the potential usefulness of this small molecule for the treatment of injured articular cartilages.
Assuntos
Cartilagem Articular/lesões , Dinoprostona/fisiologia , Receptores de Prostaglandina E/fisiologia , Regeneração/fisiologia , Animais , Proteína C-Reativa/metabolismo , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Cartilagem Articular/fisiologia , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Metaloproteinase 3 da Matriz/metabolismo , Coelhos , Receptores de Prostaglandina E/agonistas , Receptores de Prostaglandina E Subtipo EP2 , Regeneração/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Líquido Sinovial/metabolismo , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Fifteen new N-containing maltooligosaccharides were obtained using the chemoenzymatic method. Among these compounds, maltooligosaccharides having 6-amino-6-deoxy-D-sorbitol residue, (3R,4R,5R,6S)-hexahydro-3,4,5,6-tetrahydroxy-1H-azepine residue, and (3R,5R)-3,4,5-trihydroxypiperidine residue at the reducing end showed strong inhibitory activities for human pancreatic alpha-amylase (HPA) (EC 3.2.1.1) and human salivary alpha-amylase (HSA). The administration of (3R,4R,5R,6S)-hexahydro-3,5,6-trihydroxy-1H-azepine-4-yl O-alpha-D-glucopyranosyl-(1-->4)-alpha-D-glucopyranoside (13, IC50 = 4.3 x 10(-5) M for HPA, IC50 = 8.2 x 10(-5) M for HSA) and (3R,5R)-3,5-dihydroxypiperidine-4-yl O-alpha-D-glucopyranosyl-(1-->4)-alpha-D-glucopyranoside (18, IC50 = 3.4 x 10(-5) M for HPA, IC50 = 4.6 x 10(-5) M for HSA) to ICR mice suppressed postprandial hyperglycemia.
Assuntos
Azepinas/síntese química , Dissacarídeos/síntese química , Inibidores Enzimáticos/síntese química , Piperidinas/síntese química , alfa-Amilases/antagonistas & inibidores , Animais , Azepinas/farmacologia , Glicemia/metabolismo , Sequência de Carboidratos , Dissacarídeos/farmacologia , Inibidores Enzimáticos/farmacologia , Inibidores de Glicosídeo Hidrolases , Humanos , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/síntese química , Hipoglicemiantes/farmacologia , Intestino Delgado/enzimologia , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos ICR , Dados de Sequência Molecular , Pâncreas/enzimologia , Piperidinas/farmacologia , Período Pós-Prandial , Ratos , Glândulas Salivares/enzimologiaRESUMO
Ten new 6(3)-modified maltopentaoses and tetraoses were synthesized by enzymatic reactions utilizing cyclodextrin glycosyltransferase (EC 2.4.1.19) and subsequent human salivary alpha-amylase (HSA) (EC 3.2.1.1). Among these compounds, alpha-D-glucopyranosyl-(1-->4)- alpha-D-glucopyranosyl-(1-->4)-(6-deoxy-alpha-D-glucopyranosyl)-(1-->4)- alpha-D-glucopyranosyl-(1-->4)-D-glucopyranose (11) and alpha-D-glucopyranosyl-(1-->4)-(6-deoxy-alpha-D-glucopyranosyl)-(1-->4)- alpha-D-glucopyranosyl-(1-->4)-D-glucopyranose (12) showed strong inhibitory activities for human pancreatic alpha-amylase (HPA) and HSA. The IC50 of 6(3)-deoxymaltopentaose 11 (8.0 x 10(-5) M for HPA, 1.0 x 10(-4) M for HSA) and 6(3)-deoxymaltotetraose 12 (2.0 x 10(-3) M for HPA, 2.0 x 10(-3) M for HSA) were lower than that of 6(3)-deoxymaltotriose [(6-deoxy-alpha-D-glucopyranosyl)-(1-->4)-alpha-D- glucopyranosyl-(1-->4)-D-glucopyranose 13; 2.0 x 10(-3) M for HPA, 4.2 x 10(-2) M for HSA].
Assuntos
Inibidores Enzimáticos/síntese química , Glucosiltransferases/metabolismo , Oligossacarídeos/síntese química , Oligossacarídeos/farmacologia , alfa-Amilases/metabolismo , Configuração de Carboidratos , Sequência de Carboidratos , Inibidores Enzimáticos/farmacologia , Humanos , Indicadores e Reagentes , Cinética , Dados de Sequência Molecular , Estrutura Molecular , Pâncreas/enzimologia , Saliva/enzimologia , Relação Estrutura-Atividade , alfa-Amilases/antagonistas & inibidoresAssuntos
Glicosídeo Hidrolases , Oligossacarídeos/síntese química , Bacillus/enzimologia , Configuração de Carboidratos , Sequência de Carboidratos , Glicosídeo Hidrolases/metabolismo , Indicadores e Reagentes , Cinética , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Oligossacarídeos/química , Rotação OcularRESUMO
Constant exposure of mastocytoma P-815 cells to adenosine 3',5'-cyclic decylphosphoramidate (1), which is permeable to the cell membrane and resistant to the action of phosphodiesterase, caused a dose-dependent (1 to 50 microM) inhibition in the synthesis of DNA and cell proliferation. Pretreating the cells with compound 1 (20 microM, 4 h) caused considerable inhibition of the incorporation of [3H]thymidine ([3H]TdR) into [3H]deoxythymidine 5'-triphosphate ([3H]dTTP) and that of [14C]hypoxanthine into nucleic acid, but not the synthesis of [14C]dTTP from [U-14C]aspartate. These results indicate that compound 1 preferentially inhibits the salvage synthesis of intracellular nucleotides and nucleic acids. Thymidine kinase, a key enzyme in salvage synthesis of nucleotides, was almost undetectable in cells pretreated with compound 1 at 20 microM for 4 h or at 5 microM for 15 h. On the other hand, compound 1 activated partially purified cAMP-dependent protein kinase A from bovine heart. Judging from these observations, it is likely that compound 1 readily permeates the cell membrane, activates cAMP-dependent protein kinase, then inhibits the salvage synthesis of nucleotides and nucleic acids by inhibiting thymidine kinase, which results in the inhibition of cell growth.
Assuntos
AMP Cíclico/análogos & derivados , Reparo do DNA/efeitos dos fármacos , DNA de Neoplasias/biossíntese , Sarcoma de Mastócitos/metabolismo , Ácidos Nucleicos/biossíntese , Animais , Ácido Aspártico/metabolismo , Bovinos , Divisão Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , AMP Cíclico/farmacologia , Humanos , Hidrólise , Hipoxantinas/metabolismo , Miocárdio/enzimologia , Diester Fosfórico Hidrolases/metabolismo , Proteínas Quinases/metabolismo , Timidina Quinase/metabolismo , Nucleotídeos de Timina/metabolismo , Células Tumorais CultivadasRESUMO
The inhibitory effects of 12 synthetic N6-alkyl cAMPs, 8-substituted cAMPs and cAMP alkylphosphoramidate derivatives (50 or 100 mg/kg, bolus, i.p.) on serum GOT and GPT activities and hepatocyte cytoplasmic vacuolation were examined in male Fischer 344 rats, which were exposed to CCl4 (0.5 mg/kg, p.o.) 30 min prior to the administration of cAMP derivatives. In CCl4-treated rats 6 h later, serum GOT and GPT levels were elevated 10- and 12-fold higher than those of vehicle rats, respectively. Treating CCl4-exposed rats with all cAMP derivatives, except those of alkylphosphoramidate, significantly decreased the levels of serum enzymes. Based on the effects of both serum GOT and GPT elevation, N6-butyl- and N6-heptyl-cAMP were the most potent. It was also observed histopathologically, that both compounds inhibited the occurrence of cytoplasmic vacuolation in CCl4-treated liver cells. This is the first report that cAMP derivatives possess a protective effect in the liver injury model induced by CCl4.
Assuntos
Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas , AMP Cíclico/análogos & derivados , Fígado/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , AMP Cíclico/farmacologia , Citoplasma/efeitos dos fármacos , Citoplasma/ultraestrutura , Fígado/ultraestrutura , Hepatopatias/patologia , Masculino , Ratos , Ratos Endogâmicos F344 , Vacúolos/efeitos dos fármacos , Vacúolos/ultraestruturaRESUMO
A series of adenosine 3',5'-cyclic monophosphoramidates (3, cAMP amidates), including long-chain alkyl amidates, were synthesized from adenosine 3',5'-cyclic monophosphate (1, cAMP) by means of a one-pot reaction. This reaction proceeded by the treatment of cAMP tributylammonium salt (2) with phosphorus pentachloride (PCl5) and alkylamine in N,N-dimethylformamide (DMF). Compounds 3 synthesized were investigated to determine their cytotoxic activities on the growth of mouse mastocytoma P-815 cells, mouse mammary tumor FM3A cells, and human mammary tumor ZR-75 cells in culture. It was found that compounds 3h-m showed significant cytotoxic activities against these cell lines, and that cAMP decylamidate (3j) was the most cytotoxic compound (the concentration required for 50% inhibition of cell growth, ID50 = 6.0, 15.0, 2.2 microM, respectively); the antitumor effect on P-815 cells by a total packed cell volume method showed 81.8% inhibition. The cytotoxic activity of 3 increased with the increase in alkyl chain length up to 10 carbon atoms and decreased in compounds having longer alkyl chain.
Assuntos
Monofosfato de Adenosina/análogos & derivados , Antineoplásicos/síntese química , Monofosfato de Adenosina/síntese química , Monofosfato de Adenosina/farmacologia , Animais , Antineoplásicos/farmacologia , DNA de Neoplasias/biossíntese , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Derivatives of adenosine 3',5'-cyclic monophosphate (cAMP) with modifications at the 8-position were synthesized and examined for their cytotoxic effects on FM3A mouse mammary tumor cells and ZR-75 human mammary tumor cells. On in vitro tests of these derivatives, 8-amino (8-NH2) cAMP was the most effective against both cell lines. This compound showed the dose-dependent inhibition of FM3A cell growth in the concentration of over 2.5 microM with the ID50 value of 4 microM. Furthermore, antitumor activity of 8-NH2 cAMP was also tested against FM3A cells in vivo. T/C% values of 8-NH2 cAMP were respectively 162% and 138% in response to doses of 30 and 10 mg/kg by intraperitoneal injections of 8-NH2 cAMP for 5 d. 8-NH2 cAMP was converted to 8-NH2 adenosine via 8-NH2 adenosine 5'-monophosphate by some enzymes in the fetal bovine serum and the cytotoxic effect of 8-NH2 cAMP on FM3A cells was actually stemmed from 8-NH2 adenosine.