RESUMO
A pulmonary tuberculosis mouse model was used to assess the pharmacodynamic and pharmacokinetic characteristics of tuberculosis therapeutics. While membrane transporters play important roles in drug disposition and physiological homeostasis, their expressional changes and contribution have never been analysed in a tuberculosis animal model. The mRNA expression level of 20 Abc family transporters and 32 Slc family transporters in tuberculosis-infected mice were compared with those in naïve uninfected mice using real-time polymerase chain reaction (PCR). Mycobacterium tuberculosis infection induced many dramatic expression changes of families of both Abc transporters and Slc transporters at 4 and 8 weeks, as observed in the livers, kidneys, and intestines of test mice--and in a different mode, in the lungs and spleens as well. These changes were dependent on the tuberculosis progression with the tissue-specific manner, that is, in the lungs, the number of transporters of which the expression level changed due to M. tuberculosis infection had increased, and the magnitude of change also greater at 8 weeks, while in the spleen, the transcription of most transporters except Mrps had not changed or had recovered back to the same level of naïve transcription at 8 weeks. Understanding the expression changes of transporters will assist in setting up rational preclinical dosing plans through the ability to predict the pharmacokinetics of new anti-tuberculosis chemotherapeutics and, furthermore, will assist in the design of safer and more efficient drug regimens.
Assuntos
Transportadores de Cassetes de Ligação de ATP/biossíntese , Proteínas de Transporte de Ânions/biossíntese , Citocinas/metabolismo , Mycobacterium tuberculosis , RNA Mensageiro/biossíntese , Tuberculose Pulmonar/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Tuberculose Pulmonar/microbiologiaRESUMO
The effects of folic acid-induced acute renal failure on the renal excretion of belotecan were investigated in rats after intravenous administration. Both glomeruli and renal tubules were seriously damaged by folic acid-induced acute renal failure. The renal excretion clearance, CLr, of belotecan was significantly decreased by folic acid-induced acute renal failure. Furthermore, glomerular filtration rate and secretion clearance of the drug were dramatically decreased by folic acid-induced acute renal failure. In vivo renal uptake of belotecan was inhibited by p-aminohippurate, whereas renal excretion was inhibited by GF120918, but not by verapamil and bromosulphalein. This indicates that Oat1/3 and Bcrp are involved in the renal uptake and urinary excretion of belotecan, respectively. Both mRNA and protein levels of Oat1, Oat3 and Bcrp were significantly decreased in folic acid-induced acute renal failure rats. Based on the finding that belotecan is a substrate of OAT1 but not of OAT3, the decrease in CLr of belotecan in folic acid-induced acute renal failure could, therefore, mainly be attributed to the down-regulation of Oat1 and Bcrp, in addition to the decrease in glomerular filtration rate.
Assuntos
Injúria Renal Aguda/metabolismo , Antineoplásicos/farmacocinética , Antineoplásicos/urina , Camptotecina/análogos & derivados , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Transportadores de Cassetes de Ligação de ATP/metabolismo , Acridinas/farmacologia , Injúria Renal Aguda/induzido quimicamente , Animais , Antineoplásicos/química , Bloqueadores dos Canais de Cálcio/farmacologia , Camptotecina/química , Camptotecina/farmacocinética , Camptotecina/urina , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Ácido Fólico/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Indicadores e Reagentes/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Proteína 1 Transportadora de Ânions Orgânicos/antagonistas & inibidores , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Ratos , Ratos Sprague-Dawley , Tetra-Hidroisoquinolinas/farmacologia , Verapamil/farmacologia , Complexo Vitamínico B/farmacologia , Ácido p-Aminoipúrico/farmacologiaRESUMO
Cardiovascular manifestations have been reported in 7-38% of patients with Behçet's disease (BD), and mortality occurs in up to 20% of those with marked vascular involvement. Sporadic cases of endocarditis, myocarditis, pericarditis, acute myocardial infarction, aortic aneurysm, ventricular thrombosis, congestive cardiomyopathy, and valvular dysfunction have been reported. Here we report a case of acute myocardial infarction that resulted from the compression of coronary arteries by a sinus of Valsalva aneurysm in a patient with BD.
Assuntos
Aneurisma Aórtico/complicações , Síndrome de Behçet/complicações , Infarto do Miocárdio/etiologia , Seio Aórtico , Aneurisma Aórtico/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Seio Aórtico/patologiaRESUMO
OBJECTIVE: To determine the association between angiogenic factor mRNA expression and disease activity and radiographic damage in patients with rheumatoid arthritis (RA). METHODS: We enrolled 42 RA patients and assessed their disease activity (DAS28) and Larsen scores. We used a semi-quantitative reverse transcriptase-polymerase chain reaction to measure levels of angiogenin, endoglin, survivin and angiomotin mRNA in peripheral blood mononuclear cells (PBMCs) from 42 patients and in fibroblasts-like synoviocytes (FLS) from 14 RA patients. Then, we compared the angiogenic factor mRNA expression levels and parameters for disease activity and radiographic damage between RA patients and 42 healthy controls. We also compared the mRNA levels from FLS between 14 RA patients and 12 osteoarthritis (OA) patients. RESULTS: PBMCs from RA patients showed increased expression of survivin and angiomotin mRNA compared to controls, while rheumatoid FLS showed increased expression for all genes tested compared to OA FLS. Angiogenin, endoglin, and angiomotin mRNA levels of PBMCs did not show any significant correlation with DAS28, but the survivin mRNA level in PBMCs showed a significant positive correlation with DAS28 (p=0.003) and Larsen scores (p=0.012). Survivin was the only angiogenic factor that showed a significant association with the Larsen score. CONCLUSION: The systemic and local production of angiogenic factors are increased in patients with RA and, of the genes tested in this study, survivin gene expression correlated well with disease activity and radiographic damage in patients with RA.
Assuntos
Indutores da Angiogênese/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico por imagem , Angiomotinas , Antígenos CD/genética , Antígenos CD/metabolismo , Artrite Reumatoide/genética , Estudos de Casos e Controles , Endoglina , Fibroblastos/metabolismo , Humanos , Proteínas Inibidoras de Apoptose , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Leucócitos Mononucleares/imunologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Osteoartrite/genética , RNA Mensageiro/imunologia , RNA Mensageiro/metabolismo , Radiografia , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Ribonuclease Pancreático/genética , Ribonuclease Pancreático/metabolismo , Índice de Gravidade de Doença , Survivina , Membrana Sinovial/metabolismoRESUMO
This study was conducted to investigate the sensory interactions between various organic acids and flavorants in 3 types of ramen soup ('beef,' seafood, and 'kimchi') when types and levels of organic acids (citric, malic, and lactic) varied. For 'beef' and seafood ramen soup, weak suprathreshold levels of acids (0.0039% to 0.0071%) were applied to the system and medium suprathreshold of acids (0.0128% to 0.0299%) were applied to the kimchi ramen soup. The amount of acid applied to each system was chosen based on the equiweight level. Descriptive analyses were performed separately for each ramen soup system using 8 trained panelists. A total of 11, 13, and 12 flavor descriptors were generated for 'beef,' seafood, and 'kimchi' soup, respectively. Analysis of variance was conducted to evaluate the effect of organic acid on the sensory characteristics of ramen soup. Principal component analysis was conducted to summarize the relationship between the soup samples and attributes. The effect of organic acids on the flavor attributes of ramen soup was dependent on the soup system as well as adding levels of acid. Addition of lactic acid power (at 0.0066%) in 'beef'ramen soup showed enhancement effect on the sour, salty, beefy, 'mushroom' flavor, and fermented soybean paste soup flavor, whereas lactic acid powder (at 0.0071%) showed enhancement effect only on the sour and fermented soybean paste soup flavor in seafood ramen soup due to the strong 'hot' flavor characteristics of the soup. In kimchi ramen soup, flavor attributes congruent to sourness were enhanced by the addition of organic acids to the system.
Assuntos
Ácidos Carboxílicos , Aromatizantes , Paladar/fisiologia , Análise de Variância , Animais , Ácidos Carboxílicos/farmacologia , Bovinos , Ácido Cítrico/farmacologia , Relação Dose-Resposta a Droga , Aromatizantes/farmacologia , Humanos , Ácido Láctico/farmacologia , Malatos/farmacologia , Carne , Odorantes , Análise de Componente Principal , Alimentos Marinhos , Olfato/efeitos dos fármacos , Olfato/fisiologia , Alimentos de Soja , Estudantes , Paladar/efeitos dos fármacosRESUMO
One of the most important initial steps in exporting a food product to another country from the R&D perspective is to describe and translate the sensory characteristics of a food product appropriately into the language of the target country. The objectives of this study were to describe and compare the sensory characteristics of Korean and Japanese style fermented soybean products, and to cross-culturally compare the lexicons of the identical product generated by the Korean and Japanese panelists. Four types of Korean and 4 types of Japanese style fermented soybean consisting of whole bean type and paste type were analyzed. Ten Korean and 9 Japanese panelists were recruited in Korea. Two separate descriptive analyses were conducted, with the panelists differing in their country of origin. Each group was trained, developed lexicon, and conducted descriptive analysis independently. Analysis of variance and various multivariate analyses were applied to delineate the sensory characteristics of the samples and to compare the cross-cultural differences in the usage of lexicon. The Korean and Japanese panelists generated 48 and 36 sensory attributes, respectively. Cross-cultural consensus was shown for evaluating the whole bean type fermented soybean and white miso, which were relatively distinctive samples. However, for the less distinctive samples, the panelists tend to rate higher in negative attributes for the fermented soybeans that originated from the other country. The Japanese panelists grouped the samples by their country of origin and soy sauce flavor was the main attribute for cross-cultural differentiation. However, the Korean panelists did not make a cross-cultural distinction among the samples.
Assuntos
Comparação Transcultural , Fermentação , Glycine max , Olfato/fisiologia , Alimentos de Soja , Paladar/fisiologia , Adesividade , Adulto , Análise de Variância , Feminino , Humanos , Japão , Coreia (Geográfico) , Masculino , Odorantes , Análise de Componente Principal , Terminologia como Assunto , TatoRESUMO
OBJECTIVE: To relate the use of identified processes that college women use to eat enough fruits and enough vegetables to their stages of readiness to change and their fruit and vegetable (F/V) intakes. METHOD: A cross-sectional assessment of college women 18-24 years of age (n = 236) was conducted to assess stage of readiness to eat F/V. Use of seven processes, earlier confirmed in a separate sample of college students the same age (health concerns, self-reevaluation, social liberation, health commitment/action, interpersonal control, external reinforcement and helping relationships) was compared with stage of change for F/V and 3 days of dietary intakes. RESULTS: In these young college women, use of self-reevaluation, a cognitive process for change, peaked in the preparation stage for both F/V. Use of health commitment/action, a post-action process including counter-conditioning, peaked in those in action/maintenance for F/V. Weight concerns related to the counter-conditioning processes women used to eat more fruit. CONCLUSION: Health practitioners should focus on weight management, appearance and health benefits of eating fruits and vegetables for this demographic group.