RESUMO
BACKGROUND: Both irinotecan (CPT-11) and S-1 are active against colorectal cancer; however, as S-1 is a prodrug of 5-fluorouracil (5-FU), 5-FU and its metabolites might inhibit the antitumour effect of CPT-11. Therefore, we designed a sequential combination, in which CPT-11 infusion was given on day 1 and S-1 was given orally at 80 mg m(-2) per day on days 3-16 every 3 weeks. METHODS: Twelve patients entered the phase I study, and the recommended doses were determined as a CPT-11 dose of 150 mg m(-2) and an S-1 dose of 80 mg m(-2). RESULTS: In all, 36 patients entered the phase II study, of whom 4 and 16 had complete and partial responses. The overall response rate was 55.6% (95% confidence interval, 38.1-72.1%), and median progression-free survival was 7.7 months (95% confidence interval, 4.8-12.6 months). Grade 3 neutropenia was the most common haematological toxicity and occurred in 6.5% of 215 treatment courses. Grade 3 non-haematological toxicities included anorexia (1.4%) and diarrhoea (0.9%). There was no grade 4 toxicity of any kind. CONCLUSION: Our results suggest that this regimen is convenient, safe and promising, compared with conventional regimens for patients with metastatic colorectal cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Combinação de Medicamentos , Feminino , Humanos , Irinotecano , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Tegafur/administração & dosagem , Tegafur/efeitos adversosRESUMO
Glucose permeation from blood to saliva appeared to follow the paracellular pathway in rat submandibular and sublingual glands, and the permeability was much higher in the sublingual than in the submandibular gland. The duct system re-absorbed glucose in the submandibular but not the sublingual gland. The glucose concentration in sublingual saliva was inversely related to the flow rate.
Assuntos
Glucose/metabolismo , Saliva/metabolismo , Animais , Estimulação Elétrica , Glucose/antagonistas & inibidores , Masculino , Manitol/metabolismo , Ratos , Ratos Endogâmicos , Taxa Secretória , Glândula Sublingual/metabolismo , Glândula Submandibular/metabolismoRESUMO
The periodontal pocket probing depths of mandibular incisors of plaque-susceptible (Sus) rats, which spontaneously exhibit gingivitis with accumulation of plaque, were increased 20 days after injection of streptozotocin (70 mg/kg, i.v.). The accumulated plaque weights were also increased in Sus rats with streptozotocin diabetes, and a positive correlation was found between the plaque weights and the pocket depths. Histological findings showed that this inflammatory reaction in gingival tissue was higher and more extensive in diabetic Sus rats than in control Sus rats. These findings suggest that the accumulated plaque is the important factor for the severe breakdown of gingival tissue in this experimental model.
Assuntos
Placa Dentária/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Gengivite/fisiopatologia , Animais , Placa Dentária/complicações , Placa Dentária/patologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Suscetibilidade a Doenças , Bolsa Gengival/patologia , Gengivite/etiologia , Gengivite/patologia , Masculino , Ratos , Ratos Endogâmicos , Fatores de TempoAssuntos
Incisivo/fisiologia , Mandíbula/fisiologia , Mastigação , Maxila/fisiologia , Animais , Cães , Oscilometria , CoelhosAssuntos
Peroxidases/metabolismo , Saliva/metabolismo , Glândula Submandibular/metabolismo , Animais , Cateterismo , Cromatografia em Gel , Eletroforese em Gel de Poliacrilamida , Heparina/farmacologia , Imunodifusão , Imunoeletroforese , Injeções Intravenosas , Peso Molecular , Peroxidases/administração & dosagem , Pilocarpina/farmacologia , Coelhos/imunologia , Ratos , Saliva/análise , Sódio , Cloreto de Sódio/farmacologia , Glândula Submandibular/efeitos dos fármacos , Glândula Submandibular/enzimologiaRESUMO
When the chorda tympani was stimulated at 20 Hz, infused horseradish peroxidase (HRP) entered the saliva through the tight junctions in the rat submandibular gland. This response was not inhibited by atropine but was reduced by a substance P(SP)-antagonist. The increase in junctional permeability for HRP never occurred in the gland that was stimulated at 5 Hz or in the SP-depleted gland. Our data suggest that the effect of parasympathetic stimulation on the increase in junctional permeability for macromolecules was due to the release of SP in the gland.
Assuntos
Glândula Submandibular/metabolismo , Substância P/fisiologia , Animais , Permeabilidade da Membrana Celular , Nervo da Corda do Tímpano/fisiologia , Estimulação Elétrica , Peroxidase do Rábano Silvestre/metabolismo , Junções Intercelulares/metabolismo , Masculino , Microscopia Eletrônica , Sistema Nervoso Parassimpático/fisiologia , Ratos , Glândula Submandibular/ultraestrutura , Substância P/antagonistas & inibidoresRESUMO
The damage caused to rat submandibular glands by intraductal injection was examined. When a small volume of isotonic saline was injected, even if salivation was not influenced, salivary composition was greatly affected because the intercellular junctions of the duct cells were damaged. Intraductal injections of hyperosmotic solutions or highly viscous liquids were more effective in damaging intercellular junctions. When interpreting the significance of a salivary composition in clinical diagnosis, it is necessary to consider the sialographic damage which might influence the salivary composition.