RESUMO
Dulcitol was isolated chemically from Celastrus obiculatus Thumb and determined by HPLC. Effects of dulcitol were examined on collagen-induced arthritis (CIA) in DBA/1J mice. From 6 weeks after the first immunization with bovine type II collagen, dulcitol (100 mg/kg body weight/day) was administered orally to immunized mice for 9 weeks. Clinical score of CIA was improved significantly by dulcitol intervention compared with the non-treated CIA mice. Radiographic score of phalangeal destruction was also improved by dulcitol treatment. These findings suggest that dulcitol may play a role in regulation of some inflammatory responses in the present arthritis model. Significant reduction of percentage of CD4+ and CD8+ T cell subsets in the spleen leucocytes of CIA mice was observed by flow cytometry. Almost normal level of CD4+ and CD8+ T cells was observed in dulcitol-treated groups, suggesting T cell-modifying effect of dulcitol in CIA. Weight of spleen was larger in CIA mice and it was not affected by dulcitol. Anti-collagen antibody titer was increased in CIA mice, and it was not affected by dulcitol, either. Improvement of the changes of CD4+ and CD8+ T cells in the spleen by dulcitol may suggest its modulatory effect on cellular immunity.
Assuntos
Artrite/tratamento farmacológico , Colágeno/imunologia , Galactitol/uso terapêutico , Plantas Medicinais/química , Animais , Artrite/imunologia , Relação CD4-CD8 , Bovinos , Modelos Animais de Doenças , Galactitol/isolamento & purificação , Imunidade Celular , Masculino , Camundongos , Camundongos Endogâmicos DBA , Baço/imunologiaAssuntos
Antineoplásicos/uso terapêutico , Benzoquinonas , Neoplasias Ovarianas/tratamento farmacológico , Altretamine/uso terapêutico , Aminoacridinas/uso terapêutico , Amsacrina , Aziridinas/uso terapêutico , Bussulfano/análogos & derivados , Bussulfano/uso terapêutico , Carboplatina , Cisplatino/uso terapêutico , Antagonistas de Estrogênios/uso terapêutico , Feminino , Galactitol/uso terapêutico , Humanos , Ifosfamida/uso terapêutico , Mitomicinas/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Prednimustina/uso terapêutico , Progestinas/uso terapêuticoAssuntos
Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Compostos de Epóxi/efeitos adversos , Compostos de Epóxi/uso terapêutico , Galactitol/efeitos adversos , Galactitol/análogos & derivados , Galactitol/uso terapêutico , Humanos , Mitolactol/efeitos adversos , Mitolactol/uso terapêutico , Tegafur/efeitos adversos , Tegafur/uso terapêutico , Alcaloides de Vinca/efeitos adversos , Alcaloides de Vinca/uso terapêuticoAssuntos
Cárie Dentária/prevenção & controle , Álcoois Açúcares/uso terapêutico , Edulcorantes/uso terapêutico , Animais , Cariogênicos , Criança , Placa Dentária/microbiologia , Carboidratos da Dieta , Galactitol/uso terapêutico , Humanos , Lactoperoxidase/metabolismo , Manitol/uso terapêutico , Ratos , Saliva/enzimologia , Sorbitol/farmacologia , Sorbitol/uso terapêutico , Streptococcus mutans/metabolismo , Xilitol/metabolismo , Xilitol/farmacologia , Xilitol/uso terapêuticoAssuntos
Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Galactitol/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Platina/uso terapêutico , Álcoois Açúcares/análogos & derivados , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Avaliação de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Galactitol/uso terapêutico , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-IdadeRESUMO
The survival and cell kinetics effect of 1,2:5,6-dianhydrogalactitol, NSC-132313 (galactitol), were studied on mammalian cells. Nondividing or plateau-phase cells were almost two times more sensitive to galactitol than were cells treated in the dividing state (dose required to reduce survival by 63% on the exponential part of the survival curve (DO)=4.2 mug/ml/hr for dividing cells vs. DO=2.4 mug/ml/hr in nondividing cells). The survival curves were characterized as having shoulder regions, followed by exponential decreases in survival as the drug doses were increased above 12 mug/ml for 1 hour. Synchronized mitotic and G1 phase cells were equally sensitive to galacitol, with approximately 90% of the cells killed by 1-hour exposures to 12.5 mug galactitol/ml. Cells in early S phase were the least sensitive to this drug dose (survival greater than 20%); however, the cells became more sensitive as they progressed through the S phase and into the G2 phase. There were no large differences observed in survival sensitivities anywhere in the cell cycle, suggesting that galactitol was not a cell-cycle phase-specific agent. Cells in mitosis or G1 phases of the cell cycle at the time of treatment with galacitol progressed normally into the next stage of the cell cycle; however, cells exposed to galactitol in S or G2 phases exhibited dose-dependent delays in those phases of the cell cycle. Nondividing cells exposed to high doses of galactitol could not recover from potentially lethal damage (PLD); however, nondividing cells exposed to lower galactitol doses (lethal dose to 10% of the cells) did exhibit slight recovery from PLD. Dividing cells did not recover from PLD at any of the doses tested. Both dividing and nondividing cells were more sensitive (cell kill) to galactitol when it was administered in two dose fractions 4-8 hours apart than when the same total integral dose was given as a single exposure. A 25-50% greater cell kill was achieved in nondividing cell populations given two dose fractions versus a single exposure to galactitol. Up to 60% greater cell kill was obtained with fractionalated doses in dividing cell populations. These responses to fractionated dose treatments were also dose-dependent.
Assuntos
Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Galactitol/farmacologia , Álcoois Açúcares/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Galactitol/administração & dosagem , Galactitol/análogos & derivados , Galactitol/uso terapêutico , Cinética , Mitose/efeitos dos fármacos , Neoplasias/tratamento farmacológicoAssuntos
Neoplasias da Mama/tratamento farmacológico , Galactitol/uso terapêutico , Piperazinas/uso terapêutico , Razoxano/uso terapêutico , Álcoois Açúcares/uso terapêutico , Ensaios Clínicos como Assunto , Avaliação de Medicamentos , Éteres Cíclicos/uso terapêutico , Feminino , Seguimentos , Galactitol/análogos & derivados , Humanos , Mitolactol/uso terapêuticoAssuntos
Etoposídeo/uso terapêutico , Galactitol/uso terapêutico , Melanoma/tratamento farmacológico , Podofilotoxina/análogos & derivados , Álcoois Açúcares/uso terapêutico , Avaliação de Medicamentos , Quimioterapia Combinada , Éteres Cíclicos/uso terapêutico , Éteres Cíclicos/toxicidade , Etoposídeo/toxicidade , Feminino , Galactitol/análogos & derivados , Galactitol/toxicidade , Humanos , MasculinoRESUMO
Phase II chemotherapy trials of dianhydrogalactitol and VP-16-213 were conducted in patients with metastatic colorectal cancer who had measurable malignant disease which served as indicators of response to therapy. Dianhydrogalactitol was given in a 5-day course at a dosage of 30 mg/m2/day. Toxic reactions included nausea, vomiting, leukopenia, thrombocytopenia, and anemia. There was a definite tendency to a compounding of hematologic toxicity with repeated courses. No evidence of objective therapeutic response was observed among 30 patients treated. VP-16-213 was given at a dosage of 130 mg/m2 on Days 1, 3, and 5. Toxic reactions included nausea, vomiting, alopecia, leukopenia, thrombocytopenia, and anemia. Hematologic toxicity was more severe in patients with elevated serum bilirubin levels. No evidence of objective therapeutic response was observed among 28 patients treated.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Etoposídeo/uso terapêutico , Galactitol/uso terapêutico , Podofilotoxina/análogos & derivados , Neoplasias Retais/tratamento farmacológico , Álcoois Açúcares/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Ensaios Clínicos como Assunto , Avaliação de Medicamentos , Éteres Cíclicos/efeitos adversos , Éteres Cíclicos/uso terapêutico , Etoposídeo/efeitos adversos , Feminino , Galactitol/efeitos adversos , Galactitol/análogos & derivados , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Dianhydrogalactitol was given to 28 patients with a variety of advanced solid tumors on a weekly schedule in iv doses ranging from 2 to 80 mg/m2. No significant toxicity was encountered at doses up to 40 mg/m2/week for 4 weeks. At higher doses mild-to-moderate nausea and vomiting and hematologic toxicity were noted. Thrombocytopenia was more common than granulocytopenia and frequently resolved more slowly. No adverse drug-realted effects on liver, renal, coagulation, or cardiac function were seen. Although no patient had significant antitumor response (as strictly defined), objective improvement was noted in two patients, one with hypernephroma and the other with malignant melanoma. for phase II studies, a weekly dose of 70 mg/m2 is recommended for patients with normal hematopoiesis, with reduction by 25% (55 mg/m2) in patients with extensive prior radiation therapy, prior chemotherapy, and/or widespread metastasis to the bone.
Assuntos
Antineoplásicos/farmacologia , Galactitol/uso terapêutico , Álcoois Açúcares/uso terapêutico , Adulto , Idoso , Agranulocitose/induzido quimicamente , Anemia/induzido quimicamente , Antineoplásicos/efeitos adversos , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Esquema de Medicação , Éteres Cíclicos/uso terapêutico , Feminino , Galactitol/efeitos adversos , Galactitol/análogos & derivados , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Trombocitopenia/induzido quimicamenteRESUMO
A toxicologic evaluation of dianhydrogalactitol in man was completed for a 5- and a 10-day schedule. The maximum tolerated dose was 30 mg/m2/day for the 5-day schedule and 21 mg/m2/day for the 10-day schedule. Dose-limiting myelosuppression occurred with both schedules, with leukopenia and thrombocytopenia being observed at median Days 15 and 19 respectively for the 5-day course and median Days 22 and 26 of the 10-day course. Nausea was infrequent and mild. Responses were obtained in one patient with laryngeal carcinoma and in one patient with adenocarcinoma of the lung.