Aspirin ; adverse effects ; Drug Hypersensitivity ; epidemiology ; Drug Tolerance ; Humans ; Incidence

OBJECTIVE: Subsequent clinical experiences in risperidone treatment indicated that the initially recommended dose schedule resulted in too rapid increment of doses to the maintenance dose. The goal of this study was to establish a new optimal dose-schedule recommendation for risperidone in patients with schizophrenia. METHODS: Two hundred and eighteen schizophrenic patients were randomly assigned to the following three groups. For the first group, 1 mg of risperidone was administered on the first day, 2 mg on the second day, and the dose was increased from the third day depending on the clinical status of the patients. For second group, 0.5 mg was administered on the first two days, 1 mg on the 3-5th day, 1.5 mg on the 6-7th day, 2 mg on the 8th day, and the dose was increased from the 9th day depending on the clinical status. For third group, 0.5 mg was administered on the first three days, 1mg on the 4-8th day, 1.5 mg on the 9-13th day, 2 mg on the 14th day, and the dose was increased from the 15th day depending on the clinical status. The schizophrenic symptoms were rated by the Positive and Negative Syndrome Scale (PANSS) on days 0, 7, 14, 28 and 48 of the risperidone treatment. The tolerance of the treatment was checked by ESRS, modified UKU, and Global Impression of tolerability. The efficacy and tolerability were compared among the three regimen groups. RESULTS: After 8 weeks of treatment, the PANSS total scores, positive scores and negative scores were not significantly different among the three groups. There were no differences among the three groups regarding tolerability ratings and ESRS rating except gait/posture and tremor items which scores were high in first group at the end of the study. The sedation and fatigability items scores in the first group was significantly more higher than in the second and third group. CONCLUSION: These data suggest that the 2-week titration of risperidone may be the most favorable strategy in the treatment of schizophrenia.
Appointments and Schedules ; Drug Tolerance ; Humans ; Risperidone* ; Schizophrenia* ; Tremor

The benefit of tadalafil should be justified by its safety and tolerance in the chronic treatment of erectile dysfunction (ED) in general and high-risk population. The main treatment-emergent adverse events, chiefly induced by the interactions of tadalafil with PDE5 and isoforms, are mild or moderate in severity, transient and reversible, which may disappear without drug withdrawal. Tadalafil does not add to the risk and severity of cardiovascular problems, and can be safely co-administered with antihypertensives and selective a-receptor blockers.
Carbolines ; adverse effects ; therapeutic use ; Drug Tolerance ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Tadalafil ; Treatment Outcome

Blood Platelets ; physiology ; Cytokines ; blood ; Drug Therapy, Combination ; Humans ; Immune Tolerance ; Thrombocytopenia ; drug therapy ; etiology ; immunology

Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Ovarian Neoplasms ; drug therapy ; radiotherapy ; Radiation Tolerance

OBJECTIVES: The purpose of this study was to aid in the prediction of tumor cell tolerance to radiotherapy and/or chemotherapy. MATERIALS AND METHODS: Human epidermoid carcinoma A-431 cell line were irradiated by 2, 4, 6, 8, 10Gy at a dose rate of 210cGy/min using 60Co Irradiator ALDORADO 8 and then were exposed to bleomycin or cisplatin at concentration of 2mug/mul for 1 hour. The viable cells were determined for each radiation dose and/or each drug at the 4th day and cell surviving curves were obtained using semiautomated MTT assay. RESULTS: The surviving fraction after irradiation of 2Gy was 0.99, and there was not significant difference of surviving fraction in comparison with the control group on A-431 cell line(p>0.05). But there were significant differences of surviving fractions at doses of 4, 6, 8, 10Gy in comparison with the control group(p<0.05). The cytotoxicity of bleomycin or cisplatin was significantly different in comparison with the control group on A-431 cell line (p<0.05). And the cytotoxicity of cisplatin was greater than that of bleomycin on A-431 cell line (p<0.05). There were significant differences of surviving fractions after irradiation of 2, 4, 6, 8, 10Gy with bleomycin or cisplatin in comparison with each group of irradiation only on A-431 cell line(p<0.05). There were significant differences of surviving fractions between the groups of irradiation with bleomycin and cisplatin at doses of 2, 4Gy(p<0.05), but there were not significant differences of surviving fractions at doses of 6, 8, 10Gy on A-431 cell line (p>0.05).
Bleomycin ; Carcinoma, Squamous Cell ; Cell Line* ; Cisplatin ; Drug Therapy ; Humans ; Radiation Tolerance* ; Radiotherapy

OBJECTIVES: The purpose of this study was to aid in the prediction of tumor cell tolerance to radiotherapy and/or chemotherapy. MATERIALS AND METHODS: Human epidermoid carcinoma A-431 cell line were irradiated by 2, 4, 6, 8, 10Gy at a dose rate of 210cGy/min using 60Co Irradiator ALDORADO 8 and then were exposed to bleomycin or cisplatin at concentration of 2mug/mul for 1 hour. The viable cells were determined for each radiation dose and/or each drug at the 4th day and cell surviving curves were obtained using semiautomated MTT assay. RESULTS: The surviving fraction after irradiation of 2Gy was 0.99, and there was not significant difference of surviving fraction in comparison with the control group on A-431 cell line(p>0.05). But there were significant differences of surviving fractions at doses of 4, 6, 8, 10Gy in comparison with the control group(p<0.05). The cytotoxicity of bleomycin or cisplatin was significantly different in comparison with the control group on A-431 cell line (p<0.05). And the cytotoxicity of cisplatin was greater than that of bleomycin on A-431 cell line (p<0.05). There were significant differences of surviving fractions after irradiation of 2, 4, 6, 8, 10Gy with bleomycin or cisplatin in comparison with each group of irradiation only on A-431 cell line(p<0.05). There were significant differences of surviving fractions between the groups of irradiation with bleomycin and cisplatin at doses of 2, 4Gy(p<0.05), but there were not significant differences of surviving fractions at doses of 6, 8, 10Gy on A-431 cell line (p>0.05).
Bleomycin ; Carcinoma, Squamous Cell ; Cell Line* ; Cisplatin ; Drug Therapy ; Humans ; Radiation Tolerance* ; Radiotherapy

Stomach cancer is the most popular tumor in Korea but the prognosis following extensive surgery and chemotherapy has not improved for many years. Conventional external radiotherapy also has some limitation, namely, a cancerocidal dose cannot be delivered to tumors because of low radiation tolerance of adjacent critical sensitive organs. In order to overcome these limitations of curative surgery and external radiotherapy, intraoperative radiotherapy was proposed in many centers and the results were excellent. We treated two cases of locally advanced gastric cancers with IORT by using NEC 18 MeV Linear Accelerator after standard subtotal resection of the stomach. After treatment, the patients are in good conditions so far, but in order to evaluate the effectiveness of IORT, a study will be performed on the survival rates between patients treated by IORT and those treated by surgery alone.
Drug Therapy ; Humans ; Korea ; Particle Accelerators ; Prognosis ; Radiation Tolerance ; Radiotherapy ; Stomach ; Stomach Neoplasms* ; Survival Rate

The purpose of this study was to aid in the prediction of tumor cell tolerance to radiotherapy and/or chemotherapy. For this study, cell surviving curves were obtained for human epidermoid carcinoma A-253 cell line using semiautomated MTT assay. 2, 4, 6, 8, 10 Gy were irradiated at a dose rate of 210 cGy/min using 60Co Irradiator ALDORADO 8. After irradiation, A-253 cell lines(2x10(4) cells/ml) were exposed to bleomycin or cisplatin for 1 hour. The viable cells were determined for each radiation dose with/without 2 ug/ml of drug at the 3rd day. And they were compared to control values. The results were obtained as follows: 1. The surviving curve with gentle slope was obtained after irradiation of 2, 4, 6, 8, 10 Gy on A-253 cell line. 2. The cytotoxicity of bleomycin or cisplatin at the concentration of 2 ug/ml was great on A-253 cell line. But, there was no significant difference between the cytotoxicity of bleomycin and that of cisplatin. 3. There were significant differences of surviving fractions after irradiation with 2 ug/ml of bleomycin compared with irradiation only on A-253 cell line. 4. There were significant differences of surviving fractions after irradiation with 2 ug/ml of cisplatin compared with irradiation only on A-253 cell line. 5. There were no significant differences of surviving fractions between the groups of irradiation with bleomycin and the groups of irradiation with cisplatin on A-253 cell line.
Bleomycin ; Carcinoma, Squamous Cell ; Cell Line* ; Cisplatin ; Drug Therapy ; Humans ; Radiation Tolerance* ; Radiotherapy

OBJECTIVESaccharomyces albicons is the main opportunistic pathogen which is also the common member of oral microflora, and the biofilms they formed have spontaneous drug tolerance compared with planktonic ones. Saccharomyces biofilm population can produce subpopulation of cells which can tolerant high concentration of antifungal drugs. They are called persisters. Many researches indicated that drug efflux gene such as CDR or MDR gene plays the very important roles in yeast drug resistance. The objective of this study is to illuminate the mechanism of Saccharomyces albicons biofilm drug tolerance related with drug efflux gene, especially to the persisters formation.

METHODSTest the minimal inhibitory concentration (MIC) and SMIC80 (sessile minimal inhibitory concentration 80%) of 24 h biofim of totally 7 defective strains of drug efflux pump gene with Amphotercin B. And treat the 24 h biofilm by fluconazole, micronazole, clotrimazole combined with CDR1 inhibitor Enniatin B respectively and antifungal drugs alone as control, then scrapped the biofilm, cultured on the YPD agar. By CFU counting, the numbers of biofilm persisters were determined.

RESULTSAll the defective strains have the similar MIC and SMIC80 for 24 h biofilm with wide type strains. CDR1 inhibitor Enniatin B can help antifungal drugs especially micronazole and clotrimazole to eliminate the biofilm persisters.

CONCLUSIONSaccharomyces albicans drug efflux gene may minor associated with 24 h biofilm drug tolerance. Drug efflux gene CDR1 may play an role in persisiters related biofilm drug tolerance.