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Biomedical subjects

S Tsuda

Publications and source records attributed to S Tsuda.

At least 235 records · Page 13Linked to original sources
PubMed1986

[Clinical evaluation of cefmenoxime in severe infections in leukemia and related disorders].

Ninety nine patients with leukemia and/or related disorders were treated with cefmenoxime (CMX). Among them, 77 patients had severe infections, while other 22 patients did not suffer from infection, but it was expected that they would fall into serious conditions if they were infected. Sixty of the 77 patients who had severe infection were used in the evaluation of effectiveness. The remaining 17 patients were not evaluated because they were subjected to combined treatments of CMX and other therapeutic agents such as other antibiotics, gamma-globulin or interferon. Excellent responses were found in 26 (43.3%) patients and good responses in 12 (20.0%) patients. In total, the rate of effectiveness was 63.3%. Nineteen of the 22 patients who were treated prophylactically with CMX were used in the evaluation of effectiveness, while 3 patients were excluded from the evaluation because peripheral neutrophils were counted to be more than 1,000/mm3 before CMX was administrated, although these 3 patients were used in the final evaluation to examine side effects. In the prophylactic treatment, the rate of effectiveness was 89.5%. The side effects were seen in 4 patients (4/82:4.9%). A different symptom was identified in each patient. These symptoms were skin rash, mild nausea, mild diarrhea and slight elevation of serum bilirubin. Prompt improvements of these symptoms occurred as soon as CMX administration was stopped. These results show that CMX is a therapeutically effective and safe antibiotics for the treatment of severe infections or for the prophylaxis of infections in patients associated with leukemia and/or related disorders.

Adolescent↗
PubMed1985

Sister chromatid exchanges induced by cancer chemotherapeutic agents in vitro and in vivo: consideration of the hazard of drugs as possible mutagens and carcinogens causing second malignancies.

Sister chromatid exchanges (SCEs) induced by chemotherapeutic agents currently used for treating various malignancies were studied in vitro and in vivo. Whether the agents are potentially mutagenic/carcinogenic is discussed on the basis of recent clinicopathological observations on secondary malignancy. In the in vitro studies, the induction of SCEs by various anticancer agents, including three anticancer antibiotics, six alkylating agents, and three antimetabolites, was examined and compared with induction by two known carcinogens, 4-nitroquinoline 1-oxide and N-ethyl-N'-nitronitrosoguanidine. In the in vivo studies, SCE frequencies were examined in the lymphocytes from 74 blood samples drawn from 40 patients with cancer or leukemia at various times after the agents had been administered alone or in combination. The SCE frequencies induced by the anticancer antibiotics were variable because the drugs had different modes of action: generally, the drugs have strong cytotoxicity that must affect the viability of cells. On the other hand, alkylating agents induced significantly high levels of SCE frequencies in vitro; the modes of SCE inducibility were similar to those of the two carcinogens. The fact that cells were viable up to relatively high molar concentrations of the agents and that high SCE levels persisted for a long period suggests that the lesions induced by alkylating agents are long-lived and may therefore be more frequently involved in mutagenesis. This finding may be compatible with the clinical observation that the vast majority of patients with second malignancy are found in the group treated with alkylating agents. Antimetabolites generally showed only a weak SCE induction or none in vivo and in vitro.

Alkylating Agents↗
PubMed1984

Potentiated toxicity of 2-sec-butylphenyl methylcarbamate (BPMC) by O,O-dimethyl O-(3-methyl-4-nitrophenyl)phosphorothioate (fenitrothion) in mice; relationship between acute toxicity and metabolism of BPMC.

Fenitrothion of oral subtoxic dose (100 mg/kg; 4 hr pretreatment) decreased acute oral LD50 of BPMC from 360 to 66 mg/kg in male mice. The treatment prolonged the hexobarbital sleeping time and increased the plasma BPMC concentrations. The BPMC toxicity and its plasma concentrations were significantly reduced by phenobarbital treatment (80 mg/kg/day, 2 days, ip). This treatment diminished the effects of fenitrothion on BPMC toxicity and plasma BPMC concentrations. BPMC was metabolized by mixed-function oxidases of the liver in vitro. The metabolism of BPMC was competitively inhibited by the addition of fenitrothion (5 micrograms/ml). Fenitrothion remained in the liver (7 micrograms/g liver). These results suggest that competitive inhibition of BPMC metabolism by fenitrothion may, at least in part, play a role in inhibition of BPMC detoxication, resulting in potentiation of its toxicity.

Animals↗
PubMed1984

Pharmacokinetic analysis of increased toxicity of 2-sec-butylphenyl methylcarbamate (BPMC) by fenitrothion pretreatment in mice.

The potentiating effect of O,O-dimethyl O-(3-methyl-4-nitrophenyl) phosphorothioate (fenitrothion) on the toxicity of 2-sec-butylphenyl methylcarbamate (BPMC) in male mice was analyzed pharmacokinetically. The animals pretreated by dietary administration of 1000 ppm fenitrothion for 1 week (4.4% of the po LD50 daily) did not show toxic symptoms except for a slight decrease in body weight. In the fenitrothion-pretreated mice, toxicity of fenitrothion was not changed but a fivefold potentiation was observed in po and ip acute lethality and a threefold potentiation of iv lethality of BPMC. Toxic signs after BPMC administration were similar regardless of fenitrothion pretreatment or of route of administration. Fenitrothion pretreatment followed by BPMC administration (20 mg/kg po or 8 mg/kg iv, approximate LD5 in the pretreated mice) significantly increased the plasma BPMC concentration and the total area under the plasma concentration versus time curve (AUC0-infinity). The pretreatment increased the oral AUC0-infinity more greatly than the iv AUC0-infinity (for po, 6.3-fold; for iv, 2.0-fold). The oral systemic availability of BPMC (fraction reaching systemic circulation) was increased by fenitrothion treatment to 3.3-fold. These results suggest that a major cause of the potentiation may be the increase in amount of BPMC in the systemic circulation.

Animals↗
PubMed1984

Potentiation of acute toxicity of 2-sec-butylphenyl N-methylcarbamate (BPMC) by fenthion in mice.

This study was undertaken to determine whether interactions of toxicologic importance might occur during combined exposure of male mice to 2-sec-butylphenyl N-methylcarbamate (BPMC) and O,O-dimethyl O-(3-methyl-4-methylthiophenyl)phosphorothioate (fenthion). The equitoxic coadministration of BPMC and fenthion resulted in only a 1.6-fold potentiation compared to the expected LD50. However, 1 hr oral pretreatment with 3 (1/100 LD50), 7.5, 15, and 30 mg/kg of fenthion resulted in 5-, 9-, 12-, and 15-fold potentiation of the acute oral toxicity of BPMC, respectively. This fenthion pretreatment caused significant increases in the BPMC plasma concentrations and in the area under the concentration-time curve. The increase of the plasma concentrations of BPMC depended upon the fenthion dose and was associated with that of the potency ratio. The pretreatment of fenthion prolonged the hexobarbital sleeping time. The plasma concentrations of BPMC after the administration of a dose of LD2.5 (20 mg/kg) in fenthion-pretreated mice were clearly lower than those of a dose of LD2.5 (195 mg/kg) in nontreated mice. These results suggested that fenthion pretreatment caused the potentiation of the acute toxicity of BPMC partially by the inhibition of detoxification of BPMC.

Administration, Oral↗
PubMed1984

Inhalation chamber with size discriminator for liquid aerosols.

To minimize data variation in inhalation toxicity testing and to evaluate human and animal hazards of inhaled chemicals, a practical inhalation chamber with a size discriminator for mists was developed to provide high concentration liquid aerosols of defined particle sizes. Liquid aerosols generated with an atomizer were separated by an impinging separator which was composed of aerosol jets directed upward against a flat plate. The principle of the separator eliminates particles larger than a calculated cutoff size in micrometer and submicrometer ranges by changing the orifice diameter of the jet nozzle under constant air flow. The mists thus separated are introduced into the space between two concentric cylinders just above the impaction plate. Ten rats can be positioned around the periphery of the chamber wall equidistant from the impaction plate, with their snouts thrust into the inhalation space. Preliminary testing with olive oil and water aerosols using particle cutoff sizes of 1, 3, and 3.3 micron showed that the obtained separation of particles was very clear, although the cutoff point seemed to shift somewhat to smaller values than calculated; the shift was especially evident with water aerosols. The concentrations obtained were more than 1 mg/liter when the cutoff point was selected at 1 micron. The mist at the inhalation space attained a steady concentration and particle size distribution within 2 min of the onset of mist injection, remained over a 4-hr period, and was cleared within 2 min of the cessation of mist generation.

Aerosols↗
PubMed1984

Tissue calmodulin levels in normal and Graves' thyroids.

Calmodulin levels in normal human thyroids and Graves' disease thyroids were measured by specific radioimmunoassay in the presence of ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). The calmodulin levels in tissues from patients with Graves' disease treated with thionamide drugs were significantly higher than those in normal tissues from euthyroid patients with solitary cold nodules (normal: 484 +/- 50 ng/mg protein, mean +/- SE, n = 15; Graves': 901 +/- 54 ng/mg protein, n = 48, p less than 0.001). Such a rise in calmodulin levels in Graves' disease thyroids was also present even after the administration of 50 micrograms of T3 for 5 days before operation (828 +/- 137 ng/mg protein, n = 6, p less than 0.01). Calmodulin levels in Graves' disease thyroids were closely related to the cell height of follicular epithelium. Calmodulin levels in a columnar cell predominant group were significantly higher than those in a flat cell predominant or a cuboidal cell predominant group (columnar cell predominant: 1150 +/- 118 ng/mg protein, n = 13; flat cell predominant: 561 +/- 125 ng/mg protein, n = 3, p less than 0.05; cuboidal cell predominant: 596 +/- 40 ng/mg protein, n = 25, p less than 0.001). The increase in calmodulin content in Graves' disease thyroid could therefore possibly be attributed to the stimulation of the thyroid gland by the thyroid stimulating antibody. An immunofluorescence study demonstrated the presence of calmodulin immunoreactivity in the thyroid epithelial cells, particularly enriched in the apical border in the form of a granulated structure.

Calmodulin↗