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Biomedical subjects

S Tsuda

Publications and source records attributed to S Tsuda.

At least 217 records · Page 12Linked to original sources
PubMed1988

[Clinical evaluation of a combination treatment with cefmenoxime and cefsulodin of severe infections in leukemia and related disorders].

A combination of cefmenoxime (CMX) and cefsulodin (CFS) which has a broad spectrum on various bacteria including Pseudomonas aeruginosa was evaluated for severe infections associated with hematological malignancies. Seventy one patients were treated with the combination therapy. Among them, 57 patients were evaluable for the effectiveness. Fourteen patients were not evaluable because 10 patients were subjected to additional therapy such as gamma-globulin, interferon, radiation and pulse therapy of a large dose of methylprednisolone, 3 were prophylactically treated and the remaining one was a patient with disseminated bone marrow metastasis of prostatic cancer and not a patient with a hematologic malignancy. Excellent responses were obtained in 24 (42.1%) patients and good response in 12 (21.1%) patients, with a total rate of effectiveness of 63.2%. Three patients who were treated prophylactically and one patient who suffered from prostatic cancer with metastasis to bone marrow, were included in the final evaluation of side effects. Side effects were observed in only one patient (1/61, 1.6%). Mild neutropenia was identified in a patient of 78 years of age in 4 days after the combined regimen was started. Neutropenia disappeared soon after the cessation of the treatment. These results showed that a combination of CMX and CFS was an effective and safe regimen for the treatment of severe infections in patients with hematological disorders.

Adult↗
PubMed1987

Contribution of monoaminergic nervous system in potentiation of 2-sec-butylphenyl N-methylcarbamate (BPMC) toxicity by malathion in male mice.

Malathion-induced marked potentiation of BPMC toxicity (about fivefold) was analyzed by measuring LD50 as an index of acute toxicity. The acute lethality of BPMC was decreased by muscarinic blockers (atropine, methylatropine, or trihexyphenidyl) or a monoamine oxidase inhibior (pargyline) and increased by a monoamine depleter (reserpine) or a dopaminergic blocker (haloperidol). The potentiation observed with BPMC and malathion was decreased by the muscarinic blockers, monoamine depleters (reserpine, alpha-methyl-p-tyrosine), an alpha-noradrenergic blocker (phentolamine), or haloperidol. The acute toxicities of other N-methylcarbamates MPMC (3,4-dimethylphenyl N-methylcarbamate), MTMC (3-methylphenyl N-methylcarbamate), NAC (1-naphthyl N-methylcarbamate), and XMC (3,5-dimethylphenyl N-methylcarbamate) were potentiated by malathion to a lesser degree than that of BPMC. Atropine protected against the lethalities of all N-methylcarbamates. Reserpine or haloperidol potentiated the lethalities of N-methylcarbamates with a similar tendency toward malathion. When the inhibitory effect of each N-methylcarbamate on brain acetylcholinesterase (AChE) was compared with its LD50, among five N-methylcarbamates BPMC had particularly strong anti-AChE activity. This characteristic of BPMC was not observed after the treatment with reserpine. These results suggest that BPMC may act not only on cholinergic nerves as an anti-AChE, but also on monoaminergic nerves which antagonize the lethal cholinergic effect. Malathion might inhibit the effect of BPMC on the monoaminergic nerves, thereby markedly potentiating the lethal effect of BPMC.

Acetylcholinesterase↗
PubMed1987

Potentiations of N-methylcarbamate toxicities by organophosphorus insecticides in male mice.

A N-methylcarbamate insecticide, 2-sec-butylphenyl N-methylcarbamate (BPMC), is markedly potentiated by low-dose treatments of P = S type organophosphorus insecticides. As a mechanism of this potentiation, the increase of plasma BPMC concentrations due to the inhibited metabolic degradation has been suggested. In this study, acute toxicities of five N-methylcarbamates structurally related to BPMC were studied after low-dose treatments of three P = S type organophosphorus insecticides (cyanophos, fenitrothion, and malathion) and one P = O type organophosphorus insecticide (dichlorvos), and the role of plasma concentrations of N-methylcarbamates in the potentiations was examined. Acute toxicities of five N-methylcarbamates were potentiated by the treatments of the P = S types, among which the potentiation of BPMC was strongest. BPMC toxicity was not potentiated by the treatment of the P = O type. Plasma concentrations of BPMC were increased by the treatments of the P = S types, but not by the treatment of the P = O type. The acute toxicity and plasma concentrations of BPMC were increased by SKF 525-A (an inhibitor of mixed-function oxidase). These results suggest that the increase of plasma BPMC concentrations may be related to the potentiation of BPMC toxicity. The treatment of fenitrothion increased plasma concentrations of other N-methylcarbamates more than those of BPMC, although the potentiation of BPMC toxicity was strongest. SKF 525-A and fenitrothion treatments increased plasma BPMC concentrations to a similar degree, but the potentiation of BPMC toxicity by SKF 525-A was significantly less than that by fenitrothion. Thus, some other mechanism(s) may be responsible for the potentiations of the N-methylcarbamate toxicities.

Animals↗
PubMed1987

The role of epinephrine as a neuromodulator in spontaneously hypertensive rats.

The present study was carried out to elucidate the role of epinephrine as a neuromodulator in hypertension. The effects of epinephrine on norepinephrine release from the sympathetic nerve endings were examined in isolated perfused mesenteric arteries of spontaneously hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY). Norepinephrine overflow during electrical nerve stimulation (5, 15 Hz) was significantly greater in SHR than in WKY. Low concentration of exogenous epinephrine (5.5 X 10(-9) M) potentiated norepinephrine overflow during nerve stimulation in SHR, and this (at 15 Hz stimulation) was antagonized by propranolol (5.0 x 10(-7) M), whereas, the overflow in WKY was reduced by the same concentration of epinephrine. A higher concentration of epinephrine (1.4 x 10(-8) M) decreased norepinephrine overflow in both SHR and WKY, and this change (at 15 Hz stimulation) was antagonized by yohimbine (1.0 x 10(-7) M). Further, magnitudes of the suppressions were smaller in SHR than in WKY. These results suggest that altered modulations of norepinephrine release by epinephrine through presynaptic beta- and alpha 2-adrenoceptors might induce increased sympathetic nerve activity in SHR.

Animals↗
PubMed1987

Alterations in calcium-handling of erythrocytes in spontaneously hypertensive rats. Calcium-induced changes in the osmotic fragility of erythrocytes in hypertension.

To investigate the sensitivity to calcium of erythrocytes in hypertension, changes in the osmotic fragility of erythrocytes following Ca-loading were observed. Washed erythrocytes were obtained from spontaneously hypertensive rats (SHR, Okamoto and Aoki) and age-matched normotensive Wistar Kyoto rats (WKY). Treatment of erythrocytes with Ca-ionophore A23187 and Ca in the medium caused a reduction in the osmotic fragility which correlated with the Ca-concentration. The degree of alteration in the osmotic fragility of erythrocytes was greater in SHR than in WKY. Oral administration of hydralazine to SHR significantly reduced the blood pressure. However, the alterations in the osmotic fragility of erythrocytes secondary to Ca-loading were not different between hydralazine-treated and untreated SHR. In the presence of a Ca-antagonist (verapamil or diltiazem) in the medium, the reduction of the osmotic fragility of erythrocytes caused by Ca-loading was inhibited, and the differences between SHR and WKY were abolished by Ca-antagonists. These results suggest that the greater changes in osmotic fragility of erythrocytes caused by Ca-loading in SHR could be due to a genetic abnormality of Ca-handling by the cell membranes, and that this abnormality might cause an increase in intracellular Ca, which contributes, in part, to the pathogenesis of hypertension.

Animals↗
PubMed1987

[Evaluation of oral amphotericin B with serial measurement of the serum concentration in patients with leukemia and related disorders].

A total of 10 episodes in 7 patients with leukemia or related disorders was treated with oral amphotericin B (AMPH). In 8 episodes AMPH were used prophylactically for severe neutropenia, and in the remaining 2 it was given when the patients were feverish. A daily dose of 2,400 mg of AMPH was given orally once a day and serum concentrations of AMPH were determined serially with bioassay. Two hours after administration, the mean serum concentration of AMPH rose to 0.15 microgram/ml, and reached 0.27 microgram/ml after 24 hours. The concentration was maintained between 0.23 microgram/ml and 0.39 microgram/ml through the following 7 days. These concentrations exceed the minimal inhibitory concentrations of most strains of Candida albicans. In 8 occasions of prophylactic use, no fungal infection was encountered. In a patient with pneumonia, chest X-ray and physical findings improved with administration of oral AMPH. Side effect of AMPH was seen in 1 patient, which was mild proteinuria and was eased rapidly after the withdrawal of AMPH. Clinical laboratory tests showed 1 case of proteinuria and disorder of kidney but did not clear under influence of AMPH. These results suggest that oral administration of AMPH is clinically and therapeutically effective and relatively safe for the prophylaxis or the treatment of fungal infection in patients with leukemia or related disorders.

Administration, Oral↗
PubMed1986

Mechanism of potentiation of BPMC toxicity by fenthion pretreatment in mice.

The mechanism of potentiation of 2-sec-butylphenyl N-methylcarbamate (BPMC) toxicity by O,O-dimethyl O-(3-methyl-4-methylthiophenyl) phosphorothioate (fenthion) in mice was investigated in relation to BPMC metabolism in the liver. Simultaneous administration of BPMC and either one of the thiophosphates (fenthion, its sulfoxide and sulfone) in a dose of 1/40 of its LD50 resulted in a 2- to 3-fold potentiation. On the other hand, one hour pretreatment with these thiophosphates in the same dose resulted in a 7- to 9-fold potentiation of BPMC toxicity, but that with fenthion oxon resulted in only a 2-fold potentiation. Plasma levels of BPMC were significantly increased by pretreatment with the thiophosphates, but not by the oxon. In an in vitro study, an inhibition of hepatic microsomal metabolism of BPMC and a decrease of cytochrome P-450 content by thiophosphates were observed at the concentration of 10 microM, but not by 25 microM of oxon. In an in vivo study, an inhibition of hepatic microsomal metabolism of BPMC, aminopyrine and aniline by the thiophosphates pretreatment were observed in doses of 1/40 of their LD50's, but not by the oxon in doses of up to 4/10 of its LD50. Cytochrome P-450 content was decreased by the thiophosphates in doses of 4/10 of their LD50's, but not by the oxon. These results suggested that the inhibition of BPMC metabolism might be, at least in part, the mechanism for the fenthion-induced potentiation of BPMC toxicity and that desulfuration of fenthion might be responsible for the inhibition of BPMC metabolism.

Animals↗