Biomedical subjects

A Matsuda

Publications and source records attributed to A Matsuda.

At least 505 records · Page 28Linked to original sources

PubMed1978

[Toxicological studies on pepleomycin sulfate (NK 631) II. Subacute toxicity of pepleomycin sulfate in rats (author's transl)].

Studies on subactute toxicity and its recovery of pepleomycin sulfate (NK631) were carried out in both sexes of rats. NK 631 was administered intraperitoneally in dose levels of 0.3, 0.9, 2.7. 8.1 and 24.3 mg/kg/day for 30 days. After finishing administration of NK 631 for 30 days, 5 animals of each group were proceeded to recovery test for 35 days. During the course of the experiment, the body weight gains were suppressed in all dose levels except in 0.3 mg/kg group of male rats. The deaths were found in the animals treated with doses over 24.3 mg/kg during treatment period and in those over 2.7 mg/kg during recovery period. In biochemical and urinary analysis, the increases of serum GPT, BUN, Mg, Ca and urine glucose were moderately recognized in 8.1 mg/kg group. Additionally, in macroscopical and histopathological findings, bone damage was found in the animals treated with doses over 2.7 mg/kg during treatment and recovery periods. From these results, the maximum safety dose of NK 631 in subacute toxicity using rats were estimated to be about 0.3 mg/kg.

Animals↗

PubMed1978

[Toxicological studies on pepleomycin sulfate (NK631). III. Subacute toxicity of pepleomycin in dogs (author's transl)].

Subacute toxicity and its recovery of pepleomycin sulfate was studied in both sexes of beagle dogs. At dose levels of 2.4, 1.2 and 0.6 mg/kg, pepleomycin was administered intramuscularly to dogs for 30 successive days. Two dogs of the 1.2 mg/kg dose group were used for recovery test for 35 days. As general symptoms, the decrease of food intake, the loss of body weight, ulceration of foot pad, nail root necrosis and onychoptosic, ulcer of tongue and labia, and alopecia, dermatitis and necrosis at friction sites were observed the more severely in high dose groups, as those in bleomycin were. The death occurred in the 2.4 mg/kg dose group of both sexes. The lesions of liver and kidney were recognized in the 2.4 and 1.2 mg/kg dose groups of both sexes on biochemical, histopathological or urinary findings. Additionally slight fibrous change of lung was observed in all dose groups. Generally subacute toxicity of pepleomycin was revealed approximately in the same as or in a little stronger degree than that of bleomycin, and its recovery was hardly recognized during its period. The maximum safety dose in this studies is estimated to be between 0.3 and 0.6 mg/kg in dogs.

Animals↗

PubMed1978

[Toxicological studies on pepleomycin sulfate (NK631), IV. Chronic toxicity of pepleomycin sulfate in rats (author's transl)].

Studies on chronic toxicity and its recovery of pepleomycin sulfate (NK 631) were carried out in both sexes of rats. NK 631 was administered intraperitoneally in dose levels of 0.15, 0.3, 0.6, 1.2 and 2.4 mg/kg/day for 180 days. After finishing administration of NK 631 for 180 days, animals of each group were proceeded for 35 days recovery test. During the course of the experiment, the body weight gains were suppressed in all dose levels except for 0.15 mg/kg group of female. The deaths were found in all dose levels except for 0.15 mg/kg level of male during treatment and recovery periods. In biochemical and urinary findings, the increase of serum BUN, Mg, inorganic P. and urine glucose were slightly recognized in the animals treated with doses over 0.6 mg/kg. Additionally, in macroscopical and histopathological findings, bone damage and renal lesions were found in the animals treated with doses over 0.6 mg/kg during treatment and recovery periods. From these results, the maximum safety dose of NK 631 in chronic toxicity study using rats were estimated to be at less than 0.15 mg/kg.

Animals↗

PubMed1978

[Toxicological studies of pepleomycin sulfate. V. Short term intermittent toxicity in dogs (author's transl)].

The comparative studies in the short term intermittent toxicity of pepleomycin (NK631) and bleomycin (BLM) were performed on 10 beagle dogs of 13 approximately 15 months old. Two dogs per group were injected intravenously with NK631 and BLM in doses 5.0 and 2.5 mg/kg body weight every fourth day for 11 treatment. Two dogs served as control and were injected with saline solution. In the group of 5.0 mg/kg of NK631, one dog was sacrificed on day 37 of the treatment and another one dog died on day 33 of the treatment. All the dogs of other group survived until the end of the treatment. The toxicity to the hepatic and renal damage caused by NK631 was stronger than the BLM. On the contrary, the toxicity to lung and various mucocutaneous regions was weaker than the BLM. The grade of pulmonary fibrosis of NK631 was about 1/2 and 2/3 of the BLM in dose of 5 mg/kg and 2.5 mg/kg, respectively. Other toxicological changes such as anorexia and weight loss were almost similar to the BLM.

Animals↗

PubMed1978

[Safety evaluation of NK 631. Antigenicity, effect on delated hypersensitivity, irritative effect on eye mucous membrane and mutangenicity of pepleomycin (NK 631) (author's transl)].

1. Whether NK 631 is antigenic to guinea pigs and rabbits was studied by the methods of active and passive anaphylactic shock tests, Schultz-Dale reaction, passive cutaneous anaphylaxis, Ouchterlony, tanned red cell haemagglutination test and test according to the U.S. Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. However, none of the tests proved NK 631 to be antigenic. 2. The immunosuppressive effect of NK 631 was studied by delayed hypersensitivity to picryl chloride in normal and L-1210 tumor bearing mice. Therapeutic dosis of NK 631 was no immunosuppressed but toxic dosis of NK 631 was slightly decreased in ear thickness of delayed hypersensitivity. 3. The acute irritative effect of NK 631 and of bleomycin was studied by single instillation to the rabbit eye mucous membrane with 0.1 ml of either of 10, 33 and 100 mg/ml solution of the drugs in physiological saline. The irritative effect of NK 631 on the eye mucous membrane at each concentration was slightly severe than that of bleomycin at the same concentration. However, the manifestations were only mild to moderate dilatation of the conjunctival and nictating membrane blood vessels and eye mucous, and recovered or were mitigated 48 hours after the instillation. No severe changes such as corneal opacity, corneal desquamation, swelling and deaquamation of the conjunctival and nictating membrane were observed. The histopathological examination revealed no striking changes. 4. Mutagenicity of NK 631 and of bleomycin on Salmonella typhimurium strain TA 100 and TA 98 was studied. It was definitely shown that neither NK 631 nor bleomycin exerted any mutagenic action on either test strains.

Animals↗

PubMed1978

[Studies on antitumor activities and pulmonary toxicity of pepleomycin sulfate (NK631) (author's transl)].

The antimicrobial and antitumor activities, and the pulmonary toxicity of pepleomycin (NK631) were studied in comparison with bleomycin (BLM). NK631 showed a broad antimicrobial spectrum against gram positive and gram negative bacteria equally to BLM, and its activity was about twice higher than BLM. NK631 showed higher activity on cultured HeLa S3 cells and higher antitumor effect on the transplanted tumors of Ehrlich solid carcinoma in mice, AH66 and AH66F ascites hepatoma in rats, and lower antitumor effect on Ehrlich ascites carcinoma in mice than BLM. Similarly to BLM, NK631 did not show satisfactory activity on L1210 leukemia in mice. NK631 showed marked effect on chemically induced squamous cell carcinoma, spontaneous lymph sarcoma of a dog, human and dog gastric cancer heterotransplanted in nude mice equally to BLM. Furthermore NK631 exhibited remarkably higher antitumor activity on lymph node metastasis of AH66 ascites hepatoma of rats and chemically induced gastric carcinoma of rats than BLM. Pulmonary toxicity of NK631 was low as 1/3 in incidence and 1/4 in grade of the BLM in old mice system. This trend was confirmed by chemical analysis of hydroxyproline in lung.

Animals↗

PubMed1978

[Studies on organ distribution, absorption and excretion of pepleomycin sulfate (NK631) (author's transl)].

1. Organ distribution of pepleomycin (NK631) in mice and rats was studied. NK631 was found at higher levels than bleomycin (BLM) in skin, lung, stomach, solid tumor, etc. in mice and rats. Furthermore NK631 was detected in the mesenteric and lumbar lymph node, esophagus and prostate in rats and also distributed at about twice as high levels as BLM in the AH109A hepatoma cell-metastasized lymph nodes. 2. For the elucidation of reason on low pulmonary toxicity of NK631 which is in spite of 1.5 times highly distribution in lung compared with BLM, inactivation of various BLMs by high molecular fraction of lung of mice and rats was determined. The order of inactivation rate of various BLMs in lung was as follows: BLM-M5196 greater than NK631 greater than BLM greater than BLM-HPE. There is an encouraging coincidence between index of pulmonary fibrosis in mice and inactivating rate in lung. 3. A comparative study on the serum level and urinary excretion of NK631 and BLM was performed in dogs. The blood level and urinary excretion rate of both drugs were almost similar. 4. The blood levels of NK631 were comparable to those of BLM in cancer patients.

Absorption↗

PubMed1977

Intracellular reduction of the cupric ion of bleomycin copper complex and transfer of the cuprous ion to a cellular protein.

The cupric ion of the bleomycin copper complex has been shown to be reduced and transferred to a cellular protein by the following mechanism: Bleomycin approximately Cu2+ leads to Bleomycin plus Cu+ X Cu+ plus M leads to M approximately Cu+. The intracellular reducing agents (X) are suggested to be sulfhydryl compounds, because their action is inhibited by N-ethylmaleimide. The active group of the cellular protein (M) that binds with the cuprous ion is suggested to be a sulfhydryl group. The action of the bleomycin copper complex in causing DNA fragmentation in cells can be explained by the mechanism presented in this paper. This mechanism in cells is also supported by the temperature dependency of the action of the bleomycin copper complex on cells.

Animals↗

PubMed1976

Human C-peptide immunoreactivity (CPR) in blood and urine - evaluation of a radioimmunoassay method and its clinical applications.

A double-antibody radioimmunoassay method, using synthetic human connecting peptide as an immunizing antigen and standard, was evaluated for clinical assay of blood and urine samples. Normal fasting blood connecting peptide immunoreacivity (CPR) was 2.45 +/- 0.96 ng/ml, increasing promptly after a 50 g oral glucose load, but somewhat slower than insulin. Molar concentration of CPR exceeded that of insulin. CPR responses to glucose were subnormal in diabetics, very low in juvenile-type cases, and often poor in patients on insulin treatment. Fasting CPR levels were elevated in patients on corticosteroid treatment and with uraemia. A patient with insulin "auto-antibody" had high serum CPR. A considerable amount of CPR appeared in urine. Normal daily excretion of CPR was 1.52 +/- 0.55 mug/kg or 55.1 +/- 18.2 ng/mg creatinine. Urine CPR was very low in juvenile-type diabetics, and elevated in patients on corticosteroid treatment. The results confirm that blood and urine CPR are useful measures of the endocrine pancreatic function.

Antigen-Antibody Reactions↗

PubMed1976

Disappearance rate of endogenous human C-peptide from blood.

Glucagon (1 mg) and glucose (60 ml of 50% solution) were infused over 60 min to three normal and one obese subjects and two insulinoma patients. Plasma C-peptide immunoreactivity (CPR) and immunoreactive insulin (IRI) increased during the infusion. Half time of CPR after cessation of the infusion was 20.1 +/- 4.0 min, and that of IRI 9.8 +/- 1.3 min, respectively. This difference partly explains the higher molar concentration in plasma of CPR than IRI.

C-Peptide↗

PubMed1976

A new synthesis of 5'-deoxy-8,5'-cyclo-adenosine and -inosine: conformationally-fixed purine nucleosides (nucleosides and nucleotides. XVI).

A versatile method for the synthesis of 5'-deoxy-8,5'-cycloadenosine, a conformationally-fixed "anti" type of adenosine, was presented. Irradiation of 2', 3'-O-isopropylidene-5'-deoxy-5'-phenylthioadenosine with 60W Hg vapor lamp afforded 2',3'-O-isopropylidene-5'-deoxy-8,5'-cycloadenosine in high yield. The use of other 5'-alkylthio derivatives also gave the cycloadenosine, though the yields were rather poor. Deacetonation of the cyclocompound with 0.1N HCl gave 5'-deoxy-8,5'-cycloadenosine. The cycloinosine derivative was similarly prepared. The nmr, mass and CD spectra of 5'-deoxy-8,5'-cycloadenosine were given and discussed with the previously reported results.

Adenosine↗

PubMed1975

Synthesis and reaction of some 6-substituted pyrimidine nucleosides.

Treatment of 5-bromouridines with sodium cyanide afforded 6-cyanouridines. Further treatment of the 6-cyano derivatives with cyanide ion at higher temperature gave the 5-cyanouridines. The 6-cyano group was transformed to thioamido, carboxy, chloromethyl cyanomethyl, carboxymethyl, and methyl group, respectively. 5-Bromocytidines were also converted to the 6-cyanocytidines, from which cytidine 6-carboxylic acid was derived. The cyano group of 6-cyanocytidines has a leaving ability toward nucleophilic substitution reactions. The circular dichroic spectra of various 6-substituted pyrimidine nucleosides showed positive Cotton effect at B2u region, which were in contrast to the reported negative bands in 6-methyl-uridine or-cytidine.

Chemical Phenomena↗

PubMed1975