Biomedical subjects

T Tokiwa

Publications and source records attributed to T Tokiwa.

At least 73 records · Page 4Linked to original sources

PubMed1982

[Absorption, distribution, metabolism and excretion of netilmicin in rats (IV). Distribution in kidney and transmigration to fetus or suckling (author's transl)].

Distribution in kidney and transmigration to fetus or suckling in rats were studied in male, pregnant or lactating rats after intramuscular administration of 14C-netilmicin (20 mg/kg). 1. After administration to male rats, the radioactivity in the kidney declined slowly with a half-life of approximately 6 days. 2. The radioactivity in the kidney was distributed in the renal cortex. The distribution pattern was further investigated by means of microautoradiography. The radioactivity was specifically observed in lysosomal granules of the proximal tubules at 6 hours after administration and reached maximum at 24 hours after administration, then declined gradually. On the other hand, the radioactivity in the distal tubules was lower than that of the proximal tubules. The highest radioactivity in the distal tubules was detected later than 24 hours after administration. 3. In pregnant rats (20th day of gestation), the distribution of radioactivity in the tissues were almost the same as those in the male rat. The small amount of radioactivity was detected in the fetal kidney and bone. 4. In mother rats (14 days after parturition), the radioactivity in the milk was 3 approximately 4 mcg equivalent of netilmicin/ml during 24 hours after administration. The small amount of radioactivity (0.13% of dose) was observed in the gastrointestinal contents of a suckling with 6 hours after administration.

Animals↗

PubMed1982

[Absorption, excretion and metabolism of netilmicin in beagle dogs (author's transl)].

Pharmacokinetics of netilmicin (NTL), a new aminoglycoside antibiotic, injected intramuscularly to Beagle dogs were compared with those of gentamicin (GM), and the relationship between NTL dosage administered and plasma level and urinary excretion was examined. 1. When administered to 6 male Beagle dogs at a dose of 10 mg/kg, the plasma level showed a broad peak (ca. 23 mcg/ml) at 10 to 45 minutes after administration and declined thereafter with half-life of 65 minutes. On the other hand, the plasma level of GM administered at a dose of 10 mg/kg showed a peak (ca. 24mcg/ml) at 15 to 45 minutes after administration and the elimination half-life was 75 minutes. Both of the urinary concentrations of NTL and GM administered at a dose of 10 mg/kg were highest in the 4- to 6-hour urine, whereas NTL and GM recovered in the 24-hour urine were 51.7% and 57.7% of the dose administered, respectively. The pharmacokinetic profile of NTL administered intramuscularly to Beagle dogs appeared to be almost identical to that of GM. 2. The peak plasma level of ca. 50 mcg/ml was obtained at 10 to 60 minutes after administration of NTL at 20 mg/kg, and the half-life was 74 minutes. NTL recovered in the 24-hour urine was 69.7% of the dose administered. 3. TLC-bioautograms showed no biologically active metabolites of NTL in the urine collected from Beagle dogs given the antibiotic intramuscularly.

Animals↗

PubMed1982

[Subacute (5 weeks) subcutaneous toxicity study of cefsulodin using 3-week-old juvenile beagle dogs].

A subacute (5-week) subcutaneous toxicity study of cefsulodin (CFS) was carried out using 9 3-week old juvenile Beagle dogs. The dogs were distributed to 3 groups, each of which was constituted of 3 animals. Dogs in group I, II and III were given physiological saline (control), 300 mg/kg of cefazolin (CEZ, control drug) and 300 mg/kg of CFS, respectively. All animals used survived for 35 days of administration period. The changes, considered to be drug-related were histopathological changes at the sites of injection, which consisted inflammatory cellular infiltration and hyperplasia of fibroblast in subcutaneous tissue of skin. In terms of severity, CFS was less irritating than CEZ. CFS-related changes were not observed in other tests.

Animals↗

PubMed1981

[Subacute toxicity study of cefotiam in three-week old beagle puppies (author's transl)].

A subacute (5-week) subcutaneous toxicity study of cefotiam (CTM) was carried out using 9 three-week old Beagle puppies. The puppies were assigned to one of three groups, each containing three. Puppies in group I (control) were given physiological saline; puppies in group II and III were given 300 mg/kg/day of CTM and cefazolin (CEZ), respectively. No behavioral abnormalities were seen in puppies in each group. The changes, considered to be drug-related, were histopathological changes at the sites of injection, which consisted inflammatory cellular infiltration, hemorrhage and hyperplasia of fibroblast in connective tissue of skin and skeletal muscle. In terms of severity, CTM was rather more irritating than CEZ. Except the histopathological changes described above, there observed no abnormalities which were considered to be related to CTM.

Animals↗

PubMed1980

Cytological alteration of cultured rat liver cells by 3'-methyl-4-dimethylaminoazobenzene with special reference to chromosome changes, changes of growth patterns at a colony level and alpha-fetoprotein production.

A near diploid clone derived from a rat liver cell line was continuously treated with various concentrations of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) in culture. By treatment with 2.8 micrograms/ml, cells with 41 chromosomes formed a mode and which then shifted to 39. The chromosome numbers of cells treated with 5.4 micrograms/ml were widely distributed at early stages, but later the mode shifted to hypotetraploid region. Untreated control cells were confirmed as near diploid. Increased plating efficiency by 3'-Me-DAB as well as the appearance of large sized colonies was obtained. The production of alpha-fetoprotein (AFP) by the cells was slightly enhanced by treatment with 3'-Me-DAB. The cells treated with and without 3'-Me-DAB did not produce any tumor in rats 6 months after their intraperitoneal injection.

Animals↗

PubMed1979

Isolation and characterization of diploid clones from adult and newborn rat liver cell lines.

A high frequency of diploid and near-diploid clones were developed from cell lines derived from adult and newborn rat liver using micropipettes. There were some differences in morphology, biochemical properties and growth rate between clones. Cloned cells had low levels of tyrosine transaminase activity, glucose-6-phosphatase activity and albumin content. A diploid clone and pseudodiploid clone derived from adult rat liver cell line were positive for alpha-fetoprotein.

Animals↗

PubMed1979

Mechanism of cell dissociation with trypsin and EDTA.

The mechanism of cell dissociation with trypsin and EDTA was examined. Cell dissociation was possible when trypsin and EDTA were given simultaneously, when trypsin was given after EDTA treatment, but not when trypsin was given before EDTA treatment.

Animals↗

PubMed1976

Effects of 3'-methyl-4-dimethylaminoazobenzene and 4-aminoazobenzene on plating efficiency, mitotic index, and macromolecular synthesis of cultured liver cells.

The response of a cultured liver cell line to azo dyes was investigated by the application of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) and 4-aminoazobenzene (AB) with observation of, in particular, the changes which occurred in plating efficiency, macromolecular synthesis and mitotic indices. The results were as follows. (1) The application of 3'-Me-DAB resulted in a decrease in size of colonies and plating efficiency of both J-5-2 cells (derived from 7-day-old rat liver tissues) and cells of the colonical clone, J-5-2cl. (2) AB caused greater inhibition of plating efficiency than did 3'-Me-DAB. (3) Both 3'-Me-DAB and AB inhibited synthesis of DNA but not of RNA or of protein. (4) AB exhibited a greater inhibitory effect on mitotic indices than did 3'-Me-DAB.

Animals↗

PubMed1976

Effect of long-term administration of 4-(dimethylamino)azobenzene on liver cell line derived from rats fed this chemical.

Liver tissue cells derived from rats fed 4-(dimethylamino)azobenzene (DAB) were maintained in vitro for several months. These cells showed higher malignancy after treatment with 4.8 or 19.2 mug/ml of DAB. Subcutaneous back-transplantation of DAB-treated cells showed an earlier appearance of palpable tumors and a higher rate of "take" than the non-treated control cells. The tumor size at 60 days after back-transplantation was also significantly larger in the DAB-treated cells. Long-term treatment with DAB produced few morphological changes of the cells in vitro, but the plating efficiency and resistance to toxic effects of DAB were significantly higher in the treated cells than in the control cells. On the other hand, no definite differences in chromosome number were found between the treated and control cells. These findings suggested that cell malignancy could be promoted by long-term treatment with DAB in vitro

Animals↗

PubMed1975

Studies on caerulein (FI6934). Absorption, distribution, metabolism and excretion of caerulein.

35S-Caerulein (35S-FI6934) was administered intramuscularly into rats (280 mug/kg), rabbits (380 mug/kg) and mice (3.3 mg/kg). Blood level of radioactivity in rats and rabbits reached the maximum at 5 and 15 min after administration, respectively, and then decreased rapidly. In both rats and rabbits, the radioactivities were excreted mainly into the urine. The physiological activity of FI6934 was detected in the blood of rats and rabbits collected within 15 and 30 min after injection respectively, and in the bile of rats collected within the first 2 hr. In rats, the radioactivities were densely distributed in kidney, liver, pancreas, and intestine. Four metabolites of 35S-FI6934 were isolated by paper chromatography from rat urine (i.m., 500 mug/kg). The main metabolites, F-I and F-II, were negative to nynhydrin and to the Ehrlich reagent and carried no physiological activity. 35S-Chym-I, which was prepared by digesting 35S-FI6934 with chymotrypsin, was injected to rats (i.m. 16 or 8 mg/kg/. The metabolite, C-I, isolated from the urine was considered to have a very similar structure to F-I from the results of paper chromatography and paper electrophoresis. By amino acid analysis, the structure of C-I was estimated to be as follows: Pyr-Gln (or Glu)-Asp-Tyr-Thr-Gly. (see article).

Amino Acids↗

PubMed1975

Preparation of single cell suspensions from hepatoma cells in culture.

Fundamental examination was carried out on the liberation of single cells from hepatoma cells in culture. dRLa-74 cells derived from rat hepatoma, which hardly disperse as single cell suspensions with several proteolytic enzymes or EDTA alone, dispersed with a high yield of single cells by the combination of trypsin and EDTA. HUH-6 cells derived from human hepatoblastoma also showed similar results. The degree of cell dissociation by the combination was dependent on the incubation temperature or pH.

Animals↗

PubMed1975

Effect of anti-alpha-fetoprotein serum on growth and plating efficiency of alpha-fetoprotein-producing hepatoma cells in vitro.

The effect of a specific rabbit antiserum to rat alpha-fetoprotein (AFP) was examined on the growth and the plating efficiency of AFP-producing rat hepatoma cells (AH70Btc Clone 10-5) in cultures. The addition of anti-AFP serum to the culture medium inhibited cell growth moderately and inhibited plating efficiency markedly, although no inhibitory effect of complexes of AFP and antibody to AFP was observed on cell growth. Anti-AFP globulin in the immune serum was demonstrated on the cell surface by fluorescent antibody technique. Several clones producing low levels of AFP were obtained by long-term treatment of the original Clone 10-5 cells with anti-AFP serum. These treated clones showed characteristics that differed from the untreated original clone 10-5 cells: The relative plating efficiency of the treated clones on agar plates containing 5% anti-AFP serum was higher than the original Clone 10-15 cells and the amount of AFP secreted by the treated clones was lower.

Animals↗

PubMed1973