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Biomedical subjects

K Totsuka

Publications and source records attributed to K Totsuka.

At least 19 recordsLinked to original sources

Comparison of phenotypic characteristics, DNA-DNA hybridization results, and results with a commercial rapid biochemical and enzymatic reaction system for identification of viridans group streptococci.

The rapid ID 32 Strep system (bioMérieux, Marcy l'Etoile, France) was evaluated for its ability to identify 21 species of viridans group streptococci; results were compared with DNA-DNA hybridization results and results of conventional physiological tests. A total of 171 strains of the 21 species including 147 clinical strains was analyzed. Of the 156 strains of species included in the database of this system, 136 strains (87%) were correctly identified. Incorrect identification occurred for 13 strains (8%), and no identification was given for 7 strains (5%). It was difficult to differentiate S. mitis and S. oralis accurately with this system. Of the 17 strains identified as S. mitis by the rapid ID 32 Strep system, the results of DNA-DNA hybridization were in agreement for only 3 strains. S. crista and S. parasanguis, which are not included in the database, were identified as S. mitis or S. sanguis or were not identified, but S. parasanguis could probably be identified by using the rapid ID 32 Strep system because the biochemical profile is well characterized for this species. The rapid ID 32 Strep system can be used to differentiate most species for which phenotypic characteristics have been described if the database is revised according to recently reported amended criteria for the identification of viridans group streptococci. However, identification of a few species such as S. mitis and S. oralis is problematic with this system.

Bacterial Typing Techniques

Postantibiotic effects and postantibiotic sub-MIC effects of benzylpenicillin on viridans streptococci isolated from patients with infective endocarditis.

We investigated the postantibiotic effects (PAEs) and the postantibiotic sub-MIC effects of benzylpenicillin on three strains of viridans streptococci isolated from infective endocarditis patients. The PAEs of benzylpenicillin on penicillin tolerant Streptococcus sanguis TW-70 (0.4-3.9 h), penicillin tolerant S. sanguis TW-80 (0.3-6.3 h) and nontolerant Streptococcus oralis TW-186 (0.5-3.1 h) were dependent on exposure time. The PAEs were not concentration dependent for S. sanguis TW-70 and S. sanguis TW-80 above the MIC, and for S. oralis TW-186 above 16 x MIC. The antimicrobial effects of benzylpenicillin at sub-MIC concentrations were examined in bacteria pretreated with benzylpenicillin (8 x MIC) for 2 h and compared with untreated bacteria. At the sub-MICs tested, the regrowth of pretreated S. oralis TW-186 cells was more prolonged than that of untreated cells and bactericidal action was seen only in pretreated cells. These effects (so-called 'postantibiotic' sub-MIC effects') were not observed in penicillin tolerant S. sanguis TW-70. The presence of the postantibiotic sub-MIC effect may be an important factor in determining the dosing regimen for infective endocarditis.

Endocarditis, Bacterial

Metabolism of S-1108, a new oral cephem antibiotic, and metabolic profiles of its metabolites in humans.

The metabolism and pharmacokinetics of pivalic acid, a major metabolite of S-1108, were studied with three healthy volunteers. Concentrations of S-1006 (the active compound), pivalic acid, and pivaloylcarnitine in plasma and urine were measured after administration of S-1108. Recoveries in urine at the doses of S-1108 given (100 and 200 mg) were 33 to 41% for S-1006, 93% for total pivalic acid, and 89 to 94% for pivaloylcarnitine in 24 h, and maximum concentrations in plasma were 2 micrograms of S-1006 per ml, 1 micrograms of total pivalic acid per ml, and 2 micrograms of pivaloylcarnitine per ml after a 200-mg oral administration of S-1108. More than 90% of the pivalic acid was excreted as pivaloylcarnitine, and no measurable amount of free pivalic acid was present in urine samples, indicating that the pivalic acid liberated from S-1108 was almost quantitatively conjugated with carnitine in the human body. The level of free carnitine in plasma was unaffected by a single 200-mg administration of S-1108, whereas urinary excretion of free carnitine decreased as levels of acylcarnitine increased. The acylcarnitines were excreted primarily in the form of pivaloylcarnitine. This study clearly showed how the pivalic acid was metabolized and excreted in humans. The importance of monitoring carnitine, an essential cofactor in fatty acid metabolism, was also discussed in terms of its utilization by pivalic acid.

Administration, Oral

Comparative antibiotic dose-effect relations at several dosing intervals in murine pneumonitis and thigh-infection models.

Animal studies that compare antibiotics have used only a limited number of doses administered at intervals chosen without regard for their pharmacodynamic effects of pharmacokinetic profiles. We compared the relative efficacy and potency of three beta-lactams and two aminoglycosides in lung and thigh-infection models in neutropenic mice by defining the maximum attainable antimicrobial effect at 24 h (Emax) and the total dose required to reach 50% of maximum effect (P50) at several dosing intervals. For beta-lactams, Emaxs were similar, whereas P50s increased 10- to 50-fold with longer intervals in both models. Aminoglycosides were significantly more bactericidal in the lung than in the thigh, and dosing interval had little impact on P50s in either model. Recognizing the variable impact of dosing interval on efficacy for different classes of antibiotics is mandatory for the proper design and interpretation of comparative trials.

Animals

[Four cases of adult Listeria monocytogenes infection in the last 5 years--hepatic necrotic foci in the adult septic case].

We have reported on the clinical courses of 4 cases of adult Listeria monocytogenes (Lm) infection, and the autopsy findings of 2 cases, those we have observed over the past 5 years. They were 2 cases of meningitis, 1 case of meningitis and sepsis and 1 case of sepsis. These 4 cases had CML, neoplastic angioendotheliosis, SLE and post-renal transplant condition, as their underlying diseases, and all were receiving immunosuppressive therapy. One meningitis patient who recovered showed mild liver dysfunction during her clinical course. The other 3 patients who died had jaundice at the time of onset and severe liver dysfunction. The 2 cases those were autopsied were the sepsis cases. The one with an acute course and hepatic failure showed multiple miliary necrotic foci in the liver, where the presence of Lm in the cells could be verified. The other autopsy case, which had received adequate antibiotic therapy and the Lm infection had been cured, showed no necrotic foci in the liver. The case that had necrotic foci in the liver was the first such adult case in Japan. We have discussed the hepatic Lm infection in adult compromised hosts, which conventionally has not been considered a serious problem.

Aged

Thyroxine-induced molting and gonadal function of laying hens.

Twenty laying hens, 238 days of age, were divided into four groups which received daily intramuscular injections of L-thyroxine (T4) (0, 20, 100, or 500 micrograms/kg body weight per day) for 4 weeks. There was no change in body weight or egg production rate of the control (0 microgram T4) or of 20 and 100-micrograms T4 groups over time. Body weight and egg production of the 500 micrograms T4 group decreased markedly and molting started 10 days after T4 injection. Circulating iodothyronine (T4), triiodothyronine (T3), and reverse triiodothyronine (rT3) of the 500-micrograms T4 group increased markedly (30 to 150 times those of the control group) whereas serum luteinizing hormone and progesterone declined after one week and estradiol after two weeks. We concluded that a large dose of T4 (500 micrograms T4/kg, body weight per day) induced an increase in circulating iodothyronine levels, decreased secretion of gonadotropin and sex steroid hormones, and induced molting.

Animals

Nutritional implications of high-iodine egg diet in rats: effects on lipid metabolism and thyroid function.

The effects of a diet including high-iodine eggs, containing much higher amounts of iodine than ordinary eggs, were investigated on lipid metabolism and thyroid function in rats. To a non-purified diet was added at the 1% (w/w) level ordinary egg power (OE diet: 35 micrograms iodine/100 g diet) or high-iodine egg powder (IE diet: 392 micrograms iodine/100 g diet). At 7 months and 19 months, feeding of the IE diet resulted in a lowered serum triacylglycerol level, elevated tissue lipoprotein lipase activity and a lowered lipid peroxide level in the brain. Although the serum total iodine level was 5 times higher in animals given the IE diet than in those given the OE diet, serum levels of thyroid-related hormones (TSH, T3 and T4) were not affected by feeding of the IE diet. In animals exposed to cold and given antithyroid drug treatment, the IE diet seemed to improve age-related defects in thermogenic and thyroid hormone responses to cold, and also to confer resistance to the antithyroid drug. These results suggest that iodine ingestion through high-iodine eggs modulates both lipid metabolism and thyroid function in rats.

Animal Nutritional Physiological Phenomena

Iodine content of various meals currently consumed by urban Japanese.

Various meals being currently consumed by urban Japanese were determined for iodine. The meal samples were collected in 1982 and 1984. The habitual daily home meals of 4 middle-aged Japanese living in urban areas contained 45-1,921 micrograms (mean; 362, 361, 429 and 1,023 micrograms, respectively) of iodine per day. The regular meals served in two university hospitals contained 95-287 micrograms (mean; 195 micrograms) and 89-4,746 micrograms (mean; 1,290 micrograms) of iodine per day, respectively, and the diets for diabetes mellitus contained 59-144 micrograms (mean; 96 micrograms) of iodine per day. In the daily meals containing iodine exceeding ca. 300 micrograms, some kinds of seaweeds and, in some cases, several foods containing a red food color with low iodine bioavailability, erythrosine, provided a large portion of iodine. The iodine contents of refectory meals in a university were 47-203 micrograms (mean; 113 micrograms) per meal and those of lunches in two elementary schools were 25-31 micrograms (mean; 27 micrograms) and 18-43 micrograms (mean; 36 micrograms) per lunch, respectively. These results suggest that the current daily iodine intake of urban Japanese is not great and that erythrosine elevates the iodine content of meals.

Child

Pharmacokinetic studies on the concomitant administration of piperacillin and cefazolin, and piperacillin and cefoperazone in rabbits.

The pharmacokinetics of each drug on the concomitant administration of piperacillin (PIPC) and cefazolin (CEZ) or cefoperazone (CPZ) were studied in rabbits. When rabbits received the consecutive drip infusion administration of CEZ (0.71 mg/kg/minute) and PIPC (1.38 mg/kg/minute) and likewise of CPZ (0.72 mg/kg/minute) and PIPC (1.54 mg/kg/minute) for 1 hour, respectively, the serum half-lives of CEZ and CPZ were respectively prolonged about 1.8 and 1.6 times during drip infusion of PIPC than administered alone. However, when the sequence of administration were reversed, the serum levels of PIPC were not affected by the consecutive drip infusion administration of CEZ and CPZ. To study these findings in detail, the single intravenous dose of 20 mg/kg of CEZ and CPZ were administered under drip infusion of PIPC (2.65-2.93 mg/kg/minute). The serum half-lives of CEZ and CPZ were also prolonged about 5.4 and 1.9 times, respectively, whereas urinary excretion of CEZ, and urinary and biliary excretion of CPZ were reduced by PIPC. Moreover, when the single intravenous dose of 20 mg/kg of PIPC were administered under drip infusion administration of CEZ (0.96-2.60 2.60 mg/kg/minute), the pharmacokinetics of PIPC was not affected by the presence of CEZ. However, under drip infusion administration of CPZ (2.60-2.70 mg/kg/minute), the PIPC serum half-life was prolonged about 1.4 times, and biliary excretion of PIPC was reduced but urinary excretion was not. From the results of renal clearance experiments, tubular secretion appeared to be the predominant mechanism of renal elimination for these three drugs. These results indicate that PIPC influences the pharmacokinetics of both drugs by the competitively inhibiting tubular secretion in CEZ, and tubular secretion and hepatic transport system in CPZ. Therefore, in this respect PIPC seems to have probenecid-like action.

Animals

Histopathological study on rats fed iodine-enriched eggs long-term (7 and 19 months).

A histopathological study was conducted on rats fed on a diet containing iodine-enriched eggs over the long term, 7 and 19 months. A laboratory powder chow was added at the 1% (w/w) level with ordinary egg powder (ordinary egg diet as control: 35 micrograms iodine/100 g diet) or iodine-enriched egg powder (iodine-enriched egg diet: 392 micrograms iodine/100 g diet). The animals were meal-fed twice a day and allowed unrestricted voluntary wheel-running. In general, organs, tissues and endocrine glands including thyroid glands from rats of the iodine-enriched egg diet group exhibited no significant difference in histopathological features as compared with those of the ordinary egg diet group. These results suggest that long-term feeding of a considerable amount of iodine through an iodine-enriched egg diet did not cause any specific excess-iodine toxicity.

Animals

Effects of the long-term (17-19 months) feeding of high-iodine eggs on lipid metabolism and thyroid function in rats.

The present paper describes the effects of long-term (17-19 months) feeding of high-iodine eggs on lipid metabolism and thyroid function of rats, and also the effects of inorganic iodine on lipid metabolism. Rats were meal-fed on a diet containing 1% (w/w) of ordinary egg powder (OE diet as control: 35 micrograms I/100 g) or high-iodine egg powder (IE diet: 392 micrograms I/100 g). After the 19-month dietary treatment, rats fed on the IE diet, compared with the controls, showed a higher tissue lipoprotein lipase activity, a lower lipid peroxide level in the brain and a trend toward lower serum triacylglycerol levels and body fat storage without alterations in serum levels of thyroid-related hormones (TSH, T3 and T4). From the results of cold exposure and anti-thyroid drug-treatment conducted on rats fed on the OE and IE diets for 17 months, high-iodine eggs seemed to improve the age-related defects in thermogenic and thyroid hormone responses to cold, and also to result in a resistance to the anti-thyroid drug. The effects of the IE diet on lipid metabolism of rats were partly exhibited by feeding of the OE diet with an equivalent amount of iodine added as KI or KIO3. Thus, it is suggested that iodine ingestion through high-iodine eggs modulates both lipid metabolism and thyroid function in rats.

Animals

Influences of feeding of high-iodine eggs on hypo- and hyperthyroid rats.

The effects of the feeding of high-iodine eggs to rats with an abnormal thyroid status were investigated. Rats were fed for one week on a commercial diet supplemented with propylthiouracil (PTU) (10 mg/100 g diet) or thyroxine-Na (240 micrograms/100 g diet) respectively, to induce hypo- or hyperthyroidism, and then further fed for 4 weeks on the respective drug-supplemented diets, containing 1% (w/w) of either ordinary or high-iodine egg powder. Control (euthyroid) rats were maintained on the commercial diet. The induction of a hypothyroid state resulted in thyroid hyperplasia, with decreased thyroid iodine content, altered serum thyroid relating hormone levels (increased TSH and decreased T3 and T4), elevated serum total cholesterol and reduced serum triacylglycerol (TG) levels, and also increased muscle and adipose tissue lipoprotein lipase (LPL) activities. In contrast, in the hyperthyroid animals, thyroid atrophy, as well as decreased serum TSH and increased T3 and T4 levels, was associated with reduced serum total cholesterol level and muscle LPL activity. There were no essential differences between animals given high-iodine and ordinary eggs in either hypo- or hyperthyroid state, although the effects of PTU treatment on the thyroid and serum TG level appeared to be slightly lesser in rats given high-iodine eggs than in those given ordinary eggs. It is concluded that high-iodine eggs did not have any side-effect on either hypo- or hyperthyroid rat in this study.

Adipose Tissue

DNA double-strand breakage and removal of cross-links in Deinococcus radiodurans.

Mitomycin C-sensitive mutants of Deinococcus radiodurans were isolated which were either resistant to or only moderately sensitive to far UV (254 nm) or gamma rays. They were also sensitive to irradiation at 365 nm in the presence of 4,5',8-trimethylpsoralen. They were classified into seven complementary groups (mtcA through mtcG) by transformation experiments. Interstrand cross-links in the DNA duplex induced by mitomycin C were removed in the cells of two mutants (mtcD and mtcE) as in the wild type, whereas the other mutants were deficient in this repair. After a sublethal dosage of mitomycin C, single- and double-stranded cuts of cross-linked DNA were observed in the wild-type cells during postincubation. This removal of cross-links in DNA seems to be indispensable for the cells since their colony-forming ability was markedly reduced if they were postincubated under an inhibitory condition for repair of these lesions.

Chloramphenicol