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Biomedical subjects

Y Shimada

Publications and source records attributed to Y Shimada.

At least 649 records · Page 36Linked to original sources
PubMed1987

[Pharmacokinetics and clinical studies of flomoxef in the pediatric field].

Flomoxef (FMOX, 6315-S), a new intravenous cephem antibiotics, was administered to a total of 11 cases with their ages ranging from 7 years and 4 months to 10 years and 10 months. Among them, two were administered with (FMOX at) a dose level of 10 mg/kg, three each with 20 mg/kg and 40 mg/kg using one shot intravenous injection, and the remaining 3 with 40 mg/kg by intravenous drip infusion over 30 minutes. Plasma concentrations, urine concentrations and urinary recovery rates were determined. The clinical efficacy of FMOX was evaluated in 2 cases with tonsillitis, 45 with acute pneumonia, 10 with urinary tract infections, 2 with purulent lymphadenitis, and 2 with abscess, a total of 61 cases. Of these cases, one case of pneumonia in which a side effect occurred was excluded from the evaluation because the treatment was interrupted short of the required period. In the remaining 60 cases, the mean daily dose was 79.3 mg/kg in 3 or 4 divided doses and, except one case treated by 30-minute intravenous drip infusion, all cases were treated by one shot intravenous injection for a mean period of 6 days. Bacteriological effects of FMOX, its side effects and influences on laboratory test values were also investigated. 1. Maximum plasma concentrations after one shot intravenous injections of FMOX occurred at 5 minutes after administration regardless of dose levels (10 mg/kg in 2 cases, 20 mg/kg in 3 and 40 mg/kg in 3). Mean peak values obtained upon the 3 different dose levels were 62.5, 103.1 and 244.7 micrograms/ml, respectively. Mean plasma half-lives were 0.670, 0.915 and 0.595 hour, and mean AUCs were 33.0, 65.2 and 133.1 micrograms.hr/ml, respectively. Thus, a positive dose-response relationship was found among the 3 doses. 2. Plasma concentrations after 30-minute intravenous drip infusions of FMOX at 40 mg/kg always reached a peak at 30 minutes after the initiation of infusion, i.e. at the completion of infusion, and the mean value for 3 administrations was 151.0 micrograms/ml. The mean half-life was 0.973 hour and the mean AUC was 149.1 micrograms.hr/ml. 3. Maximum concentrations in urine after one shot intravenous injections of FMOX were always obtained in 0 approximately 2 hours after administration regardless of dose levels (10 mg/kg, 2 cases, 20 mg/kg, 3 cases and at 40 mg/kg, 3 cases) and mean values for the 3 dose levels were 2,570, 4,410 and 6,290 micrograms/ml, respectively. Thus, urine concentrations were also dose-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1987

[Fecal and urinary excretion of norfloxacin in adults].

Norfloxacin (NFLX) a synthetic oral antibacterial agent of quinolone carboxylic acid, was given to 6 healthy men aged 23 to 29 years and weighing 57 to 88 kg (average 64.7 kg) at a dose of 200 mg (two 100 mg tablets) once after breakfast and its fecal and urinary recoveries were determined for 5 days after the administration. Fecal and urinary recoveries of NFLX or ciprofloxacin (CPFX) were examined under various experimental conditions where the drugs were added to the urine or feces. Effects of the drug on the clinical laboratory test parameters and side effects were also examined. The following results were obtained. 1. NFLX reached the highest level in the feces in 5 cases in 24 hours and in 1 case in 48 hours; average peak fecal level was 137.1 micrograms/g in 24 hours. Fecal recoveries were 2.32 to 36.90% in 5 days after dosing with an average of 13.83%. 2. Urinary levels of the drug reached their peaks within 24 hours (average 51.46 micrograms/ml) in all cases and then decreased. Urinary recoveries were 11.15 to 46.44% in 5 days after dosing. Both fecal and urinary levels of the drug varied greatly among the subjects. 3. The sum of the fecal and the urinary recoveries in each case varied from 13.47 to 76.88% (average 42.24%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

[Effects of cefotaxime on the coagulation system, especially their dependence on vitamin K-related factors].

The authors administered cefotaxime to 20 children and studied laboratory parameters concerning peripheral blood: hemoglobin count, blood platelet count, red blood cell count, and hematocrit value, and the coagulation system: protein induced by vitamin K deficiency or by the presence of a vitamin K antagonist II (PIVKA II), hepaplastin test (HPT), prothrombin time (PT) and active partial thromboplastin time (APTT). The results obtained are summarized as follows: 1. Peripheral blood No abnormal values were observed. 2. Coagulation system (1) PIVKA II: In all cases, PIVKA II was negative. (2) HPT, PT and APTT: In all cases, no significant changes of these values which would suggest the tendency for prolonged bleeding were observed.

Adolescent↗
PubMed1987

Endogenous production of TNF-like cytotoxic factor in BCG-primed mice by heterologous fibrinogen.

The triggering activities of heterologous fibrinogen and fibrin on endogenous production of tumor necrosis factor (TNF)-like cytotoxic factor in vivo were examined. The triggering activities of fibrinogen or fibrin from four species injected into the peritoneal cavity of C3H/He mice infected i.p. with bacillus Calmette-Guérin (BCG) were tested. Heterologous, but not homologous, fibrinogen and fibrin showed triggering activity. The route of triggering by heterologous fibrinogen to elicit TNF-like activity systemically was studied. Injection of heterologous fibrinogen i.v. into mice infected i.v. with BCG resulted in a 40-fold higher serum TNF-like activity level than after its i.p. injection. The serum TNF-like activity level was maximal 1 h after i.v. injection of heterologous fibrinogen. When heterologous fibrinogen was injected several times i.v. into mice bearing solid-tumors, TNF-like activity was also released into the serum after every injection, although the activity decreased progressively on second and third injections to 10 and 1%, respectively, of that after the first injection. We used heterologous fibrinogens derived from different species for triggering every week to avoid this gradual decrease of TNF-like activity. In this way TNF-like activity was induced as highly as the primary induction. These results showed that TNF-like cytotoxic factor could be produced in vivo locally or systemically by heterologous fibrinogen or fibrin. Thus both agents should be useful as nontoxic triggering agents.

Animals↗
PubMed1987

[Pharmacokinetic and clinical studies of cefuzoname in the pediatric field].

Newly developed cefuzoname (CZON) was tested in 21 children and serum and urinary concentration and urinary recovery rates were determined. To 9 cases, 3 groups of 3 cases each, CZON was given at 10, 20 or 40 mg/kg one shot intravenously, and to 12 cases, 3 groups of 5, 3, 4 cases each, 10, 20 or 40 mg/kg was drip-infused over 1 hour. To 1 case of purulent meningitis 55.6 mg/kg was given one shot intravenously and concentrations in cerebrospinal fluid (CSF) and serum were measured. In 37 pediatric patients comprising 1 with tonsillitis, 24 with pneumonia, 1 with purulent meningitis and bacteremia, 7 with urinary tract infection, and 1 each with staphylococcal scalded skin syndrome, purulent lymphadenitis, periarthritis of jaw joint, maxillary sinusitis and orbital abscess, CZON was tried at 21.6 mg/kg (mean) per dose, 3 or 4 doses daily, one shot intravenously, for 7 days (mean). The clinical efficacy and antibacterial effectiveness were investigated. Also, the side effects were investigated and clinical laboratory tests done in the 37 pediatric cases plus 6 cases in which CZON was used but which were excluded from the efficacy analysis because they did not involve infections. The following is a summary of the results: 1. To 3 groups of 3 children each, 10, 20 or 40 mg/kg of CZON was given one shot intravenously. In each case the maximum serum concentration was observed at 5 min. after injection, and mean values of 3 groups with 10, 20 and 40 mg/kg dosing were 57.1, 147.2 and 316.7 mcg/ml respectively, indicating a dose-dependent response among the 3 groups. Mean half-lives were 0.83, 1.10 and 0.79 hours for 10, 20 and 40 mg/kg groups, respectively. The 10 mg/kg and the 40 mg/kg groups showed similar half-lives but the half-life of the 20 mg/kg group was a little longer than those of the other 2. 2. CZON was drip-infused over 1 hour to a total of 12 children divided into 3 groups of 5, 3 and 4 children at dose levels of 10, 20 and 40 mg/kg, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1987

Myogenesis in vitro as seen with the scanning electron microscope.

In this paper, we review our recent observations by scanning electron microscopy (SEM) on the differentiation of the cell surface and cytoplasmic organelles in embryonic chick skeletal muscle cells in vitro. The changes of the surface structures of myoblasts during mitosis were essentially similar to those of other cell types, but the characteristic spindle shape of myoblasts did not change throughout most of this period. Cytoskeletal structures under the sarcolemma were examined by Triton extraction and metal coating. Cells in S, G2 and M possessed a dense, and those in G1 a loose filament network under the membrane. Myotubes possessed a dense network under the sarcolemma. In the fusion area between a myoblast and a myotube, the cytoskeletal domain of the former could be distinguished from the latter because of the mosaic appearance of the subsarcolemmal cytoskeletal network. This network was composed predominantly of 10-13 nm filaments; they were identified as actin filaments because of their decoration with myosin subfragment-1. Triton treatment and thiocarbohydrazide-osmium staining allowed us to visualize myofibrils. They ran in the direction of inferred stress lines brought about by elongation and adhesion of the cells to substrate. Intracellular membranous organelles could be seen by the freeze-polishing and osmium-maceration procedure. Mitochondria exhibited complex irregular branchings. T system tubules ran a tortuous course. Sarcoplasmic reticula with occasional dilatations were connected to each other. The results are of sufficient promise to encourage more extensive analysis of myogenesis by SEM.

Animals↗
PubMed1987

[Pharmacokinetics of amikacin in children and neonates].

To evaluate pharmacokinetics of amikacin (AMK), one of the aminoglycoside antibiotics, children with ages from 2 days to 11 years were treated with various doses by various administration routes, and both plasma and urinary levels of AMK were determined. The following is a summary of the results obtained: 1. Of 6 children, three were treated with 2.0 mg/kg of AMK by a 30-minute intravenous drip infusion, and the other 3 with 4.0 mg/kg by a 60-minute. Peaks of average plasma levels were observed at the ends of the infusions in both cases, and their levels were 9.23 and 13.67 micrograms/ml, respectively, showing a dose-dependency. Both half-lives and areas under plasma concentration-time curves (AUCs) were similar to those of adults. However, the volume of distribution (Vd) showed a lower value than that of adults. Peaks of average urine levels were 149.3 micrograms/ml with 2.0 mg/kg in 0-2 hours after the start of the infusion and 223.3 micrograms/ml with 4.0 mg/kg in 2-4 hours. Average urinary recovery rates within 6 hours after the start of the infusion were 95.4% with 2.0 mg/kg and 85.7% with 4.0 mg/kg. These recoveries were equal to or higher than that of adults. 2. When 3.0, 4.0 and 6.0 mg/kg of AMK were administered to 3 groups of mature or premature babies by intramuscular injection, average peak levels of AMK in plasma were 6.26, 8.61 and 12.60 micrograms/ml, respectively, at 30 minutes after the injection, showing dose-dependency. In these groups, the younger the day age after birth was, the longer the half-life became. The AUCs were larger as the half-life became longer. The Vd was larger than that in the intravenous drip infusion group, but, any particular was not observed. Average peak levels of AMK in urine were 78.83 micrograms/ml at 4-6 hours with a dose level of 3.0 mg/kg, 99.17 micrograms/ml at 2-4 hours with 4.0 mg/kg and 139.20 micrograms/ml at 0-2 hours with 6.0 mg/kg. Average urinary recovery rates within 6 hours were 36.57% with 3.0 mg/kg, 34.67% with 4.0 mg/kg and 43.77% with 6.0 mg/kg. These recovery rates were markedly lower than those observed in adults and children. One of the causes of this low recovery is that mature and premature babies have immature renal functions. 3. When 3.0 mg/kg of AMK was administered to three premature babies by a 30-minute intravenous drip infusion, the average peak plasma levels was 7.61 micrograms/ml at the end of the drip infusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Amikacin↗
PubMed1987

[Effect of norfloxacin on bacterial flora in human feces].

Norfloxacin (NFLX), a synthetic oral antibacterial agent of quinolone carboxylic acid, was given orally for 5 full days at a dose of 200 mg, three times daily after each meal to healthy normal men with ages between 22 and 25 years weighing 53.0 to 84.0 kg (average 67.0 kg). The actual regimen followed was that the drug was administered twice after lunch and supper on the first day of dosing, and once after breakfast on the last day of dosing. On the 5th day before the start of dosing, on the first, 3rd and 5th days (last dosing day) of dosing, and on the 3rd, 5th, 10th and 20th days after the end of dosing, effects of the drug on the fecal flora were examined and its fecal levels were determined. Susceptibilities against NFLX and nalidixic acid (NA) of various fecal isolates from 7 men were determined. Adverse effects and influences on clinical laboratory tests were also examined. The results obtained are summarized below. 1. Following the drug administration, a transient decrease or disappearance of Escherichia coli, Klebsiella sp., Citrobacter sp. and Enterobacter sp. of Enterobacteriaceae was noted. The 3 strains other than E. coli were isolated from increasing number of cases after the end of dosing. No constant trend was observed in the isolation of Proteus sp. Organisms belong to Enterobacteriaceae were isolated only in 4 and 2 cases after 3 and 5 days of the start of dosing, respectively, but then gradually increased to the predose level. Among other Gram-negative bacteria, no constant trend was noted in the isolation frequency of Plesiomonas sp. Pseudomonas sp. was isolated from 6 and 5 cases on the 3rd day after dosing and on the 3rd day after the end of dosing, respectively; the frequency of isolation increased after dosing. Gram-positive bacteria such as Staphylococcus sp. were isolated with a reduced frequency on the 3rd day of dosing. However, the number of isolates increased in all cases both on the 5th day of dosing and on the 3rd day after the end of dosing, and then decreased. No change was noticed in the number of isolates of Enterococcus sp., and no constant trend was observed for Micrococcus sp. and YLO. The average count of the whole aerobic bacteria did not change. Some strains decreased significantly after the start of dosing. 2. Among anaerobes, Bacteroides fragilis and other Bacteroides were isolated on every test day.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase: tissue-selective inhibition of sterol synthesis and hypolipidemic effect on various animal species.

CS-514 is a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, a key enzyme in cholesterol synthesis. For the microsomal enzyme from rat liver, the mode of inhibition is competitive with respect to hydroxymethylglutaryl-CoA, and the Ki value is 2.3 X 10(-9) M. CS-514 also strongly inhibited the sterol synthesis from [14C]acetate in cell-free enzyme systems from rat liver and in freshly isolated rat hepatocytes; the concentrations required for 50% inhibition were 0.8 ng/ml and 2.2 ng/ml, respectively. On the other hand, the inhibition by CS-514 was much less in the cells from nonhepatic tissues such as freshly isolated rat spleen cells, and cultured mouse L cells and human skin fibroblasts. In addition, the cellular uptake of 14C-labeled CS-514 by isolated rat spleen cells or mouse L cells was less than one-tenth of that by isolated hepatocytes. These differences between hepatic and nonhepatic cells were further confirmed by the fact that CS-514 orally administered to rats inhibited sterol synthesis selectively in liver and intestine, the major sites of cholesterogenesis. CS-514 markedly reduced serum cholesterol levels in dogs, monkeys and rabbits, including Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia in man, but did not reduce those in rats and mice. In the former case, preferential lowering of atherogenic lipoproteins was observed in all of the animals tested. The biliary neutral sterols significantly decreased, whereas the amount of biliary bile acids was not affected by administration of the drug to dogs.

Animals↗
PubMed1986

Organization of filaments underneath the plasma membrane of developing chicken skeletal muscle cells in vitro revealed by the freeze-dry and rotary replica method.

Cytoskeletal organization and its association with plasma membranes in embryonic chick skeletal muscle cells in vitro was studied by the freeze-drying and rotary-shadowing method of physically ruptured cells. The cytoskeletal filaments underlying the plasma membranes were sparse in myogenic cells at the stage when cells exhibited great lipid fluidity in plasma membranes (fusion competent mononucleated myoblasts and recently fused young myotubes). Myotubes at more advanced stages of development possessed a highly interconnected dense filamentous network just underneath the cell membrane. This subsarcolemmal network was composed predominantly of 8-10 nm filaments; they were identified as actin filaments because of their decoration with myosin subfragment-1. Fine fibrils having a diameter of 3-5 nm were found on the protoplasmic surface of the plasmalemma at both the early and advanced stages of development. They were associated with the subsarcolemmal cytoskeletal filaments. Short 2-5 nm cross-linking filaments were occasionally seen between filaments in the subsarcolemmal network. We conclude that, although the subsarcolemmal cytoskeletal network contains many actin filaments, this domain appears to play some role in preserving the cell shape in the form of the membrane skeleton rather than membrane mobility.

Aging↗
PubMed1986

Changes in the peripheral vasculature of various organs in patients with sarcoidosis--possible role of microangiopathy.

Vascular involvement in sarcoidosis is briefly reviewed with emphasis on the outcome of a 10-year project-study by the Sarcoidosis Research Committee of the Japanese Ministry of Health and Welfare. Examples of vascular disorder associated with sarcoidosis are presented, including basal lamina layering of the capillaries in the skeletal muscle, cardiac muscle, and lung, glomerulopathy in the kidney, vascular changes in the ocular fundus and bronchi, and impaired peripheral circulation that could be detected by thermography. According to our tentative definition, all of these disorders should be collectively called microangiopathy. The possible role of microangiopathy in the pathogenetic mechanism of sarcoidosis is also discussed. Although microangiopathy in sarcoidosis is a comprehensive term, it should be included, in addition to systemic granulomatous disease, as part of the clinicopathological entity of sarcoidosis.

Bronchi↗
PubMed1986

Serial changes in cellular immunity of septic patients with multiple organ-system failure.

Total lymphocyte count, lymphocyte cell-surface markers (OKT3, OKT4, OKT8, and B-1), serum complement factors (C3 and C4), immunoglobulins (IgG, IgA, and IgM), ceruloplasmin (Crl), and transferrin (Trf) were determined weekly for nine septic postoperative patients, all of whom had multiple organ-system failure. The peripheral blood total lymphocyte count, its subpopulation, T-cell subset, and proliferative responses of lymphocyte to phytohemagglutinin (PHA) and concanavalin A (Con A) decreased in all patients. OKT3 and B-1 decreased progressively in the four nonsurvivors compared with the five survivors. Although immunoglobulin levels were within the normal range in both groups, they tended to increase in survivors and decrease in nonsurvivors. Serial levels of C3, C4, Crl, and Trf increased in survivors but did not change in nonsurvivors. T-cell function and antibody-producing activity diminished progressively in nonsurvivors. These changes in cellular immunity may represent another manifestation of multiple organ-system failure during sepsis.

Adult↗