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Biomedical subjects

S Iwata

Publications and source records attributed to S Iwata.

At least 307 records · Page 17Linked to original sources

[Pharmacokinetic and clinical studies on cefmenoxime in neonates and premature infants].

Pharmacokinetic and clinical studies on cefmenoxime (CMX) in neonates and premature infants were conducted. The results are summarized as follows. 1. Intravenous administration of CMX at 20 mg/kg, via bolus injection or 1-hour drip infusion, produced at sufficiently high blood concentration. As it is the case with other cephem antibiotics, the half-life varied with age and tended to become shorter with aging. 2. There were intergroup differences in urinary recovery of the drug, but urinary concentrations were generally high. 3. In the clinical evaluation, 12 out of 15 cases which were evaluable for efficacy were rated "excellent" or "good". 4. Side effects were evaluated in 27 cases. A bleeding tendency was found in 1 case, eosinophilia in 1 case, elevated GOT in 1 case, and positive PIVKA II in 4 cases. It is, therefore, concluded that CMX is a highly useful drug for the treatment of bacterial infections in neonates and premature infants.

Bacterial Infections↗

[Clinical studies on sulbactam/ampicillin in the field of pediatrics].

During 8 months from October 1986 to May 1987, the clinical efficacy of sulbactam/ampicillin (SBT/ABPC) was evaluated in 63 pediatric inpatients with various infections. Clinical efficacies were evaluable in 58 patients among them (consisting of 2 patients with sepsis, 3 with tonsillitis, 12 with bronchitis, 6 with bronchopneumonia, 24 with pneumonia, 1 with phlegmon, 2 with lymphadenitis, 1 with impetigo and 7 with urinary tract infection) and were excellent in 40 patients and good in 17 with an overall efficacy rate of 98.3%. Bacteriological efficacies were assessed in 25 patients and 27 strains of organisms (consisting of 3 strains of Staphylococcus aureus, 2 Streptococcus pneumoniae, 1 Streptococcus pyogenes, 2 beta-Streptococcus, 1 Gram-positive cocci, 5 Escherichia coli, 1 Enterobacter aerogenes, 7 Haemophilus influenzae, 2 Haemophilus parainfluenzae, 1 Branhamella catarrhalis, 1 Proteus mirabilis and 1 Salmonella subgenus I). Bacteriological eradication rates were 88.9% for Gram-positive organisms, 66.7% for Gram-negative organisms and 74.1% overall. No superinfection was observed in any of patients treated. Side effects and clinical laboratory parameter abnormalities observed consisted of diarrhea in 7 (11.1%) of the 63 patients, eosinophilia in 2 (3.3%) of 61 tested, thrombocytosis in 3 (5.5%) of 55, elevation of direct bilirubin in 1 (3.3%) of 30, elevation of total bilirubin in 1 (3.1%) of 32, elevation of GOT in 4 (6.8%) of 59 and elevation of GPT in 1 (1.7%) of 59 patients tested. As an effect on the hemostatic mechanism of this drug, PIVKA II was detected in 1 patient (4.2%) of 24 tested, but findings of other coagulation tests were normal and none of patients showed bleeding tendency or inhibition of platelet aggregation. From the above results, it appears that SBT/ABPC is an efficacious and safe drug in the treatment of bacterial infections of pediatric patients.

Adolescent↗

[The influence of cefpodoxime proxetil on the intestinal bacterial flora].

The influence of cefpodoxime proxetil (CPDX-PR, CS-807), a new oral cephalosporin, on the intestinal bacterial flora was studied in tetra-contaminated mice and in pediatric patients. CPDX-PR dry syrup was administered at a dose of 10 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of bacteria: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. No notable changes were observed in fecal viable cell counts except that slight decreases of E. coli counts were observed on the days 3 to 5 after starting administration. The subjects in the pediatric study were 5 children with infections, 3 boys and 2 girls at ages from 1 year 1 month to 6 years 10 months, with their body weights ranging from 9.3 to 23.8 kg. CPDX-PR dry syrup was administered at a dose between 3.0 to 3.7 mg/kg, 3 times a day for 4 to 7 days. Although some variations of the fecal bacterial flora were noticed between subjects during the administration of CPDX-PR, no notable changes were observed in major aerobic and anaerobic bacteria such as Enterobacteriaceae, Enterococcus, Bacteroides and Bifidobacterium in 4 of the 5 cases. Large decreases in Streptococcus, Enterobacteriaceae, Bifidobacterium, Eubacterium and anaerobic cocci and an increase in Enterococcus were observed in the other case. There was no case in which glucose non-fermenting Gram-negative rods and fungi became predominant. Regarding Enterobacteriaceae, transitory bacterial replacement was observed within the genus. Fecal concentration of CPDX during the administration of CPDX-PR was extremely low or below the detectable limit except one specimen from a case in which intestinal bacterial flora showed remarkable changes. From the above, CPDX-PR appears to be a drug with a relatively small influence on the intestinal bacterial flora.

Animals↗

[Bacteriological and clinical evaluations of cefmenoxime in neonates and premature infants].

The antimicrobial activity of cefmenoxime (CMX) against B group Streptococcus was investigated. The clinical efficacy of CMX was determined in neonates and premature infants. The results are summarized below. 1. MIC's of CMX against 39 strains of B group Streptococcus obtained from the pregnant vagina were below 0.05 micrograms/ml. 2. CMX was given in a dose of 20 mg/kg by intravenous bolus injection to 3 neonates with birth weight over 2,500 grams. Peak serum concentrations ranged from 54.0 to 199 micrograms/ml and the mean half-life was 1.8 hours. 3. Efficacies of CMX were good to excellent in 5 cases administered for treatment and in 4 cases for prophylaxis. As abnormal laboratory parameters, elevation of GOT and eosinophilia were observed in each 2 cases. 4. Examinations on intestinal bacteria in 2 cases revealed that CMX gave as much influences to the flora as other third-generation cephems. 5. The vitamin K deficiency were observed in 2 out of 6 cases examined.

Bacterial Infections↗

In vitro inhibition of lens epithelial cell growth by continuous wave Nd:YAG laser.

Bovine lens epithelial cells were suspended in MEM medium and subjected to continuous wave, low power, pulsed neodymium:yttrium-aluminum-garnet (Nd:YAG) laser irradiation. The temperature of each suspension was maintained at 36 degrees C. Laser applications ranged from 1 to 10 watts and from 100 to 2000 seconds, but the total dose to each of the epithelial cell suspension was 2000 J. Six to thirty-nine percent of the cells were dead immediately after irradiation. Surviving cells, cultured for 15 days, showed decreased attachment and failed to grow. These preliminary results suggest that the Nd:YAG laser may be used during cataract surgery to prevent subsequent lens epithelial cell proliferation and the resulting vision reduction and glare.

Animals↗

[Pharmacokinetic and bacteriological studies on sulbactam/ampicillin in the field of pediatrics].

Pharmacokinetic and bacteriological studies were carried out on sulbactam/ampicillin (SBT/ABPC) in the field of pediatrics. The results obtained are summarized as follows: 1. A total of 248 clinical isolates were employed to determine minimum inhibitory concentrations (MIC) of SBT/ABPC against various bacterial species. SBT/ABPC showed stronger antibacterial activity against Gram-positive organisms than against Gram-negative rods. 2. The peak serum level of ABPC was about twice as high as that of SBT, and serum levels of ABPC and SBT declined with time. Both drugs showed almost the same trend of changes in concentrations. The half-lives of both drugs were about 1 hour. 3. The urinary recovery rates over 6 hours after administration were 52-80% for ABPC and 70-73% for SBT. 4. The effect of SBT/ABPC on coagulation system was examined. No case showed changes in PT, APTT, TT and HPT before and after administration of SBT/ABPC. Platelet aggregation during administration of SBT/ABPC was slightly faster than that before administration, suggesting that SBT/ABPC had no effect on platelet aggregation. Generally speaking, it seemed that SBT/ABPC was a safe antibiotic for bleeding. 5. The effect of SBT/ABPC on the intestinal bacterial flora in experimental animals was examined. Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve were reduced after administration of SBT/ABPC, suggesting that the intestinal bacterial flora was affected by the administration of SBT/ABPC more greatly than by the administration of ABPC alone. In a similar investigation being made with clinical cases, both aerobes and anaerobes showed great changes. Concentrations of the drugs in feces increased with increasing dosage, resulting in greater changes of the intestinal bacterial flora. Thus, the total number of aerobes and anaerobes was reduced. No diarrhea was observed in any subjects examined. From the above results, it appeared that SBT/ABPC was a safe and useful antibiotic for various bacterial infections in the field of pediatrics.

Age Factors↗

[Pharmacokinetic, bacteriological and clinical studies on cefpodoxime proxetil in the field of pediatrics].

Pharmacokinetic, bacteriological and clinical studies on cefpodoxime proxetil (CPDX-PR, CS-807), a newly developed oral cephem, were carried out in the treatment of infectious diseases in the field of pediatrics. 1. Since CPDX demonstrates very powerful antimicrobial actions against such Gram-negative bacilli as Escherichia coli, Salmonella sp., Klebsiella pneumoniae and Serratia sp., such Gram-positive cocci as Streptococcus pyogenes and Streptococcus pneumoniae, and beta-lactamase producing Branhamella catarrhalis and Haemophilus influenzae, this drug was thought to be useful for the treatment of pediatric infectious diseases when main causative bacteria in the field of pediatrics were taken into account. 2. When changes in blood and urine concentrations of CPDX following the administration of this drug at 3.7 mg/kg before meal were determined, Cmax and T1/2 were found to be 2.98 micrograms/ml at 2-hour and 1.73 hours, respectively; an urinary excretion rate in the first 6 hours and a maximum urine concentration were 32.5% and 52 micrograms/ml, respectively. 3. Clinically, 8 of 8 patients with the upper respiratory tract infections (100%), 28 of 29 patients with bronchitis and/or pneumonia (96.6%), 3 of 4 patients with otitis media (75%), 2 of 2 patients with sinusitis (100%), 3 of 3 patients with the skin soft tissue infections (100%), 1 of 1 patient with bacterial enteritis (100%) and 11 of 14 patients with urinary tract infections (78.6%) responded well to the treatment with CPDX-PR, showing a 91.8% efficacy rate in all the patients treated. 4. Bacteriologically, Staphylococcus aureus, Staphylococcus epidermidis, S. pyogenes, S. pneumoniae, E. faecalis, B. catarrhalis, H. influenzae, E. coli and Salmonella typhimurium were all eradicated from 5, 1, 4, 6, 1, 5, 5, 11 and 1 patient, respectively. An eradication rate in all the patients examined was 97.5% (39/40). 5. Gastrointestinal symptoms appeared as side effects in 2 of 71 patients (vomiting in 1 and diarrhea in 1), hence, an incidence of side effects was 2.8% (2/71). As for abnormal laboratory findings, eosinophilia, thrombocytosis and increases in GOT and GPT were observed in 3 of 39 patients examined (7.7%), 1 of 39 patients (2.6%) and 2 of 34 patients (5.9%), respectively. In addition, we also examined the effect of the drug on the hemostatic system, but found no changes upon the treatment. Based on these results, it appeared that CPDX-PR was a useful and safe drug in treatment of infectious diseases in the field of pediatrics when administered 2-3 times a day at a dose of 3-6 mg/kg.

Absorption↗

[The influence of cefteram pivoxil on the intestinal bacterial flora].

The influence of cefteram pivoxil (CFTM-PI), a new oral cephalosporin, on the intestinal bacterial flora was studied in tetra-contaminated mice and in pediatric patients. CFTM-PI in fine granular form was administered at a dose of 10 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of organisms: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. No remarkable change was observed in the fecal viable cell count except that slight decrease in E. coli count was observed on days 2 to 5 after starting administration. The subjects in pediatric study were 5 children, 3 boys and 2 girls at ages from 6 months to 10 years 4 months, with infections. Their body weights ranged from 3.5 to 28.0 kg. CFTM-PI in fine granular form was administered at each dose of 3.0 to 3.8 mg/kg, 3 times daily for 5 to 11 days. During the administration of CFTM-PI, there were some variations in the change of the fecal bacterial flora noticed between subjects. Although Enterobacteriaceae tended to decrease and Enterococci tended to increase, other main aerobes and anaerobes were almost unchanged in most cases. There was no case in which glucose non-fermenting Gram-negative rods and fungi became predominant. In a 10 years 4 months old boy, the fecal concentration of CFTM, the active form of CFTM-PI, was 72.20 micrograms/g and a remarkable decrease of total anaerobe count was observed. In feces, CFTM-PI and CFTM were detected in 4 and 2 cases respectively, and their concentrations were 1.50 approximately 89.65 micrograms/g and 2.25 approximately 72.20 micrograms/g, respectively. beta-Lactamase activities in feces were positive in all cases. From the above, CFTM-PI is considered to be a drug with relatively less influence on the intestinal bacterial flora. But as high concentrations of drugs were detected in feces under some circumstances, we need to pay attention to fecal drug concentrations.

Animals↗

[A clinical study on cefteram pivoxil in pediatrics].

Clinical evaluations of cefteram pivoxil (CFTM-PI, T-2588) were carried out. The obtained results are summarized as follows. 1. Clinical responses to CFTM-PI of 39 patients with pediatric infections were excellent in 16, good in 21, fair in 1 and poor in 1. The overall efficacy rate was 94.9%. 2. Bacteriologically, eradication rates for 39 isolates presumed to be pathogens were evaluated. The eradication rates obtained were 94.1% in 17 strains of Gram-positive cocci, 90.9% in 22 strains of Gram-negative rods. 3. Side effects observed were diarrhea in 2 patients, diarrhea and abdominal pain in 1, erythema and edema in 1. The incidence was 8.7%. An abnormal value found in clinical laboratory tests was eosinophilia in 1 patient. The results suggested that CFTM-PI might be a very useful and safe drug for the treatment of pediatric infections.

Bacterial Infections↗

Left ventricular structural characteristics in unilateral renovascular hypertension and primary aldosteronism.

To assess the importance of the renin-angiotensin system and plasma volume as determinants of hypertensive left ventricular hypertrophy and its anatomy, patients with unilateral renovascular hypertension and primary aldosteronism were studied by echocardiography. Blood pressure, age and sex were matched as closely as possible. The 19 patients with unilateral renovascular hypertension and the 19 patients with primary aldosteronism were similar in age, sex and blood pressure (168 +/- 19/97 +/- 11 and 163 +/- 17/99 +/- 10 mm Hg, respectively), but plasma volume was increased in the patients with primary aldosteronism. Interventricular septal thickness, left ventricular posterior wall thickness, left ventricular mass index and relative wall thickness did not differ between the 2 groups of patients. There was a significant correlation between the level of systolic blood pressure and either left ventricular mass index (r = 0.34, p less than 0.05) or relative wall thickness (r = 0.58, p less than 0.001) in both groups of patients. Left ventricular end-diastolic dimension index was increased in the patients with primary aldosteronism compared with those with unilateral renovascular hypertension (3.2 +/- 0.4 vs 2.9 +/- 0.3 cm/m2, p less than 0.02). When confined to the patients with systolic pressure greater than or equal to 150 mm Hg, relative wall thickness was significantly increased in the patients with unilateral renovascular hypertension. Patients with primary aldosteronism and unilateral renovascular hypertension of similar blood pressure levels, age and sex have almost identical degrees of left ventricular hypertrophy and anatomy. In contrast, the patients with primary oldosteronism had increased left ventricular dimension index.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Inhibition of the tumor-promoting action of 12-O-tetradecanoylphorbol-13-acetate by some oleanane-type triterpenoid compounds.

Since glycyrrhetinic acid was proved to suppress tumor promoter effects, several oleanane-type triterpenes which were chemically derived from oleanolic acid and hederagenin were tested in vitro and in vivo against the action of tumor promoter, 12-O-tetradecanoylphorbol 13-acetate. By in vitro experiment monitoring with 12-O-tetradecanoylphorbol-13-acetate-induced stimulation of 32Pi incorporation into phospholipids and an in vivo test on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene and promoted with 12-O-tetradecanoylphorbol-13-acetate, 18 beta-olean-12-ene-3 beta,28-diol (= erythrodiol), 18 beta-olean-12-ene-3 beta,23,28-triol, 18 alpha-olean-12-ene-3 beta,28-diol, and 18 alpha-olean-12-ene-3 beta,23,28-triol showed remarkable suppressive effects. Especially 18 alpha-oleanane derivatives having a CH2OH grouping converted from the COOH group initially allocated at C-17 were 100 times more effective than glycyrrhetinic acid both in vitro and in vivo.

Animals↗

Studies on the mercapturic acid pathway in the rabbit lens.

We have examined the mercapturic acid pathway of the cataractous rabbit lens following induction by naphthalene as an oxidative foreign substance. 1,2-Naphthoquinone, which is formed in the eye from naphthalene diol and other naphthalene derivatives by a combination of enzymic and non-enzymic reactions, readily oxidizes GSH and GSH S-transferase [EC 2.5.1.18] in the lens scavenging system. 1,2-Naphthoquinone appeared in the rabbit aqueous humor after 8 h, and showed a maximum level in the lens 24 h after naphthalene administration, with marked accumulation in the lens nucleus. At the same time, the GSH level and GSH S-transferase activity in the lens decreased after 4 h, and lens opacification appeared 7 days after naphthalene administration. Furthermore, we identified the naphthalene metabolite, N-acetyl-S-(1,2-dihydro-2-hydroxynaphthyl) cysteine, in the lens of rabbit after naphthalene administration and in an in vitro experiment on lens homogenate using gas chromatography-mass spectrometry (GC-MS). This compound is an intermediate of the mercapturic acid pathway, and indicates that naphthalene derivatives are metabolized through the mercapturic acid pathway which acts as a scavenging system in the lens.

Acetylcysteine↗

Effect of freezing on lens epithelial cell growth.

The effect of freezing on the growth of rat lens epithelial cells was studied in vitro. We found that 80% of the lens epithelial cells died after freezing at -45 degrees C for two hours and that the surviving cells could grow with the addition of growth factors or when placed on a sheet of type 4 collagen, but not when placed on a plain plastic culture dish. These results suggest that the surviving cells are at the Go phase of the cell cycle and that type 4 collagen or growth factors can initiate cell division.

Animals↗

Light scattering caused by cells on the intraocular lens.

The anterior surface of a posterior chamber intraocular lens (IOL) was covered with cultured rat lens epithelial cells and light scattering was measured densitophotometrically. The light scattering intensity was maximum at a 30-degree scattering angle and was proportional to the number of cells per area on the IOL. Results suggests that the adhesion of lens epithelial cells on the IOL may influence its optical function.

Animals↗

The evaluation of therapeutic efficacy of hachimi-jio-gan (traditional Chinese medicine) to mouse hereditary cataract.

This study was of a series of the evaluation of Hachimi-Jio-Gan (Rehmannia Eight Formula, pa-wei-ti-huang-wan or Bawei dihuang wan) to the various cataracts. In this study, the drug was evaluated for its therapeutic efficacy to mouse hereditary cataract from the delay effect of cataract appearance age and the suppression rates of variation of some biochemical parameters. The dose of 200 mg of Hachimi-Jio-Gan/day/100 g of mouse body weight significantly delayed the cataract appearance age by 4 days as compared to that of non-treated group. We estimated that the delay effect of 4 days in mouse may be corresponded to 13.9 years, when it was converted into the case of human. This drug also suppressed variation of sodium and potassium ions level in the lens with cataractogenesis. Furthermore, the drug dramatically reactivated the sodium-potassium ATPase activity damaged with the cataract formation, and also had a slight action of reducing agent. From these facts, we presumed that the drug may have a prophylactic efficacy to the cataract caused by the inhibition of sodium-potassium ATPase activity and also the oxidation of lens protein.

Administration, Oral↗