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Biomedical subjects

Y Nakada

Publications and source records attributed to Y Nakada.

At least 91 records · Page 5Linked to original sources
PubMed1988

Molecular cloning and nucleotide sequence of Thermus thermophilus HB8 trpE and trpG.

The trpE gene of Thermus thermophilus HB8 was cloned by complementation of an Escherichia coli tryptophan auxotroph. The E. coli harboring the cloned gene produced the anthranilate synthase I, which was heat-stable and enzymatically active at higher temperature. The nucleotide sequence of the trpE gene and its flanking regions was determined. The trpE gene was preceded by an attenuator-like structure and followed by the trpG gene, with a short gap between them. No other gene essential for tryptophan biosynthesis was observed after the trpG gene. The amino-acid sequences of the T. themophilus anthranilate synthase I and II deduced from the nucleotide sequence were compared with those of other organisms.

Amino Acid Sequence↗
PubMed1988

The effect of additives on the oral mucosal absorption of human calcitonin in rats.

The oral mucosal absorption of human calcitonin (HCT) was investigated in rats. Enhanced absorption of HCT was observed by coadministration of additives such as sodium deoxycholate, sodium tauroglycocholate, quillajasaponin (Quillayannin P-20), sodium lauryl sulfate, sodium myristate and sugar esters. The contribution of sugar esters to oral mucosal absorption of HCT was studied in some detail. The addition of a sugar ester having a hydrophilic-lipophilic balance value between 11 to 16 was found to be effective in increasing the absorption of HCT. Furthermore, it suggested that the type of constituent fatty acid of sugar ester was one of several important factors for the promotion of the oral mucosal absorption of HCT.

Absorption↗
PubMed1987

Amino-acid sequence of a tetrameric, manganese superoxide dismutase from Thermus thermophilus HB8.

The amino-acid sequence of a tetrameric manganese superoxide dismutase from Thermus thermophilus HB8 has been determined. The protein was cleaved with cyanogen bromide (BrCN) into four peptides and their alignment was deduced through the fragment of partial cleavage with BrCN and the peptides were produced by cleavage of the protein with o-iodosobenzoic acid. Most of the peptides were sequenced by solid phase Edman degradation. Some of the peptides were sequenced by the Edman dansyl method after sub-fragmentation by proteinase digestion. The amino-acid sequence consists of 203 residues corresponding to a subunit molecular weight of 23,144.

Amino Acid Sequence↗
PubMed1987

[The study of flomoxef in the pediatric field].

Flomoxef (FMOX; 6315-S), a new synthetic oxacephem antibiotic, was studied in the pediatric field and pharmacokinetic and clinical results obtained were summarized below. 1. The activity of FMOX against Staphylococcus aureus isolated from clinical patients, including latamoxef resistant strains was very high and MIC was approximately less than or equal to 0.39 microgram/ml. This MIC value was lower than other cephem antibiotics such as cefotaxime, cefotiam, cefmetazole, cefamandole. The distribution of MIC's of FMOX against Escherichia coli and Salmonella spp. ranged from 0.05 to 0.78 microgram/ml and from 0.05 to 0.39 microgram/ml, respectively. 2. Serum concentrations of FMOX after dosages of 20 mg/kg and 40 mg/kg with 1 hour intravenous drip infusion were 21.5-27.5 micrograms/ml, 6.00-7.81 micrograms/ml, 0.37-0.59 micrograms/ml at 1, 2, 5 hours after administration, respectively, and T1/2(beta) were 0.61-0.83 hour. Serum concentrations after one shot intravenous injection of 20 mg/kg FMOX were 56.7-90.2 and 0.20-0.26 micrograms/ml at 3-10 minutes and 6 hours after administration, respectively, T1/2(beta) was 1.22 hours and urinary excretion rate was 66.7-69.8% in 6 hours. 3. FMOX was administered to 32 cases (upper and lower respiratory tract infection, and purulent infections) at 3-4 times daily for 4-13 days. In these cases the daily dosage amounted to 41-119 mg/kg. Clinical effectiveness was 97% overall including resistance cases upon other cephem antibiotic treatment. All bacterial species identified including Branhamella catarrhalis, Streptococcus pyogenes, S. aureus, Streptococcus agalactiae, and Haemophilus influenzae were eradicated upon the treatment with FMOX. 4. Only 3 cases of soft stool, 1 case of elevated GOT and GPT, and 1 case of elevated GPT were observed, and all of these adverse reactions were normalized after the completion of treatment.

Age Factors↗
PubMed1987

[Evaluation of cefuzonam in the pediatric field].

Cefuzonam (L-105, CZON) was studied in pediatric infections. A summary of the results it as follows: For recently isolated Staphylococcus aureus strains, Peak MICs of CZON were distributed between 0.39 and 0.78 micrograms/ml showing a greater susceptibility of S. aureus to CZON than to cefoperazone (CPZ), latamoxef (LMOX), and cefmenoxime (CMX). Peak MICs of CZON for Escherichia coli were 0.10-0.20 micrograms/ml, similar to those of CPZ, LMOX, and CMX. Ampicillin (ABPC)-resistant strains were also susceptible to CZON. MICs for Salmonella were similar to those for E. coli. Peak MICs of CZON for Vibrio parahaemolyticus were 0.20-0.39 micrograms/ml. The susceptibility of the bacteria to CZON was far greater than to ABPC, and was similar to CPZ, LMOX, and CMX. With 20 mg/kg drip infusion, serum concentrations reached their peaks at the end of administration with values of 20.6-68.7 micrograms/ml, which decreased to 0.43-1.70 micrograms/ml after 2 hours. Half-lives of CZON in serum were 0.68-1.2 hours. With 50 mg/kg drip infusion, serum concentrations reached their peaks at the end of administration with levels of 69.0-82.0 micrograms/ml, and at after 2 hours 1.85-3.45 micrograms/ml. Thus, an apparent dose response was observed. Half-lives of CZON in serum were 0.63-0.99 hours. Urinary recovery rates in 6 hours were 39.9-80.5%. A total of 44 cases of 10 different types of acute pediatric infections was treated by CZON intravenous drip infusion as the main therapeutic procedure. The efficacy rate was 93.2%, and the compound was effective on purulent infections, acute urinary tract infection, etc. with pathogens such as ABPC-resistant S. aureus, E. coli, and Enterococcus faecalis. Dosage levels per day were 50 to 80 mg/kg in most cases. In infections with S. aureus (8 strains), Streptococcus pneumoniae (3 strains), E. faecalis (1 strain), Haemophilus parahaemolyticus (1 strain), Haemophilus parainfluenzae (2 strains), Haemophilus influenzae (11 strains), Bordetella pertussis (1 strain), E. coli (3 strains), a total of 30 strains, bacterial elimination was noted with an exception of 1 strain of S. aureus. The compound was used for 4 to 15 days, but side effects observed clinically were only 1 case of diarrhea and 1 case of thrombocytosis.

Adolescent↗
PubMed1986

[Fundamental and clinical studies with imipenem/cilastatin sodium, a new carbapenem antibiotic, in the field of pediatrics].

Fundamental and clinical evaluations of imipenem/cilastatin sodium (MK-0787/MK-0791) were carried out in pediatric patients. The following results were obtained: After intravenous drip infusion of single doses of 10 mg/10 mg/kg to 20 mg/20 mg/kg of MK-0787/MK-0791 in children, peak plasma levels of MK-0787 ranged from 32.0 to 82.0 micrograms/ml at the end of the infusion. The half-life was 49.9 to 64.0 minutes. The cumulative urinary recovery at 6 to 7 hours after the 1 hour drip infusion ranged from 65.5 to 88.9%. Fecal levels of MK-0787 were 4.2 and 23.1 micrograms/g at 6 hours after a 30-minute intravenous drip infusion of 200 mg/200 mg of MK-0787/MK-0791. MK-0787/MK-0791 was administered by intravenous drip infusion to patients with purulent meningitis. Penetration into the cerebrospinal fluid was satisfactory, as were the clinical responses. MK-0787/MK-0791 was administered clinically in doses of 30 mg/30 mg/kg/day to 200 mg/200 mg/kg/day by intravenous drip infusion 3 or 4 times a day for 3 to 22 days to 26 patients with acute pediatric infections. The clinical response was excellent in 18 patients and good in 8 patients. Eradication occurred with 16 isolates; only two strains of Salmonella-B were not eradicated. Anorexia in 1 patient was the only clinical adverse effect reported, and the only adverse effects found in laboratory tests were eosinophilia and thrombocytosis in 1 patient, respectively, and elevation of the S-GOT and S-GPT in 1 patient.

Adolescent↗
PubMed1986

[General pharmacology of T-2588, a new oral cephem antibiotic].

A new oral cephem antibiotic, T-2588, the pivaloyloxymethyl ester of (+)-(6R, 7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3- [(5-methyl-2H-tetrazol-2-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2. 0]oct-2-ene-2-carboxylic acid (T-2525), is mainly absorbed from the intestinal tract and biotransformed to T-2525 thereafter. General pharmacological activities of T-2588 were studied and following results were obtained. On the central nervous system, T-2588 did not show any effects at oral doses of 500-2,000 mg/kg and T-2525 produced only a slight elevation of body temperature in rabbits without any other effects at an intravenous dose of 500 mg/kg. On the respiratory and cardiovascular systems, T-2525 caused a slight hypotension and increased both respiratory rate and femoral blood flow, but no changes were observed in heart rate and electrocardiogram in dogs at an intravenous dose of 500 mg/kg. The T-2525 exerted no significant influence on blood pressure response to isoproterenol, acetylcholine or histamine, but showed a slight tendency to decrease pressor response to adrenaline in dogs at intravenous doses of 100-500 mg/kg. For the renal function in rats, T-2588 had no effects on urine volume, electrolytes and PSP excretion at oral doses of 500-2,000 mg/kg. Intravenous administration of T-2525 caused an increase of sodium excretion at 500 mg/kg and dose-dependent increases of PSP excretion at 20-500 mg/kg. Hematological studies revealed that both T-2588 at oral doses of 500-2,000 mg/kg and T-2525 at intravenous doses of 100-500 mg/kg had no effects on bleeding time in mice, blood coagulation and platelet aggregation in rats. The T-2588 exerted no effect on the gastrointestinal system in rats or mice and had no antiinflammatory activity in rats at oral doses of 500-2,000 mg/kg. The T-2525 scarcely affected the motilities of isolated smooth muscle preparations in experimental animals including stomach, ileum, colon, uterus, vas deferens and trachea at a concentration as high as 10(-3) g/ml. The T-2525 increased bile secretion in rats at intravenous doses of 100-500 mg/kg. The T-2525 slightly decreased the twitch tension of musculus gastrocnemius induced by electrical stimulation in rats at an intravenous dose of 500 mg/kg. These results indicate that T-2588 is a pharmacologically inactive antibiotic.

Animals↗
PubMed1985

[Experimental and clinical studies on BRL 25000 (clavulanic acid-amoxicillin) granules in the pediatric field].

Fundamental and clinical studies have been performed on the BRL 25000 granules (combination of amoxicillin (AMPC) and potassium clavulanate (CVA) in 2: 1 ratio) in the pediatric field. In bacteriological studies a potentiated antibacterial activity of BRL 25000 was recognized against AMPC-resistant and beta-lactamase producing clinical isolates. The pharmacokinetics of the BRL 25000 granules were studied at dose levels from 10 to 20 mg/kg. The peak serum concentrations of AMPC and CVA achieved approximately 1 hour after dosing were 4.29-9.55 micrograms/ml and 3.87-4.78 micrograms/ml, respectively. The serum half-life was found to be 0.90-1.31 hours for AMPC and 1.01-1.22 hours for CVA. Six-hour urinary excretion rates were 29.5-62.6% for AMPC and 12.6-37.9% for CVA. In the clinical studies, the BRL 25000 granules were administered to 36 pediatric patients (15 with upper and lower respiratory tract infections, 10 with urinary tract infections and 11 with skin or soft tissue infections, etc.) at dose levels of 30-50 mg/kg/day. Clinical results in all cases were excellent or good. In particular, good bacterial and clinical effects were obtained against infections caused by beta-lactamase producing AMPC-resistant strains except E. cloacae 1 strain. No adverse reactions or abnormal laboratory findings were recognized in any patient.

Administration, Oral↗
PubMed1985

[Studies on the intravenous administration of aspoxicillin in the pediatric field].

Fundamental and clinical studies were made on the intravenous administration of aspoxicillin (ASPC) in pediatric field and the following results were obtained. The peak serum concentrations of 15.6-84.0 micrograms/ml were seen immediately after a 1-hour drip infusion of 10-30 mg/kg, there being seen a clear dose response. The half-life was 0.78-1.67 hours and the measurable concentrations were detected in the serum up to 6 hours after administration. The urinary excretion rate was 44.1-78.6% up to 6 hours after drip infusion. Twenty-four patients with acute respiratory tract infection (21 cases), urinary tract infection (3 cases) were treated with ASPC by drip infusion of 50-107 mg/kg/day for 5-15 days and resulted in 100% of good response. S. pyogenes, S. viridans, E. coli, H. influenzae and P. aeruginosa were isolated form the culture of sputum or urine in the patients, and they were all eradicated by treatment with ASPC except P. aeruginosa. No side effects were observed except the elevation of GOT and GPT in 1 case. From the above results, it is concluded that ASPC is one of useful drug for treatment of infections in pediatric field.

Amoxicillin↗
PubMed1985

[Fundamental and clinical studies of ceftizoxime rectal suppositories in the field of pediatrics].

This paper deals with fundamental and clinical results, in the field of pediatrics, of the newly developed rectal suppository (CZX-S) of a cephem antibiotic ceftizoxime (CZX). CZX-S was well absorbed in children. The mean peak serum concentrations of CZX in the 125 mg-administered group (average: 9.9 mg/kg) and the 250 mg-administered group (average: 13.4 mg/kg) were 5.10-7.71 micrograms/ml at 15-30 minutes after dosing. Serum concentrations of CZX were measurable level in almost all the children at 6 hours after administration with the half-lives were 1.34-1.55 hours. The 6-hour urinary excretion rate accounted for 16.5-22.0%. CZX-S was administered to 30 children with acute upper or lower respiratory tract infections about 20-60 mg/kg/day in 3-4 divided portions. CZX-S provided favorable therapeutic-effect in most of the children 3-5 days after administration. The effectiveness rate was 93%. The causative organisms of H. influenzae (3 cases) and S. aureus (4 cases) isolated clinically from pharyngeal mucous and sputum were eradicated after administration of CZX-S. Anal pain and diarrhea experienced in 5 of the 30 children and CZX-S was withdrawn in 4 (of the 5) children, but exhibited satisfactory therapeutic-effect in 2 of the 4 cases up to withdrawal of the drug. An increase in GOT and GPT was observed in 3 cases. The values returned to the normal range in 1 case after the treatment with CZX-S. The test was not reexamined in the other 2 cases. The present clinical result suggests the usefulness of CZX-S substituted for oral and injectable forms in the treatment of various pediatric infections caused by organisms sensitive to CZX.

Bacteria↗
PubMed1985

[Fundamental and clinical studies of aztreonam in the field of pediatric].

The fundamental and clinical studies of aztreonam (AZT) were performed. The results were as follows: The MICs of AZT for E. coli and Salmonella sp. which were recently isolated in the pediatric field were less than 0.78 micrograms/ml. AZT also was effective against ABPC/PIPC-resistant bacteria. The MIC of AZT for V. parahaemolyticus was less than 1.56 micrograms/ml. The peak serum levels of AZT which were occurred just after the 1 hour drip infusion of 10-30 mg/kg were 60.5-136.8 micrograms/ml, and at 6 hours after infusion the serum levels were 1.3-6.1 micrograms/ml; therefore, the dose response was proved. The mean half-lives (T 1/2) were between 1.21 and 1.36 hours. The excretion rates in urine up to 6 hours after intravenous drip infusion were between 32.7 and 77.5%. The ratio of the cerebrospinal fluid concentration to serum in the child with purulent meningitis was 3.5% at 1 hour after the intravenous injection at the dose of 69 mg/kg, and the ratios of the subdural fluid levels to serum were 31.3-37.5%. The levels of AZT into the feces by the multiple dosage were 0-840 micrograms/g. Twenty-five pediatric patients with acute infections had been treated by intravenous injection or drip infusion at the doses of 49-120 mg/kg/day (almost 50-100 mg/kg/day) for 4 to 13 days. The efficacy rate of excellent + good was 84% and that of excellent + good + fair was 96%. The efficacy rate of excellent + good was 100% in all cases with upper/lower respiratory tract infection, bronchopneumonia, and acute urinary tract infection caused by Gram-negative rods. The clinical efficacy was observed in all cases with acute bacterial enteritis. Although AZT was clinically effective against Salmonella enteritis, bacteriological efficacy on the causative organisms was not observed in some cases. Although AZT was bacteriologically effective in 1 patient with typhoid, it did not alleviated fever. AZT showed activity to 9 strains isolated from the culture of throat swab, urine and feces. No side effects were clinically observed in all cases, while slight elevations of laboratory findings were observed in 4 cases.

Age Factors↗
PubMed1984

[Fundamental and clinical studies of ceftazidime, a new cephem antibiotic in the field of pediatrics].

Fundamental and clinical studies of ceftazidime (CAZ) were performed, and the following results were obtained. MICs of CAZ for E. coli which was recently isolated from patients, were less than 1.56 microgram/ml and that for K. oxytoca were less than 0.39 micrograms/ml, and that for Salmonella were less than 0.39 microgram/ml, and that for B. pertussis were less than 0.20 microgram/ml. The mean serum levels after the drip infusion at the doses of 20 to 36 mg/kg for 30 to 60 minutes were between 11.8 and 66.7 micrograms/ml at 1 hour, and the mean half-lives (T 1/2) were between 58 and 105 minutes, and the excretion rates in urine up to 6 hours were between 86.3 and 96.5%. CAZ was given to 35 pediatric patients (include 2 drop cases) by intravenous injection for 4 to 10 days, and the total dosage was between 2.4 and 14.5 g. Thirty-three patients with acute respiratory tract infections, pertussis and acute urinary tract infections with ABPC-resistant E. coli were treated with CAZ by intravenous injection or drip infusion. The efficacy rate of excellent + good was 90.9% (30 cases/33 cases) and the efficacy rate of excellent + good + fair was 100%. The daily doses of CAZ were 50 to 110 mg/kg, given in 2 or 3 divided doses per day. S. pyogenes, S. aureus, H. influenzae, B. pertussis and ABPC-resistant E. coli were isolated from the culture of sputum or urine in the patients, and they were all eradicated by treatment with CAZ. No side effect was observed except for temporary eosinophilia in 2 cases and temporary platelets increased in 1 case.

Acute Disease↗