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Biomedical subjects

A Katayama

Publications and source records attributed to A Katayama.

At least 19 recordsLinked to original sources
PubMed1998

A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 1. Construction of the basic framework.

A novel class of potent, selective, and orally active non-peptide bradykinin (BK) B2 receptor antagonists were designed and synthesized starting from 8-benzyloxyimidazo[1,2-a]pyridine derivative 2. The unique screening lead (2) was discovered by a two-step intentional random screening process, involving recognition of the relationship between BK and angiotensin II (Ang II) and the common structural features. Systematic chemical modification of 2 elucidated the structural requirements essential for B2 binding affinity leading to the identification of 8-[[3-(N-acylglycyl-N-methylamino)-2,6-dichlorobenzyl]oxy]-3-halo- 2- methylimidazo[1,2-a]pyridine skeleton as the basic framework of this new series of B2 antagonists. A molecular modeling study suggested the key role of the N-methylanilide moiety at the 3-position of the 2,6-dichlorobenzene ring to allow these compounds to adopt the characteristic active conformation. The representative lead compounds inhibited the specific binding of [3H]BK to guinea pig ileum membrane preparations expressing B2 receptors, with nanomolar IC50S and also displayed in vivo functional antagonistic activities against BK-induced bronchoconstriction in guinea pigs at an oral dose of 1 mg/kg. Pharmacokinetic studies of compounds 47c and 50b in rats highlighted their excellent oral bioavailabilities, indicating that they represent the first orally active non-peptide B2 antagonists reported to date.

Administration, Oral↗
PubMed1998

Heart rate variability during the first month of smoking cessation.

BACKGROUND: Heart rate variability (HRV) is known to increase after smoking cessation. However, no work has been performed concerning HRV immediately after smoking cessation. METHODS AND RESULTS: We studied HRV before and from 1 day to 1 month after smoking cessation and also determined whether there is a relation between HRV and the withdrawal syndrome immediately after smoking cessation. We determined HRV by using a two-channel 24-hour ambulatory ECG system before and 1, 2, 3, 7, 14, 21, and 28 days after smoking cessation in 20 healthy male volunteers who had smoked one or more packs per day for 2 or more years. One day after smoking cessation, heart rate decreased significantly, and all 24-hour time and frequency domain indices of HRV increased except the standard deviations of the normal R-R intervals and the 5-minute mean R-R. The magnitude of increase in these indices peaked 2 to 7 days after smoking cessation and gradually decreased thereafter. The increase in HRV persisted 1 month after smoking cessation. In the 16 subjects with signs of withdrawal syndrome and in the four subjects without evidence of withdrawal before and immediately and 1 month after smoking cessation, HRV increased immediately after smoking cessation and remained elevated after 1 month. CONCLUSIONS: HRV increases immediately after smoking cessation and gradually declines thereafter, which suggests that the effect of smoking on autonomic activity rapidly disappears immediately after smoking cessation. HRV remained unaffected by the presence or absence of the withdrawal syndrome.

Adult↗
PubMed1997

Measurement of portal venous flow velocity with an implantable miniature Doppler probe in pig liver transplantation.

Portal venous flow (PVF) was serially monitored after pig liver transplantation (LTX) with the use of an implantable, miniature Doppler probe developed in our laboratory. Throughout the study period, the mean PVF in pigs that underwent LTX was significantly greater than that in pigs that were sham operated. For three animals with early graft failure secondary to primary nonfunction and for six that survived longer than 7 days, the mean PVF on postoperative day (POD) 1 was 18.7 +/- 3.8 cm/s and 41.7 +/- 11.2 cm/s, respectively (P < 0.05). For animals with acute cellular rejection (ACR), the mean PVF was 61.3 +/- 9.9 cm/s on POD 7 and 54.3 +/- 6.38 cm/s on POD 14. These values were significantly higher than those for animals without ACR (P < 0.05). Moreover, the increase in PVF correlated well with the degree of ACR. The actual PVF volume was measured by ex vivo perfusion, which showed a clear correlation with the PVF velocity obtained with the implanted, miniature Doppler probe. We feel that the liver graft requires increased PVF volume after transplantation to facilitate functional recovery from damage to hepatocytes due to preservation-reperfusion injury, and that ACR is also associated with an increased PVF. We conclude that monitoring the PVF in the early postoperative period after LTX is useful in the evaluation of graft function, particularly for predicting primary nonfunction and severity of ACR.

Animals↗
PubMed1997

Serotyping of Streptococcus pyogenes isolated from common and severe invasive infections in Japan, 1990-5: implication of the T3 serotype strain-expansion in TSLS. The Working Group for Group A Streptococci in Japan.

To clarify the relationship between the epidemics of severe invasive group A streptococcal infections (streptococcal Toxic Shock-Like Syndrome: TSLS) and common group A streptococcal infections in Japan, we examined the T serotypes of S. pyogenes strains (group A streptococci) isolated from clinical specimens of the streptococcal infections (17999 cases) in the period 1990-5, including the severe infections (TSLS) (29 cases) in the period 1992-5. Characteristic points of the analyses were: (1) dominant serotypes of the infections in these periods were T12, T4, T1, T28 and TB3264, which were consistently isolated; (2) isolates of T3 rapidly increased through 1990 to 1994 while T6 decreased in the period 1990-3; (3) when Japanese area was divided into three parts, T3 serotype tended to spread out from the north-eastern to the south-western area; (4) strains of T3 and T1 serotypes were dominant in the TSLS. Dominant-serotype strains of streptococcal infections did not always induce severe infections and dominance of T3 serotype in the TSLS seemed to be correlated with the increase of T3 in streptococcal infections. These results may indicate that certain clones of S. pyogenes are involved in the pathogenesis of the TSLS.

Adolescent↗
PubMed1997

The identification of an orally active, nonpeptide bradykinin B2 receptor antagonist, FR173657.

1. An orally active, nonpeptide bradykinin (BK) B2 receptor antagonist, FR173657 (E)-3-(6-acetamido-3-pyridyl)-N-[N-[2-4-dichloro-3-[(2-methyl-8-quinolin yl) oxymethyl]phenyl]-N-methylaminocarbonyl-methyl] acrylamide) has been identified. 2. This compound displaced [3H]-BK binding to B2 receptors present in guinea-pig ileum membranes with an IC50 of 5.6 x 10(-10) M and in rat uterus with an IC50 of 1.5 x 10(-9) M. It did not inhibit different specific radio-ligand binding to other receptor sites. 3. In human lung fibroblast IMR-90 cells, FR173657 displaced [3H]-BK binding to B2 receptors with an IC50 of 2.9 x 10(-9) M and a Ki of 3.6 x 10(-10) M, but did not reduce [3H]-des]Arg10-kallidin binding to B1 receptors. 4. In guinea-pig isolated preparations, FR173657 antagonized BK-induced contractions with an IC50 of 7.9 x 10(-9) M, but did not antagonize acetylcholine or histamine-induced contractions even at a concentration of 10(-6) M. FR173657 caused parallel rightward shifts of the concentration-response curves to BK at concentrations of 10(-9) M and 3.2 x 10(-9) M, and a little depression of the maximal response in addition to the parallel rightward shift of the concentration-response curve at a concentration of 10(-8) M. Analysis of the data yield a pA2 of 9.2 +/- 0.2 (n = 5) and a slope of 1.5 +/- 0.2 (n = 5). 5. In vivo, the oral administration of FR173657 inhibited BK-induced bronchoconstriction dose-dependently in guinea-pigs with an ED50 of 0.075 mg kg-1, but did not inhibit histamine-induced bronchoconstriction even at 1 mg kg-1. FR173657 also inhibited carrageenin-induced paw oedema with an ED50 of 6.8 mg kg-1 2 h after the carrageenin injection in rats. 6. These results show that FR173657 is a potent, selective, and orally active bradykinin B2 receptor antagonist.

Administration, Oral↗
PubMed1997

In vitro susceptibility of Escherichia coli O157 to several antimicrobial agents.

We evaluated the antimicrobial susceptibility of six strains of Escherichia coli O157 (E. coli O157) isolated from patients in Yamaguchi Prefecture between June and July, 1996. Seven antimicrobial agents that were expected to retain a high concentration in the intestine were selected. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of ciprofloxacin, polymyxin B, cefoperazone, and kanamycin for each strain were < or = 6.25 microg/ml. However, the MIC of fosfomycin was 3.13-100 microg/ml, and its MBC was > or = 100 microg/ml. The MIC of ampicillin and tetracycline was > 100 mcirog/ml in some strains. In a time-kill study of E. coli O157 at a drug concentration of 12.5 microg/ml, about 10(4) colony forming units/ml of E. coli O157 were eradicated within 10 min by ciprofloxacin, within 30 min by polymyxin B, within 4 h by cefoperazone, and within 16 h by kanamycin. These results suggest that the new quinolones with a poor absorption rate in the intestine (such as ciprofloxacin and norfloxacin) are effective against E. coli O157. When oral administration is impossible, bile excreting cephem antibiotics (such as cefoperazone, ceftriaxone, and cefotetan) may be useful.

Adolescent↗
PubMed1996

Liberation of vasoactive substances and its prevention with thromboxane A2 synthase inhibitor in pig liver transplantation.

There are multiple causes of liver graft nonfunction in the early post-transplant period. Since a severe microcirculatory disturbance based on ischemia-reperfusion liver injury is considered to be the main underlying pathophysiology, it is suspected that various vasoactive substances are liberated after reperfusion of the graft. In order to investigate this matter, we conducted an experimental study with pig liver allotransplantation. Two groups of animals received donor grafts with or without thromboxane synthase inhibitor (sodium ozagrel), 1.25 mg/ kg body weight intravenously, given at the time of liver harvesting. All of the recipient animals in the treatment group (n = 10) survived longer than 7 days whereas three of ten animals in the control group died within 7 days. Serum lactate dehydrogenase (LDH) in the recipient serum at 1 h after reperfusion was significantly lower in the treatment group (915.1 +/- 167.3 U/l) than in the control group (1264.4 +/- 134.7 U/l). Serum thromboxane B2 (2261.7 +/- 1055.7 pg/ml) and endothelin-1 (6.3 +/- 2.2 pg/ml) after reperfusion in the treatment group were significantly lower than those in the control group (4220.0 +/- 1711.0 pg/ml and 11.2 +/- 3.1 pg/ml, respectively). Although serum angiotensin II after reperfusion tended to be lower in the treatment group than in the controls serum renin activity was less than 3 ng/ml in both groups of animals. There were no differences in the plasma endotoxin levels between the two groups. We conclude that the administration of sodium ozagrel to the donor animals provided better graft function in recipients than no such treatment. We speculate that the inhibition of thromboxane A2 production suppresses the liberation of other vasoconstrictive substances, preventing microcirculatory disturbance and, thereby, contributing to improved graft function after liver transplantation.

Angiotensin II↗