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Biomedical subjects

K Shibata

Publications and source records attributed to K Shibata.

At least 577 records · Page 32Linked to original sources

Effects of carbon disulfide, diethyldithiocarbamate, and disulfiram on drug metabolism in the perfused rat liver.

The effects of carbon disulfide (CS2), diethyldithiocarbamate (DTC) and disulfiram (DS) on hepatic drug metabolism were studied in a noncirculating and hemoglobin-free rat liver perfusion system using p-nitroanisole (p-NA) as a substrate. Infusion of 1 mumol of CS2 into a normal rat liver instantaneously lowered the free p-nitrophenol (p-NP) concentration in the effluent perfusate; however, the effects on the levels of its glucuronide and sulfate conjugates were much less marked. The suppression of p-NP production by CS2 was also observed in livers isolated from phenobarbital (PB)- and 3-methylcholanthrene (3-MC)-treated rats; to a greater extent, in the normal and 3-MC groups. Partial recovery was observed in the normal and PB-treated groups, but it was slow and slight in the 3-MC-treated group. Infusion of DTC, up to 20 mumol, did not lower free p-NP levels, but a slight transient increase was noted, especially in the 3-MC-group. Using 50 mumol of DTC, a slight suppression resulted. DS, up to 20 mumol, did not decrease p-NP production, but rather gradually increased it, especially in the 3-MC-treated groups. Without the p-NP infusion, about 60-70% of the infused DS (10 mumol) was recovered in the effluent perfusate as DTC plus its glucuronide conjugate, the formation of the latter being greatly enhanced by the inducer treatments and markedly suppressed during the p-NP infusion. In this paper, these results are discussed with regards to the mechanisms of drug metabolism inhibition by DS administration.

Animals↗

[A study on the bactericidal action of aspoxicillin against Escherichia coli].

In an attempt to clarify the role of a side chain, N4-methyl-D-asparagine, of aspoxicillin (ASPC) in the antibacterial action, we examined the bactericidal activity of dehydroxyaspoxicillin (AB-ASPC) and its affinity for the penicillin-binding proteins (PBPs) of Escherichia coli using piperacillin (PIPC), mezlocillin (MZPC) and apalcillin (APPC) as the reference penicillins. ASPC and AB-ASPC showed high bactericidal activities against E. coli K-12 even when a large inoculum size (2 x 10(8) CFU/ml) was used. The observation of these cultures with a phase contrast microscope revealed that E. coli cells lysed after the formation of spheroplast-like or bulged structures. On the other hand, PIPC, MZPC and APPC converted the cells to long filaments, but did not show lytic action in the range of the concentrations used. These morphological changes were also observed with a scanning electron microscope. Superior bacteriolytic activities of ASPC and AB-ASPC were further shown by measuring 'triggering' autolytic activity by the penicillins. The release of labeled murein from E. coli chi 1776 after the exposure to ASPC or AB-ASPC was clearly greater than those caused by the reference penicillins. ASPC showed affinity for PBPs of E. coli K-12, 1A, 1Bs, 2 and 3, and its affinity pattern resembled the one obtained with ampicillin (ABPC). AB-ASPC behaved in a fashion similar to ASPC, although its affinities for PBP 1A and 1Bs were lower and that for PBP 3 was slightly higher. These observations suggest that the highest bactericidal activity of ASPC against E. coli with lysis among the acyl-ureidopenicillins tested is due to N4-methyl-D-asparagine in the side chain of ASPC.

Amoxicillin↗

[Clinical study of hypertensive subcortical hemorrhage: surgical indication and long-term, functional prognosis].

There has been no report available for determining surgical indications in hypertensive subcortical hemorrhage based on functional prognosis. The authors then studied the clinical results of hypertensive subcortical hemorrhage for evaluating the surgical indication in relation to functional prognosis. Sixty-five patients with hypertensive subcortical hemorrhage diagnosed by CT scan who were hospitalized to Matsue Red Cross Hospital from January 1980 up to December 1986 were studied. The 44 male and 21 female patients ranged in age from 37 to 86 years, and 38 of them were operated on. The results were as follows: 1) Patients with grade I (Kanaya's neurological grading) or a volume of hematoma less than 30 ml should be treated with conservative therapy. Those with grade II and III or a volume of hematoma = 30 - 50ml should be treated in accordance with proper therapeutic method, taking into consideration the site of the hematoma. Patients with more than grade IVa or a volume of hematoma greater than 50ml would be in danger of losing their lives unless surgical therapy was performed. 2) The follow up study of the patients' long-term prognosis after discharge revealed the majority of the patients showed aggravation of the illness and/or death due to cerebral apoplexy-like attack and re-bleeding. It is necessary to follow up these cases with careful systemic control, including monitoring of blood pressure.

Brain↗

[The clinical use of Hotz-type orthopedic plate].

In the present study a Hotz type orthopedic plate was used to improve feeding and physiological growth. In 2 patients with cleft lip it was used to improve feeding and swallowing. In 4 patients with cleft lip and palate it was used to normalize functions and aid physiological growth. The effects of the Hotz orthopedic plate were determined by recording body weight growth, milk volume per day, feeding time and comparison of the study model between before and after using Hotz orthopedic plate. Good physiological growth and improved feeding, were obtoincdinalmostall the patients who wore the Hotz type orthopedic plate correctly.

Cleft Lip↗

p-Chloromercuribenzoate-induced dissociation of cytoskeletal proteins in red blood cells of rats.

Effects of p-chloromercuribenzoate (PCMB) on the cytoskeletal organization of rat red blood cells were studied. Upon incubation with 50 microM PCMB in 10 mM Tris-HCl (pH 7.4) at 37 degrees C for 30 min, 80% of actin and 45% of spectrin were released from the ghosts, resulting in the fragmentation of ghost membranes. Addition of 2 mM Mg2+ or 0.1 M KCl, or lowering incubation temperature to 0 degree C substantially inhibited the solubilization of the cytoskeletal proteins and the fragmentation of ghost membranes, which enable to examine the effects of PCMB on the interaction between transmembrane proteins and the peripheral cytoskeletal network. Decreased recoveries of transmembrane proteins, such as band 3 and glycophorin, in Triton shell fraction were observed in the ghosts incubated with PCMB either in the presence of Mg2+ or at 0 degree C. PCMB also inhibited the in vitro association of purified spectrin with spectrin-depleted inside-out vesicles through interaction with proteins in the vesicle, such as bands 2.1 and 3. In the PCMB-treated ghosts, intramembrane particles were highly aggregated, which further supports the PCMB-induced dissociation of the transmembrane proteins from the cytoskeletal network. The decreased recovery of glycophorin in the Triton shell fraction also observed in intact red blood cells upon incubation with PCMB. These results suggest that the main action of PCMB on red cell membranes under physiological condition, at higher ionic strength and in the presence of Mg2+, is to dissociate transmembrane proteins from the peripheral cytoskeletal network, which may modify functions of these proteins.

Actins↗

Potentiation of pressor response to angiotensin II at the preoptic area in spontaneously hypertensive rat.

Cardiovascular responses to angiotensin II(AII) at the preoptic area (POA) were compared between normotensive Wistar Kyoto rat (WKY) and spontaneously hypertensive rat(SHR) by measuring blood pressure and heart rate under unrestrained, conscious state via a catheter implanted chronically into the abdominal aorta and by injection of drugs into POA through a chronic guide cannula. AII injected into POA at doses of 0.3 ng and 1 ng produced a dose-dependent pressor response, accompanied with a slight decrease of heart rate, in both WKY and SHR. However, in SHR, the pressor response to AII was more than 2 times greater than that in WKY and was quick in onset and lasted about 30 min. When AII in combination with [Sar1, Ile8]-angiotensin II (0.5 microgram), an AII receptor antagonist, were simultaneously administered to POA, the pressor response to AII was strongly inhibited in both WKY and SHR. The results suggest that the pressor response to AII due to its receptor stimulation at POA is markedly potentiated in SHR.

Angiotensin II↗