PubMed Health⌕ Search

Biomedical subjects

T Koeda

Publications and source records attributed to T Koeda.

At least 145 records · Page 8Linked to original sources
PubMed1983

Analgesic effect of novel organogermanium compound, GE-132.

A novel organogermanium compound, Ge-132, carboxyethylgermanium sesquioxide, showed enhancement of 0.5 mg/kg morphine analgesia in both administration routes of oral administration (p.o.) and intraperitoneal injection (i.p.) in the Tail-Flick test, and the effect was completely abolished by 0.5 mg/kg Naloxone, stereospecific opiate antagonist. Ge-132 alone, 250 mg/kg i.p., did not show any antinociceptive action by assessing the Tail-Flick test and the Hot-Plate test. By the intracerebral injection of Ge-132, 100-1000 micrograms, prolongation of Tail-Flick latency was observed and the action was abolished by 50 micrograms CaCl2 injection. Although bestatin which is reported to enhance the morphine analgesia inhibits enkephalinase and enkephalin aminopeptidase, Ge-132 did not show any inhibition on both enkephalin degrading enzymes. The possibility for the mode of action of Ge-132 was discussed.

Analgesics↗
PubMed1983

Synthesis and antihypertensive activity of 5-O-substituted derivatives of 5-hydroxypicolinic acid.

5-O-Substituted derivatives of 5-hydroxypicolinic acids were synthesized from nojirimycin and studied for their antihypertensive activity in unanesthetized spontaneously hypertensive rats (SHRs) restrained in wire mesh cage and acute toxicity in mice. 5-n-Butoxy-picolinic acid (ND-186) was found to have antihypertensive activity comparable to fusaric acid and lesser acute toxicity. Introduction of halogeno group, in particular trifluoromethyl group to the omega-position of 5-n-butoxy group resulted in the enhancement of antihypertensive activity. The acute toxicity was also lowered 3-5 times compared to that of fusaric acid. Replacement of alkyl group with phenyl group resulted in a slight increment of activity. Some of ester derivatives of ND-186 potentiated the antihypertensive activity and reduced the acute toxicity. There was good correlation between partition coefficient (log P) of ester groups and their antihypertensive activities; compound with higher lipophilicity showed higher antihypertensive activity under the condition of oral administration. However, esterification of other compounds such as 5-halogenoalkoxy- and 5-(substituted) phenoxypicolinic acid was not accompanied with activity increment. Considering from the balance of the antihypertensive activity in SHRs and the acute toxicity in mice, 5-(5',5',5'-trifluoropentoxy)-picolinic acid was selected as a candidate for further evaluation.

Animals↗
PubMed1982

Relationship between enhancement of morphine analgesia and inhibition of enkephalinase by 2S, 3R 3-amino-2-hydroxy-4-phenylbutanoic acid derivatives.

The effects of nineteen AHPA* derivatives were examined on morphine analgesia by tail-flick test in rats and on enkephalinase inhibition which was based on the formation of tyrosyl-glycyl-glycine from met-enkephalin. The correlation between the enhancement of morphine analgesia in vivo and enkephalinase inhibition in vitro was analyzed. The different analogs varied considerably in the degree of enhancement of morphine analgesia and inhibition of enkephalinase. A close relationship between enkephalinase inhibition expressed by IC50 in vitro and enhancement of morphine analgesia in vivo was observed in thirteen out of nineteen AHPA derivatives examined. One of other six AHPA derivatives which showed weak effectiveness in potentiating on morphine analgesia but was highly potent as an enkephalinase inhibitor, caused potent analgesic action when it was applied intracisternally indicating poor penetration of the blood brain barrier. The possibility was discussed that some of other compounds excluded from the linear relationship might act on other enkephalin degrading enzymes such as aminopeptidase.

Aminopeptidases↗
PubMed1982

Protective effect of fosfomycin on the experimental nephrotoxicity induced by dibekacin.

Protection by fosfomycin of the nephrotoxicity of dibekacin was studied using Fischer 344 rats and urinary parameters such as volume, osmolality, protein, N-acetyl-beta-D-glucosaminidase, leucine aminopeptidase, lactate dehydrogenase and nucleated cells were determined as markers of nephrotoxicity. The duration of treatment was 11 d. Fosfomycin reduced polyuria, proteinuria, enzymuria and cyturia induced by dibekacin best by the concomitant administration, followed by pre-treatment, but not by post-treatment. Protection was effective in the dose ratio of dibekacin: fosfomycin = 1:2 - 1:32, regardless of administration routes. As judged from urinalysis, protection by fosfomycin (320 mg/kg) was almost complete for the experimental nephrotoxicity induced by 10 mg/kg of dibekacin, and still significant for that by 40 mg/kg. This was supported by the histo-pathological and ultrastructural improvement of proximal tubules and by suppressed blood urea nitrogen and creatinine values. Protective activity of fosfomycin was more potent than that of cephalothin, when compared on the weight basis.

Animals↗
PubMed1982

Acute and subacute toxicity studies on collagen wound dressing (CAS) in mice and rats.

Single administration of collagen wound dressing (CAS) made from bovine derm in the form of finely ground powders was given to mice and rats via i.p., s.c. and p.o. routes and via i.v. route in the form of physiological saline extracts and it was continuously injected into mice for 28 days via s.c. route to study its acute and subacute toxicity. Examinations were made of on general conditions, body weight, food and water consumption, hematology, serum biochemistry, organ weight, and gross and microscopic findings. Results showed no marked toxicity except for local irritation which was seen only after parenteral administration. We concluded on the basis of these animal experiments that there should be no problem in regard to safety after somewhat more extensive therapeutic application of CAS as a wound dressing in clinical practice.

Animals↗
PubMed1981

Mutagenicities of carbadox and olaquindox--growth promoters for pigs.

Carbadox and olaquindox were examined for mutagenicities in the repair tests with Bacillus subtilis (rec assay) and Salmonella typhimurium (uvr assay) and in the reverse mutation test (TA100 and TA98 of S. typhimurium). Both compounds were positive in the rec and uvr assays, and were highly mutagenic for strains TA100 and TA98. Carbadox was about 6 times move mutagenic than olaquindox in the absence of S9 mix. When incubated in S9 mix or bacterial cytosol (BC) mix for various times at 37 degree C, carbadox was found to lose its mutagenic activities easier than olaquindox. The mutagenicity of carbadox was almost inactivated at 10 min after incubation with S9 mix, but olaquindox still retained its activities even at 20 min. While carbadox required 20 min to be inactivated in BC mix, olaquindox was not completely inactivated even if incubated for 60 min.

Bacillus subtilis↗
PubMed1980

Drug resistance and R plasmids in Escherichia coli strains isolated from imported pet birds.

Drug resistance in Escherichia coli strains isolated from pet birds (mynahs, macaws, finches, common bengals, parrots, and flamingos) imported into Japan from 10 foreign countries in 1977 and 1978 was investigated. Of the 309 strains isolated from 127 pet birds in the Animal Quarantine Service, 232 (75.1%) were drug resistant. Furthermore, strains resistant to oxytetracycline hydrochloride, dihydrostreptomycin, and sulfadimethoxine were relatively common. Resistance patterns varied from single to sextuple resistance, and 148 (63.8%) of the resistant strains had conjugative R plasmids. These results suggest that the high incidence of drug resistance and R plasmids in E. coli strains isolated from these pet birds may be a reflection of the prophylactic use of antibiotics for the prevention of diseases which increasingly occur with importation of the birds. Furthermore, the results suggest that the birds may be potential reservoirs of drug-resistant E. coli for families who raise and have intimate contact with such birds.

Ampicillin↗
PubMed1980

Study on the pharmacological actions of beta-adrenoceptor blockers with reference to their physico-chemical properties.

The relationship between the membrane stabilizing action of beta-adrenoceptor blockers and their physico-chemical properties was investigated. Their depressing effects on the action potential amplitude of isolated Rana sciatic nerve were examined. The orde of their depressing potencies was propranolol (PROP) greater than dichloroisoproterenol (DCI) greater than alprenolol (ALP) greater than methoxamine (MEX) greater than practolol (PRAC) = sotalol (SOTA). The order of the negative chronotropic potency on the isolated rabbit atrial rate was PROP greater than ALP greater than DCI greater than MEX greater than PRAC greater than SOTA. The order of beta-blocking activity in isolated guinea-pig tracheal chain or in isolated rabbit atrial rate was ALP greater than PROP greater than SOTA greater than DCI greater than MEX greater than PRAC or PROP greater than ALP greater than PRAC greater than DCI greater than SOTA greater than MEX respectively. A high correlation was observed between membrane stabilizing actions (depressing effect on sciatic nerve action potential and negative chronotropic effect on atrial rate) and physico-chemical properties (the apparent partition coefficient and pKb). No relation was observed between beta-blocking effect on tracheal chain or right atrial rate and physico-chemical properties. It is suggested that the active sites for beta-blocking action and membrane stabilizing action might be different.

Adrenergic beta-Antagonists↗
PubMed1980

Pharmacological analysis of the mechanism of action of phenthiazamine, a piscine anesthetic.

Phenthiazamine was developed by Sekizawa et al. as a centrally acting anesthetic for fish. Frog sympathetic ganglion was used as a model to elucidate the mechanism of its anesthetic action. The positive ganglionic potential was enhanced immediately after application; then, the potential and the late negative ganglionic potential were markedly reduced by an anesthetic concentration of this compound. The hyperpolarization caused by 1 mM dopamine was enhanced by phenthiazamine. This enhancement of dopamine hyperpolarization and of the positive ganglionic potential may coincide with the fact that cyclic adenosine monophosphoric acid (cAMP) phosphodiesterase was inhibited by the compound as shown in our previous paper. Guinea-pig ileum contraction elicited by electrical field stimulation and by dimethyl-phenyl-piperadinium (DMPP) was reduced by a similar concentration of this compound, while the contraction elicited by acetylcholine and methacholine was not inhibited. The inhibition of contraction elicited by electrical field stimulation and DMPP may thus due to inhibition of acetylcholine release by this compound. The inhibition of ileum contraction by this compound was reversed by higher doses of Ca2+ (5.5 mM). The time required to reduce the positive ganglionic potential in the sympathetic ganglion by phenthiazamine was prolonged in the presence of higher concentrations of Ca2+. The Ca2+-dependent action potential of guinea-pig ureter was reduced by this compound, whereas it did not affect the Na+-dependent action potential.

Action Potentials↗
PubMed1980

The intravenous toxicity of dibekacin sulphate (DKB) to female beagle dogs.

Dibekacin sulphate (DKB), a new aminoglycoside antibiotic developed on the theory of bacterial resistance, was given by intravenous injection to groups of female Beagle dogs at dosages of 2.5, 5.0, 10.0 or 25.0 mg/kg/day for 13 weeks. Physiological saline was given as a control. Some dogs given 5.0 or 10.0 mg/kg/day were retained undosed for a further 5 weeks in order to assess recovery. Premature deaths from acute renal tubular nephrosis occurred in dogs given 25.0 and 10.0 mg/kg/day. Dogs which survived treatment at 10.0 mg/kg/day showed marked elevation of circulating urea and creatinine concentrations after 4 weeks' treatment but thereafter the increases became less obvious. Varying degrees of renal cortical tubular dilatation, basophilia, degeneration or necrosis were seen in the kidneys of all dogs examined after 13 weeks treatment although no clinical impairment of renal function was detectable at dosages up to 5.0 mg/kg/day. These changes had essentially regressed in dogs examined 5 weeks after the last dose of DKB at 5.0 mg/kg/day. All the adverse clinical and histological effects noted, following any dose level of DKB tested, could be attributed to renal changes.

Animals↗