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Biomedical subjects

T Aikawa

Publications and source records attributed to T Aikawa.

At least 163 records · Page 9Linked to original sources
PubMed1982

Evaluation of ototoxicity of amino-glycoside antibiotics in rabbits.

It is generally accepted that the ototoxicity of aminoglycoside antibiotics is gentamicin (GM) greater than dibekacin (DKB) greater than kanamycin (KM) greater than amikacin (AMK) based on the results of animal experiments. However, clinical data reveals that the ototoxicity caused by each of the aminoglycoside antibiotics does not coincide with the ototoxicity in the animals. The present study was intended histopathologically for comparative evaluation of above-mentioned antibiotics using rabbits. The ototoxicity was GM greater than DKB greater than KM greater than AMK with the dose of 100 mg/kg, which coincide with many of the conventional reports on animal experiments. However, with the dose of 50 mg/kg, the order was GM greater than AMK greater than KM greater than DKB. With the dose of 30 mg/kg, hardly any differences were noted between the ototoxicity of GM and that of AMK. It was found out that the evaluation of the ototoxicity of drugs in high doses does not always correspond to that of lower doses. Therefore, the ototoxicity should be evaluated in strict consideration of dose of drugs. Usually, the doses of drugs used in the ototoxicity studies with animals are more than 10 times higher than those used clinically. Consequently, problems still exist in infering the ototoxicity of drugs in humans directly from the results obtained from animal experiments.

Amikacin↗
PubMed1982

Ototoxicity of aminoglycoside antibiotics by rapid intravenous injection.

The ototoxicity and nephrotoxicity of aminoglycoside antibiotics (dibekacin, gentamicin and kanamycin) administered to rabbits by rapid intravenous or intramuscular injections were histopathologically compared. Comparative evaluations between the two routes were further made concerning the levels of the antibiotics in serum and in perilymph. The results revealed that, although the peak serum level after a rapid intravenous injection was significantly higher than that observed after an intramuscular injection, no differences in the transfer into the perilymph, and in inner ear or renal damage were seen between the two different routes. In other words, the results of the present study did not support the conventional idea that the higher the peak blood levels of the aminoglycoside antibiotics, the greater the risk of damage to the inner ear or kidney.

Aminoglycosides↗
PubMed1982

Modification by Su-10'603 of the response to histamine on the production of cortisol and corticosterone in isolated canine adrenocortical cells.

The effect of Su-10'603 on the cortisol and corticosterone response to histamine in dispersed canine adrenocortical cells was examined. The production of cortisol and corticosterone in isolated dog adrenocortical cell incubations increased in a dose-dependent manner at concentrations of histamine between 0.01 and 10.0 micrograms/ml medium, with the predominant production of cortisol. When Su-10'603 (0.005 to 5.0 micrograms/ml medium), an inhibitor of 17 alpha-hydroxylation on corticosteroidogenesis, was added in cell incubations with histamine (1.0 micrograms/ml medium), the production of cortisol decreased in a reciprocal fashion, with a concomitant increase of corticosterone production. At the concentration between 0.05 and 0.1 microgram Su-10'603/ml medium, there was a shift from cortisol to corticosterone as the predominant product. These results indicate that in the dog, histamine at pathophysiological concentration stimulates steroidogenesis and acts at a relatively early stage in the biosynthetic pathway.

Adrenal Cortex↗
PubMed1982

Usefulness and rapidity of screening for the toxicity and carcinogenicity of chemicals in medaka, Oryzias latipes.

The toxicity and carcinogenicity of number of chemicals, for which there are toxicity and/or carcinogenicity data in mouse and rat, were tested in medaka, a small aquarium fish (Oryzias latipes). The water-soluble chemicals were dissolved in the water and the water-insoluble chemicals were incorporated into the diet. Observation for 24 wk revealed induction of liver cell carcinoma by 6 chemicals; aflatoxins B1 and G1, sterigmatocystin, ortho-aminoazotoluene, methylazoxymethanol acetate and N-nitrosodiethylamine. In medaka fed PCB or DDT only preneoplastic liver cell nodules were observed. No evident carcinogenicity was found in medaka treated with 2-fluorenylamine, 2-fluorenylacetamide, DL-ethionine, luteoskyrin, ochratoxin A, phenobarbital, 1-(2-tetrahydrofuryl)-5-fluorouracil, sodium benzoate, 2,3,4,5,6-penta-O-acetyl-D-gluconyl isothiocyanate, citrinin and fusarenon X, respectively, although toxic lesions or hyperplastic changes were demonstrated histologically. These results confirm the practical utility and rapidity of the use of medaka for screening carcinogenicity and toxicity of chemicals, since neoplastic or toxic morphological changes develop rapidly following administration of relatively small quantities of test materials.

Adenoma↗
PubMed1981

Adrenal secretion of aldosterone in response to anaphylactic shock in hypophysectomized-nephrectomized dogs.

The adrenal secretion of aldosterone in response to anaphylactic shock was examined in intact and hypophysectomized-nephrectomized dogs which had been sensitized by horse serum injections (s.c. and i.v.) 24-30 days before the experiment. On the day of the experiment, dogs were injected intravenously with horse serum under pentobarbital anesthesia. During anaphylactic shock induced by horse serum, the adrenal secretion of aldosterone in intact and hypophysectomized-nephrectomized dogs increased from 1.32 +/- 0.55 (mean +/- S.E.M.) to 8.43 +/- 1.99 ng/(kg.min) and from 0.23 +/- 0.10 to 2.38 +/- 0.63 ng/(kg.min), respectively. Plasma potassium concentration increased slightly and plasma sodium concentration did not change after the injection of horse serum in hypophysectomized-nephrectomized dogs. The results suggest the possibility that the adrenal secretion of aldosterone in response to anaphylactic shock in hypophysectomized-nephrectomized dogs is due mainly to a direct effect of histamine on the adrenal cortex or occurs via some unknown factors, and only in a small part to an increase in plasma potassium concentration. The adrenal secretion of corticosterone and cortisol during anaphylactic shock increased slightly but significantly in hypophysectomized-nephrectomized dogs, whereas it increased markedly in intact dogs.

Adrenal Glands↗
PubMed1981

Direct stimulatory effect of histamine on aldosterone secretion of the perfused dog adrenal gland.

The left adrenal gland of the hypophysectomized-nephrectomized dog was perfused in situ with the blood from the femoral artery of the hypophysectomized-nephrectomized donor dog. After infusion of histamine (0.1 mg/min for 5 min) into the arterial inflow circuit, the rates of secretion of aldosterone, corticosterone and cortisol (ng/100 mg adrenal wt. each min) increased from the basal level of 0.66+/-0.21 (mean+/-S.E.M.) to 2.24+/-0.45 at 10 min, from 4+/-1 to 20+/-4 at 5 min and from 19+/-5 to 64+/-15 at 5 min, respectively. The maximal increments above the basal value after the infusion of histamine in the secretory rates of aldosterone, corticosterone and cortisol were 51, 16, and 13% that of the respective steroid after the infusion of ACTH (20mIU/min for 5 min). The results indicate that histamine has a direct stimulatory effect on the secretion of aldosterone by the adrenal gland as well as on that of corticosterone and cortisol.

Adrenal Glands↗
PubMed1981

Direct effect of histamine on the production of adrenocortical hormone by guinea-pig adrenal cells.

In trypsin-dispersed adrenal cells of the guinea-pig, the production of 11-hydroxycorticosteroids in vitro was found to be significantly stimulated by 10(-7) -10(-4)M histamine and the maximum steroidogenic response (1.7-fold increase in 11-hydroxycorticosteroid production) was observed at 10(-6)M. The stimulatory action of histamine on steroidogenesis was blocked by cycloheximide treatment.

11-Hydroxycorticosteroids↗
PubMed1979

Clinical application of breath analysis for dimethyl sulfide following ingestion of DL-methionine.

After overnight-fasting, the concentration of dimethyl sulfide in expired alveolar gas (alv-DMS) was determined serially following ingestion of 2 g of DL-methionine in normal subjects and patients with liver diseases. Alv-DMS rose to a peak in 30 to 90 min, declined markedly within 3 h, and then decreased gradually. Half-disappearance times (T 1/2) (mean +/- S.E. min) in each experimental group were: normal (N = 9) 61.7 +/- 4.7, acute hepatitis (N = 6) 62.5 +/- 6.8, chronic hepatitis (N = 10) 84.0 +/- 13.0, and liver cirrhosis (N = 13) 159.2 +/- 30.4, respectively. Cirrhotics had a T 1/2 significantly longer than that of the other three groups: vs. normal P less than 0.02, vs. acute hepatitis P less than 0.05, and vs. chronic hepatitis P less than 0.05. T 1/2 of alv-DMS following ingestion of DL-methionine seems to be of clinical interest.

Breath Tests↗
PubMed1979

Enzyme immunoassay of angiotensin I.

A very sensitive and specific enzyme immunoassay has been developed for angiotensin I. Angiotensin I was coupled to beta-D-galactosidase by a novel cross-linking reagent, N-(meta-maleimidobenzoyloxy)succinimide. No decrease in the enzyme activity was observed during the coupling procedure. In the angiotensin I-beta-D-galactosidase conjugate, 0.39 mol immunoreactive angiotensin I/mol enzyme were present. A competitive assay with the enzyme-labeled angiotensin I was performed. Antibody-bound and free labeled antigen were separated from each other by the second antibody method, and the enzyme activity of the former was estimated. Using this assay, angiotensin I could be detected in the range of 1.2--50 pg. The sensitivity was 4.5-fold higher than that of the usual RIA. This assay distinguished clearly angiotensin I from angiotensin II, angiotensin III, and (Sar1, Ile8)-angiotensin II. The present method was applied to measure PRA in dogs; the results correlated fairly well with those obtained by the RIA (r = 0.94).

Angiotensin I↗
PubMed1979

Secretion of aldosterone in response to histamine in hypophysectomized-nephrectomized dogs.

In hypophysectomized-nephrectomized dogs after intravenous injection of histamine, a marked increase was observed in the rate of secretion of aldosterone, although it was smaller than that in intact dogs. Hypophysectomy plus bilateral nephrectomy greatly impaired the secretion of corticosterone and cortisol in the dog in response to histamine. However, a small yet significant increase in corticosterone and cortisol secretion was observed in hypophysectomized-nephrectomized dogs after intravenous injection of histamine. Additional experiments showed that plasma concentrations of potassium and sodium in hypophysectomized-nephrectomized dogs remained unchanged after intravenous injection of histamine. These results suggest that histamine stimulates aldosterone secretion in the dog partly by a direct effect on the adrenal cortical cells, whereas the effect of histamine on corticosterone and cortisol secretion is mediated mainly, but not totally, by pituitary release of ACTH.

Adrenocorticotropic Hormone↗