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Biomedical subjects

I Komiya

Publications and source records attributed to I Komiya.

At least 109 records · Page 6Linked to original sources
PubMed1985

[Tissue distribution of cefminox in beagle dogs].

A new cephamycin antibiotic, cefminox (MT-141, CMNX), was intravenously infused into Beagle dogs at a dose of 40 mg/kg in order to study it's distribution to various tissues. The following results were obtained. The maximum serum concentration of CMNX observed at the end of the infusion period was 102.3 micrograms/ml, and then the concentration decreased. The biological half-life of CMNX in serum was 37.0 minutes. This half-life was similar to the results of previous studies with Beagle dogs and rabbits. The maximum concentrations in tissues and body fluids were highest in B-bile followed by kidney, urinary bladder, serum, liver, vagina, uterus, pericardiac fluid, trachea, ovary, lung, gallbladder, parotid gland, heart, tonsil, thymus, spleen, pancreas, aqueous humor and cerebrospinal fluid, in that order and not detected in brain. The maximum concentrations in gallbladder, B-bile, pericardiac fluid and cerebrospinal fluid were found at 1-2 hours after administration. In other tissues and body fluids, they were obtained at the end of the infusion period. The area under the tissue concentration curve (AUC) was highest in the urinary bladder followed by the kidney, vagina, liver, uterus, gallbladder, trachea, ovary and lung, in that order. These results suggest that CMNX is useful for various infectious diseases in these tissues. The pharmacokinetic parameter (K1i/K2i) derived from serum and tissue concentrations using the deconvolution method well correlated to maximum tissue concentrations.

Animals↗
PubMed1984

Increased sensitivity of the thyrotroph to thyrotropin-releasing hormones in rats with hypothalamic hypothyroidism.

The status of TSH secretion in hypothalamic hypothyroidism was evaluated by using rats with anterior medial basal hypothalamic deafferentation as the experimental model of the disorder. In the deafferented rats, the basal serum thyroid hormone concentrations as well as that of TSH was significantly lower than normal and cold exposure failed to increase serum TSH, indicating they were in fact in a hypothalamic hypothyroid state. The minimum effective dose of TRH to elicit an increase in serum TSH was smaller in the deafferented rats than in the controls, whereas the response to the maximum dose of TRH was similar in both groups. Although the radioimmunoassayable TSH of the adenohypophysis was significantly decreased in the deafferented rats, it was qualitatively similar to that of the control rats, since the peak of TSH immunoreactivity was eluted at exactly the same position on the gel filtration column in the pituitaries from normal and deafferented rats. When the adenohypophysis was perifused in vitro with Krebs-Ringer solution buffered with Hepes, the minimum effective dose of TRH was similar in both cases. This finding suggests that the exposure to the perifusion medium completely devoid of thyroid and hypothalamic hormones erased the difference in sensitivity to TRH between the two groups as observed in vivo, although in vivo experiments on deafferented rats with normal thyroid hormone induced by exogenous thyroid hormone were not performed. Our results indicate that in hypothalamic hypothyroid rats: 1) the sensitivity but not the responsiveness of the thyrotroph to TRH is increased; and 2) the readily releasable fraction of pituitary TSH pool in response to exogenous TRH is increased. It is also suggested that the difference in the milieu between the pituitary of normal and deafferented rats in vivo is critically important for the latter to retain hypersensitivity to TRH.

Animals↗
PubMed1984

Thyrotropin-induced acceleration of calcium efflux from mouse thyroid: evidence for inhibition by excess iodide.

We investigated the effect of TSH on calcium transport in mouse thyroid, as well as the influence of iodide thereupon. Thyroid lobes were incubated in Krebs-Ringer bicarbonate buffer containing [45Ca2+] and the time-dependent uptake of [45Ca2+] by the lobes was observed. In the presence of 0.5 mU/ml TSH, the uptake of [45Ca2+] was significantly depressed at early phases of incubation (from 20 to 40 min). Similarly, (Bu)2cAMP (DBC) depressed the [45Ca2+] uptake. The efflux of calcium was also studied by using thyroid lobes preloaded with [45Ca2+]. In the presence of 0.5 mU/ml TSH, [45Ca2+] release from the lobes was doubled in comparison with the control lobes incubated without TSH. DBC similarly accelerated [45Ca2+] release from the lobes. The acute administration of excess iodide to mice fed a low iodine diet inhibits the TSH-induced adenylate cyclase activation in thyroids. The acceleration of calcium efflux induced by TSH was completely abolished by the acute administration of excess iodide in thyroids obtained from animals fed a low iodine diet. Similarly, DBC-induced acceleration of calcium efflux was inhibited by pretreatment with excess iodide. However, the inhibitory effect of iodide on TSH- or DBC-induced acceleration of calcium efflux was not observed in thyroids obtained from mice fed a regular diet. Inhibition of TSH-induced acceleration of calcium efflux by iodide was diminished by treatment of mice with methimazole before iodide. These results suggest that 1) TSH accelerates calcium efflux from the thyroid as a result of accumulation of cAMP in the thyroid, and that 2) iodide inhibits calcium efflux by inhibition of TSH-induced adenylate cyclase activation and by inhibition of the mechanism(s) which is (are) activated by cAMP.

Animals↗
PubMed1984

Inhibitory action of thyrotropin-releasing hormone on serum amylase activity and its mechanism.

The effect of im administration of 500 micrograms TRH on serum amylase activity was studied in 34 normal women, 6 women with primary hypothyroidism, 1 woman with anorexia nervosa, 6 women with hyperthyroidism due to Graves' disease, and 5 women with renal failure on chronic hemodialysis. Serum amylase activity decreased significantly in 31 of 34 normal subjects 60 to 120 min after administration of TRH. However, amylase isoenzymes were not significantly affected after administration of TRH, suggesting that TRH equally affects pancreatic and salivary amylase activity. TRH was also effective in patients on chronic hemodialysis, indicating that TRH does not reduce serum amylase activity by increasing urinary excretion of amylase. Since TRH reduced serum amylase activity in hyperthyroid patients in whom TRH failed to stimulate TSH secretion, TRH does not reduce serum amylase activity through increased secretion of TSH. The action of TRH was not mediated by serum thyroid hormone levels since TRH was similarly effective in patients with hypothyroidism or hyperthyroidism. TRH did not inhibit or interfere with amylase determination when added in vitro to heparinized blood. Perfusion of the dog pancreas with TRH reduced amylase activity in pancreatic juice and pancreatic venous blood. The magnitude of the decrease was related to the dose of TRH used. Since decrease in amylase activity of the pancreatic juice preceded that in pancreatic venous blood, TRH probably directly acts on the pancreas to reduce amylase secretion. As a result, serum amylase activity decreased after administration of TRH.

Amylases↗
PubMed1984

A novel method to predict the elimination half-lives and the renal excretion mechanisms of cephalosporins.

A novel method was proposed to predict the elimination half-lives of cephalosporins from plasma protein binding (unbound fraction, f) and fraction of the dose excreted into urine (f*) on the basis of the following four assumptions. 1) The drug is only distributed to the extracellular fluid, 2) the bound fraction of the drug in plasma is independent of the plasma drug concentration, 3) the binding protein of the drug is albumin, 4) the unbound drug in plasma is excreted by the glomerular filtration and the contribution of active secretion and reabsorption is negligible. The VSS's and t1/2 beta's of MT-141, one of cephalosporins, in rabbits, dogs and healthy human subjects were well predicted, whereas in rats, the prediction of the both values was failed. The t1/2 beta's of various cephalosporins in healthy subjects were calculated from f and f*, in reasonably good agreement with the observed ones, except for some cephalosporins which have been reported to be secreted actively in the renal tubules. Thus, the comparison of the calculated t1/2 beta's with the observed ones makes it possible to presume the renal excretion mechanism. Moreover, this method will be applicable to other drugs which satisfy the above four assumptions.

Animals↗
PubMed1984

Age-related alterations of pituitary-thyroid function in normal female subjects and in female patients with simple goitre.

Age-related alterations in pituitary-thyroid function were studied in 173 female patients with simple goitre and in 70 normal female subjects. They were divided into 4 groups according to age: A group, less than 19 years; B group, 20 to 29 years; C group, 30 to 39 years; D group, 40 to 59 years. Serum triiodothyronine (T3) concentrations decreased progressively but insignificantly with age in female patients with simple goitre and in normal female subjects, whereas serum thyroxine (T4) concentrations remained constant throughout the studied age range. Only in female patients with simple goitre, did basal serum TSH concentrations show a tendency to increase with age. However, thyrotrophin-releasing hormone (TRH)-stimulated increase of serum TSH was progressively augmented with age both in female patients with simple goitre and in normal female subjects; the magnitude of change was greater in the former group. As reflected by acute increases of serum T3 and T4 concentrations, thyroidal responsiveness to endogenous TSH was progressively depressed with age in female patients with simple goitre and in normal female subjects. This age-related thyroidal refractoriness to TSH was more apparent when the changes were expressed as delta T3 (stimulated T3 - basal T3)/delta TSH (maximum TSH after TRH - basal TSH), and delta T4 (stimulated T4 - basal T4)/delta TSH. Delta T4/delta TSH was lower in female patients with simple goitre than in normal female subjects in all age groups. However, the difference was significant only for delta T4/delta TSH in group A. Thyroidal responsiveness to exogenous TSH also gradually declined with age in female patients with simple goitre.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

[Distribution, metabolism and excretion of 14C-MT-141 in rats. I. Distribution, metabolism and excretion after single intravenous administration in male rats].

The distribution, metabolism and excretion of the radioactivity were studied in male rats after the bolus intravenous administration of 14C-MT-141. The biological half-lives obtained from the blood concentration-time curve were 0.43 hour for the data in the first 4 hours and 16.5 hours for the data from 6 hours to 24 hours after the intravenous administration of 14C-MT-141. The radioactivity was excreted mainly into urine, and the cumulative urinary and fecal excretion of the radioactivity were 75.2% and 24.1% of the dose, respectively, within 120 hours after the intravenous administration of 14C-MT-141. The cumulative biliary excretion of the radioactivity was 18% of the dose within 48 hours after the intravenous administration, and 35% of the radioactivity excreted into bile (about 6% of the dose) was reabsorbed from the intestine. The highest concentration of the radioactivity was observed in the kidneys, and also the relatively high concentrations were observed in the liver, plasma and intestine, while the concentrations in the brain, fat and muscle were low. Within 24 hours after the intravenous administration of 14C-MT-141, the radioactivity in the highly distributed organs or tissues was decreased to less than 3% of the values at 5 minutes after the intravenous administration. A small amount of N-acetyl-MT-141 was found in urine and feces as a metabolite.

Animals↗
PubMed1984

[Distribution, metabolism and excretion of 14C-MT-141 in rats. II. Distribution and excretion after multiple intravenous administration in male rats and after single intravenous administration in female rats].

The distribution and tissue accumulation of the radioactivity were studied in male rats after the multiple intravenous administration of 14C-MT-141. The distribution and the placental transfer were also studied using pregnant rats or lactating rats after the single intravenous administration of 14C-MT-141. The radioactive concentration in the fetus was low and the radioactivity was distributed almost uniformly through the fetus body. The peak time of the milk level was 2 hours after the administration and the radioactivity in milk decreased gradually thereafter. The milk levels decreased more slowly than the blood levels did. The blood level after the last dose administered daily for 7 days tended to decrease more slowly, when compared with the single administration. However the blood concentration at 48 hours after the last administration was less than 3 times as high as that after the single administration.

Animals↗
PubMed1983

[Evaluation of autopsy cases in pancreatic cancer].

The incidence of pancreatic cancer has increased recently. The average age of pancreatic cancer patients in our series was 60.6 years; the male to female ratio was 2.3:1. As for tumor location, the head (45.5%) was the most frequent followed by the body (32.7%) and the tail (20%). Pancreatic cancers were histologically classified as duct carcinoma (88.2%), acinar cell carcinoma (0.9%), islet cell carcinoma (1.8%) and undifferentiated carcinoma (9.1%). In 17 cases (15.5%), diabetes mellitus was an accompanying complication.

Adult↗
PubMed1983

[Pharmacokinetics of a new antitumor antibiotic, neothramycin, after intrapleural administration].

In 5 patients with malignant pleural effusion, neothramycin (NTM) was intrapleurally administered at a dose of 30 mg in 3 cases and 40 mg in 2 cases and the pharmacokinetics was studied by using compartment models. The results were as follows: 1) Pleural levels of NTM were described by a mono-exponential equation and the half-life ranged from 3.45 to 6.48 hr. 2) The time to reach the maximum plasma level was 1 to 2 hr after pleural administration. The maximum levels were 54 to 106.4 ng/ml with the 30 mg dosage and 74.7 to 79.2 ng/ml with the 40 mg dosage, followed by a slow decline, with T1/2 ranging from 6.54 to 17.80 hr. 3) The elimination half-life of NTM in the plasma after intrapleural administration was much longer than that after intravenous administration. This phenomenon can be explained by a "flip-flop model": in this case, the rate of transfer from the pleural space to the plasma was much slower than that of the elimination from the plasma. 4) The parameters, K1 and K2, which were obtained by the deconvolution method, seemed to reflect the transfer of NTM between the pleural space and the plasma. 5) In 3 out of the 4 evaluable cases, an extreme decrease in the pleural fluid volume and suppression of reswelling were observed, including a case found to be negative for tumor cells upon cytodiagnosis.

Adenocarcinoma↗
PubMed1982

Mode of protective action of fosfomycin against dibekacin-induced nephrotoxicity in the dehydrated rats.

We studied the mechanism on protective effect of fosfomycin against experimental nephrotoxicity induced by dibekacin. In order to simplify an experimental model, the dehydrated Wistar rats were used, because a single injection of dibekacin at 30 mg/kg induced acute renal failure in the dehydrated rats, characterized by alteration of urinalytic parameters and BUN values, and retarded elimination of dibekacin from blood. When the rats were administered simultaneously with fosfomycin at 120 mg/kg, the rate of elimination was restored almost to normal, accompanied with improvement of the nephrotoxic parameters. However, markedly accelerated elimination over normal one was not observed, indicating that the improved elimination was not the reason of protection but a result of normal kidney function. On the other hand, fosfomycin protected the proximal tubular lysosomes from the injury of aminoglycoside, as evidenced a) in vivo by suppression of myeloid body formation and protection of lysosomal membrane integrity of the rats treated with dibekacin, and b) in vitro by dose-dependent protection of the lysosomal membrane integrity of the kidney cells. A study of structure-protective activity relation revealed that phosphonate anion possessing an epoxy function was important for protection, and that the mechanism of protection differed from the antibacterial mechanism.

Animals↗
PubMed1981

Acute toxicity and pharmacokinetics of dibekacin mice.

The LD50 values of dibekacin to mice were determined following three different methods of administration, namely, intravenous constant infusion, intravenous bolus injection, and intramuscular injection. The serum levels of dibekacin were pharmacokinetically analyzed. The differences in LD50 values between the methods of administration were discussed from the viewpoints of pharmacokinetics. 1) The LD50 value following the intravenous constant infusion was higher than that following the intravenous bolus injection and approached the level of that following the intramuscular injection, when the infusion rate of the drug was decreased by increasing the infusion period. 2) The biological half-life of dibekacin in mice was 24--45 min. 3) The volume of distribution increased as its dose increased, and a linear correlation was noted between log Vd and log (dose). 4) The difference among the maximum serum concentrations calculated with dibekacin following the administration of LD50 was small, which coincided with the results of the experiment that the serum concentrations of dibekacin at the death following the administration of LD100 were almost the same regardless of the method of administration.

Animals↗
PubMed1981

Pharmacokinetics of dibekacin in rabbits and dogs.

The behaviors of dibekacin after three administration methods to rabbits and dogs were pharmacokinetically analysed. 1) In both rabbits and dogs, the pharmacokinetic constants for the intravenous constant infusion and intramuscular injection were similar to each other, and the serum levels after the intravenous constant infusion for 1 hr were similar to those after the intramuscular injection except the peak time. 2) In both rabbits and dogs, Vd increased with the dose and a linear correlation was noted between log Vd and log (dose). 3) The tissue concentrations of dibekacin decreased with the decrease in the serum concentration. 4) A correlation equation, log T 1/2 = 0.194 . log B + 1.128, was obtained, where T 1/2 and B represent the biological half-life of dibekacin and the body weight of animals, respectively. It was suggested that the pharmacokinetic behaviors of dibekacin in human beings can be predicted from the results of the animal experiments.

Animals↗