Search PubMed⌕ Search

Biomedical subjects

H Kitagawa

Publications and source records attributed to H Kitagawa.

At least 559 records · Page 31Linked to original sources
PubMed1982

Effects of diiospropyl-1,3-dithiol-2-ylidene malonate (NKK-105) on acute toxicity of various drugs and heavy metals.

The influence of NKK-105 on the acute toxicity of strychnine nitrate, potassium cyanide, chloral hydrate, atropine, tetrodotoxin, mercuric chloride, cadmium chloride, lead acetate and arsenic trioxide were examined in rats. NKK-105 prolonged the time of death induced by strychnine, potassium cyanide and tetrodotoxin in acute toxicity. Survival time was prolonged in rats treated with the toxic metals by pretreatment with NKK-105. NKK-105 counteracted the lethal effect of strychnine, potassium cyanide, chloral hydrate, mercuric chloride and cadmium chloride. NKK-105 significantly decreased the acute toxicity of these drugs but the inhibitory effect was not observed in the acute toxicity of atropine, tetrodotoxin, lead acetate and arsenic trioxide.

Animals↗
PubMed1982

Influence of maternal drug metabolism on the fetal toxicity induced by acetylsalicylic acid.

Investigations were performed to explore changes in fetal toxicity induced by acetylsalicylic acid (ASA) in pregnant animals treated by various means for maternal alterations. The fetotoxicity induced by ASA (500 mg/kg s.c.) was higher in rats than in mice. In mice with low enzyme activity, those displaying a longer sleeping time in pentobarbital-induced sleep, the ASA-fetotoxicity was higher than that of mice with shorter sleeping time. In rats pretreated with phenobarbital (0.05%), Zn (10 mg/l) and Cu (10 mg/l) in tap water and cysteine (200 mg/kg s.c.), fetal toxicity of ASA was reduced, whereas it was enhanced in rats pretreated with SKF-525A (200 mg/kg s.c.) and alpha-naphthyl acetic acid (200 mg/kg p.o.) and in nephrectomized rats. The UDPGT activity in hepatic 9000 x g supernate was higher in mice than in rats and the activity of mice was increased by phenobarbital and Cu. This study indicates that ASA-induced fetotoxicity can be positively modified by alterations in drug metabolizing activity.

Animals↗
PubMed1982

Induction of hepatic gamma-glutamyl transpeptidase in rats by repeated administration of aminopyrine.

The effect of a 20-day administration of aminopyrine (600 mg kg-1) as well as two metabolites of aminopyrine, 4-aminoantipyrine (525 mg kg-1) and 4-acetamidoantipyrine (635 mg kg-1), on several hepatic, kidney and serum enzyme activities were investigated. In the aminopyrine-treated group, a pronounced induction of gamma-glutamyl transpeptidase was shown in the whole homogenate as compared to that in the hepatic microsomes. Serum gamma-glutamyl transpeptidase activity was also increased by administration of aminopyrine or 4-aminoantipyrine. No change in gamma-glutamyl transpeptidase activity was observed in kidney and hepatic cytosolic fractions. In all cases, 4-acetamidoantipyrine treatment showed no significant change in the enzyme activities tested. Under the same experimental condition, the amounts of cytochrome P-450 and b5, the activities of aminopyrine N-demethylase, aniline hydroxylase and carboxylesterase of liver microsomes were all induced in the aminopyrine- and 4-aminoantipyrine-treated rats. The activities of NADPH cytochrome c reductase and NADH ferricyanide reductase were also increased. The results in this paper support the view that repeated administration of aminopyrine induces hepatic membrane-bound enzyme, particularly, gamma-glutamyl transpeptidase activity.

Aminopyrine↗
PubMed1982

[Role of vagus nerves in bronchoconstriction induced by chemical mediators].

The role of the vagal reflex in bronchoconstriction induced by histamine, acetylcholine, serotonin, and PGF2 alpha was investigated in anesthetized dogs using a complete vagal blockade by cooling. We devised a thermode for vagal cooling. The vagal cooling was performed by circulating cold water through the thermode attached to fit snugly around the bilateral cervical vagus nerves. Airway musculature response was measured as a change in ventilation overflow with a modification of the Konzett-Rössler method. Drugs were injected close intraarterially into the right bronchial artery and inhaled into the airway. Afferent impulses of the vagus nerve were abolished by cooling at 0 degree C. When the vagus nerves were cooled to 0 degree C, the ventilation overflow decreased. On the other hand, when the nerves were rewarmed, the ventilation overflow increased again. Bronchoconstriction was produced by close intraarterial injection of histamine, acetylcholine, serotonin, or PGF2 alpha at a dosage of 10 microgram each. The bronchoconstrictions produced by these agents were inhibited by vagal cooling. The bronchoconstrictions induced by histamine, acetylcholine, and serotonin were all 0.00125%, and that by PGF 2 alpha was 0.001%. Inhalations for 10 min were also inhibited by vagal cooling. These findings indicate that the thermode devised in this study is useful for vagal cooling and that vagally mediated bronchoconstriction is a relatively major component of bronchoconstriction induced by chemical mediators.

Acetylcholine↗
PubMed1982

[Effects of tofisopam on gastric functions in rats (author's transl)].

The effects of tofisopam on gastric functions were examined in rats. Intracerebroventricular (i.c.v.) injection of tofisopam (50 ot 100 microgram) increased both basal gastric acid output and mucosal blood flow (MBF) in rats anesthetized with urethane, while intravenous injection of tofisopam (10 mg/kg) did not change the basal gastric acid output. Ten micrograms of tofisopam, i.c.v., a dose which did not show any effect on the basal gastric acid output, significantly inhibited the decrease in gastric acid output induced by noradrenaline (5 microgram, i.c.v.). Tofisopam (10 mg/kg, i.v. or 100 microgram, i.c.v.) showed no effect on the increase in gastric acid output induced by electrical stimulation of the lateral hypothalamic area (LHA). These results, together with the previous findings, suggest the tofisopam (i.c.v.) acts on the nucleus dorsalis n. vagi and/or LHA and competes with noradrenaline. The gastric acid output was increased remarkably under water-immersion stress, and this increase lasted during the stress-loading, but the MBF did not show a corresponding increase. Pretreatment of rats with tofisopam (100 mg/kg, intraduodenal) significantly increased the MBF and inhibited the ulcer formation caused by the stress. From these results, tofisopam may restore the unbalance between sympathetic and parasympathetic nervous tones induced by stress-loading.

Animals↗
PubMed1982

Effect of hydralazine on hepatic drug metabolizing enzymes in rats.

The effects of hydralazine on hepatic drug metabolizing enzymes were studied in rats. Hydralazine inhibited aminopyrine N-demethylase and aniline hydroxylase in vitro. Kinetic studies indicated that the inhibitory natures of hydralazine were recognized as almost mixed types and a change in difference spectrum demonstrated that hydralazine could bind to cytochrome P-450 as a characteristic type II. A single administration of hydralazine inhibited the drug metabolism, but neither reduction nor induction of the mixed function oxidase system were observed after the hydralazine treatment for 7 days, except the reduction of cytochrome b5 content. In addition, acidophilic degeneration and the formation of acidophilic bodies in liver cells by hydralazine were observed.

Animals↗
PubMed1982

Species differences in hypocalcemia induced by acetyl-salicylic acid.

The study was performed to explore species differences in hypocalcemia induced by acetylsalicylic acid (ASA). ASA decreased plasma and serum calcium (Ca) level at the dose of more than 200 mg/kg s.c. and p.o. in mouse, rat and guinea pig, and a correlation between serum Ca and salicylic (SA) levels was recognized in these species. However, hypocalcemia was not observed in rabbit and dog by the oral administration of ASA 400 mg/kg though high serum levels were found. Species differences were recognized in ASA-induced hypocalcemia. It was suggested that the differences were probably due to the different activity of calcitonin decreased serum Ca level in rabbit.

Animals↗
PubMed1982

Transport of L-cysteine and reduced glutathione through biological membranes.

Comparative studies were carried out on in vivo and in situ absorption in rats and in vitro uptake by red cells of L-cysteine (CySH) and reduced glutathione (GSH). After oral administration of CySH, the plasma and liver CySH levels and liver GSH level significantly increased, but the plasma GSH level did not. In contrast to the results with CySH, when GSH given orally at a dose equivalent to that of CySH either on a weight or molar base, no increase in the levels of GSH was observed at either dose level. In a rat small intestine recirculation system in situ, CySH added to the recirculation perfusate disappeared progressively with time from the perfusate, indicating that transportation occurred across the intestinal wall, but with GSH such disappearance was not observed. CySH was taken up well by rabbit erythrocytes in vitro, but GSH was not. It was concluded, therefore, that CySH passes through biological membranes and serves as a good source of SH groups, whereas GSH is ineffective when given orally because of its poor absorption from the digestive tract and/or poor ability to permeate through the membrane.

Animals↗
PubMed1982

Fetal toxicity and hypocalcemia induced by acetylsalicylic acid analogues.

In the present study, we investigated a correlation of fetotoxicity induced by salicylic acid (SA) analogues to their hypocalcemic effect. Among of SA analogues, acetylsalicylic acid, salicylaldehyde, salicyl-alcohol, methyl salicylate and SA evoked a hypocalcemia in rats and mice but the other analogues had no effect by their single administration. The additional administration of dihydroxybenzoic acids elicited the hypocalcemia following the fetal toxicities induced by SA analogues paralleled to that of their hypocalcemic effect. A hypocalcemic effect was induced only by the benzoic acids with hydroxy group existing in ortho-position.

Abnormalities, Drug-Induced↗
PubMed1982

[Effects of methanobenzazonine (2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine) derivatives on the cough reflex and respiration].

Antitussive and respiratory effects of three newly synthesized methanobenzazonine derivatives and their d- and l-isomers were investigated to understand the relationship between the cough and respiratory centers. Antitussive effects were evaluated with the PEC (puncture electrode-induced cough) method in conscious d-, dl-, and l-ST-2123; d-, dl-, and l-ST-2121 into the right carotid artery at a dose range of 0.2-0.8 mg caused no effect on respiration. dl-ST-2121 at 0.4 to 0.8 mg and l-ST-2121 at 0.2 to 0.8 mg depressed respiration dose-dependently. Codeine (0.2-0.8 mg) depressed respiration slightly. Morphine (0.2-0.8 mg) depressed respiration more strongly. All the methanobenzazonine derivatives used, when given intraperitoneally, showed antitussive potencies that were 1/3-1/2 the potency of codeine. The antitussive potencies of the d-, dl-, and l-isomers of the three derivatives used were discussed on the bases of chemical structures and drug receptors. These results provide evidence of a discrepancy between the cough and respiratory centers in the brain stem.

Animals↗
PubMed1982

[Effects of respiratory drugs on the cough reflex].

In order to understand the relationship between the cough and respiratory centers in the brain stem, we investigated the effects of respiratory stimulants, pentylenetetrazol (PTZ) and nikethamide (NK), and a respiratory depressant, pentobarbital (PB)on the cough reflex. Coughs were induced in lightly anesthetized dogs by intraarterially into the vertebral artery. The rate (RR), amplitude (RA), and volume (RV) of the respiration and the number (NC) and amplitude (AC) of the cough reflex induced were used as indices. PTZ and NK, even at subthreshold doses for respiratory stimulation, enhanced the cough reflex (NC; not AC). On the other hand, PB at subthreshold doses for a respiratory depression decreased both NC and AC. The above findings suggest that respiratory stimulants generally enhance the cough reflex, and respiratory depressants reduce the cough reflex. Additionally, the thresholds for the cough responses to respiratory drugs are lower than those for the respiratory responses.

Animals↗