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Biomedical subjects

I Yamazaki

Publications and source records attributed to I Yamazaki.

At least 145 records · Page 8Linked to original sources
PubMed1982

Pregnancy terminating effect of a highly active LH-RH agonist by vaginal application in rats.

A potent LH-RH agonist, des-Gly10-[D-Leu6]-LH-RH-ethylamide (TAP-144), administered to pregnant rats by the intravaginal and subcutaneous routes terminated pregnancy most effectively during days 7-11 of pregnancy. A daily administration of TAP-144 during days 7-10 was more effective by the intravaginal than by the subcutaneous route. When TAP-144 was administered twice a day during this period for one to three days, the effective dose became almost the same in the two routes. Complete termination of pregnancy occurred following a dose of 1 microgram/100 g body weight/a time by a single-day administration and 0.01 microgram/100 g body weight/a time by three days administrations. Previously we found that the serum concentration of TAP-144 after vaginal administration was lower but much longer-sustained than that after subcutaneous administration. Thus, in pregnancy termination, the prolonged duration of an effective concentration of TAP-144 seems to be more important than a transient high concentration. When rats were given effective doses of TAP-144 twice a day on day 9 by either route, ovulation occurred the next day (day 10) and the fetuses were aborted on day 11. Serum concentrations of progesterone and estradiol-17 beta dropped sharply. Estrus occurred on days 11-13, cycles were established thereafter, and ovulation occurred at regular intervals.

Abortifacient Agents, Steroidal↗
PubMed1982

Differences in the pregnancy-terminating effectiveness of an LH-RH analogue by subcutaneous, vaginal, rectal, and nasal routes in rats.

A long-acting analogue of LH-RH, des-Gly10-[D-Leu6]-LH-RH-ethylamide (TAP-144), was administered once or twice on day 9 of pregnancy by subcutaneous, vaginal, rectal, and nasal routes to rats; the pregnancy-terminating effectiveness of these routes was determined on day 14. When rats were given a single dose of TAP-144, the ED50 value was 1.2 micrograms/100 g body weight by the vaginal route, the effectiveness being 752 and 1,221 times higher than those by the subcutaneous and rectal routes, respectively. Nasal administration was not effective in terminating pregnancy even at a high dose of 2,000 micrograms/100 g body weight. The addition of a surfactant (BL-9) did not increase the effectiveness by the rectal route. When TAP-144 was administered twice a day, the effectiveness was markedly increased by every route. The ED50 values were 0.32 microgram/100 g body weight/time by the subcutaneous route, which was comparable to that of the vaginal route, 14.2 micrograms of the rectal route, and 84.6 micrograms of the nasal route. The addition of the surfactant increased the effectiveness 26 times by the nasal route but not by the rectal route. The pregnancy-terminating effect of TAP-144 was reversed by treatment with progesterone.

Abortifacient Agents↗
PubMed1981

Horseradish peroxidase C.

Horseradish peroxidase C (HRP; ferric) reacts with H2O2 to form Compound I, with an equilibrium constant of about 10(14) M-1. Two-step reduction of Compound I to Compound II and further to the ferric enzyme occurs reversibly at Eo' values of 0.90 and 0.93 V (pH 7.0), respectively. The pH dependence of Eo' values for each one-electron step, ferrous leads to ferric leads to Compound II leads to Compound I indicates that presence of redox-linked ionization at pKa values of 7.3 in the ferrous state, 11.0 in the ferric and 8.6 in Compound II. Zinc-substituted HRP C is oxidized to its free-radical form at an Eo' value of 0.74 (pH 6.0) Comparison of oxidized zinc HRP C with Compound I shows that Compound I contains a porphyrin pi-cation radical. The flash photolysis study on the NO-ferric HRP C complex clearly indicates that the iron is pentacoordinated in HRP C while it is hexacoordinated in metmyoglobin. From the kinetic analysis of the acid-alkaline conversion of HRP C, the second-order rate constants of the reactions with H+ and HO- are estimated to be 1.5 X 10(10) and 6.7 X 10(4) M-1s-1, respectively. The latter rate constant greatly varies with the kind of hemoproteins. In the presence of HRP C and O2, indole-3-acetate is oxidized to its hydroperoxide form, which reacts effectively with HRP C to form Compound I and further converts Compound I to a verdohemoprotein.

Electron Transport↗
PubMed1981

Analyses of catalytic intermediates of hog thyroid peroxidase during its iodinating reaction.

The formation of Compounds I, II, and III of hog thyroid peroxidase was demonstrated in its reaction with H2O2 by spectrophotometric and kinetic methods combined with a stopped flow technique. Hog thyroid peroxidase reacted with H2O2 to form Compound I with a rate constant of 5.2 X 10(6) M-1 s-1. Compound I was then spontaneously converted to Compound II with a rate constant of 8 s-1. In the presence of 200 microM H2O2, Compound II ws further converted to Compound III (or oxyform) with a half-life of 0.8 s. During the peroxidative oxidation of tyrosine, thyroid peroxidase was present as Compound I, and the rate constant for the reaction of Compound I with tyrosine was measured at 1.4 X 10(4) M-1 s-1. The addition of iodide to the above reaction system markedly decreased the steady state concentration of Compound I. From the kinetic data, it was concluded that the reaction between Compound I and iodide occurred by way of a 2-electron transfer and the rate constant was roughly estimated at 2.1 X 10(7) M-1 s-1. This value was much higher than that obtained from overall kinetic data. Similar reactions were carried out with bovine lactoperoxidase and the kinetic data for the two enzymes were compared. The primary oxidation product of iodide was suggested to be iodinium cation (I+) in either enzyme reaction.

Animals↗
PubMed1981

Comparison of the renal excretory mechanisms of cefmenoxime and other cephalosporins: renal clearance in rats and rabbits.

The renal excretory mechanism of cefmenoxime was compared with those of 6 other cephalosporins (cefotaxime, deacetylcefotaxime, cefotiam, cefazolin, cephaloridine and cefsulodin) in rats and rabbits. In rats, renal clearance (Cf-Drug: corrected for serum protein binding) of cefmenoxime (4.06 ml/minute) was lower than that of cefazolin, similar to that of cefotiam, and higher than those of cefotaxime, deacetylcefotaxime, cephaloridine, and cefsulodin. In rabbits, the value for cefmenoxime (2,519 ml/minute) was markedly higher than those for the other drugs. If the clearance ratio (Cf-Drug/CInulin = CRf) is more than unity, tubular secretion of a drug is indicated. In rats, the tubular secretion of cefmenoxime equalled the glomerular filtration (CRf = 2.17). The tubular secretion of cefmenoxime was lower than that of cefazolin but similar to that of cefotiam. None of the other cephalosporins seemed to be secreted significantly. In rabbits, a large amount of cefmenoxime was secreted (CRf = 208). The tubular secretion was larger than those of the other cephalosporins. All the drugs except cefsulodin showed significant tubular secretion. A species difference was observed in the CRf of the cephalosporins: the values were generally higher in rabbits than in rats.

Animals↗
PubMed1981

Comparison of the renal excretory mechanisms of cefmenoxime and other cephalosporins: effect of para-aminohippurate on renal clearance and intrarenal distribution of cephalosporins in rabbits.

The renal excretory mechanism of cefmenoxime in rabbits was compared with that of 6 other cephalosporins (cefotaxime, deacetylcefotaxime, cefotiam, cefazolin, cephaloridine, and cefsulodin). The clearance ratios (Cf-Drug/CInulin=CRf) of cefmenoxime (337) and cefazolin (73) were considerably higher than those of the 5 other cephalosporins (0.9-20). When p-amino-hippurate (PAH) was administered concurrently with each of the cephalosporins, the CRf values of the cephalosporins except for cefsulodin were significantly decreased. These findings indicate that cefmenoxime and the 5 other cephalosporins except cefsulodin are actively incorporated in the proximal tubular cells and secreted into the tubular lumen. In the case of cefotiam and cefsulodin, glomerular filtration tended to exceed urinary excretion with highest dose of PAH (40 mg/kg/minute), suggesting the possibility of tubular reabsorption of these drugs. On the other hand, glomerular filtration of cefmenoxime and the 4 other cephalosporins did not exceed urinary excretion. The drug concentration ratio of the cortex to medulla indicated that the tubular cell level of cefmenoxime was lower than, higher than, and similar to those of cephaloridine, cefotaxime, and the remaining cephalosporins, respectively. These results demonstrate that the renal excretory mechanisms of cefmenoxime is similar to that of cefazolin but not to that of the remaining cephalosporins.

Aminohippuric Acids↗
PubMed1980

Formation of porphyrin pi cation radical in zinc-substituted horseradish peroxidase.

Zinc-substituted horseradish peroxidase is oxidized by K2IrCl6 to a characteristic state which retains one oxidizing equivalent more than the zinc peroxidase. The oxidized enzyme gives an optical absorption spectrum similar to that of compound I of peroxidase and catalase, and a g = 2 electron paramagnetic resonance signal which has an intensity corresponding to the porphyrin content. It is reduced back to the zinc peroxidase by a stoichiometric amount of ferrocyanide or by a large excess of K3IrCl6. From the equilibrium data, the value of E0' for the zinc peroxidase couple is estimated to be 0.74 V at pH 6. The oxidized zinc peroxidase is also formed by the addition of H2O2 or upon illumination with white light. The rate constants for the oxidation by K2IrCl6 and H2O2 at pH 8.0 are 8 x 10(5) and 8 x 10(2) M-1 s-1, respectively. No essential spectral change can be observed when K2IrCl6 is added to the metal-free peroxidase (protoporphyrin--apoperoxidase complex) or to zinc-substituted sperm whale myoglobin.

Cations↗
PubMed1980

A kinetic study on the diffusion-coupled reaction of a basic horseradish peroxidase adsorbed on the carboxymethylcellulose membrane.

The rate of reactions of a basic horseradish peroxidase adsorbed on the carboxymethylcellulose membrane was measured spectrophotometrically by monitoring the state of the enzyme. For the reactions with hydrogen peroxide and cyanide dissolved in media the diffusion process was rate limiting both in the static and flowing media, and kinetic features of the enzyme were masked. The rate of CO recombination of the ferrous enzyme was measured by flash photolysis in the static media containing varying amounts of CO. Apparently, the initial rate of CO recombination was no more affected by the diffusion factor, and the second order rate constant could be measured for the reaction of the enzyme adsorbed on the membrane. The value was about 70% of that obtained from the enzyme in solution and exhibited the same pH dependence as did the value for the enzyme in solution. The difference of the reaction pattern between the enzymes on the membrane and in solution became distinct when flash photolysis was applied to the reaction system without free CO in the medium. The kinetic data were analyzed by computer simulation.

Carbon Monoxide↗
PubMed1980

The conversion of horseradish peroxidase C to a verdohemoprotein by a hydroperoxide derived enzymatically from indole-3-acetic acid and by m-nitroperoxybenzoic acid.

A verdohemoprotein was formed from Compound I of horseradish peroxidase C upon the addition of about 2 molar equivalents of m-nitroperoxybenzoic acid (mNPBA) or hydroperoxide formed from indole-3-acetic acid during its catalytic oxidation. The formation of the verdohemoprotein occurred via two intermediates which have an absorbance peak at 965 or 940 nm. Carbon monoxide was evolved in the reaction from the 940 compound to the verdohemoprotein. From the kinetic and titration data, the following reaction sequence was proposed. (Formula: see text). The 940 compound could be reduced by dithionite and ascorbate to the ferrous and the ferric enzyme, respectively. The enzyme species that reacted with mNPBA to form the 965 and the 940 compounds was concluded to be Compound I but neither Compound II nor oxyperoxidase (Compound III).

Carbon Monoxide↗
PubMed1980

A radioimmunoassay for a highly active luteinizing hormone-releasing hormone analogue and relation between the serum level of the analogue and that of gonadotropin.

Antisera to an LH-RH analogue, des-Gly10-[D-Leu6]-LH-RH-ethylamide (TAP-144) were produced in 10 rabbits. By using these antisera, a specific and sensitive radioimmunoassay for TAP-144 was established. Sensitivity of the radioimmunoassay ranged from 5 to 100 per assay tube with these antisera. Lh, FSH, TRH, LH-RH, and the 1-6 fragment of TAP-144 did not practically cross-react with LH-RH analogues, though the degree of the cross-reactivity differed among individual sera. The average cross-reactivity of the 10 antisera showed low specificities to TAP-144 analogues which are altered at positions 2, 3, 4, 5, and 6, but showed high specificities to those altered at positions 8 and 9. The antisera also showed low cross-reactivities to LH-RH analogues replaced at position 6 by D-amino acids and those altered at position 10 by alkylamines, but they showed fairly high cross-reactivities to analogues which are altered simultaneously at both positions 6 and 10. When TAP-144 was administered intraperitoneally to rats on the diestrous day, serum concentrations of TAP-144 increased dose-dependently but maximal serum concentrations of both LH and FSH were attained in response to higher doses of TAP-144. The peak LH and FSH concentrations appeared 70 to 110 min after the peak TAP-144 concentration had been reached. Similar delays in reaching the peak LH and FSH levels were also observed when TAP-144 was administered intravenously, subcutaneously and intramuscularly. When TAP-144 was administered intravaginally, a low but constant serum level of TAP-144 was maintained from 5 to 300 min after the administration, but serum LH and FSH levels declined to a low level from 180 min after the TAP-144 administration.

Animals↗
PubMed1980

Absorption, distribution and excretion of cefmenoxime (SCE-1365), a novel broad-spectrum cephalosporin, in mice, rats, rabbits and dogs.

The levels of cefmenoxime (SCE-1365) [7 beta-[2-(2-aminothiazol-4-yl)-[Z]-2-methoxyiminoacetamido]-3-[(1-methyl-1H-tetr azol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid] and cefotaxime [7 beta-[2-(2-aminothiazol-4-yl)-[Z]-2-methoxyiminoacetamido]-3-acetoxymethyl-ceph -3-em-4-carboxylic acid] in plasma and tissues, and the excretion in urine and bile of experimental animals were compared. A single dose of 20 mg/kg of cephalosporins was administered subcutaneously to mice and intramuscularly to rats, rabbits and dogs. The cefmenoxime and cefotaxime levels in plasma and tissues reached a peak in 15 approximately 30 minutes after administration. The cefmenoxime levels in plasma were slightly higher than that of cefmenoxime in rats and slightly lower in mice, rabbits and dogs. The tissue levels of cefmenoxime, however, were much higher than those of cefotaxime. In mice and rats, cefmenoxime was distributed in high concentration to various tissues in the descending order of the kidney, plasma, liver, lung, spleen and brain; in rabbits, kidney, plasma, lung, liver, spleen and brain; and in dogs, kidney, liver, plasma, lung, spleen and brain. The plasma and tissue levels of cefmenoxime persisted much longer than those of cefotaxime. Both cephalosporins were excreted principally in the urine. A high biliary excretion of cefmenoxime was observed in rats and dogs. In the specimens from animals given cefotaxime, deacetylcefotaxime was found in various amounts.

Absorption↗
PubMed1979

The oxidation-reduction potentials of compound I/compound II and compound II/ferric couples of horseradish peroxidases A2 and C.

The reversibility of the stepwise reduction of Compound I to the ferric state via Compound II was confirmed in horseradish peroxidases A2 and C. The values of E'o (compound I/Compound II) and E'O (Compound II/ferric) were measured from equilibrium data coupled with the K2IrCl6-K3IrCl6 system in a narrow region of pH near 6.3. The ferric enzymes were also oxidized by ferricyanide to Compound II at alkaline pH and the values of E'O (Compound II/ferric) were measured from the equilibrium data. The pH dependence of E'O (Compound II/ferric) was in accord with the equation: E'O = EO + 0.058 log (Kr[H+] + [H+]2)/(KO + [H+]), where Kr and KO are proton dissociation constants in the ferric enzyme and Compound II, respectively. The pH-E'O (Compound I/Compound II) curves were likewise obtained from the equation, E'O = EO + 0.058 log (Kr + [H+]), where Kr is the proton dissociation constant in Compound II. The forward and backward rate constants were measured in each of one-electron transfer reactions of the peroxidases with the K2IrCl6-K3IrCl6 system at various pH values. The E'O values calculated on the assumption that the ratio of the rate constants equals the equilibrium constant were compared with those obtained from the equilibrium data.

Ferricyanides↗
PubMed1979

Salts- induced oxidase activity of lipoamide dehydrogenase from pig heart.

A weak NADH oxidase activity of lipoamide dehydrogenase at neutral pH is increased as much as 15-fold by the addition of KI or (NH4)2SO4. The addition of NAD+ shifts the optimum pH for the KI-induced oxidase activity from 6.3 to 5.5 without changing the maximum activity. The optimum pH is similarly shifted to 5.6 when sulfhyldryl groups of the enzyme are oxidized in the presence of small amount of cupric ion. The NADH: lipoamide and NADH: p-benzoquinone reductase activities are strongly inhibited by KI but both are increased by the presence of (NH4)2SO4. The known intermediate having a charge-transfer band at 530 nm can be seen upon an addition of NADH to the enzyme in the presence of (NH4)2SO4 but not in the presence of KI. The enzyme flavin is reductase by a stoichiometric amount of NADH when KI is present.

Animals↗
PubMed1979

The mechanism of indole-3-acetic acid oxidation by horseradish peroxidases.

The oxygen-consuming oxidation of indole-3-acetic acid (IAA) occurred much faster in the presence of horseradish peroxidase C (neutral isoenzyme) than in the presence of horseradish peroxidase A (acidic isoenzyme). An intermediate oxidation product of IAA was found to be a hydroperoxide species that reacted with the ferric enzymes to form Compound I at second order rate constants of 6.8 X 10(3) M-1--S-1 for peroxidase A and 2.0 X 10(6) M-1--S-1 for peroxidase C at pH 4.4 The hydroperoxide concentration reached about one-half of the initial IAA concentration at the end of the oxygen-consuming reaction and then decreased slowly. The main intermediate of the enzyme observed during the oxygen-consuming reaction was Compound II, which oxidized IAA to its free radical at rate constants of 1.5 X 10(3) M-1--S1 for peroxidase A and 1.2 times 10(4) M-1--S-1 for peroxidase C at pH 4.4 The results supported the mechanism that the oxygen consumption occurs mainly through the reaction of oxygen with the IAA free radical formed from the peroxidatic oxidation of IAA. The ferric enzymes were not reduced by IAA under strict anaerobic conditions in the presence of carbon monoxide but were reduced upon addition to a small amount of oxygen or hydrogen peroxide to the systems. The results suggested that the ferric enzyme is reduced by the IAA free radical but not by IAA itself. From a comparison of reactivities of oxyperoxidase and Compound II we concluded that the catalytic cycle of ferrous and oxyperoxidases is not involved in the IAA oxidase reaction.

Horseradish Peroxidase↗