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Biomedical subjects

M Moriguchi

Publications and source records attributed to M Moriguchi.

At least 91 records · Page 5Linked to original sources
PubMed1984

Effects of midecamycin acetate (miocamycin), a new macrolide antibiotic, on reproductive performances in rats and rabbits.

Miocamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic isolated from a culture broth of Streptomyces mycarofaciens. The objective of this study was to determine the effect of MOM on reproductive performance in rats and rabbits. MOM, non-crystalline solid, was suspended in 0.1% CMC solution immediately before use. In this study, reproductive performance was studied according to the following designs: Fertility test (Segment I) in Wistar rats Teratogenicity test (Segment II) in Wistar rats Peri- and post-natal tests (Segment III) in Wistar rats Behavioral test in rat newborns in Segments II and III Teratogenicity test (Segment II) in New Zealand white rabbits In conclusion, MOM, non-crystalline solid, might have no teratogenesis and little influence on dams and their fetuses and offsprings.

Abnormalities, Drug-Induced↗
PubMed1984

[Toxicological studies on a new cephamycin, MT-141 IX. Its teratogenicity test in rats and rabbits].

A teratogenicity study of MT-141 was performed in SD rats and Japanese white rabbits. The pregnant rats were administered intramuscularly (i.m.) with MT-141 at the dose levels of 200, 400, 800 and 1,600 mg/kg/day from the day 7 up to the day 17 of gestation. The pregnant rabbits were administered intravenously (i.v.) with the drug at the dose levels of 10, 20 and 40 mg/kg/day from the day 6 up to the day 18 of gestation. The results are summarized as follows. Rats: Though the administrations with MT-141 at all dose levels did not change body weight gain and water intake of treated dams, a slight suppression in the food consumption was produced by MT-141 at the dose of 1,600 mg/kg/day. The examinations on cesarean section revealed no effect of MT-141 on teratological parameters such as external malformation and frequency of visceral and skeletal anomalies in the fetuses. MT-141 at all dose levels exerted no toxic effect on developmental, functional and behavioral parameters in F1 rats and on mating, fertility and pregnancy of F1 rats. Furthermore, there was no effect of MT-141 on the findings in cesarean section of F1 rats. The fetuses from F1 rats had no malformation of external appearance, viscera and skeleton. Rabbits: MT-141 had no significant effect on body weight gain and food consumption of dams at the all dose levels, but caused a slight suppression in the water intake at the doses more than 20 mg/kg/day. One rabbit aborted in each group given 20 or 40 mg/kg/day. One rabbit died in the group given 20 mg/kg/day. Examinations on cesarean section showed that MT-141 at the dose of 40 mg/kg/day produced a decrease in body weights of females and an increase in dead or resorbed fetuses followed by a decrease in live fetuses. MT-141 is no effect malformation of external appearance, viscera and skeleton in the fetuses of all treated groups. The above-mentioned results suggest that MT-141 has no teratogenic effect on pregnant rats and rabbits. It is concluded from these results that the maximal "no effective" dose of MT-141 on fetal toxicity is above 1,600 mg/kg/day i.m. for pregnant rats and 10 mg/kg/day i.v. for pregnant rabbits.

Abnormalities, Drug-Induced↗
PubMed1983

Cardiovascular effects of a newly synthesized cardiotonic agent (TA-064) on normal and diseased hearts.

A new inotropic agent, TA-064, (-)-alpha-(3,4-dimethoxyphenethylaminomethyl)-4-hydroxybenzylalcohol, was shown to have strong effects in experimental animals. Its effectiveness and associated adverse effects were tested in humans invasively (n = 6) and noninvasively (n = 17). Increasing doses of intravenous infusion (1, 2, and 4 micrograms/kg/min) increased plasma levels to 15, 35, and 82 ng/ml, respectively, resulting in marked increases in the peak rate of left ventricular pressure rise (dP/dt) (1,450 +/- 63 to 3,042 +/- 349 mm Hg/s) (mean +/- standard error of the mean [SEM], p less than 0.01) and the ratio of dP/dt to left ventricular pressure at a developed pressure of 40 mm Hg (25 +/- 3 to 39 +/- 2 s-1) (p less than 0.01), with a reduction in left ventricular end-diastolic pressure (12 +/- 2 to 4 +/- 1 mm Hg) (p less than 0.01). Minimal or no changes were seen in heart rate and left ventricular systolic pressure. After a single oral dose (10 mg), the plasma level reached its peak at 90 minutes (16 +/- 9 ng/ml, n = 17). A positive inotropic effect was confirmed echocardiographically in both healthy volunteers (n = 8) and patients with congestive heart failure (CHF) (n = 9) who were maximally treated with conventional regimens: increase in mean velocity of circumferential fiber shortening (healthy volunteers: 1.29 +/- 0.05 to 1.60 +/- 0.11 circ/s [p less than 0.05]; patients with CHF: 0.69 +/- 0.08 to 0.93 +/- 0.09 circ/s [p less than 0.01]), ejection fraction (healthy volunteers: 68 +/- 2 to 75 +/- 2% [p less than 0.05], patients with CHF: 37 +/- 4 to 45 +/- 5% [p less than 0.01]) without change in heart rate. The cardiac index was increased only in the CHF group (2.71 +/- 0.22 to 3.21 +/- 0.24 liters/min/m2) (p less than 0.05). No significant untoward effects were observed. Thus TA-064 is a potent inotropic agent and can be used either parenterally or orally. Salutary effects can be expected in patients with congestive heart failure who are treated with digitalis and diuretic agents.

Adult↗
PubMed1982

Teratological studies on collagen wound dressing (CAS) in mice.

We subcutaneously injected collagen wound dressing (CAS) extracts equivalent to the area covering human body surface by 35 and 70%, respectively, into mouse dams from days 6 to 15 of pregnancy. No toxicity was observed in dams and no external, skeletal and visceral anomalies related to CAS treatment were observed in fetuses. It is, therefore, concluded that CAS extracts produces no teratogenesis after subcutaneous injection during organogenesis in mice.

Abnormalities, Drug-Induced↗
PubMed1981

Purification and properties of guanylate kinase from baker's yeast.

Guanylate kinase (ATP:(d)GMP phosphotransferase, EC 2.7.4.8) was purified about 200-fold with 4% yield from baker's yeast. The enzyme preparation showed a single band on polyacrylamide gel electrophoresis and the molecular weight of the enzyme was calculated to be 25 000 by gel filtration. With ATP as a phosphate donor, the kinase used only GMP as a phosphate acceptor. Km values for ATP and GMP were 0.5 and 0.048 mM, respectively. The enzyme reacted optimally at pH 7.5. The enzyme was labile during storage at 4 degrees C and inactivation was prevented by 20% glycerol.

Adenosine Triphosphate↗
PubMed1980

Inhibition of UDP-N-acetylglucosamine pyrophosphorylase by uridine.

UDP-N-acetylglucosamine pyrophosphorylases (UTP: 2-acetamido-2-deoxy-alpha-D-glucose-1-phosphate uridylyltransferase, EC 2.7.7.23) from baker's yeast and Neurospora crassa IFO 6178 were inhibited by uridine which is the nucleoside moiety of UDP-GlcNAc. The inhibition was shown in both directions of pyrophosphorolysis and of synthesis of UDP-GlcNAc. Kinetic analysis revealed that uridine demonstrated a noncompetitive type of inhibition with UDP-GlcNAc and competitive inhibition with PPi. The Ki values for the baker's yeast enzyme were 1.8 mM for UDP-GlcNAc and 0.16 mM for PPi, and the values for the Neurospora enzyme were 1.1 mM for UDP-GlcNAc and 0.15 mM for PPi, respectively. Uridine did not bind irreversibly to the enzyme, as the activity was restored with dialysis. No other nucleosides caused inhibition of the enzyme activity except uridine. Some uridine derivatives, such as 5-hydroxyuridine, 5,6-dihydrouridine and pseudouridine, also inhibited the enzyme activity. But doexyuridine showed only slight inhibition, and 5'-UMP and orotidine caused no inhibition of the enzyme activity.

Kinetics↗
PubMed1980

Purification and enzymatic properties of glyoxylate reductase II from baker's yeast.

Glyoxylate reductase II was purified about 2,400-fold from a cell extract of baker's yeast by protamine sulfate treatment, and column chromatographies on DEAE-cellulose, hydroxylapatite, Sephadex G-150, and phosphocellulose. The purified enzyme was electrophoretically homogeneous. The molecular weight was determined to be approximately 65,000 by gel filtration. The enzyme was greatly stabilized by the addition of 20% (v/v) glycerol. It catalyzed the reduction of glyoxylate and hydroxypyruvate and was specific for NADPH as an electron donor, but showed slight affinity towards NADH. The Michaelis constants for glyoxylate, hydroxypyruvate, NADPH, and NADH were found to be 16mM, 1.4 mM, 5.7 microM, and 0.43 mM, respectively. The enzyme was inhibited by p-chloromercuribenzoate (PCMB) and iodoacetate, but inhibition was prevented by dithiothreitol (DTT) or L-cysteine. The reduction of glyoxylate and hydroxypyruvate was not stimulated by anions.

Alcohol Oxidoreductases↗
PubMed1980

[Effect of fosfomycin-calcium on reproductive performance of rats. II. Fertility test (author's transl)].

Fosfomycin calcium (FOM-Ca) was orally administered to Wistar rats for 60 consecutive days in males and 14 consecutive days in females in varying doses of 140 mg/kg, 700 mg/kg and 1,400 mg/kg, and then the animals were subjected to mating. It was further administered to pregnant female rats for another week to investigate its effects upon the embryos and fetus. The following results were obtained. 1) In parent animals, soft stools were noted in both sexes of the groups with higher doses, but otherwise there was no remarkable abnormality noted. 2) No increase was seen in the rates of development of dead embryos or externally abnormal fetus. 3) Skeletal abnormality was seen only slightly in the animals of the group with 700 mg/kg, but otherwise all the other groups were similar to the control group, showing that there would be no adverse effects by the tested drug upon the fetal skeletal structure. 4) On the ground of the above-mentioned test results, it was claimed that FOM-Ca exerts adverse effects upon the fetus of rats even in the dose of 700 mg/kg and that the safe dose to fetus of rats would be 140 mg/kg. It was also judged that it has no teratogenicity through administration before or at the initial stage of gestation.

Animals↗
PubMed1980

[Effect of fosfomycin-calcium on reproductive performance of rats. III. Peri- and post-natal examination (author's transl)].

The peri- and post-natal examination of fosfomycin-Ca (FOM-Ca) was undertaken in Wistar strain rats. Rats were treated orally at dose levels of 140, 1,400 and 2,800 mg/kg/day from the 14th day of gestation to 21st day after delivery. One-third of pregnant rats in each group were sacrificed on 20th day of gestation and then their fetuses were examined for external, visceral and skeletal observation. The remaining mothers were allowed to deliver naturally, and then their offsprings were examined for postnatal development. No effect of FOM-Ca treatment to rat mothers was found except soft stool was seen in 1,400 and 2,800 mg/kg groups. No effect of FOM-Ca on rat fetuses and newborns was found except fetal body weight and survival rate decreased and skeletal variation increased in maximum dose. Consequently, it can be concluded that FOM-Ca has no effect on rat mothers, fetuses, and newborns treated during peri- and post-natal period.

Abnormalities, Drug-Induced↗
PubMed1979

Purification and some properties of uridine diphosphate N-acetylglucosamine pyrophosphorylase from Neurospora crassa.

Uridine diphosphate N-acetylglucosamine pyrophosphorylase (EC. 2.7.7.23) of Neurospora crassa has been purified approximately 210-fold with dithiothreitol as the stabilizing agent by use of chromatographic techniques. The enzyme preparation appeared to be homogeneous when subjected to electrophoresis. The molecular weight was estimated as approximately 37 000 by gel filtration. The enzyme had an isoelectric point around pH 4.4. Maximum activity of the enzyme was observed at pH 7.5. The enzyme required Mg2+, which may be replaced by other divalent cations such as Mn2+ and Co2+ for lesser degrees of effectiveness. The enzyme was strictly specific for UDP-N-acetylglucosamine as the substrate. The estimated values of Km were 2.2 mM for UDP-N-acetylglucosamine and 5.4 mM for inorganic pyrophosphate. The enzyme activity was highly stimulated by the addition of dithiothreitol or dithioerythritol but was lost by sulfhydryl inhibitory reagents.

Hydrogen-Ion Concentration↗
PubMed1979

Purification and properties of glyoxylate reductase I from baker's yeast.

The purification and properties of NADPH-linked glyoxylate reductase [EC 1. 1. 1. 79] from baker's yeast were studied. Two active fractions (peak I and peak II) were isolated by DEAE-cellulose column chromatography. The peak I fraction was purified to homogeneity by the criteria of disc gel electrophoresis and tentatively designated glyoxylate reductase I. Its molecular weight was calculated to be 31,000 from gel filtration measurements. The enzyme reduced glyoxylate 7 times faster than hydroxypyruvate and was specific for NADPH. The enzyme showed optimum activity between pH 5.5 and 7.2. The Michaelis constants for glyoxylate and NADPH were found to be 13 mM and 4 microM, respectively. The enzymic activity was not significantly affected by anions, except for nitrate and iodide, which were inhibitory.

Alcohol Oxidoreductases↗
PubMed1979

[Effect of fosmocyin-Na on reproductive performance of rats and rabbits. I. Teratogenicity test (author's transl)].

The teratogenicity study of fosfomycin-Na (FOM-Na) was undertaken in Wistar rats and New Zealand white rabbits. Rats were treated intraperitoneally at dose levels of 125, 250, 750 and 1,500 mg/kg/day from day 7 to day 17 of gestation, and rabbits were treated intravenously at dose levels of 80, 100, 200, 400 and 800 mg/kg/day from day 6 to day 18 of gestation. In the case of rats, two-thirds of pregnant mothers in each group was sacrificed on day 20 of gestation and then their fetuses were examined for external, visceral and skeletal observation. The remaining mothers were allowed to deliver naturally, and then their offsprings were examined for postnatal development. In the case of rabbits, all pregnant mothers were sacrificed on day 29 of gestation and their fetuses were examined. Body weight of rat mothers during gestation were decreased and 4 mothers were dead until day 20 of gestation in the maximum dose. In this dose, foetal toxicity was recognized too. However, external, visceral and skeletal anomalies related with FOM-Na treatment were not observed in all groups. No effect on development of offsprings was observed. No effect of treatment of FOM-Na to rabbits was found except foetal body weight was slightly decreased in the maximum dose.

Animals↗
PubMed1979

[Effect of fosfomycin-Na on reproductive performance of rats. II. Fertility test (author's transl)].

The fertility study of fosfomycin-Na (FOM-Na) was undertaken in Wistar rats. FOM-Na was administered intraperitoneally at dose levels of 125, 250, 750 and 1,500 mg/kg/day. The male rats were continuously treated with FOM-Na from 63 days before mating and the females were treated from 14 days before mating. The males and females were treated through the mating period and then the pregnant rats were treated until 7 days of gestation. All pregnant rats were sacrificed on day 20 of gestation and then their fetuses were examined for external, visceral and skeletal observation. Mean body weight of males decreased and 6 males and 3 females died in the maximum dose. However, no significant differences were found between treated groups and the control with regard to fertility rate and pregnant rate. External, visceral and skeletal anomalies related with FOM-Na treatment were not observed. In this experiment, no effects of FOM-Na for reproductive performance in rats were observed.

Abnormalities, Drug-Induced↗
PubMed1979

[Effect of fosfomycin-Na on reproductive performance of rats. III. Peri- and post-natal examination (author's transl)].

The peri- and post-natal study of fosfomycin-Na (FOM-Na) was undertaken in Wistar rats. FOM-Na was administered intraperitoneally at dose levels of 250, 750 and 1,500 mg/kg/day from day 14 of gestation to day 21 after delivery. It could be concluded that delivery rate in the 750 and 1,500 mg/kg groups decreased, but no influence of FOM-Na was found on postnatal development of offspring (F1) and neonate (F2) without maximum dose.

Animals↗
PubMed1979

[Effect of fosfomycin-calcium on reproductive performance of rat and rabbit: teratogenicity test (author's transl)].

The teratogenicity study of fosfomycin-Ca (FOM-Ca) was undertaken in Wistar strain rats and JW strain rabbits. Rats were treated orally at dose levels of 140,700 and 1,400 mg/kg/day from 7th to 17th day of gestation, and rabbits were treated orally at dose levels of 80, 140 and 420 mg/kg/day from 6th to 18th day of gestation. In the case of rats, two-thirds of pregnant mothers in each group were sacrificed on 20th day of gestation and then their fetuses were examined for external, visceral and skeletal observation. The remaining mothers were allowed to deliver naturally, and then their offsprings were examined for postnatal development. In the case of rabbits, all pregnant mothers were sacrificed on 29th day of gestation and their fetuses were examined. No effect of FOM-Ca treatment to rat and rabbit mothers was found except soft stool was seen with maximum dose in rats. Dead or resorbed rate of fetuses increased, external anomalies (short tail, abdominal hernia) were found and skeletal anomalies slight increased with maximum dose in rats. However, there was no significant difference from the control or background data. While, no effect of FOM-Ca treatment was observed in rabbits and rat offsprings. Consequently, it can be concluded that FOM-Ca has no teratogenicity effects on rats and rabbits.

Abnormalities, Drug-Induced↗