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Biomedical subjects

M Aburada

Publications and source records attributed to M Aburada.

At least 55 records · Page 3Linked to original sources

[Effects of TJ-41 (Tsumura Hochu-ekki-to) on spermatogenic disorders in mice under current treatment with adriamycin].

Experiments were performed to investigate the effects of TJ-41 on spermatogenic disorders under current treatment with adriamycin (ADR). Male ICR mice were intraperitoneally injected with ADR at the dose of 0.15 mg/kg, twice a week for 5 weeks. Simultaneously, these mice were orally administered TJ-41 at the dose of 1, 2 or 4 g/kg for 12 weeks. The effects of TJ-41 were evaluated by histological analysis of germ cells in the testis at 7 weeks after the last injection of ADR. TJ-41 at a dose of 4 g/kg significantly inhibited the decrease of testis weight in mice treated with ADR. TJ-41 at doses of 1 and 4 g/kg significantly decreased the proportion of seminiferous tubules without germ cells as compared with the ADR-treated group. On the other hand, TJ-41 at doses of 1 and 4 g/kg significantly increased the proportion of normal seminiferous tubules and the Sertoli cell ratio of spermatocytes as compared with the ADR-treated group. These results indicate that TJ-41 may qualitatively and quantitatively protect against the decrease of germ cells in the testis of mice treated with ADR.

Animals↗

A two-site solid phase enzyme immunoassay for rat epidermal growth factor.

A sensitive and simple two-site enzyme immunoassay was developed for rat epidermal growth factor (rEGF), which was purified from male rat submaxillary glands. This system is based on the sandwiching of the antigen between anti-rat EGF IgG antibody coated on a polystyrene bead and anti-rat EGF Fab' antibody-linked peroxidase, whose activity was stable at 4 degrees C for 6 months. In this system, the rat EGF was detectable at a concentration of 2 pg/tube. No interference was observed by addition of human plasma. There was no cross-reactivity with mouse EGF, human EGF, or other substances with similar chemical structures.

Animals↗

Characteristics of primary cultured neurons from embryonic mutant El mouse cerebral cortex.

To elucidate the differences between neurons of epileptogenic animals and those of normal animals, cellular characteristics of neurons of mutant strain El mice which are highly susceptible to seizures were investigated using immunocytochemical techniques. In neurons of 3-day primary cultures, the control ddY mouse neurons showed dividing stages in about 0.2% of neurofilament (NF)-positive neurons, whereas no dividing neurons were observed among the NF-positive El mouse neurons. In 7-day cultures, localization of GD3 ganglioside in the proliferating control ddY mouse neurons was observed, but there was no GD3 ganglioside in the mutant El mouse neuron. The content of GD3 ganglioside detected by high-performance thin-layer chromatography of El mouse cultured cells was ca. 1/4 of that of ddy mice. These findings suggest that neurons of the El mouse are differentiated earlier than those of the control ddY mouse.

Animals↗

Effect of anticonvulsants on pentylenetetrazol-induced power spectrum changes in electroencephalograms in rats.

The effect of anticonvulsants on pentylenetetrazol (PTZ)-induced EEG power spectrum changes was examined. When the minimum dose of PTZ (15 mg/kg) was administered intravenously twice, with an interval of 80 min, a clear EEG power spectrum change was observed after the second PTZ administration, irrespective of whether or not the first PTZ administration evoked marked EEG changes. We defined the values F/N, S/N and S/F. The value F/N, obtained by dividing the power spectrum area after the first PTZ administration by the normal power spectrum area, was 1.06 +/- 0.05 (mean +/- S.E.). The value S/N, obtained by dividing the power spectrum area after the second PTZ administration by the normal power spectrum area, was 2.00 +/- 0.21. The value S/F, obtained by dividing S/N by F/N, was 1.86 +/- 0.16. The S/F value was almost constant regardless of whether or not the first PTZ administration could evoke marked EEG changes. The effect of anticonvulsants was examined by S/F value changes, and 100 mg/kg of PHT completely inhibited the double PTZ effect. Phenobarbital, ethosuximide and sodium valproate also inhibited the double PTZ effect. Using the S/F value of the EEG power spectrum with minimum dose double PTZ administration, quantitative evaluation is possible for anticonvulsant drugs.

Animals↗

[Pharmacological study of TJ-8007 (Tsumura-Zokumeito) (I): Protective effects of TJ-8007 against anoxic brain damage].

The protective effects of TJ-8007 (Tsumura-Zokumeito, Traditional chinese medicine) against cerebral anoxia were investigated with various experimental models in mice and rats. 1) In histotoxic anoxia, TJ-8007 (0.3-3.0 g/kg, p.o.) dose-dependently demonstrated a protective effect on coma induced by a sublethal dose of KCN (1.8 mg/kg, i.v.) in mice. Ifenprodil (30 mg/kg, p.o.) tended to reduce the coma time, but papaverine (100 mg/kg, p.o.) showed a negative effect. 2) TJ-8007 (0.3-3.0 g/kg, p.o.) dose-dependently tended to prolong the survival time of mice subjected to a lethal dose of KCN (3.0 mg/kg, i.v.), TJ-8007 also improved the survival rate at the dose of 3.0 g/kg. Ifenprodil (30 mg/kg, p.o.) or papaverine (100 mg/kg, p.o.) exerted a similar effect on the survival time, but did not affect the mortality. 3) In the normobaric hypoxia with a gas mixture of 96% N2 and 4% O2, TJ-8007 (0.3-3.0 g/kg, p.o.) did not affect the survival time of mice. On the other hand, papaverine (100 mg/kg, p.o.) prolonged the survival time, and phenytoin (100 mg/kg, p.o.) showed a marked protective effect, but ifenprodil (30 mg/kg, p.o.) produced an adverse effect. 4) In the asphyxic anoxia induced by stopping artificial respiration of immovable rats, TJ-8007 (1.0, 3.0 g/kg, p.o.) showed a protective effect on the fall of systemic blood pressure and on the decline of heart rate; furthermore, it dose-dependently prolonged the disappearance time of cortical activity. Also, phenytoin (100 mg/kg, p.o.) tended to protect against the fall of blood pressure and prolonged the cortical resistance time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effects of TJN-101, a lignan compound isolated from Schisandra fruits, on liver fibrosis and on liver regeneration after partial hepatectomy in rats with chronic liver injury induced by CCl4].

TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy -6,7-dimethyl-10,11-methylenedioxy-6-dibenzo[a,c]cyclooctenol) is one of the lignan compounds isolated from Schisandra fruits. 1) Effect of TJN-101 on liver fibrosis was investigated in rats which were injected with CCl4 (1 ml/kg) subcutaneously twice a week for 12 weeks. TJN-101 was given orally at the dose of 10 or 30 mg/kg/day for 6 or 3 weeks beginning on the 6th or 9th week after the start of CCl4-intoxication, respectively. The elevations of serum transaminase activities and the increase of liver 4-hydroxyproline content were observed depending on the period of CCl4-intoxication. These changes were marked on the 9th and 12th weeks after. In the histopathological study, the degenerative fatty change on the 6th week after and the formation of pseudolobule caused by fibrosis proliferation on the 9th or 12th week after were mainly observed. When rats were treated with TJN-101, the abnormalities in biochemical parameters and the fibrosis proliferation caused by CCl4-intoxication were improved. 2) Chronic liver injury was induced by the treatment with CCl4 (1 ml/kg) subcutaneously twice a week for 10 weeks to investigate the effect of TJN-101 on liver regeneration after partial hepatectomy. TJN-101, which was given orally at the dose of 10, 30 or 100 mg/kg/day for 6 days from the 1st day after partial hepatectomy, dose-dependently increased the liver regeneration rate and improved the serum BSP retention rate. These results suggest that TJN-101 suppresses the fibrosis proliferation and accelerates both the liver regeneration and the recovery of liver function after partial hepatectomy in chronic liver injury.

Administration, Oral↗

Inhibitory effect of TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy -6,7-dimethyl-10,11- methylenedioxy-6-dibenzo[a,c]cyclooctenol) on immunologically induced liver injuries.

TJN-101, which is a lignan component isolated from schisandra fruits, inhibits hepatotoxic chemicals-induced liver injuries. In this study, effects of TJN-101 on immunologically induced liver injuries were investigated in vivo and in vitro. When a small dose of lipopolysaccharide was injected into mice previously injected with heat-killed Propionibacterium acnes, most of the animals died with acute hepatic failure which was produced by cytotoxic factors from activated adherent cells, and liver cells were injured by antibody-dependent cell-mediated cytotoxic (ADCC) reaction or activated macrophages in vitro. TJN-101 reduced the mortality of the mice with acute hepatic failure dose-dependently. Histologically, necrosis was suppressed by the treatment of TJN-101, but infiltration of non-specific inflammatory cells was not. TJN-101 inhibited the isolated liver cell injuries induced by ADCC reaction or activated macrophages in vitro. These results suggest that TJN-101 can be markedly protective against immunological liver injuries.

Alanine Transaminase↗

Effects of Chrysanthemum indicum Linn. on coronary, vertebral, renal and aortic blood flows of the anesthetized dog.

The hemodynamic effects of the water extract of flower of Chrysanthemum indicum Linn. (CIL) and adenosine were examined in anesthetized open-chest dogs by measuring simultaneously and continuously coronary (CBF), vertebral (VBF), renal (RBF) and aortic blood flows (AoF). Intravenous administration of CIL (5-20 mg/kg) as well as adenosine (10-50 micrograms/kg) produced decreases in aortic blood pressure (AoP) and RBF, and increases in AoF, VBF, CBF and left ventricular dP/dt (LVdP/dt). Calculated coronary, vertebral and total peripheral resistances were decreased by CIL or adenosine in a dose-dependent manner. The ratio (1.69 +/- 0.27) of decrease in coronary vascular resistance to that in total peripheral resistance by CIL (10 mg/kg) was apparently smaller than that (4.03 +/- 0.48) by adenosine (10 micrograms/kg). After beta-adrenergic blockade, increases in AoF and LVdP/dt were inhibited, but decreases in AoP and coronary, vertebral and total peripheral resistances and increase in renal vascular resistance were not changed. These results indicate that CIL directly and uniformly produces coronary and systemic vasodilation with renal vasoconstriction, and that adenosine directly produces vasoconstriction in renal vasculature and vasodilation which is more potent in coronary vasculature than in systemic ones.

Adenosine↗

Pharmacological studies on ginger. II. Pressor action of (6)-shogaol in anesthetized rats, or hindquarters, tail and mesenteric vascular beds of rats.

When (6)-shogaol (0.5 mg/kg, i.v.) was administered to rats, blood pressure showed a tri-phasic response which was comprised of a rapid fall, followed by a rise and a delayed fall. The rapid fall, which followed immediately after injection of (6)-shogaol, disappeared with the use of atropine and vagotomy. The marked rise, which occurred after the rapid fall, was not affected by alpha-adrenoceptor blockades, Ca antagonists and ganglion blockade. However, a combination of alpha-adrenoceptor blockade and Ca antagonist inhibited this pressor response. In hindquarters perfused with a nutrient solution, (6)-shogaol (10(-5) g)-induced peripheral pressor response was also not affected by alpha-adrenoceptor blockades and Ca antagonists, but was inhibited by the combination of an alpha-adrenoceptor blockade and a Ca antagonist. Furthermore, this peripheral pressor response was eliminated by the removal of Ca ion from the perfusate. (6)-Shogaol did not exhibit a pressor response in an artery and a vein of the tail or an artery of the femur perfused with a nutrient solution. (6)-Shogaol-induced peripheral pressor response in hindquarters was markedly potentiated during the perfusion of norepinephrine (5 X 10(-6) g/ml), but this potentiation was prevented by pretreatment with reserpine (5 mg/kg, i.p.). Moreover, repeated injections of (6)-shogaol caused a tachyphylaxis in mesenteric and tail vascular beds and a slight tachyphylaxis in hindquarters.

Anesthesia↗

Pharmacological studies on ginger. III. Effect of the spinal destruction on (6)-shogaol-induced pressor response in rats.

(6)-Shogaol-induced pressor responses in blood pressure of rats were studied. Intraventricular injection of (6)-shogaol (0.1 to 0.5 microgram) caused a pressor response in a dose-dependent manner. (6)-Shogaol (0.5 mg/kg, i.v.)-induced pressor response was markedly reduced by a spinal destruction to the sacral cord level. However, norepinephrine (10 micrograms/kg, i.v.)-induced pressor response was not affected by the spinal destruction. In rats in which the spinal cord was destroyed to the thoracic cord level, (6)-shogaol-induced pressor response was reduced by hexamethonium (10 mg/kg, i.v.) and phentolamine (10 mg/kg, i.v.), etc. When the spinal cord was destroyed to the sacral cord level, the pressor response was not affected by these blockades. In the hindquarters of rats which were perfused with rats' blood, (6)-shogaol caused two pressor responses on the perfusion pressure. The first pressor response, which was accompanied by a rise in systemic blood pressure, was reduced by hexamethonium but was not entirely eliminated by phentolamine. However, the pressor response disappeared with spinal destruction to the sacral cord level. The second pressor response, which occurred about when the systemic blood pressure regained its original pressure, was not affected by hexamethonium, phentolamine or spinal destruction. Pressor response induced by the injection of (6)-shogaol (10 micrograms) into the perfusion circuit was not affected by phentolamine and spinal destruction. Furthermore, (6)-shogaol-induced peripheral pressor response disappeared with the combined treatment of [D-Arg1, D-Pro2, D-Trp7.9, Leu11]-substance P (0.5 mg/kg, i.v.), phentolamine and the section of the sciatic nerves.

Animals↗

[Effects of gomisin A, a lignan component of Schizandra fruits, on experimental liver injuries and liver microsomal drug-metabolizing enzymes].

Effects of oral administration of gomisin A, one of the components isolated from Schizandra fruits, on liver injuries induced by CCl4, d-galactosamine and dl-ethionine and on liver microsomal drug-metabolizing enzyme activities were investigated. Gomisin A suppressed the increase of serum transaminase activities and the appearances of histological changes such as degeneration and necrosis of hepatocyte, inflammatory cell infiltration and fatty deposition in each type of liver injury. The repeated administration of gomisin A (30 or 100 mg/kg, p.o., daily for 4 days) induced an apparent increase of liver weight in liver-injured and normal rats. Gomisin A decreased serum triglyceride and lipid contents of the liver in biochemical studies. Increases of microsomal cytochrome b5 and P-450, elevations of NADPH cytochrome C reductase, aminopyrine N-demethylase and 7-ethoxycoumarin O-deethylase activities and decrease of 3,4-benzo(a)pyrene hydroxylase activity per cytochrome P-450 were observed after the administration of gomisin A. In addition, gomisin A was found to enhance the incorporation of 14C-phenylalanine into liver protein and to shorten the hexobarbital-induced sleeping time. These changes caused by gomisin A were similar to those by phenobarbital. However, gomisin A is distinctly different from phenobarbital in the finding that phenobarbital lessened the survival ratio of CCl4-intoxicated mice, but gomisin A did not. Our observation suggest that gomisin A shows an antihepatotoxic action by oral application and also has hypolipidemic (mainly triglyceridemic) and liver protein synthesis-facilitating actions and that the enlargement of the liver seen with gomisin A is the adaptive hypertrophy which is due to the induction of drug-metabolizing enzymes.

Animals↗

[Pharmacological studies on ginger. IV. Effect of (6)-shogaol on the arachidonic cascade].

(6)-Shogaol, a pungent component of ginger, which is contained in semi-dried ginger but is rarely found in fresh ginger inhibited carrageenin-induced swelling of hind paw in rats and arachidonic acid (AA)-induced platelet aggregation in rabbits. Moreover, (6)-shogaol prevented prostaglandin I2 (PGI2) release from the aorta of rats when tested as an inhibitor of platelet aggregation. These results suggest that (6)-shogaol may have an inhibitory action on the cyclo-oxygenases in both platelets and aorta. Examination of the effects of (6)-shogaol on cyclo-oxygenases in rabbit platelets and microsome fractions of rat aorta indicated that (6)-shogaol inhibited cyclo-oxygenase activities of both tissues in a concentration-dependent manner. Furthermore, when we examined the effect of (6)-shogaol on 5-lipoxygenase from RBL-1 cells, (6)-shogaol exhibited an inhibitory action on 5-lipoxygenase activity. Therefore, it seems that the inhibitory effects of (6)-shogaol on the carrageenin-induced paw edema, AA-induced platelet aggregation and PGI2 production of aorta may be caused by the inhibition of cyclo-oxygenase activity.

Animals↗

[Effects of TJN-101 ((+)-(6s,7s,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy-6,7 -dimethyl-10,11-methylenedioxy-6-dibenzo [a,c] cyclooctenol) on liver regeneration after partial hepatectomy, and on regional hepatic blood flow and fine structure of the liver in normal rats].

Effects of TJN-101, one of the components isolated from Schizandra fruits, on liver regeneration after partial hepatectomy, and on regional hepatic blood flow and fine structure of the liver were investigated in normal rats. TJN-101, which was administered orally at the doses of 10, 30 and 100 mg/kg/day for 4 days after partial hepatectomy, increased the regeneration rate of the liver and improved the serum retention rate of BSP which had been dose-dependently decreased after the operation. Elevation of serum protein to control levels, elevation of serum LCAT activity, decrease in plasma insulin and increase in plasma glucagon were all dose-dependent responses to TJN-101. The mitotic index on the 5th day after the operation was hardly influenced by TJN-101. Regional hepatic blood flow was increased after intraduodenal administration of TJN-101 (30 and 100 mg/kg). Ultrastructural studies of liver tissue using the transmission electron microscope revealed that TJN-101 stimulated an increase in rough and smooth endoplasmic reticulum in the groups receiving 100 and 300 mg/kg/day. These results suggest that TJN-101 accelerates both the proliferation of hepatocytes and the recovery of liver function after partial hepatectomy and increases hepatic blood flow. It is also thought that the liver enlargement caused by repeated administration of TJN-101 is associated with the proliferation of endoplasmic reticulum.

Animals↗

[Pharmacological studies on ginger. V. Pharmacological comparison between (6)-shogaol and capsaicin].

Pharmacological actions of (6)-shogaol and capsaicin were studied. Both (6)-shogaol (0.5 mg/kg, i.v.) and capsaicin (0.1 mg/kg, i.v.) caused a triad such as a rapid fall in blood pressure, bradycardia and aponea in rats. Both drugs-induced marked pressor responses in blood pressure, which occurred after the rapid fall, were markedly reduced by a spinal destruction. In pithed rats, both drugs-induced peripheral pressor responses were markedly reduced with the combined treatment of [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (0.5 mg/kg, i.v.), phentolamine (10 mg/kg, i.v.) and the section of sciatic nerves. In isolated guinea-pig trachea, (6)-shogaol (100 microM) and capsaicin (10 microM) induced contractile responses which were slightly inhibited by substance P antagonist (10 microM), but exhibited also a tachyphylaxis. Furthermore, although (6)-shogaol (3.6 microM) showed positive inotropic and chronotropic actions on isolated atria in rats, this effect of (6)-shogaol disappeared by repeated injections or pretreatment (100 mg/kg, s.c.) of (6)-shogaol. These results suggest that (6)-shogaol and capsaicin have similar actions, and that both drugs may cause a peripheral action by releasing an unknown active substance from nerve ends.

Animals↗

Effects of the water extract of Chrysanthemum indicum Linn. on coronary and systemic hemodynamics in the dog.

To clarify the pharmacological profile and the mechanism of action of the water extract of flower of Chrysanthemum indicum Linn. (CIL), a crude drug, the effects of CIL on coronary and systemic hemodynamics were examined in anesthetized open-chest dogs, and the coronary relaxing action of CIL was tested on isolated dog coronary arterial strips. Intravenous administration of CIL 5-20 mg/kg produced a decrease in aortic blood pressure and increases in coronary blood flow, left ventricular dP/dt and heart rate in a dose-dependent manner. Renal blood flow initially decreased and then increased to the values above the preinjection level. These changes by every dose of CIL returned to the preadministration level until 5 min. Dipyridamole (0.1 mg/kg i.v.) potentiated an increase in coronary blood flow of CIL and aminophylline (1.0 mg/kg i.v.) attenuated this response. Intravenous administration of adenosine 5-50 micrograms/kg produced effects similar to those of CIL. The doses of CIL and adenosine which produced a two-fold increase in coronary blood flow were 13.8 mg/kg and 29.5 micrograms/kg, respectively. In 30 mM potassium-induced contracture of dog coronary arterial strips, there was no difference in the relaxant response to CIL between large coronary arteries and medium-size coronary arteries. Adenosine tended to produce a larger relaxation in medium-size coronary arteries than in large coronary arteries. The results indicate that CIL has a coronary vasodilating action and a renal vasoconstricting action in the open-chest dog and that the pharmacological profile of CIL is in part similar to that of adenosine.

Adenosine↗

Effects of gomisin A on liver functions in hepatotoxic chemicals-treated rats.

The effects of gomisin A, which is a lignan component of schizandra fruits, on liver functions in various experimental liver injuries and on bile secretion in CCl4-induced liver injury were studied. Gomisin A weakly accelerated the disappearance of plasma ICG by itself at a high dose (100 mg/kg, i.p.). All of the hepatotoxic chemicals used in this study inhibited the excretion of ICG from plasma. Gomisin A showed a tendency to prevent the delays of the disappearance of plasma ICG induced by CCl4, d-galactosamine and orotic acid, but not that by ANIT. Bile flow and biliary outputs of total bile acids and electrolytes (Na+, K+, Cl- and HCO3-) were decreased in CCl4-treated rats. Gomisin A maintained bile flow and biliary output of each electrolyte nearly to the level of the vehicle-treated group, but did not affect biliary output of total bile acids. These findings suggest that gomisin A possesses a liver function-facilitating property in normal and liver injured rats and that its preventive action on CCl4-induced cholestasis is due to maintaining the function of the bile acids-independent fraction.

1-Naphthylisothiocyanate↗