RESUMEN
Effects of Juzen-taiho-toh (TJ-48) on the recovery of hemopoietic systems from radiation injury are analyzed. Female C57BL/6N mice (6-8 weeks old) were irradiated at doses of 1, 2, 3, 5, or 7 Gy from a 60Co source. After irradiation, the mice were given TJ-48 (1.25 g in 100 ml drinking water). Seven days after irradiation, the mice were sacrificed, and bone marrow (both femurs), thymus, spleen, and peripheral blood counts were made. The bone marrow cells were used for fibroblast colony-forming unit (CFU-f), spleen colony-forming unit (CFU-S), granulocyte-macrophage colony-forming unit (CFU-GM), erythroid colony-forming unit (CFU-E), and erythroid burst-forming unit (BFU-E) assays. No difference was observed between the experimental and control groups except for CFU-S counts. In the assay for day-14 CFU-S, the mice injected with TJ-48-treated bone marrow cells showed better general condition (including increased body weight) and heavier spleens with larger and more numerous colonies. The effect of TJ-48 does not seem to be elicited via the hemopoietic microenvironment, because mice that had been given TJ-48 before irradiation at 8 Gy and then injected with syngeneic bone marrow cells did not show enhanced day-14 CFU-S counts. These results suggest that TJ-48 manifests a radioprotective effect by increasing the number and size of day-14 CFU-S.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Hematopoyesis/efectos de los fármacos , Traumatismos Experimentales por Radiación/fisiopatología , Protectores contra Radiación/farmacología , Animales , Femenino , Hematopoyesis/efectos de la radiación , Células Madre Hematopoyéticas/efectos de los fármacos , Ratones , Ratones Endogámicos C57BLRESUMEN
The s.c. administration of 20 mg/kg of morphine-HCl produced a decrease in the spontaneous locomotor activity (SLMA) of rats. The decrease in SLMA was significantly antagonized by p-chlorophenylalanine (p-CPA). When rats pretreated with p-CPA were given 5-hydroxytryptophan before morphine injection, the marked sedative response to morphine was restored, suggesting that the morphine-induced decrease in SLMA of rats may depend on the release of 5-hydroxytryptamine by morphine. By contrast, the s.c. administration of 5 mg/kg of morphine-HCl produced a significant increase in SLMA of rats. The magnitude of the increase was reduced by atropine, scopolamine or alpha-methyl-p-tyrosine. It appears that both adrenergic and cholinergic mechanisms participate in the increase in SLMA of rats induced by morphine. Both the increase in SLMA produced by 5 mg/kg of morphine and the decrease in SLMA induced by 20 mg/kg of morphine were completely antagonized by the s.c. administration of naloxone-HCl, 0.0625 and 0.25 mg/kg, respectively. Thus, it appears that the receptor with which morphine interacts to produce stimulation is chemically identical with or very similar to the receptor with which morphine combines to induce depression. The former receptors, however, are likely to be located on different neurons from the latter.
Asunto(s)
Morfina/farmacología , Actividad Motora/efectos de los fármacos , Naloxona/farmacología , Neurotransmisores/fisiología , 5-Hidroxitriptófano/farmacología , Animales , Atropina/farmacología , Fenclonina/farmacología , Levodopa/farmacología , Masculino , Metiltirosinas/farmacología , Actividad Motora/fisiología , Ratas , Escopolamina/farmacologíaRESUMEN
The relationship between the focus of cobalt seizures in the cerebral cortex and neuron loss in the hippocampus, as well as the CD50 of pentylenetetrazol was examined in rats. Spike activity in EEG frequently appeared 4 days after cobalt application and reached a peak 8-16 days after cobalt application, which was sometimes accompanied by jerks in the limbs. Changes in the CD50 value showed a two-step pattern, i.e., the first decrease in CD50 appeared one day after application of cobalt and continued at the same value until the fourth day. Then a second gradual decrease of CD50 was observed from the fourth day to eighth day and continued at the same value until 20 days after cobalt application. Neuron loss in the CA1 area of the hippocampus was observed as early as two days after cobalt application and the degree of neuron loss progressively increased until the 20th day. These findings suggest that neuron loss in the hippocampus following cobalt-induced seizures is not a result of generalized convulsions.
Asunto(s)
Corteza Cerebral/fisiopatología , Cobalto , Hipocampo/patología , Convulsiones/patología , Animales , Recuento de Células , Corteza Cerebral/efectos de los fármacos , Electroencefalografía , Hipocampo/efectos de los fármacos , Masculino , Pentilenotetrazol , Ratas , Ratas Endogámicas , Convulsiones/inducido químicamente , Convulsiones/fisiopatologíaRESUMEN
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.
Asunto(s)
Corteza Cerebral/patología , Epilepsia/genética , Gangliósidos/análisis , Animales , Células Cultivadas , Corteza Cerebral/embriología , Corteza Cerebral/metabolismo , Epilepsia/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Técnicas para Inmunoenzimas , Ratones , Ratones Mutantes NeurológicosRESUMEN
The effect of cycloheximide, a protein synthesis inhibitor, on hippocampal selective neuronal death was morphologically studied in rats subjected to 10 min forebrain ischemia using a 4-vessel occlusion model. Neuronal damage in the hippocampal CA1 subfield 72 h after ischemic insult was dramatically decreased by the lasting inhibition of protein synthesis through consecutive administration of cycloheximide. Cycloheximide, which was administered once within the first 24 h of recirculation, showed protective action on ischemic cell necrosis and its most potent effect was observed when injected at 12 h of post-ischemia. After 36 h of recirculation, however, treatment with cycloheximide could no longer prevent cell death. The possibility is considered that hippocampal delayed neuronal death following transient ischemia is caused by abnormal protein(s).
Asunto(s)
Cicloheximida/farmacología , Hipocampo/patología , Ataque Isquémico Transitorio/patología , Neuronas/patología , Animales , Supervivencia Celular/efectos de los fármacos , Hipocampo/efectos de los fármacos , Masculino , Neuronas/efectos de los fármacos , Tractos Piramidales/efectos de los fármacos , Tractos Piramidales/patología , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
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.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Corteza Cerebral/fisiopatología , Pentilenotetrazol , Convulsiones/tratamiento farmacológico , Animales , Anticonvulsivantes/farmacología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , AMP Cíclico/metabolismo , Electroencefalografía , Etosuximida/farmacología , Etosuximida/uso terapéutico , Masculino , Fenobarbital/farmacología , Fenobarbital/uso terapéutico , Ratas , Ratas Endogámicas , Convulsiones/inducido químicamente , Convulsiones/fisiopatología , Ácido Valproico/farmacología , Ácido Valproico/uso terapéuticoRESUMEN
Effects of the Japanese kampo medicine 'Shosaiko-to-go-keishika-shyakuyaku-to' (TJ-960), which is a mixture of 9 herbal drugs and is practically equivalent to 'Saiko-keishi-to' (SK), on the pentylenetetrazol (PTZ)-induced EEG power spectrum changes were examined. The EEG power spectrum change with 2 PTZ administrations at an 80 min interval was clearly inhibited by oral administration of 1.0 mg/kg of TJ-960. By separate single administrations of the main component herbal drugs, Bupleuri radix, Cinnamomi cortex, Paeoniae radix and Zingiberis rhizoma, only Paeoniae radix showed statistically significant inhibition of PTZ-induced EEG power spectrum changes at a proportional dose of 1.0 mg/kg of TJ-960. The other main component herbal drugs showed no statistically significant inhibitory effect although they had a tendency to inhibit. These findings suggest that the Japanese Kampo medicine, TJ-960 (SK), has an inhibitory effect on PTZ-induced power spectrum changes and one of the component herbal drugs, Paeoniae radix, is the important component drug.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Pentilenotetrazol , Fitoterapia , Convulsiones/tratamiento farmacológico , Administración Oral , Animales , Electroencefalografía , Masculino , Ratas , Ratas Endogámicas , Convulsiones/inducido químicamenteRESUMEN
TJ-960 is a spray-dried mixture of 9 herbal drugs. The convulsions of E1 mice induced by pentylenetetrazol (18 mg/kg) were completely inhibited by p.o. administration of TJ-960 at a daily dose of 1.0 g/kg both in 8-week-old and 4-week-old E1 mice. These findings suggest that TJ-960 has an inhibitory effect on the convulsions of this hereditary animal model of epilepsy.
Asunto(s)
Anticonvulsivantes/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Pentilenotetrazol , Fitoterapia , Convulsiones/tratamiento farmacológico , Animales , Relación Dosis-Respuesta a Droga , Ratones , Ratones Mutantes Neurológicos , Convulsiones/inducido químicamente , Convulsiones/fisiopatologíaRESUMEN
Berberine has been shown to increase developed tension in cardiac muscle but its derivatives have been reported to inhibit the catalytic subunit of adenylate cyclase. In the present study, the cardiac actions of the most potent derivative, 13-propylberberine, were examined. It produced a transient increase followed by a sustained decrease in developed tension in paced left atrial muscle preparations isolated from guinea-pig heart. In the presence of 13-propylberberine, isoproterenol caused only a transient increase in developed tension; marked desensitization to the positive inotropic effect of isoproterenol occurred within 20 min. After washout of isoproterenol and an additional 15-min incubation in the presence of 13-propylberberine, the muscle lost its sensitivity to isoproterenol. Moreover, the positive inotropic effect of ouabain or effects of decrease or increase in extracellular Ca2+ concentration on the force of muscle contraction were markedly attenuated. Isoproterenol-induced elevation of tissue cyclic AMP concentration was inhibited by 13-propylberberine; however, 13-propylberberine did not alter the basal cyclic AMP concentration and its effects on inotropic actions of ouabain or extracellular Ca2+ appear unrelated to tissue cyclic AMP concentration.
Asunto(s)
Alcaloides de Berberina/farmacología , Berberina/farmacología , Calcio/metabolismo , Contracción Miocárdica/efectos de los fármacos , Animales , Berberina/análogos & derivados , AMP Cíclico/metabolismo , Espacio Extracelular/metabolismo , Femenino , Cobayas , Isoproterenol/farmacología , Cinética , Masculino , Miocardio/metabolismo , Ouabaína/farmacología , Estimulación QuímicaRESUMEN
In this preliminary study we examined the enhancing effect of D-phenylalanine on acupuncture anesthesia. We made 4 different kinds of experiments with 3 volunteers. The results show that D-phenylalanine extends the analgesic effect of acupuncture analgesia remarkably, with no exception in 3 cases. According to these facts, we believe that these findings have an important meaning for those who are engaged in acupuncture treatment or research.
Asunto(s)
Terapia por Acupuntura , Analgesia , Fenilalanina/farmacología , Adulto , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Gomisin A (TJN-101) is one of the lignan components isolated from Schisandra Fruits and expected to have some efficacies in clinical treatment of hepatitis. The serum concentrations of TJN-101 and Met. B, which was identified as a demethylenated substance and one of the major metabolites of TJN-101 in rats, were investigated. After intravenous administration at doses of 1.6, 4.0 and 10 mg/kg of body weight, the serum concentration of TJN-101 decreased biphasically, and the terminal elimination half-life at each dose was about 70 min. Dose-dependency was observed for the area under the concentration-time curve (AUC). On the other hand, the serum concentration of TJN-101 increased rapidly and reached maximum within 15 to 30 min when administered orally. This result was supported by the in situ roop method. The Cmax and the AUC values were not exactly dose-dependent, but the values increased with a dose-up of TJN-101. The biotransformation of TJN-101 to Met. B, was very rapid in both intravenous and oral administrations. The AUC value of Met. B after oral administration of TJN-101 at a dose of 1.6 mg/kg was relatively larger than any other dosages. It suggested that TJN-101 was extensively underwent the first pass effect in rats. More than 80% of TJN-101 was bound with rat serum protein in vitro and in vivo. Therefore, it seems to be necessary to pay attention when it was administered concurrently with high protein binding drugs.
Asunto(s)
Ciclooctanos , Dioxoles , Lignanos , Compuestos Policíclicos/farmacocinética , Administración Oral , Animales , Proteínas Sanguíneas/metabolismo , Cromatografía Líquida de Alta Presión , Inyecciones Intravenosas , Absorción Intestinal , Masculino , Compuestos Policíclicos/administración & dosificación , Unión Proteica , Ratas , Ratas EndogámicasRESUMEN
The absorption and excretion of gomisin A (TJN-101) in rats whose livers were injured by carbon tetrachloride (CCl4) were investigated. After intravenous administration of TJN-101 at a dose of 5 mg/kg, the terminal elimination half-life was 1.5 h in the CCl4-treated rats, which was two times that in normal rats. The mean area under the blood concentration-time curve (AUC) value of TJN-101 in the CCl4-treated rats was twice that in normal rats, and this difference was significant (p less than 0.05). Therefore, the total body clearance of TJN-101 in the CCl4-treated rats decreased less than half of that in normal rats. Similar results were observed when it was administered orally. In the CCl4-treated rats, the serum concentration of Met. B, which was identified as a demethylenated substance and one of major metabolites, tended to decrease more than that in normal rats. On the other hand, the cumulative biliary excretion ratio of TJN-101 in 24 h after dosing in the CCl4-treated rats was 2.5 times that in normal rats. The excretion rate of Met. B in the bile in the CCl4-treated rats tended to be delayed. However, the quantitative variance of biliary excretion of Met. B was not found in both groups. The urinary excretion of TJN-101 or Met. B in 72 h after dosing in the CCl4-treated rats was lower than that in normal rats. Similar results were also observed in excretion in the feces.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Intoxicación por Tetracloruro de Carbono/metabolismo , Ciclooctanos , Dioxoles , Lignanos , Compuestos Policíclicos/farmacocinética , Administración Oral , Animales , Proteínas Sanguíneas/metabolismo , Inyecciones Intravenosas , Masculino , Compuestos Policíclicos/administración & dosificación , Unión Proteica , Ratas , Ratas EndogámicasRESUMEN
Some Chinese medicines in Japan have been reported to have not only antitumour effects, but also to offer protection from the adverse effects of anti-tumour agents. However, there is controversy regarding the protective effects of such Chinese medicines against the adverse effects of anti-tumour agents, in this study, we examined the effects of Tsumura Juzentaiho-to (TJ-48) on the toxicity of mitomycin C (MMC) and cisplatin (CDDP). Both the pre-administration of TJ-48 a single time and for seven days shifted the dose response curve and LD50S of MMC and CDDP to the right. Seven days of treatment using TJ-48 delayed deaths due to lethal dose of MMC or CDDP and markedly changed their survival curves. Also, TJ-48 reduced the atrophy of the testis, thymus and spleen caused by MMC. TJ-48 also had beneficial effects on leukopenia, anemia and body weight loss caused by MMC, and increase of BUN and creatinine caused by CDDP. These results indicate that the combined use of TJ-48 may be a new way to in prevent or minimize the toxicity of MMC or CDDP.
Asunto(s)
Cisplatino/efectos adversos , Medicamentos Herbarios Chinos/farmacología , Mitomicinas/efectos adversos , Anemia/inducido químicamente , Anemia/prevención & control , Animales , Nitrógeno de la Urea Sanguínea , Cisplatino/farmacocinética , Creatinina/sangre , Dosificación Letal Mediana , Leucopenia/inducido químicamente , Leucopenia/prevención & control , Masculino , Ratones , Ratones Endogámicos C57BL , Ratas , Ratas Endogámicas , Pérdida de Peso/efectos de los fármacosAsunto(s)
Morfina/farmacología , Actividad Motora/efectos de los fármacos , Acetilcolina/fisiología , Animales , Atropina/farmacología , Derivados de Atropina/farmacología , Cafeína/farmacología , Catecolaminas/fisiología , Cocaína/farmacología , Masculino , Metanfetamina/farmacología , Metiltirosinas/farmacología , Morfina/antagonistas & inhibidores , Ratas , Escopolamina/farmacología , Derivados de Escopolamina/farmacologíaAsunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Ciclooctanos , Dioxoles , Lignanos , Hígado/efectos de los fármacos , Compuestos Policíclicos/uso terapéutico , Polisorbatos , Animales , Carboximetilcelulosa de Sodio , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Plantas Medicinales/análisis , Ratas , Ratas Endogámicas , Solventes , Transaminasas/sangreAsunto(s)
Dioxoles/farmacología , Medicamentos Herbarios Chinos , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Extractos Vegetales/farmacología , Compuestos Policíclicos/farmacología , Animales , Bloqueadores de los Canales de Calcio , Circulación Coronaria/efectos de los fármacos , Perros , Cobayas , Íleon/efectos de los fármacos , Técnicas In Vitro , Lignanos , Arterias Mesentéricas/efectos de los fármacos , Tráquea/efectos de los fármacosRESUMEN
The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.