Antiapoptosis action of aged garlic extract (AGE) protects epithelial cells from methotrexate induced injury.
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Animals↗
Biomedical subjects
T Fuwa
Publications and source records attributed to T Fuwa.
Subthalamo-pallido-striatal axis: a feedback system in the basal ganglia.
Systemic administration of a dopamine D2 receptor blocker, haloperidol, but not vehicle, significantly increased the number of c-Fos-immunoreactive neurons in the globus pallidus (GP) in rats. Dual immunohistochemistry, a combination of c-Fos immunohistochemistry and retrograde tracing experiments with cholera toxin B (ChB), revealed that a subset of the c-Fos-immunoreactive GP neurons was pallidostriatal feedback neurons. Lesioning of the subthalamic nucleus (STN) by local injection of ibotenic acid inhibited the haloperidol-induced c-Fos expression in the GP neurons, suggesting that the activation of GP neurons is a result of increased excitatory drives from the STN. Therefore, the present findings are evidence of the existence of the subthalamo-pallido-striatal axis as a feedback system in the internal circuits of the basal ganglia.
Animals↗
Alleviation by garlic of antitumor drug-induced damage to the intestine.
Antitumour drugs such as methotrexate (MTX) and 5-fluorouracil (5-FU) induce intestinal damage. This is a serious side effect of cancer chemotherapy. The present studies examined whether or not aged garlic extract (AGE) protects against damage from these antitumor drugs. Both drugs were administered orally for 4 or 5 d to rats fed a standard laboratory diet with and without 2% AGE. The small intestinal absorption of the poorly absorbable compound, fluorescein isothiocyanate--labeled dextran (FD-4; average molecular weight, 4400) was used to evaluate the damage to the intestine using the in vitro everted intestine technique and the in situ intestinal loop technique. FD-4 absorption increased in the antitumour drug-treated rats fed the diet without garlic. Interestingly, FD-4 absorption was depressed in rats fed the diet containing AGE. These results suggest that AGE may protect the small intestine of rats from antitumour drug-induced damage.
Administration, Oral↗
Differential expression of c-fos following administration of two tremorgenic agents: harmaline and oxotremorine.
The regional distribution of c-Fos expression in the brain after the administration of two tremorgenic agents was studied. In both the harmaline- and oxotremorin-treated rats, c-Fos-positive neurons were extensively distributed in the basal ganglia nuclei and the cerebellum. Additionally, in the harmaline-treated rats, numerous c-Fos-positive neurons were also distributed throughout the inferior olivary nucleus. In the oxotremorine-treated rats, while the inferior olive was not involved, c-Fos was strongly expressed in the neurons of the reticular thalamic nucleus, possibly due to the muscarinic effects of oxotremorine. The present study revealed that the inferior olive is selectively activated in the harmaline-administered animals and that the basal ganglia are involved in both harmaline- and oxotremorine-induced tremors.
Animals↗
Effects of blockade of metabotropic glutamate receptors in the subthalamic nucleus on haloperidol-induced Parkinsonism in rats.
The present study examined the postural effects of unilaterally local injection of metabotropic glutamate receptor (mGluR) antagonists into the subthalamic nucleus (STN), in rats with haloperidol-induced parkinsonism. In rats which received unilateral microinjections of (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), a selective, subtype-non-specific antagonist of mGluR, but not the vehicle, into the STN, systemic administration of haloperidol induced ipsiversive dystonic posturing. The severity of the dystonic posturing was dose-dependent. However, subtype-specific antagonists of group I, II, or III mGluRs induced no dystonic posturing. The present findings suggest that the activity of the STN under conditions of dopamine blockade is facilitated by blockade of mGluRs in the STN, suggesting that mGluRs exert inhibitory influence on glutamate release in the STN.
Animals↗
Protective effect of aged garlic extract on the small intestinal damage of rats induced by methotrexate administration.
The methotrexate (MTX) administration to rats causes the damage of small intestine. The small intestinal damage was evaluated by measuring the intestinal permeability of the poorly absorbable compound, fluorescein isothiocyanate (FITC)-labeled dextran (average molecular weight, 4,400) (FD-4) using the in vitro everted intestine technique and by determining the FD-4 that appeared in plasma using the in situ closed loop intestine technique. The MTX administration to rats fed with the standard laboratory diet increased the small intestinal permeability of FD-4 due to the damage of the small intestine. Interestingly, the permeability of FD-4, when MTX was administered to rats fed with the aged garlic extract containing diet, was depressed almost to the level of control rats without the MTX treatment. The present study showed that the aged garlic extract protected the small intestine from the damage induced by the action of MTX on the crypt cells.
Animals↗
Effects of fujibitol, a remedy for nasal symptoms of immediate and delayed type allergic reactions.
The effects of Fujibitol, a remedy for the nasal symptoms of immediate and delayed type allergic reactions were studied. Fujibitol inhibited active systemic anaphylaxis in mice, heterologous passive cutaneous anaphylaxis (PCA) in rats, Masugi's nephritis in rats and delayed type hypersensitivity induced by picryl chloride in mice, but did not affect homologous PCA or immune complex-induced glomerulonephritis in rats. These results suggested that Fujibitol is effective for treatment of allergy-induced inflammation since IgG and type IV allergic reactions were inhibited.
Anaphylaxis↗
Postural effects of unilateral blockade of glutamatergic neurotransmission in the subthalamic nucleus on haloperidol-induced akinesia in rats.
The present study examined the postural effects of the local application of glutamatergic antagonists unilaterally into the subthalamic nucleus (STN), on haloperidol-induced akinesia in rats. After intracerebral injections of MK-801, a selective antagonist of N-methyl-D-aspartate (NMDA) receptor, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) disodium, a selective alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist, or vehicle, unilaterally into the STN, haloperidol was administered systemically and the elicited behaviors were assessed quantitatively. In rats which received injections of MK-801 or CNQX, but not vehicle, unilaterally into the STN, the administration of haloperidol induced contraversive dystonic posturing. The severity of the deviated posturing was dose-dependent. The present findings revealed that the overactivity of the STN under conditions of dopamine blockade is suppressed by interruptions of glutamatergic inputs, mediated via both NMDA or AMPA receptors, to the STN. Therefore, the present study may provide functional evidence in support of a recently proposed hypothesis, that not only disinhibition from the inhibitory globus pallidus efferents but also excitatory glutamatergic inputs to the STN actually contribute to the overactivity of the STN under dopamine-depleted conditions.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Globus pallidus lesions inhibit the induction of c-Fos by haloperidol in the basal ganglia output nuclei in rats.
This study examined the induction of c-Fos expression in the substantia nigra pars reticulata (SNr) and entopeduncular nucleus (EP) in the rats with a globus pallidus (GP) lesion, following the administration of haloperidol. After a GP lesion was made unilaterally by stereotaxic administration of ibotenic acid, haloperidol was administered systemically, and the number of cells expressing c-Fos was quantitatively assessed. Haloperidol induced a high level of the expression of c-Fos in neurons of the SNr and EP, and the GP lesion significantly decreased the expression of c-Fos in the ipsilateral SNr and EP. Since it has been suggested that c-Fos expression in the SNr/EP is caused by increased excitatory inputs from the subthalamic nucleus (STN), the present results provide functional evidence indicating that neuronal activities of the basal ganglia output nuclei are not increased by GP ablation, unlike D2 receptor blockade, supporting the recently proposed hypothesis that overactivity of the STN resulting from dopamine depletion is not solely a result of disinhibition from inhibitory GP efferents.
Animals↗
Dystonic posturing and circling behaviors induced by dopaminergic agents in rats with unilateral globus pallidus lesions.
The present study examined the behavioral effects of dopamine receptor agonists, antagonists, or N-methyl-D-aspartate (NMDA) glutamate receptor antagonist in rats with a unilateral excitotoxic lesion of the globus pallidus (GP). After the unilateral GP lesions were made by injections of the ibotenic acid, drugs were systemically given and the elicited behaviors were quantitatively assessed. Systemic administration of haloperidol, but not SCH23390, dose-dependently induced contraversive dystonic posturing in unilateral GP-lesioned rats. On the other hand, systemic administration of quinpirole, but not SKF38393, induced ipsiversive circling. MK-801, only when given at a high dose, unilateral GP-lesioned rat, the D2 receptor agonist and antagonist caused ipsiversive and contraversive posturing or circling, respectively. Since the rotational behavior is induced on the basis of asymmetry of the basal ganglia output activity, there must be a marked difference between the GP ablation and the administration of D2 receptor blockade on the basal ganglia output activity, supporting a speculation that overactivity of the basal ganglia under dopamine depletion is not solely a result of the disinhibition from the inhibitory GP efferents. The present unilateral GP-lesion model appears to be a useful one for the pharmacobehavioral investigation of D2-mediated mechanisms.
Analysis of Variance↗
Effects of the globus pallidus lesion on the induction of c-Fos by dopaminergic drugs in the striatum possibly via pallidostriatal feedback loops.
c-Fos is one of the transcription factors contributing to the regulation of the downstream gene expression. Administration of dopamine D1 receptor agonist or D2 receptor antagonist have been known to induce c-Fos expressions in striatal projection neurons. We examined the effects of unilateral ablation of the globus pallidus (GP) on apomorphine- or haloperidol-induced expression of c-Fos in the striatum. Haloperidol induced a high level of c-Fos expression in the striatal neurons, predominantly those in the dorsal part, and the unilateral GP lesion caused by ibotenic acid increased the number of neurons exhibiting haloperidol-induced c-Fos expression in the striatum on the side with the GP lesion by about 2- or 3-fold. On the other hand, the unilateral GP lesion had no significant effect on the apomorphine-induced c-Fos expression in the striatal neurons. The present study provides evidence indicating that the activity of GP neurons may have an inhibitory influence on the induction of the immediate early genes by haloperidol in the striatal neurons, suggesting a function of the pallido-striatal feedback loops which have been identified anatomically.
Animals↗
Injection of a GABA antagonist into the mesopontine reticular formation abolishes haloperidol-induced catalepsy in rats.
THE pedunculopontine nucleus and its adjacent structure of the mesopontine reticular formation are known as a mesencephalic locomotor region, since either electrical or chemical stimulation of these regions induces locomotion in decerebrate animals. In parkinsonism, it is presumed that the pedunculopontine nucleus is under GABAergic overinhibition from the basal ganglia. To reveal the behavioural effects of GABAergic disinhibition of the mesopontine reticular formation in parkinsonism, picrotoxin, a GABAA antagonist, (5 or 10 ng/ 0.25 microliter) or vehicle was injected unilaterally into the mesopontine reticular formation of rats via implanted cannulae after induction of catalepsy using haloperidol (1.5 mg kg-1, i.p.). Injection of the larger dose of picrotoxin, but not the smaller dose nor the vehicle, abolished the catalepsy with or without spontaneous locomotor activity. The present result suggests that the disinhibition of the brainstem output structures contributes to the recovery of mobility in the cataleptic state induced by blocking the dopaminergic transmission of the basal ganglia.
Animals↗
Efficient gene transfer to EGF receptor overexpressing cancer cells by means of EGF-labeled cationic liposomes.
Epidermal growth factor (EGF)-labeled cationic liposomes (EGF-liposomes) were prepared for efficient gene transfer vector to EGF receptor expressing cells. Transfection activity of EGF-liposomes associating plasmid PGV-C which encodes luciferase showed a 2-fold increase in EGF receptor expressing cells, HEC-1-A, compared to that of EGF-non-labeled liposomes (N-liposomes). In EGF receptor deficient HRA cells, however, both EGF- and N-liposomes exhibited low transfection efficiency and no difference was observed between them. Furthermore, by the addition of anti EGF receptor antibody, transfection efficiency of EGF-liposomes was suppressed, suggesting EGF receptor-mediated endocytosis of EGF-liposomes. Transfection activity of EGF-liposomes was strongly dependent on the concentrations of fusogenic lipid, dioleoylphospha-tidylethanolamine in liposomes. By X-gal staining 6-8% of GCH-1(m) cells which also had EGF receptor expressed beta-galactosidase activity following the transfection by EGF-liposomes associating pSV-beta-galactosidase. These findings indicate that EGF-liposomes could be a preferable vector for EGF-receptor expressing cells.
1,2-Dipalmitoylphosphatidylcholine↗
The ipsilateral and contralateral connections of the fifth somatosensory area (SV) in the cat cerebral cortex.
THE ipsilateral and contralateral corticocortical connections to the fifth somatosensory area (SV) in the feline cortex were determined from the location of retrogradely labelled cells following a single injection of HRP into SV. The injection was made into physiologically defined components of the body representation in SV. After injection of HRP into the face regions of SV, HRP-labelled cells were located ipsilaterally in areas 6 beta, 3b and 1-2 of the primary somatosensory (SI), in the second somatosensory (SII), third somatosensory (SIII), and fourth somatosensory (SIV) areas, along the ansate sulcus, and in areas 5a and 6a beta of the ipsilateral cortex, as well as in area 1-2 of SI and in SV of the contralateral cortex. On the other hand, after HRP had been injected into the trunk/hindlimb area, HRP-labelled cells were located in areas 3a, 1-2 of SI, in area 5, in SII, in SIII and in SIV of the ipsilateral cortex, as well as in area 1-2 of SI, and in SV of the contralateral cortex. The extent of these interconnections suggests that SV receives multiple sensory inputs and may function to integrate this information.
Afferent Pathways↗
Discrimination of forearm's motions by surface EMG signals using neural network.
We tried to discriminate different forearm's motions by surface EMG signals using neural network. In order to get a higher discrimination rate, the positions of electrodes were improved. We also tried to discriminate similar motions in order to clarify the limitation of the discrimination by surface EMG signals. Two experiments were carried out. One was to discriminate five different motions: grasp, wrist flexion, wrist extension, forearm pronation, and forearm supination (Experiment 1). The other was to discriminate four similar motions which have different quantitative definitions at grasp, wrist flexion/ extension, or forearm pronation/supination (Experiment 2). Four surface electrodes were placed on the skin above the main active muscles: short radial extensor m. of wrist, supinator m., long radial extensor m. of wrist, and ulnar flexor m. of wrist, considering anatomical functions of the forearm's muscles. EMG signals were recorded during 2 sec while the subjects kept the motions. Recorded EMG signals were sampled at 200 msec intervals after full-wave rectifying and low-pass filtering. Therefore, the number of sampling data patterns of EMG signals was 10 for every motion. Three layers of neural network was used for discrimination. The number of units in the input layer is 4, and the number of units in the output layer is 5 or 4. In order to get the best discrimination rate of the motions, we changed the number of units in the hidden layer from 3 to 12. The neural network was trained by the back-propagation algorithm. In Experiment 1, the best average values of discrimination rates under three patterns of EMG signals for each subject were 96.0%, 98.0%, and 87.2% when the numbers of units in the hidden layer were 10, 11, and 3 respectively. In Experiment 2 using original EMG patterns, the best average values of discrimination rates at grasp, extension/flexion, and pronation/supination were 59.5%, 76.0%, and 25.0% respectively. By using normalized EMG patterns, these were 40.0%, 84.8%, and 55.5% respectively.
Adult↗
Dose-dependent plasma clearance of human epidermal growth factor in rats.
Exogenously administered human epidermal growth factor (hEGF) shows a marked dose-dependent plasma disposition in rats. In the present study, total plasma clearance (CLtotal) of hEGF was examined from the viewpoint of hepatic blood flow and accessible EGF receptors in a dosing range of hEGF from 30 to 1000 micrograms/kg. In rats in which down-regulation of EGF receptors caused a reduction in their number (50% below the normal level) (group 1), the CLtotal of hEGF was decreased only at a medium dose (100 micrograms/kg) compared to those in normal rats. In rats in which hepatic intoxication with carbon tetrachloride caused 50% reduction of both EGF receptor number and hepatic blood flow (group 2), CLtotal was decreased at low and medium hEGF doses. The decrease at a low hEGF dose was proportional to the decrease in the hepatic blood flow. In rats with reduced hepatic blood flow caused by hypothermia (group 3), CLtotal was decreased at all hEGF doses examined, and the decrease at a low hEGF dose (50 micrograms/kg) was proportional to the hepatic blood flow. The decreases of CLtotal at a medium hEGF dose in groups 1, 2 and 3 were well accounted for by the decrease of hepatic blood flow and/or EGF receptor number in a well-stirred model.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effect of perfusate pH on the influx of 5-5'-dimethyl-oxazolidine-2,4-dione and dissociation of epidermal growth factor from the cell-surface receptor: the existence of the proton diffusion barrier in the Disse space.
The influx clearance (PSinf.MID) of the weak acid 5,5'-dimethyl-oxazolidine-2,4-dione (DMO) was determined by the multiple indicator dilution method with the isolated perfused rat liver under various perfusate pH conditions, ranging from 6.4 to 7.6. Although the pH partition theory predicted an increase in influx clearance of ten times in proportion to the change in the unionized fraction of DMO, there was no measurable change in this value. The effect of medium pH on the steady-state cell/medium concentration ratio (C/M) ratio of DMO was also investigated using isolated hepatocytes. The C/M ratio increased while medium pH decreased, but this change was less marked than predicted by the pH partition theory. Finally the pH dependency of the dissociation rate constant (koff) of epidermal growth factor from its receptor was also investigated using both isolated rat hepatocytes and the perfused rat liver. When the extracellular pH was changed from 6.4 to 5.6, the koff value of isolated hepatocytes increased 44 times, while that of the perfused rat liver increased only 9 times. Therefore, the effect of changing the extracellular pH on pH-dependent dissociation of epidermal growth factor from its cell-surface receptor was less in the perfused liver than in isolated hepatocytes. These findings, in addition to the well-known existence of the Na(+)-H+ exchanger on the sinusoidal membrane and the possible existence of the unstirred water layer in the Disse space, seem to suggest the existence of the proton diffusion barrier in the rat liver, which remains stronger in the perfused liver than in isolated hepatocytes.
Animals↗
Harzianic acid, a new antimicrobial antibiotic from a fungus.
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Anti-Bacterial Agents↗