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Acetylcholine (ACh) modulates neurotransmitter release in the central nervous system. Although GABAergic transmission onto the striatal cholinergic interneurons (ChIN) is modulated by dopamine receptors, cholinergic modulation of the same synapse is still unknown. In the present study, modulatory roles of ACh in the GABAergic transmission from striatal medium spiny neurons (MSNs) onto ChIN were investigated using optogenetics and whole-cell patch-clamp technique in juvenile and young-adult mice brain slices. GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) were evoked by focal electrical- or blue-light stimulation. Bath application of carbachol, a muscarinic ACh receptor agonist, suppressed the amplitude of IPSCs in a concentration-dependent manner in both age groups. A choline esterase inhibitor, physostigmine, also suppressed the amplitude of IPSCs. In the presence of a membrane permeable M1 muscarine receptor antagonist, pirenzepine, carbachol-induced suppression of IPSCs was antagonized, whereas a M2 muscarine receptor antagonist, a M4 receptor antagonist, or a membrane impermeable M1 receptor antagonist did not antagonize carbachol-induced suppression of IPSCs. Retrograde cannabinoid cascade via cannabinoid receptor 1 was not involved in carbachol-induced inhibition. Furthermore, carbachol did not affect amplitude of inward currents induced by puff application of GABA, whereas coefficient of variation of IPSCs was significantly increased by carbachol. These results suggest that activation of presynaptic M1 muscarine receptors located on the GABAergic terminals including intracellular organelle of MSNs inhibits GABA release onto ChIN.

Cholinergic neurones in the basal forebrain (BF) project into various brain regions and receive excitatory inputs from the cortex and brain stem. These cholinergic neurones receive serotonergic fibres from the dorsal raphe nuclei. This study was aimed to elucidate serotonin (5-HT)-induced modulation of glutamatergic transmission onto rat BF cholinergic neurones identified with Cy3-192IgG. Excitatory postsynaptic currents (EPSCs) were evoked by focal stimulation. Bath application of either 5-HT, the 5-HT

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Spinocerebellar ataxia 42 (SCA42) is a neurodegenerative disorder recently shown to be caused by c.5144G > A (p.Arg1715His) mutation in CACNA1G, which encodes the T-type voltage-gated calcium channel CaV3.1. Here, we describe a large Japanese family with SCA42. Postmortem pathological examination revealed severe cerebellar degeneration with prominent Purkinje cell loss without ubiquitin accumulation in an SCA42 patient. To determine whether this mutation causes ataxic symptoms and neurodegeneration, we generated knock-in mice harboring c.5168G > A (p.Arg1723His) mutation in Cacna1g, corresponding to the mutation identified in the SCA42 family. Both heterozygous and homozygous mutants developed an ataxic phenotype from the age of 11–20 weeks and showed Purkinje cell loss at 50 weeks old. Degenerative change of Purkinje cells and atrophic thinning of the molecular layer were conspicuous in homozygous knock-in mice. Electrophysiological analysis of Purkinje cells using acute cerebellar slices from young mice showed that the point mutation altered the voltage dependence of CaV3.1 channel activation and reduced the rebound action potentials after hyperpolarization, although it did not significantly affect the basic properties of synaptic transmission onto Purkinje cells. Finally, we revealed that the resonance of membrane potential of neurons in the inferior olivary nucleus was decreased in knock-in mice, which indicates that p.Arg1723His CaV3.1 mutation affects climbing fiber signaling to Purkinje cells. Altogether, our study shows not only that a point mutation in CACNA1G causes an ataxic phenotype and Purkinje cell degeneration in a mouse model, but also that the electrophysiological abnormalities at an early stage of SCA42 precede Purkinje cell loss.

Acetylcholine is considered to be an endogenous modulator of hippocampal neurotransmission and synaptic plasticity. The activation of muscarinic acetylcholine receptors (mAChRs) reportedly enhances hippocampal synaptic plasticity, which plays an important role in memory function; however, the mechanism by which it enhances synaptic plasticity remains unclear. Here, we examined the involvement of the inhibition of Kv7/M K(+) channels, which are targets of mAChR modulation, during mAChR activation-induced enhancement of long-term potentiation (LTP) at rat hippocampal Schaffer collateral (SC)-CA1 synapses. When an electrical stimulus was applied to the stratum oriens before tetanic stimulation of the SCs, the magnitude of the induced SC-CA1 synapse LTP was enhanced as compared with that induced without stratum oriens stimulation. In the presence of the mAChR antagonist atropine, tetanic stimulation induced stable LTP, but the stratum oriens stimulation-evoked enhancement of LTP was abolished. The additional application of XE991, a selective blocker of Kv7/M K(+) channels, rescued the atropine-induced inhibition of LTP enhancement. The phospholipase C (PLC) inhibitor U-73122 inhibited the stratum oriens stimulation-evoked enhancement of LTP. Application of the T/R-type voltage-dependent Ca(2+) channel (VDCC) blocker Ni(2+) abolished the stratum oriens stimulation-evoked enhancement of LTP. In addition, tetanic stimulation with preceding stratum oriens stimulation was able to induce LTP during N-methyl-d-aspartate receptor blockade. We therefore propose that stratum oriens stimulation inhibits Kv7/M K(+) channels through mAChR activation-induced PLC activation, which leads to VDCC activation, and hence causes sufficient Ca(2+) influx to enhance LTP.

Hase K, Suzuki E, Matsumoto M, Fujiwara T, Liu M. Effects of therapeutic gait training using a prosthesis and a treadmill for ambulatory patients with hemiparesis. Objective To examine the short-term effects of a newly developed hemiparetic gait training in which patients walk with a prosthesis applied to the nonparetic leg in the flexed knee position. Design Pre-post nonrandomized controlled trial. Setting Rehabilitation center and gait laboratory of a university hospital. Participants Community-dwelling ambulatory volunteers (N=22) with chronic hemiparesis caused by a unilateral stroke. Intervention Study subjects participated in a gait training program using either a below-knee prosthesis or a treadmill. Treadmill gait training was performed at a speed approximating the maximum gait velocity for each patient. The 3-week program consisted of a 5-minute gait training session 2 to 3 times a day. Main Outcome Measures The ground reaction forces, stance time, step length and cadence during walking at a comfortable speed, and maximum gait speed, as well as the Berg Balance Score, were estimated before and after each training program. Results In comparison with changes after the treadmill gait training, analyses of covariance demonstrated a significant increase of the fore-aft ground reaction forces during the paretic propulsion phase and a significant increase in the relative durations of the paretic and nonparetic single stance involved in a gait cycle after the prosthetic gait training ( P Conclusions Prosthetic gait training would have different effects on a hemiparetic gait than treadmill gait training. The gait-related task inducing the dominant use of the paretic leg to support the body may be useful as a rehabilitative treatment to improve the kinetic abilities in the paretic stance period.

Hippocampal long-term potentiation (LTP), an increase in the efficacy of synaptic transmission, has been considered a powerful candidate for the physiological basis of memory. Although hippocampal LTP has been induced by high frequency electrical stimulation of the presynaptic fiber in most studies, it has been reported that pharmacological blockade of potassium ion channels also induces synaptic plasticity. Furthermore, several studies have recently used a newly developed selective blocker and opener to demonstrate that potassium ion channels play an important role in memory and learning. This article reviews studies that have shown the possible involvement of potassium ion channels in memory function and hippocampal synaptic plasticity.

Gq-protein-coupled Group I metabotropic glutamate receptors (mGluR) reportedly activate phospholipase C (PLC), leading to Ca(2+) release from intracellular stores and the formation of diacylglycerol (DAG). We electrophysiologically examined the involvement of the Group I mGluR in tetraethylammonium (TEA)-induced long-term potentiation (LTP) at mossy fiber (MF)-CA3 synapses in the rat hippocampus. TEA-induced LTP was almost completely blocked under the selective blockade of either mGluR1 or mGluR5, both of which are Group I mGluR. This result was supported by the blockade of TEA-induced LTP even in the absence of these blockers under low temperature conditions, in which the activation of Group I mGluR is thought not to be fully effective. In addition, the blockade of mGluR1 resulted in lower short-term potentiation (STP) during TEA application compared with the blockade of mGluR5. These results demonstrate the crucial roles of Group I mGluR in the TEA-induced LTP at MF-CA3 synapses and the different contributions of mGluR1 and mGluR5 to the initial component of plasticity.

Kainate-type glutamate receptors (KARs) are the third class of ionotropic glutamate receptors whose activation leads to the unique roles in regulating synaptic transmission and circuit functions. In contrast to AMPA receptors (AMPARs), little is known about the mechanism of synaptic localization of KARs. PSD-95, a major scaffold protein of the postsynaptic density, is a candidate molecule that regulates the synaptic KARs. Although PSD-95 was shown to bind directly to KARs subunits, it has not been tested whether PSD-95 regulates synaptic KARs in intact synapses. Using PSD-95 knockout mice, we directly investigated the role of PSD-95 in the KARs-mediated components of synaptic transmission at hippocampal mossy fiber-CA3 synapse, one of the synapses with the highest density of KARs. Mossy fiber EPSCs consist of AMPA receptor (AMPAR)-mediated fast component and KAR-mediated slower component, and the ratio was significantly reduced in PSD-95 knockout mice. The size of KARs-mediated field EPSP reduced in comparison with the size of the fiber volley. Analysis of KARs-mediated miniature EPSCs also suggested reduced synaptic KARs. All the evidence supports critical roles of PSD-95 in regulating synaptic KARs.

保育士養成校においては,2002年度から実施される新カリキュラムによって「音楽」に関する科目が削減される。しかし,音楽は子どもの心身の発達に大きな影響を及ぼし,豊かな人格形成に果たす音楽の役割は大きい。そして,保育士は子どもたちの音楽能力の育成に大切な役割を担っているのである。本稿では,保育士養成校における音楽教育の重要性について「音楽活動の意義」「音楽の機能」「乳幼児の音楽能力の発達と保育内容」「乳幼児の音楽活動」「保育士に求められる音楽的資質」の5つの観点から論じた。, The number of music subjects will be cut down in a new curriculum starting 2002. Music has great effects on children's mental and physical development. Nursery school teachers are responsible for helping development of children’s music ability. In this paper, I discuss the importance of five aspects of music education in teacher training programs: The role of music activities, The function of music, Development of young children’s music ability and day care programs, Young children’s music activities, Teachers' music ability.

In Saccharomyces cerevisiae , when a rich nitrogen source such as ammonium is added to the culture medium, the general amino acid permease Gap1p is ubiquitinated by the yeast Nedd4-like ubiquitin ligase Rsp5p, followed by its endocytosis to the vacuole. The arrestin-like Bul1/2p adaptors for Rsp5p specifically mediate this process. In this study, to investigate the downregulation of Gap1p in response to environmental stresses, we determined the intracellular trafficking of Gap1p under various stress conditions. An increase in the extracellular ethanol concentration induced ubiquitination and trafficking of Gap1p from the plasma membrane to the vacuole in wild-type cells, whereas Gap1p remained stable on the plasma membrane under the same conditions in rsp5 A401E and Δ end3 cells. A 14 C-labeled citrulline uptake assay using a nonubiquitinated form of Gap1p (Gap1p K9R/K16R ) revealed that ethanol stress caused a dramatic decrease of Gap1p activity. These results suggest that Gap1p is inactivated and ubiquitinated by Rsp5p for endocytosis when S. cerevisiae cells are exposed to a high concentration of ethanol. It is noteworthy that this endocytosis occurs in a Bul1/2p-independent manner, whereas ammonium-triggered downregulation of Gap1p was almost completely inhibited in Δ bul1/2 cells. We also found that other environmental stresses, such as high temperature, H 2 O 2 , and LiCl, also promoted endocytosis of Gap1p. Similar intracellular trafficking caused by ethanol occurred in other plasma membrane proteins (Agp1p, Tat2p, and Gnp1p). Our findings suggest that stress-induced quality control is a common process requiring Rsp5p for plasma membrane proteins in yeast.

The relationship between bilateral transfer and the effect of motor learning schedule was investigated using a palm force-retaining task. Thirty-three study subjects, all of whom were right-handed, were randomly divided into 2 groups, and each group was subjected to a separate practice schedule. The task was to generate and retain a force of 400 g using the right index finger for pressure. One session of practice consisted of 5 trials, and a total of 5 sessions (25 trials) were carried out exclusively with the right hand. Of the two groups, one group was set as a massed practice group (MP Group), and the other was a distributed practice group (DP Group). The former underwent an intensive practice schedule by carrying out 5 sessions of practice a day with a 1-minute recess every session, and the latter underwent a 5-day consecutive practice schedule by carrying out 1 session of practice a day. In the practice phase, visual feedback (VF) was given following the end of each trial. All of the study subjects underwent the initial test prior to the practice and retention tests at 5 minutes, 1 day and 4 days after the end of the final session of practice, without receiving VF. The data analysis was carried out by calculating the root mean squared error (RMSE). In the practice phase of the right hand, a decrease in RMSE was observed in both groups. In the retention tests of the right hand, there was a difference between these groups. The DP Group showed higher learning-retention ability, demonstrating the effect of the practice schedule. Regarding the left hand, the RMSE values in the retention tests were lower than the value observed in the initial test. This demonstrates that practice of the right hand gives a positive effect on the left hand. In addition, although no significant difference in the retention tests of the left hand was observed between these groups, the DP Group showed a tendency of higher learning-retention ability. This suggests that the practice schedule affects the effect on the non-practiced side as well.

Avoiding drug-drug interactions (DDIs) mediated through inhibition of cytochrome P450 (CYP) activity is highly desirable. Direct inhibition (DI) of CYP through new chemical entities (NCEs) or time-dependent inhibition (TDI) through reactive metabolites should be elucidated at an early stage of drug discovery research. In particular, TDI of CYP occurring through reactive metabolites may be irreversible and even sustained, causing far more serious DDIs for TDIs than for DIs. Furthermore, it is important to ascertain whether an NCE inhibits multiple CYP isoforms. Hence, using a cocktail-substrate approach that we previously established (in which the activity of 8 CYP isoforms is simultaneously evaluated in a single run), we evaluated the IC50 values of direct inhibitors and TDI parameters (kobs, shifted IC50, KI and kinact) of time-dependent inhibitors that affect multiple CYP isoforms. The IC50 values for 8 CYP isoforms obtained using the cocktail-substrate approach were nearly identical to values previously reported. The TDI parameters for CYP1A2, 2C9, 2C19, 2D6, and CYP3A4/5 obtained using the cocktail-substrate approach were also nearly identical to those obtained using a single-substrate approach. Thus, the cocktail-substrate approach is useful for evaluating DI and TDI in the early stages of drug discovery and development processes.

This paper presents a clothing-recommendation system that suggests personal combinations from a user's wardrobe. Online shopping websites use recommendation systems to suggest items that users might be interested in. Such systems make recommendations to a user on the basis of other users' behavior, under the assumption that all users behave similarly; personal preferences are not captured. However, a clothing-recommendation system should make recommendations on selections of personal items based on personal preferences rather than other users' behavior, since it is rare to find other users that own the same articles of clothing as the target user. The proposed system makes recommendations that are particularly suitable to a user based on the user's personal preference, history of clothing items and the user's evaluations of previous system recommendations. The experimental results reveal that the system can in most cases recommend more suitable combinations of clothing items than can existing systems under the same conditions.

Acetylcholine is considered to be an endogenous modulator of hippocampal neurotransmission and synaptic plasticity. The activation of muscarinic acetylcholine receptors (mAChRs) reportedly enhances hippocampal synaptic plasticity, which plays an important role in memory function; however, the mechanism by which it enhances synaptic plasticity remains unclear. Here, we examined the involvement of the inhibition of Kv7/M K(+) channels, which are targets of mAChR modulation, during mAChR activation-induced enhancement of long-term potentiation (LTP) at rat hippocampal Schaffer collateral (SC)-CA1 synapses. When an electrical stimulus was applied to the stratum oriens before tetanic stimulation of the SCs, the magnitude of the induced SC-CA1 synapse LTP was enhanced as compared with that induced without stratum oriens stimulation. In the presence of the mAChR antagonist atropine, tetanic stimulation induced stable LTP, but the stratum oriens stimulation-evoked enhancement of LTP was abolished. The additional application of XE991, a selective blocker of Kv7/M K(+) channels, rescued the atropine-induced inhibition of LTP enhancement. The phospholipase C (PLC) inhibitor U-73122 inhibited the stratum oriens stimulation-evoked enhancement of LTP. Application of the T/R-type voltage-dependent Ca(2+) channel (VDCC) blocker Ni(2+) abolished the stratum oriens stimulation-evoked enhancement of LTP. In addition, tetanic stimulation with preceding stratum oriens stimulation was able to induce LTP during N-methyl-d-aspartate receptor blockade. We therefore propose that stratum oriens stimulation inhibits Kv7/M K(+) channels through mAChR activation-induced PLC activation, which leads to VDCC activation, and hence causes sufficient Ca(2+) influx to enhance LTP.

Bilobalide, a unique constituent of Ginkgo biloba, has been reported to potentiate population spikes in hippocampal CA1 pyramidal cells and to protect the brain against cell death. In this study, the effects of bilobalide on synaptic transmission and its plasticity in rat hippocampal subfields were electrophysiologically investigated. Bilobalide (50 μM) significantly potentiated the input–output relationship at Schaffer collateral (SC)-CA1 synapses but not at medial perforant path (MPP)-dentate gyrus (DG), lateral perforant path (LPP)-DG, or mossy fiber (MF)-CA3 synapses. Facilitative effects of bilobalide on synaptic plasticity were only observed at MPP-DG synapses, in which the induction of long-term depression was blocked in the presence of bilobalide. However, no effect on synaptic plasticity was observed at SC-CA1 synapses. These results suggest that bilobalide has differential effects on synaptic efficacy in each hippocampal subfield.

Several kinds of loline-type alkaloids, norloline, loline, N-acetylnorloline, N-acetylloline, N-formylnorloline, N-formylloline and N-methylloline were detected in the urine of race-horses. Furthermore, a new compound of the alkaloids, N-senecioylnorloline, was also found and identified. These compounds were mainly identified by means of gas chromatography-mass spectrometry (GC-MS) and gas chromatography-fourier transform-infrared spectrometry (GC-FT-IR). A certain plant of Gramineae containing four kinds of loline-type alkaloids was found in a bale of hay used for the horse forage. The taxonomic feature of the plant was different from known plants containing loline-type alkaloids. The common fragmentation of loline-type alkaloids under electron ionization was briefly discussed.

Potassium ion channel blockade by tetraethylammonium (TEA) reportedly induces long-term potentiation (LTP) at hippocampal mossy fiber (MF)-CA3 synapses, but the characteristics of induction, expression, and modulation of the LTP remain unclear. In the present study, these features of TEA-induced LTP at MF-CA3 synapses were electrophysiologically examined using rat hippocampal slices. Synaptic responses recorded from MF-CA3 synapses were enhanced long-term by TEA application even under the blockade of NMDA receptors with D-AP5, whereas selective pharmacological blockade of T-type voltage-dependent calcium channels (VDCCs) strongly inhibited TEA-induced LTP. Decrease of the paired-pulse facilitation ratio after LTP induction by TEA suggests the involvement of increased neurotransmitter release probability from MF terminals as LTP expression. The facilitative modulation of MF-CA3 LTP by GABA(A) receptor activation reported previously was reversed when bumetanide, a blocker of Na(+)-K(+)-Cl(-) co-transporters (NKCCs), was applied, suggesting that the region-specific modulation of TEA-induced LTP by GABAergic inputs at MF-CA3 synapses is due to the dominance of NKCC action at MF terminals.

Devices of the extraction procedues and a recovery of the final supernatant as tiers accompanied with a transcription ability assessment of the individual tiers have enabled us to develop a variety of cell-free transcription systems. The latter step revealed that the factors necessary for faithful transcription as well as enhanced transcription form aggregates or complexes indicating an intrinsic nature of these factors to interact each other. Altogether 14 cell-free transcription systems have been developed from Bombyx mori embryos and tissues of various developmental stages and a cultured cell line, and screened for activities enhancing the basal promoter levels of the silk genes. Using these extracts a differential transcription of plural tissue-specific genes was tried. The fibroin gene was preferentially transcribed than the sericin-1 gene in the extracts from the posterior silk glands where the fibroin gene is specifically transcribed in vivo, while the sericin-1 gene was dominant to the fibroin gene in the extracts from the middle silk glands where the sericin-1 gene is specifically transcribed. Thus, these nuclear extracts offer us a biochemical clue assaying factors responsible for the differential transcription.

Tetraethylammonium (TEA), a K(+)-channel blocker, reportedly induces long-term potentiation (LTP) of hippocampal CA1 synaptic responses, but at CA3 and the dentate gyrus (DG), the characteristics of TEA-induced plasticity and modulation by inhibitory interneurons remain unclear. This study recorded field EPSPs from CA1, CA3 and DG to examine the involvement of GABAergic modulation in TEA-induced synaptic plasticity for each region. In Schaffer collateral-CA1 synapses and associational fiber (AF)-CA3 synapses, bath application of TEA-induced LTP in the presence and absence of picrotoxin (PTX), a GABA(A) receptor blocker, whereas TEA-induced LTP at mossy fiber (MF)-CA3 synapses was detected only in the absence of GABA(A) receptor blockers. MF-CA3 LTP showed sensitivity to Ni(2+), but not to nifedipine. In DG, synaptic plasticity was modulated by GABAergic inputs, but characteristics differed between the afferent lateral perforant path (LPP) and medial perforant path (MPP). LPP-DG synapses showed TEA-induced LTP during PTX application, whereas at MPP-DG synapses, TEA-induced long-term depression (LTD) was seen in the absence of PTX. This series of results demonstrates that TEA-induced DG and CA3 plasticity displays afferent specificity and is exposed to GABAergic modulation in an opposite manner.

To identify ocular complications in patients with myelodysplastic syndromes (MDS), who have a propensity to progress to acute myeloid leukemia (AML). Forty-one patients with MDS were the subjects in this retrospective study, and 21 patients with AML were selected as controls. Reviewing their clinical records, we verified that corneal ulcer, iridocyclitis, vitreous hemorrhage, retinal hemorrhage, and optic neuritis had been evaluated using slit-lamp assessment and opthalmoscopy in all the patients. In this study, the MDS patients were classified into those with refractory anemia (RA) and those with refractory anemia with excess blasts (RAEB). Ocular complications were found in 19 (46.3%) of the 41 patients with MDS, comprising corneal ulcer (two cases), iridocyclitis (five), vitreous hemorrhage (one), retinal hemorrhage (ten), cotton wool spots (one), and optic neuritis (two). (Some patients had more than one ocular complication.) Ocular complications were identified in 12 of the 21 (57.1%) patients with AML. There was no significant difference in frequency of ocular complications between MDS and AML (P = 0.4892). In MDS, retinal hemorrhage was associated with significantly reduced platelet counts (P = 0.0063). The frequency of ocular complications was significantly higher in MDS-RAEB than in MDS-RA (P = 0.0478). Retinal hemorrhage was significantly more frequent in patients with MDS-RAEB than in patients with MDS-RA (P = 0.0433). Ocular complications in MDS patients should be carefully examined as prognostic factors for progression to acute leukemia. Jpn J Ophthalmol 2005;49:377–383 © Japanese Ophthalmological Society 2005

To identify the motor strategies responsible for maintaining standing posture after deafferentation of the unilateral leg.Pretest-posttest, repeated-measures design.A Japanese university hospital rehabilitation facility.Nine healthy subjects aged 25 to 32 years.Two separate sessions that consisted of prolonged standing (control task) and standing until the H-reflex disappeared through the application of an inflated pneumatic cuff above the right knee.Center of pressure (COP), hip and ankle joint positions, and electromyographic activities.In the control task, no time-related change during prolonged standing was found in any of the measured parameters. After deafferentation, the right soleus activity decreased significantly (P.01), so the mean velocities of the COP in the anteroposterior and mediolateral directions were greater and the average COP position under the right foot shifted backward compared with those in the previous periods (P.01). Also, the left tibialis anterior and soleus were activated, as was the bilateral gluteus medius.The unilateral loss of leg and foot sensory information necessitated additional regulatory activities to stabilize the standing posture. The newly organized posture appeared to partly simulate the standing posture in patients with sensory disturbance of a unilateral leg.

The effects of exercise on the metabolism of caffeine (CA) were studied 3 h after administration of the drug to race horses which then underwent exercise sets (1000-m gallop). Analysis was made of pharmacokinetics of CA, changes in its plasma concentrations, its metabolites, i.e., theophylline (TP), theobromine (TB) and paraxanthine (PX), and the molar concentration ratios of CA to these metabolites. After exercise, AUC and t1/2 tended to decrease, and the concentration of CA decreased, while the concentrations of TP and TB significantly increased. The TP/CA ratio and TB/CA ratio significantly increased from 6 to 74h and from 25 to 50h after drug administration, respectively. This indicated promotion of metabolism of CA into TP and TB. The effects on PX were minimal.