HLPおよびDZPのVEPおよび脳波への急性効果

The acute effects of haloperidol (HLP) and diazepam (DZP) on the Visual Evoked Potential (VEP) and EEG were studied with 16 healthy male subjects (26~43 y.o.). In the two experimental session for each subject, HLP (0.02 mg/kg) were intra-venously and DZP (0.1 mg/kg) were per-orally administered. EEGs and VEPs were recorded through the two derivations (2 ch : O1→A1+2, 5 ch : O1→Cz), with 1024 msec of analysis time, averaging 100 responses. In the experimental session, EEGs and VEPs were recorded before and 15, 30, and 45 min after administration of HLP, before and 30,60, and 90 min after DZP. Consecutive change of group mean VEP were studied. Individual VEPs were subjected to the component analysis, and to the statistical assessment together with EEG. The following results were obtained. 1. After the administration of HLP, the latencies of short, middle and long latency component significantly increased, and the peak-to-peak amplitude N 1-P 2, P 5-N 5 and N 5-P 6 significantly decreased. The largest peak-to-peak amplitude P 4-N 7 significantly increased. In EEG, δ and θ-power% increased, and α2-power% decreased significantly. Significant positive correlation was found between δ, θ-power% of EEG and VEP latencies, and significant negative correlations was found between α2-power% and VEP latencies. These findings indicate the inhibitory effect of HLP all over the visual system through dopaminergic neuron system. The largest peak-to-peak amplitude (P 4-N 7) increased significantly synchronizing with increased θ waves. 2. After the administration of DZP, the latencies of short and middle latency component, P 3 and P 5, increased, P 2 latency decreased significantly. The peak-to-peak amplitude P 3-N 3, N 3-P 4, P 5-N 5, and N 5-P 6 decreased, N 2-P 3 amplitude increased significantly. In EEG, β1-power% increased, and α2-power% decreased significantly. Significant negative correlation was found between δ, θ-power% of EEG and VEP amplitudes, and positive correlations between α2-power% and VEP amplitudes. These findings indicate the inhibitory effect of DZP mainly on lateral geniculate body, optic radiation, and up to the visual cortex making BZD-receptor and GABA-receptor complex. Some exciting effect of DZP before the lateral geniculate body was suggested

An application of wavelet analysis to the human cerebral evoked potential

Adopting Wavelet analysis for the analysis of the waveform of EP (Evoked Potential), it was intended to confirm possibility of the subjective diagnosis for schizophrenia, epilepsy and healthy subject. 1. Each waveform of EPs (SEP, VEP and AEP) of 100 healthy male subjects (25.4±3.1 y.o.), 100 male schizophrenics (31.6± 10.4 y.o.) and 99 male epileptics (35.9± 13.1 y.o.) were subjected to the Wavelet analysis and the multiresolution analysis. As a result, the difference of Wavelet values among these subject groups were verified significantly. The Wavelet values was defined as the square means of each wavelet coefficients at each scale of multiresolution analysis. 2. The waveform of EPs of each subject were discriminated by use of discriminant method derived from Wavelet Function, in order to judge to which subject group the subject belongs, according to the wavelet values. Analyzing the waveform of EP, between 15~600msec of latency, the highest value of sensitivity, 89%, 87% and 88% was obtained for normal subject, schizophrenics and epileptics, respectively. As the conclusion, the possibility of the subjective diagnosis for schizophrenia, epilepsy, and normal subjects, by Wavelet analysis of EP waveform, were verified possible

The acute effects of diazepam and sodium valproate on the human SEP (Somatosensory Evoked Potential) and EEG

The acute effects of diazepam (DZP) and sodium valproate (VPA) on somatosensory evoked potential (SEP) were studied with 16 healthy male subjects (26~43 y. o.). In the two experimental sessions on different days, DZP (0.1 mg/kg) or VP A (5 mg/kg) was orally administered for each subjects. EEGs containing SEPs evoked by electric stimuli once every 5 sec were derived from the two derivations (monopolar : C3'→A1+2, bipolar : C3'→F3') and recorded into magnetic tape, before and 30, 60, and 90 min after the administration of these drugs. Reproducing the tape, SEPs with 1024 msec of analysis time were obtained by averaging 100 responses, and EEGs were subjected to the frequency analysis. Consecutive changes of group mean SEP were studied. Individual SEPs were subjected to the component analysis, and to the statistical assessment together with EEG. The following results were obtained. 1. After the administration of DZP, amplitudes of middle and long latency compenent significantly decreased and continued from early stage. The latencies were significantly increased and recovered for the middle latency component (P3~N4), while decreased for those of long latency component (N5~) later. After administration of DZP, in EEG, the power % were significantly increased for not only drug induced β but also δ and θ, and they had significant positive correlation with the latencies of middle latency component. These results suggest that DZP has the transient inhibitory effect to brainstem reticular formation, thalamus and hypothalamus, and continuous inhibitory effect to cerebral gray matter from early stage, and might facilitate transmission in cerebral white matter through GABA neuron system. 2. After the administration of VPA, the latencies did not significantly change for latencies of middle latency component, but increased for these of long latency component (P6~). Amplitudes of middle and long latency components decreased significantly. In EEG, the power % were significantly increased for α1 and decreased for β2. These results suggest that VPA has no or weak effect to brainstem reticular formation, thalamus and hypothalamus, while it has the inhibitory effect to cerebral gray matter through GABA neuron system

The acute effects of antidepressants on the human VEP and EEG

The acute effects of clomipramine hydrochloride (CMI), tricyclic antidepressant, were studied and compared with those of mianserin hydrochloride (MSR), tetracyclic antidepressant, by visual evoked potential (VEP), with each 16 and 12 healthy male subjects, respectively. In the two experimental session on different days, CMI (0.5mg/kg) or MSR (0.3mg/kg) were orally administered for each subject. EEGs containing VEPs evoked by flash stimuli once every 5sec were derived from the two derivations (2ch : O1→ A1 + 2, 5ch : O1→Cz) and recorded into magnetic tape. Reproducing the tape, VEPs before and 120min after the administration of each drug, with 1024msec of analysis time, were obtained by averaging 100 responses, and EEGs were subjected to the frequency analysis. The changes of the waveform of group mean VEP were studied and compared between these drugs. Individual VEPs were subjected to the component analysis, and to the statistical assessment together with EEG. The following, statistically significant, results were obtained. 1. After the administration of CMI, both latencies and peak-to-peak amplitudes of VEP did not significantly change. In EEG, the power% of α1 frequency band increased. These findings indicate that few effect of CMI on the visual system. 2. After the administration of MSR, latencies of short latency components (P3 and N3) significantly increased and peak-to-peak amplitudes of short latency components (P3-N3 and N3-P4) significantly decreased in VEP. In EEG, the power% of δ and θ frequency band increased, and that of α2 and β2 decreased. These findings indicate the inhibitory effect of MSR mainly on the lateral geniculate body and the optic radiation in the visual system. 3. From these results, it was considered that CMI has less effect on depression with anxiety or irritability than MSR

The acute effects of antidepressant on the human SEP (Somatosensory Evoked Potential) and EEG

The acute effects of clomipramine hydrochloride (CMI) and mianserin hydrochloride (MSR) on somatosensory evoked potential (SEP) were studied with each 12 and 16 healthy male subjects, respectively. In the two experimental sessions, CMI (0.5mg/kg) or MSR (0.3mg/ kg) was orally administered for each subject. EEGs containing SEPs evoked by electric stimuli, once every 5 sec, were derived from the two derivations (monopolar : C3'→A1+2, bipolar : C3'→F3'), and recorded into magnetic tape. Reproducing the tape, SEPs before and 120 min after the administration of these drugs, with 1024 msec of analysis time, were obtained by averaging 100 responses, and EEGs were subjected to the frequency analysis. The changes of the waveform of group mean SEP were studied. Individual SEPs were subjected to the component analysis, and to the statistical assessment together with EEG. The following, statistically significant (P<0.01, P<0.05), results were obtained. 1. After the administration of CMI, the latencies were significantly decreased for the early middle latency component (P2 and N2), and significantly increased for the long latency component (monopolar : P6~, bipolar : P7~). While those of late middle latency component (P4~P5) did not change significantly. The amplitudes of middle latency component (P3 and P4) increased significantly. In EEG, the power % were significantly increased for α1. In conclusion, stimulatory properties of CMI was verified by SEP. 2. After the administration of MSR, the latencies were significantly increased for the almost all middle and long latency component. The amplitudes of middle and long latency components (N4, P5 and P6) decreased significantly. In EEG, the power % were significantly increased for δ and θ, and significantly decreased for α2 and β2. In conclusion, sedative properties of MSR was verified by SEP

Fiber Type Conversion by PGC-1α Activates Lysosomal and Autophagosomal Biogenesis in Both Unaffected and Pompe Skeletal Muscle

PGC-1α is a transcriptional co-activator that plays a central role in the regulation of energy metabolism. Our interest in this protein was driven by its ability to promote muscle remodeling. Conversion from fast glycolytic to slow oxidative fibers seemed a promising therapeutic approach in Pompe disease, a severe myopathy caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA) which is responsible for the degradation of glycogen. The recently approved enzyme replacement therapy (ERT) has only a partial effect in skeletal muscle. In our Pompe mouse model (KO), the poor muscle response is seen in fast but not in slow muscle and is associated with massive accumulation of autophagic debris and ineffective autophagy. In an attempt to turn the therapy-resistant fibers into fibers amenable to therapy, we made transgenic KO mice expressing PGC-1α in muscle (tgKO). The successful switch from fast to slow fibers prevented the formation of autophagic buildup in the converted fibers, but PGC-1α failed to improve the clearance of glycogen by ERT. This outcome is likely explained by an unexpected dramatic increase in muscle glycogen load to levels much closer to those observed in patients, in particular infants, with the disease. We have also found a remarkable rise in the number of lysosomes and autophagosomes in the tgKO compared to the KO. These data point to the role of PGC-1α in muscle glucose metabolism and its possible role as a master regulator for organelle biogenesis - not only for mitochondria but also for lysosomes and autophagosomes. These findings may have implications for therapy of lysosomal diseases and other disorders with altered autophagy

AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells

Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis. In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF)-beta 1 stimulus. Initial screening was performed with the immortalized HK-2 renal tubule epithelial cell line. The most promising compounds were further tested in RPTEC primary renal tubule epithelial cells. We found that the synthetic lipid AM251 suppressed two hallmark events associated with EMT, the upregulation of collagen 1A1 (COL1A1) and downregulation of E-cadherin. Though AM251 is known to act as an antagonist for the cannabinoid receptor type 1 (CB1) and an agonist for the G protein-coupled receptor 55 (GRP55), the suppression of EMT by AM251 was not mediated through either receptor. Microarray analyses revealed that AM251 inhibited induction of several EMT transcription factors such as SNAIL1, which is the key inducer of EMT, and the AP-1 transcription factors FOSB and JUNB. Activation of SMAD2/3 and p38 mitogen-activated protein kinase (MAPK) was inhibited by AM251, with greater inhibition of the latter, indicating that AM251 acted upstream of SMAD/p38 MAPK in the TGF-beta signaling pathway. Our findings regarding the effects of AM251 on the TGF-beta signaling pathway may inform development of a novel therapeutic agent suppressing EMT, thus preventing kidney fibrosis

A Case of carcinoma of the duodenal bulb

A seventy-seven-year-old man was found to have a duodenal tumor by X-ray examination, which was identified to be malignant one by an endoscopic examination. On admission a slight anemia, increased erythrocyte sedimentation rate, positive occult blood reaction in stool were desclosed. An upper G.I. series revealed a filling defect of duodenal bulb. A duodenal endoscopic examination showed a protruding lesion on the greater curvature of the front wall of duodenal bulb. A biopsy specimen obtained at the same time was identified as a well differentiated adenocarcinoma tubulare by histological study. Local injection of MMC, 5Fu and predonin under endoscopic observation was performed weekly four times. Nevertheless the lesion have remained stationally. The patient have been well and still remaines under our medical supervision