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Aim: The risk of developing infectious diarrhea among elderly residents at Japanese geriatric intermediate care facilities is unclear. We investigated the incidence rate and risk factors of norovirus-related diarrhea at such facilities., Methods: This prospective cohort study followed 1727 residents from November 2018 to April 2020 at 10 geriatric intermediate care facilities in Osaka, Japan regarding the occurrence of diarrhea. Resident data were collected from their medical records using structured forms at two to three of the following three time points: at recruitment, if they developed diarrhea, and when they left the facility. Residents who developed diarrhea were tested using rapid diagnostic tests for norovirus. Cox proportional hazard model was employed to hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate the risk factors for norovirus-related diarrhea., Results: During the study period, 74 residents developed diarrhea, 13 of whom were norovirus positive. The incidence rate of norovirus-related diarrhea was 10.11 per 1000 person-years (95% CI: 4.61-15.61). In terms of risk factors, people with care-needs level 3 were at a higher risk for developing norovirus-related diarrhea (adjusted HR [aHR] = 7.35, 95% CI: 1.45-37.30). Residents with hypertension (aHR = 3.41, 95% CI: 1.05-11.04) or stroke (aHR = 8.84, 95% CI: 2.46-31.83), and those who walked with canes (aHR = 16.68, 95% CI: 1.35-206.52) also had a significantly higher risk for norovirus-related diarrhea., Conclusions: Throughout the study period, the incidence of development of diarrhea was low. Care-needs level 3, stroke, hypertension and use of a cane were identified as risk factors for norovirus-related diarrhea in Japanese geriatric intermediate care facilities. Geriatr Gerontol Int 2023; 23: 179-187., (© 2023 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Background : In Japan, freeze-dried live attenuated varicella-zoster vaccine BIKEN is available for adults aged ≥50 years to prevent herpes zoster (HZ). A prospective cohort study of 1200 healthy adults and 300 patients with underlying illness confirmed vaccine safety between 2016 and 2017. However, evidence of vaccine effectiveness (VE) is limited. Methods : VE against HZ and postherpetic neuralgia (PHN) was evaluated in the vaccinated cohort of the previous safety study in a follow-up study between 2021 and 2022 and compared with unvaccinated family members. Self-administered questionnaires determined retrospective experiences of HZ and PHN diagnosis. Logistic regression estimated the VE by calculating the outcome odds ratio (OR) in vaccinated vs. unvaccinated groups: VE = (1 - OR) × 100(%). Results : Overall, 1098 vaccinated and 518 unvaccinated subjects were analysed. Between 2016 and 2022, 26 vaccinated (2.4%) and 22 unvaccinated (4.2%) subjects reported HZ diagnosis, and 3 vaccinated (0.3%) and 2 unvaccinated (0.4%) subjects reported PHN. Adjusted VE against a clinical diagnosis was 41% for HZ [-6% to 67%], with marginal significance, and 16% [-408% to 86%] for PHN. Stratification by age, sex, or comorbidities had an adjusted VE against HZ of ~40%, which was similar between strata. Conclusion : Freeze-dried live attenuated varicella-zoster vaccine reduces the risk of HZ regardless of age, sex, or comorbidities.

Background: For the 2017-18 influenza season, A/Saitama/103/2014 (CEXP-002) (Saitama strain) was antigenically more similar to prior circulating strains than A/Hong Kong/4801/2014 (X-263) (Hong Kong strain) in a ferret model and was selected as the A(H3N2) vaccine virus strain in Japan. However, the Saitama strain grew poorly, and the Japanese government switched to the Hong Kong strain, raising public concerns of poor effectiveness. To enhance understanding of the correlation between antigenicity in experimental models and immunogenicity, as a surrogate measure of vaccine effectiveness, in the human population, we compared the immunogenicity of specially-prepared single dose monovalent influenza A(H3N2) vaccines containing the Saitama or the Hong Kong strain., Methods: A randomized controlled trial of 100 healthy adults aged 20-64 years (n = 50/group) was conducted. Virus neutralization assay was performed on sera from days 0 (pre-vaccination) and 21 (post-vaccination). Geometric mean titer (GMT), mean fold rise (MFR), seroconversion proportion (SCP), and seroprotection proportion (SPP) were calculated for vaccine strains and a representative circulating A(H3N2) virus strain (A/Osaka/188/2017)., Results: For the Hong Kong strain, post-vaccination GMT was significantly higher in the Hong Kong vaccine recipients (1:546 vs 1:260, p < 0.01), but MFR, SCP, and SPP were similar for both vaccine groups. For the Saitama strain, post-vaccination GMT (1:116 vs 1:61, p = 0.01) and SPP (86% vs 68%, p = 0.03) were significantly higher in the Hong Kong vaccine recipients, but MFR and SCP were similar for both vaccine groups. Against A/Osaka/188/2017, post-vaccination GMT and MFR were similar in both vaccine groups, but SCP (32% vs 4%, p < 0.01) and SPP (28% vs. 6%, p < 0.01) were significantly higher in the Hong Kong vaccine recipients., Conclusion: The Hong Kong vaccine induced better or equivalent immunogenicity in comparison to the Saitama vaccine. Our trial showed that antigenic similarity in experimental models does not necessarily correlate with immunogenicity in the human population., Clinical Trial Registration: UMIN000029293., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘TK has received a reward for advisor tasks from The Biken Foundation from April 2016 to March 2018. The other authors have nothing to declare’., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In Japan, freeze-dried live attenuated varicella-zoster vaccine is available for adults aged ≥50 years to prevent herpes zoster. However, limited evidence has been accumulated regarding vaccine safety for patients with underlying illnesses, who have been considered as the high-risk group for herpes zoster., Methods: A prospective cohort study of 1200 healthy adults and 300 patients with underlying illnesses such as malignancy, diabetes mellitus, autoimmune diseases, and renal diseases was conducted. All subjects were vaccinated and then their adverse events (AEs) were followed for 28 days after vaccination. Key safety measures included any AEs, severe AEs (SAEs), and vaccine-related AEs such as injection-site AEs and systemic AEs. The frequencies and 95% confidence intervals of AEs were calculated., Results: During the follow-up period, 2 SAEs (bone fracture and acute cholecystitis) among healthy adults and 1 SAE (disseminated mycobacteriosis) among patients with underlying illnesses were reported, although none of them was diagnosed as vaccine-related. Vaccine-related AEs were reported in 42% of healthy adults and patients with underlying illnesses, and the proportions were similar between the groups. The most frequent AEs were injection-site AEs in both groups (i.e., 41 and 39%), and systemic AEs were observed in 4% of both groups. Only among healthy adults, those with a history of herpes zoster were more likely to report injection-site AEs than those without a history of herpes zoster (53% vs 39%)., Conclusions: The present study confirmed the safety of freeze-dried, live attenuated varicella-zoster vaccine even in patients with underlying illnesses. A history of herpes zoster might be related to development of injection-site AEs in healthy adults., Trial Registration: The study was prospectively registered on Japic-Clinical Trials Information as JapicCTI-163415 on October 31, 2016.

Fibrillar collagen plays an essential role in ventricular remodeling, which is a major prognostic factor in various heart diseases. Inflammatory cytokines, including tumor necrosis factor alpha (TNFalpha), have been reported to play a role in various heart diseases and OPC-8212, a quinolinone derivative, has been demonstrated to reduce TNFalpha production. No studies have examined the effects of OPC-8212 on collagen metabolism in connection with inflammatory cytokine and growth factors. Using lipopolysaccharides as a tool to enhance TNFalpha, we examined the effects of OPC-8212 on the expression of type III collagen mRNA [alpha1(III)] in cultured neonatal rat cardiac fibroblasts. We also measured the concentration of TNFalpha and transforming growth factor beta (TGFbeta) in the cultured medium. Northern blot analysis revealed that LPS reduced the expression of alpha1(III) mRNA, and OPC-8212 counteracted this reduction (on average 25% above the reduced level by LPS stimulation). LPS enhanced the TNFalpha concentration in the medium, and OPC-8212 inhibited this enhancement. LPS increased the TGF-beta1 concentration in the cultured medium, while OPC-8212 did not affect this increase. In summary, OPC-8212 counteracted the reduction in type III collagen mRNA expression by LPS accompanied by suppression of the increase in TNFalpha.

This was the first dose-finding study of trazodone that was designed to be free of the concomitant use of hypnotics, in which the drug was administered in a single dose for sleep disorders combined with a depressive state. As a result, trazodone at the dosage of 50-100 mg/day improved sleep disorders, particularly at the 100 mg/day dosage. It was confirmed that trazodone improved sleep disorders combined with a depressive state when it was administered in a single dose before bedtime with no concomitant hypnotics.

A total of 6 alpha chains [alpha 1 (IV) to alpha 6 (IV)] have been identified in type IV collagen. We examined the localization of these chains in the myocardium of patients with dilated (DCM) and hypertrophic (HCM) cardiomyopathy. The localization of alpha 1 (IV)-alpha 6 (IV) in biopsy specimens of 5 patients with DCM and 4 with HCM was examined using immunohistochemistry with monoclonal antibodies. Both alpha 1 (IV) and alpha 2 (IV) immunostaining formed thin homogeneous outlines around myocytes in control hearts. In the DCM specimens, alpha 1 (IV) and alpha 2 (IV) immunostaining formed thick and irregular patterns around myocytes. Staining for alpha 1(IV) and alpha 2 (IV) was also observed in some enlarged intercellular spaces. In 3 DCM hearts, moderate staining for alpha 1 (IV) and alpha 2 (IV) was observed in small replacement fibrotic lesions. In large replacement fibrotic lesions, no alpha 1 (IV) or alpha 2 (IV) staining was observed. In the HCM specimens, alpha 1 (IV) and alpha 2 (IV) staining formed thick homogeneous patterns around myocytes. In the enlarged intercellular spaces, no alpha 1 (IV) or alpha 2 (IV) staining was observed. No labeling for alpha 3 (IV)-alpha 6 (IV) was observed in any heart examined. In conclusion, the present results demonstrate that type IV collagen consisting of alpha 1 and alpha 2 chains appears in the fibrotic lesions of DCM, indicating its contribution to the development of fibrotic changes in the myocardium of DCM patients. In contrast, type IV collagen was restricted to the myocyte membrane in the HCM hearts. Fibrotic processes in the intercellular spaces may differ between DCM and HCM hearts.

Wolfram syndrome (WFS; OMIM 222300) is an autosomal recessive neurodegenerative disorder defined by young-onset non-immune insulin-dependent diabetes mellitus and progressive optic atrophy. Linkage to markers on chromosome 4p was confirmed in five families. On the basis of meiotic recombinants and disease-associated haplotypes, the WFS gene was localized to a BAC/P1 contig of less than 250 kb. Mutations in a novel gene (WFS1) encoding a putative transmembrane protein were found in all affected individuals in six WFS families, and these mutations were associated with the disease phenotype. WFS1 appears to function in survival of islet beta-cells and neurons.

The type XVII collagen alpha 1 chain has been identified as a component of the type I hemidesmosome, and is thus thought to play a role in extracellular matrix (ECM) maintenance and signal transduction between the cell and the ECM. We examined the expression of type XVII collagen alpha 1 chain mRNA in the mouse heart by Northern blot analysis and determined the sequential changes of its expression in different developmental stages of the heart using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Northern blotting: Total RNA was extracted from 10 adult mouse hearts by the guanidine/cesium method. Hybridization was performed with mouse cDNA for alpha 1 (XVII) collagen. RT-PCR: Total RNA was extracted from 7 embryos, 4 neonates and 8 adult mice. Reverse transcription was performed using oligo-dT primer and MMLV. Amplification was carried out in alpha 1 (XVII) collagen and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDH served as an internal control. Northern blotting revealed a 5.6 kb signal that was identical to that of the alpha 1 (XVII) of skin and transformed keratinocyte reported previously. The sequences of the PCR products were also identical to those reported. The normalized expression ratios of alpha 1 (XVII) were 0.91 +/- 0.20 in the embryonic heart, 0.36 +/- 0.20 in the neonatal heart and 0.96 +/- 0.21 in the adult heart. In conclusion, we identified the expression of type XVII collagen alpha 1 chain mRNA in the mouse heart, suggesting that the type I hemidesmosome is located in the heart. The results of the RT-PCR at different developmental stages of the heart suggest that type XVII collagen contributes not only to cardiogenesis in the embryonic stage but also to maintenance of architecture and function in the adult heart.

Collagen, as a component of the extracellular matrix, have a role in the healing process after myocardial infarction (MI). For type IV collagen, a major structural protein present in the basal membrane of myocytes, six alpha chains [alpha 1 (IV)-alpha 6(IV)] have been identified. We examined the sequential changes in the appearance and localization of the alpha 1 (IV)-alpha 5(IV) after experimental MI in rats. Hearts were excised from 1 day to 8 weeks after permanent left coronary artery ligation. Immunohistochemical staining with monoclonal antibodies was performed. On day 3, staining for both alpha 1(IV) and alpha 2(IV) first appeared, forming a wavy pattern in the infarct peripheral zone, and the staining was not restricted to the cell membrane. The staining intensity and distribution for both alpha 1(IV) and alpha 2(IV) in the peripheral zone then gradually increased, reaching a maximum around day 7. The distribution progressed from the peripheral to the central zone of the infarct for 1-2 days, reaching the center point after 2 weeks. The staining distribution gradually decreased after reaching the maximum, but the staining had not completely disappeared at 8 weeks. In contrast, no positive staining for alpha 3(IV), alpha 4(IV) or alpha 5(IV) was observed at any time during the 8-week observation period. Thus, the present results demonstrated that in rats, type IV collagen consisting of alpha 1 and alpha 2 chains appears in the infarct zone at a relatively early phase after MI, indicating that type IV collagen composed of alpha 1 and alpha 2 chains contributes to infarct healing.

Serial changes of single photon emission computed tomography (SPECT) in two epileptic psychotics are reported. One patient had a decreased blood flow of the left temporal lobe with schizophrenia-like symptoms, and the other patient had a decreased blood flow of the right temporal lobe with depressive symptoms. In each case, these abnormal findings disappeared following recovery from a psychotic state. It might be suggested that the psychotic state of an epileptic patient influences the SPECT findings.

Objective: Investigation of the mechanism of the idiopathic periodic hyperthermia associated with agenesis of the corpus callosum., Setting: Tertiary care referral center., Patient: Fourteen-year-old girl who was the first case of reverse Shapiro's syndrome (ie, agenesis of the corpus callosum associated with periodic hyperthermia, as opposed to hypothermia as described in the original report by Shapiro et al)., Intervention: Magnetic resonance imaging scans, endocrinological examinations for hypothalamus, electroencephalograms, and levodopa therapy., Main Outcome Measure: Body temperature., Result: No neurologic or physical abnormalities were noted beside the callosal agenesis. Neuroimaging examinations could not reveal any structural abnormality of the diencephalon. Endocrinological examinations and electroencephalograms were found to be normal. The hyperthermia returned to normal by a small dose of levodopa, but a larger dose reversed the hyperthermia to hypothermia., Conclusions: These observations suggest that the hyperthermia observed in this case may have been caused by the dopaminergic denervation of the hypothalamic thermoregulatory center, resulting in the supersensitivity of its dopaminergic receptors.

The effects of procaine injected into the substantia innominata (SI) and the amygdala (AM) were compared in AM-kindled rats. Intra-SI injection of procaine (ipsilateral to the kindled AM) caused immediate contralateral hemiparesis lasting for about 30 min, associated with EEG amplitude reduction. When the kindled AM was stimulated at the previously established generalized seizure triggering threshold (GST), 8/15 animals had ipsilateral hemiconvulsive seizure 5 min after the injection. In all the animals, afterdischarge was readily produced with a significant reduction in its duration. When procaine was injected into the kindled AM, there was no paresis or EEG change. AM stimulation at the GST did not evoke afterdischarge 5 min after the injection, although the kindled seizure was reactivated by a more intense stimulus. After 24 hr, all the animals, regardless of the site of procaine injection, responded to GST stimulation with a kindled seizure. The data suggest that: (1) the effect of intra-SI procaine is not due to drug diffusion to the kindled AM, and (2) the kindled AM can gain access to the contralateral hemispheric motor mechanism without participation of the ipsilateral SI.

Examined hypothalamic-pituitary-adrenal axis (HPA axis) function in 30 children with attention-deficit hyperactivity disorder (ADHD) by measuring the diurnal variation and response to the dexamethasone suppression test (DST) of saliva cortisol. Normal diurnal saliva cortisol rhythm was found in only 43.3% of the ADHD children. DST showed suppression in 46.7% of the ADHD children. An abnormal diurnal rhythm and nonsuppression to the DST were more frequent in the severely hyperactive group than in the mildly were more frequent in the severely hyperactive group than in the mildly hyperactive group of children with ADHD. These results suggest abnormalities in HPA axis function in some children with ADHD, especially those exhibiting severe hyperactivity.

The plasma ratio of each neutral amino acid (tryptophan (TRP), tyrosine (TYR), valine, isoleucine, leucine (LEU) or phenylalanine) to the sum of the other neutral amino acids was measured in 16 manic and 14 depressed patients. In the manics, there was a correlation between the psychomotor activity and the plasma TRP and LEU ratios. In the depressives, the depressed mood, retardation and global severity were correlated with the TRP ratio. The zotepine responders showed an increase in the TRP ratio after treatment. In the mianserin responders, the TYR ratio, which was high before the treatment, decreased to the normal range after the treatment. But, the plasma amino acid ratios remained unchanged in the patients treated with lithium carbonate or amitriptyline. These results suggest that, in manic-depressive illness, there might be abnormalities in the metabolism of neutral amino acids, mainly of TRP and TYR, and that the plasma TRP and TYR ratios might be important indicators for determining the efficacy of some drugs.

Intraperitoneally (i.p.) administered L-aspartate (Asp) (20 mmol/kg) produced no behavioral or EEG change in nonkindled rats. Nonkindled rats that received 18, 19, or 20 mmol/kg Asp, dissolved in 10 or 15% dimethylsulfoxide (DMSO), i.p. developed masticatory movement, head nodding, and myoclonic jerks of the limbs, followed by wild running and subsequent tonic extension of the whole body. In contrast to the effects in nonkindled rats, i.p. injection of Asp 20 mmol/kg in 15% DMSO in amygdala-kindled rats precipitated electroclinical generalized seizures identical to kindled ones. When the kindled amygdala was pretreated with 2-amino-7-phosphonoheptanoic acid (2-APH), a potent and specific antagonist of N-methyl-D-aspartate (NMDA) receptors, the Asp/DMSO-induced generalized convulsion identical to kindled amygdala seizure was suppressed. 2-APH treatment of the contralateral amygdala was without such suppression. The results suggest that (a) Asp is ineffective when given alone (when given with DMSO, however, Asp evokes generalized seizures identical to kindled ones in amygdala-kindled rats, while it induces a qualitatively different generalized seizure in nonkindled rats; (b) NMDA receptors of the kindled amygdala play an important role in activation of the transsynaptic neurocircuit underlying the expression of kindled amygdala seizure; and (c) DMSO is useful in assessing potential central effects of compounds that do not readily penetrate the blood-brain barrier (BBB).

The 5HT-induced shape change (5HT-SC) of blood platelets, which had been suggested to reflect the 5HT2 receptor-mediated function of the central nervous system (CNS), was examined in patients with depression before or after antidepressant therapy. The degree of 5HT-SC did not differ between patients before treatment (n = 17) and healthy controls (n = 26). In patients after treatment (n = 12), in whom depression had been improved but drug therapy was continued, 5HT-SC in a concentration of 10(-5) M 5HT was observed more potently than that in healthy controls or untreated patients (p less than 0.05 and p less than 0.05, respectively). In 4 patients in whom 5HT-SC was measured before and after mianserin treatment, 5HT-SC increased after the treatment. These results suggest that the 5HT2 receptor-mediated function in the CNS may not be damaged in patients with depression, and that the 5HT2 receptor-mediated function in the CNS may be enhanced by antidepressants.

A-39-year-old man was admitted to our hospital because of a markedly decreased level of serum cholinesterase found incidentally by a blood test. Detailed examination did not reveal severe liver disease, malignant tumor, infection or organophosphate compound poisoning. Investigation of three generations of his family revealed two homozygous and five heterozygous family members with the cholinesterase deficiency gene E1s indicating familial serum cholinesterase deficiency.

We conducted serial EEG and SPECT studies on one female with Creutzfeldt-Jakob disease (CJD). In an analysis of EEG, a periodic synchronous discharge (PSD) was observed in the middle of the third stage (terminal stage) of Bernoulli's classification. The frequency of PSD was the highest at the beginning of the third stage, followed by a gradual decrease and disappeared at the end of the third stage. In the middle of the third stage, SPECT disclosed blood flow differences between the cerebrum and other regions (the cerebellum and the brainstem), while no such difference was observed by SPECT at the end of the third stage. It was suggested that the appearance of PSD requires the presence of a pathological change in the cerebrum precedent to other regions.

Amygdaloid-kindled rats received intravenous human copper-zinc superoxide dismutase (CuZn-SOD) either in free form or entrapped within liposomes (SOD-L), at 5, 10 or 20 mg/kg. The animals were stimulated at the generalized seizure-triggering threshold 5 min, 2 h and then every 24 h after the drug was given, until 5 consecutive stage 5 seizures were induced. Free CuZn-SOD had little or no effect. However, SOD-L, particularly at 10 mg/kg, had a prolonged anticonvulsant effect, although there was great individual variation in the onset and duration of seizure suppression. This effect of SOD-L may be due to the ability of liposomes to act as a depot for the sustained release of drugs.

The function of the hypothalamic-pituitary-adrenal axis (HPA-axis) and its association with clinical features in chronic schizophrenia were investigated. Twenty of 33 chronic schizophrenics exhibited an abnormal diurnal variation of the saliva cortisol level. The patients with abnormal diurnal variation gave higher scores for some negative symptoms than those with normal diurnal variation. On the dexamethasone suppression test (DST) of saliva samples, 13 of 34 chronic schizophrenics were abnormal. The patients with DST nonsuppression were more frequently classified into disorganized type and exhibited low scores of anxiety compared with the patients with normal suppression. The 9 patients who showed abnormal diurnal variation and DST nonsuppression were more frequently classified into disorganized type and showed higher scores of negative symptoms than the 9 patients who did not show any abnormal cortisol data. These results suggest that there might be some disturbance in the function of the HPA-axis in a group of chronic schizophrenics and that these patients might have severe negative symptoms.

Three-dimensional ESR imaging of a living rat has been performed by an L-band ESR system, which is composed of an L-band ESR spectrometer, a field gradient coil, and a data processor. The imaging was carried out by Lauterbur's method. A nitroxide, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (Carbamoyl-PROXYL), was used as an imaging agent in saline solution at a concentration of 0.2 M and administered intraperitoneally to obtain a constant concentration in the head for about an hour. It took about 40 min to obtain one set of ESR-CT images. The cross-sectional images were made, both as coronal and horizontal images. In the images of the rat head the nitroxide-rich region was clearly distinguished from the deficient region. The nitroxide-deficient areas corresponded well to the brain of the rat.

To examine the noradrenergic function in endogenous depression, binding of a selective agonist radioligand, 3H-UK14304, to platelet alpha 2-adrenergic receptors and plasma free 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) were measured in untreated depressed patients. The effects of an antidepressant, mianserin, on these parameters were also assessed. The Bmax and Kd values for 3H-UK14304 binding in 26 untreated depressed patients were significantly higher (p less than 0.05, p less than 0.01) than those in 26 normal controls. On the other hand, there were no significant differences in plasma free MHPG levels between 12 untreated depressed patients and 12 normal controls. Chronic administration of mianserin to 8 depressed patients slightly increased the Bmax and Kd values. However, plasma free MHPG levels did not change after treatment. These findings suggest that depression is related to the subsensitivity of alpha 2-receptors as indicated by a decreased affinity of platelet alpha 2-receptors. In addition, chronic administration of mianserin further decreased the affinity of alpha 2-receptors. This suggests that mianserin acts not only on alpha 2-receptors but also on the other neurotransmitter systems.

Plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) was measured in 19 patients with acute schizophrenia before and after neuroleptic therapy. Plasma antinoradrenergic activity (pANA) of the neuroleptics used was measured after treatment. Before treatment, pMHPG was higher in the patients than in 20 normal controls. There was a positive correlation between pMHPG level and the global severity of positive symptoms. After neuroleptic therapy, pMHPG was reduced, and there was a significant correlation between the decline in pMHPG and the improvement in positive symptom score. The decline in pMHPG was also correlated with pANA. These results suggest that there is a dysfunction of the noradrenergic system in the brains of some acute schizophrenics with mainly positive symptoms, and that this dysfunction may be improved, along with positive symptom score, after neuroleptic therapy.

Eye movements in response to visual stimuli (Benton Visual Retention Test) were examined in 22 temporal lobe epileptics (TLEs), 10 primary generalized epileptics (PGEs), and 20 normal controls. In the normal controls, the percent fixation time on the left peripheral figure was higher than that on the right peripheral figure, a tendency also found in the PGEs. In TLEs with right-sided foci, the percent fixation time on the left peripheral figure was higher than that on the right peripheral figure, the direction of asymmetry found in the normal controls and PGEs. However, when calculated as laterality indices (the degree of asymmetry) TLEs with right-sided foci were significantly more negative than those of both the normal controls and PGEs. In TLEs with left sided foci, the percent fixation time on the right peripheral figure tended to be higher than that on the left peripheral figure, an asymmetry which differed significantly from the normal controls, PGEs and the TLEs with right-sided foci. The results here showed that TLEs with unilateral foci had distinct eye movements which varied with the laterality of the lesion in the direction of functional overactivation of the epileptogenic hemisphere.

The possible role played by superoxide dismutase (SOD), a major defense system for counteracting the toxic effects of oxygen free radicals, in amygdaloid (AM) kindling was examined in rats. A significant increase of total SOD activity in the whole brain was observed 30 days after completion of AM kindling. Intra-AM injection of 3 ng of one of the 2 SOD enzymes present in mammalian brain, i.e. cytosolic SOD containing copper and zinc (CuZn-SOD) caused suppression of kindled seizure. These results suggest that SOD participates in the persistence of AM kindled seizure susceptibility and the initiation of kindled AM seizure.

Liposomes (LIPO), which are concentric lipid layers alternating with aqueous compartments, have been suggested as a potential carrier for various drugs. In the previous studies, we have demonstrated that anticonvulsant drugs such as valproic acid, phenytoin, and DN-1417 (an analog of thyrotropin-releasing hormone) entrapped into LIPO exert more prominent therapeutic efficacy than parent drugs. In the present study, we examined the comparative effects of Lidocaine (LDCA) which acts as a proconvulsant as well as an anticonvulsant, and LIPO-entrapped LDCA (LDCA-L) on limbic status epilepticus originating in the amygdala (AM) of rats. LDCA (LDCA hydrochloride) was dissolved in distilled water as a vehicle at a concentration of 2.5 mg/ml or 10 mg/ml. LIPO and LDCA-L were prepared from L-alpha-phosphatidylcholine, cholesterol, and stearylamine. Status epilepticus was induced by intra-AM injection of combined dibutyryl (db)-cAMP-200 micrograms/ethylene diaminetetraacetic acid (EDTA)-67.2 micrograms through the implanted cannula. The animals were divided into 4 groups which received vehicle (n = 6), LIPO (n = 5), LDCA (n = 9), and LDCA-L (n = 10). LDCA group was subdivided into 5 mg/kg (n = 4) and 20 mg/kg (n = 5) groups. LDCA-L group was treated with 5mg/kg (n = 4) or 20mg/kg (n = 6). All drugs were intravenously given at a volume of 2ml/kg via teflon tube previously inserted into cervical vein 30 min after db-cAMP/EDTA injection. Vehicle or LIPO alone did not alter the pattern of electroclinical ictal responses produced by intra-AM injection of db-cAMP/EDTA.(ABSTRACT TRUNCATED AT 250 WORDS)

The present paper reports 3 cases of aphasia with small lesions in the region of the basal ganglia to discuss whether neostrial dysfunction can cause aphasic symptoms. The Standard Language Tests of Aphasia (SLTA) was used to assess the type and degree of aphasia. Two patients with infarction either in the left putamen or in the head of the left caudate nucleus showed severe disturbance only in recalling words, especially nouns. The other patient showed the same symptom, in addition to writing disturbance that developed shortly after surgical extirpation of an arteriovenous malformation (AVM) in the left caudate nuclei. The symptoms common to the 3 patients corresponded well to the "anomic aphasia" proposed by Benson. The aphasic symptoms disappeared completely or largely within several months. This easy reversibility suggests that the aphasic disorder in the three patients was caused by damage not to the basal ganglia themselves, but to the affecting axons passing through or by the nuclei.

To assess the relative contribution of antiepileptic drugs (AEDs) toward the occurrence of congenital malformation, two prospective studies (previous and present) were compared. In the present subjects of 145 cases, the total daily dose of AEDs (drug score) in each case was decreased as much as possible, and polypharmacy was changed to monopharmacy before conception where it was possible. The incidence of malformations significantly decreased from 13.5% to 6.2% (p = 0.031) by the change in drug regimen. The drug score, number of AEDs, maternal age at delivery, seizure type, and etiology of epilepsy were statistically different between the two study groups. Even after the correction of the data by the last three factors, the difference in the incidence of malformation did not disappear, while it disappeared if data were corrected either by the drug score or number of AEDs. These results suggest that the possibility of prevention of AED related malformations is possible by an improvement in AED therapy.

gamma-D-glutamylaminomethylsulphonic acid (GAMS), a preferential antagonist of non-NMDA receptors (kainate and quisqualate receptors), was injected into the kindled amygdala (AM) of rats. When the kindled AM was stimulated at the previously established generalized seizure triggering threshold (GST) one hour after the GAMS (1 or 2 mumol) injection, afterdischarge (AD) generation was completely suppressed. However, a re-stimulation at the intensity of 40-200 microA above the GST generated AD associated with Stage 1 or 5 seizure. Our result suggests an important role played by non-NMDA receptors in the expression and generalization of AM-onset seizures.

Recent studies have demonstrated that intramuscular administration of thyrotropin-releasing hormone (TRH) or its analogue improves various clinical aspects of intractable epilepsy such as Lennox-Gastaut syndrome, West syndrome, and myoclonus epilepsy. Other clinical studies reported efficient property of intravenous TRH against status epilepticus. However, it is also true that intravenous TRH produces epileptic seizures in patients with epilepsy or organic brain damage. Thus, the utility of intravenous TRH for the treatment of status epilepticus seems to be equivocal. To further explore the problem in this regard, we examined the effect of TRH on limbic status epilepticus in rats. Thirty-eight male Wistar rats weighing 180-220g were used. Status epilepticus was induced by intracerebral injection of a combination of 200 micrograms of dibutyryl-cAMP (db-cAMP) and 67.2ng of ethylenediaminetetraacetic acid (EDTA) into the amygdala (AM) through an implanted cannula. 30 min later, TRH or vehicle (distilled water) was administered intravenously (i.v.) or intracerebroventricularly (i.c.v.). Although 3 mg/kg of TRH (n = 9), when injected i.v., did not alter the pattern of electroclinical ictal responses induced by db-cAMP/EDTA, 25 mg/kg (n = 5) and 50 mg/kg (n = 5) of TRH significantly exaggerated EEG and/or behavioral ictal seizures, beginning immediately after the injection and lasting for more than 30 min. With 50 mg/kg of TRH, the exaggerated seizure patterns were followed by marked suppression of electroclinical seizures. 50 micrograms of i.c.v. TRH (n = 5), like higher doses of i.v. TRH, caused a slight, but not a significant, build up of electroclinical ictal seizures, beginning immediately after the injection and lasting for about 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)