l-Menthol increases extracellular dopamine and c-Fos-like immunoreactivity in the dorsal striatum, and promotes ambulatory activity in mice.

Similar to psychostimulants, the peripheral administration of menthol promotes mouse motor activity, and the neurotransmitter dopamine has been suggested to be involved in this effect. The present study aimed to elucidate the effects of l-menthol on parts of the central nervous system that are involved in motor effects. The subcutaneous administration of l-menthol significantly increased the number of c-Fos-like immunoreactive nuclei in the dorsal striatum of the mice, and motor activity was promoted. It also increased the extracellular dopamine level in the dorsal striatum of the mice. These observations indicated that after subcutaneous administration, l-menthol enhances dopamine-mediated neurotransmission, and activates neuronal activity in the dorsal striatum, thereby promoting motor activity in mice.

Simultaneous blood and brain microdialysis in a free-moving mouse to test blood-brain barrier permeability of chemicals.

Neurotoxic chemicals that pass through the blood-brain barrier (BBB) can influence brain function. Efficient methods to test the permeability of the BBB to specific chemicals would facilitate identification of potentially neurotoxic agents. We report here a simultaneous blood and brain microdialysis in a free-moving mouse to test BBB permeability of different chemicals. Microdialysis sampling was conducted in mice at 3-5 days after implantation of a brain microdialysis probe and 1 day after implantation of a blood microdialysis probe. Therefore, mice were under almost physiological conditions. Results of an intravenous injection of lucifer yellow or uranine showed that the BBB was functioning in the mice under the experimental conditions. Mice were given phenyl arsenic compounds orally, and concentration-time profiles for phenyl arsenic compounds such as diphenylarsinic acid, phenylarsonic acid, and phenylmethylarsinic acid in the blood and brain dialysate samples were obtained using simultaneous blood and brain microdialysis coupled with liquid chromatography-tandem mass spectrometry. Peak area-time profiles for linalool and 2-phenethyl alcohol (fragrance compounds or plant-derived volatile organic chemicals) were obtained using simultaneous blood and brain microdialysis coupled with gas chromatography-mass spectrometry in mice given lavender or rose essential oils intraperitoneally. BBB function was confirmed using lucifer yellow in these mice, and results indicated that the phenyl arsenic compounds, linalool and 2-phenethyl alcohol, passed through the BBB. The present study demonstrates that simultaneous blood and brain microdialysis in a free-moving mouse makes it possible to test the BBB permeability of chemicals when coupled with appropriate chemical analysis methods.

N-Formyl-3,4-methylenedioxy-benzylidene-gamma-butyrolaetam, KNK437 induces caspase-3 activation through inhibition of mTORC1 activity in Cos-1 cells.

The mammalian target of rapamycin complex 1 (mTORC1: mTOR-raptor interaction) and heat shock protein 70 (Hsp70) regulate various cellular processes and are crucial for the progression of many cancers and metabolic diseases. In the recent study, we reported that interaction of Hsp70 with tuberous sclerosis complex 1 (TSC1) regulated apoptosis. This study was designed to elucidate the underlying mechanism in Cos-1 cells. Here, we show that N-formyl-3,4-methylenedioxy-benzylidene-gamma-butyrolaetam (KNK437), which inhibits the expression level of Hsp70, abrogated phosphorylation of mTOR and S6K in response to insulin, and inhibited mTORC1 activity via disruption of an interaction between mTOR and raptor. In addition, KNK437 did not alter TSC1/2 complex formation. Furthermore, KNK437 inhibited the mTOR-raptor interaction on the outer membrane of the mitochondria and triggered caspase-3 activation. A reduction in the level of Hsp70 could result in the inhibition of the mTORC1 signaling pathway, thereby inducing apoptosis.

Postoperative psychological status of children with anorectal malformations.

Our purpose was to clarify factors that influence the level of depression of Japanese children with anorectal malformations (ARM). The subjects comprised 66 children with ARM, aged 0-16 years, and their mothers. Patients were divided into three groups (Group 1: aged 0-5 years, Group 2: 6-11 years, and Group 3: 12-16 years). The level of depression of the children aged 6-16 years was investigated by Kovac's children's depression inventory (CDI). The psychological status of their mothers was assessed by Spielberger's state-trait anxiety index (STAI) and Zung's self-rating depression scale (SDS). The classification of ARM and the clinical condition were also investigated. Defecation scores were assigned for the degree of bowel dysfunction. The level of depression in the patients was more marked in Group 3 than in Group 2 according to the CDI score. Significant correlations between the CDI score of the child and the STAI-1, STAI-2 and SDS scores of the mother were observed in Group 2, but not in Group 3. In Group 2, the STAI-1 score of the mothers was significantly influenced by the degree of bowel dysfunction in her child. In Group 3, the CDI score was significantly correlated with the constipation score. This study revealed that bowel dysfunction is the important factor that influences the level of depression of the children with ARM. In the period of childhood during which the child attends primary school, bowel dysfunction indirectly influences the level of depression of children through the psychological status of mothers. However, bowel dysfunction directly influences the level of depression of children in adolescent patients.

[A cases of schizencephaly associated psychosis].

Schizencephalyis a rare disorder of brain development resulting in the formation of abnormal unilateral or bilateral clefts in the cerebral hemispheres. One patient is described with psychotic symptoms with unilateral schizencephaly. The implications of the association between schizencephaly and psychosis in these patients for understanding the biology of the psychoses are discussed.

Psychosocial liaison-consultation for the children who have undergone repair of imperforate anus and Hirschsprung disease.

OBJECTIVE: The aim of this study was to investigate the psychological status of Japanese children with congenital anorectal malformation and their mothers to develop appropriate psychiatric interventions. METHOD: The subjects comprised 50 children with congenital anorectal malformation aged 0 to 16 years and their mothers. The psychology of children aged 7 to 16 years was investigated by Kovacs' Children's Depression Inventory (CDI). The psychology of their mothers was assessed by Spielberger's State-Trait Anxiety Index (STAI) and Zung's Self-rating Depression Scale (SDS). RESULTS: Depression was more marked in the children aged 12 to 16 years than in those aged 7 to 11 years according to the CDI. The mothers of preschool children showed higher levels of anxiety and depression than those of school-aged children, according to the STAI and SDS. Significant correlations between the CDI score of the children and the STAI or SDS score of the mothers were observed only among children aged 7 to 11 years. CONCLUSIONS: The frequency of depression and anxiety among children with congenital anorectal malformation and that among their mothers was associated with the age of the child. Long-term postoperative psychosocial support for the children and their mothers may be required, taking into account the age of the child.

Social adaptation of children with congenital fecal dysfunction: from the viewpoint of the mother-child relationship.

Excretory dysfunction associated with congenital anal anomalies (a generic term that includes anal atresia and Hirschsprung's disease) is presumed to greatly affect the psychology of the affected children. In this study, we conducted a survey on the psychological status of children with excretory dysfunction, and investigated the relationship between the affected children and their families in addition to their social life. Four children with fecal dysfunction due to a congenital anal anomaly and their mothers were interviewed. The results of psychological tests in the children and mothers along with our findings in the interviews with the children and mothers, were included in the data analysis. We found that regardless of the degree of excretory dysfunction, the child's state of mind was influenced by whether the mother exhibited warmth or criticism towards her child and whether there was a support system for the mother and child. We suggest that psychiatric consultation is necessary for these children.

Recent progress in artificial organ research at Tohoku University.

Tohoku University has developed various artificial organs over the last 30 years. Pneumatic driven ventricular assist devices with a silicone ball valve have been designed by the flow visualization method, and clinical trials have been performed in Tohoku University Hospital. On the basis of these developments, a pneumatic driven total artificial heart has been developed and an animal experimental evaluation was conducted. The development of artificial organs in Tohoku University has now progressed to the totally implantable type using the transcutaneous energy transmission system with amorphous fibers for magnetic shielding. Examples of implantable systems include a vibrating flow pump for ventricular assist device, an artificial myocardium by the use of shape memory alloy with Peltier elements, and an artificial sphincter for patients with a stoma. An automatic control system for artificial organs had been developed for the ventricular assist devices including a rotary blood pump to avoid suction and to maintain left and right heart balance. Based upon the technology of automatic control algorithm, a new diagnostic tool for evaluating autonomic nerve function has been developed as a branch of artificial organ research and this new machine has been tested in Tohoku University Hospital. Tohoku University is following a variety of approaches aimed at innovation in artificial organs and medical engineering fields.

Phenolic compounds from Gastrodia rhizome and relaxant effects of related compounds on isolated smooth muscle preparation.

Gastrol (1), together with 10 known phenolic compounds, has been isolated from the MeOH extract of the rhizomes of Gastrodia elata Blume (Orchidaceae), and their structures were elucidated by detailed spectral analyses including by 2D NMR spectroscopic analyses. The relaxant effects of these constituents on smooth muscle preparations isolated from guinea-pig ileum were also studied in order to reveal their characteristic pharmacological activities.