Impaired memory and executive function associated with decreased medial temporal and prefrontal blood flow in Clinical Dementia Rating 0.5 status: the Osaki‐Tajiri project

Aim: The Clinical Dementia Rating (CDR) is an assessment of dementia severity based on observations of activities of daily living, and a CDR of 0.5 (CDR 0.5) represents questionable dementia. A combination of the Cognitive Abilities Screening Instrument (CASI) and the Trail Making Test (TMT) scores discriminated CDR 0.5 subjects from healthy participants with a high degree of accuracy. We investigated the neurological background of CDR 0.5 subjects by correlating CASI and TMT scores with regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT). Methods: From a community‐based cohort, 22 CDR 0.5 participants were recruited. CASI and TMT scores, rCBF measure using [¹²³I]‐N‐isopropyl‐p‐iodoamphetamine and SPECT were obtained. We evaluated the relationships between the CASI domain scores, between TMT scores and rCBF in a regions‐of‐interest‐based analysis, and voxel‐based analysis using Statistical Parametric Mapping 5 software. Results: We found that lower rCBF in the left medial temporal cortex correlated with a decreased CASI domain recent memory score both in the regions‐of‐interest and statistical parametric mapping analysis. In both the regions‐of‐interest and statistical parametric mapping analysis, the rCBF in the left prefrontal cortex correlated with CASI domain remote memory and mental manipulation and concentration. Conclusions: Our results indicate that some CDR 0.5 subjects have functional impairments in the medial temporal lobe as well as in the prefrontal cortex, as reflected in the cognitive decline measured by CASI and TMT.     

A Novel Missense Mutation Causing a G487R Substitution in the S2–S3 Loop of Human ether‐à‐go‐go‐Related Gene Channel

hERG(G487R) Channel . Introduction: Mutations of human ether‐à‐go‐go‐related gene (hERG), which encodes a cardiac K⁺ channel responsible for the acceleration of the repolarizing phase of an action potential and the prevention of premature action potential regeneration, often cause severe arrhythmic disorders. We found a novel missense mutation of hERG that results in a G487R substitution in the S2–S3 loop of the channel subunit [hERG(G487R)] from a family and determined whether this mutant gene could induce an abnormality in channel function. Methods and Results: We made whole‐cell voltage‐clamp recordings from HEK‐293T cells transfected with wild‐type hERG [hERG(WT)], hERG(G487R), or both. We measured hERG channel‐mediated current as the “tail” of a depolarization‐elicited current. The current density of the tail current and its voltage‐ and time‐dependences were not different among all the cell groups. The time‐courses of deactivation, inactivation, and recovery from inactivation and their voltage‐dependences were not different among all the cell groups. Furthermore, we performed immunocytochemical analysis using an anti‐hERG subunit antibody. The ratio of the immunoreactivity of the plasma membrane to that of the cytoplasm was not different between cells transfected with hERG(WT), hERG(G487R), or both. Conclusion: hERG(G487R) can produce functional channels with normal gating kinetics and cell‐surface expression efficiency with or without the aid of hERG(WT). Therefore, neither the heterozygous nor homozygous inheritance of hERG(G487R) is thought to cause severe cardiac disorders. hERG(G487R) would be a candidate for a rare variant or polymorphism of hERG with an amino acid substitution in the unusual region of the channel subunit. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1246–1253, November 2012)     

ONO-4817对实验性变态反应性脑脊髓炎的治疗作用

 目的探讨一种新合成的含氧肟酸的基质金属蛋白酶(MMP)抑制剂——ONO-4817对实验性变态反应性脑脊髓炎(EAE)的治疗效果。方法给EAE大鼠口服ONO-4817，观察临床症状、T淋巴细胞增殖以及血清肿瘤坏死因子(TNF)α水平。结果ONO-4817能显著改善EAE临床症状(P＜0.01)，同时明显抑制T淋巴细胞增殖(P＜0.01)，显著降低大鼠血清TNFα水平(P＜0.05)。结论研究表明，ONO-4817通过抑制MMPs活性、T淋巴细胞增殖和减少TNF-α生成，进而能显著减轻血脑屏障(BBB)的破坏，又可以抑制炎细胞浸润和髓鞘破坏，从而有效缓解EAE。     

Psychosomatic tendency for suicide among the elderly in Mie Prefecture, Japan

Background: The aim of the present study is to show the causative factors of suicide among the elderly (over 65) in Mie Prefecture, Japan, and to discuss the prevention of the suicidal influences in elderly patients. Methods: We investigated all inquest records during the 14‐year period 1989–2002 in cooperation with the First Department of Criminal Investigation of Mie Prefectural Police Headquarters. From all cases classified as suicides, we extracted data on age, sex and background, and we focused on suicide in the elderly group. Results: During the test period, there were 5048 suicides (3276 male and 1772 female suicides) of which 1513 (691 male and 822 female) were in the elderly group. The rate of suicide in the elderly group was approximately 30% of the total in all age groups. The rate of female suicides in the elderly group was approximately 46.3%. The major causative factors of suicide among the elderly were ‘suffering from physical illness’, and ‘psychiatric disorders’. ‘Physical diseases’ were not negligible backgrounds in middle and elderly groups. Among physical diseases, the number of malignant neoplasm was clearly less than the other diseases. Notably, ‘cardiovascular disease’ and ‘orthopedic disorders’ were most frequent causative factors of suicide other than malignant neoplasm. Conclusion: It is consequently concluded that improvements in the system of home nursing and health care should be involved in the suicidal prevention of the elderly who ‘suffer from physical illness’. The patients who ‘suffer from physical illness’ should be given physical and mental support. In order to prevent suicide, not only psychiatrists but also general practitioners as well as medical staff and general public should be provided with education regarding depression among ‘psychiatric disorders’.