マウスの神経細胞において、Ischemic postconditioningはmitochondrial permeability transition poreとKATPチャネルの開口を介してNMDA受容体電流を低下させる。

Ischemic postconditioning (PostC) is known to reduce cerebral ischemia/reperfusion (I/R) injury; however, whether the opening of mitochondrial ATP-dependent potassium (mito-KATP) channels and mitochondrial permeability transition pore (mPTP) cause the depolarization of the mitochondrial membrane that remains unknown. We examined the involvement of the mito-KATP channel and the mPTP in the PostC mechanism. Ischemic PostC consisted of three cycles of 15 s reperfusion and 15 s re-ischemia, and was started 30 s after the 7.5 min ischemic load. We recorded N-methyl-D-aspartate receptors (NMDAR)-mediated currents and measured cytosolic Ca²⁺ concentrations, and mitochondrial membrane potentials in mouse hippocampal pyramidal neurons. Both ischemic PostC and the application of a mito-KATP channel opener, diazoxide, reduced NMDAR-mediated currents, and suppressed cytosolic Ca2+ elevations during the early reperfusion period. An mPTP blocker, cyclosporine A, abolished the reducing effect of PostC on NMDAR currents. Furthermore, both ischemic PostC and the application of diazoxide potentiated the depolarization of the mitochondrial membrane potential. These results indicate that ischemic PostC suppresses Ca²⁺ influx into the cytoplasm by reducing NMDAR-mediated currents through mPTP opening. The present study suggests that depolarization of the mitochondrial membrane potential by opening of the mito-KATP channel is essential to the mechanism of PostC in neuroprotection against anoxic injury.博士（医学）・甲第781号・令和3年3月15日© Springer Science+Business Media, LLC, part of Springer Nature 2020This is a post-peer-review, pre-copyedit version of an article published in Cellular and molecular neurobiology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s10571-020-00996-y

Treatment of Symptomatic Non-Parasitic Liver Cysts–Surgical Treatment Versus Alcohol Injection Therapy

Fourteen patients with benign symptomatic non-parasitic cysts of the liver were either surgically treated, had alcohol injected into the cysts, underwent deroofing of the cyst or in 5, a cystectomy was done. Alcohol was injected into 6 patients and there has been no recurrence for as long as 5 years and 8 months after the treatment. Liver dysfunction occurred in 3 patients given blood transfusion during the surgery and/or postoperative course, an elevated temperature (over 39℃) occurred in one patient. Adverse effects of alcohol injections were minor and transient. Based on our experience, the injection of alcohol is an effective treatment for benign symptomatic cyst of the liver. When a malignancy is suspected on imaging and/or cytologic studies, or when alcohol administration is ineffective, then surgery is indicated

トクシマケン イシカイ トウニョウビョウ タイサクハン ダイ1ジ ダイ2ジ カツドウ ノ セイカ

Objective : The effectiveness of diabetes prevention programs for the general population in Tokushima Prefecture was investigated. The programs were designed by Tokushima Medical Association’ s（TMA’s）Steering Committee for Diabetes Prevention. Research design and methods : The committee promoted diabetes prevention by disseminating educational messages on diabetes to the general public and medical care providers, and establishing a referral system among public health centers and medical institutes throughout Tokushima Prefecture during the period from ２００４ to ２００９. The outcome of these activities were evaluated by analyzing data from the Prefectural Health and Nutrition Survey in Tokushima conducted in１９９７（n＝ ９９８）,２００３ （n＝１００８） and ２０１０ （n＝１１３０）, and then comparing these results with those of the national survey at the corresponding times. Results : The percentage of subjects with glucose intolerance at the time of initiation of the prevention program in Tokushima tended to increase from １９９７ to ２００３, but was slightly decreased in ２０１０, although the differences were not statistically significant. However, the percentage of subjects with glucose intolerance was significantly increased throughout Japan during the same period. Obesity parameters, physical activity evaluated by the number of steps and the average total energy intake changed favorably in parallel with changes in the prevalence of diabetes during the study period in Tokushima. Conclusion : The diabetes prevention programs initiated by the TMA’s committee may be useful in ameliorating the situation of diabetes in Tokushima Prefecture

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million personyears of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eG FR values 105 mL.min(-1).1.73 m(-2), compared with those with eG FR between 60 and 105 mL.min(-1).1.73 m(-2). Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL.min(-1).1.73 m(-2). Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin Alc, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function

イシ コッカ シケン ニオケル ヒンシュツ ジコウ ニ ツイテノ カイセキ

第95～100回の医師国家試験問題を分析し,繰り返し出題されている重要事項を具体的かつ客観的に明らかにした.それぞれの問題を平成17年度版医師国家資格試験出題基準(ガイドライン)項目と照合し,それぞれの項目別に出題割合を計算した.また,ガイドライン別の出題回数について,過去6年間(95～100回)の医師国家試験で何回出題されていたかを調べた.必修の基本的事項では,主要疾患・外傷・症候群で,医学総論領域では,症候・検査・治療で,医師国家試験設計表の出題割合を上回って出題されていた.すなわち,臨床実習で学んだ内容についての出題が増えている傾向であった.さらに,ガイドラインであげられている事項の55.2%以上は,過去6年間に一度も出題されておらず,限られた項目の内容が頻回に出題されていた.本検討結果は,医学教育者にとって重要な点を再認識し,教育のウエイトを検討するための良い材料になったと思われる.医学教育に携わる者は,医学生が欠いてはならない最重要点を正確に把握することが重要である.The National Examination for Physician\u27s is based on its guideline which consists of various kinds of items. To focus on frequently asked items, we analyzed the questions found in the National Examination for Physician\u27s administered from 2001 through 2006. Each question was examined in accordance with the items of the guideline. More than half of the items in the guideline have not been asked, otherwise less than 1.4% of the items were frequently (more than 5 times) asked in the examinations administered during the past six years. Furthermore, since questions concerning clinical signs, symptoms and examinations are asked more frequently than expected, the items in which usually are learned from bed-side visits have been emphasized recently. As we clarified the important items frequently asked in the recent National Examination for Physician\u27s, this information might be useful for medical educators to stress for the minimal essential points in the medical education

Magnetic Resonance Imaging in Breath-Hold Divers with Cerebral Decompression Sickness

The mechanism of cerebral decompression sickness (DCS) is still unclear. We report 2 cases of breath-hold divers with cerebral DCS in whom magnetic resonance imaging (MRI) demonstrated distinctive characteristics. One case presented right hemiparesthesia, diplopia, and gait disturbance after breath-hold diving into the sea at a depth of 20 m. Brain MRI with fluid-attenuated inversion recovery (FLAIR) sequence revealed multiple hyperintense lesions in the right frontal lobe, bilateral thalamus, pons, and right cerebellar hemisphere. The second case presented visual and gait disturbance after repetitive breath-hold diving into the sea. FLAIR imaging showed hyperintense areas in the bilateral occipito-parietal lobes. In both cases, diffusion-weighted imaging and apparent diffusion coefficient mapping revealed hyperintense areas in the lesions identified by FLAIR. Moreover, follow-up MRI showed attenuation of the FLAIR signal abnormalities. These findings are suggestive of transient hyperpermeability in the microvasculature as a possible cause of cerebral DCS

Cerebral Venous Thrombosis in the Superior Sagittal Sinus as a Rare Cause of a Paroxysmal Kinetic Tremor

Cerebral venous thrombosis (CVT) has a broad spectrum of clinical presentation compared to arterial etiology. Seizure is one of the common symptoms and is more frequent than in other stroke types. Hence, transient neurological symptoms in CVT patients are usually due to epileptic seizures, while transient repetitive movement disorder is extremely rare except as a complication of epilepsy. We report a case of CVT in the superior sagittal sinus with a 1-year history of paroxysmal kinetic tremor without evident epilepsy