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A 59-year-old man with progressive cognitive decline and mood disturbances was admitted to the hospital. Brain magnetic resonance imaging revealed marked white matter hyperintensity (WMH) and widespread lobar cerebral microbleeds. Because he had untreated hypertension, we started antihypertensive treatment and found a significantly improved cognitive function and WMH regression. We diagnosed him with cerebral amyloid angiopathy (CAA) based on the modified Boston Criteria with the rare apolipoprotein E (ApoE) ε2/ε4 genotype. The mechanism underlying reversible leukoencephalopathy in CAA may be related to the loss of autoregulation of brain circulation: cerebrovascular amyloid β deposits damaged the blood-brain barrier of the capillaries, which led to vasogenic edema induced by blood pressure surges.

Patients with neurological diseases are potentially at high risk for developing deep venous thrombosis (DVT). We sought the prevalence and clinical background of patients with neurological diseases in whom DVT was detected during hospitalization.Consecutive patients admitted due to neurological diseases were prospectively registered. Those who were at risk for DVT were screened using venous duplex ultrasonography of the lower extremities. Predictors for DVT detection were analyzed.During the study period, 192 of 785 patients received duplex ultrasonography. There were 34 patients with DVT identified (18%, age 63 ± 17 years). Three patients had DVT in the popliteal or femoral vein and the others had below the knee; all of the DVT were asymptomatic. DVT was observed most frequently in patients with systemic vasculitis, followed by demyelinating disease. In patients with DVT, the median D-dimer level was 2.1 µg/mL. On multiple logistic regression analysis, female ([odds ratio, 95% confidence interval] 3.2, 1.2-8.4), supine or sitting position for 48 h (5.3, 1.8-15.0), D-dimer level ≥ 2.0 µg/mL (6.2, 2.3-16.4), and white blood cell count ≥ 7,600 (4.2, 1.6-11.3) were independent predictors of DVT detection at the first screening ultrasonography. DVT was detected in 1, asymptomatic pulmonary embolism was detected in 2, and both in 1 on chest computed tomography.DVT is not rare in patients with neurological diseases. Clinicians should be mindful of subclinical DVT in hospitalized neurological disease patients with decreased daily activity and elevated D-dimer levels or blood cell counts, especially in women.

Objective To investigate the frequency and clinical characteristics of ischemic stroke patients with early seizures, especially with cortical involvement contralateral to their focal seizures. Methods We retrospectively studied patients with ischemic stroke admitted to our hospital. We compared the clinical characteristics of patients with and without early seizures (occurring within seven days of the stroke onset). In addition, we divided the patients with early focal seizures into two groups (patients with and without cortical involvement of a recent infarct contralateral to their focal seizure) and compared the clinical characteristics of the groups. Results Of the 5,806 patients with ischemic stroke, 65 (1.2%) were diagnosed with early seizures. A history of ischemic stroke (odds ratio [OR] 1.71), a history of seizures (OR 27.58), and a National Institutes of Health Stroke Scale score on admission (OR 1.07) were significant and independent factors associated with the presence of early seizures. Of these 65 patients, 56 had focal seizures, while the others had generalized or undetermined seizures. Cortical involvement of a recent infarct contralateral to their focal seizures was observed in 24 of these 56 patients (43%). Glucose and hemoglobin A1c levels were significantly higher in patients with cortical involvement of a recent infarct contralateral to their focal seizures than in those with infarcts in other regions. Conclusion These findings suggest that recent infarcts play a role as systemic causes of acute symptomatic seizures as well as an epileptogenic lesion in ischemic stroke patients with early focal seizures.

Antiosteoclastogenic-guided screening was conducted with 120 extracts of the medicinal plants collected in Egypt that led to the selection of Artemisia judaica L. (Asteraceae). Three undescribed davanone-related terpenoids, arteperoxides A-C, were isolated from the extract with two known derivatives, hydroxydavanone and davana acid. Structural analysis revealed that arteperoxides A-C were tris-normonoterpene-sesquiterpene conjugates with peroxide bridges. Although davanone derivatives with peroxides, such as a hydroperoxyl and peroxyhemiketal groups, have been isolated from Artemisia species, arteperoxides A-C are the first variations observed to contain peroxide bridges between two terpene-derived units. The absolute configurations of arteperoxides A and B were studied based on their spectroscopic data compared with those of the semisynthetic analogs that have ether linkages. The natural and synthetic compounds were tested for the antiosteoclastogenic activity, and arteperoxide C and hydroxydavanone were more potent than other compounds at 20 μM.

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by non-enzymatic reaction between reducing-sugar and Arg/Lys in proteins and are involved in various diabetic complications. GA-pyridine is derived from glycolaldehyde and is one of the most cytotoxic AGEs. Here, we established a single-chain Fv (scFv) antibody against GA-pyridine, 73MuL9-scFv, and examined the details of its specificity and antigen recognition by using various techniques involving biophysics, chemical biology and structural biology. We also synthesized several compounds that differ slightly in regard to the position and number of GA-pyridine substituent groups, and revealed that GA-pyridine was specifically bound to 73MuL9-scFv. Thermodynamic analysis revealed that the association of GA-pyridine to 73MuL9-scFv was an exothermic and enthalpy driven reaction, and thus that the antigen recognition involved multiple specific interactions. Crystallographic analysis of the Fv fragment of 73MuL9-scFv revealed that several CH-π and hydrogen bond interactions took place between the Fv-fragment and GA-pyridine, which was consistent with the results of thermodynamic analysis. Further studies using 73MuL9-scFv as a tool to clarify the relevance of GA-pyridine to diabetic complications are warranted.

Aphasia induced by an infratentorial stroke has rarely been reported, and its mechanism has not been fully identified. We evaluated two individuals who had been admitted to Saiseikai Kumamoto Hospital in Kumamoto, Japan, due to acute ischemic stroke in order to determine whether their aphasia was induced by an infratentorial stroke. The first patient, a 59-year-old man with a history of left parietal embolic stroke with very mild sequelae of anomia, developed Wernicke's aphasia, nonfluent speech, and right limb ataxia as a result of the stroke. The second patient, a 76-year-old woman with a history of chronic renal failure, experienced transcortical sensory aphasia and right one-and-a-half syndrome as a result of the stroke. Both patients' recent ischemic lesions were limited to the right cerebellar hemisphere and the right medial portion of the midbrain. However, SPECT showed low-uptake lesions in both patients' left cerebral hemisphere that did not include the recent ischemic lesions but that had spread to an extent that was difficult to be explained by the old or recent ischemic lesions and that might be responsible for their recent aphasia. We believe that the aphasia experienced by these two patients may have been caused by crossed cerebello-cerebral diaschisis.

To investigate the clinical characteristics of patients with ischemic stroke following the 2016 Kumamoto earthquake. We retrospectively studied patients with ischemic stroke admitted to 5 stroke centers for 1 year after the earthquake. We compared clinical characteristics in these patients (the post-earthquake group) to those in the patients with ischemic stroke admitted during the same period from the previous 3 years (the pre-earthquake group). Additionally, we analyzed the trend of the incidence rate of stroke before and after the earthquake. A total of 1979 patients were admitted after the earthquake; 5670 (1,890/year on average) patients were admitted before the earthquake. A first-ever ischemic stroke (71 vs. 75%) and premorbid modified Rankin Scale > 1 (26 vs. 29%) were found significantly more frequently in patients after the earthquake. National Institutes of Health Stroke Scale score ≤ 2 at discharge (60 vs. 65%) was found more frequently in patients after the earthquake, although non-discharge to home (65 vs. 70%) was more frequent in patients after the earthquake. Trend analysis revealed a decrease of small vessel occlusion and large artery atherosclerosis in the month after the earthquake. The 2016 Kumamoto earthquake may have affected the characteristics of stroke during the early phase of the earthquake and increased the difficulty in returning home.

Lymphomatoid gastropathy (LyGa)/natural killer (NK)-cell enteropathy (NKCE) is recognized as a benign NK-cell lymphoproliferative disease. Due to its histological similarity to NK/T cell lymphoma, it is easy to misdiagnose, leading to unnecessary chemotherapy and poor quality of life. This disease is typically observed in the small and large intestines in North America, whereas almost all cases in Japan occur locally in the stomach. Only 11 LyGa/NKCE cases involving both gastric and intestinal lesions have been reported, and there are few reports providing endoscopic images throughout the gastrointestinal tract. We report a case of LyGa/NKCE involving both the stomach and small and large intestines with detailed upper gastrointestinal endoscopy, colonoscopy, capsule endoscopy and pathology images. Its pathogenesis currently remains elusive, but most patients with LyGa/NKCE in Japan have Helicobacter pylori (H. pylori) infection. Our patient was also positive for H. pylori infection at disease onset, but after receiving eradication therapy, ulcerative lesions in both stomach and intestine regressed and no recurrence was observed. This case suggests a link between the pathogenesis of LyGa/NKCE and H. pylori infection.

Tremor-like movements in patients with the grasp phenomenon are reported rarely.We clinically and neuroradiologically studied four patients with tremor-like movements related to the grasp phenomenon.All of the patients were women aged between 61 and 98 years. In the present cases, tremor-like movements were observed in the right arm and/or leg. The movements occurred suddenly in three of the patients and chronically in one. The movements were stereotypic, often rhythmical, tremor-like, and accompanied with groping or picking-like movements. All of the patients displayed the grasp phenomenon, including grasp reflex and/or instinctive grasping reaction ipsilateral to the movements. Two patients had a recent broad infarct ipsilateral to the movements. One patient had meningioma contralateral to the movements, which had been surgically resected. The other patient did not have any radiologically proven cerebral lesions, although she had a history of focal seizures contralateral to the movements.It was suggested that their abnormal movements were closely related to the grasp phenomenon. We concluded that their characteristic tremor-like movements, a "tremor-like grasp phenomenon," was a variation of the grasp phenomenon that was due to hyperexcitation of the frontal lobe contralateral to the movements.

Objective Limited data exist regarding the comparative detailed clinical characteristics of patients with ischemic stroke (IS)/transient ischemic attack (TIA) and intracerebral hemorrhage (ICH) receiving oral anticoagulants (OACs). Methods The prospective analysis of stroke patients taking oral anticoagulants (PASTA) registry, a multicenter registry of 1,043 stroke patients receiving OACs [vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulant (NOACs)] across 25 medical institutions throughout Japan, was used. Univariate and multivariable analyses were used to analyze differences in clinical characteristics between IS/TIA and ICH patients with atrial fibrillation (AF) who were registered in the PASTA registry. Results There was no significant differences in cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, or alcohol consumption (all p0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p0.0001] were independently associated with ICH, and high brain natriuretic peptide/N-terminal pro B-type natriuretic peptide levels (OR, 1.89; p=0.0390) were independently associated with IS/TIA among NOAC users. A history of ICH (OR, 13.59; p=0.0279) and the high prothrombin time-international normalized ratio (PT-INR) (OR, 1.17; p0.0001) were independently associated with ICH, and a history of IS/TIA (OR, 3.37; 95% CI, 1.34-8.49; p=0.0101) and high D-dimer levels (OR, 2.47; 95% CI, 1.05-5.82; p=0.0377) were independently associated with IS/TIA among VKA users. Conclusion The presence of CMBs, a history of stroke, natriuretic peptide and D-dimer levels, and PT-INR may be useful for risk stratification of either IS/TIA or ICH development in patients with AF receiving OACs.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. The inflammatory activation of microglia participates in dopaminergic neurodegeneration in PD. Therefore, chemicals that inhibit microglial activation are considered to have therapeutic potential for PD. Aromatic (ar)-turmerone is a main component of turmeric oil extracted from Curcuma longa and has anti-inflammatory activity in cultured microglia. The aims of the present study are (1) to investigate whether naturally occurring S-enantiomer of ar-turmerone (S-Tur) protects dopaminergic neurons in midbrain slice cultures and (2) to examine ar-turmerone analogs that have higher activities than S-Tur in inhibiting microglial activation and protecting dopaminergic neurons. R-enantiomer (R-Tur) and two analogs showed slightly higher anti-inflammatory effects in microglial BV2 cells. S- and R-Tur and these two analogs reversed dopaminergic neurodegeneration triggered by microglial activation in midbrain slice cultures. Unexpectedly, this neuroprotection was independent of the inhibition of microglial activation. Additionally, two analogs more potently inhibited dopaminergic neurodegeneration triggered by a neurotoxin, 1-methyl-4-phenylpyridinium, than S-Tur. Taken together, we identified two ar-turmerone analogs that directly and potently protected dopaminergic neurons. An investigation using dopaminergic neuronal precursor cells suggested the possible involvement of nuclear factor erythroid 2-related factor 2 in this neuroprotection.

Nonconvulsive status epilepticus with neuropsychological symptoms other than aphasia or amnesia is rare. We report two such cases. Case 1, a 62-year-old man with a history of a subcortical hemorrhage in the right lateral temporal lobe and a brain infarct in the left medial temporo-occipital lobes, suddenly developed left unilateral spatial neglect and visual object agnosia. Diffusion-weighted imaging indicated status epilepticus, not stroke. His deficits resolved immediately after treatment with diazepam and phenytoin sodium. Case 2, a 61-year-old man with a history of brain infarcts in the right lateral temporal and left medial temporo-occipital lobes, suddenly developed global aphasia and cortical deafness. An MRI revealed no new lesions, including infarcts. An EEG revealed lateralized periodic discharges in the left temporo-parieto-occipital area, and single-photon emission computed tomography revealed a transient high-uptake lesion in the left temporoparietal lobes, indicating status epilepticus. His deficits also resolved immediately after treatment with diazepam and phenytoin sodium. The two patients' neuropsychological symptoms-visual object agnosia and cortical deafness-were associated with focal nonconvulsive status epilepticus and were successfully treated with anti-epileptic medications. It is suggested that individuals with acute neuropsychological symptoms be diagnosed with MRI and/or EEG as well as CT for differential diagnoses other than cerebrovascular diseases.

Objective Patients with neurological diseases are liable to develop deep venous thrombosis (DVT) due to various factors. We investigated the prevalence, related factors, and prognosis of DVT in patients with neurological diseases. Methods Patients admitted to four hospitals due to neurological diseases were prospectively recruited. Those with cerebrovascular diseases were excluded. To screen for DVT, ultrasonography was performed in patients with possible DVT risk, such as D-dimer > 1.0 µg/dL, recent surgery, active malignant diseases, recent bone fracture, decreased activity, or treatment with immunoglobulin or steroid therapy. Clinical characteristics were compared between patients with and without DVT. Results A total of 106 patients (54 women, median 71 years old) were included. DVT was detected in 27 patients (26.0%) at the first assessment. All had DVT only in the calf; encephalopathy/meningitis (n = 4, 40.0%) had the highest prevalence of DVT among the underlying neurological diseases, followed by parkinsonian syndrome (n = 6, 37.5%). Independent predictors for DVT detection were malignant diseases (odds ratio, 11.7; 95% confidence interval, 1.0–301.4), modified Rankin Scale score ≥ 4 (5.4; 1.9–16.6), and D-dimer ≥ 2.0 µg/dL (5.7; 2.1–16.7). Ten patients were treated with anticoagulants, and no patients developed a symptomatic pulmonary embolism. No clinically evident pulmonary embolisms, systemic embolisms, or severe bleeding complications were observed in patients with DVT. Conclusions Asymptomatic DVT is not rare in patients with neurological diseases, especially in those with malignancy, decreased activity, or elevated D-dimer. The overall prognosis is favorable, but the potential risk of development of a pulmonary embolism should be recognized.

Background Stroke severity can be mitigated by preceding anticoagulant administration in acute ischemic stroke patients with atrial fibrillation (AF). We investigated if such mitigative effects are different between warfarin and direct oral anticoagulants (DOACs). Material and methods We collected data from a regional multicenter stroke registry. Ischemic stroke or transient ischemic attack patients with AF were included. Background characteristics, National Institutes of Health Stroke Scale (NIHSS) score on admission, lesion characteristics, and in-hospital death were analyzed according to preceding antithrombotic agents at onset. Results A total of 2173 patients had AF; 628 were prescribed warfarin, 272 DOACs, 429 antiplatelets alone, and 844 no antithrombotics. The NIHSS score on admission was lowest in the DOACs group compared to the other groups. In neuroimaging analysis, small ischemic lesions were observed more frequently in the DOACs group, while large ischemic lesions were less frequent in this group. When the no antithrombotics group was used as a reference, the adjusted odds ratio for moderate to severe stroke was 0.56 (95% confidence interval, 0.40–0.78) in the DOACs group, while it was 0.98 (0.77–1.24) in the warfarin group and 0.94 (0.72–1.22) in the antiplatelets group. In-hospital mortality was lowest in the DOACs group compared to the other groups. Conclusion Preceding DOAC administration might mitigate the severity of stroke in AF patients more strongly than other antithrombotics, possibly leading to a better outcome in patients with stroke.

The first catalytic enantioselective aldol reaction of various unprotected carboxylic acids is described. In the presence of a chiral bis(phosphine oxide) as a Lewis base catalyst, carboxylic acids were activated with silicon tetrachloride to form the corresponding bis(trichlorosilyl)enediolates in situ, which subsequently underwent an aldol reaction with an aldehyde or a ketone to produce β-hydroxycarboxylic acids in high enantioselectivities of up to 92 % ee.

Purpose To investigate the clinical characteristics of patients with seizure following the 2016 Kumamoto earthquake. Methods We retrospectively studied patients with seizure admitted to our hospital for 12 weeks following the earthquake. We compared the clinical backgrounds and characteristics of the patients: before (the same period from the previous 3 years) and after the earthquake; and the early (first 2 weeks) and late (subsequent 10 weeks) phases. Results A total of 60 patients with seizure were admitted to the emergency room after the earthquake, and 175 (58.3/year) patients were admitted before the earthquake. Of them, 35 patients with seizure were hospitalized in the Department of Neurology after the earthquake, and 96 (32/year) patients were hospitalized before the earthquake. In patients after the earthquake, males and non-cerebrovascular diseases as an epileptogenic disease were seen more frequently than before the earthquake. During the early phase after the earthquake, female, first-attack, and non-focal-type patients were seen more frequently than during the late phase after the earthquake. Conclusions These characteristics of patients with seizure during the early phase after the earthquake suggest that many patients had non-epileptic seizures. To prevent seizures following earthquakes, mental stress and physical status of evacuees must be assessed.

The Michael reaction of malonates with maleates afforded the corresponding adducts in high yields with high enantioselectivities (up to 98% enantiomeric excess (ee)) by using dilithium 3,3'-dichlorobinaphtholate as a catalyst. The obtained Michael adducts could be converted to optically active tricarboxylic acid (TCA) derivatives via the Krapcho reaction.

Background After previous earthquakes, a high prevalence of deep vein thrombosis (DVT) has been reported. We examined DVT prevalence and risk factors in evacuees of the Kumamoto earthquakes by performing mobile DVT screening at various evacuation centers around the epicenter. Methods and Results: For 1 month after the Kumamoto earthquake on 14 April 2016, mobile DVT screening using portable ultrasonography (US) was performed at 80 evacuation centers. Questionnaires, physical examination, and US of the lower limb were carried out, and simple D-dimer measurements were undertaken for DVT-positive examinees. The total number of examinees was 1,673, of whom 178 (10.6%) had DVT. The prevalence of DVT seemed to be gradually decreasing in the screening period, but age, use of sleep medication, prevalence of hypertension, dyslipidemia, leg edema, and lower leg varix were significantly higher in the DVT positive group than in the negative group. On multivariable logistic regression analysis, high age (≥70 years old), use of sleep medication, lower leg edema, and lower leg varix were significant predictors of DVT. In examinees with these 4 predictors, the DVT positive rate was 71.4%. Conclusions In the first month after the Kumamoto earthquakes, DVT prevalence and severity, evaluated on D-dimer level, decreased with the passage of time. Mobile DVT screening indicated significant factors stratifying DVT risk in the evacuees.

Chiral phosphine oxide sequentially activates silicon tetrachloride and trichlorosilyl enol ethers to facilitate asymmetric aldol/vinylogous aldol reaction of 4-methoxy-3-penten-2-one and conjugated aldehydes in a highly enantioselective fashion, and the subsequent cyclization produced optically active 2,6-disubstituted 2,3-dihydro-4-pyranones bearing stereogenic centers at a remote position in a single operation.

A 52-year-old woman suddenly presented with right conjugate eye deviation, anarthria and quadriplegia, and appeared to be in a deep coma. MRI revealed a new infarct in the left cerebellar hemisphere and stenosis in the distal portion of the basilar artery caused by arterial dissection. Her deficits improved within 6 hours of onset. Moreover, on day 1, she described that she had been alert and her vision, hearing and somatic sensation had been preserved during the illness. Total locked-in syndrome should be considered while assessing patients with total immobility who are unable to communicate.

Accelerated atherosclerosis of intra- or extracranial large arteries is a major cause of radiation-induced strokes. Recent development of MRI techniques has enabled detection of another important vasculopathy: microinfarcts or microbleeds after cranial irradiation. The purpose of this study was to investigate the incidence and characteristics of small vessel disease after cranial irradiation. MR images and clinical records of 102 outpatients who had undergone cranial irradiation to brain tumors were retrospectively reviewed. Only those who had undergone T1WI, T2WI, FLAIR, and T2∗WI during follow-up were included. Small vessel disease including small subcortical infracts, microbleeds, and volume of white matter lesions were assessed on the latest MR images of each patient. Ischemic or hemorrhagic stroke during the follow-up period was also reviewed. Twelve patients (mean age at the latest MRI, 38.5years; 8men) were assessed. The total radiation dose was 52.3±9.7Gy in these patients, 9 of whom received whole brain irradiation. Small subcortical infarcts (mean 2.3) were detected in 8 patients, microbleeds (mean 19.4) were detected in 11, and white matter lesion volume was 38.3±11.6ml. During the follow-up period of 19.8±9.7years, 5 patients experienced stroke (4 lacunar, 1 hemorrhagic). These strokes occurred as long as a median 21.9 (range, 10.4-30.2) years after cranial irradiation. In conclusion, small vessel disease is not a rare complication after cranial irradiation, even in young patients. Patients after cranial irradiation should be followed up with MR imaging including a hemosiderin-sensitive sequence.

Reports of involuntary ipsilateral movements after a stroke are rare, and none have described a patient with both an instinctive grasp reaction and tremor-like movement ipsilateral to the acute stroke lesion. We here report such a patient. A 76-year-old right-handed woman with a past history of left thalamic hemorrhage developed left hemiparesis, an instinctive grasp reaction, and a peculiar involuntary movement of her right arm. This involuntary movement was stereotyped and sometimes rhythmical, with a groping or picking-like action. The lesion responsible for her motor deficits was a broad infarct in the right internal carotid artery territory. We suggest that her characteristic involuntary tremor-like movement was a variation of the instinctive grasp reaction caused by an ipsilateral ischemic lesion that included the frontal lobe. We illustrate her movements with a video, Supplemental Digital Content 1, http://links.lww.com/CBN/A65.

We herein present the cases of two patients with multiple ischemic events, presumably due to varying degrees of middle cerebral artery (MCA) stenosis. The first patient was treated medically, and the symptoms and degree of MCA stenosis varied over several months. The second patient received emergent bypass surgery and experienced no further events, although the MCA stenosis progressed over four months. Emergent intracranial bypass surgery is an option for preventing further ischemic events in patients with symptomatic MCA stenosis.

To investigate the clinical characteristics of patients with ischemic stroke following the 2016 Kumamoto earthquake. We retrospectively studied patients with ischemic stroke admitted to our hospital for 12weeks following the earthquake. We compared the clinical backgrounds and characteristics of the patients: before (the same period from the previous 3years) and after the earthquake; and the early (first 2weeks) and late (subsequent 10weeks) phases. A total of 194 patients with ischemic stroke were admitted to our hospital after the earthquake; 496 (165.3/year) patients were admitted before the earthquake. No differences between the two groups were noted for the clinical backgrounds, characteristics, or biomarkers. Past history of sleeping in a shelter or small vehicle was found in 13% and 28% of patients, respectively. Sleeping in a shelter (27% vs. 10%, p=0.013) was found more frequently in patients during the early phase than during the late phase after the earthquake. Admission of patients with ischemic stroke increased after the earthquake; however no differences between before and after the earthquake were noted for their clinical characteristics. To prevent ischemic stroke following earthquakes, mental stress and physical status of evacuees must be assessed.

The synthesis of optically active α,α-disubstituted amino acid derivatives is achieved through asymmetric amination of β-keto esters with azidodicarboxylates using a chiral lithium binaphtholate derived from BBI as catalyst.

By using a phosphine oxide-catalyzed enantioselective double aldol reaction, we achieved the concise construction of C2 -symmetric 1,9-diarylnonanoids, enabling the synthesis of (-)-ericanone from p-hydroxybenzaldehyde in 6 steps with 65 % overall yield. The enantioselective double aldol reaction is useful for establishing C2 -symmetric 1,9-diaryl-3,7-dihydroxy-5-nonanones with a single operation. Furthermore, the use of o-nosyl-protected p-hydroxybenzaldehyde and a 4,4'-disubstituted BINAP dioxide catalyst dramatically improved the reactivity and selectivity in the double aldol reaction, enabling the total synthesis of (-)-ericanone with high yield and with excellent enantiopurity.

The enantioselective addition of Grignard reagents to ketones was promoted by a BINOL derivative bearing alkyl chains at the 3,3′-positions. This is the first asymmetric direct aryl Grignard addition to ketones reported to date. A variety of tertiary diaryl alcohols could be obtained in high yields and enantioselectivities without using any other metal source.

2,3-Dihydro-4-pyranones were synthesized stereoselectively using a chiral phosphine oxide as the catalyst. The phosphine oxide sequentially activated silicon tetrachloride and promoted the double aldol reaction of 4-methoxy-3-buten-2-one with aldehydes. Subsequent stereoselective cyclization afforded the corresponding highly functionalized 2,3-dihydro-4-pyranones bearing three contiguous chiral centers in good yields and with high diastereo- and enantioselectivities.

Diffusion-weighted imaging can depict secondary signal changes of the substantia nigra in patients with ipsilateral striatal infarction. We report four patients who demonstrated obvious signal changes of the substantia nigra in the subacute phase of stroke. Embolic stroke was diagnosed in all of the cases, and none of the patients presented clinical deterioration in their course. Embolic mechanism might be more closely related to the secondary change of the substantia nigra than thrombosis. The relationship between secondary nigral degeneration and stroke etiology or between the nigral lesions and recanalization of the middle cerebral artery remains unclear.

A 60-year old man with a 10-year history of multiple system atrophy (MSA) was found in respiratory arrest. After 4 months of respiratory support with two episodes of septic shock, he died. Autopsy disclosed severe atrophy of the mesencephalon, brainstem, medulla oblongata and cerebellum. Gallyas-Braak, alpha-synuclein and ubiquitin-positive inclusions in the cytoplasm of glial cells were evident, despite the severe ischaemic damage due to respiratory arrest and subsequent respiratory support for 4 months. The cause of respiratory arrest was not identified, but could be explained by the natural history of MSA. The bereaved family, who had suspected malpractice, was satisfied with the explanation based on the investigation performed by eight expert doctors, one expert nurse, two coordinator nurses and two lawyers in the model project promoted by the Japanese government.

Forensic pathologists often hesitate to use biochemical blood markers due to the risk of large postmortem changes and deviations from healthy subjects. Biochemical analyses of postmortem blood, if possible, may help to evaluate pathological status and determining the cause of death in forensic diagnosis, for example, in sudden unexpected death without obvious cause, or young adults with no apparent cause of death or antemortem information. Even commercially available biochemical markers were re-evaluated in the blood samples of 164 forensic autopsy cases. Biochemical markers examined were HbA1c, fructosamine, blood nitrogen urea (BUN), creatinine, total protein, total bilirubin, gamma-glutamyl transpeptidase (gamma-GTP), triglyceride, total cholesterol, C-reactive protein (CRP) and pseudocholine esterase (pChE). We collected cardiac blood (left cardiac blood and right cardiac blood) and peripheral blood (femoral vein blood) to clarify the differences in measured values by sampling site. The measured values were analyzed in relation to postmortem interval, etiology of death and sampling sites. Of all eleven markers, HbA1c is the most useful and reliable because of its negligible postmortem changes and small deviation from healthy subjects. Total bilirubin, BUN, CRP and total cholesterol can be useful if we set appropriate limit ranges and pay attention to the interpretation. For the evaluation of changes due to postmortem intervals, none of the markers except for triglyceride showed significant changes up to three days postmortem. As for sampling sites, femoral vein blood is generally recommended considering postmortem changes, but left cardiac blood was suitable for creatinine, pChE, and total cholesterol. For clinical forensic diagnosis of biochemical blood markers, we must determine the "forensic abnormal value" after collecting more cases by known causes with more information about the population.

2,3-Dihydro-4-pyranones were synthesized stereoselectively using a chiral phosphine oxide as the catalyst. The phosphine oxide sequentially activated silicon tetrachloride and promoted the double aldol reaction of 4-methoxy-3-buten-2-one with aldehydes. Subsequent stereoselective cyclization afforded the corresponding highly functionalized 2,3-dihydro-4-pyranones bearing three contiguous chiral centers in good yields and with high diastereo- and enantioselectivities.

Among 4 cyanoamines tested, the derivative (II) bearing 2 cyclohexyl groups is found to be the most efficient agent.

TiCl4-promoted aldol reaction of ketones as aldol acceptors followed by elimination of the titanoxy group from the Ti-aldolates affords β,β-disubstituted α,β-unsaturated carbonyl compounds in a one-pot procedure. The use of additives, such as DMF, N,N,N',N'-tetramethylethylenediamine, and pyridine, in the elimination step was found to be important.

A 78-year-old man with Parkinson's disease, paroxysmal atrial fibrillation, and congestive heart failure was admitted to our hospital due to global aphasia and right-sided hemiparesis. A cardioembolic stroke from a left ventricular thrombus was diagnosed; several days later, anticoagulants were started. On the seventh day, the patient suddenly developed severe acidosis and kidney and liver dysfunction. He died the following afternoon. Autopsy revealed an isolated celiac artery embolism from the left ventricular thrombus. This is the first reported case of isolated celiac artery embolism occurring after acute ischemic stroke.

A tartaric acid derivative catalyzes the conjugate addition of diboron (III) to α,β-unsaturated ketones with moderate to good enantioselectivities.

Asymmetric Michael addition of acyclic α-alkyl-β-keto esters with vinyl ketones catalyzed by a chiral lithium binaphtholate is described.

The enantioselective addition of styrylboronic acid (II) to symmetrical and unsymmetrical dienones, catalyzed by O-monoacyltartaric acid, affords monostyrylated adducts [ct.

The development of catalytic enantioselective reactions is a challenging area in synthetic organic chemistry. In the last decade, numerous chiral metal complexes, which act as Lewis acids, have been very successful. However, Lewis base catalyzed asymmetric reactions are also attracting attention. Recent developments in silicon-based chemistry have led to new asymmetric reactions, which involve so-called hypervalent silicates as intermediates, wherein new types of organocatalysts are often utilized as promoters. This review presents the progress in silicate-mediated asymmetric reactions catalyzed by chiral Lewis bases, particularly those based on various types of silicon compounds.

Coronary artery occlusion increased the TNF alpha level in the membrane fraction of the rat heart, almost maximally at 30 min. TNF alpha immunofluorescence labeled streak-like reticular structures inside of the cardiomyocyte but not vascular or interstitial cells in myocardial ischemia. Immuno-electron microscopy confirmed the localization of TNF alpha between myofibrils, mitochondria, or other membrane structures in the ischemic cardiomyocyte. Ischemic preconditioning (IP) is the protection of myocardium conferred by cycles of brief ischemia-reperfusion. The increases in TNF alpha production, as well as phosphorylation of p38 MAP kinase and S6 kinase after ischemia were inhibited by IP or p38 MAP kinase inhibitors (SB203580, FR167653). TNF alpha production appeared to be regulated possibly at the post-transcriptional step by ribosomal S6 phosphorylation given that IP did not suppress TNF alpha mRNA up-regulation and was independent of NFkappaB activation. Electron microscopy (EM) showed mitochondria damage in ischemic cardiomyocyte, which was inhibited either by IP or SB203580. This is the first demonstration of the TNF alpha up-regulation in membrane structures of ischemic cardiomyocyte through p38 MAP kinase-mediated post-transcriptional mechanism, in association with mitochondrial damage.

Objective – Acute stroke patients with dysphagia are usually fed by nasogastric tube. However, this method sometimes causes pneumonia or diarrhea. We investigated the use of a new feeding procedure called intermittent oro-esophageal (IOE) tube feeding in acute stroke patients with severe dysphagia. Materials and methods – The IOE method was used in 13 acute stroke patients (68 ± 14 years old; 12 had a brainstem infarction), who were alert, but had severe dysphagia and a weak pharyngeal reflex. IOE tube feeding was carried out as follows. A feeding tube was passed orally into the lower portion of the esophagus, food supplements were administered through the tube at a rate of approximately 50 ml/min, and the tube was removed after finishing the supplement infusion. Results – We found that the IOE method had the following advantages: (i) IOE feeding took approximately 15 min; (ii) potentially reduced a risk of complications such as pneumonia and diarrhea; and (iii) oral tube insertion stimulated the oral cavity and pharynx, which may improve the swallowing function. However, the IOE feeding method should not be used in patients who: (i) could not understand the IOE procedure; (ii) had an esophageal hiatal hernia or incomplete peristalsis of the esophagus, as such patients are at risk of having the supplement reflux into the oral cavity. Conclusion – The IOE feeding method may be one of the alternatives to continuous nasogastric tube feeding in acute stroke patients with severe dysphagia, who are alert.

The link between endothelial nitric oxide synthase (eNOS) activation and vascular diameter during ischemia-reperfusion was investigated in the rat heart. After short (30 min) and long (45 min) time of ischemia conferred by coronary artery occlusion of the rats, reperfusion caused dilatation and constriction of arterioles, respectively. Partial oxygen pressure (pO2) measurement of the heart by the electrode confirmed the hyper-perfusion and no-reflow phenomena during reperfusion, as well as myocardial ischemia. The vascular diameter was correlated with phosphorylation of Akt and serine 1177 residue of eNOS, and formation of NO-bound guanylate cyclase (GC) by immuoflorescence study. Western blotting confirmed the phosphorylation of eNOS-Ser1177 depending on ischemia time. The constriction during reperfusion after 45 min of ischemia is supposedly caused by the inhibition of Akt-mediated eNOS-Ser1177 phosphorylation, which was suppressed by a PKC inhibitor chelerythrine, or ROS scavengers N-2-mercaptopropionyl glycine (MPG) and 4,5-Dihydroxy-1, 3-benzenedisulfonic acid disodium salt (Tiron). However, an endothelin receptor antagonist BQ123 alleviated the vasoconstriction by increasing NO availability but not eNOS-Ser1177 phosphorylation. Thus, vascular patency is correlated with eNOS-Ser1177 phosphorylation in association with ROS, and PKC during reperfusion. Endothelin inhibits vasodilatation by reducing NO availability during reperfusion.

A catalytic, enantioselective Michael addition of β-keto esters to α,β-unsaturated carbonyl compounds was achieved by using a chiral biquinoline N , N ′-dioxide–scandium trifluoromethanesulfonate complex as a catalyst. The corresponding Michael adducts were obtained in high yields and with enantioselectivities up to 84% ee.

Objective The aim of this study was to clarify the characteristics of transient ischemic attack (TIA) patients with atrial fibrillation (AF) compared to those without. Methods We divided 67 TIA patients with left hemispheric involvement into two groups; patients with AF (AF group) and without AF (Non-AF group) and compared the clinical characteristics between the two groups. Patients AF group included 12 patients (73.0±9.7 years old) and the Non-AF group 55 patients (64.1±9.8 years old). Results Clinically, arterial disease was less frequently seen in the AF group than in the Non-AF group (17% vs 53%, p=0.028). No significant differences were observed between the two groups in the duration (

The phosphine oxide-catalyzed asymmetric intramolecular aldol reactions of diketones were investigated. The combination of tetrachlorosilane and a chiral phosphine oxide catalyst promoted the acetyl-selective enolization of diketones, and the subsequent intramolecular aldol reaction occurred in an enantioselective manner. The introduction of two trimethylsilyl groups at the 4- and 4′-positions in BINAP dioxide catalyst improved the enantioselectivity. This reaction provides an effective synthetic method to access β-tertiary-hydroxy cyclohexanones in high yields and with high enantioselectivity.