Synthesis of Dithia[5]helicenes and Enantioselective Synthesis of Helically Chiral Thia[6]helicenes via Rh-Catalyzed Intramolecular [2 + 2 + 2] Cycloaddition of Triynes.

Dithia[5]helicenes and helically chiral thia[6]helicenes were synthesized in high yields via a cationic Rh-catalyzed intramolecular [2 + 2 + 2] cycloaddition of triynes bearing sulfur-containing 1,6-diynes. Thia[6]helicene could be obtained with a high enantiomeric excess of P-isomers by using (S)-SEGPHOS as a chiral ligand. This protocol is the first example of the synthesis of thiahelicenes via [2 + 2 + 2] cycloaddition and can also be used for the asymmetric construction of an aza[6]helical skeleton.

Consideration of the Intracranial Pressure Threshold Value for the Initiation of Traumatic Brain Injury Treatment: A Xenon CT and Perfusion CT Study.

BACKGROUND: Monitoring of intracranial pressure (ICP) is considered to be fundamental for the care of patients with severe traumatic brain injury (TBI) and is routinely used to direct medical and surgical therapy. Accordingly, some guidelines for the management of severe TBI recommend that treatment be initiated for ICP values >20 mmHg. However, it remained to be accounted whether there is a scientific basis to this instruction. The purpose of the present study was to clarify whether the basis of ICP values >20 mmHg is appropriate. SUBJECT AND METHODS: We retrospectively reviewed 25 patients with severe TBI who underwent neuroimaging during ICP monitoring within the first 7 days. We measured cerebral blood flow (CBF), mean transit time (MTT), cerebral blood volume (CBV), and ICP 71 times within the first 7 days. RESULTS: Although the CBF, MTT, and CBV values were not correlated with the ICP value at ICP values ≤20 mmHg, the CBF value was significantly negatively correlated with the ICP value (r = -0.381, P < 0.05) at ICP values >20 mmHg. The MTT value was also significantly positively correlated with the ICP value (r = 0.638, P < 0.05) at ICP values >20 mmHg. CONCLUSION: The cerebral circulation disturbance increased with the ICP value. We demonstrated the cerebral circulation disturbance at ICP values >20 mmHg. This study suggests that an ICP >20 mmHg is the threshold to initiate treatments. An active treatment intervention would be required for severe TBI when the ICP was >20 mmHg.

Early Cerebral Circulation Disturbance in Patients Suffering from Severe Traumatic Brain Injury (TBI): A Xenon CT and Perfusion CT Study.

Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). Ischemia is a common and deleterious secondary injury following TBI. Detecting early ischemia in TBI patients is important to prevent further advancement and deterioration of the brain tissue. The purpose of this study was to clarify the cerebral circulatory disturbance during the early phase and whether it can be used to predict patient outcome. A total of 90 patients with TBI underwent a xenon-computed tomography (Xe-CT) and subsequently perfusion CT to evaluate the cerebral circulation on days 1-3. We measured CBF using Xe-CT and mean transit time (MTT: the width between two inflection points [maximum upward slope and maximum downward slope from inflow to outflow of the contrast agent]) using perfusion CT and calculated the cerebral blood volume (CBV) using the AZ-7000W98 computer system. The relationships of the hemodynamic parameters CBF, MTT, and CBV to the Glasgow Coma Scale (GCS) score and the Glasgow Outcome Scale (GOS) score were examined. There were no significant differences in CBF, MTT, and CBV among GCS3-4, GCS5-6, and GCS7-8 groups. The patients with a favorable outcome (GR and MD) had significantly higher CBF and lower MTT than those with an unfavorable one (SD, VS, or D). The discriminant analysis of these parameters could predict patient outcome with a probability of 70.6%. During the early phase, CBF reduction and MTT prolongation might influence the clinical outcome of TBI. These parameters are helpful for evaluating the severity of cerebral circulatory disturbance and predicting the outcome of TBI patients.

Effect of ninjin'yoeito, a Kampo (traditional Japanese) medicine, on cognitive impairment and depression in patients with Alzheimer's disease: 2 years of observation.

BACKGROUND: Only a few approved drugs are capable of alleviating the cognitive and behavioural symptoms of people living with Alzheimer's disease (AD). In recent years, however, the number of studies examining the clinical effects of herbal medicines on cognitive function in patients with AD has increased considerably. This study evaluated the long-term effects of a traditional Japanese medicine (Kampo medicine) known as ninjin'yoeito (NYT) on cognitive impairment and mood status in patients with AD over a 2-year period. METHODS: Twenty-three patients with mild-to-moderate probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria were included. Each participant had exhibited an insufficient response to treatment with donepezil alone before the start of the trial. Eleven patients received treatment with donepezil alone, and the remaining patients received a combined treatment of donepezil and NYT for 2 years. Patients were assessed by the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version for cognitive function, and the Neuropsychiatric Inventory was used to evaluate the patients' mood status at baseline and every 6 months for 2 years. RESULTS: The Mini-Mental State Examination results showed no significant differences between the two groups. Significant improvements were observed on the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version and the Neuropsychiatric Inventory depression scores of patients who received the combined therapy with donepezil and NYT (Alzheimer's Disease Assessment Scale-cognitive component-Japanese version, 12 months: P < 0.01, 18 months: P = 0.04, 24 months: P < 0.01; Neuropsychiatric Inventory depression, 6 months: P < 0.05, 24 months: P < 0.05). CONCLUSIONS: A 2-year follow-up of patients receiving donepezil and NYT treatment showed an improved cognitive outcome and alleviation of AD-related depression.

Early cerebral circulation disturbance in patients suffering from different types of severe traumatic brain injury: a xenon CT and perfusion CT study.

INTRODUCTION: Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). In particular, secondary brain insults have been reported to decrease CBF. The purpose of this study was to clarify the cerebral circulation in different types of TBI. METHODS: Sixty-nine patients with TBI were divided into four groups, the subdural hematoma group, the contusion/intracerebral hematoma group, the diffuse axonal injury group, and the diffuse brain swelling group. In these patients, we simultaneously performed Xe-CT and perfusion CT to evaluate the cerebral circulation on post-injury days 1-3. We measured CBF using Xe-CT and mean transit time using perfusion CT and calculated the cerebral blood volume using the AZ-7000 W98 computer system. RESULTS: There were no significant differences in the Glasgow Coma Scale score on arrival or the Glasgow Outcome Scale score between the groups. The patients who had suffered focal TBI displayed more significant cerebral circulation disturbances than those that had suffered diffuse TBI. We were able to evaluate the cerebral circulation of TBI patients using these parameters. CONCLUSION: Moderate hypothermia therapy, which decreases CBF, the cerebral metabolic rate oxygen consumption (CMRO2), and intracranial pressure might be effective against the types of TBI accompanied by cerebral circulation disturbance. We have to use all possible measures including hypothermia therapy to treat severe TBI patients according to the type of TBI that they have suffered.

The study of systemic general circulation disturbance during the initiation of therapeutic hypothermia: Pit fall of hypothermia.

AIMS: Neurointensive care has reduced the mortality and improved the outcome of patients for severe brain damage, over recent decades, and made it possible to perform this therapy in safety. However, we have to understand the complications of this therapy well. The purpose of our study was to determine the systemic circulation disturbance during the initiation of therapeutic hypothermia by using this continuous neurointensive monitoring system. MATERIALS AND METHODS: Ten severe brain damage patients treated with hypothermia were enrolled. All patients had Glasgow Coma Scale (GCS) less than or equal to 8, on admission. RESULTS: We verified that heart rate, cardiac output, and oxygen delivery index (DO2I) decreased with decreasing core temperature. We recognized that depressed cardiac index (CI) was attributed to bradycardia, dehydration, and increased systemic vascular resistance index (SVRI) upon initiation of hypothermia. CONCLUSION: Although the hypothermia has a therapeutic role in severe brain damage patients, we have to carry out this therapy while maintaining their cardiac output using multimodality monitoring devices during hypothermia period.

Early cerebral circulatory disturbance in patients suffering subarachnoid hemorrhage prior to the delayed cerebral vasospasm stage: xenon computed tomography and perfusion computed tomography study.

Subarachnoid hemorrhage (SAH) causes dynamic changes in cerebral blood flow (CBF), and results in delayed ischemia due to vasospasm, and early perfusion deficits before delayed cerebral vasospasm (CVS). The present study examined the severity of cerebral circulatory disturbance during the early phase before delayed CVS and whether it can be used to predict patient outcome. A total of 94 patients with SAH underwent simultaneous xenon computed tomography (CT) and perfusion CT to evaluate cerebral circulation on Days 1-3. Cerebral blood flow (CBF) was measured using xenon CT and the mean transit time (MTT) using perfusion CT and calculated cerebral blood volume (CBV). Outcome was evaluated with the Glasgow Outcome Scale (good recovery [GR], moderate disability [MD], severe disability [SD], vegetative state [VS], or death [D]). Hunt and Hess (HH) grade II patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. HH grade III patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. Patients with favorable outcome (GR or MD) had significantly higher CBF and lower MTT than those with unfavorable outcome (SD, VS, or D). Discriminant analysis of these parameters could predict patient outcome with a probability of 74.5%. Higher HH grade on admission was associated with decreased CBF and CBV and prolonged MTT. CBF reduction and MTT prolongation before the onset of delayed CVS might influence the clinical outcome of SAH. These parameters are helpful for evaluating the severity of SAH and predicting the outcomes of SAH patients.