Maoto, a Traditional Japanese Herbal Medicine, Inhibits Uncoating of Influenza Virus.

We previously reported in randomized controlled trials that maoto, a traditional herbal medicine, showed clinical and virological efficacy for seasonal influenza. In this study, a culturing system for influenza was used to test the effect of maoto. A549 cells in the culture were infected with influenza virus A (PR8) and followed after treatment with maoto; the virus titers in the culture supernatant, intracellular viral proteins, and viral RNA were determined. When infected cells were cultured with maoto for 24 hr, the virus titer and protein were significantly reduced compared with medium only. Other subtypes, A/H3N2, H1N1pdm, and B, were also inhibited by maoto. Proliferation of viral RNA in a 6 hr culture was inhibited by maoto in the early phase, especially in the first 30 min. Focusing on the entry step of the influenza virus, we found that endosomal pH, regulated by vacuolar-type H+ ATPase (V-ATPase) located in the membrane, was increased when treated with maoto. We also found that uncoating of influenza viruses was also inhibited by maoto, resulting in the increase of the number of virus particles in endosomes. These results strongly suggest that the inhibition of endosomal acidification by maoto results in blocking influenza virus entry to cytoplasm, probably through the inhibition of V-ATPase. The present study provides evidence that supports the clinical use of maoto for the treatment of influenza.

Multiple thalamo-cortical disconnections in anterior thalamic infarction: implications for thalamic mechanisms of memory and language.

Amnesia and linguistic deficits that are associated with thalamic damage have attracted the attention of researchers interested in identifying the neural networks involved in memory and language. The Papez circuit, which is composed of the hippocampus, mammillary body and anterior thalamic nuclei, was first proposed to be critical for memory. However, subsequently, the roles of the neural circuit consisting of the rhinal/parahippocampal cortices and the mediodorsal thalamic nuclei became evident. The ventral lateral nuclei or its adjacent structures have been found to be involved in semantic processing, but the specific neural circuits dedicated to language functions have not been identified. Anterior thalamic infarcts, which affect very circumscribed regions of the ventral anterior portion of the thalamus, often cause paradoxically prominent memory and language deficits. We conducted tractography analyses in 6 patients with left anterior thalamic infarcts to identify neural connections or circuits in which disruptions are associated with memory and language deficits in this condition. The current study demonstrated that the mammillothalamic tract, which connects the mammillary body with the anterior thalamic nuclei, and the anterior and inferior thalamic peduncles, which contain neural fibers that extend from several thalamic nuclei to the anterior temporal, medial temporal and frontal cortices, are disrupted in anterior thalamic infarction. These extensive thalamo-cortical disconnections appear to be due to the dissection of the neural fibers that penetrate the ventral anterior nucleus of the thalamus. Our results suggest the following: (1) amnesia that is associated with anterior thalamic infarction is best interpreted in the context of dual/multiple-system theories of memory/amnesia that posit that multiple neural circuits connecting the anterior and mediodorsal thalamic nuclei with the hippocampus and rhinal/parahippocampal cortices work in concert to support memory function; and (2) the semantic deficits observed in this syndrome may be associated with thalamo-anterior temporal and thalamo-lateral frontal disconnections.

Correlation of right frontal hypoperfusion and urinary dysfunction in iNPH: a SPECT study.

OBJECTIVES: To elucidate the pathophysiology of urinary dysfunction in idiopathic normal-pressure hydrocephalus (iNPH) by single-photon emission computed tomography (SPECT) and statistical brain mapping. METHODS: Urinary symptoms were observed and N-isopropyl-p-[(123)I]-iodoamphetamine (IMP)-SPECT imaging was performed in 97 patients with clinico-radiologically definite iNPH. The patients included 56 men and 41 women; mean age, 74 years. The statistical difference in normalized mean tracer counts was calculated and visualized between patients with urinary dysfunction of severer degrees (>grade 2/4) and milder degrees (

Neuroanatomy of a neurobehavioral disturbance in the left anterior thalamic infarction.

BACKGROUND AND PURPOSE: Cognitive and behavioural symptoms represent primary clinical manifestations of anterior thalamic infarcts (ATIs) in the tuberothalamic artery territory. The aim of the study is to understand the pathomechanism of cognitive and behavioural disturbances in left ATI (LATI). METHODS: 6 patients with isolated LATIs were investigated using neuropsychological assessments, MRI stereotactic lesion localisation and positron emission tomography. RESULTS: The patients were characterised clinically by verbal memory impairment, language disturbances dominated by anomia and word-finding difficulty and apathy. The ventral anterior nucleus (VA) proper, magnocellular VA (VAmc), ventral lateral anterior nucleus (VLa), ventral lateral posterior nucleus (VLp) and mammillothalamic tract were involved in all patients. Compared with healthy controls, the regional cerebral blood flow was lower in the thalamus, the dorsolateral, medial and orbital frontal lobes, the anterior temporal lobe, the inferior parietal lobule and the occipital lobe of the left hemisphere. CONCLUSIONS: The authors propose that the Papez circuit disruption at the mammillothalamic tract and possibly thalamomedial temporal disconnection at the VA region is responsible for memory impairment and that the thalamo-anterior temporal disconnection is associated with language disturbance in LATI, respectively.

Voxel-based analysis of gray matter and CSF space in idiopathic normal pressure hydrocephalus.

AIMS: To investigate regional morphologic changes in idiopathic normal pressure hydrocephalus (INPH) based on diagnosis with INPH Guidelines using voxel-based morphometry. METHOD: Three-dimensional magnetic resonance imaging was performed in 34 INPH patients, who met probable INPH criteria, probable 34 Alzheimer disease patients, and 34 normal control subjects. RESULTS: Statistical parametric mapping was used to conduct voxel-based morphometry analysis of the morphologic data and revealed enlarged ventricles and sylvian fissures and stenotic sulci of high convexity, especially in the precuneus in the INPH group, with decreased gray matter density in the insula, caudate and thalamus. CONCLUSION: In INPH, morphologic change occurs in the frontoparietal high convexity with ventricular dilatations, dilated sylvian fissures and tight sulci in the medial parietal lobes.

Prediction of hyperperfusion after carotid endarterectomy by brain SPECT analysis with semiquantitative statistical mapping method.

BACKGROUND AND PURPOSE: Hyperperfusion syndrome is a rare but disastrous complication after carotid endarterectomy (CEA). The aim of this study was to investigate the relationship between preoperative cerebral blood flow (CBF) abnormalities and postoperative hyperperfusion through the use of statistical brain mapping analysis. METHODS: For 41 patients with unilateral carotid stenosis >or=70%, CBF and cerebral vasoreactivity (CVR) were investigated with resting and acetazolamide-challenge single photon emission CT before CEA. CBF 1 day after CEA was also measured. Three-dimensional stereotactic surface projection (3D-SSP) analysis of CBF changes was performed by use of a control database of 20 subjects. RESULTS: Patients with reduced CVR (CVR <10%, n=15) were categorized into 2 groups based on the severity of CBF reduction relative to the control database by 3D-SSP analysis without normalization: type I (ipsilateral CBF decrease <20%, n=8) and type II (ipsilateral CBF decrease >or=20%, n=7). With thalamic normalization, the patients were also categorized into 2 groups: type A (ipsilateral Z score 2, n=5). Severe CBF reduction (>or=20% or Z score >2) was significantly associated with postoperative hyperperfusion (CBF increase >or=100%). However, 3D-SSP with thalamic normalization (Z score) demonstrated a higher predictive value (80%) and specificity (91%) for hyperperfusion than 3D-SSP without normalization (percent reduction) (57% and 73%, respectively). No patients with normal CVR (CVR >or=10%, n=26) demonstrated postoperative hyperperfusion. CONCLUSIONS: Objective evaluation of abnormalities of CBF and CVR with 3D-SSP could identify patients at risk for postoperative hyperperfusion.

Gender differences in cerebral glucose metabolism: a PET study.

OBJECTIVE: Some studies have examined gender differences in brain function based on cerebral blood flow and cerebral metabolism by using positron emission tomography (PET). However, the findings of these studies are controversial and most of them were analyzed by the regions of interest (ROIs) method. Here, we evaluated gender differences of cerebral glucose metabolism under the resting state in a voxel-based analysis. METHODS: We studied 44 healthy volunteers (22 females, 63.0+/-6.3 years, and 22 males, 63.1+/-8.4 years). Cerebral glucose metabolic images were obtained with (18)F-fluorodeoxyglucose (FDG) and PET. All individual data were transformed to standard brain space and the male and female groups were compared using statistical parametric mapping (SPM). RESULTS: The males had significantly higher glucose metabolism in the right insula, middle temporal gyrus, and medial frontal lobe than the females. Glucose metabolism in the hypothalamus was significantly higher in females than in males. There was a significant correlation between aging and glucose metabolism in the left thalamus in males and in the left caudate nucleus and hypothalamus in females. In males, but not females, there was a significant asymmetry between the bilateral hemispheres. CONCLUSION: We found that there were obvious gender differences in regional cerebral glucose metabolism and this is the first report of higher glucose metabolism in the hypothalamus in females than in males.