Auraptene in the Peels of Citrus Kawachiensis (Kawachibankan) Contributes to the Preservation of Cognitive Function: A Randomized, Placebo-Controlled, Double-Blind Study in Healthy Volunteers.

OBJECTIVES: Dementia, which is characterized by a progressive decline in cognitive function, is a major concern in aging societies. Although a number of treatments have been approved, an effective therapy to prevent the disorder is lacking. A supplement that improves cognitive function would benefit patients. The aim of this study was to assess whether auraptene, a citrus coumarin, has a protective effect on cognitive decline. DESIGN: A randomized, placebo-controlled, double-blind study SETTING: Outpatient medical check-up program for cognitive disorders PARTICIPANTS: 84 adult volunteers (they are cognitively normal) met inclusion and exclusion criteria to participate. INTERVENTION: 42 participants received auraptene enriched (containing 6.0 mg/day of auraptene) test juice, and another participants received placebo juice. MEASUREMENTS: 1) Mild Cognitive Impairment (MCI) Screen using the 10-word immediate recall test. 2) The Mini-Mental State Examination (MMSE). Cognitive assessment ware carried out baseline and at 24 weeks. RESULTS: Auraptene enriched test juice did not improve cognitive function after 24 weeks compared with baseline data. However, there was a significant difference in the percentage change in cognitive function between the test and placebo orange juice groups (6.3 ± 18.9 vs. -2.4 ± 14.8, P < 0.05). Multiple regression analysis demonstrated a significant independent relationship between the percentage change in the 10-word immediate recall test score and test juice consumption including baseline 10-word immediate recall test score in all subjects. CONCLUSION: This is the first study to assess the effectiveness of auraptene in the prevention of cognitive decline. Our results suggest that auraptene is a safe supplement for the prevention of cognitive decline.

Stenting procedure for sinus stenosis with transverse-sigmoid dural arteriovenous fistulas. A case report.

SUMMARY: We reported the dural AVF case with sinus stenosis, that was entirely treated through the stenting procedure. 61-year-old male had been realizing the attack which causes bilateral visual problem. He would have suffered from the intracranial hypertension caused by dural AVF in the right transverse sinus and left transverse sinus stenosis.We performed TVE and sinus stenting, then used the antiplatelet and the anticoagulant. However, six months later, he suffered from SAH due to recurrence of dural AVF. We performed TVE again, denser packing than usual. Two years later, he have no symptom, angiographically, there was no recurrence of dural AVF and patency of stented sinus. We think denser embolizations should have performed in case of dural AVF with sinus stenting.

[Usefulness of time-resolved projection MRA on evaluation of hemodynamics in cerebral occlusive diseases].

The usefulness for evaluation of cerebral hemodynamics using time-resolved projection MRA was studied in normal volunteers and patients of cerebrovascular diseases. Six normal volunteers and ten patients with cerebrovascular occlusive diseases including 6 of IC occlusion and 4 of post EC/IC bypass surgery underwent time-resolved projection MRA on a 1.5 T clinical MRI system. Projection angiograms are acquired with 2 D-fast SPGR sequence with a time resolution of approximately one image per second, 40 images being acquired consecutively before and after bolus injection Gd-DTPA. And all images were calculated by complex subtraction from the background mask in a work station. In normal volunteers, the quality of images of time-resolved projection MRA was satisfactory. The arteries from internal carotid artery through M 2 segment of middle cerebral artery and all major venous systems were well portrayed. In 4 cases of IC occlusion who were assessed the collateral flow through the anterior communicating artery and posterior communicating artery, there were delayed to demonstrate the ipsilateral MCA. However, in 2 cases of IC occlusion that were assessed the collateral flow through leptomeningeal anastomosis, ipsilateral MCA and collateral circulation were not demonstrated. In all patients of post EC/IC bypass surgery, the patency of EC/IC bypass could be evaluated as properly with time-resolved projection MRA as 3 D-TOF MRA. Although the temporal and spatial resolutions are insufficient, time-resolved projection MRA was powerful non-invasive method to evaluate the cerebral hemodynamics via the basal communicating arteries in IC occlusion and identify the patency of EC/IC bypass.

[A case of adult moyamoya disease progressed after vascular reconstructive surgery].

We report an adult onset patient with moyamoya disease showing acute progress after contralateral vascular reconstructive surgery. A 47-year-old female developed cerebral infarction in the left corona radiata. A magnetic resonance (MR) angiography and a cerebral angiogram revealed severe stenosis extending from the terminal portion of left internal carotid artery (ICA) to the M1 portion. The right ICA showed slight stenosis. We performed direct bypass surgery (STA-MCA anastomosis) on the affected left side. MR angiography 1 month after surgery revealed the progressive stenosis of the C1 portion of the right ICA. While measurement of cerebral blood flow (CBF) showed a slight impairment of vascular reactivity to acetazolamide loading in the region of the right MCA, we continued without vascular reconstructive surgery for the right side because there was no ischemic attack. The patient had a transient sensory disturbance of the left upper extremity 16 months after surgery. MR angiography and a cerebral angiogram revealed more progressive stenosis extending from the right ICA to the M1 portion. CBF study showed a low CBF at rest and a negative response to acetazolamide loading in the region of the right MCA. Direct bypass surgery was performed on the right hemisphere. Follow-up study revealed an increment of rest CBF and improvement of vascular reactivity. We underlined the necessity for careful postoperation observation of progressive contralateral arterial stenosis using MR angiography and CBF study in adult onset patients with moyamoya disease.

An 18-mer peptide fragment of prosaposin ameliorates place navigation disability, cortical infarction, and retrograde thalamic degeneration in rats with focal cerebral ischemia.

It was previously reported that prosaposin possesses neurotrophic activity that is ascribed to an 18-mer peptide comprising the hydrophilic sequence of the rat saposin C domain. To evaluate the effect of the 18-mer peptide on ischemic neuronal damage, the peptide was infused in the left lateral ventricle immediately after occlusion of the left middle cerebral artery (MCA) in stroke-prone spontaneously hypertensive (SP-SH) rats. The treatment ameliorated the ischemia-induced space navigation disability and cortical infarction and prevented secondary thalamic degeneration in a dose-dependent manner. In culture experiments, treatment with the 18-mer peptide attenuated free radical-induced neuronal injury at low concentrations (0.002 to 2 pg/mL), and the peptide at higher concentrations (0.2 to 20 ng/mL) protected neurons against hypoxic insult. Furthermore, a saposin C fragment comprising the 18-mer peptide bound to synaptosomal fractions of the cerebral cortex, and this binding decreased at the 1st day after MCA occlusion and recovered to the preischemic level at the 7th day after ischemia. These findings suggest that the 18-mer peptide ameliorates neuronal damage in vivo and in vitro through binding to the functional receptor, although the cDNA encoding prosaposin receptor has not been determined yet.

Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery.

Erythropoietin (EPO) prevents the ischemia-induced delayed neuronal death in the hippocampal CA1 field in gerbils. EPO receptor (EPOR) is also expressed in the cerebral cortex but its function is not known. To examine whether EPO has a neuroprotective action in the cortex, EPO was infused into the cerebroventricles of stroke-prone spontaneously hypertensive rats with permanent occlusion of the left middle cerebral artery. Morris water maze test indicated that EPO infusion alleviated the ischemia-induced place navigation disability. The left (ischemic)-to-right (contralateral nonischemic) (L/R) ratio of cerebrocortical area in the EPO-infused ischemic group was larger than that in the vehicle-infused ischemic group. The occlusion caused secondary thalamic degeneration but infusion of EPO prevented the decrease in the L/R ratio of thalamic area and supported neuron survival in the ventroposterior thalamic nucleus. In situ hybridization indicated that EPOR mRNA was upregulated in the periphery (ischemic penumbra) of a cerebrocortical infarct after occlusion of the middle cerebral artery, suggesting that an increased number of EPOR in neurons facilitates the EPO signal transmission, thereby preventing the damaged area from enlarging.

Suppression by platelet factor 4 of the myogenic activity of basic fibroblast growth factor.

The effect of platelet factor 4 (PF4) on myoblast cultures with or without basic fibroblast growth factor (bFGF) or other growth factors was investigated in the present in vitro experiments, with reference to bFGF binding to myoblast membrane fraction. When PF4 was added to the culture medium 1 day after myoblast cultivation, the nuclei of both myoblasts and myotubes were markedly reduced in number in a dose-dependent manner, whereas the inhibitory effect of PF4 on myoblast development was not observed when PF4 was added to the culture medium 3, 7, or 14 days after myoblast cultivation. In contrast, bFGF significantly increased the numbers of myoblast and myotube nuclei. When bFGF and PF4 were simultaneously added to the culture medium, PF4 abolished the facilitatory effects of bFGF on myogenesis. The real-time biospecific interaction analysis (BLA) core system showed that the myoblast membrane fraction at 1 day after cultivation contains bFGF-binding elements which are blocked by PF4 in a dose-dependent manner. Moreover, [126I]-bFGF binding experiments indicated the existence of both high and low affinity binding sites on myoblast membranes, although the high affinity binding sites decreased in number and the dissociation constant increased in value as the culture period was prolonged. Among the six other growth factors examined, acidic fibroblast growth factor and platelet-derived growth factor-BB stimulated myogenesis, and their effects were blocked by PF4 treatment. These findings suggest that: 1) PF4 inhibits myoblast proliferation and myotube formation only for a limited initial period of cultivation, possibly because of the time-dependent down-regulation of high affinity bFGF receptors: and 2) PF4 may be used as a tool to investigate the function of endogenous heparin-binding growth factors upregulated transiently at a certain developmental stage or in case of tissue damage and repair, even though it is not monospecific to bFGF.

Usefulness of thallium-201 single photon emission computed tomography to quantify the malignancy grade of brain tumors.

Preoperative thallium-201 (201Tl) single photon emission computed tomography (SPECT) was used to evaluate the histological malignancy in 24 patients with brain tumors. A corrected L/E ratio was calculated based on the ratio of thallium uptake in the tumor on early images versus the tumor in the delayed images (L/E ratio) corrected for thallium uptake in the contralateral cerebral hemisphere. The corrected L/E ratio in benign brain tumors was 0.79 +/- 0.23, significantly different to 1.32 +/- 0.25 in high grade astrocytomas (p < 0.01) and 1.19 +/- 0.05 in metastatic brain tumors (p < 0.01), respectively. The corrected L/E ratio in low grade astrocytomas was 0.64 +/- 0.32, significantly lower than that in high grade astrocytomas (p < 0.01) and metastatic brain tumors (p < 0.05). There was one false positive result among 24 patients using a threshold of 1.0 to separate malignant and benign tumors. 201Tl SPECT using the corrected L/E ratio is effective for determining the malignant viability of tumors.

Interleukin-6 prevents ischemia-induced learning disability and neuronal and synaptic loss in gerbils.

Interleukin-6 (IL-6) has been shown to have potent neurotrophic activity on peripheral and central neurons in vitro. However, it remains to be determined whether or not IL-6 rescues hippocampal CA1 neurons from lethal ischemia and prevents ischemia-induced learning disability. In the present in vivo study, we infused IL-6 continuously for 7 days into the lateral ventricle of gerbil starting 2 h before 3-min forebrain ischemia. IL-6 infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner as revealed by a step-down passive avoidance task. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the CA1 region of the hippocampus as well as synapses within the strata moleculare, radiatum and oriens of the region were significantly more numerous in gerbils infused with IL-6 than in those receiving vehicle infusion. These findings suggest that IL-6 has a trophic effect on ischemic hippocampal neurons.

[A case of dural AVM detected after STA-MCA anastomosis].

A case of dural arteriovenous malformation (AVM) in the posterior cranial fossa detected after STA-MCA anastomosis surgery. A 52-year-old male consulted a neighbourhood hospital for sudden headache and vomiting. He was diagnosed as having intraventricular hemorrhage on CT scan. Though the obstruction of the right internal carotid artery was revealed angiographically, his symptoms improved after conservative therapy. Two weeks after onset, his consciousness deteriorated and he developed left hemiparesis. Thereafter, he was transferred to our hospital. After thorough examination, right STA-MCA anastomosis surgery was performed. Approximately 2 months after surgery, right tinnitus developed and gradually exacerbated. Since it was thought to be due to increased blood flow in the right superficial temporal artery, it was kept under observation. On angiogram, 8 months after surgery, good blood flow supplied from the right superficial temporal artery to the territory of the right middle cerebral artery was shown, and a dural AVM fed by the right occipital artery was found. Fourteen months after the surgery, an enlarged dural AVM with backflow to the superficial cerebral veins fed by the enlarged right occipital artery and right ascending pharyngeal artery was revealed. Embolization therapy to the right occipital and ascending pharyngeal artery was performed using coils and ivalon, and irradiation of 30 Gy was added. After this treatment, right tinnitus improved. On angiography 2 years later, transverse sinus was slightly visible via the right occipital artery and ascending pharyngeal artery, but the dural AVM was significantly reduced. The origin of dural AVMs remains controversial. In our case, dural AVM was not found before the STA-MCA anastomosis surgery, and sinus thrombosis was not found throughout the course of observation. It is thought that the occult dural AVM was disclosed and enlarged by the increased blood flow through the external carotid artery via the STA-MCA anastomosis. Therefore, the dural AVM seemed to be congenital in origin.