Oral Ingestion of Collagen Hydrolysate Leads to the Transportation of Highly Concentrated Gly-Pro-Hyp and Its Hydrolyzed Form of Pro-Hyp into the Bloodstream and Skin.

Collagen hydrolysate is a well-known dietary supplement for the treatment of skin aging; however, its mode of action remains unknown. Previous studies have shown that the oral ingestion of collagen hydrolysate leads to elevated levels of collagen-derived peptides in the blood, but whether these peptides reach the skin remains unclear. Here, we analyzed the plasma concentration of collagen-derived peptides after ingestion of high tripeptide containing collagen hydrolysate in humans. We identified 17 types of collagen-derived peptides transiently, with a particular enrichment in Gly-Pro-Hyp. This was also observed using an in vivo mouse model in the plasma and skin, albeit with a higher enrichment of Pro-Hyp in the skin. Interestingly, this Pro-Hyp enrichment in the skin was derived from Gly-Pro-Hyp hydrolysis, as the administration of pure Gly-Pro-Hyp peptide led to similar results. Therefore, we propose that functional peptides can be transferred to the skin by dietary supplements of collagen.

Effects of L-serine ingestion on human sleep.

To investigate the effects of L-serine intake on human sleep, we conducted two randomized double-blinded crossover studies. In Study 1, healthy subjects who were dissatisfied with their sleep were given L-serine or a placebo 30 min before going to bed. After waking the next morning, subjective sleep quality was rated using the Ogri-Shirakawa-Azumi subjective sleep rating scale. In Study 2, subjective sleep quality was rated using the St. Mary's Hospital sleep questionnaire, and objective parameters, including sleep initiation time, number of nighttime awakenings, and hours of sleep, were evaluated using actigraphy. In Study 1, factors related to "sleep initiation" and "sleep maintenance" during the L-serine intake period were significantly improved compared to the placebo intake period (p = 0.02 and p = 0.008, respectively). In Study 2, scores for "How well did you sleep last night?" and "How satisfied were you with last night's sleep?" were significantly better during L-serine intake compared to placebo (p = 0.04 and p = 0.03, respectively). Subjective evaluation of sleep quality on waking was thus improved. In addition, objective evaluation using actigraphy showed that the "number of nighttime awakenings" tended to be decreased (p = 0.08). These findings suggest that intake of L-serine before going to bed may improve human sleep.

Extracts of Cistanche deserticola Can Antagonize Immunosenescence and Extend Life Span in Senescence-Accelerated Mouse Prone 8 (SAM-P8) Mice.

The senescence accelerated mouse prone 8 substrain (SAM-P8), widely accepted as an animal model for studying aging and antiaging drugs, was used to examine the effects of dietary supplementation with extracts of Cistanche deserticola (ECD) which has been used extensively in traditional Chinese medicine because of its perceived ability to promote immune function in the elderly. Eight-month-old male SAM-P8 mice were treated with ECD by daily oral administrations for 4 weeks. The results showed that dietary supplementation of 150 mg/kg and 450 mg/kg of ECD could extend the life span measured by Kaplan-Meier survival analysis in dose-dependent manner. Dietary supplementation of SAM-P8 mice for 4 weeks with 100, 500, and 2500 mg/kg of ECD was shown to result in significant increases in both naive T and natural killer cells in blood and spleen cell populations. In contrast, peripheral memory T cells and proinflammatory cytokine, IL-6 in serum, were substantially decreased in the mice that ingested 100 and 500 mg/kg of ECD daily. Additionally, Sca-1 positive cells, the recognized progenitors of peripheral naive T cells, were restored in parallel. Our results provide clear experimental support for long standing clinical observational studies showing that Cistanche deserticola possesses significant effects in extending life span and suggest this is achieved by antagonizing immunosenescence.

Fomiroid A, a novel compound from the mushroom Fomitopsis nigra, inhibits NPC1L1-mediated cholesterol uptake via a mode of action distinct from that of ezetimibe.

Hypercholesterolemia is one of the key risk factors for coronary heart disease, a major cause of death in developed countries. Suppression of NPC1L1-mediated dietary and biliary cholesterol absorption is predicted to be one of the most effective ways to reduce the risk of hypercholesterolemia. In a screen for natural products that inhibit ezetimibe glucuronide binding to NPC1L1, we found a novel compound, fomiroid A, in extracts of the mushroom Fomitopsis nigra. Fomiroid A is a lanosterone derivative with molecular formula C30H48O3. Fomiroid A inhibited ezetimibe glucuronide binding to NPC1L1, and dose-dependently prevented NPC1L1-mediated cholesterol uptake and formation of esterified cholesterol in NPC1L1-expressing Caco2 cells. Fomiroid A exhibited a pharmacological chaperone activity that corrected trafficking defects of the L1072T/L1168I mutant of NPC1L1. Because ezetimibe does not have such an activity, the binding site and mode of action of fomiroid A are likely to be distinct from those of ezetimibe.

Hemodynamics and changes after STA-MCA anastomosis in moyamoya disease and atherosclerotic cerebrovascular disease measured by micro-Doppler ultrasonography.

Moyamoya disease (MMD) and atherosclerotic cerebrovascular disease (ACVD) differ in angiographic appearance and probably hemodynamics. Pediatric MMD (PMMD) usually presents with cerebral ischemia, while intracranial hemorrhage is more common in adult MMD (AMMD), suggesting differences in cerebral hemodynamics. We analyzed the cortical flow velocity and direction of recipient arteries using micro-Doppler ultrasonography to evaluate the cortical circulation before and after anastomosis in MMD and ACVD. Twenty-eight patients with adult MMD (AMMD), 7 with pediatric MMD (PMMD), 16 with ACVD, and 12 control patients were studied. A micro-Doppler probe was applied on the cortical recipient artery (A4 or M4) before and after anastomosis. Systolic maximum flow velocity (V max) and blood flow direction were investigated at proximal and distal parts of anastomosed sites in recipient arteries. Pre- and postoperative regional cerebral blood flow was measured by cold xenon-computed tomography (Xe-CT). Before anastomosis, retrograde cortical flow was significantly more common in PMMD patients, and V max in cortical artery was significantly lower in AMMD patients. Bypass surgery changed the direction of blood flow from the anastomosis site to proximal and distal sites of the recipient artery in most patients, but pre-anastomosis flow direction was preserved more frequently in PMMD patients. The rate of V max increase after anastomosis was significantly higher in AMMD than in PMMD (11.6 ± 9.8 vs. 3.9 ± 1.8; P = 0.01). Micro-Doppler ultrasonography identified differences in cortical circulation among AMMD, PMMD, and ACVD. In AMMD, significantly low velocity in the cortical artery was observed before anastomosis, and bypass surgery reversed the flow and significantly increased flow velocity. The data of PMMD showed unique hemodynamics of the cortical artery before anastomosis, characterized by a higher frequency of retrograde flow and preserved velocity. The V max increase rate was significantly higher in patients with postoperative cerebral hyperperfusion on Xe-CT, and further study is warranted to validate the clinical use of intraoperative micro-Doppler monitoring to predict postoperative hyperperfusion.

Limitations of fetal ultrasonography and magnetic resonance imaging in prenatal diagnosis of congenital cerebral arteriovenous malformations with hemorrhagic onset.

A fetus at 30 gestational weeks was observed on fetal ultrasonography to have a dilated right lateral ventricle. After delivery, the entity was diagnosed as a prenatal intracerebral hemorrhage (ICH) due to a ruptured arteriovenous malformation (AVM). Ultrasonography and MRI examinations performed before birth indicated a cerebral aneurysm in the territory of the right middle cerebral artery. However, digital subtraction angiography revealed an intracystic hemorrhage due to a ruptured cerebral AVM. Arteriovenous malformations in children are rare, difficult to diagnose, and result in permanent sequelae after delayed treatment. Patient prognosis depends on early and accurate diagnosis and intervention. Outcomes can be improved if an AVM in a child is detected at the onset of ICH for young infants in the prenatal or early postnatal periods. Early AVM diagnosis is limited to fetal ultrasonography and MRI, and special consideration through invasive examination including neonatal digital subtraction angiography is urged unless a correct and clear diagnosis is made at an early stage. Prenatal ICH due to an AVM is rare. The authors discuss their observations and findings.

Technical options for the surgical management of extracranial carotid artery aneurysms. Three case reports.

Three cases of extracranial carotid artery (ECA) aneurysm were treated with various surgical options. Two female patients (74 and 37-year-old women) presented with pulsatile masses in their necks, which were confirmed as ECA aneurysms. Another 65-year-old woman presented with a calcified mass in her neck caused by an ECA aneurysm. The first case was treated with aneurysmorrhaphy with primary closure, the second with replacement of the involved site with vascular prosthesis, and the third with a high flow bypass with proximal ligation of the internal carotid artery. All three different surgical techniques were successful. ECA aneurysms are rare and require careful selection of the surgical method according to etiology, shape, and location of the ECA aneurysm. Proficiency in various vascular reconstruction techniques is a desirable prerequisite for the surgeon in-charge.

The efficacy of superficial temporal artery-middle cerebral artery anastomosis in patients with moyamoya disease complaining of severe headache.

OBJECT: Some patients with moyamoya disease complain of severe headache, which may be closely related to cerebral ischemia. The efficacy of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis in these patients was evaluated by clinicoradiological studies. METHODS: Of 117 consecutive patients with ischemic moyamoya disease, 25 complained mainly of severe headache (headache group) and 92 had no significant headache (nonheadache group). Intensity of headache was evaluated pre- and postoperatively. Furthermore, regional cerebral blood flow (rCBF) and cerebrovascular reactivity (CVR) were assessed pre- and postoperatively. RESULTS: The headache group was significantly younger than the nonheadache group. In a group corrected for the age distribution, preoperative rCBF and CVR were similar in headache and nonheadache groups. After STA-MCA anastomosis, 16 patients with headache experienced complete relief from headache, 7 patients showed remarkable improvements and discontinued medications for headache, and the remaining 2 patients had some alleviation of headache but sometimes required medication. In the headache group, the postoperative rCBF was significantly greater than the preoperative value. The postoperative rCBF in this group was also significantly greater than the postoperative rCBF in the nonheadache group. CONCLUSIONS: These data suggest that severe headache is one of the main symptoms in young patients with moyamoya disease probably related to cerebral circulatory disturbances. An STA-MCA anastomosis is effective in relieving headache in patients with ischemic moyamoya disease manifesting severe headache, probably by improving perfusion pressure and cerebral circulation.

Effects of kale ingestion on pharmacokinetics of acetaminophen in rats.

Kale is a cruciferous vegetable (Brassicaceae) that contains a large amount of health-promoting phytochemicals. The chronic ingestion of cabbage of the same family is known to accelerate conjugating acetaminophen (AA) and decrease the plasma AA level. Therefore, we examined to clarify the effects of kale on the pharmacokinetics of AA, its glucuronide (AA-G) and sulfate (AA-S). AA was orally administered to rats pre-treated with kale or cabbage (2000 mg/kg/day) for one week. Blood samples were collected from the jugular vein, and the concentrations of AA, AA-G and AA-S were determined. In results, kale ingestion induced an increase in the area under the concentration-time curve (AUC) and a decrease in the clearance of AA, whereas cabbage had almost no influence. In addition, there were significant differences in the AUC of AA-G between the control and kale groups. mRNA expression levels of UDP-glucuronosyltransferases, the enzymes involved in glucuronidation, in the kale group were significantly higher than those in the control group. In conclusion, kale ingestion increased the plasma concentrations of both AA and AA-G. The results suggest that kale ingestion accelerates the glucuronidation of AA, but an increase of plasma AA levels has a different cause than the cause of glucuronidation.

Melanin biosynthesis inhibitors from Tarragon Artemisia dracunculus.

The EtOH extract of tarragon Artemisia dracunculus, a perennial herb in the family Asteraceae, was found to potently inhibit α-melanocyte-stimulating hormone (α-MSH) induced melanin production in B16 mouse melanoma cells. Bioassay-guided fractionation led to the isolation of two alkamide compounds, isobutyl (1) and piperidiyl (2) amides of undeca-2E,4E-dien-8,10-dynoic acid. The respective EC(50) values for melanin biosynthesis inhibition were 1.8 and 2.3 µg/mL for 1 and 2.

Usefulness of intraoperative laser Doppler flowmetry and thermography to predict a risk of postoperative hyperperfusion after superficial temporal artery-middle cerebral artery bypass for moyamoya disease.

We investigated whether postoperative hyperperfusion in moyamoya disease can be predicted using intraoperative laser Doppler flowmetry and/or thermography. A prospective study was conducted on 27 patients (39 hemispheres) with moyamoya disease who underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass. During surgery, regional cerebral blood flow (rCBF) was measured with a laser Doppler flowmeter and the temperature of the cortical surface was measured with an infrared thermograph. Postoperative hyperperfusion was assessed immediately after surgery based on CBF study under sedation (propofol) as >100% increase in corrected rCBF compared to preoperative values. Postoperative hyperperfusion on CBF was observed in two patients (7.4%). A significant correlation was observed between intraoperative rCBF changes and postoperative rCBF increase (Pearson's method: r=0.555, p=0.0003; simple regression: Y=1.22X+3.289, r (2)=0.308, p=0.0004). Furthermore, the rCBF changes measured by laser Doppler flowmetry were significantly greater in patients with postoperative hyperperfusion (p=0.0193) and CHS (p=0.0193). The present study suggests that intraoperative rCBF measurement using laser Doppler flowmetry may predict a risk of post-EC-IC bypass cerebral hyperperfusion in moyamoya disease.

Meningioma of the internal auditory canal with rapidly progressive hearing loss: case report.

A 38-year-old male presented with a meningioma within the internal auditory canal (IAC) manifesting as rapidly progressive hearing loss over a period of one month. He had a 2-year history of tinnitus. Magnetic resonance imaging revealed a 10-mm intracanalicular tumor, which was surgically resected by a retrosigmoid lateral suboccipital approach. The histological findings showed meningothelial meningioma. The patient had no facial palsy after surgery, but his cochlear function did not recover. Common symptoms of IAC meningiomas are tinnitus and hearing loss, but rapidly progressive hearing loss is very rare. IAC meningioma is rare but should be taken into consideration as a cause of rapidly progressive hearing loss.

Incidence and predictive factors of cerebral hyperperfusion after extracranial-intracranial bypass for occlusive cerebrovascular diseases.

BACKGROUND: Although many studies of postoperative cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy have been reported, there are few reports related to extracranial-intracranial (EC-IC) bypass for atherosclerotic occlusive cerebrovascular diseases. OBJECTIVE: To examine the incidence of cerebral hyperperfusion and CHS after EC-IC bypass and to investigate predictive factors. METHODS: Fifty consecutive patients undergoing EC-IC bypass for atherosclerotic occlusive cerebrovascular diseases were studied. Immediately after bypass surgery, resting regional cerebral blood flow was determined under continuous sedation, and postoperative hyperperfusion was evaluated according to the definitions as follows: >50% increase in regional cerebral blood flow compared with the contralateral side (method 1) and>100% increase in corrected regional cerebral blood flow compared with preoperative values (method 2). Logistic regression analysis was conducted to determine the effect of multiple variables on postoperative hyperperfusion. RESULTS: Transient symptoms of CHS were observed in 3 patients. Cerebral hyperperfusion was detected in 12 patients (24%) as defined by method 1 and in 9 patients (18%) by method 2. Postoperative hyperperfusion occurred significantly more frequently in patients with the steal phenomenon (regional cerebral vasoreactivity≤0%; P=.001 by method 1 and P=.001 by method 2) and correlated with impaired preoperative regional cerebral vasoreactivity (P<.001). Logistic regression analysis revealed that the steal phenomenon was a significant risk factor for hyperperfusion as defined by both methods 1 (P=.009) and 2 (P=.03). CONCLUSION: The incidence of cerebral blood flow-assessed postoperative hyperperfusion after EC-IC bypass for atherosclerotic occlusive cerebrovascular diseases was not rare. Post EC-IC bypass CHS could be reduced by continuous, strict blood pressure control under sedation.

Effects of Korean white ginseng extracts on obesity in high-fat diet-induced obese mice.

The present study examined the anti-obesity effect and mechanism of action of Korean white ginseng extracts (KGE) using high-fat diet (HFD)-induced obese mice. Mice were fed a low-fat diet (LFD), HFD or HFD containing 0.8 and 1.6% (w/w) KGE diet (HFD + 0.8KGE and HFD + 1.6KGE) for 8 weeks. We also examined the effects of KGE on plasma triglyceride (TG) elevation in mice administrated with oral lipid emulsion. Body weight gain and white adipose tissue (WAT) weight were significantly decreased in the HFD + 1.6KGE group, compared with the HFD group. The plasma TG levels were also significantly reduced in both HFD + 0.8KGE and HFD + 1.6KGE groups, while leptin levels were significantly decreased in only the HFD + 1.6KGE group, compared with the HFD group. The HFD + 1.6KGE group showed significantly lower mRNA levels of lipogenesis-related genes, including peroxisome proliferator-activated receptorγ2 (PPARγ2), sterol regulatory element binding protein-1c (SREBP-1c), lipoprotein lipase (LPL), fatty acid synthase (FAS) and diacylglycerol acyltransferase 1 (DGAT1), compared with the HFD group. In addition, a dose of 1000 mg/kg KGE inhibited the elevation of plasma TG levels compared with mice given the lipid emulsion alone. These results suggest that the anti-obesity effects of KGE may be elicited by regulating expression of lipogenesis-related genes in WAT and by delaying intestinal fat absorption.

Successful superficial temporal artery-anterior cerebral artery direct bypass using a long graft for moyamoya disease: technical note.

BACKGROUND: Although some patients with moyamoya disease need revascularization in the anterior cerebral artery (ACA) territory, there are few reports on direct bypass in the ACA territory because of the difficult surgical technique. OBJECTIVE: To report our technical strategy for superficial temporal artery (STA)-ACA bypass. METHODS: We performed simultaneous STA-ACA and STA-middle cerebral artery direct bypasses in 7 patients with moyamoya disease using the following strategies: creating 2 separate craniotomies for the 2 bypasses, dissecting a long STA graft and securing a recipient ACA around the bregma for the STA-ACA bypass, and using loose stitches at the anastomoses. One branch of the STA was dissected for a length of approximately 10 cm. The graft coursed on the brain surface under the bone bridge and was directly anastomosed to the cortical branch of the ACA. At the anastomoses, the stitches were widely spaced and loose to facilitate expansion of the orifice. RESULTS: This method prevented kinking of the graft. Postoperative angiograms revealed good patency of the STA-ACA bypass in all patients. After the bypasses, 5 patients no longer had transient ischemic attacks or stroke, 1 patient was almost completely free of transient ischemic attacks, and 1 patient had only residual contralateral symptoms. In all 7 patients, patency of the bypass was satisfactory during follow-up periods ranging from 9 to 23 months (mean 16.4 months). CONCLUSION: This method of STA-ACA bypass provides successful and reliable direct revascularization of the ACA territory in patients with moyamoya disease. Further investigation of the possible merit of this surgery in improving cognitive function is warranted.

Inhibitory effects of bakuchiol, bavachin, and isobavachalcone isolated from Piper longum on melanin production in B16 mouse melanoma cells.

An EtOH extract of fruits of Piper longum was found to exhibit a potent inhibitory effect against alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanin production in B16 mouse melanoma cells. Bioassay-directed fractionation led to the isolation of prenylated phenolic compounds bakuchiol, bavachin, and isobavachalcone. These compounds and the crude extract of the fruits of P. longum may have suppressive effects against pigmentation by melanin in the skin.

Nobiletin improves hyperglycemia and insulin resistance in obese diabetic ob/ob mice.

Nobiletin is a polymethoxylated flavone found in certain citrus fruits that exhibits various pharmacological effects including anti-inflammatory, antitumor and neuroprotective properties. The present study investigated the effects of nobiletin on insulin sensitivity in obese diabetic ob/ob mice, and the possible mechanisms involved. The ob/ob mice were treated with nobiletin (200mg/kg) for 5 weeks. Nobiletin significantly improved the plasma glucose levels, homeostasis model assessment index, glucose tolerance in an oral glucose tolerance test and plasma adiponectin levels. In white adipose tissue (WAT), nobiletin significantly decreased the mRNA expression levels of inflammatory adipokines such as interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 and increased the mRNA expression levels of adiponectin, peroxisome proliferator-activated receptor (PPAR)-gamma and its target genes. At the same time, nobiletin increased the glucose transporter (Glut) 4 expression levels in the whole plasma membrane, and Glut1 and phospho-Akt expression in the whole cell lysates in WAT and muscle. Nobiletin also increased Glut4 protein expression level in the whole cell lysates of the muscle. Taken together, the present results suggest that nobiletin improved the hyperglycemia and insulin resistance in obese diabetic ob/ob mice by regulating expression of Glut1 and Glut4 in WAT and muscle, and expression of adipokines in WAT.

Silybin from Silybum Marianum Seeds Inhibits Confluent-Induced Keratinocytes Differentiation as Effectively as Retinoic Acid without Inducing Inflammatory Cytokine.

Retinoic acid (RA) has been effective for improving wrinkles. However, it has also been reported that RA induces skin irritation. In this study, we explored new botanical compounds that show RA-like activity, but do not induce inflammation in vitro. Keratinocytes were maintained in a confluent condition and induced differentiation. Under this condition keratinocytes were treated with many botanical extracts and their morphological change were observed and compared with RA-treated. We found that silybin, which is a major flavonolignan from Silybum Marianum seeds, induced RA-like morphological change and prevented differentiation. We showed that silybin, like RA, reduced the expression of keratinocyte terminal differentiation markers and stimulated the expression of basement membrane component proteins. In contrast, silybin, unlike RA, did not stimulate the secretion of IL-1alpha, which is a skin irritation mediator. These results suggest that silybin has RA-like activity on keratinocytes and has the potential to improve winkle without inducing skin irritation.

Pressure-controlled dual irrigation-suction system for microneurosurgery: technical note.

OBJECTIVE: We designed a new irrigation-suction system consisting mainly of a pressure-resistant irrigation fluid container, dual irrigation and suction devices, and an intracontainer pressure regulator. METHODS: The intracontainer pressure can be regulated from 0 to 0.02 MPa. This system is simple and can be operated simultaneously by both an operator and an assistant. It is powered by compressed air, which is available in regular operating rooms of any hospital. RESULTS: No complications including blood clots in the brain and vascular injuries related to this system were observed. CONCLUSION: The excellent and safe performance of this dual irrigation-suction system in clearing the operating field by an operator and/or an assistant has been proven in more than 300 neurosurgical operations.

Postcarotid endarterectomy cerebral hyperperfusion can be prevented by minimizing intraoperative cerebral ischemia and strict postoperative blood pressure control under continuous sedation.

OBJECTIVE: Cerebral hyperperfusion syndrome is a major complication after carotid endarterectomy (CEA). We investigated whether our strategy of minimizing intraoperative cerebral ischemia and strict postoperative blood pressure control under continuous sedation prevented postoperative hyperperfusion. METHODS: Eighty consecutive patients undergoing CEA were studied. A shunt was used in all patients during CEA. All patients were managed postoperatively under continuous sedation for as long as 48 hours on the basis of the regional cerebral blood flow (rCBF) measured immediately after CEA. Postoperative hyperperfusion was assessed, on the basis of the cerebral blood flow study under sedation (propofol) after CEA, either as a greater than 30% increase in rCBF compared with the contralateral side, or a greater than 100% increase in the corrected rCBF (calculated from percentage reduction of the contralateral rCBF induced by propofol) compared with preoperative values. RESULTS: No patient developed cerebral hyperperfusion syndrome. Postoperative hyperperfusion was found at very low rates (2.5% in the middle cerebral artery territory and 1.3% in the anterior cerebral artery territory by definition 1, and 0% in both territories by definition 2). Ratios of regional oxygen saturation after internal carotid artery clamping to preclamp baseline values were greater than 0.9 in 78 of 80 patients, indicating very mild intraoperative cerebral ischemia. Parameters related to cerebral ischemia during CEA, such as regional oxygen saturation, internal carotid artery cross-clamping duration, and stump pressure (index), did not affect the incidence of postoperative hyperperfusion. CONCLUSION: The present study suggests that minimizing intraoperative cerebral ischemia using a shunt, followed by strict postoperative blood pressure control under continuous sedation, can prevent post-CEA hyperperfusion.