Protective Effect of Hydroxygenkwanin against Hair Graying Induced by X-Ray Irradiation and Repetitive Plucking.

Hair graying in mice is caused by various injuries such as X-ray radiation and repeated plucking that ultimately damage melanocytes and their stem cells (melanocyte stem cells). In X-ray‒induced hair graying, injuries first manifest as a loss-of-niche function of hair follicular keratinocyte stem cells to maintain melanocyte stem cells. Thus, we hypothesized that hair follicular keratinocyte stem cells could be a practical target to prevent hair graying. In this study, we investigated the in vivo effect of the flavonoid hydroxygenkwanin, which has been shown to exert the best protection on human epidermal keratinocytes against in vitro X-ray‒induced cytological effects, using X-ray‒induced and repeated hair plucking‒induced hair graying mice models. We found that hydroxygenkwanin exerted a remarkable effect in preventing hair graying; however, when receptor Y kinase Kit-mutant mice were used, no prevention effect was observed. Therefore, we propose that Kit signaling might be involved in the hydroxygenkwanin-induced protective effect against hair graying.

Discovery of remogliflozin etabonate: A potent and highly selective SGLT2 inhibitor.

We optimized the structure of an active metabolite (1) of WAY-123783, which was obtained from mouse urine after oral administration, to improve selectivity for SGLT2 and oral bioavailability. O-glucoside derivative 24 (remogliflozin etabonate) was subsequently identified as a potent, highly selective, and orally available SGLT2 inhibitor.

Fluid Pressure Monitoring-Based Strategy for Delicate Grasping of Fragile Objects by A Robotic Hand with Fluid Fingertips.

In this study, we propose a strategy for delicately grasping fragile objects using a robotic gripper with highly deformable fluid fingertips. In an earlier study, we developed a soft fingertip, referred to as a fluid fingertip, which was fabricated from a deformable rubber bag filled with incompressible fluid. The proposed strategy detects the preferable grasping point where fracturing of the target object is avoided while the applied force or pressure from the fluid fingertip is substantially transmitted to the target. In this grasping point, the behavior of the fluid pressure changes with respect to the pushing distance when pushing at a constant speed. The other features of the strategy determining the grasping point are as follows: (1) the threshold for the detection of the grasping point is fixed or constant with respect to the type of target object; (2) information regarding the deformation and stiffness of the fingertips and target object is not required. The detection of the grasping point through behavioral changes in the pressure is performed by comparing the fitting accuracies of fitting models utilizing information of the fluid pressure and pushing distance. The validity of the proposed approach is verified through several experiments.

The importance of CH/pi hydrogen bonds in rational drug design: An ab initio fragment molecular orbital study to leukocyte-specific protein tyrosine (LCK) kinase.

The interaction energy was calculated, by the ab initio FMO method, for complexes between LCK protein and four inhibitors (staurosporine, BMS compound 2, and our compounds 3 and 4). In every case a number of CH/pi hydrogen bonds have been disclosed in the so-called adenine pocket. In complexes of 2, 3, and 4, CH/pi and NH/pi hydrogen bonds have been observed in another pocket. In view of the above results, the aniline ring of 3 was replaced by 2,6-dimethyl aniline to increase the potency for LCK kinase. A 10-fold increase in the potency has been achieved for 4 over 3. We suggest that the concept of weak hydrogen bonds is useful in the rational design of drugs.

Novel pyrazolo[1,5-a]pyrimidines as c-Src kinase inhibitors that reduce IKr channel blockade.

To improve the in vitro potency of the c-Src inhibitor 1a and to address its hERG liability, a structure-activity study was carried out, focusing on two regions of the lead compound. The blockade of the delayed cardiac current rectifier K(+) (I(Kr)) channel was overcome by replacing the ethylenediamino group with an amino alcohol group at the 7-position. In addition, modifying the substituents at the 5-position and the side chain groups on the amino alcohols at the 7-position enhanced the intracellular c-Src inhibitory activity and increased central nervous system (CNS) penetration. In the present study, 6l exhibited significant in vivo efficacy in a middle cerebral artery (MCA) occlusion model in rats.

Quantitative assessment of mammographic density and breast cancer risk for Japanese women.

We conducted a case-control study to examine the relationship between breast density (BD) on mammography and breast cancer risk for postmenopausal Japanese women. The mammograms (205 cases and 223 controls) were classified by two doctors employing Wolfe's classification and used to measure BD with original computer software. A weak relationship between breast cancer risk and the parenchymal pattern of Wolfe's classification was found. The BD measured with the computer software, however, showed a significant relationship with breast cancer risk. Analysis after adjustment for epidemiologic factors showed that women in the quintile with the highest BD had a 3.02 times higher risk of breast cancer than those in the quintile with the lowest density. Since mammographic BD is clearly associated with breast cancer risk for postmenopausal Japanese women, our software can be expected to become a useful tool for objective risk assessment of breast cancer.

A contour extraction method using active contour model on ultrasonic images.

At excision operations of a breast tumor, a navigation to display three-dimensional models during the operations is demanded to grasp a position and a size of the tumor, and to decide an area of the excision. Speckle noises which are characteristic of an ultrasonic image are caused by interference of sound waves. The noises cause a low resolution of a region of interest (ROI), and those are obstacle of constructing recognizable three-dimensional image. To reconstruct a three-dimensional model from two-dimensional ultrasonic tomograms, a speckle reduction and a contour extraction of the ROI are demanded. The purpose of this study is a contour extraction of a ROI on ultrasonic images. An active contour model using a gradient vector flow was employed. The contour of a lesion area of the ultrasonic images which speckle are reduced was extracted.

Reduced speckle noise on medical ultrasound images using cellular neural network.

Speckle noise is indispensable get from ultrasound image. In general tends to reduce the image resolution and contrast. In addition to the doctor diagnosis, is lacking for judgment accuracy. This paper is reduced the speckle noise and enhanced boundary of a tumor in the medical ultrasound images. The proposed method is valuated using numerical phantom simulating ultrasound B-mode images, and the effect is confirmed by applying to medical ultrasound images. Therefore, some important features such as tissue boundaries and small tumors may be overlooked. A cellular neural network which is a kind of recurrent neural network can deal with images by the weight of neurons called a cell. It could be obtained more detail images recognition compared with the previous studies. Determination template parameters of the cellular neural network for ultrasound image processing are discussed. The experimental results show effectiveness of applying the proposed method to boundary enhancement and the speckle noise reduction of medical ultrasound image.

Discovery of novel 2-anilinopyrazolo[1,5-a]pyrimidine derivatives as c-Src kinase inhibitors for the treatment of acute ischemic stroke.

We synthesized a series of novel 2-anilinopyrazolo[1,5-a]pyrimidine derivatives and evaluated their ability to inhibit c-Src kinase; 7-(2-amino-2-methylpropylamino)-5-cyclopropyl-2-(3,5-dimethoxyphenylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide 7o and 7-(2-amino-2-methylpropylamino)-2-(3,5-dimethoxyphenylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide 7f showed potent inhibitory activity. Compound 7f inhibited c-Src selectively and exhibited satisfactory central nervous system (CNS) penetration. Furthermore, 7f.HCl reduced the infarct volume in vivo in a rat middle cerebral artery (MCA) occlusion model when administrated intraperitoneally.

Synthesis and c-Src inhibitory activity of imidazo[1,5-a]pyrazine derivatives as an agent for treatment of acute ischemic stroke.

We synthesized and evaluated a series of C-5 substituted imidazo[1,5-a]pyrazine derivatives to identify potent c-Src inhibitors as potential therapeutic agents for acute ischemic stroke. Among these compounds, compound 14c.HCl demonstrated remarkable central nervous system (CNS) penetration and significant neuroprotective efficacy in vivo in rat models.

[Basic experimental study of intraosseous venography using carbon dioxide contrast agent in percutaneous vertebroplasty].

PURPOSE: In percutaneous vertebroplasty (PVP), intraosseous venography is performed using water-soluble ionic iodinated contrast media (iodine contrast media) before injecting bone cement. However, because of contrast medium remaining in the fractured cleft, we experienced the persistence of intravertebral opacification that obscured visualization of the cement under X-ray fluoroscopy. To solve this problem, we examined carbon dioxide (CO(2)) as a contrast medium. METHODS: We measured the contrast of iodine contrast media and CO(2) and performed a subjective assessment of imaging by enforcing intraosseous venography by changing the tube voltage and image intensifier (I.I.) entrance dose in a bone sample of a cadaver using iodine contrast media and CO(2). In vivo study, we performed a subjective assessment of images obtained by intraosseous venography using CO(2) under two kinds of X-ray views. RESULTS: We determined that the contrast of CO(2) is 1/6-1/7.5 that of iodine contrast media, and that CO(2) fluctuates less in its contrast value with changes in tube voltage. In our assessment of the image of the bone sample, CO(2) performed worse that iodine contrast media. However, if the I.I. entrance dose is kept above 2.5 microGy/F, CO(2) is considered to be of clinical use. In the clinical image assessment, the best conditions were an image collection rate of 7.5 F/S and matrix of 1024 x 1024. CONCLUSIONS: CO(2) did not cause any obstacles when we injected bone cement, and its I.I. entrance dose, image collection rate, and matrix size indicate that it can be used for intraosseous venography.

A novel neural network with Non-Recursive IIR Filters on EEG Artifacts Elimination.

The artifacts caused by various factors, EOG (electrooculogram), blink and EMG (electromyogram), in EEG (Electroencephalogram) signals increase the difficulty in analyzing them. In addition, EEG signals containing artifacts often cannot be used in analyzing them. So, it is useful and indispensable to eliminate the artifacts from EEG signals. In this paper, a neural network with non-recursive IIR (Infinite Impulse Response) filters are used to eliminate the artifacts from EEG signals. The proposed method is a new approach that is respect to slotting a non-recursive IIR filter into individual neurons of a neural network. First of all, in order to investigate the usefulness of the proposed method in eliminating the artifacts from EEG signals, we apply it to the artificial EEG signals that are weakly stationary process. As the result, the artifacts can be eliminated from EEG signals almost exactly using the proposed method, and it is suggested the proposed method should be useful in eliminating the artifacts from EEG signals.

An investigation of EEG artifacts elimination using a neural network with non-recursive 2nd order volterra filters.

The artifacts caused by various factors, EOG (electrooculogram), blink and EMG (electromyogram), in EEG (electroencephalogram) signals increase the difficulty in analyzing them. In addition, EEG signals containing artifacts often cannot be used in analyzing them. So, it is useful and indispensable to eliminate the artifacts from EEG signals. A neural network with non-recursive 2nd order volterra filters is used to eliminate the artifacts from EEG signals. The proposed method is a new approach in respect to slotting a non-recursive 2nd order volterra filter into individual neurons of a neural network. First of all, in order to investigate the usefulness of the proposed method in eliminating the artifacts from EEG signals, we apply it to the artificial EEG signals mat are weakly stationary process. As the result, the artifacts can be eliminated from EEG signals almost exactly using the proposed method, and ft is suggested the proposed method should be useful in eliminating the artifacts from EEG signals.

Morphological image sharpening by double structuring elements for ultrasound images.

We discuss a new morphological operations using double structuring elements (DSEs) and apply them to image sharpening of ultrasound B-mode images with speckle pattern. The DSEs, a couple of two different structuring elements, varying with the local characteristics of the input image, yield an edge-sharpening effect. General single structuring element does not have the sharpening function. Our method improves contrast at the tissue boundary without speckle emphasis and does not generate overshoot nor undershoot around the boundary. We demonstrate its effectiveness in experiments using human thyroid images.

Absolute configuration of the thyroid hormone analog KAT-2003 as determined by the 1H NMR anisotropy method with a novel chiral auxiliary, MalphaNP acid.

The absolute configuration of the chiral thyroid hormone analog KAT-2003 (+)-2, showing hypocholesterolemic activities, decreases of hepatic triglyceride contents with lowering cardiac side effects, and significant inhibitory effect for the second primary hepatocellular carcinoma, was determined as S by the (1)H NMR anisotropy method using a novel chiral auxiliary, 2-methoxy-2-(1-naphtyl)propionic acid (MalphaNP acid).

Asymmetric borane reduction of prochiral ketone using chiral bis(alpha, alpha-diphenyl-2-pyrrolidinemethanol) carbonate.

Chiral bis(alpha, alpha-diphenyl-2-pyrrolidinemethanol) carbonate (DPP(2).H(2)CO(3)) is a useful asymmetric auxiliary for the asymmetric borane reduction of prochiral ketones. Chiral DPP(2).H(2)CO(3) is recoverable from the reaction and directly reusable for the reaction. The intermediate of KUR-1246, which we are developing as a new uterine relaxant, was synthesized using the methodology.