The present study examines the level of secondary hyperlipidemia in a useful model of doxorubicin () -induced nephrotic rats, and the hypolipidemic effects of fenofibrate (FF) and bezafbrate (BF) on this model. A single intravenous administration of at 5 mg / kg showed mild nephrotic symptoms, and a slight increase in serum lipid levels. at the dose levels of 7.5 and 10 mg / kg caused severe nephrotic syndrome and hyperlipidemia. However, rats with at 10 mg / kg showed distinct differences in the degree of nephrotic and hyperlipidemic levels, and the abnormal behavioral profiles observed, such as piloerection, emaciation and hyperirritability. Therefore, rats administered 7.5 mg/kg of seemed to be a useful model for evaluating the efficacy of hypolipidemic drugs. FF and BF inhibited increases in TC, TG, LDL, VLDL, and chylomicron induced by the administration of at 7.5 mg/kg. The low dose of FF and BF especially inhibited secondary hyperlipidemia caused by the nephrotic syndrome without the exacerbation of nephrotic symptoms. These results suggest that FF and BF may also inhibit secondary hyperlipidemia induced by other diseases such as diabetes, cholestasis and hypothyroidism.

抄録全体を表示

We synthesized a delta opioid receptor (

) antagonist naltrindole (NTI) derivative SYK-165 with a 2,2,2-trifluoroethyl substitute on the 17-nitrogen and reported it showed partial inverse agonist activity in [³⁵S] GTPγS binding assays (Bioorg. Med. Chem. Lett., 2015, 25, 2927-2930.). For the purpose of investigating the further structure-activity relationship, we designed and synthesized NTI derivatives with various electron-withdrawing groups at the 17-position to find a full inverse agonist SYK-623, possessing a 17-cyclopropanecarbonyl group. SYK-623 was over 100-fold more potent than ICI-174,864, a standard inverse agonist. We applied such modification to other antagonists, 7-benzylidenenaltrexone (BNTX) and naltriben (NTB), which have respective chemotypes different from that of NTI. As a result, 17-cyclopropanecarbonyl derivatives SYK-723 (BNTX type) and SYK-724 (NTB type) were also potent full inverse agonists. SYK-623, SYK-723, and SYK-724 are very interesting compounds because these compounds elicited potent full inverse agonist activities in spite of the fact that they have no basic nitrogen, which is known to be indispensable functionality for the interaction with the opioid receptors.

We previously reported that opioidergic nerves system contributed to the control of cough reflex and that

antagonists induced antitussive effects (Pulm. Pharmacol. Ther., 2002, 15, 235-240.). We attempted to examine the effects of inverse agonists on the cough reflex induced by citric acid in mice. Both SYK-623 and SYK-723 showed marked antitussive effects in a dose-dependent manner. We will report detailed results of in vitro and in vivo assays for inverse agonists.

抄録全体を表示

Delta-opioid receptors (

) are highly expressed in the insular cortex, which regulates various autonomic functions including cardiovascular responses. However, the functional roles of in the insular cortex are yet unknown. In the present study we investigated the effects of KNT-127, an agonist of , on the heart rate and neuronal activities in the insular cortex of mice. ddY male mice (5-9 weeks) were used. The electrocardiogram was recorded using wire electrodes inserted subcutaneously in freely moving mice. The extracellular neuronal activities were recorded in the insular cortex in anesthetized mice. The field excitatory postsynaptic potentials (fEPSP) were recorded in the acute insular cortex slices. Microinjection of KNT-127 (46 ng /mouse) in the right, but not left, side of the insular cortex significantly decreased the heart rate. The firing frequency of insular neurons was reduced by intracerebroventricular administration of KNT-127 (230 ng /mouse). Moreover, the fEPSP amplitude was reduced by bath-application of KNT-127 (1-100 μM). Together, activation of in the insular cortex modulates the heart rate via the suppression of neuronal activities.

抄録全体を表示

Resultative constructions are argued to have a generalization called the Direct Object Restriction (

) that states that a resultative predicate is predicated of only a direct object. Some literature argues against the generalization, and claims that the is not attainable. However, Matushansky et al. (2012) provide the syntactic evidence for the . Following them, this paper shows additional evidence in favor of the , and that counter-examples to the are not of the typical type of resultative constructions. Moreover, I argue that some modifications should be made in their proposal, and propose that a functional head forms a resultative predicate by taking a predicative XP as its complement and the semantic subject of XP in its specifier.

抄録全体を表示

We design a new oblivious routing algorithm for two-dimensional mesh-based Networks-on-Chip (NoCs) called LEF (Long Edge First) which offers high throughput with low design complexity. LEF's basic idea comes from conventional wisdom in choosing the appropriate dimension-order routing (

) algorithm for supercomputers with asymmetric mesh or torus interconnects: routing longest dimensions first provides better performance than other strategies. In LEF, we combine the XY and the YX . When routing a packet, which algorithm is chosen depends on the relative position between the source node and the destination node. Decisions of selecting the appropriate algorithm are not fixed to the network shape but instead made on a per-packet basis. We also propose an efficient deadlock avoidance method for LEF in which the use of virtual channels is more flexible than in the conventional method. We evaluate LEF against O1TURN, another effective oblivious routing algorithm, and a minimal adaptive routing algorithm based on the odd-even turn model. The evaluation results show that LEF is particularly effective when the communication is within an asymmetric mesh. In a 16×8 NoC, LEF even outperforms the adaptive routing algorithm in some cases and delivers from around 4% up to around 64.5% higher throughput than O1TURN. Our results also show that the proposed deadlock avoidance method helps to improve LEF's performance significantly and can be used to improve O1TURN's performance. We also examine LEF in large-scale NoCs with thousands of nodes. Our results show that, as the NoC size increases, the performance of the routing algorithms becomes more strongly influenced by the resource allocation policy in the network and the effect is different for each algorithm. This is evident in that results of middle-scale NoCs with around 100 nodes cannot be applied directly to large-scale NoCs.

抄録全体を表示

The Network-on-Chip (NoC) is limited by the reliability constraint, which impels us to exploit the fault-tolerant routing. Generally, there are two main design objectives: tolerating more faults and achieving high network performance. To this end, we propose a new multiple-round dimension-order routing (NMR-). Unlike existing solutions, besides the intermediate nodes inter virtual channels (VCs), some turn-legally intermediate nodes inside each VC are also utilized. Hence, more faults are tolerated by those new introduced intermediate nodes without adding extra VCs. Furthermore, unlike the previous solutions where some VCs are prioritized, the NMR- provides a more flexible manner to evenly distribute packets among different VCs. With extensive simulations, we prove that the NMR- maximally saves more than 90% unreachable node pairs blocked by faults in previous solutions, and significantly reduces the packet latency compared with existing solutions.

抄録全体を表示

Diminished ovarian reserve (

) refers to the decline in fertility caused by the loss of normal ovarian function. is associated with adverse reactions to ovarian stimulation during in vitro fertilization and embryo transfer (IVF-ET), increasing cycle cancellation rates and reducing pregnancy rates. Although it is well known that dehydroepiandrosterone (DHEA) can be used as a dietary supplement for age-related diseases, its potential has gradually been shown for many diseases. In this review, we focus on the effects of DHEA on , briefly analysing its clinical benefits and limitations and describing the mechanism of function and the clinical trials conducted. Therefore, we summarize the mechanisms and indications of DHEA for .

抄録全体を表示

Based on recent analytical, experimental and numerical studies, a new state-of-the-art of oblique-shock-wave reflections in steady flows has been established. The main findings of these analytical, experimental and numerical studies are summarized. The recently established state-of-the-art is summarized in the conclusion section of this review article.

抄録全体を表示

Background: The survival of stem cells upon transplantation into ischemic myocardium is a major concern in cell-based therapy. In this study, we tested the hypothesis that activation of opioid receptors would enhance the survival of mesenchymal stem cells (MSCs) upon exposure to an injury stimulus. Methods and Results: MSCs were obtained from rat bone marrow and cultured in basal DMEM cell culture medium. Delta-opioid receptor () was present in MSCs as examined by reverse transcription-polymerase chain reaction and immunochemistry. Activation of with 5μmol/L SNC80 ( agonist) for 24h significantly enhanced MSC viability upon exposure to 5μg/ml actinomycin D as determined by TUNEL and MTT assays. The cytoprotection was abolished with 20μmol/L naltrindole hydrochloride (a antagonist). Treatment of the cells with 1.5μmol/L chelerythrine (protein kinase C inhibitor) and 1.25μmol/L WP1066 (signal transducer and activator of transcription 3 (STAT3) inhibitor) blocked SNC80-induced cytoprotection. Furthermore, treatment of the cells with chelerythrine also blocked STAT3-phosphorylation and Mcl-1 gene expression. Conclusions: Taken together, the results indicate that plays a critical role in MSC survival upon exposure to actinomycin D through activation of protein kinase C and its downstream signaling molecules STAT3 and Mcl-1. may be a novel therapeutic target for stem cell survival during cell-based therapy. (Circ J 2012; 76: 204-212)

抄録全体を表示

β-Endorphin is an endogenous ligand for both mu- and delta-opioid receptors (MOR and ), and has an important role in feeding behavior in the central nervous system in mammals. The present study was done to elucidate whether central injection of β-endorphin enhances feeding behavior in neonatal chicks and to investigate the interaction with the MOR and . We found that the intracerebroventricular (ICV) injection of β-endorphin (50pmol) significantly stimulated food intake in neonatal chicks during the 60-min period postinjection. In addition, the orexigenic effect of β-endorphin was significantly attenuated by the MOR, but not by the antagonist. These results indicate that the administration of β-endorphin into the chick brain produces the orexigenic effect through the MOR.

抄録全体を表示

Kinematic coupling is attracting attention as one of the technologies to achieve development of a large highly precise space structured system in the space engineering field in recent years. The location difference between upper and lower parts of kinematic coupling can cause position error. So elucidation of a mechanical mechanism is required about the influence by which this difference gives it to the whole structure. In this research, we investigate vibration transfer characteristics of the kinematic coupling by using the finite element analysis. We construct a precise finite element analysis model which can consider the frictional contact effects at joints. The kinematic coupling constructed is the twodimensional model in which 1

and 2 are included. Vibration is given to the base plate when the coupling has been completed, and the transfer characteristics are evaluated at 3 points, the center of lower side, 1 contact point, and the center of upper side. In the analysis, we investigate the effects of the friction and the pressing load on the transfer characteristics.

抄録全体を表示

C'est l'ancien feuille à la tradition japonaise que est la plus mince feuille dans le monde. Dans ce dèrniere procèdéde la feuille , on a été usé l'ancien papier japonaise qui contiens des argiles au nom de HAKUUCHIGAMI (Najiokami)
Nous avons maintenant examiné d'éffects d'argiles (kaolinite, smectite et ctr.) sur HAKUUCHIGAMI par les diffraction rayon-X, microscope d'éléctronique et ctr.
En ce qui concerne de la mallèabilité , les argiles forment la face deglissement, alienent entre or et surface de papier, et refrigerent de l'énergie en frappant.
D'autre part, nous avons éxamine que les atoms sont rearrangee à la face de (1, 0, 0, ) et nous avons supposeé le transparent de lumiere dans la feuille par ce phenomene. La supposition de ce phenomene conduira le grand problem physique sur le cohérrence entre l'éléctron libere de metal et lumiere

抄録全体を表示

Our institution introduced laparoscopic surgery for esophageal achalasia in 2001. The present report summarizes 15 cases of achalasia treated with laparoscopic Heller myotomy and anterior fundoplication according to the method of , and we have investigated the therapeutic effects on specific symptoms such as dysphagia, reflux, and chest pain. From February 2001 through January 2007, the laparoscopic Heller- operation was performed in 15 patients, including 7 men and 8 women. Achalasia was classified morphologically on esophagography as spindle type in 11 cases, flask type in 3 cases and sigmoid type in 1 case. The degree of esophageal dilatation was classified as grade I in 8 cases, grade II in 6 cases, and grade III in 1 case. Dysphagia was the main symptom and was present in all cases. The mean disease duration was 4.3 years (range, 5 months to 20 years), and the mean weight loss was 4.2 kg. All patients underwent endoscopic dilatation preoperatively. Intraoperative blood loss ranged from 0 to 100 mL (mean, 21 mL). Adequate Heller myotomy was considered more than 6 cm and more than 3 cm in the esophagus and the stomach, respectively. Injury to the esophageal mucosa occurred during the myotomy in 3 cases but could be repaired in all cases during the laparoscopic procedure. All patients reported an excellent level of satisfaction postoperatively. In conclusion, the laparoscopic Heller- operation for esophageal achalasia is a useful procedure because the postoperative satisfaction level of patients is excellent. Despite the risk of mucosal injury, adequate Heller myotomy should be achieved to obtain a good prognosis. It is, therefore, of utmost importance to obtain mastery over the surgical technique to repair any mucosal injury that might occur.

抄録全体を表示

Sleep is closely related with mental health, and affected by drug therapy in psychiatric disorders, and vice versa. The delta opioid receptor (

) agonist KNT-127 has been reported to have anxiolytic effects. Unlike benzodiazepines, KNT-127 has no side effects such as dizziness and amnesia. However, its effects on sleep have not been studied. In the present study, we investigated the effects of KNT-127 on sleep in the light period in mice. The vigilance states (e.g., wakefulness, rapid eye movement (REM) and non-REM sleep) of the ddY-mice (6-10 weeks) were classified based on the hippocampal local field potential (LFP) and neck muscle electromyogram. KNT-127 (3-30 mg/kg, i.p.) dose-dependently decreased the mean REM and non-REM sleep period, and prolonged the mean wakefulness period during 5 hr after its injection. At the wakefulness and REM sleep periods after the KNT-127 treatment, the gamma power and theta peak frequency were increased in the hippocampal LFP, suggesting that KNT-127 enhanced the neuronal activities. Pre-treatment of naltrindole (10 mg/kg, s.c.), a antagonist, prevented the KNT-127-induced decrease in non-REM, but not REM, sleep. Naltrindole alone did not influence the vigilance states. Together, KNT-127 increased wakefulness by decreasing non-REM and REM sleep via -dependent and -independent mechanisms, respectively.

抄録全体を表示

Les produits pharmaceutiques des sels , out-its faction stimulante sur la réaction immunologique chez les animaux? En se servant de la méthode habituelle, l'auteur a calcule le taux d'hémolysine dans le serum des lapins. préalablement injectés par voie intraveineuse de la solution d'un sel , Gurgol (Aurothiophenol-m-carbonsaures Natrium: Takecla). Las résultats nous ont permis de constater que le taux d'anticorps s'éléve remarquablernent par l'injection du sel a dose favorable. Mais, au contraire, cette action stimulante devient de plus en plus obscure quant les animaux expérimentaux sont ext&eacuée;nues par les injections de ce remède à dose intoxicante.

抄録全体を表示

Despite the improvements in the treatment of myocardial infarction that have translated into a decline in mortality rates, the incidence of heart failure has increased and, because of the limited number of cardiac donors, non-transplant heart surgery has developed in the past 10 years. Surgical ventricular reconstruction was launched by and defined as endoventricular circular patch plasty repair. It represents a relatively novel surgical approach aiming to restore (bring back to normal) the dilated, distorted left ventricular (LV) cavity in order to improve function. The term `surgical ventricular reconstruction/restoration' includes operative methods that reduce LV volume and restore its shape. The concept of reducing wall stress through surgical restoration of chamber size and geometry remains the guiding principle behind this innovative technique. Results from different Institutions are uniform and show an improvement in cardiac and clinical status and in survival. The present review will approach the rationale to re-shape the heart on the basis of pathophysiology and cardiac architecture, and will describe the efficacy of the procedure in ischemic dilated cardiomyopathy, as well as some technical aspects and patient selection pathway. (Circ J 2009; Suppl A: A-1-A-5)

抄録全体を表示