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91.
Noriyasu Kamei Shingo Kikuchi Mariko Takeda-Morishita Yoshiaki Terasawa Akihito Yasuda Shuichi Yamamoto Nobuo Ida Reiji Nishio Kozo Takayama 《Journal of pharmaceutical sciences》2013,102(2):469-479
Our recent work has shown that the intestinal absorption of insulin can be improved significantly by coadministration of cell-penetrating peptides (CPPs), especially penetratin. However, a relatively high dose of penetratin is required to adequately stimulate the intestinal absorption of insulin. Therefore, in this study, we sought to determine the CPP that most effectively enhanced intestinal insulin absorption. An in situ loop absorption study using 26 penetratin analogues suggested that the chain length, hydrophobicity, and amphipathicity of the CPPs, as well as their basicity, contribute to their absorption-enhancing efficiency. Moreover, a molecular orbital method with self-organizing maps (SOMs) classification suggested that multiple factors, including the molecular weight, basicity, the lowest unoccupied molecular orbital energy, absolute hardness, and chemical potential of CPPs, are associated with their effects on intestinal insulin absorption. Furthermore, the new CPPs proposed by SOM clustering had a marked capacity to interact with insulin, and their ability to enhance insulin absorption was much stronger than that of the original penetratin. Therefore, the peptide sequence that optimally enhances intestinal insulin absorption could be defined by SOM with the molecular orbital method, and our present work emphasizes the utility of such methodologies in the development of effective drug delivery systems. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:469–479, 2013 相似文献
92.
Noriyasu Hashida Kei Nakai Norimitsu Saitoh Kohji Nishida 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2014,252(4):687-693
Purpose
To investigate if the site of ocular lesions and prophylactic treatment in patients with primary vitreoretinal lymphoma (PVRL) are associated with the time to onset of central nervous system (CNS) involvement.Methods
We retrospectively studied 26 patients (seven men, 19 women; mean age, 67.0?±?11.1 years) with a diagnosis of PVRL at our hospital between January 2001 and October 2011 and a minimum 2-year follow-up after treatment. We classified the PVRL lesions as: (1) the vitreous opacity type, vitreous opacity of 2+ or higher without retinal lesions, (2) the retina type, vitreous opacity of 1+ or less with retinal lesions only, or (3) the concomitant type, with both. We also evaluated whether prophylactic treatment of systemic chemotherapy such as high-dose methotrexate (HD-MTX) and intrathecal MTX (IT-MTX), or topical ocular treatments such as intravitreal injections of MTX and rituximab, inhibited the onset of CNS involvement in patients with PVRL without cerebral involvement.Results
During a mean follow-up of 44.0?±?18.7 months, CNS involvement began in 14 patients (53.8 %), i.e., three (60 %) of five patients with retina-type lesions, five (41.7 %) of 12 patients with vitreous opacity-type lesions, and six (66.7 %) of nine patients with concomitant-type lesions. There was no significant (P?=?0.496) association between the site of the ocular lesions and the onset of brain lesions. In addition, CNS involvement occurred in eight of 11 patients receiving CNS prophylactic chemotherapy and six of 15 patients receiving no prophylaxis; the difference between the two did not reach significance (P?=?0.131). The time to onset of cerebral involvement in the CNS prophylactic chemotherapy group (42.8?±?13.8 months) was significantly (P?=?0.0005) longer than in the group that did not receive prophylaxis (10.2?±?2.0 months). Preventive systemic chemotherapy, especially HD-MTX, significantly prolonged the time to the onset of brain lesions compared to IT-MTX and local ocular therapy.Conclusions
While prophylactic systemic chemotherapy did not inhibit the onset of CNS involvement in most of patients with PVRL, it significantly prolonged the time to cerebral involvement. 相似文献93.
94.
The larval stage of Echinococcus multilocularis causes alveolar echinococcosis in human. In serodiagnosis of alveolar echinococcosis, specific reactions have been noted not only against protein antigens but also carbohydrates. With regard to protein antigens, the recent development of recombinant antigens has contributed to an improvement in serodiagnostic examination. On the contrary, the preparation of carbohydrate antigen still depends on extraction from crude antigens, and isolation is usually accompanied with difficulty; consequently, it is rare to examine individual antigenicity of carbohydrates. However, parasitic helminths express various antigenic carbohydrates. In the case of Echinococcus granulosus, antigenic glycoproteins of the laminated layer have been reported. Furthermore, the laminated layer of E. multilocularis contains Em2 antigen which is a famous mucin-type glycoprotein and which seems to play an important role in metacestode survival mechanisms within the immunologically reacting host; nevertheless, the anomeric configurations and the individual antigenicity of Em2 O-glycans have not been confirmed so far. Under these circumstances, we introduced a chemical synthesis to get pure oligosaccharides in order to assess diagnostic performance. In our previous study, 11 oligosaccharides have already been prepared by stereocontrolled syntheses. Among them, three synthetic oligosaccharides showed antigenicity. Our aim is to investigate correct sequence and serodiagnostic potential of the dominant epitope of Em2. This study provided important diagnostic information: (1) the trisaccharide Galα1-4Galβ1-3GalNAc sequence is the dominant epitope of Em2 (sensitivity 95.0 %), (2) Trematoda expresses carbohydrates with the similar trisaccharide sequence, and (3) the terminal Galα1-4Gal sequence is a candidate for the widely common epitope that accounts for the cross-reaction. 相似文献
95.
Ota N Soga S Haramizu S Yokoi Y Hase T Murase T 《Nutrition (Burbank, Los Angeles County, Calif.)》2011,27(9):955-959
Objective
Extended periods of muscle disuse, physical inactivity, immobilization, and bedrest result in a loss of muscle mass and a decrease in muscle force, which are accompanied by an increase in oxidative stress. We investigated the effects of the intake of green tea catechins on unloading-induced muscle dysfunction in tail-suspended mice.Methods
Ten-week-old male BALB/c mice were fed a purified control diet or a diet containing 0.5% tea catechins for 14 d. Thereafter, the mice were subjected to continuous tail suspension for 10 d. On the final day, muscle mass, contractile force production, antioxidant potential, and carbonylated protein levels were evaluated.Results
Hind limb unloading caused a loss of soleus muscle weight and muscle force. Intake of tea catechins significantly inhibited the unloading-induced decrease in force in isolated soleus muscle by 19% compared with the control group, although tea catechins did not affect muscle weight. In addition, intake of tea catechins suppressed the decrease in antioxidant potential and the increase in carbonyl myofibrillar protein.Conclusion
Ingestion of tea catechins minimized contractile dysfunction in skeletal muscle and muscle atrophy in unloaded muscle. This effect might be partly due to the lower oxidative modification of myofibrillar protein through the antioxidant activity of tea catechins. 相似文献96.
Akihiro Furuta Hideo Onishi Noriyasu Yamaki Nobuhiro Yada Hizuru Amijima 《Radiological physics and technology》2018,11(3):294-302
We evaluated quantitation accuracy of the specific binding ratio (SBR) and specific uptake ratio (SUR) of dopamine transporter for various correction methods by using a novel three-dimensional striatum digital brain (3D-SDB) phantom comprised of segments containing the striatum, ventricle, brain parenchyma, and skull bone extracted from T2-weighted MR images. A process image was reconstructed by projection data sets with blurring, scatter, and attenuation from 3D-SDB phantom data. A 3D-iterative reconstruction algorithm was used without correction (OSEM), or with scatter (SC), attenuation (AC), AC?+?SC (ACSC), AC?+?resolution recovery (RR; ACRR), SC?+?RR (SCRR), AC?+?SC?+?RR (ACSCRR), AC?+?SC?+?RR?+?partial volume (PVC; ACSCRRP), and AC?+?SC?+?RR?+?PVC?+?ventricle (ACSCRRPV). Data were then quantified using SBR and SUR. Differences between measured and true SBR values were (in order): ACSCRR?<?ACSC?<?ACRR?<?AC?<?SCRR?<?SC?<?OSEM: the maximal error was 45.3%. The trend of differences between measured and true SUR values was similar to that of SBR; maximal error was 65%. The ACSCRR-corrected SUR, which was closer to the true value, was underestimated by 30.4%. However, the ACSCRRP-corrected SUR was underestimated by a maximum of 22.5%. The SUR in the ACSCRRPV was underestimated by 6.2%. The accuracy of quantitation was improved using various types of compensation and correction. Accuracy improved more for the SUR when PVC and ventricle correction were added. 相似文献
97.
98.
Ohtsu H Kuramasu A Tanaka S Terui T Hirasawa N Hara M Makabe-Kobayashi Y Yamada N Yanai K Sakurai E Okada M Ohuchi K Ichikawa A Nagy A Watanabe T 《European journal of immunology》2002,32(6):1698-1708
Histidine decarboxylase (HDC) synthesizes endogenous histamine from histidine in mammals. To evaluate the role of histamine in skin allergic reaction, we used HDC gene knockout mice lacking histamine. No plasma extravasation reaction was observed in HDC-/- mice after passive cutaneous anaphylaxis (PCA) test. Compound 48/80, a mast cell granule depletor, produced plasma extravasation inHDC+/+ mice but no extravasation in HDC-/- mice. Interestingly, orally administered histamine was distributed in the skin in HDC-/- mice and in these histamine-supplemented mice the plasma extravasation reaction was observed after the injection of compound 48/80 and the PCA test. Cultured bone marrow-derived mast cells of HDC-/- mice took up histamine from the histamine-supplemented medium into the secretory granules. The absorbed histamine was released in response to the same antigen and antibody combination used as in PCA test. In contrast to the immediate-type response, the delayed-type hypersensitive response, observed as a thickening of the ear skin after trinitrochlorobenzene challenge (following sensitization), showed no differences between HDC+/+ and HDC-/- mice. Therefore, among the allergic skin reactions, histamine is revealed to be an important mediator especially for the plasma extravasation in an immediate-type allergy model. 相似文献
99.
Hiroshi Goto Masahiro Zako Kenichi Namba Noriyasu Hashida Toshikatsu Kaburaki Masanori Miyazaki 《Ocular immunology and inflammation》2019,27(1):40-50
Purpose: Report global adalimumab safety and efficacy outcomes in patients with non-infectious uveitis.Methods: Adults with non-infectious intermediate, posterior, or panuveitis were randomized 1:1 to receive placebo or adalimumab in the VISUAL I (active uveitis) or VISUAL II (inactive uveitis) trials. Integrated global and Japan substudy results are reported. The primary endpoint was time to treatment failure (TF).Results: In the integrated studies, TF risk was significantly reduced (hazard ratio [95% CI]) with adalimumab versus placebo (VISUAL I: HR = 0.56 [0.40–0.76], p < 0.001; VISUAL II: HR = 0.52 [0.37–0.74], p < 0.001). In Japan substudies, no consistent trends were observed between groups (VISUAL I: HR = 1.20 [0.41–3.54]; VISUAL II: HR = 0.45 [0.20–1.03]). Adverse event rates were similar between treatment groups in both studies (854 to 1063 events/100 participant-years).Conclusions: Adalimumab lowered time to TF versus placebo in the integrated population; no consistent trends were observed in Japan substudies. Safety results were consistent between studies. 相似文献
100.
Sonoda Y Hada N Kaneda T Suzuki T Ohshio T Takeda T Kasahara T 《Biological & pharmaceutical bulletin》2008,31(6):1279-1283
Numerous studies have demonstrated the participation of glicolipids in signal transduction and the regulation of melanoma cell growth and apoptosis. Hoping to discover new anticancer drugs, we have synthesized ten glycolipids found in various invertebrates that do not have sialic acids. These compounds were tested for antiproliferative effects on a melanoma cell line, B16F10. A synthetic compound, Manbeta(1-4)[Fucalpha(1-3)]Glcbeta1-Cer, (glycosphingolipid 7), which was identified in the millipede Parafontaria laminata armigera, had an antiproliferative effect on the melanoma cells. This compound suppressed the activation of the focal adhesion kinase (FAK)-Akt pathway as well as the activation of extracellular signal-regulated kinase (Erk)1/2 pathway involved in cell proliferation. Expression of the cell cycle proteins, cyclin D1 and CDK4, was suppressed by glycosphingolipid 7. From these results, glycosphingolipid 7 suppressed the activation of the FAK-Akt pathway and of Erk1/2, which resulted in a decrease in the expression of cyclin D1 and CDK4. Glycosphingolipid 7 might be a candidate for an inhibitor of cell proliferation in melanomas. 相似文献