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991.
Akira Yamashita Asami Hamada Yuki Suhara Rui Kawabe Makoto Yanase Naoko Kuzumaki Michiko Narita Ryosuke Matsui Hideyuki Okano Minoru Narita 《Synapse (New York, N.Y.)》2014,68(6):235-247
Insomnia, depression, and anxiety disorder are common problems for people with neuropathic pain. In this study, mild noxious heat stimuli increased the duration and number of spontaneous pain‐like behaviors in sciatic nerve‐ligated mice. We used functional magnetic resonance imaging to visualize the increased blood oxygenation level‐dependent signal intensity in the anterior cingulate cortex (ACC) of mice with sciatic nerve ligation under mild noxious stimuli. Such stimuli significantly increased the release of glutamate in the ACC of nerve‐ligated mice. In addition, sciatic nerve ligation and mild noxious stimuli changed the morphology of astrocytes in the ACC. Treatment of cortical astrocytes with glutamate caused astrocytic activation, as detected by a stellate morphology. Furthermore, glutamate induced the translocation of GAT‐3 to astrocyte cell membranes using primary cultured glial cells from the mouse cortex. Moreover, the GABA level at the synaptic cleft in the ACC of nerve‐ligated mice was significantly decreased exposure to mild noxious stimuli. Finally, we investigated whether astrocytic activation in the ACC could directly mediate sleep disorder. With the optogenetic tool channel rhodopsin‐2 (ChR2), we demonstrated that selective photostimulation of these astrocytes in vivo triggered sleep disturbance. Taken together, these results suggest that neuropathic pain‐like stimuli activated astrocytes in the ACC and decreased the extracellular concentration of GABA via an increase in the release of glutamate. Furthermore, these findings provide novel evidence that astrocytic activation in the ACC can mimic sleep disturbance in mice. Synapse 68:235–247, 2014 . © 2014 Wiley Periodicals, Inc. 相似文献
992.
Takumi Fukumoto MD Masahiro Tominaga MD Masahiro Kido MD Atsushi Takebe MD Motofumi Tanaka MD Kaori Kuramitsu MD Ippei Matsumoto MD Tetsuo Ajiki MD Yonson Ku MD 《Annals of surgical oncology》2014,21(3):971-978
Background
Sorafenib is currently recommended as first-line therapy for patients with intermediate or advanced hepatocellular carcinoma (HCC) per Barcelona Clinic Liver Cancer staging. However, the median overall survival (OS) with sorafenib in these patients is 10.7 months with an overall response rate of 2 %. We retrospectively investigated the long-term outcomes and prognostic factors with reductive hepatectomy and sequential percutaneous isolated hepatic perfusion (PIHP) for refractory intermediate or advanced HCC.Methods
A total of 68 patients who had intermediate or advanced stage HCC without extrahepatic metastases were scheduled for reductive hepatectomy plus PIHP. All patients underwent reductive hepatectomy and PIHP with mitomycin C 20–40 mg/m2 and/or doxorubicin 60–120 mg/m2 1–3 months after surgery (mean, 1.51 times/patient).Results
The objective response rate of PIHP was 70.6 % (complete plus partial response). The median OS of all 68 patients was 25 months, and the 5-year OS rate was 27.6 %. Univariate and multivariate analyses indicated that tumor response to PIHP and normalization of serum des-γ-carboxy prothrombin concentrations after PIHP were independent prognostic factors for OS.Conclusions
The median OS of the study population treated by reductive hepatectomy and sequential PIHP was 25 months. This treatment strategy can offer a possible curative treatment to patients with refractory intermediate and advanced HCC. 相似文献993.
994.
Naoki Yanagisawa Takashi Muramatsu Yasuyuki Yamamoto Ken Tsuchiya Kosaku Nitta Atsushi Ajisawa Katsuyuki Fukutake Minoru Ando 《Clinical and experimental nephrology》2014,18(4):600-605
Background
In 2012, the Kidney Disease: Improving Global Outcomes (KDIGO) updated the 2002 Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guideline for chronic kidney disease (CKD). The 2012 KDIGO guideline elaborated the identification and prognosis of CKD by combining albuminuria with estimated glomerular filtration rate (eGFR). Identification of CKD with a high risk for a poor prognosis was investigated in human immunodeficiency virus (HIV)-infected individuals by applying the new guideline.Methods
A total of 1,447 HIV-infected patients (1,351 male, 96 female; mean age 44.4 ± 11.5 years) were classified using a combination of eGFR and dipstick proteinuria, as a convenient alternative to albuminuria. Proteinuria was classified into 3 grades—(A1) – and +/? , (A2) 1+ and 2+ , and (A3) 3+ and 4+. eGFR was classified into 6 grades—(G1) ≤90, (G2) 60–89, (G3a) 45–59, (G3b) 30–44, (G4) 15–29, and (G5) <15 mL/min/1.73 m2.Results
Mean CD4 cell count was 487 ± 214 /μL, with 80.7 % of patients having an undetectable HIV-RNA level. The prevalence of CKD stage ≤2 and stage ≥3 classified according to KDOQI staging was 93.4 and 6.6 %, respectively. Using the new KDIGO classification, the prevalence of CKD with either a low (green) or moderately increased (yellow) risk was 96.9 %, while the prevalence for a high (orange) and very high (red) risk was 3.1 %.Conclusion
The use of the new KDIGO classification may reduce the prevalence of HIV-infected CKD individuals who are at high risk for a poor prognosis by nearly a half. 相似文献995.
Seiko Hirono Manabu Kawai Masaji Tani Ken-ichi Okada Motoki Miyazawa Atsushi Shimizu Yuji Kitahata Hiroki Yamaue 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2014,399(4):461-471
Purpose
Combined portal vein and/or superior mesenteric vein (PV/SMV) resection with pancreatic resection sometimes leads to prolonged survival for patients with pancreatic cancer. In this study, we evaluated perioperative outcomes of patients with PV/SMV reconstruction and considered indications for the use of a graft during this procedure.Methods
We performed PV/SMV resection with pancreatic resection in 128 patients, including 14 using grafts. Complications associated with PV/SMV reconstruction and harvesting venous grafts and reconstructed PV/SMV patency during follow-up were assessed.Results
Of the 128 patients, 5 underwent total pancreatectomy, 99 pancreaticoduodenectomy, and 24 distal pancreatectomy. In the 14 patients who underwent PV/SMV reconstruction with grafts, the grafts were harvested from the external iliac vein (EIV) in 10 patients and internal jugular vein (IJV) in the other 4. Five patients (3.9 %) had an intraoperative or postoperative acute thrombus or stenosis of reconstructed PV/SMV after direct end-to-end anastomosis. However, PV/SMV patency was excellent after reconstruction using grafts. There were no significant differences in other complications between groups with and without the use of grafts. Three patients (30 %) with EIV grafts had postoperative leg edema, and one of them required analgesics until his death because of leg pain caused by compartment syndrome, whereas no patients with IJV grafts had complications associated with sacrificing veins.Conclusions
Depending on the length and/or position of the removed PV/SMV segment, interposed graft may be required for reconstruction in some patients, and the use of graft vein, particularly using IJV, is an appropriate procedure that is not associated with any complications. 相似文献996.
Md. Zahorul Islam Kaori Miyagi Tsukasa Matsumoto Ha Thi Thanh Nguyen Emi Yamazaki-Himeno Mitsuya Shiraishi Atsushi Miyamoto 《Naunyn-Schmiedeberg's archives of pharmacology》2014,387(7):697-702
Our previous in vitro study demonstrated that bradykinin (BK) induced relaxation and contraction of porcine basilar artery (PBA) mediated via activation of endothelial B2 receptors. The main relaxing and contracting factors appeared to be nitric oxide (NO) and prostaglandin (PG) H2, respectively, but not thromboxane A2. After obtaining these findings, we succeeded in cultivating endothelial cells isolated from the PBA. Although PGH2 has different functionally active isoforms, including PGD2, PGE2, and PGF2α, we have not yet clarified which of them is responsible for BK-induced contraction. Therefore, we attempted to quantify NO and PG production from cultured porcine basilar arterial endothelial cells (PBAECs) and to identify which of the PGs was involved in this contraction. The cultured PBAECs produced NO spontaneously, and BK enhanced this production in a concentration-dependent manner. The NO synthase inhibitor Nω-nitro-l-arginine (L-NNA) and the B2 receptor antagonist HOE-140, but not the B1 receptor antagonist des-Arg9, [Leu8]-BK, completely abolished it. In a functional study, PGD2, PGE2, and PGF2α induced concentration-dependent contractions in isolated porcine basilar arterial rings, the order of maximum contraction being PGF2α?>?PGE2?>?PGD2. The cultured PBAECs produced PGD2, PGE2, and PGF2α spontaneously, and BK significantly enhanced the production of PGF2α, but not that of PGD2 and PGE2. The B2, but not B1, antagonist completely abolished the BK-enhanced production of PGF2α. These results suggest that BK induces production of NO and PGF2α simultaneously from PBAECs via B2 receptor activation. 相似文献
997.
Y Hiroshima H Miyamoto F Nakamura D Masukawa T Yamamoto H Muraoka M Kamiya N Yamashita T Suzuki S Matsuzaki I Endo Y Goshima 《British journal of pharmacology》2014,171(2):403-414
Background and Purpose: L-DOPA is generally considered to alleviate the symptoms of Parkinson''s disease by its conversion to dopamine. We have proposed that DOPA is itself a neurotransmitter in the CNS. However, specific receptors for DOPA have not been identified. Recently, the gene product of ocular albinism 1 (OA1) was found to exhibit DOPA-binding activity. Here, we have investigated whether OA1 is a functional receptor of DOPA in the nucleus tractus solitarii (NTS).Experimental Approach: We examined immunohistochemical expression of OA1 in the NTS, and the effects of DOPA microinjected into the depressor sites of NTS on blood pressure and heart rate in anaesthetized rats, with or without prior knock-down of OA1 in the NTS, using shRNA against OA1.Key Results: Using a specific OA1 antibody, OA1-positive cells and nerve fibres were found in the depressor sites of the NTS. OA1 expression in the NTS was markedly suppressed by microinjection into the NTS of adenovirus vectors carrying the relevant shRNA sequences against OA1. In animals treated with OA1 shRNA, depressor and bradycardic responses to DOPA, but not those to glutamate, microinjected into the NTS were blocked. Bilateral injections into the NTS of DOPA cyclohexyl ester, a competitive antagonist against OA1, suppressed phenylephrine-induced bradycardic responses without affecting blood pressure responses.Conclusion and Implications: OA1 acted as a functional receptor for DOPA in the NTS, mediating depressor and bradycardic responses. Our results add to the evidence for a central neurotransmitter role for DOPA, without conversion to dopamine. 相似文献
998.
K Kasutani E Fujii S Ohyama H Adachi M Hasegawa H Kitamura N Yamashita 《British journal of pharmacology》2014,171(22):5049-5058
Background and Purpose
IL-31, which is described as a pruritogenic cytokine, is linked to the itching that is associated with allergic and non-allergic eczema, but the precise pruritogenic mechanism of IL-31 and its potential as a therapeutic target for atopic dermatitis (AD) have not been determined.Experimental Approach
We investigated the effects of existing drugs on the scratching behaviour induced by an i.v. injection of IL-31 to clarify whether IL-31 induced pruritus indirectly. In addition, we studied the effects of an anti-IL-31 receptor α subunit (anti-IL-31 receptor α) neutralizing antibody on chronic pruritus-inducing dermatitis in an AD-like model to determine whether IL-31 not only induces scratching behaviour, but is also the causative factor in an AD phenotype.Key Results
The scratching behaviour induced by an i.v. injection of IL-31 was inhibited by pretreatment with an anti-IL-31 receptor α-neutralizing antibody. In contrast, it was not inhibited significantly by a non-sedative antihistamine (terfenadine), immunosuppressants (dexamethasone and tacrolimus), or a μ-opioid receptor antagonist (naloxone). The anti-IL-31 receptor α-neutralizing antibody reduced the ear swelling and dermatitis score in a chronic pruritus-inducing AD-like model. Moreover, treatment with the anti-IL-31 receptor α-neutralizing antibody showed therapeutic effects on the dermatitis even if it was injected after the disease had developed.Conclusions and Implications
Anti-IL-31 receptor α is a potential novel therapeutic approach for escaping from the itch–scratch cycle and also a treatment for dermatitis in AD. 相似文献999.
Ryosuke Matsuura Chieh-Wen Lo Satoshi Wada Junichi Somei Heihachiro Ochiai Takeharu Murakami Norihito Saito Takayo Ogawa Atsushi Shinjo Yoshimi Benno Masaru Nakagawa Masami Takei Yoko Aida 《Viruses》2021,13(5)
SARS-CoV-2 is the causative agent of COVID-19, which is a global pandemic. SARS-CoV-2 is transmitted rapidly via contaminated surfaces and aerosols, emphasizing the importance of environmental disinfection to block the spread of virus. Ultraviolet C radiation and chemical compounds are effective for SARS-CoV-2 disinfection, but can only be applied in the absence of humans due to their toxicities. Therefore, development of disinfectants that can be applied in working spaces without evacuating people is needed. Here we showed that TiO2-mediated photocatalytic reaction inactivates SARS-CoV-2 in a time-dependent manner and decreases its infectivity by 99.9% after 20 min and 120 min of treatment in aerosol and liquid, respectively. The mechanistic effects of TiO2 photocatalyst on SARS-CoV-2 virion included decreased total observed virion count, increased virion size, and reduced particle surface spike structure, as determined by transmission electron microscopy. Damage to viral proteins and genome was further confirmed by western blotting and RT-qPCR, respectively. The multi-antiviral effects of TiO2-mediated photocatalytic reaction implies universal disinfection potential for different infectious agents. Notably, TiO2 has no adverse effects on human health, and therefore, TiO2-induced photocatalytic reaction is suitable for disinfection of SARS-CoV-2 and other emerging infectious disease-causing agents in human habitation. 相似文献
1000.
Koki Chiba Hiroshi Nomoto Akinobu Nakamura Kyu Yong Cho Kumiko Yamashita Yui Shibayama Aika Miya Hiraku Kameda Yoshio Kurihara Shin Aoki Tatsuya Atsumi Hideaki Miyoshi 《Journal of diabetes investigation.》2021,12(2):176-183
Aims/IntroductionSodium–glucose cotransporter 2 inhibitors (SGLT2i) are used worldwide because of their multiple benefits for patients with type 2 diabetes. The purpose of this study was to determine the efficacy and safety of SGLT2i in patients with type 1 diabetes.Materials and MethodsPatients with type 1 diabetes who had been treated with SGLT2i for >12 weeks were included in this retrospective observation study. We recorded the changes in body mass, insulin dose, blood and urine test data, and adverse events. The changes in day‐to‐day glucose variability, as the primary end‐point, was evaluated using the interquartile range (P25/P75) of the ambulatory glucose data obtained using continuous glucose monitoring.ResultsA total of 51 patients (37 women; mean age 52.7 years) were included. Glycated hemoglobin and body mass significantly decreased by 0.4% and 1.6 kg, respectively. The total required insulin dose decreased by 9.4% (42.7 ± 26.6–38.7 ± 24.3 units/day). Continuous glucose monitoring data were obtained from 30 patients. P25/P75 decreased by 17.6 ± 20.7% during SGLT2i treatment (P < 0.001). The percentage of time per day within the target glucose range of 70–180 mg/dL significantly increased (from 42.2 to 55.5%, P < 0.001), without an increase in the percentage of time spent in the hypoglycemic range (<70 mg/dL). Urinary ketone bodies were detected in four patients (7.8%), but none developed ketoacidosis.ConclusionsSGLT2i improved day‐to‐day glucose variability and time in the target glucose range, without increasing frequency of hypoglycemia, in patients with type 1 diabetes, and reduced glycated hemoglobin, body mass and the required insulin dose. 相似文献