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1.
Depolarization-induced retrograde synaptic inhibition in the mouse cerebellar cortex is mediated by 2-arachidonoylglycerol 总被引:3,自引:0,他引:3
Bela Szabo Michal J. Urbanski Tiziana Bisogno Vincenzo Di Marzo Aitziber Mendiguren Wolfram U. Baer Ilka Freiman 《The Journal of physiology》2006,577(1):263-280
Endocannabinoids acting on CB1 cannabinoid receptors are involved in short- and long-term depression of synaptic transmission. The aim of the present study was to determine which endocannabinoid, anandamide or 2-arachidonoylglycerol (2-AG), is involved in depolarization-induced suppression of inhibition (DSI) in the cerebellar cortex, which is the most widely studied form of short-term depression. Depolarization of Purkinje cells in the mouse cerebellum led to an increase in intracellular calcium concentration and to suppression of the inhibitory input to these neurons (i.e. DSI occurred). Orlistat and RHC80267, two blockers of sn -1-diacylglycerol lipase, the enzyme catalysing 2-AG formation, abolished DSI by acting downstream of calcium influx. In contrast, DSI occurred also in the presence of a phospholipase C inhibitor. Intact operation of the calcium-dependent messengers calmodulin and Ca2+ –calmodulin-dependent protein kinase II were necessary for DSI. DSI was potentiated by an inhibitor of the main 2-AG-degrading enzyme, monoacylglycerol lipase. Interference with the anandamide metabolizing enzyme, fatty acid amide hydrolase, did not modify DSI. Thus, three kinds of observations identified 2-AG as the endocannabinoid involved in DSI in the mouse cerebellum: DSI was abolished by diacylglycerol lipase inhibitors; DSI was potentiated by a monoglyceride lipase inhibitor; and DSI was not changed by an inhibitor of fatty acid amide hydrolase. Further experiments indicated that 2-AG is the endocannabinoid mediating short-term retrograde signalling also at other synapses: orlistat abolished DSI in the rat cerebellum, DSI in the mouse substantia nigra pars reticulata and depolarization-induced suppression of excitation in the mouse cerebellum. 相似文献
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M. Luisa Antelo Ane Altuna J. José Gimeno J. Javier Ferreiro Cristina Amunárriz J. José Mateos Saioa Zalba Aitziber Alkorta José Rifón J. Luis Arroyo Amaia Uresandi J. Antonio Moreno M. Josefa Nájera Sergio Pinzón Alejandro García J. Carlos Vallejo 《Transfusion and apheresis science》2021,60(3):103130
Plerixafor (PLX) appears to effectively enhance hematopoietic stem-cell mobilization prior to autologous hematopoietic stem cell transplantation (auto-HCT). However, the quality of engraftment following auto-HCT has been little explored. Here, engraftment following auto-HCT was assessed in patients mobilized with PLX through a retrospective, multicenter study of 285 consecutive patients. Information on early and 100-day post-transplant engraftment was gathered from the 245 patients that underwent auto-HCT. The median number of PLX days to reach the stem cell collection goal (≥2 × 106 CD34+ cells/kg) was 1 (range 1–4) and the median PLX administration time before apheresis was 11 h (range 1–18). The median number of apheresis sessions to achieve the collection goal was 2 (range 1–5) and the mean number of CD34+ cells collected was 2.95 × 106/kg (range 0–30.5). PLX administration was safe, with only 2 mild and transient gastrointestinal adverse events reported. The median time to achieve an absolute neutrophil count (ANC) >500/μL was 11 days (range 3–31) and the median time to platelet recovery >20 × 103/μL was 13 days (range 5–69). At 100 days after auto-HCT, the platelet count was 137 × 109/L (range 7–340), the ANC was 2.3 × 109/L (range 0.1–13.0), and the hemoglobin concentration was 123 g/L (range 79–165). PLX use allowed auto-HCT to be performed in a high percentage of poorly mobilized patients, resulting in optimal medium-term engraftment in the majority of patients in whom mobilization failed, in this case mainly due to suboptimal peripheral blood CD34+ cell concentration on day +4 or low CD34+ cell yield on apheresis. 相似文献
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Aize Pellon Andoni Ramirez-Garcia Idoia Buldain Aitziber Antoran Leire Martin–Souto Aitor Rementeria Fernando L. Hernando 《International journal of antimicrobial agents》2018,51(1):10-15
The number of fungal isolates resistant to antifungal drugs has increased dramatically over the last few years and has become an important concern for clinicians. Among these isolates, fungi showing multidrug resistance are particularly worrying because of the difficulties associated with their treatment. These factors hamper the successful recovery of patients and drastically raise mortality rates. Antifungal resistance is multifactorial and several mechanisms in different fungi have been described. There is a need to study these mechanisms in depth; however, the study of antifungal drug resistance separately for each individual species makes progress in the field very slow and tedious. The selection of a multiresistant microorganism as a model for understanding resistance mechanisms and extrapolating the results to other species could help in the search for a solution. In this mini-review, we describe the pathobiology of Lomentospora (Scedosporium) prolificans, paying special attention to its intrinsic resistance to all currently available antifungal agents. The characteristics of L. prolificans offer several advantages: the possibility of using a single microorganism for the study of resistance to different drugs, even cases of double and triple resistance; it is biologically safe for society in general as no new genetically–modified strains are needed for the experiments; it is homologous with other fungal species, and there is repetitiveness between different strains. In conclusion, we propose L. prolificans as a candidate for consideration as a fungal model for the study of resistance mechanisms against antifungal agents. 相似文献
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Aitziber Aguinaga Jorge Díaz-González Alejandra Pérez-García Laura Barrado Iván Martínez-Baz Itziar Casado Regina Juanbeltz Carmen Ezpeleta Jesús Castilla 《Enfermedades infecciosas y microbiología clínica》2018,36(6):325-331
Objective
To estimate the prevalence of hepatitis C virus (HCV) infection in Navarra, Spain, as well as to distinguish between diagnosed and undiagnosed infections.Methods
A study was conducted on patients scheduled for surgery unrelated to HCV infection. They were all tested for HCV antibodies, under a routine scheme, from January 2014 to September 2016. Patients with a positive result by enzyme immunoassay were confirmed using immunoblot and/or HCV-RNA. Previous laboratory results were also taken into account. The prevalence was adjusted to the sex and age structure of the Navarra population.Results
The study included a total of 7,378 patients with a median age 46 years, of whom 50% women. HCV antibodies were detected in 69 patients, which is a prevalence in the population of 0.83% (95% confidence interval: 0.64-1.05), and was higher in men (1.11%) than in women (0.56%; P = .0102). Among the HCV positive patients, 67 (97%) had had another previous positive result. Population prevalence of previous positive HCV was 0.80%, and was 0.03% for a new diagnosis. Of the HCV positive patients, 78% had detectable HCV-RNA. It was estimated that 0.65% of the population had had detectable HCV-RNA, and 0.51% continued to have it when recruited into the study.Conclusion
Previous estimates of prevalence of HCV infection should be revised downwards. Only a small proportion of HCV positive patients remain undiagnosed, and only a small part have active infection. 相似文献6.
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Alvarez-Manceñido Felipe Jimenez-Fonseca Paula Carmona-Bayonas Alberto Arrazubi Virginia Hernandez Raquel Cano Juana M. Custodio Ana Pericay Pijaume Carles Aguado Gema Martínez Lago Nieves Sánchez Cánovas Manuel Cacho Lavin Diego Visa Laura Martinez-Torron Alba Arias-Martinez Aranzazu López Flora Limón M. Luisa Vidal Tocino Rosario Fernández Montes Ana Alsina Maria Pimentel Paola Reguera Pablo Martín Carnicero Alfonso Ramchandani Avinash Granja Mónica Azkarate Aitor Martín Richard Marta Serra Olbia Hernández Pérez Carolina Hurtado Alicia Gil-Negrete Aitziber Sauri Tamara Morales del Burgo Patricia Gallego Javier 《Gastric cancer》2021,24(4):926-936
Gastric Cancer - Advanced esophageal adenocarcinoma (EAC) is generally treated similarly to advanced gastroesophageal junction (GEJ-AC) and gastric (GAC) adenocarcinomas, although GAC clinical... 相似文献
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Antonio Fernández-Ortiz L. Jesús Jiménez-Borreguero José L. Peñalvo José M. Ordovás Agustín Mocoroa Leticia Fernández-Friera Martín Laclaustra Laura García Jesús Molina José M. Mendiguren Beatriz López-Melgar Vicente Martínez de Vega Juan C. Alonso-Farto Eliseo Guallar Henrik Sillesen James H.F. Rudd Zahi A. Fayad Borja Ibañez Ginés Sanz Valentín Fuster 《American heart journal》2013
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M C Medrano I Gerrikagoitia L Martínez-Millán A Mendiguren J Pineda 《British journal of pharmacology》2013,169(8):1781-1794
Background and Purpose
Excitatory amino acid transporters (EAATs) in the CNS contribute to the clearance of glutamate released during neurotransmission. The aim of this study was to explore the role of EAATs in the regulation of locus coeruleus (LC) neurons by glutamate.Experimental Approach
We measured the effect of different EAAT subtype inhibitors/enhancers on glutamate- and KCl-induced activation of LC neurons in rat slices. EAAT2–3 expression in the LC was also characterized by immunohistochemistry.Key Results
The EAAT2–5 inhibitor DL-threo-β-benzyloxaspartic acid (100 μM), but not the EAAT2, 4, 5 inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (100 μM) or the EAAT2 inhibitor dihydrokainic acid (DHK; 100 μM), enhanced the glutamate- and KCl-induced activation of the firing rate of LC neurons. These effects were blocked by ionotropic, but not metabotrobic, glutamate receptor antagonists. DHK (100 μM) was the only EAAT inhibitor that increased the spontaneous firing rate of LC cells, an effect that was due to inhibition of EAAT2 and subsequent AMPA receptor activation. Chronic treatment with ceftriaxone (200 mg·kg−1 i.p., once daily, 7 days), an EAAT2 expression enhancer, increased the actions of glutamate and DHK, suggesting a functional impact of EAAT2 up-regulation on the glutamatergic system. Immuhistochemical data revealed the presence of EAAT2 and EAAT3 surrounding noradrenergic neurons and EAAT2 on glial cells in the LC.Conclusions and Implications
These results remark the importance of EAAT2 and EAAT3 in the regulation of rat LC by glutamate. Neuronal EAAT3 would be responsible for terminating the action of synaptically released glutamate, whereas glial EAAT2 would regulate tonic glutamate concentrations in this nucleus. 相似文献10.
Fernando Domínguez Valentín Fuster Juan Miguel Fernández-Alvira Leticia Fernández-Friera Beatriz López-Melgar Ruth Blanco-Rojo Antonio Fernández-Ortiz Pablo García-Pavía Javier Sanz José M. Mendiguren Borja Ibañez Héctor Bueno Enrique Lara-Pezzi José M. Ordovás 《Journal of the American College of Cardiology》2019,73(2):134-144