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Claudia A. Grillo Gerardo G. Piroli Robert C. Lawrence Shayna A. Wrighten Adrienne J. Green Steven P. Wilson Randall R. Sakai Sandra J. Kelly Marlene A. Wilson David D. Mott Lawrence P. Reagan 《Diabetes》2015,64(11):3927-3936
Insulin receptors (IRs) are expressed in discrete neuronal populations in the central nervous system, including the hippocampus. To elucidate the functional role of hippocampal IRs independent of metabolic function, we generated a model of hippocampal-specific insulin resistance using a lentiviral vector expressing an IR antisense sequence (LV-IRAS). LV-IRAS effectively downregulates IR expression in the rat hippocampus without affecting body weight, adiposity, or peripheral glucose homeostasis. Nevertheless, hippocampal neuroplasticity was impaired in LV-IRAS–treated rats. High-frequency stimulation, which evoked robust long-term potentiation (LTP) in brain slices from LV control rats, failed to evoke LTP in LV-IRAS–treated rats. GluN2B subunit levels, as well as the basal level of phosphorylation of GluA1, were reduced in the hippocampus of LV-IRAS rats. Moreover, these deficits in synaptic transmission were associated with impairments in spatial learning. We suggest that alterations in the expression and phosphorylation of glutamate receptor subunits underlie the alterations in LTP and that these changes are responsible for the impairment in hippocampal-dependent learning. Importantly, these learning deficits are strikingly similar to the impairments in complex task performance observed in patients with diabetes, which strengthens the hypothesis that hippocampal insulin resistance is a key mediator of cognitive deficits independent of glycemic control. 相似文献
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Clinical efficacy of amiodarone as an antiarrhythmic agent 总被引:28,自引:0,他引:28
Mauricio B. Rosenbaum MD FACC Pablo A. Chiale MD M.Susana Halpern MD Gerardo J. Nau MD Julio Przybylski MD Raúl J. Levi MD Julio O. Lzzari MD Marcelo V. Elizari MD FACC 《The American journal of cardiology》1976,38(7):934-944
Amiodarone, administered orally in doses of 200 to 600 mg/day, was remarkably effective in the treatment and prevention of a wide variety of atrial and ventricular arrhythmias. Total suppression and control was provided in 98 (92.4 percent) of 106 patients with supraventricular arrhythmias and in 119 (82 percent) of 145 patients with ventricular arrhythmias. The rates of total control of the arrhythmia were: 96.6 percent in 30 patients with recurrent atrial flutter or fibrillation, 96.6 percent in 59 patients with repetitive supraventricular tachycardia, 100 percent in 27 patients with Wolff-Parkinson-White syndrome and 77.2 percent in 44 patients with recurrent ventricular tachycardia unsuccessfully treated with other drugs. Excellent results were obtained in 6 of 8 patients with repetitive ventricular tachycardia and ventricular fibrillation related to postinfarction ventricular aneurysm and in 12 of 14 patients with ventricular extrasystoles and ventricular tachycardia related to Chagasic myocarditis. Amiodarone proved safe in patients with severe congestive heart failure and severe myocardial damage. Its clinical efficacy was related to its electrophysiologic properties and to two unique properties: its wide safety margin and its cumulative effect. The latter liberates patients from a rigid hourly schedule and provides for continuous antiarrhythmic control, days and even weeks after treatment is discontinued. 相似文献
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Héctor Eloy Tamez-Pérez Dania Lizet Quintanilla-Flores René Rodríguez-Gutiérrez José Gerardo González-González Alejandra Lorena Tamez-Pe?a 《World journal of diabetes》2015,6(8):1073-1081
Steroids are drugs that have been used extensively in a variety of conditions. Although widely prescribed for their anti-inflammatory and immunosuppressive properties, glucocorticoids have several side effects, being hyperglycemia one of the most common and representative. In the present review, we discuss the main epidemiologic characteristics associated with steroid use, with emphasis on the identification of high risk populations. Additionally we present the pathophysiology of corticosteroid induced hyperglycemia as well as the pharmacokinetics and pharmacodynamics associated with steroid use. We propose a treatment strategy based on previous reports and the understanding of the mechanism of action of both, the different types of glucocorticoids and the treatment options, in both the ambulatory and the hospital setting. Finally, we present some of the recent scientific advances as well as some options for future use of glucocorticoids. 相似文献
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Laura Villarreal‐Martínez Jaime García‐Chvez Berenice Snchez‐Jara Aida Mashenka Moreno‐Gonzlez Janet Soto‐Padilla Efraín Aquino‐Fernndez Rogelio Paredes‐Aguilera Karla Maldonado‐Silva Cecilia Rodríguez‐Castillejos Ana Itamar Gonzlez‐vila María Mora‐Torres Hector Manuel Tiznado‐García Natalia Elizabeth Padilla‐Durn Nuria Citlali Luna‐Silva Eric Israel Gutirrez‐Jurez Jorge Nemi‐Cueto Claudia Sofia Gmez‐Gonzlez Ricardo De Len‐Figueroa Adela Lpez‐Miranda Mirna Guadalupe Ríos‐Osuna Edna Liliana Tamez‐Gmez Elio Aarn Reyes‐Espinoza Irving Armando Domínguez‐Varela Gerardo Gonzlez‐Martínez Elias Adn Godoy‐Salinas 《Haemophilia》2020,26(2):290-297
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Fabio Pagni Marta Jaconi Alberto Delitala Mattia Garancini Matteo Maternini Francesca Bono Alessandro Giani Andrew Smith the San Gerardo Hospital collaborators group 《Endocrine pathology》2014,25(3):288-296
The recent increase in the detection of papillary thyroid carcinoma (PTC) has been influenced by the finding of incidental tumours. To this group, carcinomas measuring less than 1 cm (the so-called microcarcinomas) as well as those above 1 cm belong. Analyzing a case series from our own experience, this paper focuses on the current pre-operative diagnostic challenges that can lead to PTC incidental discovery. For this retrospective study, 287 patients with a PTC diagnosis were selected. For each, the following variables were analysed: sex, age, ultrasound (US) appearance, number of thyroid nodules, PTC size, PTC variants and presence of other associated pathology. Pre-operative fine needle aspiration (FNA) results were classified according to the five-tiered SIAPEC system. For 281 patients, the US-guided FNA results were available. Cytohistological correlation was evaluated in terms of FNA sensitivity and false negative rate. An incidental PTC was found in 45.2 % of patients. The majority of these were due to unsuccessful US detection of malignant nodules (103 cases); incorrect cytological diagnosis was responsible for the other 24 cases. The most powerful clinical confounding factors were: multinodular background versus single nodule presentations (p?0.001) and histotype (follicular vs conventional variant, p?0.05). Of course, tumour size remains a strongly influential feature on pre-operative diagnosis, with greater difficulties arising for carcinomas <5 mm. Moreover, FNA sensitivity was lower also in large PTCs (>2 cm) due to tumour heterogeneity. Although with limitations related to the tumour’s intrinsic features and the thyroid background, US-guided FNA, especially if performed by a dedicated multidisciplinary team, is a powerful diagnostic tool for detecting malignant thyroid nodules. To the state of the art, we propose a practical clinical-pathological cut-off for this procedure, setting it at 5 mm. 相似文献
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