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101.
Inhibition of c-Jun N-terminal kinase decreases cardiomyocyte apoptosis and infarct size after myocardial ischemia and reperfusion in anaesthetized rats 总被引:15,自引:0,他引:15
Ferrandi C Ballerio R Gaillard P Giachetti C Carboni S Vitte PA Gotteland JP Cirillo R 《British journal of pharmacology》2004,142(6):953-960
1 Myocardial ischemia/reperfusion is associated with inflammation, apoptosis and necrosis. During this process, c-jun N-terminal kinase is activated in cardiac myocytes resulting in apoptosis. 2 This study investigates the effects of AS601245, a nonpeptide ATP competitive JNK inhibitor, on infarct size caused by myocardial ischemia/reperfusion in anaesthetized rats. The left descending coronary artery of anaesthetized rats was occluded for 30 min and then reperfused for 3 h. AS601245 was administered 5 min before the end of the ischemia period as an i.v. bolus (1.5, 4.5 or 15 mg kg(-1) i.v.) followed by continuous i.v. infusion (18, 55 and 183 microg kg(-1) min(-1), respectively) during reperfusion. Controls received saline only. 3-Aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, was used as reference compound at 10 mg kg(-1) i.v. bolus plus 0.17 mg kg(-1) min(-1) continuous infusion. 3 AS601245 significantly reduced infarct size at 4.5 mg kg(-1) (-44%; P<0.001) and 15 mg kg(-1) i.v. (-40.3%; P<0.001) similarly to 3-aminobenzamide (-44.2%; P<0.001). This protective effect was obtained without affecting hemodynamics or reducing ST-segment displacement. 4 The beneficial effects on infarct size correlated well with the reduction of c-jun phosphorylation (-85%; P<0.001 versus control) and of TUNEL-positive cells (-82.1%; P<0.001) in post-ischemic cardiomyocytes. No change in the phosphorylation state of p38 MAPK and ERK in post-ischemic heart was observed in the presence of AS601245 in comparison to the vehicle-treated group. 5 These results demonstrate that blocking the JNK pathway may represent a novel therapeutic approach for treating myocardial ischemia/reperfusion-induced cardiomyocyte death. 相似文献
102.
Clinical, hormonal and magnetic resonance imaging (MRI) predictors of transsphenoidal surgery outcome in acromegaly 总被引:1,自引:0,他引:1
Bourdelot A Coste J Hazebroucq V Gaillard S Cazabat L Bertagna X Bertherat J 《European journal of endocrinology / European Federation of Endocrine Societies》2004,150(6):763-771
OBJECTIVE: Progress in the treatment of acromegaly with drugs is making it necessary to improve the prediction of the outcome of transsphenoidal surgery. DESIGN: We evaluated clinical, hormonal and radiologic predictors based on magnetic resonance imaging (MRI) of surgical outcome in patients with acromegaly. METHODS: This retrospective analysis included 125 consecutive patients investigated for acromegaly in a single endocrine unit since the use of MRI imaging began (1988). Eighty-three of these patients (50 women) underwent transsphenoidal surgery and were investigated before and after surgery in our department. A neuroradiologist unaware of the surgical outcome analyzed the results of pituitary gland MRI investigations. RESULTS: Surgical remission rates were 44%, 43%, 61% and 59% based on mean basal GH concentration under 2.5 microg/l, GH/oral glucose tolerance test (OGTT) of <1 microg/l, GH/OGTT of <2 microg/l or IGF-I concentration normal for age and sex respectively. In univariate logistic regression analysis with IGF-I concentration used as the criterion for cure, young age (P<0.001), high IGF-I concentration before surgery (P<0.01), high basal GH concentration before surgery (P<0.02), and high nadir GH/OGTT before surgery (P=0.03) were predictors of poor outcome. The following results in standardized MRI analysis were associated with a higher probability of not being cured: adenoma greater than 15 mm in diameter (P<0.02), infrasellar extension (P=0.04), suprasellar extension (P<0.005) and invasive adenoma (0.02) according to MRI staging. MRI analysis of the intracavernous extension showed that stages above B2 (possible sinus extension with sign of invasion of the space below the carotid artery) were associated with a lower probability of postoperative normal GH plasma levels (P=0.01). In multivariate analysis, age, preoperative hormonal levels and adenoma size remained the major predictors of surgical outcome. CONCLUSIONS: This report provides the first evidence that detailed MRI analysis of adenoma size, location and potential invasion, together with preoperative clinical and hormonal parameters, can be used for the prediction of hormonal outcome after transsphenoidal surgery for acromegaly. 相似文献
103.
PURPOSE: Studies using magnetic resonance imaging have shown that reduced hippocampal volume is associated with a history of febrile seizures, the duration of epilepsy, and the number of generalized tonic-clonic seizures. It is uncertain whether these factors have the same influence on functional as on structural measures of the integrity of the epileptogenic zone. METHODS: We used positron emission tomography (PET) with fluorine 18 2-deoxyglucose to study 91 patients with temporal lobe seizure foci localized by ictal video-EEG. PET was performed in the awake interictal resting state with ears plugged and eyes patched. We recorded surface EEG during injection (5 mCi) and the 30-min uptake period. We used a standard template to analyze PET scans. RESULTS: A significant negative relation was found between the duration of epilepsy and hippocampal glucose metabolism ipsilateral to the epileptic focus. Patients with a history of either any febrile seizures, or complex, or prolonged febrile seizures, did not have greater hypometabolism ipsilateral to the epileptic focus than did patients without a febrile seizure history. We found no effect of generalized tonic-clonic seizure history. CONCLUSIONS: Longer epilepsy duration is associated with greater hypometabolism, suggesting that epilepsy is a progressive disease. 相似文献
104.
Blin N Morineau N Gaillard F Morin O Milpied N Harousseau JL Moreau P 《Leukemia & lymphoma》2004,45(10):2161-2163
The incidence of mucormycosis, defined as systemic infection caused by fungi of the class Phycomycetes has been increasing over the past 2 decades, especially in profoundly immunocompromised hosts. We report a new case in a patient presenting with post-transplant high-grade non-Hodgkin's lymphoma who received a prolonged treatment with voriconazole and caspofungin for an invasive pulmonary aspergillosis. Definite diagnosis of mucormycosis was made by liver biopsy of nodules mimicking progressive lymphoma. The patient died 1 week after the diagnosis of mucormycosis despite the administration of liposomal amphotericin B. The role of voriconazole and caspofungin in the emergence of mucormycosis is discussed. 相似文献
105.
The present study investigated whether facial EMG measures are sensitive to the effects of fatigue. EMG activity of the corrugator and frontalis muscles was recorded during and after a simulated workday. Fatigue was evaluated in four ways: (a) the building up of fatigue effects during the workday, (b) the building up of fatigue during a test period, (c) examination of after-effects of the workday in two test sessions in the evening, and (d) comparison of subjects with a high-and low-score on an Emotional Exhaustion questionnaire. EMG activity decreased during the workday and increased again in the evening. EMG activity also increased during a test period, reflecting increased mobilization to maintain performance. High-score subjects showed a lower level of EMG activity throughout the entire workday. They reported a higher need for recovery, experienced the workday as more fatiguing, and were less well rested when getting up. EMG measures seem to reflect that high-score subjects have problems with investing sufficient energy to maintain performance during a workday. 相似文献
106.
Microglial changes accompanying the promotion of retinal ganglion cell axonal regeneration into peripheral nerve grafts 总被引:4,自引:0,他引:4
Intravitreal injection of the microglia inhibitor tuftsin 1-3 leads to an increase in retinal ganglion cell axonal regeneration into peripheral nerve grafts and a decrease in phagocytic cells in the retina. However, the relation of phagocytic cells and particularly microglia towards axonal regeneration remains unclear. Initially, to assess this, tuftsin 1-3's effect on axonal regeneration was reexamined by doing a dose-response study. Optimal doses were found to be 2.5 g/ml and 250 g/ml in rats and hamsters respectively. We then studied retinal phagocytic cells in rats. Microglial cells were classified as resting or activated based on their morphology following OX42 immunolabelling. In controls, most microglial cells were in the resting state. Optic nerve cut led to an increase in the total number of microglia and a ten-fold elevation in the proportion of activated cells; changes were more pronounced at the optic nerve stump. Anastomosis of an autologous segment of sciatic nerve to the stump of the freshly cut optic nerve minimized the overall increase in microglia, and combined with 2.5 g/ml tuftsin 1-3, lead to a marked blunting of activation. Preservation within the retina of a higher proportion of resting over active form of microglia, and not the prevention of microglial proliferation per se, may be a crucial factor in allowing additional retinal ganglion cell axons to regenerate into peripheral nerve grafts. 相似文献
107.
Foehrenbach H Albérini JL Maszelin P Bonardel G Tenenbaum F de Dreuille O Richard B Gaillard JF Devaux JY 《Presse medicale (Paris, France : 1983)》2003,32(6):276-283
A NEW FORM OF MEDICAL IMAGING: Positron emission tomography (PET) is used for the non-invasive in vivo visualisation of biochemical cell processes. It reveals the metabolic characteristics of neoplastic lesions and hence their identification by compensating the lack of lesion specificity of radiological techniques. VARIOUS INDICATIONS: Using the current oncology marker, 18F-fluorodeoxyglucose (FDG), excellent results with PET have been established at all stages of neoplasia, notably for the diagnosis of initial malignancy and the identification of residual lesions and early detection of relapses. Moreover, the fact that the whole of the body can be explored makes PET the tool of choice in the control of the extension and operability of cancers. With the close correlation between imaging and the metabolism of the lesions, PET is the earliest and most precise for assessing the effects of treatment. LIMITS AND PERSPECTIVES: The existence of benign inflammatory FDG binding should lead to the development of markers of other metabolisms directly linked to cell proliferation. The lack of anatomical reference points characteristic of PET does not permit the precise localisation of the lesions detected and could be corrected by combining, in a single apparatus, the PET camera and an X scan, the anatomical resolution of which is irreplaceable. This type of equipment represents the development of a new branch of medical imaging, oncological imaging. 相似文献
108.
Survival of extremely preterm infants has improved with modern neonatal intensive care. Chronic lung disease of prematurity, however, remains an important clinical problem and this article reviews the changing presentation and discusses new concepts of its aetiology. 相似文献
109.
Harrap SB Tzourio C Cambien F Poirier O Raoux S Chalmers J Chapman N Colman S Leguennec S MacMahon S Neal B Ohkubo T Woodward M;PROGRESS Collaborative Group 《Hypertension》2003,42(3):297-303
The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 individuals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly (P<0.0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline; neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment. 相似文献
110.