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991.
992.
Corrias A Grugni G Crinò A Di Candia S Chiabotto P Cogliardi A Chiumello G De Medici C Spera S Gargantini L Iughetti L Luce A Mariani B Ragusa L Salvatoni A Andrulli S Mussa A Beccaria L;Study Group for Genetic Obesity of Italian Society of Pediatric Endocrinology Diabetology 《Clinical endocrinology》2012,76(6):843-850
Objective A recent study evidenced by metyrapone test a central adrenal insufficiency (CAI) in 60% of Prader–Willi syndrome (PWS) children. These results were not confirmed in investigations with low [Low‐Dose Tetracosactrin Stimulation Test (LDTST), 1 μg] or standard‐dose tetracosactrin stimulation tests. We extended the research by LDTST in paediatric patients with PWS. Design Cross‐sectional evaluation of adrenal stress response to LDTST in a PWS cohort of a tertiary care referral centre. Patients Eighty‐four children with PWS. Measurements Assessment of adrenal response by morning cortisol and ACTH dosage, and 1‐μg tetracosactrin test. Response was considered appropriate when cortisol reached 500 nm ; below this threshold, patients were submitted to a second test. Responses were correlated with the patients’ clinical and molecular characteristics to assess genotype–phenotype correlation. Results Pathological cortisol peak responses to the LDTST were registered in 12 patients (14·3%) who had reduced basal (169·4 ± 83·3 nm ) and stimulated (428·1 ± 69·6 nm ) cortisol levels compared to patients with normal responses (367·1 ± 170·6 and 775·9 ± 191·3 nm , P < 0·001). Body mass index standard deviation score was negatively correlated with basal and peak cortisol levels (both P < 0·001), and the patients’ ages (P < 0·001). In patients with deletion on chromosome 15, the cortisol peak was significantly lower than that in uniparental disomy (UPD) cases (P = 0·030). At multiple regression analysis, the predictors of peak response were basal cortisol, age, and UPD subclass (r2 = 0·353, P < 0·001). Standard‐dose (250 μg) tetracosactrin test confirmed CAI in 4/12 patients (4·8% of the cohort). Conclusions Our results support the hypothesis that, albeit rare, CAI may be part of the PWS in childhood. 相似文献
993.
Calland N Albecka A Belouzard S Wychowski C Duverlie G Descamps V Hober D Dubuisson J Rouillé Y Séron K 《Hepatology (Baltimore, Md.)》2012,55(3):720-729
Here, we identify (-)-epigallocatechin-3-gallate (EGCG) as a new inhibitor of hepatitis C virus (HCV) entry. EGCG is a flavonoid present in green tea extract belonging to the subclass of catechins, which has many properties. Particularly, EGCG possesses antiviral activity and impairs cellular lipid metabolism. Because of close links between HCV life cycle and lipid metabolism, we postulated that EGCG may interfere with HCV infection. We demonstrate that a concentration of 50 μM of EGCG inhibits HCV infectivity by more than 90% at an early step of the viral life cycle, most likely the entry step. This inhibition was not observed with other members of the Flaviviridae family tested. The antiviral activity of EGCG on HCV entry was confirmed with pseudoparticles expressing HCV envelope glycoproteins E1 and E2 from six different genotypes. In addition, using binding assays at 4°C, we demonstrate that EGCG prevents attachment of the virus to the cell surface, probably by acting directly on the particle. We also show that EGCG has no effect on viral replication and virion secretion. By inhibiting cell-free virus transmission using agarose or neutralizing antibodies, we show that EGCG inhibits HCV cell-to-cell spread. Finally, by successive inoculation of na?ve cells with supernatant of HCV-infected cells in the presence of EGCG, we observed that EGCG leads to undetectable levels of infection after four passages. CONCLUSION: EGCG is a new, interesting anti-HCV molecule that could be used in combination with other direct-acting antivirals. Furthermore, it is a novel tool to further dissect the mechanisms of HCV entry into the hepatocyte. 相似文献
994.
995.
Autoimmune thyroid disease (AITD) is an inflammatory thyroiditis that in some cases is characterized by lymphocytic infiltration of the thyroid gland, also referred to as chronic lymphocytic thyroiditis or Hashimoto thyroiditis. Hashimoto thyroiditis is one of the commonest causes of hypothyroidism. Hypothyroidism has been associated with osteoarthritis (OA) and inflammatory forms of arthritis and with several well defined connective tissue diseases, which in turn can cause arthritis. The presence of arthritis in patients with AITD with normal thyroid function is now being increasingly recognized. There is also considerable evidence to suggest that AITD is highly associated with fibromyalgia syndrome. We review the current literature on the rheumatologic manifestations of AITD and describe the features in its presentation that set it apart from other forms of autoimmune arthritis. 相似文献
996.
Grisafi D Tassone E Dedja A Oselladore B Masola V Guzzardo V Porzionato A Salmaso R Albertin G Artusi C Zaninotto M Onisto M Milan A Macchi V De Caro R Fassina A Bordigato MA Chiandetti L Filippone M Zaramella P 《Lung》2012,190(4):419-430
Background
Moderate normobaric hyperoxia causes alveolar and vascular lung derangement in the newborn rat. Endogenous nitric oxide (NO), which promotes lung growth, is produced from the metabolism of l-arginine to l-citrulline in endothelial cells. We investigated whether administering l-citrulline by raising the serum levels of l-arginine and enhancing NO endogenous synthesis attenuates moderate hyperoxia-induced lung injury.Methods
Newborn rats were exposed to FiO2?=?0.6 or room air for 14?days to induce lung derangement and then were administered l-citrulline or a vehicle (sham). Lung histopathology was studied with morphometric features. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for analysis. Lung vascular endothelial growth factor (VEGF), nitric oxide synthase (eNOS), and matrix metalloproteinase 2 (MMP2) gene and protein expressions were assessed.Results
Serum l-arginine rose in the L-citr?+?hyperoxia group (p?=?0.05), as well as the Von Willebrand factor stained vessels count (p?=?0.0008). Lung VEGF immune staining, localized on endothelial cells, was weaker in the sections under hyperoxia than the l-citr?+?hyperoxia and room air groups. This pattern was comparable with the VEGF gene and protein expression profiles. Mean alveolar size increased in the untreated hyperoxia and sham-treated groups compared with the groups reared in room air or treated with l-citrulline under exposure to hyperoxia (p?=?0.0001). Lung VEGF and eNOS increased in the l-citrulline-treated rats, though this treatment did not change MMP2 gene expression but regulated the MMP2 active protein, which rose in BALF (p?=?0.003).Conclusions
We conclude that administering l-citrulline proved effective in improving alveolar and vascular growth in a model of oxygen-induced pulmonary damage, suggesting better lung growth and matrix regulation than in untreated groups. 相似文献997.
998.
999.
The clinical development of lenalidomide (Revlimid?), then pomalidomide (Actimid?) as members of immunomodulatory drugs (IMiDs) for the treatment of multiple myeloma (MM), exemplifies how insight into disease biology can lead to design of effective therapeutic agents. Increased experience and understanding of IMiD's diverse biological effects has lead to rational design of lenalidomide‐based treatment‐regimens over recent years. However, much about lenalidomide is yet to be understood and fully exploited. Here, we review what is known of lenalidomide's biological effects, clinical certainties and uncertainties in the treatment of MM, and explore its future potential with other synergistic therapeutic agents. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc. 相似文献
1000.
Romaric Lacroix Laurent Plawinski Stéphane Robert Lo?c Doeuvre Florence Sabatier Sara Martinez de Lizarrondo Anna Mezzapesa Francine Anfosso Aurelie S. Leroyer Pascale Poullin Noémie Jourde Makon-Sébastien Njock Chantal M. Boulanger Eduardo Anglés-Cano Fran?oise Dignat-George 《Haematologica》2012,97(12):1864-1872