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Drug-eluting bioresorbable scaffolds represent the last frontier in the field of angioplasty and stenting to treat coronary artery disease, one of the leading causes of morbidity and mortality worldwide. In particular, sirolimus-eluting magnesium-based scaffolds were recently introduced in clinical practice. Magnesium alloys are biocompatible and dissolve in body fluids, thus determining high concentrations of magnesium in the local microenvironment. Since magnesium regulates cell growth, we asked whether high levels of magnesium might interfere with the antiproliferative action of sirolimus. We performed in vitro experiments on rabbit coronary artery endothelial and smooth muscle cells (rCAEC and rSMC, respectively). The cells were treated with sirolimus in the presence of different concentrations of extracellular magnesium. Sirolimus inhibits rCAEC proliferation only in physiological concentrations of magnesium, while high concentrations prevent this effect. On the contrary, high extracellular magnesium does not rescue rSMC growth arrest by sirolimus and accentuates the inhibitory effect of the drug on cell migration. Importantly, sirolimus and magnesium do not impair rSMC response to nitric oxide. If translated into a clinical setting, these results suggest that, in the presence of sirolimus, local increases of magnesium concentration maintain normal endothelial proliferative capacity and function without affecting rSMC growth inhibition and response to vasodilators. 相似文献
63.
Carlo Palmieri Darren K. Patten Adam Januszewski Giorgia Zucchini Sacha J. Howell 《Molecular and cellular endocrinology》2014
Endocrine therapy forms a central modality in the treatment of estrogen receptor positive breast cancer. The routine use of 5 years of adjuvant tamoxifen has improved survival rates for early breast cancer, and more recently has evolved in the postmenopausal setting to include aromatase inhibitors. The optimal duration of adjuvant endocrine therapy remains an active area of clinical study with recent data supporting 10 years rather than 5 years of adjuvant tamoxifen. However, endocrine therapy is limited by the development of resistance, this can occur by a number of possible mechanisms and numerous studies have been performed which combine endocrine therapy with agents that modulate these mechanisms with the aim of preventing or delaying the emergence of resistance. Recent trial data regarding the combination of the mammalian target of rapamycin (mTOR) inhibitor, everolimus with endocrine therapy have resulted in a redefinition of the clinical treatment pathway in the metastatic setting. This review details the current endocrine therapy utilized in both early and advanced disease, as well as exploring potential new targets which modulate pathways of resistance, as well as agents which aim to modulate adrenal derived steroidogenic hormones. 相似文献
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Patrizia Bisiacchi Giorgia Cona Vincenza Tarantino Sami Schiff Sara Montagnese Piero Amodio Giovanna Capizzi 《Metabolic brain disease》2014,29(4):945-953
Recent evidence reveals that inter- and intra-individual variability significantly affects cognitive performance in a number of neuropsychological pathologies. We applied a flexible family of statistical models to elucidate the contribution of inter- and intra-individual variables on cognitive functioning in healthy volunteers and patients at risk for hepatic encephalopathy (HE). Sixty-five volunteers (32 patients with cirrhosis and 33 healthy volunteers) were assessed by means of the Inhibitory Control Task (ICT). A Generalized Additive Model for Location, Scale and Shape (GAMLSS) was fitted for jointly modeling the mean and the intra-variability of Reaction Times (RTs) as a function of socio-demographic and task related covariates. Furthermore, a Generalized Linear Mixed Model (GLMM) was fitted for modeling accuracy. When controlling for the covariates, patients without minimal hepatic encephalopathy (MHE) did not differ from patients with MHE in the low-demanding condition, both in terms of RTs and accuracy. Moreover, they showed a significant decline in accuracy compared to the control group. Compared to patients with MHE, patients without MHE showed faster RTs and higher accuracy only in the high-demanding condition. The results revealed that the application of GAMLSS and GLMM models are able to capture subtle cognitive alterations, previously not detected, in patients’ subclinical pathologies. 相似文献
66.
Marianna Minnetti Silvana Caiulo Rosario Ferrigno Barbara Baldini-Ferroli Giorgia Bottaro Daniele Gianfrilli Emilia Sbardella Maria Cristina De Martino Martin O. Savage 《Clinical endocrinology》2020,92(2):98-108
Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities can be caused by direct effects of adrenal hormones, particularly glucocorticoids and sex steroids, or be mediated by indirect mechanisms such as the disturbance of the growth hormone-insulin-like growth factor-1 axis and aromatization of androgens to oestrogens. The early diagnosis and optimal treatment of adrenal disorders can prevent or minimize growth disturbance and facilitate improved height gain. Mechanisms of growth disturbance in the following abnormal states will be discussed; hypercortisolaemia, hyperandrogenaemia and obesity. Prevalence and features of growth disturbance will be discussed in ACTH-dependent and ACTH-independent Cushing's syndrome, adrenocortical tumours, premature adrenarche, congenital adrenal hyperplasia and adrenal insufficiency disorders. Recommendations for management have been included. 相似文献
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Beta defensin‐1 gene polymorphisms and susceptibility to Atypical Squamous Cells of Undetermined Significance lesions in Italian gynecological patients
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69.
Laura Deroma Mattia Guerra Annalisa Sechi Giovanni Ciana Giorgia Cisilino Andrea Dardis Bruno Bembi 《European journal of pediatrics》2014,173(6):805-813
Glycogenosis type II, a genetic muscle-wasting disorder, results in a spectrum of clinical phenotypes. Enzyme replacement therapy is effective in the infantile form of the disease, while little is known about its effectiveness in late-onset disease, especially in juvenile patients. The purpose of this retrospective cohort study was to assess the long-term effects of enzyme replacement therapy (ERT) in juvenile glycogenosis type II (GSDII). Eight Italian juvenile GSDII patients, receiving biweekly infusions of 20 mg/kg recombinant human α-glucosidase for at least 72 months, were enrolled (median age at therapy start was 11.8 years). Six-minute walk test (6MWT) and forced vital capacity (FVC), measured in upright position, were chosen as the principal outcome measures. Global motor disability (modified Walton scale (WS)), muscle enzymes levels [creatine phosphokinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT)] and body mass index (BMI) were also analysed both at baseline (therapy start) and annually afterwards. At baseline, most patients (six out of eight) did not show muscle function impairment (WS?≤?2). The performance at 6MWT showed a slight improvement during follow-up as well as FVC. Muscle enzymes levels showed a clear decrease after the 1st year of treatment while remained stable afterwards. An overall decrease in BMI was also observed during follow-up, although at the individual level, trends were variable. Conclusion: ERT is effective in stabilising both motor and lung functions in juvenile patients with GSDII, possibly slowing down the rate of disease progression. Randomised controlled trials are needed to understand whether early treatment allows juvenile patients to reach adulthood with a more beneficial residual muscular function than untreated patients. 相似文献
70.
Federico Scottoni Barbara Daniela Iacobelli Antonio Maria Zaccara Giorgia Totonelli Antonio Maria Salvatore Schingo Pietro Bagolan 《Pediatric surgery international》2014,30(8):829-831