The emerging role of microRNAs in Alzheimer's disease

MicroRNAs (miRNAs) are small non-coding RNA which have been shown to regulate gene expression. The alteration ofmiRNAs expression has been associated with several pathological processes, including neurodegeneration. In the search for easily accessible and non-invasive biomarkers for Alzheimer's disease (AD) diagnosis and prognosis, circulating miRNAs are among the most promising candidates. Some of them have been consistently identified as AD-specific miRNAs and their targets also seem implicated in pathophysiological processes underlying AD. Here, we review the emerging role for miRNA in AD, giving an overview on general miRNAs biology, their implications in AD pathophysiology and their potential role as future biomarkers

Adrenergic Drugs Blockers or Enhancers for Cognitive Decline ? What to Choose for Alzheimer's Disease Patients?

The adrenergic system has an important role in normal central nervous system function as well as in brain disease. The locus coeruleus, the main source of norepinephrine in brain, is involved in the regulation of learning and memory, reinforcement of sleep-wake cycle and synaptic plasticity. In Alzheimer's disease, locus coeruleus degeneration is observed early in the course of the disease, years before the onset of clinical cognitive signs, with neurofibrillary detected at the stage of mild cognitive impairment, preceding amyloid deposition. Thus, in the last years, a great interest has grown in evaluating the possibility of central adrenergic system modulation as a therapeutic tool in Alzheimer's disease. However, evidences do not show univocal results, with some studies suggesting that adrenergic stimulation might be beneficial in Alzheimer's Disease and some others favoring adrenergic blockade. In this review, we summarize data from both hypothesis and describe the pathophysiological role of the adrenergic system in neurodegeneration

βARKct gene-therapy improves β2-adrenergic receptor-dependent neoangiogenesis following hindlimb ischemia

Following hindlimb ischemia (HI) increased catecholamine levels within the ischemic muscle can cause dysregulation of β2-adrenergic receptor (β2AR) signaling leading to reduced revascularization. Indeed, in vivo β2AR overexpression, via gene therapy, enhances angiogenesis in a rat model of HI. G protein-coupled receptor kinase 2 (GRK2) is a key regulator of βAR signaling, and βARKct, a peptide inhibitor of GRK2, has been shown to prevent βAR down-regulation and to protect cardiac myocytes and stem cells from ischemic injury, through restoration of β2AR protective signaling (i.e. Akt/eNOS). Herein, we tested potential therapeutic effects of adenoviral-mediated βARKct gene transfer in an experimental model of HI and its effects on βAR signaling and on endothelial cell (EC) function in vitro. Accordingly, in this study, we surgically induced HI in rats by femoral artery resection (FAR). Fifteen days of ischemia resulted in significant βAR down-regulation that was paralleled by an about 2-fold increase in GRK2 levels in the ischemic muscle. Importantly, in vivo gene transfer of the βARKct in the hindlimb of rats at the time of FAR resulted in a marked improvement of hindlimb perfusion, with increased capillary and βAR density in the ischemic muscle, compared to control groups. The effect of βARKct expression was also assessed, in vitro in cultured ECs. Interestingly, in ECs expressing the βARKct, fenoterol, a β2AR-agonist, induced enhanced β2AR pro-angiogenic signaling and increased EC function. In conclusion, our results suggest that βARKct gene-therapy and subsequent GRK2 inhibition promotes angiogenesis in a model of HI by preventing ischemia-induced β2AR downregulation

Infective Endocarditis: A Focus on Oral Microbiota

Infective endocarditis (IE) is an inflammatory disease usually caused by bacteria entering the bloodstream and settling in the heart lining valves or blood vessels. Despite modern antimicrobial and surgical treatments, IE continues to cause substantial morbidity and mortality. Thus, primary prevention and enhanced diagnosis remain the most important strategies to fight this disease. In this regard, it is worth noting that for over 50 years, oral microbiota has been considered one of the significant risk factors for IE. Indeed, among the disparate recommendations from the American heart association and the European Society of Cardiology, there are good oral hygiene and prophylaxis for high-risk patients undergoing dental procedures. Thus, significant interest has grown in the role of oral microbiota and it continues to be a subject of research interest, especially if we consider that antimicrobial treatments can generate drug-resistant mutant bacteria, becoming a severe social problem. This review will describe the current knowledge about the relationship between oral microbiota, dental procedures, and IE. Further, it will discuss current methods used to prevent IE cases that originate from oral pathogens and how these should be focused on improving oral hygiene, which remains the significant persuasible way to prevent bacteremia and systemic disorders

An adrenal beta-arrestin 1-mediated signaling pathway underlies angiotensin II-induced aldosterone production in vitro and in vivo.

Aldosterone produces a multitude of effects in vivo, including promotion of postmyocardial infarction adverse cardiac remodeling and heart failure progression. It is produced and secreted by the adrenocortical zona glomerulosa (AZG) cells after angiotensin II (AngII) activation of AngII type 1 receptors (AT(1)Rs). Until now, the general consensus for AngII signaling to aldosterone production has been that it proceeds via activation of G(q/11)-proteins, to which the AT(1)R normally couples. Here, we describe a novel signaling pathway underlying this AT(1)R-dependent aldosterone production mediated by beta-arrestin-1 (betaarr1), a universal heptahelical receptor adapter/scaffolding protein. This pathway results in sustained ERK activation and subsequent up-regulation of steroidogenic acute regulatory protein, a steroid transport protein regulating aldosterone biosynthesis in AZG cells. Also, this betaarr1-mediated pathway appears capable of promoting aldosterone turnover independently of G protein activation, because treatment of AZG cells with SII, an AngII analog that induces betaarr, but not G protein coupling to the AT(1)R, recapitulates the effects of AngII on aldosterone production and secretion. In vivo, increased adrenal betaarr1 activity, by means of adrenal-targeted adenoviral-mediated gene delivery of a betaarr1 transgene, resulted in a marked elevation of circulating aldosterone levels in otherwise normal animals, suggesting that this adrenocortical betaarr1-mediated signaling pathway is operative, and promotes aldosterone production and secretion in vivo, as well. Thus, inhibition of adrenal betaarr1 activity on AT(1)Rs might be of therapeutic value in pathological conditions characterized and aggravated by hyperaldosteronism

Efekty wstępnego wytrawiania ubytków klasy V wypełnionych materiałami kompozytowymi na bazie siloranów i metakrylanów

n/

Breast cancer surgery in elderly patients: postoperative complications and survival

AIMS AND BACKGROUND: Old age is associated with comorbidity and decreased functioning which influences treatment decisions in elderly breast cancer patients. The purpose of this study was to identify risk factors for complications after breast cancer surgery in elderly patients, and to assess mortality in patients with postoperative complications. METHODS: We retrospectively considered all female patients aged 65 years and older with invasive and in situ breast cancer who were diagnosed and treated between 1997 and 2012 in the Department of General and Geriatric Surgery of the University of Naples "Federico II". RESULTS AND CONCLUSION: 449 patients received surgery, of whom 18,2% (n = 82) developed one or more postoperative complications. The odds ratio of having postoperative complications show an increase with age, reaching statistical significance only for patients older than 85 [OR 5,75 (95% confidence interval 2,38-14,04); p < 0,001]. Number of concomitant diseases [OR 2,51 (95% CI 1,17 - 5,45); p = 0,01 for 3 or more concomitant diseases] and polypharmacy [OR 16,7 (95% CI 9,12 - 30,58); p < 0,0001) are associated to an increased risk of postoperative complications. Overall survival was worse in patients with postoperative complications [HR 2,06 (95% CI 1,52-2,70), p < 0,001]. This increased risk of mortality is probably due to geriatric parameters such as comorbidity or poor physical function, more than to higher complication rates