Antioxidant Supplementation in the Treatment of Aging-Associated Diseases

Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented

The 5 C\u27s: A Problem-Solving Approach to Study Skills

The most expansive and mobilizing impression a student can acquire is that what is, may be, but it can be otherwise. The attitude that all life and circumstances are amenable to analysis and some measure of modification is the avowed purpose of the strategy to improve Study Skills described below

ON EXISTENCE OF BOUNDED FEASIBLE SOLUTIONS TO NEUMANN BOUNDARY CONTROL PROBLEM FOR p-LAPLACE EQUATION WITH EXPONENTIAL TYPE OF NONLINEARITY

We study an optimal control problem for mixed Dirichlet-Neumann boundary value problem for the strongly non-linear elliptic equation with p-Laplace operator and L1-nonlinearity in its right-hand side. A distribution u acting on a part of boundary of open domain is taken as a boundary control. The optimal control problem is to minimize the discrepancy between a given distribution yd 2 L2( ) and the current system state. We deal with such case of nonlinearity when we cannot expect to have a solution of the state equation for any admissible control. After dening a suitable functional class in which we look for solutions and assuming that this problem admits at least one feasible solution, we prove the existence of optimal pairs. We derive also conditions when the set of feasible solutions has a nonempty intersection with the space of bounded distributions L1( )

Sirtuin 1 and Aging Theory for Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary disease (COPD) is an inflammatory syndrome that represents an increasing health problem, especially in the elderly population. Drug therapies are symptomatic and inadequate to contrast disease progression and mortality. Thus, there is an urgent need to clarify the molecular mechanisms responsible for this condition in order to identify new biomarkers and therapeutic targets. Processes including oxidant/antioxidant, protease/antiprotease, and proliferative/antiproliferative balance and control of inflammatory response become dysfunctional during aging as well as in COPD. Recently it was suggested that Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to oxidative stress and chronic inflammation, is implicated in both development and progression of COPD. The present review focuses on the involvement of SIRT1 in the regulation of redox state, inflammation, and premature senescence, all crucial characteristics of COPD phenotypes. Recent evidence corroborating the statement of the "aging theory for COPD" was also discussed

Persistent itching associated to silodosin in an elderly patient: Implications for drug-drug interactions and pharmacogenetics

Itching is a complaint affecting especially the elderly, in whom comorbidities and polypharmacy increase the risk of adverse drug reactions. We reported the case of an 83-year-old man with a generalized itching lasting more than 3 years underwent to our attention during his enrollment in a clinical study at University Hospital of Salerno, Italy where he was planned for a thromboendoarteriectomy because of left internal carotid artery stenosis. His medical history included arterial hypertension, ischemic heart disease, chronic cerebrovasculopathy, dyslipidaemia and prostatic hyperplasia. His therapy was olmesartan medoxomil 10 mg/die, nebivolol 5 mg x 1/2/die, acetylsalicylic acid 100 mg/die, omeprazole 20 mg/die, atorvastatin 20 mg/die, supplements contain ing EPA and DHA, vitamins K2, B6, B12 and folic acid (vit B9) and silodosin 8 mg/die. The patient’s demographic clinic, laboratory data and a pharmacological anamnesis were collected. Screening of two ABCB1 polymorphisms associated to a decrease of P-glycoprotein (P-gp) activity was performed by realtime PCR. An iatrogenic cause of the itching was suspected and the Naranjo algorithm was applied, revealing possible association between such an adverse reaction and all used drugs. Because the patient reported the beginning of the itching in concomitance with the aspirin assumption, this agent was discontinued but without improvement. Then, because silodosin-atorvastatin interaction may increase the silodosin plasma concentration, this drug was switched to doxazosin and the itching disappeared. This clinical case stresses the potential misleading based on the patients’ beliefs and the importance to consider all the patients’ available information to ascertain the cause of adverse drug reactions

The Effect of the Association between Donepezil and Choline Alphoscerate on Behavioral Disturbances in Alzheimer's Disease: Interim Results of the ASCOMALVA Trial

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are a group of psychological reactions, psychiatric symptoms, and behaviors commonly found in Alzheimer's disease (AD). Four clusters of BPSD have been described: mood disorders (depression, anxiety, and apathy), psychotic symptoms (delusions and hallucinations), aberrant motor behaviors (pacing, wandering, and other purposeless behaviors), and inappropriate behaviors (agitation, disinhibition, and euphoria). Most of them are attributed to acetylcholine deficiency. OBJECTIVE: To evaluate if a higher amount of acetylcholine obtained by associating donepezil and choline alphoscerate might have a favorable effect on BPSD. METHODS: BPSD were measured at baseline and after 24 months in 113 mild/moderate AD patients, included in the double-blind randomized trial ASCOMALVA, by the Neuropsychiatric Inventory (NPI). Two matched groups were compared: group A treated with donepezil (10 mg/day) plus choline alphoscerate (1200 mg/day), and group B treated with donepezil (10 mg/day) plus placebo. RESULTS: Data of NPI revealed a significant decrease of BPSD severity and distress of the caregiver in patients of group A compared with group B. Mood disorders (depression, anxiety and apathy) were significantly decreased in subjects treated with donepezil and choline alphoscerate, while their severity and frequency was increased in the other group. CONCLUSIONS: Patients treated with donepezil plus choline alphoscerate showed a lower level of behavioral disturbances than subjects treated with donepezil only, suggesting that the association can have beneficial effect

Biomarkers to personalize the treatment of rheumatoid arthritis: Focus on autoantibodies and pharmacogenetics

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is very complex and heterogeneous. If not adequately treated, RA patients are likely to manifest excess of morbidity and disability with an important impact on the quality of life. Pharmacological treatment is based on the administration of the disease-modifying antirheumatic drugs (DMARDs), subdivided into conventional synthetic (csDMARDs), targeted synthetic (tsDMARDs), and biological (bDMARDs). bDMARDs are now frequently administered in patients, both as alternative treatment and together with csDMARDs. Unfortunately, there is a therapeutic response variability both to old and new drugs. Therefore, to identify pre-therapeutic and on-treatment predictors of response is a priority. This review aims to summarize recent advances in understanding the causes of the variability in treatment response in RA, with particular attention to predictive potential of autoantibodies and DMARD pharmacogenetics. In recent years, several biomarkers have been proposed to personalize the therapy. Unfortunately, a magic bullet does not exist, as many factors concur to disease susceptibility and treatment outcomes, acting around the patient’s congenital background. Models integrating demographic, clinical, biochemical, and genetic data are needed to enhance the predictive capacity of specific factors singularly considered to optimize RA treatment in light of multidisciplinary patient management

Migration and Localization of Metal Atoms on Strained Graphene

Reconstructed point defects in graphene are created by electron irradiation and annealing. By applying electron microscopy and density functional theory, it is shown that the strain field around these defects reaches far into the unperturbed hexagonal network and that metal atoms have a high affinity to the nonperfect and strained regions of graphene. Metal atoms are attracted by reconstructed defects and bonded with energies of about 2 eV. The increased reactivity of the distorted π-electron system in strained graphene allows us to attach metal atoms and to tailor the properties of graphene.Peer reviewe