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

Oral administration of polyphenolic compounds from cognac decreases ADP-induced platelet aggregation and reduces chronotropic effect of isoprenaline in rats

This study sought to evaluate whether consumption of polyphenol extract from Cognac (CPC) modulates platelet activation and cardiovascular reactivity in rats. Male Wistar rats were treated daily for 4 weeks by intra-gastric gavage receiving CPC at 80 mg/kg/day or vehicle (5 % glucose). Platelet adhesion and aggregation in response to different activators were assessed. Cardiac and vascular reactivity in response to various agonists as well as NO measurement by electron paramagnetic resonance technique were investigated in isolated heart and thoracic aorta. Oral administration of CPC decreased platelet aggregation induced by ADP but not by collagen. CPC did not affect adhesion to collagen. The chronotropic but not the inotropic response to isoprenaline was reduced without alteration of NO production in hearts from CPC-treated rats. CPC treatment did not affect ex vivo relaxation to acetylcholine nor NO content of rat aorta. CPC did not significantly alter the response to phenylephrine in aorta despite the participation of endothelial vasoconstrictor products. In summary, chronic treatment with CPC has no impact on ex vivo vascular and cardiac reactivity; however, it reduced heart work and platelet aggregation. These data suggest the existence of compounds in Cognac that may decrease the risk of coronary thrombosis and protect against some cardiac diseases

Mense e personale addetto alle cucine: valutazione dei rischi occupazionali

The aim of the study is to evaluate the occupational risks among food service workers and cooks. During the occupational risks assessment the following risk factors must be evaluated: musculoskeletal disorders, chemical risk (cleaning kitchen work surface, dishes, utensils ecc.) biological risk (contact with foods or biological agents) cancerogenic risk (by baking smoke inhalation), and psycho-social stress. In this study the preventive measures and protective equipment to prevent health hazards for these workers have been evaluated (i.e. aspiration hood, adapted ventilation, chosen of less harmful methods of baking, ecc.). In particular the performance of rigid behavioural norms and hygienic procedures is very important for cooks and food service workers to reduce the risk of occupational infections

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer.

BACKGROUND: A randomized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2. PATIENTS AND METHODS: Among 124 patients randomized, 123 are assessable for toxicity and 118 for response. Patients received weekly paclitaxel single agent (80 mg/m2) or combined with trastuzumab (4 mg/kg loading dose, then weekly 2 mg/kg). HER-2 overexpression was determined by immunohistochemistry (IHC). Patients with 2+/3+ IHC scores were eligible. IHC was compared with HER-2 serum extracellular domain (ECD). RESULTS: Patient characteristics were similar in the two arms. Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity. No patient developed cardiac toxicity. The combined treatment was statistically significant superior for overall response rate (ORR) (75% vs. 56.9%; P = 0.037), particularly in the subset of IHC 3+ patients (84.5% vs. 47.5%; P = 0.00050). A statistically significant better median time to progression was seen in the subgroup with IHC 3+ (369 vs. 272 days; P = 0.030) and visceral disease (301 vs. 183 days; P = 0.0080) treated with combination. Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR (P = 0.0035). CONCLUSION: Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3+

Case studies and evidence-based approaches to addressing urban soil lead contamination

Urban soils in many communities in the United States and internationally have been contaminated by lead (Pb) from past use of lead additives in gasoline, deterioration of exterior paint, emissions from Pb smelters and battery recycling and other industries. Exposure to Pb in soil and related dust is widespread in many inner city areas. Up to 20–40% of urban children in some neighborhoods have blood lead levels (BLLs) equal to or above 5 μg per decilitre, the reference level of health concern by the U.S. Centers for Disease Control. Given the widespread nature of Pb contamination in urban soils it has proven a challenge to reduce exposure. In order to prevent this exposure, an evidence-based approach is required to isolate or remediate the soils and prevent children and adult's ongoing exposure. To date, the majority of community soil Pb remediation efforts have been focused in mining towns or in discrete neighborhoods where Pb smelters have impacted communities. These efforts have usually entailed very expensive dig and dump soil Pb remediation techniques, funded by the point source polluters. Remediating widespread non-point source urban soil contamination using this approach is neither economical nor feasible from a practical standpoint. Despite the need to remediate/isolate urban soils in inner city areas, no deliberate, large scale, cost effective Pb remediation schemes have been implemented to isolate inner city soils impacted from sources other than mines and smelters. However, a city-wide natural experiment of flooding in New Orleans by Hurricane Katrina demonstrated that declines in soil Pb resulted in major BLL reductions. Also a growing body of literature of smaller scale pilot studies and programs does exist regarding low cost efforts to isolate Pb contaminated urban soils. This paper reviews the literature regarding the effectiveness of soil Pb remediation for reducing Pb exposure and BLL in children, and suggests best practices for addressing the epidemics of low-level Pb poisoning occurring in many inner city areas

Oxaliplatin plus high-dose folinic acid and 5-fluorouracil i.v. bolus (OXAFAFU) versus irinotecan plus high-dose folinic acid and 5-fluorouracil i.v. bolus (IRIFAFU) in patients with metastatic colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase III trial

The primary end point of this phase III trial was to compare the response rate (RR) of oxaliplatin (OXA) plus levo-folinic acid (l-FA) and 5-fluorouracil (5-FU) bolus with that of irinotecan (IRI) plus l-FA and 5-FU bolus in advanced colorectal carcinoma

Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101)

Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations

Targeting oxidative stress for improving cardiovascular performance in the elderly

Oxidative stress is implicated in the pathophysiology of several cardiovascular diseases, as evidenced by correlation between oxidative stress markers and Heart Failure (HF) and by direct molecular evidence for an etiological role of reactive oxygen species (ROS). ROS play an important role in signalling processes, but their overproduction generates oxidative stress. Previous studies demonstrated that HF was associated with antioxidant deficit as well as increased oxidative stress. Furthermore, these changes correlated with the hemodynamic function, suggesting their role in the pathogenesis of cardiac dysfunction. An important mechanism involved in cellular cardiovascular response is represented by sirtuins. SIRT1 inhibition determines suppression of genes ac tivated by exposure to heat shock, on the contrary, SIRT1 activation enhances the heat shock response. Then the ability of SIRT1 to modulate stress resistance is multifaceted and not only linked to oxidative stress, but also to other stressful stimuli. Recently several studies have demonstrated the capability of physical activity to induce SIRT1 activity and, in turn, the ability of this enzyme to mediate the favourable antioxidant effects of the exercise training. Other agents able to induce SIRT1 activity have demonstrated some effects on cardiac function. Resveratrol supplementation has been shown to decrease cardiovascular risk factors, and the positive effect of resveratrol on training response and aerobic capacity in rats to be mediated via SIRT1. The future research should be addressed to better clarify the possible role of the antioxidants therapy in clinical studies, in particular defining a standardization of procedures, doses and duration of treatment