Selenium Concentrations and Mortality among Community-Dwelling Older Adults: Results from IlSIRENTE Study.

BACKGROUND: Selenium has a wide range of pleiotropic effects, influencing redox homeostasis, thyroid hormone metabolism, and protecting from oxidative stress and inflammation. Serum selenium levels are reduced in the older population. OBJECTIVES: to investigate the association of serum selenium levels with all-cause mortality in a sample of community-dwelling older adults. DESIGN AND SETTING: Data are from the 'Invecchiamento e Longevità nel Sirente' (Aging and Longevity in the Sirente geographic area, ilSIRENTE) study, a prospective cohort study that collected information on individuals aged 80 years and older living in an Italian mountain community (n=347). The main outcome was risk of death after ten years of follow-up. PARTICIPANTS AND MEASUREMENTS: Participants were classified according to the median value of selenium (105.3 µg/L) in two groups: high selenium and low selenium. RESULTS: A total of 248 deaths occurred during a 10-year follow-up. In the unadjusted model, low levels of selenium was associated with increased mortality (HR, 0.66; 95% CI 0.51-0.85). After adjusting for potential confounders the relationship remained significant (HR, 0.71; 95% CI 0.54-0.92). CONCLUSIONS: Low serum levels of selenium are associated with reduced survival in elderly, independently of age and other clinical and functional variables.

Frailty and muscle metabolism dysregulation in the elderly.

The frailty syndrome is increasingly recognized by geriatricians to identify elders at an extreme risk of adverse health outcomes. The physiological changes that result in frailty are complex and up to now have been extremely difficult to characterize due to the frequent coexistence of acute and chronic illness. Frailty is characterized by an decline in the functional reserve with several alterations in diverse physiological systems, including lower energy metabolism, decreased skeletal muscle mass and quality, altered hormonal and inflammatory functions. This altered network leads to an extreme vulnerability for disease, functional dependency, hospitalization and death. One of the most important core components of the frailty syndrome is a decreased reserve in skeletal muscle functioning which is clinically characterized by a loss in muscle mass and strength (sarcopenia), in walking performance and in endurance associated with a perception of exhaustion and fatigue. There are a number of physiological changes that occur in senescent muscle tissues that have a critical effect on body metabolism. The causes of sarcopenia are multi-factorial and can include disuse, changing hormonal function, chronic diseases, inflammation, insulin resistance, and nutritional deficiencies. In this review, we will explore the dysregulation of some biological mechanisms that may contribute to the pathophysiology of the frailty syndrome through age-related changes in skeletal muscle mass and function.

The cost-effectiveness of doxazosin for the treatment of hypertension in type II diabetic patients in the UK and Italy.

The objective of this analysis was to assess the cost-effectiveness of achieving 'tight control' versus 'less tight control' of blood pressure, as defined in the UK Prospective Diabetics Study 38, in type II diabetic patients in the UK and Italy. The effect of including doxazosin in a 'tight control' combination therapy was analysed. Given doxazosin's positive impact on lipid levels in addition to its antihypertensive effect, it is hypothesised that treatment including doxazosin will reduce the incidence of macrovascular complications. For each country, a Markov model was constructed to simulate macrovascular outcomes of patients on various drug combinations. Transitional probabilities were based on the risk rates presented in UKPDS 38. Risk rates were adjusted for the ageing of the cohort and the lipid-lowering properties of doxazosin using Framingham risk equations. Incremental cost-effectiveness ratios ranged from 2224 Pounds to 4867 Pounds (US$3225-7057) per life-year saved for the UK and from L1.8-9.3 million (US$818-4159) per life-year saved for Italy. Doxazosin is a cost-effective agent when included in a combination therapy in the treatment of hypertension in the diabetic populations of the UK and Italy.

Equivalence of pharmacokinetic characteristics and bronchodilating effect between two combined formulations of nedocromil sodium and salbutamol: MDI and nebulizer solution.

The aim of this study was to determine the equivalence of single doses of two nedocromil sodium/salbutamol combined formulations, namely (a) metered dose inhaler (MDI) (nedocromil sodium 4 mg + salbutamol 0.2 mg) and (b) nebulizer solution (nedocromil sodium 10 mg + salbutamol 1.5 mg), in a group of healthy volunteers. The plasma pharmacokinetic profiles of nedocromil sodium and the pharmacodynamic effect (bronchodilation) of salbutamol were evaluated. Twelve healthy volunteers entered this randomized, cross-over study. All subjects completed the pharmacokinetic section of the study. Nine of them completed also the pharmacodynamic part of the study. After preliminary controls, treatments were administered on separate days and in random order. Blood samples were collected 5, 10, 20, 30, 45 min, 1, 1.5, 2, 3 and 4h after test medication. Specific airways resistance (sRaw) was measured 5, 10, 20, 30, 40, 50 and 60 min following test treatment administration. The pharmacokinetic profiles of nedocromil sodium were evaluated using the maximum plasma concentration (Cmax), the time to peak plasma concentration (tmax) and the area under the curve from 0 to infinity (AUCzero-->infinity), derived from the plasma concentration/time curves. The bronchodilating effect of the two test treatments were evaluated as sRaw percentage change at each time point, maximum sRaw percentage change (sRawMAX) and area under the curve (AUC) of sRaw percentage change plotted against the time of recording. The mean pharmacokinetic results for MDI and nebulizer solution were, respectively: Cmax = 7.59 ng.ml-1 +/- 4.99 and 9.64 ng.ml-1 +/- 5.22 (p = 0.36), tmax = 0.21 hour +/- 0.08 and 0.28 hour +/- 0.14 (p = 0.19), AUCzero-->infinity = 6.28 ng.ml-1.h +/- 2.91 and 12.91 ng.ml-1.h +/- 4.12 (p = 0.008), while the mean pharmacodynamic results were: sRawMAX = -37.91% +/- 13.77 and -39.69% +/- 9.69 (p = 0.69), AUC = -1465.5 delta %.h +/- 799.3 and -1683.4 delta %.h +/- 496.3 (p = 0.45). No statistically significant differences between treatments were found also for sRaw percentage change at each time point. The absorption of nedocromil sodium was proportional to the two administered nominal doses and similar to values obtained after administration of nedocromil sodium alone. The two combined formulations of nedocromil sodium and salbutamol produce an equivalent bronchodilating effect. These results confirm the pharmacological equivalence of the two products, whichever may be used according to specific therapeutic needs.