NMR-Based Metabolomics for the Assessment of Inhaled Pharmacotherapy in Chronic Obstructive Pulmonary Disease Patients.

The aim of this proof-of-concept, pilot study was the evaluation of the effects of steroid administration and suspension of an inhaled corticosteroid (ICS)-long-acting ß2-agonist (LABA) extrafine fixed dose combination (FDC) on metabolomic fingerprints in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that a comprehensive metabolomics approach discriminates across inhaled pharmacotherapies and that their effects on metabolomic signatures depend on the biological fluids analyzed. We performed metabolomics via nuclear magnetic resonance (NMR) spectroscopy in exhaled breath condensate (EBC), sputum supernatants, serum, and urine. Fourteen patients suffering from COPD who were on regular inhaled fluticasone propionate/salmeterol therapy (visit 1) were consecutively treated with 2-week beclomethasone dipropionate/formoterol (visit 2), 4-week formoterol alone (visit 3), and 4-week beclomethasone/formoterol (visit 4). The comprehensive NMR-based metabolomics approach showed differences across all pharmacotherapies and that different biofluids provided orthogonal information. Serum formate was lower at visits 1 versus 3 (P = 0.03), EBC formate was higher at visit 1 versus 4 (P = 0.03), and urinary 1-methyl-nicotinamide was lower at 3 versus 4 visit (P = 0.002). NMR-based metabolomics of different biofluids distinguishes across inhaled pharmacotherapies, provides complementary information on the effects of an extrafine ICS/LABA FDC on metabolic fingerprints in COPD patients, and might be useful for elucidating the ICS mechanism of action.

An 1H NMR study of the cytarabine degradation in clinical conditions to avoid drug waste, decrease therapy costs and improve patient compliance in acute leukemia.

Cytarabine, the 4-amino-1-(ß-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C) is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers' instructions, once the components-sterile water and cytarabine powder-are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4°C. To evaluate how to avoid wasting the drug in short-term, low-dose treatment regimens, the reconstituted samples, stored at 25°C and 4°C, were analyzed every day of the test week by reversed-phase HPLC and high-field NMR spectroscopy. All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4°C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. Our findings show that an cytarabine solution prepared and stored in the original vials retains its efficacy and safety and can, therefore, be divided into small doses to be administered over more days, thus avoiding unnecessary expensive and harmful waste of the drug preparation. Moreover, patients who require daily administration of the drug could undergo the infusion at home without need to go to hospital. The stability of the aliquots would help decrease hospitalization costs.

Ionic liquids as lubricants or lubrication additives: an ecotoxicity and biodegradability assessment.

This paper reports on the (eco)toxicity and biodegradability of ionic liquids considered for application as lubricants or lubrication additives. Ammonium- and pyrrolidinium-based cations combined with methylsulphate, methylsulphonate and/or (CF(3)SO(2))(2)N(-) anions were investigated in tests to determine their aquatic toxicity using water fleas Daphnia magna, green algae Selenastrum capricornutum and marine bacteria (Vibrio fischeri). Additional test systems with an isolated enzyme (acetylcholinesterase) and isolated leukaemia cells from rats (IPC-81) were used to assess the biological activity of the ionic liquids. These compounds generally exhibit low acute toxicity and biological activity. Their biodegradability was screened according to OECD test procedures 301 B and 301 F. For choline and methoxy-choline ionic liquids ready biodegradability was observed within 5 or 10 d, respectively. Some of the compounds selected have a considerable potential to contribute to the development of more sustainable products and processes.

Depressive symptoms are associated with hospitalization, but not with mortality in the elderly: a population-based study.

OBJECTIVES: Subjects with depression might request more healthcare services. The aim of this study was to evaluate the association of depressive symptoms with hospitalization and mortality rates in a general unselected older population. METHODS: We assessed the association of the 30-items Geriatric Depression Scale (GDS) score with one-year hospitalization and mortality in all 344 subjects aged 75+ living in Tuscania (Italy). This population had been enrolled in a national study of the genetic determinants of health status. Analyses were conducted using continuous, as well as categorical GDS score levels. RESULTS: After adjusting for potential confounders, depressive symptoms were associated in Cox regression modelling with hospitalization (relative risk, RR = 1.05; 95% confidence interval, CI = 1.01-1.09; p = 0.016), but not with mortality (RR = 1.06; 95% CI = 0.96-1.16; p = 0.246). Increasing GDS score levels were associated with increasing risk of hospitalization (p for trend = 0.033). Up to 39% of hospitalizations might be attributed to depression. CONCLUSION: Depressive symptoms are not associated with increased mortality rates in general older populations. However, depressive symptoms represent a potentially reversible determinant of increased hospitalization rates in these subjects, independent of the presence and severity of other medical conditions.