Acetyl-L-carnitine Slows the Progression from Prefrailty to Frailty in Older Subjects: A Randomized Interventional Clinical Trial.

BACKGROUND: Ageing is characterized by a gradual decline in body function, representing the clinical situation called "frailty". Prefrailty is the intermediate stage between frailty and robust condition. L-carnitine (LC) plays an important role in energy production from long-chain fatty acids in mitochondria, and its serum level is lower in prefrail and frail subjects. OBJECTIVE: This study aims to evaluate the effect of Acetyl-L-carnitine (ALCAR) in pre-frail older patients. METHODS: We scheduled 3 months of treatment and then 3 months of follow-up. A total of 92 subjects were selected from May, 2009 to July, 2017, in a randomized, observational, double-blind, placebo-controlled study. We scheduled 3 months of treatment and then 3 months of follow-up. ALCAR (oral 1.5 g/bis in die - BID) or placebo groups were used. RESULTS: After the treatment, only the treated group displayed a decrease in C reactive protein (CRP) p < 0.001 and an increase in serum-free carnitine and acetylcarnitine (p < 0.05) in Mini-Mental state (MMSE) p < 0.0001 and 6-walking distance (p < 0.0001); ALCAR group vs. placebo group showed a decrease in HDL cholesterol and CRP (p < 0.01), an increase in MMSE score (p < 0.001) and in the 6-walking distance (p < 0.001). CONCLUSIONS: ALCAR treatment delays the incidence and severity of onset of degenerative disorders of the elderly in prefrail subjects with improvement in memory and cognitive processes.

[Evaluation of mercury exposure in populations living near the industrial Augusta Bay (Sicily Region, Southern Italy)]. / Valutazione dell'esposizione al mercurio nelle popolazioni residenti in prossimità dell'area industriale della Rada di Augusta (Siracusa).

OBIETTIVI: valutare e quantificare l'esposizione umana al mercurio (Hg) ed esplorare i fattori chiave che influenzano la contaminazione nelle popolazioni residenti in prossimità della Rada di Augusta, un'area a elevato rischio ambientale a causa degli effetti degli sversamenti incontrollati di Hg da parte di uno dei più grandi impianti cloro-soda d'Europa. DISEGNO: un campione di residenti nei comuni di Augusta, Priolo e Melilli (Sicilia orientale) è stato selezionato per lo studio di biomonitoraggio umano. Un questionario dettagliato è stato somministrato a ogni partecipante per raccogliere informazioni anagrafiche sulle abitudini di vita e alimentari. I livelli di Hg in sangue e capelli, usati come traccianti di esposizione a metilmercurio, sono stati messi in relazione al consumo di pesce locale. Il contenuto di Hg nelle urine è stato utilizzato per esplorare eventuali esposizioni atmosferiche a Hg inorganico. Una regressione lineare multivariata è stata applicata con l'obiettivo di esplorare i fattori che influenzano l'esposizione umana al Hg. L'approccio tossicocinetico è stato impiegato al fine di calcolare la dose settimanale provvisoria tollerabile ( provisional tolerable weekly intake, PTWI) e di predire le concentrazioni di Hg attese nel sangue degli individui con una dieta alimentare basata esclusivamente su pesce locale. SETTING E PARTECIPANTI: 224 individui residenti nei comuni di Augusta, Melilli e Priolo. RISULTATI: eccessi di Hg sono stati misurati nel sangue e nei capelli del campione considerato. I più alti livelli sono stati rilevati ad Augusta, dove anche il consumo di pesce locale risulta maggiore. I valori di dose settimanale tollerabile provvisoria (PTWI) calcolati eccedono, nella maggior parte dei casi, le raccomandazioni internazionali, specialmente nei residenti ad Augusta. CONCLUSIONI: gli elevati livelli di Hg registrati nei campioni di sangue e capelli derivano, con ogni probabilità, dal consumo di pesce locale. Rispetto ad Augusta, gli individui di Priolo e Melilli subiscono un impatto più limitato. L'esposizione a Hg inorganico può essere considerata trascurabile.

Assessment of mercury exposure in human populations: A status report from Augusta Bay (southern Italy).

Here we investigate mercury concentrations in the blood (HgB), urine (HgU) and human hair (HgH) of 224 individuals from a coastal area (Eastern Sicily, SE Italy) strongly affected by Hg contamination from one of the largest chlor-alkali plants in Europe. The factors affecting the distribution of Hg and the extent of the exposure of individuals have been explored with a multidisciplinary approach. Multiple regression analyses, together with evidence of high levels of HgB (exceeding the HBMI recommended levels in 50% of cases) and HgH (exceeding the EPA reference dose in 70% of cases), primarily suggest that the consumption of local fish is the main source of Hg for humans. no. significant exposure to inorganic mercury was identified. Toxicokinetic calculations produced a provisional tolerable weekly intake (PTWI) level that, in most cases, exceeds international recommendations, particularly for residents in the studied area.

Very low doses of ethanol induce behavioral changes involving dopamine D2 receptors.

In male rats, pretreatment for 20 days with very low (0.5, 1%, v/v) but not with high (5, 10%, v/v) oral doses of ethanol delayed the initiation and reduced the duration of narcosis induced by an acute high intraperitoneal (i.p.) dose of the drug (3 g/kg in 25% saline solution). Furthermore, the treatment improved the acquisition of shuttle-box active avoidance response but did not affect the emission of ultrasonic calls, an index of emotional state of animals. These effects were inhibited by peripheral administration of the dopamine D2 receptor antagonist, sulpiride (1 mg/kg). A higher dose of sulpiride (10 mg/kg) prolonged the duration of narcosis in rats pretreated with high-dose ethanol and reduced the number of conditioned avoidance responses in the shuttle-box paradigm. The pretreatment with the dopamine D2 receptor agonist, (+/-)-2-(N-phenethyl-N-propylamino)-5-hydroxytetralin (PPHT, 0.1 mg/kg), enhanced the effects of ethanol very low doses in delaying the initiation and reducing the duration of narcosis induced by an acute i.p. dose of the drug. A pharmacokinetic study in ethanol-pretreated animals revealed that administration of 0.5% or 1% ethanol for 20 days did not modify significantly the bioavailability of acute ethanol administered i.p. in a dose of 3 g/kg in 25% saline solution. Thus, repeated administration of ethanol very low doses may have affected the sensitivity of presynaptic dopamine D2 receptors. The influence on dopamine release through an action on presynaptic receptors may be involved in these effects of small doses of ethanol.