Administering atropine and ketamine before less invasive surfactant administration resulted in low pain scores in a prospective study of premature neonates.

AIM: Less invasive surfactant administration (LISA) can avoid tracheal intubation for neonatal respiratory distress syndrome, but can be painful because it requires laryngoscopy. The aim of this study was to assess the efficacy and tolerance of intravenous atropine plus ketamine administration before LISA. METHODS: We conducted a prospective observational study of all premature infants hospitalised in our French neonatal intensive care unit treated with LISA between March 2015 and March 2016. Ketamine was titrated by 0.5 mg/kg increments. The technical conditions, pain scores, emergent intubations and vital signs were collected and analysed. RESULTS: Values are reported as medians (interquartile ranges). We included 29 patients with a gestational age of 29.6 (28.6-30.9) weeks and birth weight of 1290 (945-1600) grams. Technical conditions were satisfying for 24 infants (83%). The Faceless Acute Neonatal Pain Scale score was 2 (2-4); seven infants (24%) required tracheal intubation before LISA could be performed; 17 (59%) had a pulse oxymetry value under 80% that lasted more than 60 seconds. Heart rate and mean arterial blood pressure transiently increased. CONCLUSION: Atropine plus ketamine before LISA resulted in low pain scores and stable haemodynamic parameters, but prolonged desaturations or apnoea leading to tracheal intubation were frequently observed.

Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats.

BACKGROUND AND PURPOSE: mTOR inhibitors are currently used as immunosuppressants in transplanted patients and as promising anti-cancer agents. However, new-onset diabetes is a frequent complication occurring in patients treated with mTOR inhibitors such as rapamycin (Sirolimus). Here, we investigated the mechanisms associated with the diabetogenic effects of chronic Sirolimus administration in rats and in in vitro cell cultures. EXPERIMENTAL APPROACH: Sirolimus was administered to rats fed either a standard or high-fat diet for 21 days. Metabolic parameters were measured in vivo and in ex vivo tissues. Insulin sensitivity was assessed by glucose tolerance tests and euglycaemic hyperinsulinaemic clamps. Rapamycin effects on glucose metabolism and insulin signalling were further evaluated in cultured myotubes. KEY RESULTS: Sirolimus induced a decrease in food intake and concomitant weight loss. It also induced specific fat mass loss that was independent of changes in food intake. Despite these beneficial effects, Sirolimus-treated rats were glucose intolerant, hyperinsulinaemic and hyperglycaemic, but not hyperlipidaemic. The euglycaemic hyperinsulinaemic clamp measurements showed skeletal muscle is a major site of Sirolimus-induced insulin resistance. At the molecular level, long-term Sirolimus administration attenuated glucose uptake and metabolism in skeletal muscle by preventing full insulin-induced Akt activation and altering the expression and translocation of glucose transporters to the plasma membrane. In rats fed a high-fat diet, these metabolic defects were exacerbated, although Sirolimus-treated animals were protected from diet-induced obesity. CONCLUSIONS AND IMPLICATIONS: Taken together, our data demonstrate that the diabetogenic effect of chronic rapamycin administration is due to an impaired insulin action on glucose metabolism in skeletal muscles.

Mercury distribution in waters and fishes of the upper Madeira rivers and mercury exposure in riparian Amazonian populations.

In this paper, the results of mercury concentrations in two abiotic compartments (river water and suspended particles) and two biotic compartments (fish and human hair) from the upper Madeira rivers of the Bolivian Amazon basin are presented. Because of the local hydrological regimes and a high deposition rate in the plain, due to the presence of a subsidence zone at the bottom of the Andean piedmont, in the dry season, the highest mercury concentrations and fluxes were not found in rivers where mining activities took place (2.25-6.99 ng l(-1); and 1.07-8.67 mg Hg d(-1) km(-2)), but at the outlet of the Andean basins exploited for their alluvial gold (7.22-8.22 ng l(-1); and 9.47-9.52 mg Hg d(-1) km(-2)). The total mercury concentrations measured in surface waters of the upper Beni basin varied during the dry season, from 2.24 to 2.57 ng l(-1) in the glacial waters of the Zongo river, to 7.00 ng l(-1) in the Madeira River at Porto Velho and 9.49-10.86 ng l(-1) at its confluence with the Amazon. The results obtained from fish indicate, on one hand, that 86% of the piscivorous fishes collected in the Beni river were contaminated, and, on the other hand, their high mercury concentrations could exceed by almost four times the WHO (1976) safety limit. In the Beni River, the mercury concentrations found in omnivorous and mud-feeding fish ranged from 0.02 to 0.19 microg g(-1) (wet wt.), and in piscivorous fish, from 0.33 to 2.30 microg Hg g(-1) (wet wt.). The mercury accumulated by carnivorous fishes was mainly present in its organic form; methylmercury represented 73-98% of the total mercury analysed. Eighty persons were studied in the entire Bolivian Amazonian basin. Unlike the gold miners, who are more affected by tropical diseases, such as malaria and yellow fever, the indigenous people living on the banks of the Beni river, present elevated levels of mercury (9.81 microg g(-1) on average). We observed an increase in contamination in young children still being breast-fed, confirming that hair mercury concentration in babies was significantly affected by maternal mercury contamination during pregnancy. These results show that the major health impacts caused by mercury affect people who are not working directly in gold mining activities but who have a regular fish diet.