Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake.

The worldwide prevalence of diabetes has risen to 8.5% among adults, which represents a staggering rise in prevalence from 4.7% in 1980. Whilst some treatments work by increasing insulin secretion, over time their effectiveness decreases. We aim to increase insulin secretion by developing strategies that work through mechanisms independent of current treatment options. Isolated CD1 mouse islets, INS-1 pancreatic ß-cells, or C2C12 mouse myotubes were incubated in standard tissue culture media, or media supplemented with 28 mM glucose, 200 µM palmitic acid, and 200 µM oleic acid as a cellular model of diabetic glucolipotoxicity. Intracellular reactive species content was assayed using 2',7'-dichlorofluorescein diacetate dye, inducible nitric oxide synthase levels determined by Western blot, 3-nitrotyrosine and 4-hydrpxnonenal both assayed by ELISA, insulin secretion quantified using ELISA or radioimmunoassay, and glucose uptake determined through 2-deoxy glucose 6 phosphate luminescence. Our data indicate that carnosine, a histidine containing dipeptide available through the diet, is an effective scavenger of each of the aforementioned reactive species. This results in doubling of insulin secretion from isolated mouse islets or INS-1 ß-cells. Crucially, carnosine also reverses glucolipotoxic inhibition of insulin secretion and enhances glucose uptake into skeletal muscle cells. Thus, carnosine, or non-hydrolysable carnosine analogs, may represent a new class of therapeutic agent to fight type 2 diabetes.

The normal and the challenging pediatric airway.

Management of a child's airway is one of the main sources of stress for anesthetists who do not routinely anesthetize children. Unfortunately, trainees are gaining less experience in pediatric airway management than in the past, which is particularly difficult at a time when some beliefs about airway management are being challenged and airway management is less standardized. Fortunately, most children have an easily managed, normal airway. Nevertheless, it is of vital importance to teach our trainees the basic airway skills that are probably the most important skill in an anesthetists' repertoire when it comes to a difficult airway situation. This review focuses on the airway management in children with a normal and a challenging airway. Different choices of airway management in children, and their advantages and disadvantages are discussed. Furthermore, the three broad causes of a challenging airway in children and infants are highlighted - the difficulty obtaining a mask seal, difficulty visualizing the vocal cords, and the third cause in which the larynx can be visualized but the difficulty lies at or beyond that level. Guidelines are given how to deal with these patients as well as with the feared but rare scenario of 'cannot ventilate, cannot intubate' in children.

Exercise-induced immunosuppression: roles of reactive oxygen species and 5'-AMP-activated protein kinase dephosphorylation within immune cells.

We previously proposed 5'-AMP-activated protein kinase (AMPK) dephosphorylation within immune cells as an intracellular mechanism linking exercise and immunosuppression. In this study, AMPK phosphorylation underwent transient (<1 h) decreases (53.8+/-7.2% basal) immediately after exercise (45 min of cycling at 70% VO2max) in a cohort of 16 adult male participants. Similar effects were seen with running. However, because exercise-induced inactivation of AMPK was previously shown to occur in an AMP-independent manner, the means by which AMPK is inactivated in this context is not yet clear. To investigate the hypothesis that exercise-induced inactivation of AMPK is mediated via signaling mechanisms distinct from changes in cellular AMP-to-ATP ratios, reactive oxygen species (ROS) and intracellular Ca2+ signaling were investigated in mononuclear cells before and after exercise and in cultured monocytic MM6 cells. In in vitro studies, treatment with an antioxidant (ascorbic acid, 4 h, 50 microM) decreased MM6 cell intracellular ROS levels (88.0+/-5.2% basal) and induced dephosphorylation of AMPK (44.7+/-17.6% basal). By analogy, the fact that exercise decreased mononuclear cell ROS content (32.8+/-16.6% basal), possibly due to downregulation (43.4+/-8.0% basal) of mRNA for NOX2, the catalytic subunit of the cytoplasmic ROS-generating enzyme NADPH oxidase, may provide an explanation for the AMPK-dephosphorylating effect of exercise. In contrast, exercise-induced Ca2+ signaling events did not seem to be coupled to changes in AMPK activity. Thus we propose that the exercise-induced decreases in both intracellular ROS and AMPK phosphorylation seen in this study constitute evidence supporting a role for ROS in controlling AMPK, and hence immune function, in the context of exercise-induced immunosuppression.

Laryngeal mask airway is associated with an increased incidence of adverse respiratory events in children with recent upper respiratory tract infections.

BACKGROUND: The laryngeal mask airway (LMA) has been advocated as an alternative technique to tracheal intubation for airway management of children with recent upper respiratory tract infections (URIs). The authors determined the occurrence of adverse respiratory events and identified the associated risk factors to assess the safety of LMA in children. METHODS: During a period of 5 months, parents of children scheduled to undergo general anesthesia with an LMA were asked to fill out a questionnaire regarding their child's medical history and potential symptoms of URI. In addition, all episodes of adverse respiratory events in the perioperative period (laryngospasm, bronchospasm, coughing, airway obstruction, and oxygen desaturation) as well as details of anesthesia management were recorded. RESULTS: Among the 831 children included in the study, 27% presented with a history of a recent URI within the last 2 weeks before anesthesia. The presence of a recent URI doubled the incidence of laryngospasm (odds ratio, 2.6; 95% confidence interval, 1.3-5.0), coughing (odds ratio, 2.7; 95% confidence interval, 1.7-4.3), and oxygen desaturation (odds ratio, 1.9; 95% confidence interval, 1.2-2.8). This incidence was even higher in young children; in those undergoing ear, nose, and throat surgery; and when there were multiple attempts to insert the LMA. CONCLUSION: An LMA used in children with recent URIs was associated with a higher incidence of laryngospasm, cough, and oxygen desaturation compared with healthy children. However, the overall incidence of adverse respiratory events was low, suggesting that if anesthesiologists allow at least a 2-week interval after a URI, they can safely proceed with anesthesia using an LMA.

Unplanned anesthesia-related admissions to pediatric intensive care - a 6-year audit.

BACKGROUND: Unplanned admissions to the intensive care unit may result from unexpected events related to anesthesia, and are recommended by some healthcare organizations as a clinical indicator. The rate of anesthesia-related unplanned admissions in adults ranges between 0.04% and 0.45% of procedures. However, there is a paucity of data relating to the rate in children. METHODS: Admissions to the pediatric intensive care unit (PICU) occurring within 24 h of anesthesia were identified through retrospective chart review. Only those admissions from a complication of anesthesia were included and not those from communication errors or surgical problems. The aim was to determine the rate of unplanned admissions, as well as the causes and management of this group of unplanned admissions. RESULTS: Seventy-six children requiring admission to the PICU were identified from 55196 procedures during the 6-year study period. The rate of unplanned admission was 0.14% of procedures. A total of 47% of these admissions were related to airway problems and 68% of children requiring admission were aged less than 5 years. Most children required only observation after their admission. CONCLUSIONS: We found the unplanned admission rate to the PICU in our hospital population to be similar to that reported for adults, and is a relatively rare event in pediatric anesthesia. Most admissions were for children aged less than 5 years and were as a result of airway problems. Most cases were deemed potentially predictable.