Ease of Intubation with the McGRATH® MAC, C-MAC® or Macintosh Laryngoscopes by Novice Operators in Simulated Difficult Airways – A Manikin Study.

A variety of video laryngoscopes have been introduced to facilitate endotracheal intubations as failed intubations can result in morbidity and mortality. We aimed to compare the use of the conventional Macintosh laryngoscope, McGRATH® MAC and C- MAC® video laryngoscopes among novice operators. 37 medical students were recruited to perform oro-tracheal intubations in a human patient stimulator with simulated ‘difficult airway’ scenario using 3 devices: The Macintosh laryngoscope, McGRATH® MAC and C- MAC® video laryngoscopes. The success rate of tracheal intubation using the C-MAC® video laryngoscope (84%) was higher than both the McGRATH® MAC (59%) and the Macintosh laryngoscope (57%) (p=0.005). The use of video laryngoscopes were associated with lower incidence of oesophageal intubation (p<0.001) and deemed easier to use (p<0.001). Overall, the C-MAC® yielded a higher rate of successful tracheal intubation, a shorter time to glottic visualisation and was deemed to provide the greatest ease of intubation with novice practitioners.

Dopamine-related and caspase-independent apoptosis in dopaminergic neurons induced by overexpression of human wild type or mutant alpha-synuclein.

Human wild type (WT) and mutant alpha-synuclein (alpha-syn) genes were overexpressed using a Tet-on expression system in stably transfected dopaminergic MN9D cells. Their overexpression induced caspase-independent and dopamine-related apoptosis not rescued by general caspase inhibitor Z-VAD-FMK. While apoptosis due to overexpression of WT alpha-syn was completely abrogated by a specific tyrosine hydroxylase (TH) inhibitor, alpha-methyl-p-tyrosine (alpha-MT), the inhibitor only partially rescued apoptosis caused by overexpression of alpha-syn mutants. In addition, overexpression of mutants enhanced the toxicity of 1-methyl-4-phenylpyridinium (MPP+) and 6-hydroxyldopamine (6-OHDA) to MN9D cells, whereas overexpression of WT protected MN9D cells against MPP+ toxicity, but not against 6-OHDA. We conclude that WT alpha-syn is beneficial to dopaminergic neurons but its overexpression in the presence of endogenous dopamine makes it a potential threat to the cells. In contrast, mutant alpha-syn not only caused the loss of WT protective function but also the gain-of-toxicity which becomes more serious in the presence of dopamine and neurotoxins.

Compensatory caspase activation in MPP+-induced cell death in dopaminergic neurons.

Many have hypothesized that cell death in Parkinson's disease is via apoptosis and, specifically, by the mitochondrial-mediated apoptotic pathway. We tested this hypothesis using a mouse dopaminergic cell line of mesencephalic origin, MN9D, challenged with the Parkinsonism-causing neurotoxin MPP+ (1-methyl-4-phenylpyridinium ion). Apoptosis was the main mode of cell death when the cells were subjected to MPP+ treatment under serum-free conditions for 24 h. Caspase-3 and caspase-9, however, were not activated, thus indicating the existence of alternate or compensatory cell death pathway(s) in dopaminergic neuronal cells. Using caspase inhibitors, we demonstrated that these pathways involve caspase-2, -8, -6 and -7. A time-course study indicated that activation of caspase-2 and -8 occurred upstream of caspase-6 and caspase-7. Upon MPP+ challenge, the apoptosis-inducing factor was translocated from the mitochondria into the MN9D cytosol and nucleus. These results suggest the existence of alternative apoptotic pathways in dopaminergic neurons.