Melanocortin analogue Org2766 binds to rat Schwann cells, upregulates NGF low-affinity receptor p75, and releases neurotrophic activity

Binding of the stable melanocortin(4-9) analogue, Org2766 [Met(O2)-Glu-His-Phe-D-Lys-Phe] to cultured rat sciatic nerve Schwann cells was demonstrated using a biotinylated derivative in semiquantitative histochemical and CELISA assays. Org2766 bound to Schwann cells, but not to fibroblasts, and was displaced maximally by unlabeled Org2766, alpha-MSH and ACTH(1-24). Displacement of Org2766 from the binding sites was considerably reduced by N- and C-truncation of the peptide. Specific binding of Org2766 was also demonstrated in the immortal rat Schwann cell line SCL4.1/F7 and was more pronounced in cells displaying a differentiated morphology. Org2766 and alpha-MSH increased cyclic AMP content of Schwann cells but neither stimulated DNA synthesis when applied alone. However, in the presence of a priming (subthreshold) concentration of the mitogen, cholera toxin, Org2766 and alpha-MSH caused a delayed increase in DNA synthesis. Org2766 did not modulate the expression of several differentiation-related Schwann cell markers. However, Org2766 increased immunoreactivity for p75 low-affinity NGF receptor on Schwann cells and evoked the release of neurotrophic factor(s) that synergized with NGF in stimulating neurite outgrowth in rat DRG neurons. The results indicate that Schwann cells are a primary target for the action of Org2766 and provide evidence for an indirect mechanism by which melanocortins might stimulate neurite sprouting in regenerating peripheral nerve axons.     

Measuring battering: development of the Women's Experience with Battering (WEB) Scale

Measuring only the physical markers of violence (e.g., slapping, beating) fails to capture the chronic vulnerability and gendered nature of battered women's experiences. Instruments that measure only observable discrete events may mask the continuous nature of battering and the relation between events and experience. Our approach to measuring battering operationalizes the experiences of battered women rather than the abusive behaviors they encounter. This alternative approach emphasizes the meanings battered women attach to the violence and to battering as an enduring presence in their lives. Focus groups with 22 battered women generated qualitative data for developing scale items (Smith, Tessaro, & Earp, 1995) and a known-groups survey with 185 battered and 204 nonbattered women determined the final scale items. Factor analysis of 40 initial items revealed a strong single-factor solution. The resulting 10-item Women's Experiences with Battering (WEB) Scale demonstrated high internal consistency reliability, was significantly correlated with known-group status, exhibited good construct validity, and was not significantly correlated with a measure of social desirability. The WEB Scale provides researchers with a valid and concise measure for studying relations between battering and health or health behavior, as well as evaluating the impact of interventions on battered women or prevalence.     

Atorvastatin calcium: an addition to HMG-CoA reductase inhibitors

Atorvastatin calcium is an HMG-coenzyme A (CoA) reductase inhibitor that was approved by the Food and Drug Administration on December 17, 1996. Like other such agents, it inhibits the action of HMG-CoA reductase and thereby decreases endogenous cholesterol synthesis, leading to a decrease in circulating low-density lipoprotein cholesterol. In addition to its effect on lipoprotein profile, atorvastatin reduces triglycerides to a greater extent than other HMG-CoA reductase inhibitors. These actions occur in a dose-dependent fashion. The adverse effect profile is similar to that of other agents in this class. Indications for atorvastatin include primary hypercholesterolemia as well as other lipid disorders.     

The effects of age and gender on the single dose pharmacokinetics of avitriptan administered to healthy volunteers

The effects of age and gender on the single dose pharmacokinetics of avitriptan and its three metabolites were assessed in 15 young men, 15 young women, 15 elderly men and 15 elderly women. Avitriptan was administered as a 150-mg capsule after a 10-hour fast and serial plasma and urine samples were collected up to 36 hours after the dose. Plasma samples were analyzed for avitriptan and its metabolites, N-desmethyl avitriptan (ND048), O-desmethyl avitriptan (OD048), and methoxypyrimidinyl piperazine (MPP). Urine samples were analyzed for only avitriptan and MPP. Avitriptan was well tolerated in all four groups. The drug was rapidly absorbed with a median time to maximum plasma concentration (tmax) between 0.5 and 1.5 hours. No significant gender-related differences were found in the maximum plasma concentration (Cmax) and area under the concentration-time curve extrapolated to infinity (AUC0-infinity) of avitriptan. Renal clearance of avitriptan was significantly smaller in young women compared with young men, but this is clinically not relevant because only 2% to 3% of the total dose is excreted unchanged. Compared with the young volunteers, mean Cmax was approximately 50% higher in the elderly but there was no difference in the AUC0-infinity between the 2 age groups. Plasma concentrations of ND048, OD048, and MPP were each 50 to 100 fold lower than those of avitriptan. Hence some age- and gender-related differences found in the pharmacokinetics of avitriptan metabolites are probably not relevant in the assessment of overall safety and efficacy of avitriptan. Based on the pharmacokinetics and tolerability, no age or gender-related dose adjustment is necessary for avitriptan.     

Emergency airway management

Maintenance of the airway is the most important and one of the most challenging functions that an emergency physician has to perform. This article is a review of the various techniques that can be used by both emergency and nonemergency physicians to secure the airway. It includes standard orotracheal intubation, nasotracheal intubation, fiberoptic intubation, and cricothyroidotomy. The medications used in these procedures and in rapid sequence intubation are discussed.