Akt and MAPK/ERK signaling regulate neurite extension in adult neural progenitor cells but do not directly mediate disruption of cytoskeletal structure and neurite dynamics by low-level silver nanoparticles.

Silver nanoparticles (AgNPs) are an environmental contaminant of emerging concern. Ionic and colloidal silver has long been used for its antimicrobial properties, but with the development of engineered AgNPs, these are increasingly incorporated in the manufacture of nano-enhanced products. AgNPs are released into the environment from manufacturing plants and they can be shed from products during use and after disposal. This can lead to chronic low-level environmental exposure in animals. Unlike traditional forms of silver, the unique physical properties of AgNPs allow them to bypass biological barriers and enter tissues, like the brain, where they can bioaccumulate. Thus, it is important to understand if low-level AgNPs induce physiological changes in brain cells. Previously we found that 1.0 µg/mL AgNP exposure resulted in disruption of f-actin organization and neurite collapse in cultured differentiating adult neural stem cells, and that interaction with ß-catenin signaling was involved. Here, we report that AgNP exposure may interact with pAkt signaling irreversibly or indirectly to disrupt cytoskeleton and inhibit neurite extension. Furthermore, the MAPK/ERK signaling pathway is not a target for AgNP-mediated dysregulation. Environmental exposure to low-level AgNPs therefore appears to target specific cellular mechanisms to alter brain cell physiology. Understanding these underlying mechanisms is important for decisions regulating the use and disposal of manufactured AgNPs.

Safety and acceptability of implantation of internal cardioverter-defibrillators under local anesthetic and conscious sedation.

BACKGROUND: Implantation and testing of implantable defibrillators (ICDs) using local anesthetic and conscious sedation is widely practiced; however, some centers still use general anesthesia. We assessed safety and patient acceptability for implantation of defibrillators using local anesthetic and conscious sedation. METHODS: The records of 500 consecutive device implants from two UK cardiac centers implanted under local anesthetic and conscious sedation from January 1996 to December 2004 were reviewed. Procedure time, left ventricular ejection fraction (LVEF) sedative dosage (midazolam), analgesic dosage (fentanyl or diamorphine), requirement for drug reversal, and respiratory support were recorded. Patient acceptability of the procedure was also assessed. RESULTS: Of 500 implants examined, 387 were ICDs, 88 were biventricular ICDs, and 25 were generator changes. Patients with biventricular-ICDs had significantly longer (mean +/- SD) procedure times 129.7 +/- 7.6 minutes versus 63.3 +/- 32.3 minutes; P < 0.0001 and lower LVEF 24.4 +/- 8.4% versus 35.7 +/- 15.4%; P < 0.0001. There were no differences in the doses (mean +/- SD) of midazolam 8.9 +/- 3.5 mg versus 8.0 +/- 3.1 mg; P = NS, diamorphine 4.3 +/- 2.0 mg versus 3.8 +/- 1.7 mg; P = NS or fentanyl 94.4 +/- 53.7 mcg versus 92.2 +/- 48.6 mcg; P = NS, between the two groups. There were no deaths or tracheal intubations in either group. Acceptability was available for 373 of 500 (75%) patients, 41 of 373 (11%) described "discomfort," but from these 41 patients only 14 of 373 (3.8%) declined a second procedure under the same conditions. CONCLUSIONS: Implantation of defibrillators under local anesthetic and sedation is safe and acceptable to patients. General anesthesia is no longer routinely required for implantation of defibrillators.