Electrophysiological studies on isolated segments of peripheral rodent nerve have been able to replicate oxaliplatin’s effect on axonal hyperexcitability in vitro. In the present study we have used this in vitro model to examine whether flupirtine, a clinically available analgesic, which activates slow axonal potassium (Kv7) channels, can suppress axonal hyperexcitability resulting from exposure of peripheral nerve to oxaliplatin. In the presence of oxaliplatin (30 mu M), the A-fibre compound action potential response of isolated rat nerve segments to a brief electrical stimulus (0.1 ms) changed considerably with the emergence
of after-activity that persisted for a period of tens of milliseconds after the electrical stimulus. Lowering the bath temperature by 4 degrees C enhanced the magnitude and prolonged the time course of this axonal after-activity. Application of flupirtine (10 mu M) reduced both the
magnitude and duration of oxaliplatin-induced axonal after-activity VE-822 manufacturer in myelinated axons. These findings were also confirmed in isolated human sural nerve segments. The data indicate that activation of slow potassium channels in the A-fibres of peripheral nerve may attenuate the acute neuropathy Selleckchem JQ-EZ-05 associated with oxaliplatin in humans. (C) 2010 Elsevier Inc. All rights reserved.”
“The Countdown to 2015 for Maternal, Newborn, and Child Survival monitors coverage of priority interventions to achieve the Millennium Development Goals (MDGs) for child mortality and maternal health. We reviewed progress between 1990 and 2010 in coverage of 26 key interventions in 68 Countdown priority countries accounting for more than 90% of maternal and child deaths worldwide. 19 countries studied
were on track to meet MDG 4, in 47 we noted acceleration in the yearly rate of reduction in mortality of children younger than 5 years, and in 12 countries progress had decelerated since 2000. Progress towards reduction of neonatal deaths has been Amyloid precursor protein secretase slow, and maternal mortality remains high in most Countdown countries, with little evidence of progress. Wide and persistent disparities exist in the coverage of interventions between and within countries, but some regions have successfully reduced longstanding inequities. Coverage of interventions delivered directly in the community on scheduled occasions was higher than for interventions relying on functional health systems. Although overseas development assistance for maternal, newborn, and child health has increased, funding for this sector accounted for only 31% of all development assistance for health in 2007. We provide evidence from several countries showing that rapid progress is possible and that focused and targeted interventions can reduce inequities related to socioeconomic status and sex. However, much more can and should be done to address maternal and newborn health and improve coverage of interventions related to family planning, care around childbirth, and case management of childhood illnesses.