133 research outputs found
From Science to Guidelines: The Future for Resuscitation
No full textThe periodic development and publication of treatment guidelines is integral to the field of cardiopulmonary resuscitation
and emergency cardiovascular care. The methods for guideline development have evolved over the past few decades, and
the process itself has become the subject of increasing scientific investigation. An internationally validated tool for assessing
the quality of clinical practice guidelines is The Appraisal of Guidelines for Research and Evaluation (AGREE) instrument.
Applying this tool to the ILCOR 2010 International Consensus on CPR (cardiopulmonary resuscitation) and ECC (emergency
cardiac care) Science with Treatment Recommendations (CoSTR) and the resulting member council guidelines will be a
valuable initial step in evaluating both the process and the product. By doing so, important strengths can be recognized
as well as opportunities for improvement moving forward. Beyond validated tools to assess and improve the quality of the
traditional guidelines process, a critical reassessment of the overall strategy for improving cardiac arrest outcomes is indicated.
From the lay-provider perspective, innovative approaches to facilitate performance of bystander CPR are needed.
This is likely to entail more individualized instructional methods that are titrated to the provider’s capabilities for learning
and performance. What the future might hold for professional providers is a more individualized treatment strategy titrated
to real-time physiologic monitoring with mechanized delivery of therapies guided by real-time computer-aided medical
decision-making. These individualized instructional and treatment strategies could revolutionize our approach to cardiac
arrest resuscitation, and dramatically change how guidelines are developed, implemented and evaluated
Cross-talk between calpain and caspase proteolytic systems during neuronal apoptosis
No full textCross-talk between calpain and caspase proteolytic systems has complicated efforts to determine their distinct roles in apoptotic cell death. This study examined the effect of overexpressing calpastatin, the specific endogenous calpain inhibitor, on the activity of the two proteolytic systems following an apoptotic stimulus. Human SH-SY5Y neuroblastoma cells were stably transfected with full-length human calpastatin cDNA resulting in 20-fold overexpression based on Western blot and 5-fold greater calpain inhibitory activity in cell extracts. Wild type and calpastatin overexpressing (CST1) cells were neuronally differentiated and apoptosis-induced with staurosporine (0.1-1.0 µm). Calpastatin overexpression decreased calpain activation, increased caspase-3-like activity, and accelerated the appearance of apoptotic nuclear morphology. Following 0.1-0.2 µm staurosporine, plasma membrane integrity based on calcein-acetoxymethyl fluorescence was significantly greater at 24 h in differentiated CST1 compared with differentiated wild type cells. However, this protective effect was lost at higher staurosporine doses (0.5-1.0 µm), which resulted in pronounced caspase-mediated degradation of the overexpressed calpastatin. These results suggest a dual role for calpains during neuronal apoptosis. In the early execution phase, calpain down-regulates caspase-3-like activity and slows progression of apoptotic nuclear morphology. Subsequent calpain activity, facilitated by caspase-mediated degradation of calpastatin, contributes to plasma membrane disruption and secondary necrosis.Journal ArticleFinal article publishe
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