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Overall adherence with the SHEA/IDSA guidelines for management of CDAD at a tertiary medical center was poor; this was most pronounced in severe, severe-complicated and recurrent cases. Educational interventions aimed at improving guideline adherence are warranted.

Bioscavenger prophylactic therapy using purified human acetylcholinesterase (AChE) or butylcholinesterase (BChE) is a promising treatment for future protection against chemical warfare agent (CWA) exposure. However, the potential limitations of this approach has led to our investigation of alternative bioscavenger approaches using Forskolin, an inducer of cyclic AMP (cAMP). The optimal dose found for repeated treatment of Forskolin was 12-24 µM. Exposure to the organophosphate diisopropylflurophophate (DFP) showed that Forskolin treatment protects the cells from DFP cytotoxicity. These results indicate that transcriptional inducers, such as Forskolin, can sufficiently upregulate AChE production and protect cells against CWA exposure. INTRODUCTIONExposure to organophosphorous (OPs) chemical warfare nerve agent result in several biological effects; mainly, the inhibition of acetylcholinesterase (AChE) and decreased catalyzed hydrolysis of the enzyme, causing excessive accumulation of extracellular acetylcholine (ACh). The presence of excess ACh in the synaptic cleft triggers hyper-activation of ACh receptors and leads to various toxic effects, including hyper-secretions, convulsions, respiratory distress, coma, and death. Acute treatment of OP poisoning consists of combined administration of an AChE re-activator (an oxime), a muscarinic ACh receptor antagonist (e.g. atropine), and an anticonvulsant (e.g. diazepam) [1;2]. Recent investigations show that prophylactic enzyme therapy using purified fetal bovine AChE or human plasma butyrylcholinestrase (BChE) appears to be a more promising treatment against OP exposure [3;3;4]. However, the complex structure of the cholinesterases, posttranslational modifications and genetic variations, which could lead to antibody generation, raise certain concerns about this approach. Intense labor, the large amounts of serum needed for purification, low yield of purified enzyme and the high-dose regimens required for therapy are additional drawbacks that have necessitated a search for alternative approaches to nerve agent bio-scavenger treatment. One new approach is to induce the expression of endogenous cholinesterases using transcriptional inducers. In addition to complementing the studies on the regulation of cholinesterase expression, transcriptional upregulation of cholinesterases is also useful to produce large quantities of recombinant enzymes to facilitate purification of cholinesterases. Accumulating evidence suggests that the cellular expression of AChE is regulated both transcriptionally and posttranscriptionally. The promoter of human AChE is activated by a cyclic AMP (cAMP)-dependent pathway and augmented by cAMP [5;6]. Forskolin, a strong inducer of intracellular cAMP, also has been shown to induce AChE expression. Several binding sites of vitamin D3 and 17β-estradiol have been reported in human AChE promoters [7] and both these factors enhance transcription of the AChE gene. Constitutively activated Gα s and activation transcription factor-1 showed 10-and 4-f...