Wheat dependent exercise induced anaphylaxis: is this an appropriate terminology?

BACKGROUND: The presentation of wheat dependent exercise induced anaphylaxis (WDEIA) can be variable. A high index of clinical suspicion is required to initiate the investigation pathway. Double blind placebo controlled food-exercise challenge is the gold standard investigation but the practicality of this test limits its application. AIM: To critically analyse the symptoms of WDEIA and their correlation with serum specific IgE (sIgE) to romega-5-gliadin. METHODS: 17 patients were tested for serum sIgE to romega-5-gliadin. The clinical response to a diet/exercise intervention protocol was used to assess specificity of a positive sIgE to romega-5-gliadin. Length of time to diagnosis, clinical likelihood scores, exercise intensity involved and the severity of allergic reactions were examined retrospectively. RESULT: 8/10 patients with positive sIgE to romega-5-gliadin had a confirmed diagnosis of WDEIA. Half of the WDEIA patients had a prolonged time lag to diagnosis (32-62 months) and were initially diagnosed with idiopathic anaphylaxis or chronic idiopathic urticaria and angioedema. Only three patients had experienced life threatening symptoms (Mueller grading 4). A close association was observed between requirements of lower exercise intensity to provoke a reaction and diagnostic delay. CONCLUSION: Specific IgE to romega-5-gliadin can provide supportive evidence for WDEIA without the need of a food-exercise challenge. The wheat-exercise association is not obvious in many patients, highlighting the need to consider WDEIA in the differential diagnosis of all patients presenting with idiopathic systemic reactions. The term anaphylaxis may be inappropriate and it is therefore worth considering an alternative terminology such as 'activity dependent wheat allergy' to describe this condition.

Recombinant human arginase inhibits proliferation of human hepatocellular carcinoma by inducing cell cycle arrest.

Human hepatocellular carcinoma (HCC) has an elevated requirement for arginine in vitro, and pegylated recombinant human arginase I (rhArg-PEG), an arginine-depleting enzyme, can inhibit the growth of arginine-dependent tumors. While supplementation of the culture medium with ornithine failed to rescue Hep3B cells from growth inhibition induced by rhArg-PEG, citrulline successfully restored cell growth. The data support the roles previously proposed for ornithine transcarbamylase (OTC) in the arginine auxotrophy and rhArg-PEG sensitivity of HCC cells. Expression profiling of argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL) and OTC in 40 HCC tumor biopsy specimens predicted that 16 of the patients would be rhArg-sensitive, compared with 5 who would be sensitive to arginine deiminase (ADI), another arginine-depleting enzyme with anti-tumor activity. Furthermore, rhArg-PEG-mediated deprivation of arginine from the culture medium of different HCC cell lines produced cell cycle arrests at the G(2)/M or S phase, possibly mediated by transcriptional modulation of cyclins and/or cyclin dependent kinases (CDKs). Based on these results, together with further validation of the in vivo efficacy of rhArg-PEG against HCC, we propose that the application of rhArg-PEG alone or in combination with existing chemotherapeutic drugs may represent a specific and effective therapeutic strategy against HCC.