The temporal patterns of edema and accumulation of the PMN marker enzyme, myeloperoxidase (MPO), were examined following application of tetradecanoylphorbol acetate (TPA) to mouse ears. After application of 2.5 micrograms TPA, edema peaked at 6 hr, while MPO activity peaked at 24 hr. Pharmacological agents with defined mechanisms of action, delivered orally or topically, were assessed for effects on these responses. For oral administration, compounds were delivered 1 hr before and 6 hr after TPA and for topical administration compounds were delivered at 15 min and 6 hr after TPA. Topical and oral corticosteroids inhibited both edema and MPO accumulation. Cyclooxygenase and lipoxygenase inhibitors were very effective against MPO accumulation but were either inactive or moderately active vs edema. Anti-histamine/anti-serotonin agents had little effect on edema, but could inhibit or exacerbate MPO accumulation depending on dose and route of administration. Topically applied histamine itself did not effect TPA-induced edema, but markedly suppressed MPO accumulation. Acetone, the vehicle, when topically applied between 0.5 and 2 hr after TPA inhibited MPO accumulation by 60-80%, but had little effect on edema. Acetone applied before 0.5 hr or after 2 hr had no effect on either parameter. These results indicate that in the TPA-induced ear inflammation model the MPO response at 24 hr may be a useful additional indicator of drug activity.

Lagocephalus sceleratus, or better known as the pufferfish, or fugu, is widespread in Asia and Indo-Pacific regions. It is a poisonous fish containing tetrodotoxin (TTX) which is a potent neurotoxin. In the Far East, fugu is considered a delicate dish, especially in Japan where it is prepared by experts. Nevertheless, poisoning from Lagocephalus sceleratus is not a rare event. Recent data from Japan indicate an incidence of 45 patients per year and a mortality rate of 11%. Mediterranean sea is not the natural habitat of Lagocephalus sceleratus. However, by now multiple reports have established a firm presence of Lagocephalus sceleratus in Mediterranean region as well. This phenomenon is explained by migration of pufferfish across the Suez Channel (lessepsian migration) (Eisenman et al., 2008, Bentur et al., 2008). With lessepsian migration came the first reports of TTX poisoning in the Mediterranean region. We report a patient with a particularly severe and life-threatening TTX poisoning caused by consumption of Lagocephalus sceleratus and treated by cholinesterase inhibitor to a complete and uneventful recovery.

A single, 10 ng intradermal injection of human recombinant interleukin-1 beta (rIL-1 beta) into rat ears produced acute inflammation. Tissue wet weight (edema) and total myeloperoxidase activity (PMN accumulation), peaked at 3 hours and returned to base line at 3 days. Given orally, 1 hour prior to rIL-1 beta injection, cyproheptadine, dexamethasone, conventional NSAID's, or mixed cyclooxygenase/lipoxygenase inhibitors were potent antagonists of edema and moderate antagonists of PMN accumulation. In addition, the putative DMARD's, auranofin, dapsone, and levamisole were effective inhibitors of rIL-1 beta induced inflammation.

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Purpose. Patients with severe acute respiratory distress syndrome (ARDS) and hypercapnia present a formidable treatment challenge. We examined the use of esophageal balloon for assessment of transpulmonary pressures to guide mechanical ventilation for successful management of severe hypercapnia. Materials and Methods. Patients with severe ARDS and hypercapnia were studied. Esophageal balloon was inserted and mechanical ventilation was guided by assessment of transpulmonary pressures. Positive end expiratory pressure (PEEP) and inspiratory driving pressures were adjusted with the aim of achieving tidal volume of 6 to 8 mL/kg based on ideal body weight (IBW), while not exceeding end inspiratory transpulmonary (EITP) pressure of 25 cm H2O. Results. Six patients with severe ARDS and hypercapnia were studied. Mean PaCO2 on enrollment was 108.33 ± 25.65 mmHg. One hour after adjustment of PEEP and inspiratory driving pressure guided by transpulmonary pressure, PaCO2 decreased to 64.5 ± 16.89 mmHg (P < 0.01). Tidal volume was 3.96 ± 0.92 mL/kg IBW before and increased to 7.07 ± 1.21 mL/kg IBW after intervention (P < 0.01). EITP pressure before intervention was low with a mean of 13.68 ± 8.69 cm H2O and remained low at 16.76 ± 4.76 cm H2O (P = 0.18) after intervention. Adjustment of PEEP and inspiratory driving pressures did not worsen oxygenation and did not affect cardiac output significantly. Conclusion. The use of esophageal balloon as a guide to mechanical ventilation was able to treat severe hypercapnia in ARDS patients.