Docosahexaenoic acid (DHA; 22:6) is known to have anticancer activity, but its mechanisms of action remain to be further elucidated. We recently demonstrated that DHA downregulates superoxide dismutase (SOD) 1 gene expression, thereby weakening cellular antioxidant forces and enhancing cytotoxicity in various human cancer cells. The objective of this study was to investigate the mechanism of the inhibitory effect of DHA on SOD-1 gene expression in human cancer cells. A reporter gene assay indicated that DHA suppresses SOD-1 gene transcription in a time-and concentration-dependent manner in human cancer cells. Pretreatment with vitamin E did not block the inhibitory effect of DHA, indicating that this suppression does not depend on lipid peroxidation. The suppressive effect of DHA on SOD-1 gene transcription could be mimicked by the peroxisome proliferator-activator receptor (PPAR) ␣ ligand clofibrate but not the PPAR␥ ligand troglitazone, suggesting the involvement of PPAR␣ signaling. Deletion analysis of the key DNA binding elements in the SOD-1 gene promoter identified the distal hypoxia response element (HRE), but not the peroxisome proliferator response element or nuclear factor-B element, as essential for the suppressive effects of DHA. Coimmunoprecipitation confirmed that PPAR␣, but not PPAR␥, forms a complex with hypoxia-inducible factor (HIF)-2␣ in cancer cells. Chromatin immunoprecipitation analysis indicated that both DHA and clofibrate reduce HIF-2␣ binding to the HRE. Thus, we have identified the distal HRE in the SOD-1 gene promoter that mediates the suppression on the transcription of this gene by DHA, and we have demonstrated the involvement of PPAR␣ and HIF-2␣ signaling in this event.

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Acephate is a commercial organophosphate pesticide formerly used in households and now used primarily for agriculture. Poisoning symptoms include salivation, lacrimation, urination, defecation, gastrointestinal illness, and emesis. In addition to these classic symptoms, neurodegeneration can result from increased and continued exposure of organophosphates. This 55-year-old woman presented with organophosphate-induced delayed neuropathy in the form of quadriplegia due to the commonly used pesticide acephate. She was exposed to this pesticide through multiple sprayings in her work office with underrecognized poisoning symptoms. She presented to her primary care physician with neuropathic pain and paralysis in her arm following the sprayings and eventual complete paralysis. The patient lived for 2 years following her toxic exposure and quadriplegia. A complete autopsy after her death confirmed a transverse myelitis in her spinal cord. We conclude that in susceptible individuals, acephate in excessive amounts can produce severe delayed neurotoxicity as demonstrated in animal studies.

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RoundsHuman serum albumin has been in clinical use for more than 60 years, since World War II. The Cohn fractionation process was instrumental in bringing about albumin availability to the battlefield and the hospital. The clinical role of albumin has been debated over time and has changed; however, the substance is still widely used despite reservations about its usefulness in certain contexts. The overall safety profile of human albumin has been excellent; nevertheless, some individuals experience an allergic reaction against infused albumin that can result in anaphylaxis.¹ Case SummaryThe patient is a 74-year-old man with a history of gingival recurrent squamous cell carcinoma who was undergoing neck dissection to treat his lymph nodes. He was given 500 mL of 5% human albumin (Octapharma) but did not receive any other blood products. After administration of albumin, he suddenly developed intractable hypotension (Table 1). Also, once the surgical drapes were removed, the patient exhibited a rash and flushing on his chest and abdomen. He was treated with 30 μg of epinephrine and 10 U of vasopressin; the attending anesthesiologist recorded his severe reaction to albumin in the allergy-alert section of his medical record. This complication resulted in the cessation of the surgical procedure, which had to be rescheduled to a later time, once the condition of the patient had become stable again. ResolutionA specimen from the patient was sent for immunoglobulin A (IgA) testing to rule out an anaphylactic IgA-deficiency reaction; the results were normal. The medical records for ABSTRACT Reactions to human albumin are rare, but happen at a frequency to warrant caution since it is routinely produced from batched human plasma. Albumin preparations have advanced substantially in purity since their inception, but despite this achievement severe reactions may still occur. These reactions may include a rash, urticarial, hypotension, dyspnea, or even anaphylaxis. The patient is a 74 year old male with history of recurrent squamous cell carcinoma of gingiva undergoing a neck dissection for lymph nodes. The patient was given 500 mL of albumin and suddenly developed intractable hypotension. In addition, once the surgical drapes were removed, the patient exhibited a rash and flushing on both the chest and abdomen. The patient was treated with pressor agents and a severe reaction to albumin was logged in the allergy alert section of the patient chart. Although human albumin has an excellent safety profile, it is important to recognize allergic transfusion reaction symptoms quickly and initiate an appropriate investigation.