Case Report of Methemoglobinemia: An Illustration That It Is Time to Report all Results with Arterial and Venous Blood Gas Result Reporting.

BACKGROUND: Methemoglobinemia and carbon monoxide poisoning are potentially life-threatening conditions that can present with nonspecific clinical features. This lack of specificity increases the probability of misdiagnosis or avoidable delays in diagnosis and management. These conditions are both treatable with antidotes of methylene blue and oxygen, respectively. Modern blood gas analyzers have the ability to measure carboxyhemoglobin (COHb) and methemoglobin (MetHb) levels without any additional resources. However, these results, although readily available from the machine used to perform the analysis, are not fully reported by some hospital clinical laboratories. CASE REPORT: A 49-year-old male presented with shortness of breath and cyanosis after inhaling cocaine via a nasal route ("snorting"). Methemoglobinemia was not initially considered in the differential diagnosis. However, the diagnosis of methemoglobinemia was made once newly routinely reported laboratory results revealed an elevated MetHb level. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Routinely reporting MetHb and COHb levels with arterial and venous blood gas results will facilitate making the diagnoses of these infrequently diagnosed causes of hypoxia more quickly so that early treatment of these uncommon but potentially lethal conditions can be initiated promptly.

Artemisinin blocks prostate cancer growth and cell cycle progression by disrupting Sp1 interactions with the cyclin-dependent kinase-4 (CDK4) promoter and inhibiting CDK4 gene expression.

Artemisinin, a naturally occurring component of Artemisia annua, or sweet wormwood, is a potent anti-malaria compound that has recently been shown to have anti-proliferative effects on a number of human cancer cell types, although little is know about the molecular mechanisms of this response. We have observed that artemisinin treatment triggers a stringent G1 cell cycle arrest of LNCaP (lymph node carcinoma of the prostate) human prostate cancer cells that is accompanied by a rapid down-regulation of CDK2 and CDK4 protein and transcript levels. Transient transfection with promoter-linked luciferase reporter plasmids revealed that artemisinin strongly inhibits CDK2 and CDK4 promoter activity. Deletion analysis of the CDK4 promoter revealed a 231-bp artemisinin-responsive region between -1737 and -1506. Site-specific mutations revealed that the Sp1 site at -1531 was necessary for artemisinin responsiveness in the context of the CDK4 promoter. DNA binding assays as well as chromatin immunoprecipitation assays demonstrated that this Sp1-binding site in the CDK4 promoter forms a specific artemisinin-responsive DNA-protein complex that contains the Sp1 transcription factor. Artemisinin reduced phosphorylation of Sp1, and when dephosphorylation of Sp1 was inhibited by treatment of cells with the phosphatase inhibitor okadaic acid, the ability of artemisinin to down-regulate Sp1 interactions with the CDK4 promoter was ablated, rendering the CDK4 promoter unresponsive to artemisinin. Finally, overexpression of Sp1 mostly reversed the artemisinin down-regulation of CDK4 promoter activity and partially reversed the cell cycle arrest. Taken together, our results demonstrate that a key event in the artemisinin anti-proliferative effects in prostate cancer cells is the transcriptional down-regulation of CDK4 expression by disruption of Sp1 interactions with the CDK4 promoter.