Droxidopa as an effective treatment for refractory neurogenic orthostatic hypotension and reflex bradycardia in amyloid light-chain amyloidosis: a case report.

BACKGROUND: Droxidopa is an oral treatment for the stepwise treatment of neurogenic orthostatic hypotension from autonomic dysfunction. It has been shown to be useful predominantly with neurogenic orthostatic hypotension secondary to Parkinson's disease, but only a few cases have documented its usefulness in patients with neurogenic orthostatic hypotension due to amyloidosis, which is often severe and refractory. In addition, only one source in the literature reports the concomitant use of midodrine and droxidopa for such patients. Finally, we argue that droxidopa seems to have a protective effect against episodes of reflex bradycardia, which is not previously reported. CASE PRESENTATION: A 64-year-old white man was admitted for 1 year of worsening syncopal episodes, diarrhea, failure to thrive, heart failure, and neuropathy. Medical emergencies were called five times on the overhead hospital intercom over a 4-day period in the beginning of his admission due to severe hypotension and bradycardia. He was eventually diagnosed as having amyloid light-chain amyloidosis and myeloma. After starting droxidopa, both his systolic blood pressure and reflex bradycardia improved, and no more medical emergency events were called during the remaining 30 days of admission. He felt much better subjectively and was able to sit upright and engage in physical therapy. CONCLUSIONS: We show that droxidopa is effective when used with midodrine to treat refractory neurogenic orthostatic hypotension in patients with amyloidosis. There are very few cases reporting the use of droxidopa in amyloidosis, with only one study that uses droxidopa and midodrine concomitantly. In addition, our patient's reflex bradycardia improved drastically after starting droxidopa, which we believe is mediated by increased systemic norepinephrine. There were no side effects to droxidopa, and the benefits lasted well beyond the reported duration of 1-2 weeks that was noted to be a limitation in some studies.

Anaerobic Heme Degradation: ChuY Is an Anaerobilin Reductase That Exhibits Kinetic Cooperativity.

Heme catabolism is an important biochemical process that many bacterial pathogens utilize to acquire iron. However, tetrapyrrole catabolites can be reactive and often require further processing for transport out of the cell or conversion to another useful cofactor. In previous work, we presented in vitro evidence of an anaerobic heme degradation pathway in Escherichia coli O157:H7. Consistent with reactions that have been reported for other radical S-adenosyl-l-methionine methyltransferases, ChuW transfers a methyl group to heme by a radical-mediated mechanism and catalyzes the ß-scission of the porphyrin macrocycle. This facilitates iron release and the production of a new linear tetrapyrrole termed "anaerobilin". In this work, we describe the structure and function of ChuY, an enzyme expressed downstream from chuW within the same heme utilization operon. ChuY is structurally similar to biliverdin reductase and forms a dimeric complex in solution that reduces anaerobilin to the product we have termed anaerorubin. Steady state analysis of ChuY exhibits kinetic cooperativity that is best explained by a random addition mechanism with a kinetically preferred path for initial reduced nicotinamide adenine dinucleotide phosphate binding.