Amifampridine overdose leading to refractory status epilepticus.

3,4-Aminopyridine or Amifampridine belongs to the aminopyridine class of drugs which is used to treat multiple sclerosis and Lambert-Eaton Myasthenic Syndrome (LEMS). Aminopyridine pharmaceuticals inhibit presynaptic potassium channels. This increases available acetylcholine in the nerve cleft which leads to improved strength in this patient population. While overdoses have been reported of 4-Aminopyridine, no case reports of acute 3.4-Aminopyridine overdose are currently available. A 67 year old man presented to the emergency department 30 min after ingesting 100 mg of amifampridine in a suicide attempt. Within an hour of ingestion he experienced tachycardia, tachypnea, hypertension and tremor. The patient then started to experience seizures and had a cardiac arrest 3 h after the ingestion. The patient achieved return of spontaneous circulation but proceeded to have refractory seizures. Despite significant and escalating doses of anti-epileptic medications, the patient continued to have seizures until 18 h after ingestion. His anti-epileptic medications were weaned over the following days and he had no more seizures. This is a report of a novel overdose of 3,4-Aminopyridine, a medication that belongs to the aminopyridine class of pharmaceuticals that have been well used for many years. Aminopyridine overdoses are commonly thought to carry low morbidity and mortality; however, our patient had both a cardiac arrest and refractory status epilepticus. Ultimately, this case suggests that patients who overdose on 3,4-Aminopyridine could become critically ill and their presentation may be far more severe than that of other medications of the same class.

Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells.

Smooth muscle formation and function are critical in development and postnatal life. Hence, studies aimed at better understanding SMC differentiation are of great importance. Here, we report that multipotent adult progenitor cells (MAPCs) isolated from rat, murine, porcine, and human bone marrow demonstrate the potential to differentiate into cells with an SMC-like phenotype and function. TGF-beta1 alone or combined with PDGF-BB in serum-free medium induces a temporally correct expression of transcripts and proteins consistent with smooth muscle development. Furthermore, SMCs derived from MAPCs (MAPC-SMCs) demonstrated functional L-type calcium channels. MAPC-SMCs entrapped in fibrin vascular molds became circumferentially aligned and generated force in response to KCl, the L-type channel opener FPL64176, or the SMC agonists 5-HT and ET-1, and exhibited complete relaxation in response to the Rho-kinase inhibitor Y-27632. Cyclic distention (5% circumferential strain) for 3 weeks increased responses by 2- to 3-fold, consistent with what occurred in neonatal SMCs. These results provide evidence that MAPC-SMCs are phenotypically and functionally similar to neonatal SMCs and that the in vitro MAPC-SMC differentiation system may be an ideal model for the study of SMC development. Moreover, MAPC-SMCs may lend themselves to tissue engineering applications.