Although corticospinal tract axons cannot regenerate long distances after spinal cord injury, they are able to sprout collateral branches rostral to an injury site that can help form compensatory circuits in cases of incomplete lesions. We show here that inosine enhances the formation of compensatory circuits after a dorsal hemisection of the thoracic spinal cord in mature rats and improves coordinated limb use. Inosine is a naturally occurring metabolite of adenosine that crosses the cell membrane and, in neurons, activates Mst3b, a protein kinase that is part of a signal transduction pathway that regulates axon outgrowth. Compared to saline-treated controls, rats with dorsal hemisections that were treated with inosine showed three times as many synaptic contacts between corticospinal tract collaterals and long propriospinal interneurons that project from the cervical cord to the lumbar level. Inosine-treated rats also showed stronger serotonergic reinnervation of the lumbar cord than saline-treated controls, and performed well above controls in both open-field testing and a horizontal ladder rung-walking test. Inosine was equally effective whether delivered intracranially or intravenously, and has been shown to be safe for other indications in humans. Thus, inosine might be a useful therapeutic for improving outcome after spinal cord injury.
Adrenocortical carcinoma (ACC) is a rare malignancy associated with poor prognosis despite available treatments. In patients with localized or locally advanced disease, complete resection with negative margins offers the only potential for cure. Unfortunately, most patients develop local and distant recurrence following initial resection highlighting the importance of meticulous surgical technique in the hands of an experienced surgeon. While minimally invasive surgery (MIS) has supplanted open surgery for small to medium-sized benign adrenal tumors, controversy surrounds the use of MIS for resection of ACC. We sought to provide an overview of the key oncological principles in the surgical management of ACC and to critically review the literature comparing outcomes between the open and MIS approaches.
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