Search

Introduction: Intranasal (IN) deferoxamine (DFO) has emerged over the past decade as a promising therapeutic in preclinical experiments across neurodegenerative and neurovascular diseases. As an antioxidant iron chelator, its mechanisms are multimodal, involving the binding of brain iron and the consequent engagement of several pathways to counter pathogenesis across multiple diseases. We and other research groups have shown that IN DFO rescues cognitive impairment in several rodent models of Alzheimer Disease (AD). Methods: This study was designed to probe dosing regimens to inform future clinical trials, while exploring mechanisms within the intracerebroventricular (ICV) streptozotocin (STZ) model. Results: Five weeks of daily IN dosing of Long Evans rats with 15 μL of a 1% (0.3 mg), but not 0.1% (0.03 mg), solution of DFO rescued cognitive impairment caused by ICV STZ administration as assessed with the Morris Water Maze (MWM) test of spatial memory and learning. Furthermore, IN DFO modulated several aspects of the neuroinflammatory milieu of the ICV STZ model, which was assessed through a novel panel of brain cytokines and immunohistochemistry. Using RNA-sequencing and pathway analysis, STZ was shown to induce several pathways of cell death and neuroinflammation, and IN DFO engaged multiple transcriptomic pathways involved in hippocampal neuronal survival. Discussion: To our knowledge this study is the first to assess the transcriptomic pathways and mechanisms associated with either the ICV STZ model or DFO treatment, and the first to demonstrate efficacy at this low dose. [ABSTRACT FROM AUTHOR]

Ectopic variceal bleeding is a potentially under recognized source of gastrointestinal (GI) hemorrhage. While vascular complications following pancreatic transplant are relatively common, the development of symptomatic ectopic venous varices has rarely been reported. We report two patients with a remote history of simultaneous kidney pancreas transplant (SPK) presenting two decades after transplant with an occult GI bleed. In both cases, a lengthy diagnostic course was required. The varices were treated with coil embolization via transhepatic approach. Our findings add to the limited literature on this topic and aid in the recognition, diagnosis, and management of this unusual presentation. [ABSTRACT FROM AUTHOR]