A negative allosteric modulator of PDE4D enhances learning after traumatic brain injury.

Traumatic brain injury (TBI) significantly decreases cyclic AMP (cAMP) signaling which produces long-term synaptic plasticity deficits and chronic learning and memory impairments. Phosphodiesterase 4 (PDE4) is a major family of cAMP hydrolyzing enzymes in the brain and of the four PDE4 subtypes, PDE4D in particular has been found to be involved in memory formation. Although most PDE4 inhibitors target all PDE4 subtypes, PDE4D can be targeted with a selective, negative allosteric modulator, D159687. In this study, we hypothesized that treating animals with D159687 could reverse the cognitive deficits caused by TBI. To test this hypothesis, adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. After 3 months of recovery, animals were treated with D159687 (0.3 mg/kg, intraperitoneally) at 30 min prior to cue and contextual fear conditioning, acquisition in the water maze or during a spatial working memory task. Treatment with D159687 had no significant effect on these behavioral tasks in non-injured, sham animals, but did reverse the learning and memory deficits in chronic TBI animals. Assessment of hippocampal slices at 3 months post-TBI revealed that D159687 reversed both the depression in basal synaptic transmission in area CA1 as well as the late-phase of long-term potentiation. These results demonstrate that a negative allosteric modulator of PDE4D may be a potential therapeutic to improve chronic cognitive dysfunction following TBI.

Removal of Polymer Clips From the Gallbladder Fossa in a Patient With Ehlers-Danlos Syndrome (EDS) to Treat Mast Cell Activation Syndrome (MCAS): A Case Report.

Ehlers-Danlos syndrome (EDS) is a group of hereditary disorders characterized by fragility of connective tissue. Clinical manifestations of the disorder involve the skin, joints, blood vessels, and other internal organs. We report the case of a 29-year-old female suffering from EDS and mast cell activation syndrome (MCAS). Her history includes multiple orthopedic surgeries leading to the worsening of her symptoms. This was determined to be due to medical implants placed during her multiple procedures predisposing her to severe immunological reactions. This case report emphasizes the importance of meticulous surgical intervention when managing patients with EDS.

Use of Seprafilm in a Patient With Recurrent Small Bowel Obstruction: A Case Report.

Small bowel obstruction (SBO) is an emergency that should be managed early to reduce the risk of bowel perforation, strangulation and subsequent life-threatening organ dysfunction caused by sepsis. A prompt diagnostic workup including imaging and lab studies is required to assess the severity of the obstruction and to establish if emergency surgery is required. We report the case of a 55-year-old male with a history of recurrent SBO, previous ventral hernia repair and indications of previous colonic tubular adenoma per colonoscopy findings. The patient underwent an exploratory laparotomy procedure and adhesiolysis to release the SBO. This case report emphasizes the safety and efficacy of Seprafilm placement intraoperatively in decreasing the occurrence of postoperative adhesions in abdominal laparotomy procedures.