The use of angiotensin-converting enzyme inhibitors (ACEis) has been reported to reduce symptoms of cognitive decline in patients with Alzheimer’s disease (AD). Yet, the protective role of ACEis against AD symptoms is still controversial. Here, we aimed at determining whether oral treatment with the ACEi lisinopril has beneficial effects on cognitive and physical functions in a Drosophila melanogaster model of AD that overexpresses the human amyloid precursor protein and the human β-site APP-cleaving enzyme in neurons. We found a significant impairment in learning and memory as well as in climbing ability in young AD flies compared to control flies. After evaluation of the kynurenine pathway of tryptophan metabolism, we also found that AD flies displayed a >30-fold increase in the levels of the neurotoxic 3-hydroxykynurenine (3-HK) in their heads. Furthermore, compared to control flies, AD flies had significantly higher levels of the reactive oxygen species (ROS) hydrogen peroxide in their muscle-enriched thoraces. Lisinopril significantly improved deficits in learning and memory and climbing ability in AD flies. The positive impact of lisinopril on physical function might be, in part, explained by a significant reduction in ROS levels in the thoraces of the lisinopril-fed AD flies. However, lisinopril did not affect the levels of 3-HK. In conclusion, our findings provide novel and relevant insights into the therapeutic potential of ACEis in a preclinical AD model.

Oxygen at high pressure (OHP) and X-irradiation can interact in the fruit fly Drosophila melanogaster to potentiate toxic actions characteristic of one agent alone. 1000 kvp X-irradiation in doses of 30, 60, and 75 kr accelerated the acute immobilization of young male Drosophila by oxygen at 7.8 atm, up to rates twice that observed with such oxygen pressure alone. X-irradiation alone in these dosages did not acutely immobilize the Drosophila. X-irradiation during exposure to 7.8 atm pO2 was more effective and consistent in producing this potentiation than was X-irradiation that preceded exposure to OHP. Acute OHP toxicity in young female Drosophila was not potentiated by 75 kr of Xirradiation. On the other hand, shortening of the life span of young male Drosophila by the above doses of X-irradiation was augmented significantly by a concurrent 40 min exposure to OHP (which alone did not significantly decrease life span). This shows, for the first time, that oxygen can affect not only the acute effects of radiation, but also the residual irreversible effects indicated by the life span shortening.

Introduction: Budd Chiari Syndrome (BCS) is a very rare disease affecting approximately 1 in 100,000 people in the general population.  It is caused by an obstruction of the hepatic veins leading to blood backing up in the liver. Treatment options to improve hepatic blood flow and relieve ascites are well documented. However, there are no established guidelines or treatment preferences for pain associated with BCS while patients are awaiting other treatment options.  Case: A 22-year-old African American female was diagnosed with Budd Chiari Syndrome.  The initial attempt at a transjugular intrahepatic portosystemic shunt (TIPS) procedure failed.  While awaiting a second attempt at the procedure, the patient presented to her primary care provider complaining of abdominal and right upper quadrant pain.  Treatment guidelines were searched for acute pain management options; however, no BCS pain management guidelines exist. Discussion: Individuals with BCS often present with abdominal pain, however, no guidelines outlining analgesic options in BCS exists.  Acetaminophen, NSAIDs, and opioids are commonly used prescription medications for moderate to severe pain.  Acetaminophen use was not considered due to acute liver injury and portal venous thrombosis.  Anticoagulation with apixaban prevented concurrent use with NSAIDs.  Opioid medications combined with acetaminophen were excluded to minimize exacerbating the liver injury.  Tramadol 25 mg was chosen due to its lower abuse profile than other opioid analgesics, and was initiated for pain management. Conclusion: The patient reported adequate pain control with tramadol, tolerated the medication with no complications, and underwent a successful TIPS procedure one month later.  Abdominal pain is a common symptom of BCS and needs to be effectively managed.  Guidelines on treating pain associated with BCS in the outpatient setting would improve quality of life for patients and provide guidance to primary care providers requiring direction on how to address pain associated with Budd Chiari Syndrome safely and adequately.