Intraperitoneal injection of amylin or its analog reduces Alzheimer’s disease (AD) pathology in the brains. However, self-injecting amylin analogs is difficult for patients due to cognitive deficits. This work aims to study the effects of amylin on the brain could be achieved by oral delivery as some study reported that amylin receptor may be present in the gastrointestinal tract. A 6-week course of oral amylin treatment reduced components of AD pathology, including the levels of amyloid-β, phosphorylated tau, and ionized calcium binding adaptor molecule 1. The treatment reduced active forms of cyclin-dependent kinase 5. Oral amylin treatment led to improvements in social deficit in AD mouse. Using immunofluorescence, we observed the amylin receptor complexed with the calcitonin receptor and receptor activity-modifying proteins in the enteric neurons. The study suggests the potential of the oral delivery of amylin analogs for the treatment of AD and other neurodegenerative diseases through enteric neurons.
Focused ultrasound (FUS) is a minimally invasive treatment that utilizes high-energy ultrasound waves to thermally ablate tissue. Magnetic resonance imaging (MRI) guidance may be combined with FUS (MRgFUS) to increase its accuracy and has been proposed for lung tumor ablation/debulking. However, the lungs are predominantly filled with air, which attenuates the strength of the FUS beam. This investigation aimed to test the feasibility of a new approach using an intentional lung collapse to reduce the amount of air inside the lung and a controlled hydrothorax to create an acoustic window for transcutaneous MRgFUS lung ablation. Eleven pigs had one lung mechanically ventilated while the other lung underwent a controlled collapse and subsequent hydrothorax of that hemisphere. The MRgFUS lung ablations were then conducted via the intercostal space. All the animals recovered well and remained healthy in the week following the FUS treatment. The location and size of the ablations were confirmed one week post-treatment via MRI, necropsy, and histological analysis. The animals had almost no side effects and the skin burns were completely eliminated after the first two animal studies, following technique refinement. This study introduces a novel methodology of MRgFUS that can be used to treat deep lung parenchyma in a safe and viable manner.
A combination of surgery and chemotherapy is the most effective treatment available for Malignant Pleural Mesothelioma (MPM). However, both cause significant collateral damage and cannot eliminate residual microscopic disease. This investigation aimed to compare and determine the feasibility of utilizing Radiofrequency Ablation (RFA) and Magnetic-Resonance-guided Focused Ultrasound Surgery (MRgFUS) as alternative treatments for MPM. A large animal tumor model was developed in 13 Yorkshire female pigs using the MSTO211H cell line. Two pigs were initially used to determine the cyclosporine dose required for immunosuppression and tumor development. Subsequently, 11 other pigs underwent tumor development. Of these 11, 2 died during cell inoculation. Small tumor masses and adhesions were present in the other 9, indicating mesothelioma development. Five pigs then received RFA treatment, and 4 pigs received MRgFUS treatment. Tumor model development and effect of the two treatments were examined using MRI and by necropsy. RFA and MRgFUS both successfully ablated approximately the same sized area in the same treatment time. This study demonstrates that RFA and MRgFUS are feasible for tumor debulking, and while MRgFUS requires more pretreatment planning compared to RFA, MRgFUS is a completely noninvasive procedure.