Bowel perforation associated with Cushing's disease: a case report with literature review.

Although rare, endogenous hypercortisolemia, including Cushing's disease (CD), is known to cause bowel perforation and to mask typical symptoms of bowel perforation, leading to delayed diagnosis. Additionally, elderly patients with CD are considered to be at a higher risk for bowel perforation because intestinal tissue fragility tends to increase in the elderly. Herein, we describe a rare case in which a young adult patient with CD was diagnosed with bowel perforation associated with CD following severe abdominal pain. A 24-year-old Japanese man was admitted to the hospital for the evaluation of ACTH-dependent Cushing's syndrome. He suddenly complained of severe abdominal pain on the 8th day of hospitalization. Computed tomography revealed free air around the sigmoid colon. The patient was diagnosed with bowel perforation, underwent emergency surgery, and was saved. He was subsequently diagnosed with CD, and the pituitary adenoma was resected transsphenoidally. To date, eight cases of bowel perforation due to CD had been reported, with a median age of 61 years at the time of bowel perforation. Hypokalemia was detected in half of the patients, and all had a history of diverticular disease. Nevertheless, not many patients complained of peritoneal irritation. In conclusion, this is the youngest reported case with bowel perforation due to CD and the first report of bowel perforation in a patient without a history of diverticular disease. Bowel perforation may occur in patients with CD, irrespective of age and the presence of hypokalemia, diverticular disease, or peritoneal irritation.

Development of spray-freeze-dried siRNA/PEI powder for inhalation with high aerosol performance and strong pulmonary gene silencing activity.

In the present study, a novel dry small interfering RNA (siRNA) powder for inhalation, containing polyethyleneimine (PEI) as a delivery vector, was produced by spray freeze drying (SFD). The powder had spherical and highly porous structure of approximately 10 µm in diameter with high aerosol performance for emission and lung delivery. The reconstituted siRNA/PEI complex after dissolution of the powder had almost the same physicochemical properties and in vitro gene silencing activity as the original one constituted in the sample solution before SFD, showing that the integrity of the siRNA was maintained. In in vivo studies of intratracheal administration into lung metastasis mice and healthy mice, powder with a low dose of 3 µg siRNA exhibited strong and specific gene silencing activity against tumors metastasized to the lungs, whereas it caused no significant histological changes, lactate dehydrogenase leakage, or inflammatory cytokine induction in the lungs. These results strongly indicated that inhalable dry siRNA/PEI powders can provide effective pulmonary gene silencing without severe lung injury and that SFD can be applied to the production of such powders.