An Unsuspecting Case of Familial Adenomatous Polyposis (FAP).

Familial adenomatous polyposis (FAP) is an inherited and rare disease that typically manifests in the second decade of life. FAP presents as an asymptomatic disease state in its early stages, which affects the gastrointestinal (GI) tract, making it difficult to diagnose. The disease is characterized by numerous adenomatous polyps in the colon or rectum. Adenomatous polyposis coli (APC) gene mutation allows for the unchecked growth of polyps and provides the path for cancerous proliferation. In FAP, APC mutation inheritance has a moderate preponderance for paternal origin. A family history of FAP is an indicator to start early screening in patients, especially those with a paternal family history of the disease. We present a 21-year-old male patient who presented to the clinic with normal hemoglobin, heme-positive stools, and no family history of FAP or colon cancer. The initial assessment and plan was an endoscopy to look for upper and lower GI causes, but if negative, a further hematologic workup would be required. This case highlighted the need for thorough follow-up and workup of occult GI bleed. Clinical suspicion for FAP should be kept in mind, especially in young patients without a family history and unexplained heme-positive stool. Other findings that could suggest FAP include a personal or family history of extra-colonic manifestations such as fibromas, osteomas, or dentition abnormalities.

MEHP induces alteration of mitochondrial function and inhibition of steroid biosynthesis in MA-10 mouse tumor Leydig cells.

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is widely used in manufacturing. Previous studies have shown that mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of DEHP, has inhibitory effects on luteinizing hormone (LH)-stimulated steroid biosynthesis by Leydig cells. The molecular mechanisms underlying its effects, however, remain unclear. In the present study, we examined the effects of MEHP on changes in mitochondrial function in relationship to reduced progesterone formation by MA-10 mouse tumor Leydig cells. Treatment of MA-10 cells with MEHP (0-300 µM for 24 h) resulted in dose-dependent inhibition of LH-stimulated progesterone biosynthesis. Biochemical analysis data revealed that the levels of the mature steroidogenic acute regulatory protein (STAR), a protein that works at the outer mitochondrial membrane to facilitate the translocation of cholesterol for steroid formation, was significantly reduced in response to MEHP exposures. MEHP also caused reductions in MA-10 cell mitochondrial membrane potential (ΔΨm) and mitochondrial respiration as evidenced by decreases in the ability of the mitochondria to consume molecular oxygen. Additionally, significant increases in the generation of mitochondrial superoxide were observed. Taken together, these results indicate that MEHP inhibits steroid formation in MA-10 cells at least in part by its effects on mitochondrial function.