pyrimidinones and Intestinal-Diseases

Pneumatosis intestinalis (PI) is a rare entity which refers to the presence of gas within the wall of the small bowel or colon which is a radiographic sign. The etiology and clinical presentation are variable. Patients with PI may present either with chronic mild non-specific symptoms or with acute abdominal pain with peritonitis. Some cases of intestinal pneumatosis have been reported as adverse events of new oncological treatments such as targeted therapies that are widely used in multiple tumors.. A 59-year-old caucasian female with radioactive iodine-refractory metastatic thyroid papillary carcinoma with BRAF. This case report is, in our knowledge, the first description of PI in a patient treated with dabrafenib-trametinib. Conservative treatment is feasible if there are no abdominal symptoms.

Topics: Emphysema; Female; Humans; Imidazoles; Intestinal Diseases; Iodine Radioisotopes; Middle Aged; Oximes; Positron Emission Tomography Computed Tomography; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Skull Base Neoplasms; Thyroid Cancer, Papillary; Thyroid Neoplasms

1,6-Dimethyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido 1,2-a pyrimidine-3-carboxamide (Ch-127) significantly inhibited the intestinal ulceration induced by a single dose of indomethacin (15 mg/kg p.o.). Moreover, indomethacin produced 75% lethality in the dose of 3.5 mg/kg p.o. administered daily for 2 weeks. The concurrent daily administration of Ch-127 (50 mg/kg p.o. +25 mg/kg s.c.) with indomethacin prevented the gastrointestinal mucosa from histologically detectable changes, and none of the animals died. The 80% lethality following the daily administration of naproxen (60 mg/kg p.o.) for two weeks was also significantly decreased by combining it with Ch-127 (50 mg/kg p.o.).

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Combinations; Indomethacin; Intestinal Diseases; Male; Naproxen; Pyrimidinones; Rats; Rats, Inbred Strains; Ulcer