Clinical Factors Affecting the Serum Retention of a Teratogenic Etretinate after the Acitretin Administration.

Etretinate, an acitretin metabolite, has a long retention duration in adipose tissues with a teratogenic potential. FDA advises a contraceptive period of at least three years after discontinuing acitretin. However, the effect of accumulated etretinate in adipose tissues on fetus is unknown. Although the teratogenic threshold for serum concentration of etretinate has been presented as higher than 2 ng/mL, that of acitretin is unknown. To examine factors affecting body retention of acitretin and etretinate, effects of acitretin dosage, acitretin-taking duration, elapsed time after stopping acitretin, age, sex, concomitant alcohol consumption, and foods and supplements rich in vitamin A intake on serum concentrations of acitretin and etretinate were analyzed in 14 acitretin-taken patients and 58 controls without taking acitretin or etretinate. Serum concentrations of acitretin, but not etretinate, tended to be inversely related to the discontinuation duration. They were also related to old age. Different from a published result that alcohol consumption could promote the metabolism of acitretin into etretinate, alcohol intake did not affect serum concentrations of etretinate. Unexpectedly, more frequent intake of vitamin A or provitamin A-rich food and supplements was associated with higher serum acitretin, whereas less frequent intake of vitamin A or provitamin A-rich food and supplements was associated with higher serum levels of etretinate in acitretin-taken patients. Despite preliminary data, inter-individual variations in serum retention of etretinate suggest the necessity of further research before applying the same guidelines to everyone to minimize unnecessary contraception.

Anti-Tumor Effect of IDF-11774, an Inhibitor of Hypoxia-Inducible Factor-1, on Melanoma.

Melanoma is one of the most aggressive skin cancers. Hypoxia contributes to the aggressiveness of melanoma by promoting cancer growth and metastasis. Upregulation of cyclin D1 can promote uncontrolled cell proliferation in melanoma, whereas stimulation of cytotoxic T cell activity can inhibit it. Epithelial mesenchymal transition (EMT) plays a critical role in melanoma metastasis. Hypoxia-inducible factor-1α (HIF-1α) is a main transcriptional mediator that regulates many genes related to hypoxia. CoCl2 is one of the most commonly used hypoxia-mimetic chemicals in cell culture. In this study, inhibitory effects of IDF-11774, an inhibitor of HIF-1α, on melanoma growth and metastasis were examined using cultured B16F10 mouse melanoma cells and nude mice transplanted with B16F10 melanoma cells in the presence or absence of CoCl2-induced hypoxia. IDF-11774 reduced HIF-1α upregulation and cell survival, but increased cytotoxicity of cultured melanoma cells under CoCl2-induced hypoxia. IDF-11774 also reduced tumor size and local invasion of B16F10 melanoma in nude mice along with HIF-1α downregulation. Expression levels of cyclin D1 in melanoma were increased by CoCl2 but decreased by IDF-11774. Apoptosis of melanoma cells and infiltration of cytotoxic T cells were increased in melanoma after treatment with IDF-11774. EMT was stimulated by CoCl2, but restored by IDF- 11774. Overall, IDF-11774 inhibited the growth and metastasis of B16F10 melanoma via HIF-1α downregulation. The growth of B16F10 melanoma was inhibited by cyclin D1 downregulation and cytotoxic T cell stimulation. Metastasis of B16F10 melanoma was inhibited by EMT suppression.

Synchronous Orofacial Granulomatosis in a Patient with Brain Cavernous Hemangioma.

Orofacial granulomatosis is a rare granulomatous inflammatory disease, characterized by recurrent orofacial swelling. Infectious, genetic, and immunologic etiologies are suggested, but not fully understood. Herein, we report a case of synchronous orofacial granulomatosis with brain cavernous hemangioma in a 44-year-old female patient, which may be considered paraneoplastic syndrome.

Correlation between complicated diverticulitis and visceral fat.

The aim of this study was to examine the relationship of complications related to diverticulitis and visceral obesity. The study was based on a retrospective case note review conducted at the Hanyang University Hospital. Patients were diagnosed with diverticulitis based on clinical symptoms and abdominal computed tomography (CT) findings and divided into two groups: those admitted with complicated diverticulitis and those with a simple diverticulitis episode. We compared the body mass index (BMI) and degree of visceral obesity, measured by abdominal CT. The study included 140 patients, 87 (62.1%) were simple diverticulitis and 53 (37.9%) were complicated diverticulitis. In the complicated diverticulitis group, 9 (6.4%) cases were recurrent, 29 (20.7%) were perforation or abscess patients, and 28 (20%) were patients with systemic inflammatory response syndrome (SIRS). Of the SIRS patients, 13 were involved in other complication groups. When comparing in the two groups, the complicated diverticulitis group had a significantly higher visceral fat area (128.57 cm(2) vs 102.80 cm(2), P = 0.032) and a higher ratio of visceral fat area/subcutaneous fat area (0.997 vs 0.799, P = 0.014). Visceral obesity is significantly associated with complications of diverticulitis.