Effects of Diabetes Mellitus on the Disposition of Tofacitinib, a Janus Kinase Inhibitor, in Rats

Tofacitinib, a Janus kinase inhibitor, was developed for the treatment of rheumatoid arthritis. Recently, it has been associated with an increased change in arthritis development in patients with diabetes. Herein, we evaluated the pharmacokinetics of tofacitinib after intravenous (10 mg/kg) and oral (20 mg/kg) administration to rats with streptozotocin-induced diabetes mellitus and control rats. Following intravenous administration of tofacitinib to rats with streptozotocin-induced diabetes mellitus, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was significantly smaller (33.6%) than that of control rats. This might be due to the faster hepatic intrinsic clearance (112%) caused by an increase in the hepatic cytochrome P450 (CYP) 3A1(23) and the faster hepatic blood flow rate in rats with streptozotocin-induced diabetes mellitus than in control rats. Following oral administration, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was also significantly smaller (55.5%) in rats with streptozotocin-induced diabetes mellitus than that in control rats. This might be due to decreased absorption caused by the higher expression of P-glycoprotein and the faster intestinal metabolism caused by the higher expression of intestinal CYP3A1(23), which resulted in the decreased bioavailability of tofacitinib (33.0%) in rats with streptozotocin-induced diabetes mellitus. In summary, our findings indicate that diabetes mellitus affects the absorption and metabolism of tofacitinib, causing faster metabolism and decreased intestinal absorption in rats with streptozotocin-induced diabetes mellitus.

Treatment and Rehabilitation of Repetitively Recurrent Langerhans Cell Histiocytosis: A Case Report

Langerhans cell histiocytosis (LCH) is characterized by proliferation of histiocyte-like cells (Langerhans cell histiocytes) with characteristic Birbeck granules, accompanied by other inflammatory cells. Treatments of LCH include surgery, chemotherapy, and radiotherapy. One of the representative forms of chemotherapy is intralesional injection of steroids. Surgical treatment in the form of simple excision, curettage, or even ostectomy can be performed depending on the extent of involvement. Radiotherapy is suggested in case of local recurrence, or a widespread lesion. This article shows the case of repetitively recurrent LCH of a 56-year-old man who had been through surgical excision and had to have marginal mandibulectomy and radiotherapy when the disease recurred. After the first recurrence occurred, lesions involved the extensive part of the mandible causing pathologic fracture, so partial mandibular bone resection was performed from the right molar area to the left molar area followed by the excision of the surrounding infected soft tissues. The resected mandibular bone was reconstructed with a segment of fibula osteomyocutaneous free flap and overdenture prosthesis supported by osseointegrated implants.

Recovery of inferior alveolar nerve injury after bilateral sagittal split ramus osteotomy (BSSRO): a retrospective study / 대한악안면성형재건외과학회지

BACKGROUND: Bilateral sagittal split ramus osteotomy (BSSRO) is the most widely used mandibular surgical technique in orthognathic surgery and is easy to relocate the distal segments, accelerating bone repair by the large surface of bone contact. However, it can cause neurosensory dysfunction (NSD) or sensory loss by injury of the inferior alveolar nerve. The purpose of the present study was to evaluate NSD after BSSRO and modifiers at NSD recovery. METHODS: In this study, NSD characteristics after BSSRO from 2009 to 2014 at the Kyung Hee University Dental Hospital were evaluated. The pattern of sensory recovery over time was also evaluated based on factors such as field of sensory dysfunction, surgical procedure, presence of pre-operative facial asymmetry, and postoperative medications. RESULTS: Most of the patients had shown NSD immediately after orthognathic surgery. Among the 1192 sides of 596 patients, NSD was observed in 953 sides and 544 patients. Sexual predilection was shown in males (p value = 0.0062). In the asymmetric group of 132 patients, NSD was observed in 128 patients (96.97%). In the symmetric group of 464 patients, NSD was observed in 416 patients (89.45%); on the other hand, NSD was observed significantly higher in the asymmetric group (p = 0.025). NSD-associated factors were analyzed, and vitamin B12 may be beneficial for NSD recovery. CONCLUSIONS: There was a difference between the symmetric group and the asymmetric group in NSD recovery. Vitamin B12 can be regarded as an effective method to nerve recovery. However, a further prospective study is needed.