Intestinal Atp8b1 dysfunction causes hepatic choline deficiency and steatohepatitis.

Choline is an essential nutrient, and its deficiency causes steatohepatitis. Dietary phosphatidylcholine (PC) is digested into lysoPC (LPC), glycerophosphocholine, and choline in the intestinal lumen and is the primary source of systemic choline. However, the major PC metabolites absorbed in the intestinal tract remain unidentified. ATP8B1 is a P4-ATPase phospholipid flippase expressed in the apical membrane of the epithelium. Here, we use intestinal epithelial cell (IEC)-specific Atp8b1-knockout (Atp8b1IEC-KO) mice. These mice progress to steatohepatitis by 4 weeks. Metabolomic analysis and cell-based assays show that loss of Atp8b1 in IEC causes LPC malabsorption and thereby hepatic choline deficiency. Feeding choline-supplemented diets to lactating mice achieves complete recovery from steatohepatitis in Atp8b1IEC-KO mice. Analysis of samples from pediatric patients with ATP8B1 deficiency suggests its translational potential. This study indicates that Atp8b1 regulates hepatic choline levels through intestinal LPC absorption, encouraging the evaluation of choline supplementation therapy for steatohepatitis caused by ATP8B1 dysfunction.

Blue-violet light-emitting diode irradiation in combination with hemostatic gelatin sponge (Spongel) application ameliorates immediate socket bleeding in patients taking warfarin.

OBJECTIVE: The control of bleeding after tooth extraction is a major concern in patients taking warfarin. Light-emitting diode (LED) irradiation with hemostatic gelatin sponge application was investigated. STUDY DESIGN: Patients who took warfarin and required tooth extraction were divided randomly into 3 groups. The first group was irradiated with blue-violet LED after tooth extraction. The second group was treated with a hemostatic gelatin sponge and LED irradiation. The third group was treated with only hemostatic gelatin sponges. Hemostasis was evaluated at 30 seconds after treatment. RESULTS: Less than 30% of the patients achieved hemostasis within 30 seconds in the hemostatic sponge group; approximately 50% of the patients in the simple LED irradiation group achieved hemostasis within 30 seconds; and 86.7% of the patients in the LED and hemostatic sponge combined group achieved hemostasis within 30 seconds, indicating that combined treatment with LED and hemostatic sponges provided a significantly higher hemostasis than in the hemostatic sponge group (P < .01). CONCLUSIONS: Blue-violet LED irradiation combined with hemostatic gelatin sponge treatment yielded hemostasis of the extraction socket within 30 seconds without suture in most cases.

Blue-violet light emitting diode (LED) irradiation immediately controls socket bleeding following tooth extraction: clinical and electron microscopic observations.

OBJECTIVE: Bleeding control is a major concern during dental surgery. A novel photocoagulation method using an irradiating blue-violet light emitting diode (LED) was investigated. BACKGROUND: Some dental light-curving units can emit blue-violet wavelengths around 380-515 nm with two peaks (410 nm and 470 nm). These wavelengths can cover the maximum absorption spectra of hemoglobin (430 nm). MATERIALS AND METHODS: Blue-violet LED 380-515 nm, 750 mW/cm(2), 10 sec (7.5 J/cm(2)) was used. Irradiation was performed for 10 sec or an additional 10 sec for 10 cases of tooth extraction at a distance of 1 cm from the socket. Bleeding was stopped by conventional roll pressure in another five cases as a control. Bleeding time for both procedures was measured. A Mann-Whitney U test was used for statistical analysis. In vitro transmission electron microscope (TEM) studies were performed to clarify the mechanism of hemostasis by blue-violet LED irradiation. RESULTS: Irradiation with the blue-violet LED yielded immediate hemostasis of the socket. Five cases showed coagulation within the first 10 sec, and another five cases required an additional 10 sec to fully control the bleeding. In contrast, the conventional method required 2-5 min (median 180 sec) to obtain hemostasis. The difference between the time required to stop the bleeding in the two methods was found to be statistically significant (p = 0.0014). A week later, the LED-irradiated sockets were healed uneventfully with epithelial covering. TEM showed the formation of a thin amorphous layer and an adjacent agglutination of platelets and other cellular elements under the layer at the interface of the irradiated blood. CONCLUSION: Blue-violet LED irradiation of bleeding sockets caused immediate clot formation and hemostasis. This procedure was safe and reliable and showed no adverse effects.

[Nedaplatin (NDP)-combination therapy (NDP/5-FU,NDP/S-1) for oral cancer].

PURPOSE: The present study evaluated the efficacy and safety of nedaplatin-combination therapy (NDP/5-FU [5-FU arm] or NDP/S-1 [S-1 arm] ) for the treatment of oral squamous cell carcinoma. PATIENTS AND METHOD: Previously non-treated oral squamous cell carcinoma patients were eligible. Patients received 5-FU 600 mg/m(2)iv, as a 24-hour infusion (day 1 to 5) followed by NDP 80 to 100 mg/m(2) iv (day 1), or S-1 60 to 80 mg/m(2) orally twice a day (day 1 to 14) followed by NDP 80 mg/m(2) iv (day 8) every 28 days for one or two cycles. RESULTS: In total, 32 patients (18 in the 5-FU arm, 14 in the S-1 arm) were enrolled. Twenty patients were male and 12 were female. Median age was 57 years (range 20 years to 87 years). Thirty-one patients had a performance status (PS) oF 0, and 1 patient had a PS 1. Three patients were stage I, 12 stage III, and 12 were stage IV. The overall response rate was 69% (5-FU arm,72%;S-1 arm,64%). Two patients achieved a complete response, 20 patients a partial response, and 10 patients had no change. Grade 3 leucopenia, grade 3 and 4 thrombocytopenia and liver injury occurred in 6% (one in the 5-FU arm, and one in the S-1 arm), 9% (two in the 5-FU arm, and one in the S-1 arm), and 3% (one in the 5-FU arm), respectively. No other severe toxicities were observed. RESULTS: Response rate and toxicities were similar in both arms. However, the psychosocial stress on patients in the S-1 arm was reduced compared to that in the 5-FU arm, which required hospitalization for a longer period. The outcome in the present study needs further investigation.