The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis

Dental calculus (DC) is a common deposit in periodontitis patients. We have previously shown that DC contains both microbial components and calcium phosphate crystals that induce an osteoclastogenic cytokine IL-1β via the NLRP3 inflammasome in macrophages. In this study, we examined the effects of cytokines produced by mouse macrophages stimulated with DC on osteoclastogenesis. The culture supernatants from wild-type (WT) mouse macrophages stimulated with DC accelerated osteoclastogenesis in RANKL-primed mouse bone marrow macrophages (BMMs), but inhibited osteoclastogenesis in RANKL-primed RAW-D cells. WT, but not NLRP3-deficient, mouse macrophages stimulated with DC produced IL-1β and IL-18 in a dose-dependent manner, indicating the NLRP3 inflammasome-dependent production of IL-1β and IL-18. Both WT and NLRP3-deficient mouse macrophages stimulated with DC produced IL-10, indicating the NLRP3 inflammasome-independent production of IL-10. Recombinant IL-1β accelerated osteoclastogenesis in both RANKL-primed BMMs and RAW-D cells, whereas recombinant IL-18 and IL-10 inhibited osteoclastogenesis. These results indicate that DC induces osteoclastogenic IL-1β in an NLRP3 inflammasome-dependent manner and anti-osteogenic IL-18 and IL-10 dependently and independently of the NLRP3 inflammasome, respectively. DC may promote alveolar bone resorption via IL-1β induction in periodontitis patients, but suppress resorption via IL-18 and IL-10 induction in some circumstances.     

Surgical therapy for hepatocellular carcinoma with liver cirrhosis

Approximately 80% of hepatocellular carcinoma (HCC) patients in Japan have associated liver cirrhosis, which increases the difficulty of surgical treatment. Liver dysfunction associated with liver cirrhosis is one of the most important predictive prognostic factors for HCC patients. Percutaneous ethanol injection therapy (PEIT) is useful for patients with small HCC or with poor hepatic functional reserve. Transcatheter arterial chemoembolization (TACE) is also useful both for patients with unresectable HCC and patients with multiple intrahepatic recurrence. Liver resection, however, lead to better outcome than other treatments when liver function is maintained after surgery. To determine operative procedures, it is important to evaluate the exact function of remnant liver, based on the preoperative liver function test and the evaluation of tumor character. For advanced HCC patients with vascular invasion, non-surgical treatments such as PEIT or TACE are not indicated, and surgical intervention can be an effective modality to improve their survival. Improvements of surgical technique and perioperative management have decreased fatal complications at a major liver resection and allowed us to carry out liver resection on patients with advanced HCC.     

A 0.18-μm 256-Mb DDR-SDRAM with low-cost post-mold tuning methodfor DLL replica

A 200-MHz double-data-rate synchronous-DRAM (DDR-SDRAM) was developed. The chip contains a delay-locked loop (DLL) which performs over a wide range of operating conditions. Post-mold-tuning allows precise replica programming. A 200-MHz intra-chip data bus is suitable for DDR operation     

Axial plastic collapse behavior of plates

In the present study, the collapse behavior of a plate subjected to axial compression is investigated parametrically using the finite element method. It is shown that the axial collapse of the plate, which has various hardening characteristics, is controlled by two dominant factors: the stress limitation of the material and the limitation of in-plane lateral deformation at the side edges of the plate. Then, a simplified collapse condition, which corresponds to two collapse types, is derived based on the effective width concept and the plastic theory, and the validity of the collapse condition is then verified by the comparison of numerical results obtained under various material and geometric properties. Furthermore, a method for predicting the collapse stress is proposed based on the present collapse condition.     

Migration of dehydroabietic and abietic acids from paper and paperboard food packaging into food-simulating solvents and Tenax TA

An investigation was undertaken to establish the concentration in paper products of dehydroabietic (DHA) and abietic (AA) resin acids, present in rosin, which are major toxicants of pulp- and paper-mill effluent. Their migration was studied from paper and paperboard products into various food-simulating solvents and the substitute fatty food simulant Tenax TA (modified polyphenylene oxide). DHA and AA were detected in five of 10 virgin paper products and in all 10 recycled paperboard products for food-contact use at concentrations of 14-500 and 110-1200 µg/g, respectively. In virgin paper products, the highest migration was into 95% ethanol or heptane, with negligible or no migration into other solvents. In recycled paperboard products, migration was highest into 95% ethanol, but was also observed into 20% ethanol, water and heptane. Migration to Tenax TA was also observed and the migration level increased with time. The maximum migration levels of DHA and AA into food simulants were 0.853 and 3.14 µg/g, respectively. The results suggest that, in the worst case, the daily intake of DHA and AA from paper and paperboard products was 50 times lower than the tolerable daily intake of rosin.     

Determination of alkylphenols,bisphenol A,benzophenone and phthalates in containers of baby food,and migration into food simulants

Infants, whose growth and development are highly dependent upon the endocrine system, are particularly vulnerable to endocrine disruptor exposure. In our study, we examined whether or not alkylphenols, bisphenol A, benzophenone, di(2-ethylhexyl)adipate and 10 phthalates are present in containers of baby food. Furthermore, the migration into food-simulating solvents was also examined. Sixteen types of containers of baby food, obtained on the Japanese market in 2001, were examined: 8 glass bottle types, 1 plastic type, 1 metallic package (laminated with plastic) and 6 multilayered laminated film packages. Alkylphenols, benzophenone, bisphenol A and di(2-ethylhexyl)adipate were not detected in any of the samples. On the other hand, dibutylphthalate (DBP) was detected in 7 samples (1.2-9.1 micrograms/sample), and di(2-ethylhexyl)phthalate (DEHP) was detected in 15 samples (1.3-18 micrograms/sample). Migration tests were carried out for 5 samples, and the levels of DBP and DEHP that migrated into n-heptane were 0.68-1.7 micrograms/sample and 0.33-3.5 micrograms/sample, respectively. From these results, a baby's intake levels of DBP and DEHP were estimated to be about 1/2,500 and 1/90-300 of the tolerable daily intake (TDI), respectively.     

Late phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical cancer. ETP 21 Study Group--Cervical Cancer Group

We conducted a multi-site late phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical cancer in cooperation with 32 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Treatment cycles were to be repeated at 4- to 5-week intervals. Eighty patients were enrolled and 70 patients were evaluated. The overall response rate (95% CI), including one complete response patient and 18 partial response patients, was 27.1% (19/70). The most commonly observed toxicity was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were gastrointestinal toxicities such as anorexia, nausea, stomatitis and vomiting, as well as fatigue and alopecia. These adverse effects were well tolerated and controlled with medications. From these results we concluded oral etoposide administered for 21 consecutive days was an effective drug against cervical cancer.