Postmarketing surveillance of safety and effectiveness of etanercept in Japanese patients with rheumatoid arthritis

Our aim was to evaluate real-world safety and effectiveness in a 6-month postmarketing surveillance study covering all Japanese patients with rheumatoid arthritis (RA) who received etanercept during a 2-year period. Data for 13,894 patients (1334 sites) enrolled between March 2005 and April 2007 were collected. Adverse events (AEs) and serious adverse events (SAEs) were reported in 4336 (31.2%) and 857 (6.2%) patients, respectively. The most frequent AEs were injection site reactions (n = 610, 4.4%) and rash (n = 339, 2.4%), whereas pneumonia (n = 116, 0.8%) and interstitial lung disease (n = 77, 0.6%) were the most frequent SAEs. Significant improvement in the proportion of patients with a good European League Against Rheumatism (EULAR) response was observed from week 4 (17.6%) to week 24 (31.6%) (p < 0.001); 84.3% of patients had good or moderate EULAR responses at week 24. The percentage of patients achieving remission increased significantly from week 4 (9.3%) to week 24 (18.9%) (p < 0.001). Patients with early moderate RA were less likely to experience SAEs and were more likely to achieve remission compared with patients with more severe disease. The safety and effectiveness of etanercept was demonstrated in Japanese patients in one of the largest observational trials conducted thus far in RA patients treated with biologics

Functional Analyses of MMPs for Aragonite Crystal Formation in the Ligament of Pinctada fucata

The mollusk class, Bivalvia, plays an important role in the formation of calcium carbonate in the ocean. The bivalve hinge ligament is a hard but pliant tissue that resists the stress placed on the hinge during opening and closing. The ligament comprises a fine microstructure of fibrous aragonite crystals surrounded by a dense organic matrix. The matrix consists of organic fibers that are aligned with the fibrous aragonite crystals. Previous studies identified a tissue inhibitor of metalloproteinase (Pf-TIMP: Pinctada fucata-Tissue Inhibitor of Metalloproteinase) in the organic fibers of P. fucata ligaments. This enzyme exhibited strong inhibition of matrix metalloproteinase (MMP) activity in vitro, suggesting that MMPs also play a role in formation of the organic fibers of the ligament. Using transcriptome data, we identified MMP genes from the mantle isthmus, which is a soft tissue attached to the ligament. To investigate the function of MMP genes in vivo, we performed RNA interference experiments. The expression of MMP14973 and MMP07860 genes was inhibited after injection of each dsRNA. Cumulative injection of MMP07860 dsRNA induced aggregated aragonite fiber orientation, whereas the injection of MMP14973 showed minor effects. When the decalcified ligament was incubated in a solution saturated with calcium carbonate, aragonite fibers aligned along the surface. When the decalcified ligament was treated with recombinant human (hr) MMP-13, the precipitation of calcium carbonate was inhibited. To investigate general MMP functions in calcium carbonate crystallization in detail, we precipitated aragonite crystals in collagen gels treated with or without recombinant human (hr) MMP-1. Treatment with hrMMP-1 increased the interaction between collagen gels and calcium carbonate. These results imply that Pinctada fucata (Pf)-MMPs degrade extracellular matrices in the ligament to produce the fine organic fibers that regulate the orientation of fibrous aragonite crystals

Evolution of Epidermal Growth Factor (EGF)-like and Zona Pellucida Domains Containing Shell Matrix Proteins in Mollusks

Several types of shell matrix proteins (SMPs) have been identified in molluskan shells. Their diversity is the consequence of various molecular processes, including domain shuffling and gene duplication. However, the evolutionary origin of most SMPs remains unclear. In this study, we investigated the evolutionary process EGF-like and zona pellucida (ZP) domains containing SMPs. Two types of the proteins (EGF-like protein (EGFL) and EGF-like and ZP domains containing protein (EGFZP)) were found in the pearl oyster, Pinctada fucata. In contrast, only EGFZP was identified in the gastropods. Phylogenetic analysis and genomic arrangement studies showed that EGFL and EGFZP formed a clade in bivalves, and their encoding genes were localized in tandem repeats on the same scaffold. In P. fucata, EGFL genes were expressed in the outer part of mantle epithelial cells are related to the calcitic shell formation. However, in both P. fucata and the limpet Nipponacmea fuscoviridis, EGFZP genes were expressed in the inner part of the mantle epithelial cells are related to aragonitic shell formation. Furthermore, our analysis showed that in P. fucata, the ZP domain interacts with eight SMPs that have various functions in the nacreous shell mineralization. The data suggest that the ZP domain can interact with other SMPs, and EGFL evolution in pterimorph bivalves represents an example of neo-functionalization that involves the acquisition of a novel protein through gene duplication

Percutaneous Endoscopic Gastrostomy, Duodenostomy and Jejunostomy

Although enteral feeding by nasal gastric tube is popular for the patients who have a swallowing disability and require long-term nutritional support, but have intact gut, this tube sometimes causes aspiration pneumonia or esophageal ulcer. For these patients, conventional techniques for performance of a feeding gastrostomy made by surgical laparotomy have been used so far. However, these patients are frequently poor anesthetic and operative risks. Percutaneous endoscopic gastrostomy (PEG) which can be accomplished with local anesthesia and without the necessity for laparotomy has become popular in the clinical treatment for these patients. PEG was performed in 31 cases, percutaneous endoscopic duodenostomy (PED) in 1 case, and percutaneous endoscopic jejunostomy (PEJ) in 2 cases. All patients were successfully placed, and no major complication and few minor complications (9%) were experienced in this procedure. After this procedure, some patients could discharge their sputa easily and their pneumonia subsided. PED and PEJ for the patients who had previously received gastrostomy could also be done successfully with great care. Our experience suggests that PEG, PED, and PEJ are rapid, safe, and useful procedures for the patients who have poor anesthetic or poor operative risks

Relationship between sintering temperature and bending strength for Y2O3 partially stabilized zirconia

The objective of this study was to verify the stability of Y2O3 partially stabilized zirconia (zirconia) sintered at 1,350℃ and 1,450℃ in a simulated oral environment over a long period of time. After sintering, zirconia was immersed in physiological saline, 1% lactic acid solution, and 1% malic acid solution which can be produced in the oral cavity for 3 or 6 months. The bending strength and strain were measured. The following results were obtained. Before immersion, there was no difference in the bending strength of zirconia sintered at 1,350℃ and 1,450℃. For zirconia sintered at 1,350℃, there was no difference among solutions in the bending strength after exposure. However, for zirconia sintered at 1,450℃, the bending strength and strain were lower after exposure to 1% lactic acid solution for 3 months. There was no effect on the strain after exposure to any solutions for zirconia sintered at 1,350℃. For zirconia sintered at 1,350℃, fracture was not observed during exposure to any of the solutions. However, when sintered at 1,450℃, zirconia was fractured during exposure to 1% lactic acid solution and 1% malic acid solution for 6 months. It was clarified that zirconia sintered at 1,350℃ was more suitable than that sintered at 1,450℃ as an implant material

The Incidence of Proximal Extension of Ulcerative Proctitis in Japan and Factors Related to Proximal Extension

The incidence of proximal extension in patients with ulcerative proctitis is reported to be 18%-46%, but recent data on the incidence in Japan is inadequate. The aim of this study was to investigate the incidence of proximal extension of ulcerative proctitis and factors associated with the extension in Japan. This is a retrospective observational study involving a cohort of 53 patients with an initial diagnosis of ulcerative proctitis. Following verification of the diagnoses, demographic and clinical data were compiled. The cumulative incidence of proximal extension was estimated as ‘person-years’ and cumulative probability was calculated by the Kaplan-Meyer method. Univariate and multivariate analyses were performed to identify association factors. During a mean follow-up of 6.8 years, proximal extension was observed in 14 patients (26.4%). The cumulative incidence of proximal extension was 4.22/100 person-years and the cumulative probability at 5 years was 20.1%, consistent with recent reports from Western countries and data obtained in Japan over 2 decades ago. Univariate analysis showed active smoking (P = 0.025) and corticosteroid therapy (P = 0.006) to be risk factors in proximal extension, however multivariate analysis revealed that corticosteroid therapy was the only significant factor (P = 0.005) separating patients with and without proximal extension. No patient underwent colectomy. The incidence of proximal extension in ulcerative proctitis in Japan is comparable to that in Western countries and has not changed significantly over the past two decades. Corticosteroid therapy was identified as the only significant factor in proximal extension

A liquid diet supplement containing structured medium‐ and long‐chain triacylglycerols does not increase body fat accumulation in healthy young women

The effects of a liquid‐formula diet supplement containing structured medium‐ and long‐chain triacylglycerols (SMLCT) composed of medium (10%) and long chain (90%) fatty acids were compared with those of long chain triacylglycerols (LCT) on body fat accumulation in 10 healthy female volunteers aged 18‐29 years. The subjects were randomly assigned SMLCT or LCT group. The subjects in each group received a liquid‐formula diet supplement of SMLCT or LCT, which provided 1040kJ plus daily energy intake for 12 weeks. Mean energy intake containing liquid diet throughout the 12‐week period did not differ between the SMLCT and LCT groups. Body weight of subjects in both groups increased slightly from baseline throughout the 12‐week period, but the differences were not significant. Rates of variation of body fat percentage were lower in the SMLCT group than in the LCT group throughout the 12‐week period, particularly at 8 weeks, the difference was significant. Comparisons between the SMLCT and LCT groups at baseline and 12 weeks showed no significant differences in any of the biochemical blood parameters. These results suggest that replacing LCT with SMLCT over long periods of time could produce body fat loss in the absence of reduced energy intake.10%の中鎖脂肪酸と90%長鎖脂肪酸からなる構造化中長脂肪酸トリグリセリド（SMLCT油）および長鎖脂肪酸トリグリセリド（LCT油）が体脂肪蓄積に及ぼす影響を、18‐29歳の若年健常女性10名を用いて比較検討した。被験者をランダムに5名ずつに分け、それぞれSMLCT群およびLCT群とした。おのおののグループの被験者にそれぞれSMLCT油あるいはLCT油を含む液体補助食品（1040kJ/day）を毎日、12週間にわたり摂取させた。液体補助食品を含むエネルギー摂取量の平均値はSMLCT群およびLCT群の間に差を認めなかった。12週間の実験期間を通して、体重は増加傾向にあったが、SMLCT群およびLCT群の体重増加量は同程度であった。体脂肪率の増加率は実験期間を通して、SMLCT群に比べてLCT群で高値であり、特に8週目で有意であった。実験前後の血液生化学検査値には、全ての検査項目においてSMLCT群およびLCT群間に差は見られなかった。これらの結果から、SMLCT油はLCT油に比べて体脂肪蓄積を増加させない油脂であり、食用油脂をLCT油からSMLCT油へ代えることは、減量のための食事療法として利用可能であることが示唆された。departmental bulletin pape

Aspergillus oryzae PrtR alters transcription of individual peptidase genes in response to the growth environment

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