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Background Lipopolysaccharide (LPS) often presents in high concentrations in particulate matter (PM), few studies have reported the enhancing effects of both LPS and PM on airway inflammation in mice and the role of toll-like receptors (TLRs) in this process. Asian sand dust (ASD) is observed most frequently during the spring. This study aimed to clarify the role of TLRs in murine lung eosinophilia exacerbated by ASD and LPS. Methods The effects of LPS and ASD co-treatment on ovalbumin (OVA)-induced lung eosinophilia were investigated using wild-type (WT), TLR2−/−, TLR4−/−, and adaptor protein myeloid differentiation factor 88 (MyD88)−/− BALB/c mice. ASD was heated (H-ASD) to remove the toxic organic substances. WT, TLR2−/−, TLR4−/− and MyD88−/− BALB/c mice were intratracheally instilled with four different combinations of LPS, H-ASD and OVA treatment. Subsequently, the pathological changes in lungs, immune cell profiles in bronchoalveolar lavage fluid (BALF), inflammatory cytokines/chemokines levels in BALF and OVA-specific immunoglobulin (Ig) in serum were analyzed. Results In WT mice, H-ASD + LPS exacerbated OVA-induced lung eosinophilia. This combination of treatments increased the proportion of eosinophils and the levels of IL-5, IL-13, eotaxin in BALF, as well as the production of OVA-specific IgE and IgG1 in serum compared to OVA treatment alone. Although these effects were stronger in TLR2−/− mice than in TLR4−/− mice, the expression levels of IL-5, IL-13, eotaxin were somewhat increased in TLR4−/− mice treated with OVA + H-ASD + LPS. In MyD88−/− mice, this pro-inflammatory mediator-induced airway inflammation was considerably weak and the pathological changes in lungs were negligible. Conclusions These results suggest that LPS and H-ASD activate OVA-induced Th2 response in mice, and exacerbate lung eosinophilia via TLR4/MyD88, TLR4/TRIF and other TLR4-independent pathways.

Level of Evidence: Level V.

Objectives: To clarify the effect of combining medial capsule interposition with modified scarf osteotomy for hallux valgus. Methods: A multicenter, retrospective study included 64 cases [59 osteoarthritis patients (excluding rheumatoid arthritis); age 68.8 years, range 40–93 years] of modified scarf osteotomy which were performed from 2013 to 2017 and followed for 26.6 (range, 13–50) months. Patients were treated by either (1) without medial capsule interposition (33 cases) or (2) combined with interposition (31 cases) at each senior surgeon’s discretion. The Japanese Society for Surgery of the Foot (JSSF) hallux metatarsophalangeal (MTP)-interphalangeal scale was evaluated along with radiographic parameters (hallux valgus angle [HVA], first and second metatarsals intermetatarsal angles, and Hardy grade). Results: All JSSF scale and radiographic parameters were similar at baseline and significantly improved at final follow-up in both groups (pre-operation vs. final follow-up: p p value between the two groups at final follow-up) for pain (without interposition: 19.4–34.2, interposition: 18.4–37.1; p = .02), function (without interposition: 20.8–33.6, interposition: 18.3–36.6; p = .005), total score (without interposition: 41.5–81.8, interposition: 38.5–88.5; p < .001), and the MTP joint space (without interposition: 1.4–1.5 mm, interposition: 1.6–2.6 mm; p < .001) with significant correlation between the total JSSF score (r = .40; p = .001). Conclusion: Combining medial capsule interposition with modified scarf osteotomy significantly improved mid-term clinical outcomes.

Objectives: To evaluate the effectiveness of add-on iguratimod (IGU) in patients with rheumatoid arthritis (RA) who showed an inadequate response to tocilizumab (TCZ), especially patients who were ...

Bone stock reconstruction using allograft-bones, bone marrow (BM), and teriparatide (TPTD) is reported. Huge and extensive bone losses occurred in the medullary cavity of the femur and tibia of a 55-year-old female rheumatoid arthritis patient with severe osteoporosis after debridement of her infected total knee arthroplasty. Because of the risks of unstable prosthetic fixation and intra-operation fracture, we first reconstructed the bone stock. Chipped allograft bones mixed with BM were implanted in the bone defects, and TPTD was administrated for the osteoporosis therapy. Good bone formation was found by computed tomography after 4 months. Bone turnover markers and bone mineral density (BMD) were increased at 6 months. We confirmed good bone formation at the re-implantation surgery. The newly formed bone harvested during the re-implantation surgery showed active osteoblast-like lining cells. TPTD is known to enhance allograft bone union, mesenchymal stem cell differentiation into osteoblasts, and BMD. This tissue engineering-based technique might be improved by the various effects of TPTD. This method without any laboratory cell culture might be a good option for bone stock reconstruction surgery in ordinary hospitals.

The objectives of this study were to measure the morphometric parameters of preoperative distal femurs to determine the differences by diagnosis and gender after accounting for skeletal size. One-hundred and seventy-nine Japanese patients who underwent total knee arthroplasty (TKA) (25 males and 154 females) were assessed. The anteroposterior length (AP), mediolateral width (ML), aspect ratio (AR), surgical epicondylar axis (SEA) to posterior condylar axis (PCA) angle, and Whiteside to SEA angle were measured on preoperative computed tomography scans. The AP/ML, AR/ML, SEA/PCA, and Whiteside/PCA relationships were evaluated and compared by patient diagnosis and gender. The results were also compared with the sizes of 10 currently available TKA implants in Japan. The mean AP, ML, AR, SEA/PCA angle, and Whiteside/PCA angle were 58.8 mm, 64.7 mm, 0.91, external rotation (ER) 3.5°, and ER 1.6°, respectively. AP and AR each were significantly correlated with ML (p

The quality and quantity of toxic materials adsorbed onto Asian sand dust (ASD) are different based on dust source regions and passage routes. The aggravating effects of two ASDs (ASD1 and ASD2) transported from the source regions of Inner Mongolia and northeast China on lung eosinophilia were compared to clarify the role of toxic materials in ASD. The ASDs contained different amounts of lipopolysaccharides (LPS) and β-glucan (ASD1ASD2) and SiO2 (ASD1ASD2). CD-1 mice were instilled intratracheally with ASD1, ASD2 and/or ovalbumin (OVA) four times at 2-week intervals. ASD1 and ASD2 enhanced eosinophil recruitment induced by OVA in the submucosa of the airway, with goblet cell proliferation in the bronchial epithelium. ASD1 and ASD2 synergistically increased OVA-induced eosinophil-relevant cytokines interleukin-5 (IL-5), IL-13 (ASD1ASD2) and chemokine eotaxin (ASD1ASD2) in bronchoalveolar lavage fluid. ASD2 aggravating effects on lung eosinophilia were greater than ASD1. The role of LPS and β-glucan in ASD2 on the production of pro-inflammatory mediators was assessed using in vitro bone marrow-derived macrophages (BMDMs) from wild type, Toll-like receptor 2-deficient (TLR2-/-), TLR4-/-, and MyD88-/- mice (on Balb/c background). ASD2-stimulated TLR2-/- BMDMs enhanced IL-6, IL-12, TNF-α, MCP-1 and MIP-1α secretion compared with ASD2-stimulated TLR4-/- BMDMs. Protein expression from ASD2-stimulated MyD88-/- BMDM were very low or undetectable. The in vitro results indicate that lung eosinophilia caused by ASD is TLR4 dependent. Therefore, the aggravation of OVA-related lung eosinophilia by ASD may be dependent on toxic substances derived from microbes, such as LPS, rather than SiO2.

BackgroundEpidemiological studies have implicated Asian sand dust (ASD) in the increased prevalence of respiratory disorders, including asthma. It has been observed that fungal elements such as β-glucan can be adsorbed onto ASD. In the present study, the exacerbating effect of the combined exposure to zymosan A (ZymA) containing yeast β-glucan and heat-inactivated ASD on ovalbumin (OVA)-induced murine lung eosinophilia was investigated.MethodsBALB/c mice were repeatedly instilled intratracheally with one of eight immunogenic formulations consisting of various combinations of (1) ZymA, (2) ASD that was briefly heated to remove organic substances (H-ASD), and (3) OVA in normal saline, or each of the above alone. Pathologic changes, cytological alterations in bronchoalveolar lavage fluid (BALF), changes in inflammatory cytokines and chemokines in BALF, and OVA-specific IgE and IgG1 antibodies in serum were investigated.ResultsExposure to ZymA with or without OVA had no effect on most indicators of lung inflammation. Exposure to H-ASD with OVA increased the recruitment of inflammatory cells to the lungs and the serum levels of OVA-specific IgE and IgG1. The combination OVA+ZymA+H-ASD induced a marked recruitment of eosinophils and upregulation of T helper 2 (Th2) cytokines (interleukin [IL]-4 and IL-13), IL-6, eotaxin/CCL11, and monocyte chemotactic protein (MCP)-3/CCL7 in BALF and OVA-specific IgE in serum. This treatment also induced the most severe pathological changes in the lungs of mice. ZymA was found to boost the effects of H-ASD, thereby exacerbating the OVA-induced allergic inflammation, even though ZymA alone did not have such effect.ConclusionsThe results suggest that fungal elements such as β-1,3-glucan aggravate the allergic inflammation caused by ASD. Our findings may facilitate prophylaxis of some allergic diseases in Asia.

Tocilizumab (TCZ) shows good retention in patients with rheumatoid arthritis (RA), but no previous reports demonstrated hopeful treatment options against inadequate response to TCZ. Tacrolimus (TAC) has proved to show efficacy against inadequate response to tumor necrosis factor alpha inhibitors, yet its add-on effects on TCZ remain unknown.Twenty patients with RA (17 women, age 58.6 years, disease duration 12.1 years, prior TCZ duration 2.6 years, 18 intravenous [8 mg/kg/month] and 2 subcutaneous [324 mg/month] TCZ treatments, methotrexate 6.1 mg/week [70.0%]) who showed an inadequate response to TCZ (clinical disease activity index [CDAI] ≥ 5.8, 18 secondary non-responders) were additionally treated with TAC (1.1 mg/day), and enrolled in this 24-week, prospective study.Seventeen patients (85.0%) continued the treatment for 24 weeks. Statistically significant decreases in outcome measures were as follows: disease activity score based on 28 joints with C-reactive protein (DAS28-CRP) from 3.3 at baseline to 2.1 at week 24 (p 0.001), CDAI from 17.7 to 7.6 (p 0.001), and serum matrix metalloproteinase-3 levels from 232.8 to 66.2 ng/ml (p 0.001). About 15 patients (75%) achieved low disease activity or remission (DAS28-CRP ≤2.7 or CDAI ≤10) at week 24.Adding low-dose TAC to inadequate responders to TCZ may be a promising complementary treatment option.

Asian sand dust (ASD) event may result in a significant influence on an asthmatic patient. However, for obvious reasons, there is no experimental study in which asthmatic patients are exposed to ASD. This study was undertaken to clarify the effects of ASD on lung eosinophiliain mice immunized beforehand by ovalbumin (OVA). CD-1 mice were instilled intratracheally with OVA four times at 2-week intervals. Simultaneous intratracheal administration of OVA and ASD (OVA + ASD sim) at the last OVA treatment or intratracheal administration with ASD 1 day before (OVA + ASD pre) /after (OVA + ASD post) the last OVA treatment was performed to investigate the effects of OVA and ASD exposure timing. The three kinds of treatment (OVA + ASD pre; OVA + ASD sim; OVA + ASD post) aggravated allergic lung inflammation and proliferation of goblet cells in the airway epithelium in mice, as evidenced by the cellular profile of bronchoalveolar lavage fluid (BALF) and pathological examination. As an overall trend, these changes were paralleled with the expression of Th2-associated effecter molecules and eosinophil relevant cytokine chimokines in BALF as well as the production of OVA-specific IgG1 compared with OVA treatment alone. OVA + ASD sim aggravated lung eosinophilia remarkably compared with the other treatments. The order of the potency of the aggravation was OVA+ASD preOVA+ASD postOVA+ASD sim. These results indicate that ASD has a potent effect in activating lung eosinopilia in mice immunized beforehand by OVA. The simultaneous exposure of asthmatic patients to ASD and its antigen may have serious consequences for such individuals.

Urban particulate matter (UPM) has been shown to have an aggravating effect on Th2-associated immune systems in adult mice. However, the effects of fetal exposure to UPM on immune response in offspring have not been elucidated. In the present study, we administered UPM (200 µg/animal) by intratracheal injection to pregnant dams on days 7 and 14 of gestation. Subsequently, 9- and 24-week-old male offspring were intratracheally injected with ovalbumin (OVA) (four times at 2-week intervals) to create a mouse model of bronchial asthma. We then evaluated the progression of allergic manifestations in the offspring through histological findings, the number of inflammatory cells in bronchoalveolar lavage fluid (BALF), and protein concentration of cytokines and chemokines in BALF 5, 10, 15, and 30 weeks after birth. Histological examination showed that fetal exposure to UPM alone caused slight eosinophil and lymphocyte infiltration in the submucosa of the airway and bronchial epithelium and significant increases in the number of macrophages. Moreover, postnatal intratracheal administration of OVA to offspring exposed to UPM in utero caused significant increases in the numbers of macrophages, eosinophils, and lymphocytes and in the concentrations of their relevant cytokines and chemokines, showing that fetal exposure to UPM aggravated the chemically sensitized immune system of male offspring.

Atmospheric pollution caused by airborne particulate matter in the winter season in Ulaanbaatar, Mongolia is a very serious problem. However, there is a complete lack of scientific observation data to define the situation prior to any remediation. PM10 and PM2.5 average monthly values obtained by continuous monitoring showed the concentrations of particles of both size categories exceeded 100 μg m −3 during November to February (winter). PM10 particles were sampled with filters in January (i.e. during the heating period) and June (i.e.non-heating period) of 2008 in central Ulaanbaatar. To determine the composition of urban airborne particulate matter we analyzed a range of ionic components, multiple elements including heavy metals, and organic and inorganic carbon (soot). We also measured the stable carbon isotope ratio of the soot. Total carbon (sum of organic carbon and inorganic carbon) accounted for 47% of the mass of the PM10 during the heating period and 33% during the non-heating period, and was the largest component of urban airborne particulate matter in Ulaanbaatar. Stable isotope ratios (δ 13 C) of soot generated during the heating period (−23.4 ± 0.2‰) approximated the ratios for coal used in Ulaanbaatar (−21.3 to −24.4‰), while the ratios during the non-heating period (−27.1 ± 0.4‰) were clearly different from the coal values. In the heating period, a very high correlation was observed between soot and organic carbon, SO 4 2– , NO 3 − , F − , Zn, As, and Pb, and we concluded that they were derived from coal combustion along with soot. In addition, the concentrations and their ratios relative to each other of Al, Fe, Ca, K, Na, Mg, and Mn hardly differed between the heating period and the non-heating period, and it was concluded that they were derived from soil dust.

Samples of the muscle of two species of tilapia (Oreochromis mossambicus and O. niloticus; 17–20 cm length) were obtained from at least one reservoir in each of the six river basins (Aruvi Aru, Kala Oya, Kirindi Oya, Ma Oya, Mahaweli, and Walawe Ganga catchments) in Sri Lanka. The metals Ca, Cu, Fe, K, Mg, Mn, Na, and Zn were consistently detected in the muscle tissue. Overall, there were few differences in the concentration of metals between the two species of fish, although there were also some statistically significant differences (p < 0.05) in the concentrations of some metals in fish obtained from some of the reservoirs. Aruvi Aru stands out as a river basin in which the two fish species have significantly lower concentration of metals when compared to other river basins. The concentration of the metals studied were below WHO and FSANZ guideline values for fish, suggesting that the consumption of the metals found in tilapia from these reservoirs poses little risk to human health.

We classified 182 consecutive patients (195 hips) treated by primary cementless minimally invasive total hip arthroplasty (MIS-THA) into 2 groups via the surgical approaches: direct anterior approach (DAA, 99 hips) and a mini-posterior approach (MPA, 96 hips). Ninety-nine percent of the cups in the DAA group and 91% in the MPA group had been implanted within the safe zone (P = .008). Patients in the DAA group could get single-leg stance of more than 5 seconds by 16.6 days (P = .0004), had positive Tredelenburg's sign by 29%, got 50-m walking time of 52.3 seconds (P = .017), and showed improvement in the use of assistive walking aids (P = .031) at 3 weeks postoperatively. The results of this study suggest more rapid recovery for hip function and gait ability after MIS-THA via a DAA when compared to an MPA.

Sulfur isotopic ratios (δ(34)S) in size separated aerosol particles (PM2.5 and coarse particles) were measured at Niigata-Maki facing the Sea of Japan. Non-sea salt δ(34)S (δ(34)Snss) in PM2.5 showed seasonal variations with relatively high values in winter (1.0-3.9‰ in spring, 2.8-4.5‰ in summer, 1.3-4.5‰ in autumn, 3.7-5.7‰ in winter). Taking into consideration air mass transport routes, δ(34)Snss in the air masses which originated in the Asian continent and were transported over the Sea of Japan to the monitoring sites were higher than those values for air masses which were transported over the Japanese islands after leaving the Asian continent for each season. Considering that the δ(34)Snss in sulfuric acid derived from domestic emissions in Japan are lower than those of δ(34)Snss in coal, the lower δ(34)Snss for the air mass transported over the Japanese islands suggest that sulfuric acid in PM2.5 modified the δ(34)Snss due to aerosol mixing with sulfuric acid in Japan. Material balance calculations suggested that the relative contribution of transboundary transport in winter was also higher than for other seasons (40-75% in spring, 51-63% in summer, 45-73% in autumn, and 53-81% in winter). In particular, the contribution to the air masses which were transported directly from the Asian continent was relatively large (75% in spring, 59% in autumn, 78% in winter) in comparison with that for the air masses which were transported over Japan.

Background: Bisphenol A (BPA) is useful in many manufacturing processes and is also found in commonly used consumer products. Previous experimental studies have reported that perinatal exposure to BPA promotes the development of allergic lung inflammation in childhood and even into adulthood. In this study, the effects of BPA on allergic lung inflammation in adults were investigated in murine lungs. Methods: CD-1 mice were orally administrated with 1 mg of BPA/mouse four times at one-week intervals with or without ovalbumin (OVA). The pathologic changes in the airways, cytological alterations in bronchoalveolar lavage fluid (BALF), levels of inflammatory cytokines/chemokines in BALF, and OVA-specific IgE and IgG1 antibodies in serum were measured in the treated CD-1 mice. In vitro study using RAW264.7 cells, which are macrophage-like cells derived from BALB/c male mice, was conducted. The gene expression of cytokines and chemokines were measured. Results: BPA enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. BPA increased Th2 cytokines-interleukin-13 (IL-13), eosinophil-relevant cytokines and chemokines, such as IL-5, and CCL2 induced by OVA, in BALF. BPA induced adjuvant effects on OVA-specific IgG1 production. In the in vitro study using RAW264.7 cells, BPA increased the mRNA expression of IL-1β, IL-6, CCL2 and CCL3 compared with the control and OVA groups. Conclusions: These results suggest that (1) the exposure of BPA could synergize with an OVA challenge to aggravate the severity of lung eosinophilia in adult mice, possibly by promoting a Th2-biased immune response and (2) the activation of macrophages and inflammatory cytokines released from these cells by BPA could be participating in this phenomenon.

Hydroxyapatite (HA) has been evaluated for use in a variety of applications in bone reconstruction surgery because of its high affinity with host bone and biocompatibility. However, because of the difficulty in combining porosity (for bone ingrowth) and strength in HA, it is generally considered inappropriate to use HA for high-load applications such as spinal interbody fusion. In the present study, we constructed a HA implant for spinal interbody fusion, composed of a dual HA composite (DHC) that combines two HA materials with different porosities: HA with 75% porosity, for bone ingrowth; and HA with 0% porosity, for load bearing. We used a canine lumbar interbody fusion model to evaluate bone conduction of the implant and its efficacy for bony fusion. Six months after the operation, DHC exhibited almost the same efficacy for bony fusion as iliac bone grafts. Moreover, pores of the porous part of the DHC were completely filled with newly formed bone and bone marrow cells. The present findings indicate that DHC is suitable for use as an implant material for spinal interbody fusion as a substitute for iliac bone grafts, which could eliminate the disadvantages associated with autograft harvesting.

We reviewed 21 patients with rheumatoid arthritis who had a total ankle replacement between 1984 and 2000. The average follow-up was 72 (15-169) months. Clinical results were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score. At the latest review, three ankles had been revised. Two ankles were excellent, seven good, three fair, and 12 poor. Eleven patients with 13 ankles had residual pain, with radiographs showing a high incidence of radiolucent lines. Migration of the tibial component was seen in 13 ankles and collapse of talus in nine. Although clinical results were poor, patient satisfaction was not.

Objective: The purpose of this study was to examine the relationship between fetal lead exposure and birth weight, using deciduous incisor enamel as a biomarker and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for analysis of lead.Methods: We asked dental clinics (n=11) and kindergartens (n=11), mainly in the Tokyo metropolitan area and Miyagi Prefecture, and parents to enroll donors of exfoliate deciduous incisors. Donors who consented to this study voluntarily sent deciduous incisors and questionnaires to the authors between March and October, 2003. The Pb/Ca ratios of inner enamel samples were determined by LA-ICP-MS. The relationship between the lead-to-calcium ratio in the enamel and the birth weight was evaluated by stepwise multiple linear regression analysis.Results: One hundred forty-one subjects (male, 72; female, 69) were enrolled in this study. The mean Pb/Ca ratio in the enamel was as low as 0.24mg-Pb/kg-Ca (SD=0.17). Stepwise multiple linear regression analysis extracted the following maternal variables with a positive coefficient with birth weight: gestational age (p

Objective FR167653 is a potent inhibitor of p38 mitogen-activated protein kinase (MAPK) and inhibits tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) production in inflammatory cells. In this study we investigated the effect of FR167653 on collagen-induced arthritis (CIA). Methods Rats with CIA were subcutaneously injected with FR167653 (32 mg/kg/day) starting on the day of the booster injection (day 7) in the prophylactic treatment group and after the onset of arthritis (day 21) in the therapeutic treatment group. Hind-paw swelling, body weight, radiographic and histologic scores, and osteoclast number were evaluated. Cytokine levels in the serum and tissue were assessed by enzyme-linked immunosorbent assays. Flow cytometric analysis of T lymphocytes from bone marrow was performed. The effect of FR167653 on in vitro osteoclast formation induced by soluble receptor activator of nuclear factor κB ligand (sRANKL) and TNFα was examined. Results Swelling of hind paws and loss of weight occurred in the CIA rats, but this was not evident in the prophylactic treatment group. Therapeutic treatment also significantly reduced paw swelling. The mean radiographic and histologic scores as well as the osteoclast numbers were significantly lower in the treatment group than in the CIA rats without treatment. FR167653 treatment reduced the serum levels of TNFα and IL-1β, lowered the IL-1β concentration in the ankle joints, and decreased the CD4−,CD8a+ T cell population in bone marrow. Furthermore, FR167653 inhibited the osteoclast-like cell differentiation induced by both sRANKL and TNFα in vitro. Conclusion FR167653 prevents the onset of arthritis in a prophylactic treatment model and suppresses the progression of joint destruction in a therapeutic treatment model, suggesting that p38 MAPK is a potential therapeutic target for rheumatoid arthritis.

中国の大気中PAHs汚染の実情を明らかにするため, 3都市 (北京, 銀川, 成都) で1998～2000年に採取した大気粉じん63検体と石炭関連試料8検体についてPAHs分析を行った。大気中23PAHsの総濃度 (Σ23PAHs) は北京323±431ng/m3, 銀川898±902ng/m3, 成都249±203ng/m3であり, 粉じん重量あたりのΣ23PAHsは各々, 545±592μg/g, 1135±1357μg/g, 566±321μ/gであった。中国の大気のPAHs濃度は岡山県の環境大気濃度レベルの35～450倍, サンティアゴの20～80倍, アルジェの17～61倍と高値であり, 重工業地域の影響を強く受けたシカゴ大気の濃度値と同程度であった。3都市のPAHs濃度プロファイル及び縮合環数別PAHsの総PAHsに占める比率では, 傾向を伴った季節変動を観測した。石炭燃焼の寄与が高い時4-ring PAHsの相対濃度が特徴的に高いが, 中国3都市の場合, 石炭燃焼の割合が高まる冬季に4-ring PAHsの相対濃度が上昇する傾向があった。環境大気中PAHsのbenzo [e] pyreneに対する相対濃度比 (BeP ratio) と特徴的なPAHs比 (molecular diagnostic ratio) を用いた解析から, 3都市の主要な発生源の影響を推定した。3都市とも共通して石炭燃焼の特徴が強く反映していたほか, 北京では自動車のパターン, 成都では火力発電所のパターン, 銀川では家庭で使用する小型ボイラーのパターンがそれぞれ特徴的であった。

Background The organic chemicals present in Asian sand dust (ASD) might contribute to the aggravation of lung eosinophila. Therefore, the aggravating effects of the Tar fraction from ASD on ovalbumin (OVA)-induced lung eosinophilia were investigated. Methods The Tar fraction was extracted from ASD collected from the atmosphere in Fukuoka, Japan. ASD collected from the Gobi desert was heated at 360°C to inactivate toxic organic substances (H-ASD). ICR mice were instilled intratracheally with 12 different test samples prepared with Tar (1 μg and 5 μg), H-ASD, and OVA in a normal saline solution containing 0.02% Tween 80. The lung pathology, cytological profiles in the bronchoalveolar lavage fluid (BALF), inflammatory cytokines/chemokines in BALF and OVA-specific immunoglobulin in serum were investigated. Results Several kinds of polycyclic aromatic hydrocarbons (PAHs) were detected in the Tar sample. H-ASD + Tar 5 μg induced slight neutrophilic lung inflammation. In the presence of OVA, Tar 5 μg increased the level of eosinophils slightly and induced trace levels of Th2 cytokines IL-5 and IL-13 in BALF. Also mild to moderate goblet cell proliferation and mild infiltration of eosinophils in the submucosa of airway were observed. These pathological changes caused by H-ASD + OVA were relatively small. However, in the presence of OVA and H-ASD, Tar, at as low a level as 1 μg, induced severe eosinophil infiltration and proliferation of goblet cells in the airways and significantly increased Th2 cytokines IL-5 and IL-13 in BALF. The mixture showed an adjuvant effect on OVA-specific IgG1 production. Conclusions These results indicate that H-ASD with even low levels of Tar exacerbates OVA-induced lung eosinophilia via increases of Th2-mediated cytokines. These results suggest that ASD-bound PAHs might contribute to the aggravation of lung eosinophila.

Purpose.To evaluate disease activity, knee function, and walking ability of patients with rheumatoid arthritis (RA) over 10 years after total knee arthroplasty (TKA).Methods.Four men and 26 women (mean age, 59.9 years) underwent 42 TKAs for RA with a mean duration of 151.3 months and were followed up for a mean of 142.3 months. Preoperatively, disease activity was assessed by C-reactive protein (CRP) level only, and the range of knee motion was recorded. At the final follow-up, tender joint count, swollen joint count, visual analogue scale of RA symptoms, and the Modified Health Assessment Questionnaire (MHAQ) score were assessed. Disease activity was evaluated using CRP, matrix metalloproteinase-3, and Disease Activity Score. Range of motion and Knee Society knee and function scores were also assessed.Results.The use of methotrexate increased from 4 patients preoperatively to 20 patients at the final follow-up (pConclusion.Walking ability in patients with RA after TKA was generally poor. Poor function was associated with a history of spinal or lower extremity fracture surgery and the MHAQ score.

Background Bjerkandera adusta (B. adusta) is one of the most important etiological fungi associated with chronic cough. However, precise details of the inflammatory response to exposure are not well understood yet. B. adusta was recently identified in Asian sand dust (ASD) aerosol. Therefore, in the present study the exacerbating effects of ASD on B. adusta-induced lung inflammation and B. adusta + ASD on ovalbumin (OVA)-induced murine lung eosinophilia were investigated using experimental mice. Methods In order to prepare testing samples, B. adusta obtained from ASD aerosol was inactivated by formalin and ASD collected from the atmosphere was heated to remove toxic organic substances (H-ASD). CD-1 mice were instilled intratracheally with 12 different samples prepared with various combinations of B. adusta, H-ASD, and OVA in a normal saline solution. The lung pathology, cytological profiles in bronchoalveolar lavage fluid (BALF), and the levels of inflammatory cytokines/chemokines in BALF were investigated. Results H-ASD aggravated the lung eosinophilia induced by B. adusta alone, which also aggravated the lung eosinophilia induced by OVA. The mixture of OVA, H-ASD, and B. adusta caused serious fibrous thickening of the subepithelial layer, eosinophil infiltration, and proliferation of goblet cells in the airways along with remarkable increases of IL-13, eotaxin, IL-5, and MCP-3 in BALF. Conclusions The results of the present study demonstrated that B. adusta isolated from ASD aerosol induces allergic lung diseases. H-ASD enhanced allergic reactions caused by OVA or B. adusta. A mixture of B. adusta, H-ASD, and OVA caused the most remarkable exacerbation to the allergic airway inflammation via remarkable increases of pro-inflammatory mediators.

BackgroundA previous study has shown that the aggravation of Asian sand dust (ASD) on ovalbumin (OVA)-induced lung eosinphilia was more severe in lipopolysaccharide (LPS)-rich ASD than in SiO2-rich ASD. Therefore, the effects of different LPS contamination levels in ASD on the aggravation of OVA-induced lung eosinophilia were investigated in the present study.MethodsBefore beginning the in vivo experiment, we investigated whether the ultra-pure LPS would act only on TLR4 or not using bone marrow-derived macrophages (BMDMs) of wild-type, TLR2-/-, TLR4-/- and MyD88-/- BALB/c mice. ASD collected from the desert was heated to remove toxic organic substances (H-ASD). BALB/c mice were instilled intratracheally with 12 different testing samples prepared with LPS (1ng and 10ng), H-ASD, and OVA in a normal saline solution. The lung pathology, cytological profiles in the bronchoalveolar lavage fluid (BALF), the levels of inflammatory cytokines/chemokines in BALF and OVA-specific immunoglobulin in serum were investigated.ResultsThe LPS exhibited no response to the production of TNF-α and IL-6 in BMDMs from TLR4-/-, but did from TLR2-/-. H-ASD aggravated the LPS-induced neutrophilic lung inflammation. In the presence of OVA, LPS increased the level of eosinophils slightly and induced trace levels of Th2 cytokines IL-5 and IL-13 at the levels of 1ng and 10ng. In the presence of OVA and H-ASD, LPS induced severe eosinophil infiltration and proliferation of goblet cells in the airways as well as remarkable increases in Th2 cytokines IL-5 and IL-13 in BALF. The mixture containing LPS (1ng) showed adjuvant activity on OVA-specific IgE and IgG1 production.ConclusionsThe results suggest that H-ASD with naturally-occurring levels of LPS enhances OVA-induced lung eosinophilia via increases in Th2-mediated cytokines and antigen-specific immunoglobulin. These results indicate that LPS is a strong candidate for being a major aggravating substance in ASD.

Background Atmospheric contamination caused by Asian sand-dust (ASD) storms aggravates asthma in both human adults and children. This study aims to investigate a series of manifestations in allergic airway disease caused by co-exposure to allergens and ASD for 6 weeks and 14 weeks. Methods CD-1 Mice were instilled intratracheally with 0.1 mg of ASD/mouse four times (6 weeks) or eight times (14 weeks) at 2-week intervals (total dose of 0.4 mg or 0.8 mg/mouse) with or without ovalbumin (OVA). The pathologic changes in the airway, cytological alteration in bronchoalveolar lavage fluid (BALF), and levels of inflammatory cytokines/chemokines in BALF, and OVA-specific IgE and IgG1 antibodies in serum were measured in the treated CD-1 mice. Results Four-time co-exposure to OVA and ASD aggravates allergic airway inflammation along with Th2-cytokine IL-13 and eosinophil-relevant cytokine/chemokines IL-5, Eotaxin and MCP-3 in BALF, and fibrous thickening of the subepithelial layer in the airway. On the other hand, eight-time co-exposure attenuates these changes along with a significant increase of TGF-β1 in BALF. Adjuvant effects of ASD toward IgG1 and IgE production in sera were, however, still seen in the eight-time co-exposure. Conclusions These results indicate that the immune responses in airways are exacerbated by four-time co-exposure to ASD with OVA, but that there is a shift to suppressive responses in eight-time co-exposure, suggesting that the responses are caused by TGF-β1-related immune tolerance.

It has been reported that ambient particulate matter (PM) in some large cities, such as Beijing, China, causes adverse respiratory health effects. However, there is currently no experimental report on the relationship between bronchial asthma and urban PM (UPM) in northeast Asia. In this study, the microbial and chemical substances adsorbed onto UPM collected in Beijing were excluded by heat-treatment at 360 degrees C for 30 min. The effects of UPM or heated UPM (H-UPM) toward allergic lung inflammation were compared in murine lungs to investigate the role of organic substances. ICR mice were administrated intratracheally with the two kinds of UPM and/or ovalbumin (OVA) 4 times at 2-week intervals. UPM and H-UPM enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. UPM and H-UPM synergistically increased Th-2 cytokines--interleukin (IL)-4 and IL-13, eosinophil-relevant cytokines and chemokines, such as IL-5 and monocyte chemotactic protein-3 (MCP-3), induced by OVA in bronchoalveolar lavage fluid (BALF). The enhancing effects were much greater in UPM than in H-UPM. UPM induced adjuvant effects on specific immunoglobulin E (IgE) and IgG1 production by OVA. In an in vitro study using RAW264.7 cells, UPM increased the expression of Toll-like receptor 2 (TLR2) mRNA, but not TLR4 mRNA. H-UPM caused no expression of both TLR mRNAs. These results suggest that the aggravated lung eosinophilia in UPM was due to activation of a Th2-associated immune response via the activation of TLR2 by microbial materials. Chemical materials of air pollutant origin contained in UPM, and inorganic components (elemental carbon, mineral elements) in H-UPM, could also cause the aggravation.

Limited systematic data on herb-drug interaction are available, despite many opportunities to concomitant use of herb with prescribed drugs. We investigated the effects of 15 herbal extracts in dietary supplements on CYP2C9, CYP2D6 and CYP3A4 activities in human liver microsomes. Strong inhibition of these CYP activities was found by the addition of green tea extracts (GTE) or grape seed extracts (GSE) in vitro. To examine the effects of these extracts on CYP3A activities in vivo, the pharmacokinetics of midazolam (MDZ) was analyzed in rats. Although single treatments with these extracts had negligible effects, 1 week of treatment with them resulted in a significant increase in the ke of intravenously administered MDZ, indicating the induction of CYP3A in the liver. In contrast, 1 week of treatment with GTE, but not GSE, caused a significant increase in the C(max) and AUC(0-infinity) of orally administered MDZ without change in the t(1/2), suggesting a reduction in CYP3A activity in the small intestines. These studies indicate that subchronic ingestion of GTE or GSE may alter the pharmacokinetics of MDZ, and the effects of GTE on CYP3A activity appear opposite between liver and small intestine, which could not be predicted from in vitro experiments.

Orthopedics has long been associated with the development of tissue engineering techniques and biomaterials through the use of bone grafting techniques, including autograft, allograft, and xenograft, as well as through bone lengthening techniques with distraction osteogenesis; fixation devices made of metal, ceramic, or biodegradable materials; and organic or nonorganic bone substitutes. However, in the current clinical scene, when bone grafts are required autogenous bone grafting has been the gold standard because of its obvious advantages in osteogenic capacity, osteoconduction, mechanical properties, and the lack of adverse immunological response. In fact, autograft accounts for nearly 70% of surgical procedures involving bone grafts or bone substitutes in Japan according to a survey by the Japanese Orthopedic Association. [1] On the other hand, autogenous bone grafting techniques have some limitations, [2] such as the requirement of additional surgery for harvesting and the availability of grafts of the correct size and shape. Furthermore, autograft techniques all carry the risk of donor site morbidity, [3-5] which can include long-lasting pain, fracture, nerve damage, and infection, none of which are experienced when other techniques are employed.