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31.
Wouter de Munter Arjen B Blom Monique M Helsen Birgitte Walgreen Peter M van der Kraan Leo AB Joosten Wim B van den Berg Peter LEM van Lent 《Arthritis research & therapy》2013,15(6):R178
Introduction
Osteoarthritis (OA) is associated with the metabolic syndrome, however the underlying mechanisms remain unclear. We investigated whether low density lipoprotein (LDL) accumulation leads to increased LDL uptake by synovial macrophages and affects synovial activation, cartilage destruction and enthesophyte/osteophyte formation during experimental OA in mice.Methods
LDL receptor deficient (LDLr−/−) mice and wild type (WT) controls received a cholesterol-rich or control diet for 120 days. Experimental OA was induced by intra-articular injection of collagenase twelve weeks after start of the diet. OA knee joints and synovial wash-outs were analyzed for OA-related changes. Murine bone marrow derived macrophages were stimulated with oxidized LDL (oxLDL), whereupon growth factor presence and gene expression were analyzed.Results
A cholesterol-rich diet increased apolipoprotein B (ApoB) accumulation in synovial macrophages. Although increased LDL levels did not enhance thickening of the synovial lining, S100A8 expression within macrophages was increased in WT mice after receiving a cholesterol-rich diet, reflecting an elevated activation status. Both a cholesterol-rich diet and LDLr deficiency had no effect on cartilage damage; in contrast, ectopic bone formation was increased within joint ligaments (fold increase 6.7 and 6.1, respectively). Moreover, increased osteophyte size was found at the margins of the tibial plateau (4.4 fold increase after a cholesterol-rich diet and 5.3 fold increase in LDLr−/− mice). Synovial wash-outs of LDLr−/− mice and supernatants of macrophages stimulated with oxLDL led to increased transforming growth factor-beta (TGF-β) signaling compared to controls.Conclusions
LDL accumulation within synovial lining cells leads to increased activation of synovium and osteophyte formation in experimental OA. OxLDL uptake by macrophages activates growth factors of the TGF-superfamily. 相似文献32.
Krzysztof Dziewiszek Raymond F. Schinazi Ting-Chao Chou Tsann-Long Su Jolanta M. Dzik Wojciech Rode 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):77-94
Abstract A number of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil and -cytosine nucleosides substituted at the 5 position with a nitrophenyl or nitrobenzyl group were synthesized from 5-phenyl- and 5-benzyluracil via condensation of the fluorinated sugar, followed by nitration. The corresponding amino analogues were also prepared by reduction of the nitro nucleosides. The uracil nucleosides were converted into the corresponding cytosine nucleosides by way of the triazole intermediates. None of these nucleosides exhibited significant activity against herpes simplex virus type 1 in Vero cells. However, cytosine nucleosides containing the o-nitrophenyl, p-nitrophenyl, p-nitrobenzyl or p-aminobenzyl substituent were found to be toxic (even at 1 μM) to uninfected Vero cells, although they were essentially nontoxic in HL-60 cells. The 5′-monophosphates of the uracil nucleosides were inhibitors of the reaction catalyzed by purified Ehrlich ascites carcinoma thymidylate synthase, the 5-phenyluracil nucleotides causing a strong inhibition, competitive vs dUMP, described by the Ki value of 0.01 μM. 相似文献
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Background
Although aerobic fitness is regarded as an overall prognostic measure of morbidity and mortality, its evaluation in the chronic progressive sinopulmonary disease primary ciliary dyskinesia (PCD) has been infrequently and inconsistently reported. Here we assessed peak oxygen uptake (VO2peak) in a large well-characterized cohort of PCD patients, and explored whether VO2peak was associated with parameters of pulmonary function, self-reported physical limitations, and physical activity level.Methods
VO2peak, spirometry, diffusing capacity, whole-body plethysmography, and nitrogen multiple breath inert gas washout (N2 MBW) were assessed in a cross-sectional, single-occasion study of clinically stable children and young adults with PCD. We used a questionnaire including self-reported physical limitations in everyday life or in vigorous activities, and estimation of weekly hours of strenuous physical activity. VO2peak in PCD patients was compared with that in matched, healthy control subjects and a national reference.Results
Forty-four PCD patients aged 6–29 years exhibited reduced VO2peak compared to healthy controls (P<0.001) and the national reference. VO2peak was abnormal (z-score <–1.96) in 34% of PCD patients. Spirometric values, RV/TLC, and indices of N2 MBW were significantly abnormal, but VO2peak only correlated with FEV1 and DLCO/VA. VO2peak correlated with complaints of moderate or significant limitations in vigorous activities (P = 0.0001), exhibited by 39% of PCD patients.Conclusion
One-third of PCD patients exhibited substantially lower aerobic fitness than healthy subjects. Aerobic fitness correlated with FEV1, DLCO/VA and self-reported complaints of limitations in vigorous physical activity. These findings are most likely explained by PCD pulmonary disease and its impact on pulmonary function and physical ability. Considering fitness as an important outcome and including regular strenuous physical activity in PCD treatment would probably altogether increase pulmonary clearance, lung function, aerobic fitness, and quality of life, and prevent lifestyle-related diseases. 相似文献35.
36.
John F. Moxnes Birgitte Freiesleben de Blasio Truls Michael Leegaard Aina E. Fossum Moen 《PloS one》2013,8(8)
Background
Accurate estimates of the incidence and prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections are needed to inform public health policies. In Norway, where both MRSA infection and carriage are notifiable conditions, the reported incidence of MRSA is slowly increasing. However, the proportion of MRSA in relation to all S. aureus isolates is unknown, making it difficult to determine if the rising incidence is real or an artifact of an increasing number of tests performed.Aim
To characterize recent trends in MRSA infections and obtain a more complete understanding of the MRSA level in Norway.Methods
All reported cases of MRSA and methicillin-sensitive S. aureus (MSSA) from Oslo County (1997–2010) and Health Region East (2008–2008), representing approximately 11% and 36% of the Norwegian population, respectively, were analyzed using a stochastic time series analysis to characterize trends.Results
In Oslo County, the proportion of methicillin-resistant cases increased from 0.73% to 3.78% during the study period and was well modeled by an exponential growth with a doubling constant of 5.7 years (95% CI 4.5–7.4 years). In Health Region East, the proportion of MRSA cases increased from 0.4% to 2.1% from 2002 to 2008, with a best-fitting linear increase of 0.26% (95% CI 0.21–0.30%) per year. In both cases, the choice of a linear or exponential model for the time trend produced only marginally different model fits. We found no significant changes due to revised national MRSA guidelines published in June 2009. Significant variations in the increasing time trend were observed in the five hospitals within the region. The yearly reported incidence of MSSA was relatively stable in both study areas although we found seasonal patterns with peaks in August.Conclusion
The level of MRSA is increasing in Norway, and the proportion of methicillin resistance in all S. aureus isolates are higher than the reported proportion of MRSA in invasive infections. 相似文献37.
Early Weight Loss with Liraglutide 3.0 mg Predicts 1‐Year Weight Loss and is Associated with Improvements in Clinical Markers
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38.
Elizabeth P. St. John Birgitte B. Simen Gregory S. Turenchalk Michael S. Braverman Isabella Abbate Jeroen Aerssens Olivier Bouchez Christian Gabriel Jacques Izopet Karolin Meixenberger Francesca Di Giallonardo Ralph Schlapbach Roger Paredes James Sakwa Gudrun G. Schmitz-Agheguian Alexander Thielen Martin Victor Karin J. Metzner Martin P. D?umer HIV- Alpha Study Group 《PloS one》2016,11(1)
39.
40.
The possibility of improving a two-stage (68 degrees C/55 degrees C) anaerobic digestion concept for treatment of cattle manure was studied. In batch experiments, a 10-24% increase of the specific methane yield from cattle manure and its fractions was obtained, when the substrates were inoculated with bacteria of the genus Caldicellusiruptor and Dictyoglomus. In a reactor experiment inoculation of a 68 degrees C pretreatment reactor with Caldicellusiruptor resulted in a 93% increase in the methane yield of the pretreatment reactor for a period of 18 days, but gave only a slight increase in the overall methane yield of the two-stage setup. 相似文献