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Defective implant osseointegration under protein undernutrition: prevention by PTH or pamidronate. 总被引:1,自引:0,他引:1
Romain Dayer Isabelle Badoud René Rizzoli Patrick Ammann 《Journal of bone and mineral research》2007,22(10):1526-1533
Protein deficiency is associated with impaired titanium osseointegration. We studied whether systemic treatment with PTH or pamidronate could influence the resistance to pull-out of titanium rods implanted into rats proximal tibia under normal and isocaloric low protein intake. PTH or pamidronate prevented the deleterious effects of protein undernutrition on bone microarchitecture close to the implant and on mechanical fixation. PTH even significantly improved implant osseointegration. INTRODUCTION: Protein deficiency is highly prevalent among elderly patients hospitalized in orthopedic wards. Reduced protein intake impairs titanium osseointegration in rats. Whether stimulator of bone formation or inhibitor of bone resorption could improve implant osseointegration under protein deprivation is not known. We studied the effects of systemic treatment with PTH or pamidronate on the resistance to pull-out of titanium rods implanted into rats proximal tibia under normal and isocaloric low protein intake. MATERIALS AND METHODS: We measured the resistance to pull-out 1-mm-diameter titanium rods implanted into the proximal tibias of 49 adult female rats receiving a normal or an isocaloric low protein diet. After 2 wk on either diet, the implants were inserted, and the rats received PTH(1-34), pamidronate or saline vehicle for 8 wk. The tibias were removed for microCT morphometry, followed by the evaluation of pull-out strength. RESULTS: Pull-out strength was lower in rats fed an isocaloric low protein diet compared with rats fed a normal protein intake (-29%). PTH and pamidronate significantly increased pull-out strength in animals fed a normal or a low protein diet, the effect of PTH being of higher magnitude. The PTH- or pamidronate-mediated increase in pull-out strength was associated with significant increases of relative bone volume, bone-to-implant contact, and trabecular thickness, whereas trabecular spacing was reduced, in the vicinity of the implants. CONCLUSIONS: We confirmed that isocaloric low protein intake impairs titanium implant osseointegration. PTH or pamidronate prevented the deleterious effects of protein undernutrition and even significantly improved the implant osseointegration. These results indicate that systemic administration of PTH or pamidronate could be considered for preventing uncemented arthroplasty loosening in protein undernourished patients. 相似文献
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S Sohen P L Romain D M Rothstein T Yamane S Tanaka P Anderson S F Schlossman C Morimoto 《The Journal of rheumatology》1991,18(11):1649-1654
We analyzed the cell surface phenotype of CD8+ cells in both peripheral blood and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Utilizing the monoclonal antibodies anti-CD45RA, anti-CD29 and anti-S6F1-, one can define both suppressor effector (CD45RA+CD29-S6F1-) and killer effector (CD45RA-CD29+S6F1+) cells within the CD8 population. In patients with OA, normal proportions of CD8+CD45RA+, CD8+CD29+ and CD8+S6F1+ cells were found in both peripheral blood and SF. The peripheral blood of patients with RA, in contrast, showed a decreased percentage of CD8+CD45RA+ cells (13.4 +/- 2.6) (p less than 0.05), but a normal percentage of CD8+CD29+ and CD8+S6F1+ cells. In the SF of patients with RA, we observed a more dramatic decrease in CD8+CD45RA+ suppressor effector cells (6.4 +/- 5.0) (p less than 0.001), a significant increase in killer effector cells as measured by both CD8 + CD29+ (35.5 +/- 9.9) (p less than 0.001) and CD8 + S6F1+ cells (28.2 +/- 11.4) (p less than 0.01). These changes may contribute to the immunologic abnormalities previously noted in this disease and may provide some insight into the pathophysiologic mechanisms of RA. 相似文献
6.
Peter MA Calverley Romain A Pauwels Paul W Jones Julie A Anderson J?rgen Vestbo 《INT J CHRONIC OBSTR》2006,1(3):209-218
Guidelines recommend that patients with COPD are stratified arbitrarily by baseline severity (FEV1) to decide when to initiate combination treatment with a long-acting β2-agonist and an inhaled corticosteroid. Assessment of baseline FEV1 as a continuous variable may provide a more reliable prediction of treatment effects. Patients from a 1-year, parallel-group, randomized controlled trial comparing 50 μg salmeterol (Sal), 500 μg fluticasone propionate (FP), the combination (Sal/FP) and placebo, (bid), were categorized post hoc into FEV1 <50% and FEV1 ≥50% predicted subgroups (n=949/513 respectively). Treatment effects on clinical outcomes – lung function, exacerbations, health status, diary card symptoms, and adverse events – were investigated. Treatment responses based on a pre-specified analysis explored treatment differences by severity as a continuous variable. Lung function improved with active treatment irrespective of FEV1; Sal/FP had greatest effect. This improvement appeared additive in milder disease; synergistic in severe disease. Active therapy significantly reduced exacerbation rate in patients with FEV1 <50% predicted, not in milder disease. Health status and breathlessness improved with Sal/FP irrespective of baseline FEV1; adverse events were similar across subgroups. The spirometric response to Sal/FP varied with baseline FEV1, and clinical benefits were not restricted to patients with severe disease. These data have implications for COPD management decisions, suggesting that arbitrary stratifications of baseline severity are not necessarily indicative of treatment efficacy and that the benefits of assessing baseline severity as a continuous variable should be assessed in future trials. 相似文献
7.
Thomas Barba Romain Fort Vincent Cottin Steeve Provencher Isabelle Durieu Sabine Jardel Arnaud Hot Quitterie Reynaud Jean-Christophe Lega 《Autoimmunity reviews》2019,18(2):113-122
Objective
Interstitial lung disease (ILD) is the most severe complication of idiopathic inflammatory myositis (IIM), resulting in significant increase in morbidity and mortality and for which the best treatment remains controversial. We conducted a meta-analysis to evaluate the efficacy of therapies used for the management of IIM-related ILD.Methods
Studies were selected from MEDLINE up to July 2017. Two investigators independently extracted data on study design, patient characteristics, clinical features, treatment, follow-up and outcomes. Global survival rates and objectively confirmed lung function improvements were extracted as the main outcome for rapidly progressive IIM-related ILD (RP-ILD) and chronic forms of ILD (C-ILD), respectively, and pooled using the weighted mean proportion with fixed or random-effects models in case of significant heterogeneity (I2?>?50%).Results
Twenty-seven studies encompassing 553 patients (male: 30.5%, age: 53.5?±?5.5?years) were included in the meta-analysis. Globally, retrieved studies were of limited methodological quality (no controlled studies and only 2 prospective studies). Dermatomyositis (40%) and anti-tRNA synthetase syndrome (45%) were the most represented IIM subtypes. In C-ILD, functional improvement rates were 89.2% (95%CI 82.5–93.6; 7 studies, n?=?124) for corticosteroids alone, 80.7% (95%CI 49.6–94; 6 studies, n?=?38) for cyclosporine A, 64.1% (95%CI 46.3–78.7; 4 studies, n?=?32) for azathioprine, 86.2% (95%CI 61.5–96; 2 studies, n?=?23) for tacrolimus, 56.4% (95%CI 44–68.0; 8 studies, n?=?71) for cyclophosphamide, and 76.6% (95%CI 50.4–96.0; 2 studies, n?=?20) for rituximab. In RP-ILD, survival rates at 3?months were 51.7% (95%CI 24.2–78.1; 2 studies, n?=?11) for corticosteroids alone, 69.2% (95%CI 55.0–80.5; 8 studies, n?=?146) for cyclosporine A and 72.4% (95%CI 6.4–99.0, 2 studies, n?=?16) for cyclophosphamide.Conclusion
Despite aggressive immunosuppressive therapies, the short-term mortality of RP-ILD remains high. While immunosuppressive therapies are associated with significant functional improvements in most patients with C-ILD, substantial uncertainty remains about the best treatment strategy in the absence of good quality evidence. 相似文献8.
Romain Guinamard Aurélien Chatelier Marie Demion Daniel Potreau Sylvie Patri Mohammad Rahmati Patrick Bois 《The Journal of physiology》2004,558(1):75-83
Cardiac arrhythmias, which occur in a wide variety of conditions where intracellular calcium is increased, have been attributed to the activation of a transient inward current ( I ti ). I ti is the result of three different [Ca]i -sensitive currents: the Na+ –Ca2+ exchange current, a Ca2+ -activated chloride current and a Ca2+ -activated non-selective cationic current. Using the cell-free configuration of the patch-clamp technique, we have characterized the properties of a Ca2+ -activated non-selective cation channel (NSCCa ) in freshly dissociated human atrial cardiomyocytes. In excised inside-out patches, the channel presented a linear I–V relationship with a conductance of 19 ± 0.4 pS. It discriminated poorly among monovalent cations (Na+ and K+ ) and was slightly permeable to Ca2+ ions. The channel's open probability was increased by depolarization and a rise in internal calcium, for which the K d for [Ca2+ ]i was 20.8 μ m . Channel activity was reduced in the presence of 0.5 m m ATP or 10 μ m glibenclamide on the cytoplasmic side to 22.1 ± 16.8 and 28.5 ± 8.6%, respectively, of control. It was also inhibited by 0.1 m m flufenamic acid. The channel shares several properties with TRPM4b and TRPM5, two members of the 'TRP melastatin' subfamily. In conclusion, the NSCCa channel is a serious candidate to support the delayed after-depolarizations observed in [Ca2+ ] overload and thus may be implicated in the genesis of arrhythmias. 相似文献
9.
Robert F. Todd Stefan C. Meuer Paul L. Romain Stuart F. Schlossman 《Human immunology》1984,10(1):23-40
Previous studies using conventional hetero- or isoantisera have indicated the involvement of class II (Ia) molecules in presentation of soluble by monocytes to inducer T lymphocytes, stimulation of inducer T cells in MLR, and recognition of Ia-bearing targets cells by cytotoxic T lymphocytes (CTL). The experience in using monoclonal anti-Ia reagents capable of blocking these phenomena in the human system is limited. Recently, however, we have characterized a lytic IgG2a monoclonal antibody, 9–49, that binds to functionally significant class II molecules. This antibody blocks (in the absence of complement): (1) specific binding of peripheral blood lymphocytes (PBL) to antigen-pulsed monocyte monolayers, (2) proliferation of PBL in response to soluble antigen (tetanus toxoid or mumps) or cell surface class II antigen stimulation in allogeneic or autologus MLR, (3) proliferation of cloned T4+ (inducer) lymphocyte cell lines to class II antigens, (4) generation of cytotoxic lymphocytes during allogenic MLR, and (5) recognition (and killing) of class II-bearing target cells by T4+ CTL clones. Proliferation and CTL activity of a T8+ clone is unaffected by the 9–49 antibody. These results indicate the usefulness of this monoclonal reagent in studies evaluating the functional role of Ia molecules in immune recognition phenomena. 相似文献
10.
Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite 总被引:1,自引:0,他引:1
R. J. Bischof K. Snibson R. Shaw E. N. T Meeusen 《Clinical and experimental allergy》2003,33(3):367-375
Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti‐asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail. Objective To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model. Methods Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post‐mortem (48 h post‐challenge) for histology and immunohistochemical analyses. Results Immunizations with 50 μg house dust mite induced an allergen‐specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG1 but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post‐challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late‐phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post‐challenge, representing 10 to 33% of BAL leucocytes in allergen‐challenged allergic sheep compared to 0 to 3% in allergen‐challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4+ T cells and were more activated than lymphocytes in blood. There was significant down‐regulation of CD62L (L‐selectin) and CD49d (VLA‐4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM‐1 (ligand for VLA‐4) was up‐regulated on blood vessels of allergen‐challenged lungs. Eosinophils, CD4+ T cells and CD45R+ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge. Conclusion This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. This novel sheep model of allergic lung inflammation using relevant human allergens, exhibits similarities to human asthmatic disease and will be a useful tool for studies of the immunological and physiological mechanisms of allergic asthma. 相似文献