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Background: Peri-prosthetic bone loss can result from chemical, biological, and mechanical factors. Mechanical stimulation via fluid pressure and flow at the bone–implant interface may be a significant cause. Evidence supporting mechanically induced osteolysis continues to grow, but there is no synthesis of published clinical and basic science data. Questions/Purposes: We sought to review the literature on two questions: (1) What published evidence supports the concept of mechanically induced osteolysis? (2) What is the proposed mechanism of mechanically induced osteolysis, and does it differ from that of particle-induced osteolysis? Methods: A systematic review was performed of the PubMed and Web of Science databases. Additional relevant articles were recommended by the senior authors based on their expert opinion. Abstracts were reviewed and the manuscripts pertaining to the study questions were read in full. Studies showing support of mechanically induced osteolysis were quantified and findings summarized. Results: We identified 49 articles of experimental design supporting the hypothesis that mechanical stimulation of peri-prosthetic bone from fluid pressure and flow can induce osteolysis. While the molecular mechanisms may overlap with those implicated in particle-induced osteolysis, mechanically induced osteolysis appears to be mediated by distinct and parallel pathways. Conclusions: The role of mechanical stimuli is increasingly recognized in the pathogenesis of peri-prosthetic osteolysis. Current research aims to elucidate the molecular mechanisms to better target therapeutic interventions. [ABSTRACT FROM AUTHOR]

Abstract: Resource extraction and transportation activities in subarctic Canada can result in the unintentional release of contaminants into the surrounding peatlands. In the event of a release, a thorough understanding of solute transport within the saturated zone is necessary to predict plume fate and the potential impacts on peatland ecosystems. To better characterize contaminant transport in these systems, approximately 13,000 L/day of sodium chloride tracer (200 mg/L) was released into a bog in the James Bay Lowland. The tracer was pumped into a fully penetrating well (1.5 m) between July 5 and August 18, 2015. Horizontal and vertical plume development was measured via in situ specific conductance and water table depth from an adaptive monitoring network. Over the spill period, the bulk of the plume travelled a lateral distance of 100 m in the direction of the slight regional groundwater and topographical slope. The plume shape was irregular and followed the hollows, indicating preferential flow paths due to the site microtopography. Saturated transport of the tracer occurred primarily at ~25 cm below ground surface (bgs), and at a discontinuous high hydraulic conductivity layer ~125 cm bgs due to a complex and heterogeneous vertical hydraulic conductivity profile. Plume measurement was confounded by a large amount of precipitation (233 mm over the study period) that temporarily diluted the tracer in the highly conductive upper peat layer. Longitudinal solute advection can be approximated using local water table information (i.e., depth and gradient); microtopography; and meteorological conditions. Vertical distribution of solute within the peat profile is far more complex due to the heterogeneous subsurface; characterization would be aided by a detailed understanding of the site‐specific peat profile; the degree of decomposition; and the type of contaminant (e.g., reactive/nonreactive). The results of this research highlight the difficulty of tracking a contaminant spill in bogs and provide a benchmark for the characterization of the short‐term fate of a plume in these complex systems. [ABSTRACT FROM AUTHOR]

Background: Long-term fixation of uncemented joint implants requires early mechanical stability and implant osseointegration. To date, osseointegration has been unreliable and remains a major challenge in cementless total knee arthroplasty. We developed a murine model in which an intra-articular proximal tibial titanium implant with a roughened stem can be loaded through the knee joint. Using this model, we tested the hypothesis that intermittent injection of parathyroid hormone (iPTH) would increase proximal tibial cancellous osseointegration. Methods: Ten-week-old female C57BL/6 mice received a subcutaneous injection of PTH (40 μg/kg/day) or a vehicle (n = 45 per treatment group) five days per week for six weeks, at which time the baseline group was killed (n = 6 per treatment group) and an implant was inserted into the proximal part of the tibiae of the remaining mice. Injections were continued until the animals were killed at one week (n = 7 per treatment group), two weeks (n = 14 per treatment group), or four weeks (n = 17 per treatment group) after implantation. Outcomes included peri-implant bone morphology as analyzed with micro-computed tomography (microCT), osseointegration percentage and bone area fraction as shown with backscattered electron microscopy, cellular composition as demonstrated by immunohistochemical analysis, and pullout strength as measured with mechanical testing. Results: Preimplantation iPTH increased the epiphyseal bone volume fraction by 31.6%. When the data at postimplantation weeks 1, 2, and 4 were averaged for the iPTH-treated mice, the bone volume fraction was 74.5% higher in the peri-implant region and 168% higher distal to the implant compared with the bone volume fractions in the same regions in the vehicle-treated mice. Additionally, the trabecular number was 84.8% greater in the peri-implant region and 74.3% greater distal to the implant. Metaphyseal osseointegration and bone area fraction were 28.1% and 70.1% higher, respectively, in the iPTH-treated mice than in the vehicle-treated mice, and the maximum implant pullout strength was 30.9% greater. iPTH also increased osteoblast and osteoclast density by 65.2% and 47.0%, respectively, relative to the values in the vehicle group, when the data at post-implantation weeks 1 and 2 were averaged. Conclusions: iPTH increased osseointegration, cancellous mass, and the strength of the bone-implant interface. [ABSTRACT FROM AUTHOR]

Glucocorticoid (GC)-induced bone loss is the most common cause of secondary osteoporosis but its pathogenesis is controversial. GCs clearly suppress bone formation in vivo but the means by which they impact osteoblasts is unclear. Because bone remodeling is characterized by tethering of the activities of the two cells, the osteoclast is a potential modulator of the effect of GCs on osteoblasts. To address this issue we compared the effects of dexamethasone on wild-type (WT) osteoclasts with those derived from mice with disruption of the GC receptor in osteoclast lineage cells and found that the bone-degrading capacity of GC-treated WT cells is suppressed. The inhibitory effect of dexamethasone on bone resorption reflects failure of osteoclasts to organize their cytoskeleton in response to M-CSF. Dexamethasone specifically arrests M-CSF activation of RhoA, Rac, and Vav3, each of which regulate the osteoclast cytoskeleton. In all circumstances, mice lacking the GC receptor in osteoclast lineage cells are spared the impact of dexamethasone on osteoclasts and their precursors. Consistent with osteoclasts modulating the osteoblast-suppressive effect of dexamethasone, GC receptor-deficient mice are protected from the steroid's inhibition of bone formation. [ABSTRACT FROM AUTHOR]

A tight balance between bone resorption by osteoclasts and bone formation by osteoblasts is required for the maintenance of bone mass and integrity. A net increase in bone resorption over formation results in osteoporosis, a disease associated with significantly morbidity and mortality. Following attachment via the integrin αvβ3, osteoclasts degrade bone by generation of the ruffled border, the unique resorptive organelle of the cell. The adherent cell then secretes into the subcellular space protons and acidic proteases. We review here the concepts relating to the mechanisms of regulated secretion and provide preliminary data on the role of one protein important for secretion by osteoclasts. [ABSTRACT FROM AUTHOR]

We encountered 16 patients with connective tissue disease in whom pulmonary fibrosis developed. Routine light microscopic, ultrastructural, and direct immunofluorescent analyses were conducted, and circulating antibodies, including those of endothelial cell derivation, were assessed using indirect immuno-fluorescence and Western blot assays. Underlying diseases were dermatomyositis, scleroderma, mixed connective tissue disease, sclerodermatomyositis, Sjögren syndrome, rheumatoid arthritis, and anti-Ro-associated systemic lupus erythematosus. Antibodies to one or more Ro, RNP, Jo 1, OJ, and/or nucleolar antigens were seen in all cases and antiphospholipid antibodies in half. All biopsies revealed microvascular injury in concert with intraparenchymal fibrosis; in some cases, there were corroborative ultrastructural findings of microvascular injury. Patterns of fibroplasia represented nonspecific interstitial pneumonitis and usual interstitial pneumonitis. We noted IgG, IgA, and/or complement in the septal microvasculature. In 6 cases with available serum samples, indirect immunofluorescent endothelial cell antibody studies were positive and Western Blot studies showed reactivity of serum samples to numerous endothelial cell lysate-derived proteins.Pulmonary fibrosis, a recognized complication of systemic connective tissue disease, develops in connective tissue disease syndromes with pathogenetically established immune-based microvascular injury at other sites. A similar mechanism of antibody-mediated endothelial cell injury may be the basis of the tissue injury and fibrosing reparative response. [ABSTRACT FROM AUTHOR]

Understanding of the process by which an individual with same sex sexual orientation becomes aware of his homosexuality and eventually embraces homosexual idetity is of great interest and importance to social work and the other helping professions. The coming out process appears to take place over an extended period of time and to have identifiable and predictable stages. This paper explored the process of coming out in a sample of 15 self-identified gay men who had been married to women. Four patterns of reasons for marriage in this group emerged, which we call: Repressed, Naive, Wistful and Pragmatic. Implications for social work practice are presented. [ABSTRACT FROM PUBLISHER]

This paper reports on an exploratory study of motivations for marriage among fifteen actively homosexual men who were either currently or formerly married to women. The middle class sample had married young and most had at least one child. Currently divorced and openly gay, most believed that cultural and religious socialization were the major forces behind their behavior. One third claimed to have had no awareness that they might be homosexual at the time on marriage and one-third reported love for the wife as an important motivating factor. Implication of the results for theory and for social work practice are presented. [ABSTRACT FROM PUBLISHER]

Osteoblasts are thought to secrete factors that regulate the rate of osteoclastic bone resorption. We studied the effect of osteoblast conditioned medium on bone degradation by multinucleated osteoclast-like cells generated in vitro from mononuclear precursors and found that the medium stimulates bone degradation primarily through interactions with osteoclast precursors. The conditioned medium also stimulates expression of the osteoclast-specific antigen 121F. The increased bone degradation, but not increased 121F expression, is due to the conditioned medium maintaining activity of the osteoclast precursors. Although the osteoclast precursors exhibit the DNA fragmentation characteristic of apoptosis, the osteoblast conditioned medium does not prevent such fragmentation. Chicken macrophage growth factor neither mimics nor augments the ability of the conditioned medium to stimulate bone degradation. Studies of osteoclast generation or function should carefully consider whether the effects are dependent on the viability of the resorbing cells. [ABSTRACT FROM AUTHOR]

We have recently shown that the heterodimeric β[sub 2] integrin family plays an important role in the development of MLDSTZ diabetes. Specifically, we reported that deficieney of CD 18 protects against the development of diabetes and insulitis. In this study, we examined the importance of CD18 and CD11a expression for NOD/LtJ CD3 T cell adhesion to islet microvascular endothelial cells under hydrodynamic flow conditions. Genetic deficiency of CD18 causes a significant decrease in the number of NOD/LtJ CD3 T cells adherent to TNFα activated islet endothelium versus wild type NOD/LtJ CD3 T cells. Moreover, addition of a cyclic peptide antagonist against CD 18 (cLBE.C) similarly decreased wild type NOD/LtJ CD3 T cell adhesion to TNF-α treated islet endothelium versats scrambled control peptide. Importantly, cLBE.C treatment of NOD/LtJ CD18 null T cells had no further effect on T cell adhesion to TNF-α activated islet endothelium demonstrating specificity of action. Cyclic peptide inhibition of the heterodimeric partner CD11 a with cLAB.L yielded similar results as cLBE.C, with a significant decrease in wild type NOD/LtJ CD3 T cell adhesion to activated islet endothelium. Inhibition of CD18 dependent NOD/LtJ CD3 T cell adhesion was due to blockade of firm adhesion as the number and velocity of rolling CD3 T cells was not significantly altered. Lastly, treatment with either cLBE.C or cLAB.L revealed no change in basal NOD/LtJ CD3 T cell adhesion indicating that these agents do not interfere with immune surveillance. Together, these data suggest that specific disruption of T cell Beta 2 integrin function may be useful in attenuating diabetogenic T cell adhesion and homing. [ABSTRACT FROM AUTHOR]

Leukocyte recruitment into pancreatic islets is believed to play an important pathophysiological rule in autoimmune diabetes. Previous reports have suggested that the chemokine stromal-cell derived factor-1 (SDF-1) controls trafficking and homing of lymphoid cells via chemoattraction and that genetic polymorphisms of SDF-1 are associated with development of T1D. Here we examined the manner in which SDF-1 modulates adhesion of diabetogenic lymphocytes to islet microvascular endothelium. Islet microvascular endothelial cell monolayers were stimulated with 10 ng/ml TNFα and subsequently coated with varying concentrations of SDF-1 (1-100 ng/ml) and subjected to parallel plate flow chamber analysis for T-cell/endothelial cell interactions. TNFα stimulation significantly increased NOD/LtJ CD3[sup +] T-cell adhesion 3-4 fold, which was surprisingly blocked by SDF-1 in a dose dependent manner. Conversely, SDF-1 enhanced C57BL/6J CD3[sup +] T cell adhesion to TNFα activated islet endothelium indicating that SDF-1 treatment is not chemorepulsive to non-diabetogenic T cells. Chemorepulsion of T cell adhesion by SDF-1 was reversed using the G-protein coupled receptor antagonist Pertussis Toxin. SDF-1 chemorepulsion did not diminish the number or velocity of rolling NOD/LtJ CD3[sup +] T cells suggesting that SDF-1 mediates a defect in firm adhesion. Firm adhesion interactions were measured using a cell detachment assay whereby adherent cells are exposed to varying degrees of shear stress over time. NOD/LtJ CD3[sup +] T cells adherent to TNF α activated islet endothelium were significantly resistant to shear mediated detachment. However, SDF-1 treatment completely prevented resistance of NOD/LtJ CD3[sup +] T cells to shear mediated detachment which was reversed by Pertussis Toxin. These data identify a novel function for SDF-1 in mediating chemorepulsion of diabetogenic T cells suggesting that SDF-1 may be useful in disrupting leukocyte recruitment into pancreatic islets seen during autoimmune diabetes. [ABSTRACT FROM AUTHOR]

Members of the integrin protein family consist of heterodimeric alpha and beta chains that govern cell-cell adhesion, motility, and signal transduction of all cell types. As such, targeted interruption of integrin function in hematopoetic and immune cells has shown considerable therapeutic potential in various inflammatory disease states. However, identification of critical integrin family members modulating autoimmune responses during Type I diabetes is lacking. In this study, we determined the effect of genetic deletion of the Itgb2 (the β[sub 2] integrin sub-family) and a complimentary alpha chain partner ItgaL on autoimmune diabetes in the NOD/LtJ mouse model. Gene targeted null deficiencies of either Itgb2 or ItgaL were backcrossed onto the NOD/LtJ strain. Female wild type NOD/LtJ, NOD/LtJ-Itgb2 deficient, or NOD/LtJ-ItgaL deficient mice were used to evaluate blood glucose levels, incidence of diabetes, insulitis, and CD3 T cell firm adhesion to activated islet microvascular endothelial cells under physiological blood flow conditions. Genetic deficiency of Itgb2 or ItgaL delayed the development of hyperglycemia compared to wild type NOD/LtJ mice. Moreover, Itgb2 deficient mice revealed a complete absence of insulitis; whereas, the ItgaL null mice showed very minor insulitis. CD3 T cell adhesion to activated islet microvascular endothelials was examined to evaluate the effects of integrin deficiencies on diabetogenic T cell recruitment. Genetic deficiency of Itgb2 attenuated NOD CD3 T cell adhesion to TNF-α activated islet microvascular endothelium. Conversely, ItgaL null NOD CD3 T cells showed no defect in firm adhesion to activated islet microvascular endothelium. These data demonstrate dichotomous roles of the integrin beta and alpha chains suggesting that they may control separate aspects of cell-cell adhesion, motility, and signal transduction activity necessary for diabetogenic T cell recruitment and the development of autoimmune diabetes. ADA-Funded Research [ABSTRACT FROM AUTHOR]