168 research outputs found

    Etiology of Experimental Osteoarthritis: Early Events and Potential Clinical Implications

    Get PDF
    Introduction Osteoarthritis (OA) is the most common form of arthritis and accounts for 50% of all chronic conditions in the elderly. One in two adults reported a chronic musculoskeletal condition in 2005, twice the rate of reported chronic heart or respiratory conditions(2). In addition, persons aged 45 to 64 account for an increasingly greater proportion of total musculoskeletal disease treatment costs and lost wages, a trend that will continue for the next several decades(3). Surgical treatment culminating in total joint replacement (TJR) remains the most effective therapy for late stage OA. Current treatment of pre-surgical OA consists of pain relieving medications (i.e. NSAIDs), physical therapy, and mechanical supports (i.e. braces, canes, and walkers). Despite the wealth of clinical data on OA, there is currently no cure for the disease. Our previous work in developing potential disease-modifying osteoarthritis drugs (DMOADs) had yielded promising results, showing a decrease in OA cartilage lesion areas and histological grades (Figure 1). Interestingly, we noted that animals treated for only the first 3 weeks demonstrated near 6-week levels of OA reduction. These differences in treatment responsiveness necessitate a better characterization of the specific cellular phases of OA throughout the natural disease progression. The current study was undertaken to clarify this progression of early OA events. Methods OA was induced in the right knees of 10-week-old male 129 S6/SvEv (Taconic) mice via DMM surgery. Mice receiving sham surgery with no destabilization were used as negative controls. Both groups were sacrificed at 4, 8, 12, 16, and 20-day intervals in order to evaluate OA progression. Knees were harvested, processed, and sectioned at 6um intervals. Sections were stained for cartilage composition (Safranin-O) and scored for progression and severity of OA by 3 blinded observers using a 0-5 scale (modified Mankin System)(4). Both ‘mean maximal’ scores (highest scores per knee), and ‘mean summed scores (sum of scores per knee) were generated using this scale. All scores were averaged across observers. Cartilage lesion area, subchondral bone area (sclerosis), and apoptosis (TUNEL method) were measured using a histomorphometric analysis package (ImageJ)(5). Conclusions Measurable osteoarthritic changes in articular cartilage and underlying bone following meniscal injury occur far earlier than previously described. Some changes are clearly degenerative (OA grade, stage & lesion area), however, some changes (subchondral bone thickening) could be regarded as compensatory supportive mechanisms. Cell death (apoptosis) is an acute event following relatively minor changes to knee biomechanics. Our results suggest an opportunity for intervention early on in OA before the resulting articular changes become irreversible. Specifically, consideration of anti-apoptosis based therapies could prevent much of the subsequent structural changes in articular cartilage. Future Directions Apoptosis data suggests pursuing an anti-apoptotic therapy strategy in the DMM model of OA Early bone sclerotic events suggest bone tissue as a target for anti-OA therapy. Translationally, preventing or delaying OA due to soft tissue injuries (e.g., sports injuries) may be possible with early medical treatment of OA proximal to the time of injury. References (1) International Bone and Joint Decade 2000-2010 Organization, 1999. (2) National Center for Health Statistics, National Health Interview Survey, 2005. (3) Kurtz, SM, Lau, E, et al. Future Young Patient Demand for Primary and Revision Joint Replacement: National Projections from 2010 to 2030. Clinical Orthopaedics and Related Research, April 2009. (4) Kurtz, SM, Ong, K, et. al. Projections of Primary and Revision Hip and Knee Arthroplasty in the United States from 2005 to 2030. The Journal of Bone and Joint Surgery, 2007;89:780-5. (5) http://rsbweb.nih.gov/ij

    Astaxanthin profiles and corresponding colour properties in Australian farmed black tiger prawn (Penaeus monodon) during frozen storage

    Get PDF
    The colour of commercial cooked black tiger prawns (Penaeus monodon) is a key quality requirement to ensure product is not rejected in wholesale markets. The colour, due to the carotenoid astaxanthin, can be impacted by frozen storage, but changes in colour or astaxanthin profile, during frozen storage, have not been studied in detail. Subsequently in this study, the aims were to define the astaxanthin (as cis, trans, mono-ester and di-ester forms) content, together with the colour properties, in both pleopods (legs) and abdominal segments. Changes in astaxanthin content and colour properties were further determined during frozen storage (−20°C). Total astaxanthin content was seen to decrease in all samples over time, with the rate of degradation being significantly greater (P < 0.05) in pleopods than abdomen. In both pleopods and abdomen, rate of degradation of esterified forms was significantly greater (P < 0.05) than non-esterified forms. Hue angle (increase), a* value (decrease) and L value (increase) were all seen to significantly change (P < 0.05) during storage, with changes being more prevalent in the pleopods. The pleopods are the key indicator of astaxanthin and colour loss in cooked black tiger prawns and preservation strategies are required to preserve astaxanthin and colour during frozen storage

    The Varus Knee Reveals Differential Expression Patterns of miRNAs in Spared vs. Non-spared Compartments

    Get PDF
    Introduction MicroRNAs (miRNAs) function by repressing cellular protein levels to provide a sophisticated level of gene regulation that coordinates a broad spectrum of biological processes. MiRNA inhibition of mRNA translation has emerged as an important regulator of chondrogenic and osteogenic development, osteoblast, osteoclast and chondrocyte cell growth and differentiation, and tissue homeostasis in the adult skeleton. MiRNAs control many layers of regulation in adult tissues connected to both normal biological and pathologic cellular activities. The study of miRNAs in skeletal disorders is in its infancy. Osteoarthritis (OA) is a disease that progresses from degeneration of the articular cartilage to remodeling of the underlying subchondral bone over many years. While miRNAs have been identified with the inflammatory pathogenesis of rheumatoid arthritis (RA), only a few studies have been performed on OA tissue (1,2) . Here we performed a systematic analysis of the articular cartilage from varus OA knee replacements, comparing multiple tissue samples from the lateral (spared) and medial (diseased) compartments. Before proceeding to a miRNA profiling, each sample was analyzed for expression of a small set of miRNAs that have been reported in association with RA, OA and cartilage formation. These preliminary findings have identified a spectrum of changes in surface cartilage between control and diseased tissue. Methods Human tissues: 6 individual articular cartilage samples were harvested from a total of 5 osteoarthritic varus human knees. Cartilage samples were exempt from IRB review as they are discarded materials. Samples were removed with a biopsy punch and were approximately 6 x 2mm (diameter x thickness). Cartilage specimens were harvested from the more normal-appearing lateral (‘spared’) compartments and from the more OA-affected, medial compartments of the knees. This sampling technique allows direct comparison of more significantly OA-affected cartilage samples with those of lower OA grade from the same set of individuals. Knee ages ranged from 53-74 years old and averaged 65 years old. RNA and miRNA Isolation: Each osteochondral specimen was placed in RNA Later (Sigma) immediately following surgical removal, in order to preserve the integrity of the total RNA. Specimens were transported to the lab where individual samples were removed carefully with RNase-treated tools and were transferred intofresh RNA Later solution and incubated overnight at 4C to allow penetration and maximal inhibition of RNase activity. Samples were then removed from RNA Later, blotted briefly and frozen in liquid N2, and then pulverized using a Bessman tissue pulverizer (Fisher). The pulverized samples were immediately placed into Trizol (InVitrogen) and homogenized using a polytron device. Total RNA was isolated to include small RNAs of \u3e17 nucleotides, according to the manufacturer’s protocol (InVitrogen). Purified RNA was obtained using precipitated total RNAs filtered through glass columns according to the manufacturer’s protocol (Zymo Research). RNAs were reverse-transcribed into DNA using 900ng of each purified RNA sample using the TaqMan microRNA Reverse Transcription Kit (Applied Biosystems). TaqMan qPCR analysis for small RNAs was performed using the following human primer-probe sets from Applied Biosystems: hsa-miRs-: 9, 22, 27a, 29a and 34a. Human U6 was used to normalize all qPCR data and data was plotted as normalized relative values. Normalized relative values were averaged for each of the complement of medial vs. lateral samples. Results MiRs were found to be either up- or down-regulated in a manner that suggests a mechanism of de-repression of pro-inflammatory cytokine signaling and repression of pro-inflammatory events in medial vs. lateral varus knee OA cartilage samples, respectively. MiRs 9, 27a, and 29a were found to up-regulated in lateral varus knee cartilage samples vs. medial varus knee cartilage samples (Fig.1. A,C,E,F). Conversely, miRs 22 and 34a were found to upregulated in medial vs. lateral cartilage samples (Fig1, B, D). Discussion The functional characterization of global gene expression patterns through miRNAs in OA is lacking. Particularly, the roles of miRs in OA disease development, as biomarkers, and in disease outcomes are at question. A few large-scale microarray approaches have previously identified expression signatures of potential OA-involved miRNAs (2). By comparing cartilage samples that derive from more advanced (medial) vs. less advanced (lateral) OA stages in varus human knees, we seek to combine miRNA expression analysis with clinicopathologic features. MiRs -9, -22 and -34a are known to be involved in regulating pro-inflammatory events in OA. Higher levels of miRs, -9, -27a & -140 in less-affected lateral compartment cartilage are consistent with previous reports of reduced TNFa, MMP-13 & ADAMTS-5 expression events, respectively (Fig.1, F, E & A) (3,4,5). MiRs -22 and -34a have been shown to be associated with promoting tissue catabolism by their presence and are here shown to be increased in more affected medial compartment cartilage (Fig.1, B, D) (4). In addition, miR-34a deficiency has been previously shown to inhibit chondrocyte apoptosis, consistent with the lower expression level found in lateral cartilage (Fig.1, D) (6). MiR-29a was found in a previous microarray analysis to be the highest-fold down-regulated miRNA in OA vs. normal cartilage, consistent with our finding of under-expression in medial cartilage samples (Fig.1, C) (1). The goal of these studies is to begin to understand how miRNAs can both contribute to and protect against OA. Here we show that the comparison of cartilage-derived miRNAs in medial and lateral compartment pairs from the same knee may facilitate validation of candidate OA miRNAs. Significance The aims of this project are to provide an internally-controlled platform of study for the miRNAs of OA using the natural disease differences inherent in spared vs. non-spared cartilage compartments from a varus OA knee. Such efforts may provide an alternative methodology when compared to the significant barrier of obtaining age-matched, non-OA control knee cartilage. References 1.) Iliopoulus D. PLoS One. 2008;3(11):e3740. Epub 2008 Nov 17. 2.) Goldring MB. Curr Opin Rheumatol. 2011 Jul 22. [Epub]. 3.) Yu C. J Int Med Res. 2011;39(1):1-9. 4.) Alcaraz MJ. Biochem Pharmacol. 2010 Jul 1;80(1):13-21. 5.) Miyaki S. Genes Dev. 2010 Jun 1;24(11):1173-85. 6.) Abouheif MM. Rheumatology. 2010 Nov;49(11):2054-60

    Annual Bands in Vertebrae Validated by Bomb Radiocarbon Assays Provide Estimates of Age and Growth of Whale Sharks

    Get PDF
    Publisher's version (Ăștgefin grein)Conservation and management strategies for endangered and threatened species require accurate estimates of demographic parameters such as age and growth. The whale shark, Rhincodon typus, is the largest fish in the world and is highly valued in the eco-tourism sector. Despite conservation concerns and advances in our understanding of their life history, basic demographic parameters for growth, longevity and mortality are of questionable accuracy; previous growth studies could not agree whether the vertebral growth bands were formed annually or biannually. Here, we provide the first validation of the annual formation of growth bands within the vertebrae of the whale shark using bomb radiocarbon assays. Ages of up to 50 years were estimated from sectioned vertebrae of sharks collected in Taiwan and Pakistan. There was no cessation of the formation of growth bands in the vertebrae of older sharks and our study provides the oldest observed longevity for this species. Initial estimates of growth (k = 0.01–0.12) and natural mortality rates (M = 0.09–0.14) are consistent with those expected of long-lived sharks, which highlights their sensitivity to fishing pressure and conservation concerns.This work was supported by the Fisheries and Oceans Canada, US National Science Foundation Grant OCE-9985884, and the University of Iceland. Travel funding was provided by the Australian Institute of Marine Science.Peer Reviewe

    1946: Abilene Christian College Bible Lectures - Full Text

    Get PDF
    Abilene Christian College Lectures - 1946 INTRODUCTION It has been our purpose at Abilene Christian College down through the years to provide in the Annual Bible Lectureship programs that which would be appropriate for the time and most useful to the students and to the Lectureship visitors. The general subject for the 1946 lectures is “Things That Cannot Be Shaken.” This subject was selected because one of the battles, if not the battle, which the church faces today is against those forces which would undermine the bases of gospel truth. Many denominational leaders, in one way or another, are denying even the fundamentals of fundamentals— God is, the Bible is God\u27s Revelation, Jesus Christ is the Son of God and The Kingdom Cannot Be Shaken. Many others, some without knowing what they do, are accepting false teachings and ideologies which, if allowed to run their course, will destroy all true religion. It is believed that the 1946 lectures and this edition of the lectures will help toward establishing in the hearts of men the truth of the important theses discussed. It was the purpose of those who arranged the program that the Lectureship should, also, hold up Christianity as a working, practical religion; hence, the meetings on “Work in New Fields” and “The Church at Work.” The attendance of this Lectureship was the largest in the history of these yearly meetings. On Wednesday evening Brother Nichol spoke to a crowd of approximately 1700 persons. Other evening lectures were attended by crowds almost as large. Visitors came from more than a score of States and, also, from Canada and Mexico. It is the hope of all of us at the College that the fellowship of the 1946 Lectureship and the instruction given by the various speakers will continue to do good for years without end. DON H. MORRIS

    Sedentary time in older men and women: an international consensus statement and research priorities

    Get PDF
    Sedentary time is a modifiable determinant of poor health, and in older adults, reducing sedentary time may be an important first step in adopting and maintaining a more active lifestyle. The primary purpose of this consensus statement is to provide an integrated perspective on current knowledge and expert opinion pertaining to sedentary behaviour in older adults on the topics of measurement, associations with health outcomes, and interventions. A secondary yet equally important purpose is to suggest priorities for future research and knowledge translation based on gaps identified. A five-step Delphi consensus process was used. Experts in the area of sedentary behaviour and older adults (n=15) participated in three surveys, an in-person consensus meeting, and a validation process. The surveys specifically probed measurement, health outcomes, interventions, and research priorities. The meeting was informed by a literature review and conference symposium, and it was used to create statements on each of the areas addressed in this document. Knowledge users (n=3) also participated in the consensus meeting. Statements were then sent to the experts for validation. It was agreed that self-report tools need to be developed for understanding the context in which sedentary time is accumulated. For health outcomes, it was agreed that the focus of sedentary time research in older adults needs to include geriatric-relevant health outcomes, that there is insufficient evidence to quantify the dose-response relationship, that there is a lack of evidence on sedentary time from older adults in assisted facilities, and that evidence on the association between sedentary time and sleep is lacking. For interventions, research is needed to assess the impact that reducing sedentary time, or breaking up prolonged bouts of sedentary time has on geriatric-relevant health outcomes. Research priorities listed for each of these areas should be considered by researchers and funding agencies

    The presence of Aspergillus fumigatus in asthmatic airways is not clearly related to clinical disease severity

    Get PDF
    Background: It is suggested that airway fungi, in particular Aspergillus may impinge on clinical phenotype in asthma. Indeed, the term severe asthma with fungal sensitization (SAFS) has been coined. We aimed to ascertain whether the presence of fungi, in particular Aspergillus fumigatus, in the airway correlated with asthma severity and control. Furthermore, we aimed to determine whether traditional markers of Aspergillus sensitization related to the presence of Aspergillus within the airway. Methods: Sixty‐nine patients characterized by asthma severity (GINA) and level of control (ACQ‐7) underwent bronchoscopy and bronchoalveolar lavage (BAL). Serum was assessed for A fumigatus‐specific IgE and total IgE. Galactomannan and relevant cytokine levels were assessed in serum, plasma and BAL. BAL was analyzed for the presence of A fumigatus. Results: In BAL, fungi were visible by microscopy in 70% and present by qPCR in 86% of patients, while A fumigatus was detectable by qPCR in 46%. Plasma and BAL IL‐4, IL‐6, IL‐10, IL‐13 and TNF‐α correlated with BAL fungal presence, while plasma IL‐17 correlated with BAL fungal presence. Aspergillus positive BAL correlated with increased plasma and BAL IL‐6 and BAL IL‐13. There was no relationship between fungal airway presence and steroid dose, asthma severity or control. The presence of Aspergillus within the airway did not relate to serum IgE positivity for Aspergillus. Conclusions: Fungi were present in a large proportion of our asthmatic patients’ airways, but their presence was not predicted by traditional markers of sensitization, nor did it appear to be related to measures of disease severity or control
    • 

    corecore