Long Term Effect of P188 on Meniscus Preservation Following Blunt Trauma

2012 ◽  
Author(s):  
Adam C. Abraham ◽  
Megan L. Killian ◽  
Roger C. Haut ◽  
Tammy L. Haut Donahue
Keyword(s):  
Cell Death ◽  
Articular Cartilage ◽  
Early Stage ◽  
Subsequent Treatment ◽  
Joint Injury ◽  
Secondary Osteoarthritis ◽  
Tissue Degeneration ◽  
Long Term Effect ◽  
Tissue Matrix

Acute knee joint injury has been associated with the development and progression of secondary osteoarthritis (OA). Previous work implicates that acute damage to tissue matrix and cells of the meniscus and articular cartilage may play important roles in early-stage OA [1]. Additionally, it has been shown that articular cartilage matrix repair hinges on chondrocyte preservation [2]. Therefore, inhibition of cell death may halt tissue degeneration. Recently, the FDA-approved surfactant Poloxamer 188 (P-188) has been shown to decrease acute cell death by repair of its plasma membrane, as well as mediate p38 signaling and subsequent inflammatory and apoptotic signaling leading to a reduction in degeneration of impacted cartilage [3, 4]. Therefore, it was hypothesized that matrix glycosaminoglycans of the meniscus will be preserved in the long-term following traumatic impaction and subsequent treatment with P-188.

Functionally Graded Dental Implant and its Effect on Bone Remodeling

2008 ◽  
Vol 47-50 ◽  
pp. 1035-1038 ◽  
Author(s):  
Daniel Lin ◽  
Qing Li ◽  
Wei Li ◽  
Michael V. Swain
Keyword(s):  
Dental Implant ◽  
Bone Remodelling ◽  
Early Stage ◽  
Titanium Implant ◽  
Functionally Graded ◽  
Critical Problem ◽  
Long Term Effect ◽  
Graded Material ◽  
Bio Compatibility

Currently, titanium dominates the dental implant materials due to its strength and bio-inerrability. The use of titanium implant had demonstrated considerable surgical success. However, researchers are spontaneously pursuing better materials to achieve better osseointegration in the early stage of implantation. Recently, dental implants based on functionally graded material (FGM) were introduced in pursuit for the goal of enhanced bio-compatibility. The concept for FGM dental implant is that the property would vary in certain pattern to match the biomechanical characteristics required at different regions in the oral bone. However, mating properties do not necessarily guarantee better osseointegration and bone remodelling. There is no existing report available on the long-term effect of FGM dental implant on its hosting bone tissues. This paper aims at exploring this critical problem by using computational bone remodelling technique. The magnitude of bone remodelling due to use of FGM implant is identified over a healing period of four years. Comparisons were made between titanium and various FGM designs, the interesting differences were observed and the optimum FGM design was suggested based on the remodelling results.

scholarly journals A Reachable Governance to Fight COVID-19: Democracy and the Legacy of Embedded Autonomy in Taiwan

2020 ◽  
Vol 5 (3) ◽  
pp. 18
Author(s):  
Peters Li-ying Chen
Keyword(s):  
Political Theory ◽  
Political System ◽  
Early Stage ◽  
Developmental State ◽  
Effective Response ◽  
Democratic State ◽  
Long Term Effect ◽  
Embedded Autonomy ◽  
Democratic Country

Different country showed different governing capacity to the COVID-19 pandemic in 2020. With reference to the classical concept of embedded autonomy, as used in developmental state of political theory, this paper aims to study the capacity and progression of democratic country, Taiwan, in its fight with the emergence of the COVID-19 pandemic and how democratic state, civil society and bureaucrats have affected the response and measures. Taiwan’s case provides a valuable empirical contribution to the understanding of the long term effect of embedded autonomy in a democratic country. This study argues that democracy does matter to fight Covid-19 pandemic, moreover, the legacy of embedded autonomy can be expanded beyond economic development, and successfully used to explain Taiwan’s capacity to fight the COVID-19 pandemic in its early stage. Key observations and discussion addressed in this study includes, first, the extent to which the concept of embedded autonomy is applicable in evaluating and in shaping Taiwan’s efforts to manage the pandemic; second, the extent to which the political system is better at managing COVID-19 crisis by comparing democratic Taiwan and authoritarian China. A central finding of this paper is that, democracy has proven it has the edge in coping with COVID-19 pandemic practically. Theoretically, Taiwan’s case demonstrates a valuable and supplementary example to Evans and Heller (2018) on their broadening view of embedded autonomy. The legacy of the developmental state is applicable to explain Taiwan’s immediate and effective response to the COVID-19 outbreak. A reachable governance to fight COVID-19 lies in ‘the nature of democracy’ and ‘the legacy of embedded autonomy’.

Long-term effect of barotropic instability across the moat in double-eyewall tropical cyclone-like vortices in forced and unforced shallow-water models

2021 ◽  
Author(s):  
Tsz-Kin Lai ◽  
Eric A. Hendricks ◽  
M. K. Yau
Keyword(s):  
Shallow Water ◽  
Early Stage ◽  
Term Effect ◽  
Substantial Contribution ◽  
Barotropic Instability ◽  
Secondary Eyewall Formation ◽  
Long Term Effect ◽  
Intensity Changes

AbstractSecondary eyewall formation and the ensuing eyewall replacement cycles may take place in mature tropical cyclones (TCs) during part of their lifetime. A better understanding of the underlying dynamics is beneficial to improving the prediction of TC intensity and structure. Previous studies suggested that the barotropic instability (BI) across the moat (a.k.a. type-2 BI) can make a substantial contribution to the inner eyewall decay through the associated eddy radial transport of absolute angular momentum (AAM). Simultaneously, the type-2 BI can also increase the AAM of the outer eyewall. While the previous studies focused on the early stage of the type-2 BI, this paper explores the long-term effect of the type-2 BI and the underlying processes in forced and unforced shallow water experiments. Under the long-term effect, it will be shown that the inner eyewalls repeatedly weaken and strengthen (while the order is reversed for the outer eyewalls). Sensitivity tests are conducted to examine the sensitivity of the long-term effect of the type-2 BI to different vortex parameters and the strength of the parameterised diabatic heating. Implication of the long-term effect for the intensity changes of the inner and outer eyewalls of real TCs are also discussed.

scholarly journals Altered swelling and ion fluxes in articular cartilage as a biomarker in osteoarthritis and joint immobilization: a computational analysis

2015 ◽  
Vol 12 (102) ◽  
pp. 20141090 ◽  
Author(s):  
Sara Manzano ◽  
Raquel Manzano ◽  
Manuel Doblaré ◽  
Mohamed Hamdy Doweidar
Keyword(s):  
Articular Cartilage ◽  
Computational Model ◽  
Three Dimensional ◽  
Ion Distribution ◽  
Tissue Degeneration ◽  
Structural Deterioration ◽  
Healthy Cartilage ◽  
Tissue Degradation

In healthy cartilage, mechano-electrochemical phenomena act together to maintain tissue homeostasis. Osteoarthritis (OA) and degenerative diseases disrupt this biological equilibrium by causing structural deterioration and subsequent dysfunction of the tissue. Swelling and ion flux alteration as well as abnormal ion distribution are proposed as primary indicators of tissue degradation. In this paper, we present an extension of a previous three-dimensional computational model of the cartilage behaviour developed by the authors to simulate the contribution of the main tissue components in its behaviour. The model considers the mechano-electrochemical events as concurrent phenomena in a three-dimensional environment. This model has been extended here to include the effect of repulsion of negative charges attached to proteoglycans. Moreover, we have studied the fluctuation of these charges owning to proteoglycan variations in healthy and pathological articular cartilage. In this sense, standard patterns of healthy and degraded tissue behaviour can be obtained which could be a helpful diagnostic tool. By introducing measured properties of unhealthy cartilage into the computational model, the severity of tissue degeneration can be predicted avoiding complex tissue extraction and subsequent in vitro analysis. In this work, the model has been applied to monitor and analyse cartilage behaviour at different stages of OA and in both short (four, six and eight weeks) and long-term (11 weeks) fully immobilized joints. Simulation results showed marked differences in the corresponding swelling phenomena, in outgoing cation fluxes and in cation distributions. Furthermore, long-term immobilized patients display similar swelling as well as fluxes and distribution of cations to patients in the early stages of OA, thus, preventive treatments are highly recommended to avoid tissue deterioration.

Mechanical Chondrocyte Damage Thresholds

2012 ◽  
Author(s):  
Mark C. van Turnhout ◽  
Stefan A. H. de Vries ◽  
Corrinus C. van Donkelaar ◽  
Cees W. J. Oomens
Keyword(s):  
Cell Death ◽  
Articular Cartilage ◽  
Mechanical Loading ◽  
Early Stage ◽  
Cartilage Degeneration ◽  
Chondrocyte Apoptosis ◽  
Tissue Volume ◽  
Mechanical Thresholds

Chondrocyte content in articular cartilage is very low. Only 2% to 5% of the tissue volume consists of chondrocytes [1]. Yet, these cells are responsible for maintenance of the tissue. Hence, the loss of chondrocytes that is often occurring at an early stage of cartilage degeneration is detrimental to articular cartilage. Excessive mechanical loading is known to be a cause of cell death. However, mechanical thresholds beyond which chondrocyte apoptosis would be induced are unknown.

scholarly journals Experimental Study on Creep Characteristics of Microdefect Articular Cartilages in the Damaged Early Stage

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Huchen Gong ◽  
Yutao Men ◽  
Xiuping Yang ◽  
Xiaoming Li ◽  
Chunqiu Zhang
Keyword(s):  
Articular Cartilage ◽  
Damage Evolution ◽  
Early Stage ◽  
Image Correlation ◽  
Defect Depth ◽  
Cartilage Sample ◽  
Joint Injury ◽  
Creep Characteristics ◽  
Creep Curves ◽  
Articular Cartilages

Traumatic joint injury is known to cause cartilage deterioration and osteoarthritis. In order to study the mechanical mechanism of damage evolution on articular cartilage, taking the fresh porcine articular cartilage as the experimental samples, the creep experiments of the intact cartilages and the cartilages with different depth defect were carried out by using the noncontact digital image correlation technology. And then, the creep constitutive equations of cartilages were established. The results showed that the creep curves of different layers changed exponentially and were not coincident for the cartilage sample. The defect affected the strain values of the creep curves. The creep behavior of cartilage was dependent on defect depth. The deeper the defect was, the larger the strain value was. The built three-parameter viscoelastic constitutive equation had a good correlation with the experimental results and could predict the creep performance of the articular cartilage. The creep values of the microdefective cartilage in the damaged early stage were different from the diseased articular cartilage. These findings pointed out that defect could accelerate the damage of cartilage. It was helpful to study the mechanical mechanism of damage evolution.

scholarly journals Efficacy and safety of stem cell therapy for the early-stage osteonecrosis of femoral head: a systematic review and meta-analysis of randomized controlled trials

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Lianghao Mao ◽  
Pan Jiang ◽  
Xuan Lei ◽  
Chenlie Ni ◽  
Yiming Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Femoral Head ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Hip Replacement ◽  
Early Stage ◽  
Cell Number ◽  
Long Term Effect

Abstract Background Osteonecrosis of femoral head (ONFH) is a seriously degenerative disease with no effective therapies to slow its progression. Several studies have reported short-term efficacy of stem cells on early-stage ONFH. However, its long-term effect was still unclear especially on progression events. This study was performed to evaluate the long-term efficacy and safety of stem cells and analyze its optimal age group and cell number. Methods Our review was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42020136094. Following PRISMA guideline, we searched 8 electronic databases on January 5, 2020, and rigorous random controlled trials (RCTs) utilizing stem cell therapy on early-stage ONFH were included. Quality and bias were analyzed. Pooled analysis was performed to assess difference between various outcomes. Results A total of 13 RCTs (619 patients with 855 hips) were included. The application of stem cells significantly delayed collapse of femoral head(I2, 70%; RR, 0.54; 95% CI, 0.33 to 0.89; P < .00001) and total hip replacement (THR) (I2, 68%; RR, 0.55; 95% CI, 0.34 to 0.90; P = .02) in the long term. It effectively decreased the events of collapse of femoral head (≥ 60 months) (I2, 0%; RR, 0.37; 95% CI, 0.28 to 0.49; P < .00001) and THR (> 36 months) (I2, 0%; RR, 0.32; 95% CI, 0.23 to 0.44; P < .00001). There existed a beneficial effect for patients under 40 (Collapse of femoral head: I2, 56%; RR, 0.41; 95% CI, 0.23 to 0.76; P = .004) (THR: I2, 0%; RR, 0.31; 95% CI, 0.23 to 0.42; P < .00001). In addition, quantity of stem cells at 108 magnitude had better effects on disease progression events (I2, 0%; RR, 0.34; 95%CI, 0.16 to 0.74; P = .007). Besides, there were no significant differences on adverse events between the stem cell group and control group (I2, 0%; RR, 0.82; 95% CI, 0.39 to 1.73; P = .60). Conclusion Our findings build solid evidence that stem cell therapy could be expected to have a long-term effect on preventing early-stage ONFH patients from progression events, such as collapse of femoral head and total hip replacement. Furthermore, patients under 40 may be an ideal age group and the optimal cell number could be at 108 magnitude for this therapy. Further studies including strict RCTs are required to evaluate a clear effect of stem cells on ideal patient profile and the procedures of implantation.

P188 Reduces Cell Death and IGF-I Reduces GAG Release Following Single-Impact Loading of Articular Cartilage

2008 ◽  
Vol 130 (4) ◽  
Author(s):  
Roman M. Natoli ◽  
Kyriacos A. Athanasiou
Keyword(s):  
Mechanical Properties ◽  
Cell Death ◽  
Articular Cartilage ◽  
High Impact ◽  
Individual Treatment ◽  
Joint Injury ◽  
Bovine Articular Cartilage ◽  
Treatment Type ◽  
Igf I ◽  
High Level

Prior joint injury predisposes an individual to developing post-traumatic osteoarthritis, for which there is presently no disease modifying treatment. In this condition, articular cartilage degenerates due to cell death and matrix breakdown, resulting in tissue with diminished biomechanical function. P188, a nonionic surfactant, and the growth factor IGF-I have been shown to decrease cell death. Additionally, IGF-I is known to have beneficial effects on cartilage matrix. The objective of this study was to determine the efficacy of P188, IGF-I, and their combination following articular cartilage impact injury with two energy levels, 1.1J (“low”) and 2.8J (“high”), at 24h and 1week. Bovine articular cartilage with attached underlying bone was impacted at the low or high level. Impact sites were explanted and examined immediately, or cultured for 24h or 1week in serum-free media supplemented with P188 (8mg∕ml), IGF-I (100ng∕ml), or their combination. Gross morphology, cell viability, GAG release to the media, and tissue mechanical properties were assessed. Immediately postimpact, high level impacted tissue had significantly increased gross morphology scores, indicating tissue damage, which were maintained over 1week. Gross scores following low impact were initially similar to nonimpacted controls, but, at 24h and 1week, low impact gross scores significantly increased compared to nonimpacted controls. Additionally, at 24h, high impact resulted in increased cell death, and both low and high impacts had increased GAG release compared to nonimpacted controls. Furthermore, high impact caused decreased tissue stiffness at 24h that appeared to worsen over 1week, evident by the percent decrease from nonimpacted controls increasing from 16% to 26%. No treatment type studied mitigated this loss. The combination did not perform better than either individual treatment; however, following low impact at 1week, P188 reduced cell death by 75% compared to no treatment and IGF-I decreased GAG release from the tissue by 49%. In conclusion, high impact resulted in immediate tissue changes that worsened over 1week. Though not causing immediate changes, low impact also resulted in tissue degeneration evident by 24h. No treatment studied was effective at 24h, but by 1week P188 and IGF-I ameliorated established detrimental changes occurring in articular cartilage postimpact. However, further work is needed to optimize treatment strategies to prevent and/or reverse cell death and matrix destruction in a way that maintains tissue mechanical properties, and hence its functionality.

Sign in / Sign up

Export Citation Format

Share Document