Effects Of Drugs On Osteoarthrosis
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Effects Of Drugs On Osteoarthrosis
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Author : Eimar Munthe
language : en
Publisher: Hogrefe & Huber Publishing
Release Date : 1984
Effects Of Drugs On Osteoarthrosis written by Eimar Munthe and has been published by Hogrefe & Huber Publishing this book supported file pdf, txt, epub, kindle and other format this book has been release on 1984 with Medical categories.
Effects Of Drugs On Osteoarthrosis
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Author :
language : en
Publisher:
Release Date : 1984
Effects Of Drugs On Osteoarthrosis written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1984 with categories.
Osteoarthritis
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Author : Mohit Kapoor
language : en
Publisher: Springer
Release Date : 2015-07-20
Osteoarthritis written by Mohit Kapoor and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-07-20 with Medical categories.
This comprehensive book grants readers exclusive insight into current advancements in the field of osteoarthritis (OA). Contributions from leading scientists and clinicians provide a detailed introduction into current understanding of the pathogenesis of OA, different joint structures affected by this debilitating disease (hip, knee, elbow, shoulder, foot, ankle, hand, wrist, and spine), current knowledge and practice in imaging, joint conservative strategies, OA biomarkers as well as currently available treatments, their safety profile and future therapeutic targets. This book further discusses the potential of regenerative therapies and recent advances in OA Personalized Medicine, and how collection of OA patient’s phenotypic, genetic and proteomic data is able to direct treatment strategies through Bio-Informatics.
Intra Extracellular Multi Drug Delivery For Osteoarthritis
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Author : Yamini Krishnan (Ph. D.)
language : en
Publisher:
Release Date : 2020
Intra Extracellular Multi Drug Delivery For Osteoarthritis written by Yamini Krishnan (Ph. D.) and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020 with categories.
Osteoarthritis (OA), the most common form of arthritis, affects hundreds of millions of people worldwide and tens of millions of people within the United States. This disease is typically diagnosed only after extensive and irreparable damage to the joints. There are currently no clinically effective disease modifying drugs that can slow or stop disease progression. While cartilage degeneration is the hallmark of OA, there is increasing recognition that OA is a disease of the whole joint, and multiple joint tissues contribute to disease progression. Due to the complex pathogenic processes that involve interactions between different joint tissues, a successful disease modifying therapy will likely require treatment with multiple drugs, each having a different target. While several disease modifying drug candidates have shown promise in disease models both in vitro and in vivo, delivering these drugs effectively and with minimal side effects remains challenging. Cartilage does not have a blood supply, which decreases the efficacy of systemic drug administration methods. In intra-articular injections, drugs are directly injected into the affected joints. But any drugs injected into the joint are rapidly cleared out by the joint capsule over the span of a few hours to a day. As a result, there is limited drug penetration into cartilage. Frequent injections with high drug doses can overcome this challenge, but such a treatment would lead to undesirable systemic side effects and increase the risk of infections within the joint. Recent prior work in our lab has demonstrated that positively charged drug delivery carriers can bind to negatively charged extracellular matrix components in cartilage and thereby improve drug uptake and retention. In this thesis, we characterized the effect of varying the charge of drug delivery carriers on their uptake and penetration into human and bovine cartilage tissues and cells. We identified optimally charged carriers that can be used to deliver drugs to extracellular or intracellular targets. We successfully used these carriers to provide sustained and targeted delivery of growth factors to full-thickness human cartilage explants in vitro, and developed a mathematical model that predicts in vivo transport behavior in human knee joints. We further established an in vitro cartilage-synovium co-culture model that captures physiologically relevant tissue interactions that contribute to OA progression. We also tested drugs targeting inflammatory pathways in this co-culture model, and the results provide a starting point for developing a combination therapy of growth factors and anti-inflammatory drugs conjugated to optimally charged carriers. This thesis is organized as follows: Chapter 1 provides a broad overview of different diseases affecting cartilage, including osteoarthritis. In Chapter 2, we used engineered green fluorescent proteins (GFPs) with a range of net positive charges and surface charge distributions to characterize the effects of charge on carrier transport in cartilage. In both bovine and human cartilage, the uptake of GFPs into cartilage tissue explants decreased with increasing net charge. In contrast, cellular uptake of GFPs increased with increasing charge. Experiments with three neutrally charged GFP variants demonstrated that the surface charge distribution of the carrier also plays an important role in determining its transport properties. Based on the results of this study, we identified optimally charged GFP carriers for delivering drugs to extracellular matrix or cell-surface targets, as well as to intracellular targets. In Chapter 3, we tested the delivery of Insulin-like growth factor 1 (IGF-1), a proanabolic drug, using engineered GFP carriers. Since the target for IGF-1 is the extracellular domain of a cell-surface receptor, and a cationic GFP variant with a net charge of +9 (abbreviated as +9 GFP) was found to be optimal for extracellular targets, we designed, expressed and purified fusion proteins of IGF-1 with +9 GFP. Five fusion protein variants had flexible or rigid polypeptide linkers of different sizes connecting the IGF-1 and +9 GFP domains. A sixth fusion protein with no linker was also synthesized. Single doses of two of the fusion proteins had sustained IGF-1 bioactivity in both normal and cytokine-treated human cartilage explants for 7 to 10 days. These fusion proteins increased sGAG biosynthesis rates in normal cartilage and rescued the loss of sGAG biosynthesis in cytokine-treated cartilage, but could not rescue the increase in cumulative sGAG loss caused by cytokine treatments. These responses are consistent with the effects of free IGF- 1 in human cartilage explant cultures. However, the main difference is that free IGF-1 needs to be continuously replenished to achieve these effects, whereas a single dose at the start of the experiments was sufficient for the fusion proteins. All of the experimental work in this thesis was performed using in vitro cartilage explant cultures. In order to successfully translate these results to preclinical and clinical studies, it is important to predict the transport behavior of GFP carriers and carrier-drug conjugates once they are injected into the joints. In Chapter 4, we developed a mathematical transport model and fit model predictions to data from in vitro dynamic uptake experiments to estimate the transport properties of engineered GFPs and GFP-IGF-1 fusion proteins in cartilage. This model was then used to predict the concentration of GFPs and GFP-IGF fusion proteins in synovial fluid and inside human knee cartilage in an intact knee joint as a function of time after intra-articular injection. The model predicted that significant amounts of the injected molecules could quickly penetrate cartilage tissue before being cleared out by the joint capsule. These cartilage concentration predictions will enable the estimation of injection doses that can achieve appropriate drug doses within cartilage. Additionally, the model also predicts the amount of GFPs and GFP-IGF fusion proteins that are cleared out into the systemic circulation by the joint capsule. These predictions will be useful in assessing the likelihood of potential systemic side effects and estimating safe injection doses. In Chapter 5, we established an in vitro model of post-traumatic osteoarthritis (PTOA) in which cartilage and synovium explants were cultured together. In these experiments, the injury caused by cutting synovium explants triggered the release of large quantities of cytokines. In both human and bovine co-cultures, the cytokine levels were comparable to those observed clinically in the days and weeks following a traumatic joint injury. Cytokine and chemokine levels in co-culture decreased with time, which is also similar to clinical observations. Co-culture with synovium led to significant decreases in the sGAG biosynthesis rate, explant sGAG content, explant metabolic rate and cell viability in cartilage explants. There were no changes in the sGAG (sulfated glycosaminoglycan) biosynthesis rate or explant sGAG content of human cartilage explants that were co-cultured with synovium over the 2-week duration of the experiments. In chapter 6, we tested toll-like receptor (TLR) inhibitors and MAPK pathway inhibitors in the human cartilage-synovium co-culture system. In experiments with tissues from two human donors, treatment with these inhibitors decreased the levels of cytokines and chemokines released by synovium. Future directions could include further characterization with multiple donor tissues (in order to account for donor-to-donor variability), and conjugating the inhibitors to optimally charged GFPs for combination therapy with GFP-IGF fusion proteins.
Osteoarthritis
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Author : J.-Y. Reginster
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
Osteoarthritis written by J.-Y. Reginster and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Medical categories.
Musculoskeletal diseases are rapidly becoming a major health concern. The incidence of osteoarthritis, the most common arthritic disorder, is increasing steadily due to the graying of the world population. This disease is responsible of human life, a time in for significant morbidity, particularly in the second half which the quality of life is of primary importance. The aim of this publication is to bring to physicians and scientists a comprehensive overview of the field, from molecules to men. The direct costs related to osteoarthritis have been increasing steadily over the years and will soon be comparable to those of other major illnesses, such as cardiovascular diseases. This, of course, does not take into account all of the other costs related to the disease which often cannot be simply calculated in dollars and cents. There has been a great deal of renewed interest in osteoarthritis in the last few decades. This has been brought on by the need to improve our knowledge of all aspects of the disease, especially with regard to its etiopathogenesis and treatment. The most recent findings and developments on the structural, bio chemical, biomechanical and molecular changes observed in clinical and ex perimental osteoarthritis are presented in this book.
Mayo Clinic On Arthritis
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Author : Gene G. Hunder
language : en
Publisher:
Release Date : 1999
Mayo Clinic On Arthritis written by Gene G. Hunder and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999 with Family & Relationships categories.
Covers the causes and symptoms of arthritis; offers tips on pain control, diet, and exercise; and describes such treatment options as medications, surgical procedures, and alternative therapies.
Selected Health Conditions And Likelihood Of Improvement With Treatment
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Author : National Academies of Sciences, Engineering, and Medicine
language : en
Publisher: National Academies Press
Release Date : 2020-07-12
Selected Health Conditions And Likelihood Of Improvement With Treatment written by National Academies of Sciences, Engineering, and Medicine and has been published by National Academies Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-07-12 with Medical categories.
The Social Security Administration (SSA) administers two programs that provide disability benefits: the Social Security Disability Insurance (SSDI) program and the Supplemental Security Income (SSI) program. SSDI provides disability benefits to people (under the full retirement age) who are no longer able to work because of a disabling medical condition. SSI provides income assistance for disabled, blind, and aged people who have limited income and resources regardless of their prior participation in the labor force. Both programs share a common disability determination process administered by SSA and state agencies as well as a common definition of disability for adults: "the inability to engage in any substantial gainful activity by reason of any medically determinable physical or mental impairment which can be expected to result in death or which has lasted or can be expected to last for a continuous period of not less than 12 months." Disabled workers might receive either SSDI benefits or SSI payments, or both, depending on their recent work history and current income and assets. Disabled workers might also receive benefits from other public programs such as workers' compensation, which insures against work-related illness or injuries occurring on the job, but those other programs have their own definitions and eligibility criteria. Selected Health Conditions and Likelihood of Improvement with Treatment identifies and defines the professionally accepted, standard measurements of outcomes improvement for medical conditions. This report also identifies specific, long-lasting medical conditions for adults in the categories of mental health disorders, cancers, and musculoskeletal disorders. Specifically, these conditions are disabling for a length of time, but typically don't result in permanently disabling limitations; are responsive to treatment; and after a specific length of time of treatment, improve to the point at which the conditions are no longer disabling.
Total Knee Arthroplasty
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Author : James Alan Rand
language : en
Publisher: Lippincott Williams & Wilkins
Release Date : 1993
Total Knee Arthroplasty written by James Alan Rand and has been published by Lippincott Williams & Wilkins this book supported file pdf, txt, epub, kindle and other format this book has been release on 1993 with Medical categories.
This comprehensive reference on total knee arthroplasty describes all surgical techniques and prosthetic designs for primary and revision arthroplasty, discusses every aspect of patient selection, preoperative planning, and intraoperative and postoperative care.
Bone And Osteoarthritis
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Author : Felix Bronner
language : en
Publisher: Springer Science & Business Media
Release Date : 2007-09-26
Bone And Osteoarthritis written by Felix Bronner and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007-09-26 with Medical categories.
The molecular and cellular approaches to the relationship of joint and bone problems distinguish this from other books on the topic. Advances in bone and joint biology enable practitioners to approach clinical problems more comprehensively. Emphasis on genetics and on newer viewpoints and approaches, exemplified by the possible effect of subchondral bone on osteoarthritis, gives a wider viewpoint to the reader and may enable novel approaches to solving a clinical problem.
Advances In The Canine Cranial Cruciate Ligament
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Author : Peter Muir
language : en
Publisher: John Wiley & Sons
Release Date : 2017-11-10
Advances In The Canine Cranial Cruciate Ligament written by Peter Muir and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-11-10 with Medical categories.
Advances in the Canine Cranial Cruciate Ligament, Second Edition presents in-depth, focused, and updated coverage of current knowledge on cruciate ligament rupture, using a multidisciplinary, evidence-based approach. Presents a state-of-the-art summary of the most recent knowledge on this important cause of lameness in dogs Led by a highly respected surgeon and researcher, with chapters written by leading experts in the field Provides an update to the groundbreaking first edition, with six new chapters