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1
Cornelis, Frederique M. F., Silvia Monteagudo, Laura-An K. A. Guns, Wouter den Hollander, Rob G. H. H. Nelissen, Lies Storms, Tine Peeters, Ilse Jonkers, Ingrid Meulenbelt, and Rik J. Lories. "ANP32A regulates ATM expression and prevents oxidative stress in cartilage, brain, and bone." Science Translational Medicine 10, no. 458 (September 12, 2018): eaar8426. http://dx.doi.org/10.1126/scitranslmed.aar8426.
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Osteoarthritis is the most common joint disorder with increasing global prevalence due to aging of the population. Current therapy is limited to symptom relief, yet there is no cure. Its multifactorial etiology includes oxidative stress and overproduction of reactive oxygen species, but the regulation of these processes in the joint is insufficiently understood. We report that ANP32A protects the cartilage against oxidative stress, preventing osteoarthritis development and disease progression. ANP32A is down-regulated in human and mouse osteoarthritic cartilage. Microarray profiling revealed that ANP32A protects the joint by promoting the expression of ATM, a key regulator of the cellular oxidative defense. Antioxidant treatment reduced the severity of osteoarthritis, osteopenia, and cerebellar ataxia features in Anp32a-deficient mice, revealing that the ANP32A/ATM axis discovered in cartilage is also present in brain and bone. Our findings indicate that modulating ANP32A signaling could help manage oxidative stress in cartilage, brain, and bone with therapeutic implications for osteoarthritis, neurological disease, and osteoporosis.
2
De Francesco, Francesco, Pasquale Gravina, Alice Busato, Luca Farinelli, Carlo Soranzo, Luis Vidal, Nicola Zingaretti, et al. "Stem Cells in Autologous Microfragmented Adipose Tissue: Current Perspectives in Osteoarthritis Disease." International Journal of Molecular Sciences 22, no. 19 (September 22, 2021): 10197. http://dx.doi.org/10.3390/ijms221910197.
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Osteoarthritis (OA) is a chronic debilitating disorder causing pain and gradual degeneration of weight-bearing joints with detrimental effects on cartilage volume as well as cartilage damage, generating inflammation in the joint structure. The etiology of OA is multifactorial. Currently, therapies are mainly addressing the physical and occupational aspects of osteoarthritis using pharmacologic pain treatment and/or surgery to manage the symptomatology of the disease with no specific regard to disease progression or prevention. Herein, we highlight alternative therapeutics for OA specifically considering innovative and encouraging translational methods with the use of adipose mesenchymal stem cells.
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Yunus, Mohd Heikal Mohd, Abid Nordin, and Haziq Kamal. "Pathophysiological Perspective of Osteoarthritis." Medicina 56, no. 11 (November 16, 2020): 614. http://dx.doi.org/10.3390/medicina56110614.
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Osteoarthritis (OA) is the most well-known degenerative disease among the geriatric and is a main cause of significant disability in daily living. It has a multifactorial etiology and is characterized by pathological changes in the knee joint structure including cartilage erosion, synovial inflammation, and subchondral sclerosis with osteophyte formation. To date, no efficient treatment is capable of altering the pathological progression of OA, and current therapy is broadly divided into pharmacological and nonpharmacological measures prior to surgical intervention. In this review, the significant risk factors and mediators, such as cytokines, proteolytic enzymes, and nitric oxide, that trigger the loss of the normal homeostasis and structural changes in the articular cartilage during the progression of OA are described. As the understanding of the mechanisms underlying OA improves, treatments are being developed that target specific mediators thought to promote the cartilage destruction that results from imbalanced catabolic and anabolic activity in the joint.
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Zacharjasz, Julian, Anna M. Mleczko, Paweł Bąkowski, Tomasz Piontek, and Kamilla Bąkowska-Żywicka. "Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments." International Journal of Molecular Sciences 22, no. 11 (May 27, 2021): 5711. http://dx.doi.org/10.3390/ijms22115711.
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Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world's population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.
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Anikin, S. G., and L. I. Alekseeva. "Etoricoxib in the treatment of osteoarthritis." Meditsinskiy sovet = Medical Council, no. 2 (March 4, 2020): 97–102. http://dx.doi.org/10.21518/2079-701x-2020-2-97-102.
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Osteoarthritis (OA) is one of the most common diseases of the musculoskeletal system.The main symptoms of osteoarthritis are pain, stiffness, joint swelling. According to epidemiological studies, about one-third of the chronic moderate and severe pain is associated with OA. Currently, OA is considered as a multifactorial disease resulting from the interaction of various genetic, biological, mechanical, and metabolic factors. Inflammation plays a central role in development and progression of ОА. In patients with OA, histological studies of the synovial membrane detected signs of chronic inflammation. The level of some proinflammatory cytokines may increased and the level of anti-inflammatory cytokines may decreased in blood serum, synovial fluid and joint tissue. Also, adaptive immune cell responses are detected in the joint tissues in patients of OA. Due to its high effectiveness, non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in OA. Oral or local forms of NSAIDs are the drugs of choice in the initial stages of therapy in all guidelines. Etoricoxib is a selective inhibitor of cyclooxygenase 2 (COX-2) and is used for the treatment of OA and other rheumatic diseases. The article discusses the use of etoricoxib in patients with OA.
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Viswanath, J., Chakrapani Cheekavolu, Renu Dixit, and S. Sankaraiah. "Prevalence of osteoarthritis patients in South Indian hospital." International Journal Of Community Medicine And Public Health 4, no. 8 (July 22, 2017): 3043. http://dx.doi.org/10.18203/2394-6040.ijcmph20173369.
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Background: Osteoarthritis is multifactorial in aetiology. Both systemic factors (e.g. age, sex, genes) and local factors (e.g. muscle weakness, joint deformity) appear to influence the risk of individual joints developing the disease. Methods: Total 60 patient’s prospective data was collected in S.V. Ayurvedic Medical College and Hospital. Collected data were family history, physical activity, illness, addiction, digestive power etc., in patients with osteoarthritis. Results: The study showed 53.33% of previous family history of osteoarthritis and 46.66% were no family history of osteoarthritis. 76.66% gradual disease onset and 23.33% were insidious onset. 100% were having joint pain with swelling. 50% were average digestive power, 36.66% good and 13.33% poor. 30% patients were having addiction of alcohol, 16.66% smoking and alcohol, 16.66% smoking, 3.33% tobacco and 33.33% were no addiction. 66.66% patients were having irregular bowel habit and 33.33% was regular. 41.66% sedentary, 40% active and 18.33% were moderately active. 40% illness was observed during the period of 0-6 months, 30% 1-2 years, 16.66% 6-12 months and 13.33% were 2-5 yrs. 60% cold season and 40% were other seasons. Conclusions: Present study demonstrated that, incidence of osteoarthritis was very high especially in earlier family history of osteoarthritis, gradual disease, joint pain, average digestive power, No addiction, bowel habit Irregular, sedentary, illness during the period of last 6 months and cold season patients.
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Lazetic, Aleksandar, Mirka Lukic-Sarkanovic, Dragan Savic, Oliver Dulic, Srdjan Radic, and Mirko Obradovic. "Knee osteoarthritis and arthroplasty of the knee joint." Medical review 69, suppl. 1 (2016): 41–45. http://dx.doi.org/10.2298/mpns16s1041l.
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According to the Public Health Institute of Vojvodina one of the main causes of morbidity, invalidity and absence from work in Vojvodina are musculoskeletal diseases. Osteoarthritis is a multifactorial joint disease, with catabolism and inflammation in its background. For radiological classification of knee osteoarthritis stage Kellgren-Lawrence scale is used. It consists of five levels, from stage ?0? to stage ?4?. The goal of osteoarthritis treatment is to reduce pain and muscle spasms, improve limb function, prevent joint contractures and train patients to function in everyday life and professional activities. The therapy is divided into conservative (medical and physical) and surgical. Arthroplasty is a surgical procedure that involves destruction of articular surfaces and replacement of degenerative joints with endoprostheses, which result in increased general and working ability. Modern endoprostheses enable a high success rate of the procedure. At the Department of Orthopedics and Traumatology, Clinical Center of Vojvodina in Novi Sad, the first knee aloarthroplasty was performed in 1989. Since then, more than 3000 knee aloarthro?plasties have been done. Clinical patient evaluation was obtained through subjective status, functional evaluation and use of scoring systems. More than 80% of patients had a good or a great score.
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Jarecki, Jaromir. "CARTILAGE AGEING AND TREATMENT POSSIBILITIES." Wiadomości Lekarskie 72, no. 9 (2019): 1671–75. http://dx.doi.org/10.36740/wlek201909112.
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Osteoarthritis is the disease connected with aging which is characterised by progressive degeneration of all elements building the joint but also influencing the muscles constituting motor unit with the affected joint. The effective and unified therapy has not been yet introduced despite the broad multi-site studies concentrating on metabolic pathways responsible for the development of the disease. The reason of which is probably its multifactorial aetiology. The treatment methods are based on decreasing of cartilage destruction activity, retardation of proinflammatory factors activity and fighting with pain. Physiotherapy, movement rehabilitation, painkillers, anti-inflammatory drugs, glucosamine sulphates and hyaluronic acids are used as therapeutic strategies. The methods recently introduced are platelet rich plasma concentrates and stem cells injected directly into the affected joint. The aim of this review article was the presentation of differential therapeutic options offered to patients in different stages of osteoarthritis.
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Miranda-Duarte, Antonio. "DNA Methylation in Osteoarthritis: Current Status and Therapeutic Implications." Open Rheumatology Journal 12, no. 1 (March 30, 2018): 37–49. http://dx.doi.org/10.2174/1874312901812010037.
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Background: Primary Osteoarthritis (OA) is a multifactorial disease in which genetic factors are strongly associated with its development; however, recently it has been observed that epigenetic modifications are also involved in the pathogenesis of OA. DNA methylation is related to gene silencing, and several studies have investigated its role in the loci of different pathways or molecules associated to OA. Objective: This review is focused on the current status of DNA methylation studies related to OA pathogenesis. Method: A review of the literature was conducted on searching in PUBMED for original papers on DNA methylation in OA. Conclusion: The DNA methylation research of loci related to OA pathogenesis has shown a correlation between methylation and gene repression; however, there are some exceptions to this rule. Recently, the development of genome-wide methylation and genome-wide hydroxymethylation profiles has demonstrated that several genes previously associated with OA can have changes in their methylation status, favoring the development of the disease, and these have even shown the role of other epigenetic markers.
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Magnuszewski, Lukasz, Marta Swietek, Agnieszka Kasiukiewicz, Bartlomiej Kuprjanowicz, Jan Baczek, and Zyta Beata Wojszel. "Health, Functional and Nutritional Determinants of Falls Experienced in the Previous Year—A Cross-Sectional Study in a Geriatric Ward." International Journal of Environmental Research and Public Health 17, no. 13 (July 2, 2020): 4768. http://dx.doi.org/10.3390/ijerph17134768.
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Falls are a serious health problem in older adults. A limited number of studies assessed their multifactorial nature in geriatric ward patients. The aim of this study is to explore health, functional and nutritional correlates of experiencing fall(s) in the previous year by older inpatients. A cross-sectional study of patients admitted to the department of geriatrics was conducted. A “faller status” was defined based on positive history of falls in the previous 12 months. Health, functional and nutritional factors associated with falls were evaluated, and multivariable logistic regression analysis models were built. A total of 358 patients (median age 82 (IQR 76–86) years, 77.9% women) were recruited, 43.9% of whom reported falls. The “fallers” presented with a significantly higher number of chronic diseases, higher prevalence of Parkinson’s disease, peripheral arterial disease, chronic osteoarthritis, more frequently reported urinary incontinence and were dependent on others for daily living activities. They had significantly worse results for the assessment of gait, balance and frailty status. The Mini Nutritional Assessment-Short Form scores and the mean value of serum albumin were significantly lower in the fallers’ group. Parkinson’s disease (OR = 2.82, CI—1.07–7.45; p = 0.04) and osteoarthritis (OR = 2.08, CI—1.02–4.23; p = 0.04) were the main variables for the outcome prediction, according to the direct multivariable logistic regression analysis. Our findings suggest that Parkinson’s disease and osteoarthritis are the main predictors independently associated with a history of falls in patients admitted to the geriatric ward, although the influence of some factors may be underestimated due to the tendency of not taking the history of falls in very frail, functionally dependent and bedridden individuals.
11
Loughlin, John. "The genetic epidemiology of human primary osteoarthritis: current status." Expert Reviews in Molecular Medicine 7, no. 9 (May 23, 2005): 1–12. http://dx.doi.org/10.1017/s1462399405009257.
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Osteoarthritis (OA) is a common disease characterised by the degeneration of the cartilage of synovial joints such as the hip and knee. In the past ten years a large number of twin-pair, sibling-risk and segregation studies have been conducted on the disease, and these have revealed a major genetic component that is transmitted in a nonmendelian manner. OA therefore fits best into the complex, multifactorial class of common diseases. With a genetic component established, genome-wide linkage scans were performed, and these uncovered several genomic intervals likely to harbour OA susceptibility. In the past few years these intervals have started to yield genes containing OA-associated variants. This is therefore a very exciting period in the molecular genetic analysis of this common disease. The genes that have so far been implicated in susceptibility include the interleukin 1 gene (IL1) cluster at chromosome 2q11.2-q13, the matrilin 3 gene (MATN3) at 2p24.1, the IL-4 receptor α-chain gene (IL4R) at 16p12.1, the secreted frizzled-related protein 3 gene (FRZB) at 2q32.1, the metalloproteinase gene ADAM12 at 10q26.2 and, most recently, the asporin gene (ASPN) at 9q22.31. The evidence for involvement of these genes in OA is more compelling for some than others, with the IL1 and ASPN associations being the most convincing to date. It is imperative that the veracity of each of the associations be tested by genotyping additional cohorts and that their global relevance be assessed by genotyping OA cohorts from different ethnic backgrounds. The gene products of IL1, IL4R, FRZB and ASPN regulate cartilage chondrocyte differentiation and survival, and their effects on the chondrocyte are potentially amenable to therapeutic intervention. The latest genetics is therefore providing new insights for the development of novel OA treatments.
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Rezuş, Elena, Alexandra Burlui, Anca Cardoneanu, Luana Andreea Macovei, Bogdan Ionel Tamba, and Ciprian Rezuş. "From Pathogenesis to Therapy in Knee Osteoarthritis: Bench-to-Bedside." International Journal of Molecular Sciences 22, no. 5 (March 7, 2021): 2697. http://dx.doi.org/10.3390/ijms22052697.
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Osteoarthritis (OA) is currently the most widespread musculoskeletal condition and primarily affects weight-bearing joints such as the knees and hips. Importantly, knee OA remains a multifactorial whole-joint disease, the appearance and progression of which involves the alteration of articular cartilage as well as the synovium, subchondral bone, ligaments, and muscles through intricate pathomechanisms. Whereas it was initially depicted as a predominantly aging-related and mechanically driven condition given its clear association with old age, high body mass index (BMI), and joint malalignment, more recent research identified and described a plethora of further factors contributing to knee OA pathogenesis. However, the pathogenic intricacies between the molecular pathways involved in OA prompted the study of certain drugs for more than one therapeutic target (amelioration of cartilage and bone changes, and synovial inflammation). Most clinical studies regarding knee OA focus mainly on improvement in pain and joint function and thus do not provide sufficient evidence on the possible disease-modifying properties of the tested drugs. Currently, there is an unmet need for further research regarding OA pathogenesis as well as the introduction and exhaustive testing of potential disease-modifying pharmacotherapies in order to structure an effective treatment plan for these patients.
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de Sire, Alessandro, Nicola Marotta, Cinzia Marinaro, Claudio Curci, Marco Invernizzi, and Antonio Ammendolia. "Role of Physical Exercise and Nutraceuticals in Modulating Molecular Pathways of Osteoarthritis." International Journal of Molecular Sciences 22, no. 11 (May 27, 2021): 5722. http://dx.doi.org/10.3390/ijms22115722.
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Osteoarthritis (OA) is a painful and disabling disease that affects millions of patients. Its etiology is largely unknown, but it is most likely multifactorial. OA pathogenesis involves the catabolism of the cartilage extracellular matrix and is supported by inflammatory and oxidative signaling pathways and marked epigenetic changes. To delay OA progression, a wide range of exercise programs and naturally derived compounds have been suggested. This literature review aims to analyze the main signaling pathways and the evidence about the synergistic effects of these two interventions to counter OA. The converging nutrigenomic and physiogenomic intervention could slow down and reduce the complex pathological features of OA. This review provides a comprehensive picture of a possible signaling approach for targeting OA molecular pathways, initiation, and progression.
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Sahoo, S. S., O. K. Choudhari, J. Bhadra, and B. C. Kabi. "Association of BTNL2 gene single nucleotide polymorphism with knee osteoarthritis." RUDN Journal of Medicine 25, no. 2 (December 15, 2021): 89–95. http://dx.doi.org/10.22363/2313-0245-2021-25-2-89-95.
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Relevance. Osteoarthritis (OA) is one of the chronic debilitating condition mostly seen in the aged population. The etiology behind the OA is multifactorial and the exact cause of the disease often remains uncertain. Apart from the conventional risk factors, there are the speculations of role of genetics playing a pivotal role in the causation of OA. The available literature showed BTNL2 gene polymorphism association with risk of Osteoarthritis whether the same relation is present in north Indian population needs to be elucidated. Objective. To find the association between single nucleotide polymorphism (SNP) (rs10947262) in BTNL2 gene and the susceptibility in knee Osteoarthritis (OA) subjects from northern Indian population. Materials and Methods. Blood samples of 100 patients of knee osteoarthritis and 100 healthy subjects were collected after institutional ethical clearance and participants consent. The BTNL2 gene fragment was amplified using Amplification Refractory Mutation System (ARMS-PCR) with predesigned primers after DNA extraction. The corresponding product bands were identified on the gel electrophoresis for 200 samples and the results were statistically analyzed. Results and Discussion. The genotypic distribution of the SNP followed Hardy-Weinberg Equilibrium. The genotype frequency analysis of the polymorphism was statistically significant (2=7.788; P=0.005) with Odds Ratio of CT+TT/CC: OR=2.303; P=0.008 revealing association of BTNL2 polymorphism with risk of Knee Osteoarthritis. Conclusion. The SNP (rs10947262) in the BTNL2 gene region is associated with risk of knee osteoarthritis.
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Qu, Yanlong, Chunlei Wang, Ning Liu, Chengzhe Gao, and Fei Liu. "Morin Exhibits Anti-Inflammatory Effects on IL-1β-Stimulated Human Osteoarthritis Chondrocytes by Activating the Nrf2 Signaling Pathway." Cellular Physiology and Biochemistry 51, no. 4 (2018): 1830–38. http://dx.doi.org/10.1159/000495684.
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Background/Aims: Osteoarthritis (OA) is a multifactorial disease that is associated with inflammation in joints. The purpose of the present study was to investigate the anti-inflammatory activity and mechanism of morin on human osteoarthritis chondrocytes stimulated by IL-1β. Methods: The levels of NO and PGE2 were measured by the Griess method and ELISA. The levels of MMP1, MMP3, and MMP13 were also measured by ELISA. Results: The results revealed that IL-1β significantly increased the production of NO, PGE2, MMP1, MMP3, and MMP13. Additionally, the increases were significantly attenuated by treatment with morin. Furthermore, IL-1β-induced NF-κB activation was suppressed by morin. In addition, the expression of Nrf2 and HO-1 were increased by morin and knockdown of Nrf2 could prevent the anti-inflammatory effects of morin. Conclusion: In conclusion, this study suggested that morin attenuated IL-1β-induced inflammation by activating the Nrf2 signaling pathway.
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Zonova, E. V., and A. E. Karateev. "A sound approach to choosing nonsteroidal anti-inflammatory drugs for osteoarthritis." Modern Rheumatology Journal 12, no. 4 (December 10, 2018): 47–53. http://dx.doi.org/10.14412/1996-7012-2018-4-47-53.
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The current guidelines for prescribing analgesic therapy for osteoarthritis (OA) are based on the latest knowledge about the pathogenesis of this disease and the mechanism of action of analgesics. The leading principle of choosing analgesics is to assess the nature of pain and the patient's condition, adverse drug reactions. This is directly related to nonsteroidal anti-inflammatory drugs (NSAIDs) that are now the most important class of painkillers used in OA. Among the drugs of this class, meloxicam, a representative of the oxicam group, which relatively equally inhibits cyclooxygenase 1 and 2 and also affects the activity of microsomal prostaglandin E2 synthase 1, should be identified. This drug is characterized by a proven efficacy and a favorable safety profile. Nevertheless, the need for multifactorial evaluation of treatment-associated complications should be recognized as a priority when using any NSAIDs.
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Kittelson, Andrew J., Steven Z. George, Katrina S. Maluf, and Jennifer E. Stevens-Lapsley. "Future Directions in Painful Knee Osteoarthritis: Harnessing Complexity in a Heterogeneous Population." Physical Therapy 94, no. 3 (March 1, 2014): 422–32. http://dx.doi.org/10.2522/ptj.20130256.
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This perspective article proposes a conceptual model for the pain experience for individuals diagnosed with knee osteoarthritis (OA). Pain in knee OA is likely a heterogeneous, multifactorial phenomenon that involves not only the OA disease process but also elements specific to patient psychology and pain neurophysiology. The relevant contributions to the pain experience for any individual patient remain difficult, if not impossible, to definitively determine, and the rationale for many clinical treatment decisions arises primarily from a mechanistic understanding of OA pathophysiology. The Osteoarthritis Research Society International (OARSI) recently identified “phenotyping” of OA pain as a research priority to “better target pain therapies to individual patients.” This perspective article proposes that contributions from 3 domains—knee pathology, psychological distress, and pain neurophysiology—should be considered equally important in future efforts to understand pain phenotypes in knee OA. Ultimately, characterization of pain phenotypes may aid in the understanding of the pain experience and the development of interventions specific to pain for individual patients.
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Tchetina, Elena V., Galina A. Markova, and Eugeniya P. Sharapova. "Insulin Resistance in Osteoarthritis: Similar Mechanisms to Type 2 Diabetes Mellitus." Journal of Nutrition and Metabolism 2020 (May 22, 2020): 1–16. http://dx.doi.org/10.1155/2020/4143802.
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Osteoarthritis (OA) and type 2 diabetes mellitus (T2D) are two of the most widespread chronic diseases. OA and T2D have common epidemiologic traits, are considered heterogenic multifactorial pathologies that develop through the interaction of genetic and environmental factors, and have common risk factors. In addition, both of these diseases often manifest in a single patient. Despite differences in clinical manifestations, both diseases are characterized by disturbances in cellular metabolism and by an insulin-resistant state primarily associated with the production and utilization of energy. However, currently, the primary cause of OA development and progression is not clear. In addition, although OA is manifested as a joint disease, evidence has accumulated that it affects the whole body. As pathological insulin resistance is viewed as a driving force of T2D development, now, we present evidence that the molecular and cellular metabolic disturbances associated with OA are linked to an insulin-resistant state similar to T2D. Moreover, the alterations in cellular energy requirements associated with insulin resistance could affect many metabolic changes in the body that eventually result in pathology and could serve as a unified mechanism that also functions in many metabolic diseases. However, these issues have not been comprehensively described. Therefore, here, we discuss the basic molecular mechanisms underlying the pathological processes associated with the development of insulin resistance; the major inducers, regulators, and metabolic consequences of insulin resistance; and instruments for controlling insulin resistance as a new approach to therapy.
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Calabrese, Giovanna, Agata Zappalà, Anna Dolcimascolo, Rosaria Acquaviva, Rosalba Parenti, and Giuseppe Antonio Malfa. "Phytochemical Analysis and Anti-Inflammatory and Anti-Osteoarthritic Bioactive Potential of Verbascum thapsus L. (Scrophulariaceae) Leaf Extract Evaluated in Two In Vitro Models of Inflammation and Osteoarthritis." Molecules 26, no. 17 (September 5, 2021): 5392. http://dx.doi.org/10.3390/molecules26175392.
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Osteoarthritis (OA) is a complex disease, source of pain and disability that affects millions of people worldwide. OA etiology is complex, multifactorial and joint-specific, with genetic, biological and biomechanical components. Recently, several studies have suggested a potential adjuvant role for natural extracts on OA progression, in terms of moderating chondrocyte inflammation and following cartilage injury, thus resulting in an overall improvement of joint pain. In this study, we first analyzed the phenylethanoid glycosides profile and the total amount of polyphenols present in a leaf aqueous extract of Verbascum thapsus L. We then investigated the anti-inflammatory and anti-osteoarthritic bioactive potential of the extract in murine monocyte/macrophage-like cells (RAW 264.7) and in human chondrocyte cells (HC), by gene expression analysis of specifics inflammatory cytokines, pro-inflammatory enzymes and metalloproteases. Six phenylethanoid glycosides were identified and the total phenolic content was 124.0 ± 0.7 mg gallic acid equivalent (GAE)/g of extract. The biological investigation showed that the extract is able to significantly decrease most of the cellular inflammatory markers, compared to both control cells and cells treated with Harpagophytum procumbens (Burch.) DC. ex Meisn, used as a positive control. Verbascum thapsus leaf aqueous extract has the potential to moderate the inflammatory response, representing an innovative possible approach for the inflammatory joint disease treatment.
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Шаповалова, Д. А., А. В. Тюрин, and Р. И. Хусаинова. "Study of genetic predisposition to osteoarthritis in women with connective tissue dysplasia from the Republic of Bashkortostan." Nauchno-prakticheskii zhurnal «Medicinskaia genetika», no. 8(217) (August 31, 2020): 67–69. http://dx.doi.org/10.25557/2073-7998.2020.08.67-69.
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Остеоартрит (ОА) - наиболее распространенное многофакторное заболевание суставов. Одним из вероятных факторов риска развития ОА является недифференцированная дисплазия соединительной ткани (нДСТ) - генетически детерминированное нарушение структуры соединительной ткани, в том числе и в суставах. Вопрос о коморбидности ОА с нДСТ чрезвычайно актуален, и решение данной задачи будет способствовать разработке подходов ранней диагностики ОА в целях профилактики заболевания. Osteoarthritis (OA) is a common multifactorial joint disease. Undifferentiated connective tissue dysplasia (uCTD) is a genetically determined lesion of the connective tissue structures, including joints, and it can be one of the factors, predisposing to development of OA. Solving the problem of comorbidity OA and uCTD signs will contribute to the early diagnosis and preventive of OA.
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Jaggard, M. K. J., C. L. Boulangé, G. Graça, U. Vaghela, P. Akhbari, R. Bhattacharya, H. R. T. Williams, J. C. Lindon, and C. M. Gupte. "Can metabolic profiling provide a new description of osteoarthritis and enable a personalised medicine approach?" Clinical Rheumatology 39, no. 12 (June 1, 2020): 3875–82. http://dx.doi.org/10.1007/s10067-020-05106-3.
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AbstractOsteoarthritis (OA) is a multifactorial disease contributing to significant disability and economic burden in Western populations. The aetiology of OA remains poorly understood, but is thought to involve genetic, mechanical and environmental factors. Currently, the diagnosis of OA relies predominantly on clinical assessment and plain radiographic changes long after the disease has been initiated. Recent advances suggest that there are changes in joint fluid metabolites that are associated with OA development. If this is the case, biochemical and metabolic biomarkers of OA could help determine prognosis, monitor disease progression and identify potential therapeutic targets. Moreover, for focussed management and personalised medicine, novel biomarkers could sub-stratify patients into OA phenotypes, differentiating metabolic OA from post-traumatic, age-related and genetic OA. To date, OA biomarkers have concentrated on cytokine action and protein signalling with some progress. However, these remain to be adopted into routine clinical practice. In this review, we outline the emerging metabolic links to OA pathogenesis and how an elucidation of the metabolic changes in this condition may provide future, more descriptive biomarkers to differentiate OA subtypes.
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Roman, Mihai Dan, Radu Sorin Fleaca, Adrian Boicean, Dan Bratu, Victoria Birlutiu, Luca Liviu Rus, Cristian Tantar, and Sebastian Ioan Cernusca Mitariu. "Assesment of Synovial Fluid pH in Osteoarthritis of the HIP and Knee." Revista de Chimie 68, no. 6 (July 15, 2017): 1242–44. http://dx.doi.org/10.37358/rc.17.6.5649.
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Osteoarthritis (OA) is a developing process with a multifactorial causality in which changes of the synovial fluid characteristics occur. Hypothesis: synovial fluid pH in severe OA is correlated with other patient parameters. Synovial fluid pH from 50 patients with severe OA (knee/hip) was determined. The results were assessed and correlations with the patients antropologic data and biological markers were analyzed. 50 patients (26 knee OA and 24 hip OA) were analyzed. The average synovial fluid pH was 7.35 indicating slightly lower levels than in normal joints. Higher pH values were observed in males, under 60 years, secondary OA, Rh+ and Hbg under 13.5g/dL. Lower pH values were obtained in females, age under 60 years, primary OA, Rh-, Hbg over 13.5g/dL, hypertensive and diabetic patients. The synovial fluid pH may not be an appropriate biomarker for severe OA disease. Some patient variables might be correlated with synovial blood pH.
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Koeshardiandi, Mirza. "Regenerative Pain Medicine, the New Era of Interventional Pain Management, Restart Now!" Journal of Anaesthesia and Pain 2, no. 2 (May 30, 2021): 63–64. http://dx.doi.org/10.21776/ub.jap.2021.002.02.01.
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Musculoskeletal conditions become the leading contributor of the total years lived disability (YLD) by causing 21.3% of the YLDs, after mental and behavioral problems. Several musculoskeletal conditions give a disproportional impact on low back pain, one of the leading causes of disability. Lateral epicondylitis with a prevalence of 1-2%, commonly suffered by adults in their 30-65 years old. Epicondylitis was also suffered by a small population of athletes, such as professional tennis players (10% of epicondylitis population). The severe repetitive injuries that affect the individual daily activity also increase the daily health care cost. Osteoarthritis and tendinopathy often become the cause of pain and musculoskeletal disability. However, the etiology of pain in osteoarthritis is multifactorial. The incidence of osteoarthritis reaches 6% in 30 years old population and increases due to aging. Degenerative disease, the reduction of function or structure of the tissue or organ due to aging, encourages the pain specialist to perform a reliable pain management/therapy. Prolotherapy, especially dextrose prolotherapy, has become a promising technique by providing a safe degenerative therapy, easy to performed, and highly available in health facilities. Nowadays, it is necessary to pay more attention to causative-based treatment strategies than symptom-based treatment. A multidisciplinary team is also needed to provide appropriate treatment.
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Pandey, Suresh. "Osteoarthritis: Review of Etiopathology, Diagnosis and Management." Journal of College of Medical Sciences-Nepal 16, no. 2 (June 30, 2020): 107–13. http://dx.doi.org/10.3126/jcmsn.v16i2.28320.
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Abstract
Osteoarthritis (OA) is the most common type of arthritis in the world characterized by articular cartilage degeneration with inflammatory components in ageing population. It involves about 10% of adult population and is among the most disabling disease condition. It is multifactorial in its etiology with a number of non-modifiable and modifiable risk factors. Ageing is the most important risk factor followed by obesity in probably genetically susceptible individuals. The end result of inflammation and articular cartilage degeneration arising from repeated overloading of joint, mechanical or biochemical imbalance of repair and degeneration affects not only joint cartilage but also subchondral bone and periarticular structures. Patient mainly presents with variable degree of pain, stiffness and functional limitation with or without swelling and deformity. Diagnosis is clinical and plain imaging is useful for documentation, to see the grading and plan the suitable treatment. There are a number of treatment options in practice each having their pros and cons but no single treatment method is superior to all. There is no cure for it but judicious use of non-pharmacological and pharmacological measures, often in combination in tailored fashion help to ease the patient’s symptoms. Operative intervention in the form of arthroplasty is reserved for end stage arthritis with disabling symptoms not responding with conservative management. Numerous newer treatment modalities are under different phases of clinical trial to test the efficacy and clinical use.
Aim of this narrative review article is to analyze literatures obtained from electronic database and present the synthesized relevant clinical update on etiopathology, diagnosis and treatment modalities of symptomatic osteoarthritis.
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D’Adamo, Stefania, Silvia Cetrullo, Manuela Minguzzi, Ylenia Silvestri, Rosa Maria Borzì, and Flavio Flamigni. "MicroRNAs and Autophagy: Fine Players in the Control of Chondrocyte Homeostatic Activities in Osteoarthritis." Oxidative Medicine and Cellular Longevity 2017 (2017): 1–16. http://dx.doi.org/10.1155/2017/3720128.
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Osteoarthritis (OA) is a debilitating degenerative disease of the articular cartilage with a multifactorial etiology. Aging, the main risk factor for OA development, is associated with a systemic oxidative and inflammatory phenotype. Autophagy is a central housekeeping system that plays an antiaging role by supporting the clearance of senescence-associated alterations of macromolecules and organelles. Autophagy deficiency has been related to OA pathogenesis because of the accumulation of cellular defects in chondrocytes. Microribonucleic acids (microRNAs or miRs) are a well-established class of posttranscriptional modulators belonging to the family of noncoding RNAs that have been identified as key players in the regulation of cellular processes, such as autophagy, by targeting their own cognate mRNAs. Here, we present a state-of-the-art literature review on the role of miRs and autophagy in the scenario of OA pathogenesis. In addition, a comprehensive survey has been performed on the functional connections of the miR network and the autophagy pathway in OA by using “microRNA,” “autophagy,” and “osteoarthritis” as key words. Discussion of available evidence sheds light on some aspects that need further investigation in order to reach a more comprehensive view of the potential of this topic in OA.
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Bragg, Robert, William Gilbert, Ahmed M. Elmansi, Carlos M. Isales, Mark W. Hamrick, William D. Hill, and Sadanand Fulzele. "Stromal cell-derived factor-1 as a potential therapeutic target for osteoarthritis and rheumatoid arthritis." Therapeutic Advances in Chronic Disease 10 (January 2019): 204062231988253. http://dx.doi.org/10.1177/2040622319882531.
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With age, joints become subject to chronic inflammatory processes that lead to degeneration of articular cartilage. Although multifactorial, cytokines have been shown to play a role in the pathogenesis of these chronic disease states. Stromal cell-derived factor 1 (SDF-1) is a chemokine that has been shown to be active in homeostatic mechanisms and developmental processes throughout the body, such as endochondral bone formation. SDF-1 plays a role in the transition from cartilage to bone. Although it has been shown to be a factor in normal development, it has also been shown to involve in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA). In RA, SDF-1 has been shown to stimulate the recruitment of proinflammatory cells, as well as osteoclasts to the synovium, aiding in the facilitation of synovial degradation. Similarly, in OA, SDF-1 has been shown to regulate key proteins involved in the degradation of the cartilage of the joint. Because of its role in degenerative joint disease, SDF-1 has been investigated as a potential therapeutic target. Animal studies have been employing SDF-1 inhibitors, such as AMD3100 and T140, to study their effects on attenuating degenerative joint disease. These studies have shown promising results in slowing the progression of cartilage degradation and could potentially be used as therapeutic target for humans OA and RA.
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O'Malley, Michael J., and Constance R. Chu. "Arthroscopic Optical Coherence Tomography in Diagnosis of Early Arthritis." Minimally Invasive Surgery 2011 (2011): 1–6. http://dx.doi.org/10.1155/2011/671308.
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Osteoarthritis (OA) is a progressive, debilitating disease that is increasing in prevalence. The pathogenesis of OA is likely multifactorial but ultimately leads to progressive breakdown of collagen matrix and loss of chondrocytes. Current clinical modalities employed to evaluate cartilage health and diagnose osteoarthritis in orthopaedic surgery include, radiography, MRI, and arthroscopy. While these assessment methods can show cartilage fissuring and loss, they are limited in ability to diagnose cartilage injury and degeneration prior breakdown of the articular surface. An improved clinical ability to detect subsurface cartilage pathology is important for development and testing of chondroprotective and chondrorestorative treatments because the pathological changes following surface breakdown are generally considered to be irreversible. Optical Coherence Tomography (OCT), is a novel, non-destructive imaging technology capable of near-real time cross-sectional images of articular cartilage at high resolutions comparable to low power histology. This review discusses a series of bench to bedside studies supporting the potential use of OCT for enhanced clinical diagnosis and staging of early cartilage injury and degeneration. OCT was also found to be useful as a translations research tool to assist in clinical evaluation of novel quantitative MRI technologies for non-invasive evaluation of articular cartilage.
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Kotteeswaran, K., P. Sindhura, P. Mohith Sesikiran, and Vengata Subramani Manoharan. "A comparative study to find the effectiveness of weight bearing exercises on stable platform versus wobble board, to improve balance and functional outcome of individuals with knee osteoarthritis." Biomedicine 40, no. 3 (November 9, 2020): 381–85. http://dx.doi.org/10.51248/.v40i3.34.
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Introduction and Aim: Knee osteoarthritis is a common degenerative disease, with its prevalence increasing with age and with multifactorial aetiology. It is a common cause of disability worldwide. Aim of the study is to compare the effect of weight bearing exercises on wobble board and stable platform in improving balance and functional outcome by the pre and post analysis.
Materials and Methods: Experimental study was conducted in Saveetha hospital, Chennai. Forty subjects including both males and females diagnosed with osteoarthritis knee within the age of 40 to 70 years were recruited and divided into two groups with 20 subjects in each group (Group A- 20 subjects, Group B- 20 subjects). Group A was given weight bearing exercises on wobble board along with interferential therapy, in 4 sets with 6 repetitions in each set and a rest interval of one minute between each set, 15 minutes per session, 3 days/week for 4 weeks and Group B was given weight bearing exercises on stable platform along with interferential therapy in 4 sets with 6 repetitions in each set and a rest interval of one minute between each set, 15 minutes per session, 3 days/week for 4 weeks.
Results: At the end of the study, data was analysed and there was improvement in balance and functional outcome.
Conclusion: This study concluded that patients with knee osteoarthritis had improvement in balance and functional outcome through weight bearing exercises given on wobble board along with interferential therapy compared to the patients who were given weight-bearing exercises on stable platform along with interferential therapy.
Keywords: Osteoarthritis; wobble board; stable platform; interferential therapy.
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Kokkotis, Christos, Serafeim Moustakidis, Vasilios Baltzopoulos, Giannis Giakas, and Dimitrios Tsaopoulos. "Identifying Robust Risk Factors for Knee Osteoarthritis Progression: An Evolutionary Machine Learning Approach." Healthcare 9, no. 3 (March 1, 2021): 260. http://dx.doi.org/10.3390/healthcare9030260.
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Knee osteoarthritis (KOA) is a multifactorial disease which is responsible for more than 80% of the osteoarthritis disease’s total burden. KOA is heterogeneous in terms of rates of progression with several different phenotypes and a large number of risk factors, which often interact with each other. A number of modifiable and non-modifiable systemic and mechanical parameters along with comorbidities as well as pain-related factors contribute to the development of KOA. Although models exist to predict the onset of the disease or discriminate between asymptotic and OA patients, there are just a few studies in the recent literature that focused on the identification of risk factors associated with KOA progression. This paper contributes to the identification of risk factors for KOA progression via a robust feature selection (FS) methodology that overcomes two crucial challenges: (i) the observed high dimensionality and heterogeneity of the available data that are obtained from the Osteoarthritis Initiative (OAI) database and (ii) a severe class imbalance problem posed by the fact that the KOA progressors class is significantly smaller than the non-progressors’ class. The proposed feature selection methodology relies on a combination of evolutionary algorithms and machine learning (ML) models, leading to the selection of a relatively small feature subset of 35 risk factors that generalizes well on the whole dataset (mean accuracy of 71.25%). We investigated the effectiveness of the proposed approach in a comparative analysis with well-known FS techniques with respect to metrics related to both prediction accuracy and generalization capability. The impact of the selected risk factors on the prediction output was further investigated using SHapley Additive exPlanations (SHAP). The proposed FS methodology may contribute to the development of new, efficient risk stratification strategies and identification of risk phenotypes of each KOA patient to enable appropriate interventions.
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Fang, Yang, Pingping Wang, Lin Xia, Suwen Bai, Yonggang Shen, Qing Li, Yang Wang, Jinhang Zhu, Juan Du, and Bing Shen. "Aberrantly hydroxymethylated differentially expressed genes and the associated protein pathways in osteoarthritis." PeerJ 7 (February 25, 2019): e6425. http://dx.doi.org/10.7717/peerj.6425.
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Background The elderly population is at risk of osteoarthritis (OA), a common, multifactorial, degenerative joint disease. Environmental, genetic, and epigenetic (such as DNA hydroxymethylation) factors may be involved in the etiology, development, and pathogenesis of OA. Here, comprehensive bioinformatic analyses were used to identify aberrantly hydroxymethylated differentially expressed genes and pathways in osteoarthritis to determine the underlying molecular mechanisms of osteoarthritis and susceptibility-related genes for osteoarthritis inheritance. Methods Gene expression microarray data, mRNA expression profile data, and a whole genome 5hmC dataset were obtained from the Gene Expression Omnibus repository. Differentially expressed genes with abnormal hydroxymethylation were identified by MATCH function. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the genes differentially expressed in OA were performed using Metascape and the KOBAS online tool, respectively. The protein–protein interaction network was built using STRING and visualized in Cytoscape, and the modular analysis of the network was performed using the Molecular Complex Detection app. Results In total, 104 hyperhydroxymethylated highly expressed genes and 14 hypohydroxymethylated genes with low expression were identified. Gene ontology analyses indicated that the biological functions of hyperhydroxymethylated highly expressed genes included skeletal system development, ossification, and bone development; KEGG pathway analysis showed enrichment in protein digestion and absorption, extracellular matrix–receptor interaction, and focal adhesion. The top 10 hub genes in the protein–protein interaction network were COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL6A1, COL8A1, COL11A1, and COL24A1. All the aforementioned results are consistent with changes observed in OA. Conclusion After comprehensive bioinformatics analysis, we found aberrantly hydroxymethylated differentially expressed genes and pathways in OA. The top 10 hub genes may be useful hydroxymethylation analysis biomarkers to provide more accurate OA diagnoses and target genes for treatment of OA.
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Scrivo, Rossana, Massimiliano Vasile, Ulf Müller-Ladner, Elena Neumann, and Guido Valesini. "Rheumatic Diseases and Obesity: Adipocytokines as Potential Comorbidity Biomarkers for Cardiovascular Diseases." Mediators of Inflammation 2013 (2013): 1–14. http://dx.doi.org/10.1155/2013/808125.
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Inflammation has been recognized as a common trait in the pathogenesis of multifactorial diseases including obesity, where a low-grade inflammation has been established and may be responsible for the cardiovascular risk related to the disease. Obesity has also been associated with the increased incidence and a worse outcome of rheumatoid arthritis (RA) and osteoarthritis (OA). RA is characterized by systemic inflammation, which is thought to play a key role in accelerated atherosclerosis and in the increased incidence of cardiovascular disease, an important comorbidity in patients with RA. The inflammatory process underlying the cardiovascular risk both in obesity and RA may be mediated by adipocytokines, a heterogeneous group of soluble proteins mainly secreted by the adipocytes. Many adipocytokines are mainly produced by white adipose tissue. Adipocytokines may also be involved in the pathogenesis of OA since a positive association with obesity has been found for weight-bearing and nonweight-bearing joints, suggesting that, in addition to local overload, systemic factors may contribute to joint damage. In this review we summarize the current knowledge on experimental models and clinical studies in which adipocytokines were examined in obesity, RA, and OA and discuss the potential of adipocytokines as comorbidity biomarkers for cardiovascular risk.
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Novakov, V. B., O. N. Novakova, and M. I. Churnosov. "Risk factors and molecular entities of the etiopathogenesis of the knee osteoarthritis (literature review)." Genij Ortopedii 27, no. 1 (February 2021): 112–20. http://dx.doi.org/10.18019/1028-4427-2021-27-1-112-120.
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Introduction Osteoarthritis (OA) is a heterogenic group of disorders of different etiology with similar biological, morphological and clinical manifestations and outcomes. OA is now considered a disease of the whole joint, including alterations in the articular cartilage, subchondral bone, synovial membrane, ligaments, capsule and periarticular muscles. OA of the knee as the most commonly affected joint accounts for the great medical, medical, social and economic impact. Material and methods A literature review assessing Russian and foreign studies on molecular mechanisms of etiology and pathogenesis of knee OA identified a set of factors for which there was consistent evidence for their association with onset of knee OA. A search of studies published in Russian and in English for the last ten years was conducted using bibliographic databases, including PubMed, PubMedCentral, GoogleScholar, eLIBRARY. Search terms included 'knee osteoarthritis', 'etiology', 'pathogenesis', 'risk factors'. Results Review of the literature showed that patients with knee OA are characterized by changes in cartilage, subchondral bone, synovium, suggesting common mechanisms of joint degeneration during OA development. Osteoarthritis (OA) is multifactorial in origin and closely associated with a wide spectrum of local (previous injury, muscle weakness, knee malalignment, knee surgeries, abnormal mechanical loading, excessive high impact sports, occupational physical activities) and systemic risk factors (advanced age, female sex, height, greater body mass index and obesity, hormone status, family history, mineral bone density, vitamin D deficiency, ethnicity). The prevalence of the knee OA and patterns of joint involvement vary among different racial and ethnic groups. Conclusion The literature review allowed us to identify the molecular mechanisms of etiopathogenesis of knee OA and the major risk factors for the pathology.
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Bai, Hui, Zhiheng Zhang, Yue Li, Xiaopeng Song, Tianwen Ma, Chunpeng Liu, Lin Liu, Rui Yuan, Xinyu Wang, and Li Gao. "L-Theanine Reduced the Development of Knee Osteoarthritis in Rats via Its Anti-Inflammation and Anti-Matrix Degradation Actions: In Vivo and In Vitro Study." Nutrients 12, no. 7 (July 3, 2020): 1988. http://dx.doi.org/10.3390/nu12071988.
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The etiology of osteoarthritis (OA) is multifactorial, with no effective disease-modifying-drugs. L-theanine has been reported to inhibit inflammatory responses in some diseases and this study aimed to investigate the effect of L-theanine on Interleukin-1(IL-1)β-stimulated chondrocytes, and in an injury-induced OA rat model. Primary chondrocytes were stimulated by IL-1β (10 ng/mL) for 24 h and then co-cultured with L-theanine for 24 h. The effects of L-theanine on IL-1β-stimulated expression of pro-inflammatory cytokines and hydrolytic enzyme were analyzed using Western blotting, quantitative polymerase chain reaction (q-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. An immunofluorescence assay was used to detect nuclear factor kappa B (NF-κB) phosphorylation. OA was induced by anterior cruciate ligament transection (ACLT) surgery in rats and celecoxib was used as a positive control. OA severity was measured using the Osteoarthritis Research Society International (OARSI) grading system to describe histological changes. The results showed that L-theanine decreased the expression of pro-inflammatory mediators, including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), both in vivo and in vitro. L-theanine treatment inhibited IL-1β-induced upregulation of matrix metalloproteinases (MMP)-3 and MMP-13, as well as inhibited NF-κB p65 activation. In vivo animal model showed that L-theanine administration (200 mg/kg) significantly alleviated OA lesions and decreased OARSI score. Our data indicated that L-theanine decreased inflammatory cytokines and protected extracellular matrix degradation through inhibition of the NF-κB pathway, and L-theanine may be considered a promising therapeutic strategy in OA prevention.
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Yimam, Mesfin, Young-Chul Lee, Tae-Woo Kim, Breanna Moore, Ping Jiao, Mei Hong, Hyun-Jin Kim, et al. "UP3005, a Botanical Composition Containing Two Standardized Extracts ofUncaria gambirandMorus alba, Improves Pain Sensitivity and Cartilage Degradations in Monosodium Iodoacetate-Induced Rat OA Disease Model." Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/785638.
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Osteoarthritis (OA) is a multifactorial disease primarily noted by cartilage degradation in association with inflammation that causes significant morbidity, joint pain, stiffness, and limited mobility. Present-day management of OA is inadequate due to the lack of principal therapies proven to be effective in hindering disease progression where symptomatic therapy focused approach masks the actual etiology leading to irreversible damage. Here, we describe the effect of UP3005, a composition containing a proprietary blend of two standardized extracts from the leaf ofUncaria gambirand the root bark ofMorus alba, in maintaining joint structural integrity and alleviating OA associated symptoms in monosodium-iodoacetate- (MIA-) induced rat OA disease model. Pain sensitivity, micro-CT, histopathology, and glycosaminoglycans (GAGs) level analysis were conducted. Diclofenac at 10 mg/kg was used as a reference compound. UP3005 resulted in almost a complete inhibition in proteoglycans degradation, reductions of 16.6% (week 4), 40.5% (week 5), and 22.0% (week 6) in pain sensitivity, statistically significant improvements in articular cartilage matrix integrity, minimal visual subchondral bone damage, and statistically significant increase in bone mineral density when compared to the vehicle control with MIA. Therefore, UP3005 could potentially be considered as an alternative therapy from natural sources for the treatment of OA and/or its associated symptoms.
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Kwon, Yu-Jin, Il-Hyun Koh, Kwangho Chung, Yong-Jae Lee, and Hyoung-Sik Kim. "Association between platelet count and osteoarthritis in women older than 50 years." Therapeutic Advances in Musculoskeletal Disease 12 (January 2020): 1759720X2091286. http://dx.doi.org/10.1177/1759720x20912861.
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Background: Osteoarthritis (OA) is a multifactorial disease involving inflammatory processes. Platelets play important roles in both hemostasis and the inflammatory response; however, the relationship between platelet count and OA is unclear. Our aim was to evaluate the association between platelet count and knee and hip OA in Korean women. Methods: In this cross-sectional designed study, we included a total of 6011 women aged ⩾50 years from the 2010–2013 Korea National Health and Nutrition Examination Survey. Knee and hip OA were defined as Kellgren–Lawrence grade ⩾2 and presence of knee or hip pain, respectively. Platelet counts were divided into quartiles as follows: Q1, 150–212 (103/µl); Q2, 213–246 (103/µl); Q3, 247–283 (103/µl); and Q4, 284–450 (103/µl). Multiple logistic-regression analysis was conducted to calculate odds ratios and 95% confidence intervals. Receiver operating characteristic analysis was performed to determine the optimal platelet count cut-off with which to discriminate participants with knee and/hip OA versus those without OA. Results: Of the 6011 participants, 1141 (18.1%) had knee or hip OA. The mean age of participants without OA was 60.6 years, and that of participants with OA was 68.0 years. Compared with the lowest quartile, odds ratios (95% confidence intervals) for OA were 1.08 (0.84–1.39) for Q2, 0.94 (0.73–1.23) for Q3, and 1.35 (1.08–1.69) for Q4 after adjusting for confounders. The prevalence of OA was significantly higher with platelet counts ⩾288 × 103/µl, compared with platelet counts <288 × 103/µl. Conclusion: High platelet counts within the normal range are significantly associated with knee and hip OA.
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Gao, Xiang, Shuangpeng Jiang, Zhangzhen Du, Angtin Ke, Qingwei Liang, and Xu Li. "KLF2 Protects against Osteoarthritis by Repressing Oxidative Response through Activation of Nrf2/ARE Signaling In Vitro and In Vivo." Oxidative Medicine and Cellular Longevity 2019 (November 19, 2019): 1–18. http://dx.doi.org/10.1155/2019/8564681.
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Osteoarthritis (OA) is a multifactorial and inflammatory disease characterized by cartilage destruction that can cause disability among aging patients. There is currently no effective treatment that can arrest or reverse OA progression. Kruppel-like factor 2 (KLF2), a member of the zinc finger family, has emerged as a transcription factor involved in a wide variety of inflammatory diseases. Here, we identified that KLF2 expression is downregulated in IL-1β-treated human chondrocytes and OA cartilage. Genetic and pharmacological overexpression of KLF2 suppressed IL-1β-induced apoptosis and matrix degradation through the suppression of reactive oxygen species (ROS) production. In addition, KLF2 overexpression resulted in increased expression of heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1) through the enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Further, Nrf2 inhibition abrogated the chondroprotective effects of KLF2. Safranin O/fast green and TUNEL staining demonstrated that adenovirus-mediated overexpression of KLF2 in joint cartilage protects rats against experimental OA by inhibiting cartilage degradation and chondrocyte apoptosis. Immunohistochemical staining revealed that KLF2 overexpression significantly decreases MMP13 expression caused by OA progression in vivo. This in vitro and in vivo study is the first to investigate the antioxidative effect and mechanisms of KLF2 in OA pathogenesis. Our results collectively provide new insights into OA pathogenesis regulated by KLF2 and a rationale for the development of effective OA intervention strategies.
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Kokkotis, Christos, Serafeim Moustakidis, Giannis Giakas, and Dimitrios Tsaopoulos. "Identification of Risk Factors and Machine Learning-Based Prediction Models for Knee Osteoarthritis Patients." Applied Sciences 10, no. 19 (September 28, 2020): 6797. http://dx.doi.org/10.3390/app10196797.
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Knee Osteoarthritis (KOA) is a multifactorial disease that causes low quality of life, poor psychology and resignation from life. Furthermore, KOA is a big data problem in terms of data complexity, heterogeneity and size as it has been commonly considered in the literature with most of the reported studies being limited in the amount of information they can adequately process. The aim of this paper is: (i) To provide a robust feature selection (FS) approach that could identify important risk factors which contribute to the prediction of KOA and (ii) to develop machine learning (ML) prediction models for KOA. The current study considers multidisciplinary data from the osteoarthritis initiative (OAI) database, the available features of which come from heterogeneous sources such as questionnaire data, physical activity indexes, self-reported data about joint symptoms, disability and function as well as general health and physical exams’ data. The novelty of the proposed FS methodology lies on the combination of different well-known approaches including filter, wrapper and embedded techniques, whereas feature ranking is decided on the basis of a majority vote scheme to avoid bias. The validation of the selected factors was performed in data subgroups employing seven well-known classifiers in five different approaches. A 74.07% classification accuracy was achieved by SVM on the group of the first fifty-five selected risk factors. The effectiveness of the proposed approach was evaluated in a comparative analysis with respect to classification errors and confusion matrices to confirm its clinical relevance. The results are the basis for the development of reliable tools for the prediction of KOA progression.
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Shapovalova, D. A., A. V. Tyurin, S. S. Litvinov, E. K. Khusnutdinova, and R. I. Khusainova. "The role of VNTR aggrecan gene polymorphism in the development of osteoarthritis in women." Vavilov Journal of Genetics and Breeding 22, no. 7 (November 9, 2018): 865–72. http://dx.doi.org/10.18699/vj18.427.
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Osteoarthritis (OA) is a common multifactorial joint disease. Undifferentiated connective tissue dysplasia (uCTD) is a genetically determined lesion of the connective tissue structures, including joints, and it can be one of the factors predisposing to development of OA. Solving the problem of comorbidity of OA and uCTD signs will contribute to the early diagnosis and prophylactics of OA. Aggrecan is one of the major structural components of cartilage and it provides the ability to resist compressive loads throughout life. We examined 316 women (mean age 50.5 ± 4.77) for signs of uCTD and OA. A study of the aggrecan gene (ACAN) VNTR polymorphism, which is represented by a variable number of 57 nucleotide repeats, was performed. We searched for associations between the VNTR locus and OA in general and with an account of the localization of the pathological process, as well as with the presence of uCTD signs. Twelve allelic variants and 24 genotypes of the VNTR polymorphism of the aggrecan gene (ACAN) were identified, the most frequent variants were alleles with 27, 28 and 26 repeats. A significance of allele *27 (х2= 6.297, p = 0.012, odds ratio (OR) = 1.50; 95 % confidence interval (CI) 1.09-2.05) in the development of OA in general, knee OA (х2= 4.613, p = 0.031, OR = 1.52; 95 % CI 1.04-2.23), and multiple OA (х2= 4.181, p = 0.04, OR = 1.68; 95 % CI 1.02-2.78) was revealed. Homozygous genotype *27*27 was associated with OA (х2= 3.921, р = 0.047, OR = 1.72; 95 % CI 1-2.96), and OA with uCTD signs in women (х2= 5.415, p = 0.019, OR = 2.34; 95 % CI 1.13-4.83).
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Arias, Consuelo, Nicolás Saavedra, Kathleen Saavedra, Marysol Alvear, Alejandro Cuevas, Silvya Stuchi Maria-Engler, Dulcineia S. P. Abdalla, and Luis A. Salazar. "Propolis Reduces the Expression of Autophagy-Related Proteins in Chondrocytes under Interleukin-1β Stimulus." International Journal of Molecular Sciences 20, no. 15 (August 1, 2019): 3768. http://dx.doi.org/10.3390/ijms20153768.
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Background: Osteoarthritis (OA) is a progressive and multifactorial disease that is associated with aging. A number of changes occur in aged cartilage, such as increased oxidative stress, decreased markers of healthy cartilage, and alterations in the autophagy pathway. Propolis extracts contain a mixture of polyphenols and it has been proved that they have high antioxidant capacity and could regulate the autophagic pathway. Our objective was to evaluate the effect of ethanolic extract of propolis (EEP) on chondrocytes that were stimulated with IL-1β. Methods: Rabbit chondrocytes were isolated and stimulated with IL-1β and treated with EEP. We evaluated cell viability, nitric oxide production, healthy cartilage, and OA markers, and the expression of three proteins associated with the autophagy pathway LC3, ATG5, and AKT1. Results: The EEP treatment reduces the expression of LC3, ATG5, and AKT1, reduces the production of nitric oxide, increases the expression of healthy markers, and reduces OA markers. Conclusions: These results suggest that treatment with EEP in chondrocytes that were stimulated with IL-1β has beneficial effects, such as a decrease in the expression of proteins associated with autophagy, MMP13, and production of nitric oxide, and also increased collagen II.
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Ahmed, Zara, Lydia C. Powell, Navid Matin, Andrew Mearns-Spragg, Catherine A. Thornton, Ilyas M. Khan, and Lewis W. Francis. "Jellyfish Collagen: A Biocompatible Collagen Source for 3D Scaffold Fabrication and Enhanced Chondrogenicity." Marine Drugs 19, no. 8 (July 22, 2021): 405. http://dx.doi.org/10.3390/md19080405.
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Osteoarthritis (OA) is a multifactorial disease leading to degeneration of articular cartilage, causing morbidity in approximately 8.5 million of the UK population. As the dense extracellular matrix of articular cartilage is primarily composed of collagen, cartilage repair strategies have exploited the biocompatibility and mechanical strength of bovine and porcine collagen to produce robust scaffolds for procedures such as matrix-induced chondrocyte implantation (MACI). However, mammalian sourced collagens pose safety risks such as bovine spongiform encephalopathy, transmissible spongiform encephalopathy and possible transmission of viral vectors. This study characterised a non-mammalian jellyfish (Rhizostoma pulmo) collagen as an alternative, safer source in scaffold production for clinical use. Jellyfish collagen demonstrated comparable scaffold structural properties and stability when compared to mammalian collagen. Jellyfish collagen also displayed comparable immunogenic responses (platelet and leukocyte activation/cell death) and cytokine release profile in comparison to mammalian collagen in vitro. Further histological analysis of jellyfish collagen revealed bovine chondroprogenitor cell invasion and proliferation in the scaffold structures, where the scaffold supported enhanced chondrogenesis in the presence of TGFβ1. This study highlights the potential of jellyfish collagen as a safe and biocompatible biomaterial for both OA repair and further regenerative medicine applications.
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Said, F. MM, I. F. Akhtyamov, A. I. Kudryavtsev, and A. N. Nuriakhmetov. "Etiopathogenic bases for patellofemoral arthritis development." Kazan medical journal 99, no. 2 (April 15, 2018): 270–78. http://dx.doi.org/10.17816/kmj2018-270.
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Patellofemoral arthritis is nowadays an actual issue of traumatology and orthopedics. High prevalence of this pathology around the world (6.9 to 36.1%) is associated with multiple etiological causes, responsible for certain difficulties in diagnosis and complexity of determining an individualized pathogenetic method of treatment. The pathology, often occurring in the young age, is called «delayed or late arthritis», due to the fact that it is often ignored in the early stages of its development. This leads, in the final stages of disease, to manifestation of classic osteoarthritis involving all the structures of the knee joint in the process. The literature review is devoted to the study of etiology, pathogenesis and anatomical features of the development of patellofemoral arthritis. From the clinical point of view, the most important factors, influencing patellofemoral arthritis course, are analyzed. They include mechanisms of the disease, anatomical features of patella, trochlear surface and femoral condyles, which affect the disease course. The article discusses the risk factors of patellofemoral arthritis, such as weakness of vastus muscles of quadriceps femoris, increased knee Q-angle, increased femoral anteversion and tibial rotation, abnormalities of patellar and tibial epicondyles morphology. In addition the study presents some data about dysplasia of the condyles and femoral trochlea and patella, disposition of the patella and dysplasia of the quadriceps. Variations of configuration and position of patella affecting its stability are described and presented. The article also focuses on the influence of internal tibial rotation and femoral anteversion on the development of disease, as well as patellar instability as a multifactorial cause.
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Krylov, M. Yu, L. I. Alekseeva, and E. P. Scharapova. "Association of the rs2167270 polymorphism of the leptin gene (LEP) with the intensity of pain in patients with osteoarthritis of the knee." Obesity and metabolism 18, no. 2 (July 24, 2021): 210–17. http://dx.doi.org/10.14341/omet10189.
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Background: Osteoarthritis (OA) is a significant social problem as it is the most common disease of the joints. OA is a multifactorial disease in which great attention is paid to hereditary factors. Recently, a number of studies have demonstrated the contribution of a number of genes to the subjective assessment of pain in OA, which is the main symptom of this disease. The association of P2X7, TRPV1 and TACR1 genes and some others with pain sensitivity has been shown. One of the risk factors of pain among many others, is the increased weight. Abdominal adipose tissue is a source of release of pro-inflammatory adipokines that cause systemic inflammation associated with damage to many tissues, including subchondral bone, synovial membrane. Leptin is an endogenous hormone from the adipokine family encoded by the obesity gene leptin (LEP) and which is synthesized primarily in adipocytes.Aims: To investigate the possible association of rs2167270 (A19G) polymorphism of the LEP gene with pain intensity in patients with knee OA.Materials and methods: The study was conducted among women diagnosed with OA. Using the VAS scale (Visual analog scale), patients with mild knee pain — group 1 (VAS ≤ 40 mm) and patients with moderate or severe pain — group 2 (VAS>40 mm) were selected for pain assessment. Genetic variants of A19G leptin gene polymorphism were studied by polymerase chain reaction followed by restriction fragment length analysis (PCR-RFLP) method.Results: In the group of patients with moderate or severe pain intensity (group 2, n=61), a statistically significant association was shown with a higher body mass index (p=0.006) and an increased frequency of carriers of the 19GG genotype (p=0,051) compared to group 1 (n=36). Carriers of the 19GG genotype statistically significantly had a higher rate of knee pain and an early age of OA debut compared to carriers of the 19AA genotype (p=0,035 and p=0,015, respectively).Conclusions: The findings open up new possibilities for predicting pain symptoms in patients with knee OA by genetic testing of A19G polymorphic variants of the leptin gene.
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Kao, M. H., and Y. F. Tsai. "Development and psychometric testing of a Scale for Evaluating Self-management Needs of Knee Osteoarthritis (SMNKOA) in Taiwan." European Psychiatry 33, S1 (March 2016): S614. http://dx.doi.org/10.1016/j.eurpsy.2016.01.2298.
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IntroductionKnee OA is a chronic and multifactorial disease; self-management needs are complex, which requires a multidimensional management plan. There is a need for healthcare providers to provide patients with knowledge of knee OA and how to effectively manage the disease.ObjectiveSelf-management-needs scales are one means of determining the management requirements of an individual patient. There is no suitable instrument available for assessing self-management needs of adult patients with knee OA in Taiwan. This study developed an instrument that could assess the self-management needs of knee OA patients using Orem's self-care theory as a theoretical framework.AimsThis study developed and psychometrically tested a new instrument for measuring adult patients’ self-management needs of knee OA (SMNKOA).MethodsDevelopment of the instrument involved three phases: item generation and scale development; content and face validity of the initial instrument; and evaluation of validity and reliability of the new instrument. Participants (n = 372) were purposively sampled from orthopaedic clinics at medical centres in Taiwan.ResultsThe self-care theory guided the development of the 35-item SMNKOA scale. The content validity index was 0.83. Principal components analysis identified a 3-factor solution, accounting for 53.19% of the variance. The divergent validity was –0.67; convergent validity was –0.51. Cronbach's α was 0.95, Pearson correlation coefficient was 0.88, and the intraclass correlation coefficient was 0.95.ConclusionsThe SMNKOA scale can measure and identify the individual self-management needs of knee OA patients. It will help healthcare providers better evaluate strategies that can help these patients cope with this chronic disease.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Panagiotopoulou, Olga, Todd C. Pataky, and John R. Hutchinson. "Foot pressure distribution in White Rhinoceroses (Ceratotherium simum) during walking." PeerJ 7 (May 15, 2019): e6881. http://dx.doi.org/10.7717/peerj.6881.
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White rhinoceroses (Ceratotherium simum) are odd-toed ungulates that belong to the group Perissodactyla. Being second only to elephants in terms of large body mass amongst extant tetrapods, rhinoceroses make fascinating subjects for the study of how large land animals support and move themselves. Rhinoceroses often are kept in captivity for protection from ivory poachers and for educational/touristic purposes, yet a detrimental side effect of captivity can be foot disease (i.e., enthesopathies and osteoarthritis around the phalanges). Foot diseases in large mammals are multifactorial, but locomotor biomechanics (e.g., pressures routinely experienced by the feet) surely can be a contributing factor. However, due to a lack of in vivo experimental data on rhinoceros foot pressures, our knowledge of locomotor performance and its links to foot disease is limited. The overall aim of this study was to characterize peak pressures and center of pressure trajectories in white rhinoceroses during walking. We asked two major questions. First, are peak locomotor pressures the lowest around the fat pad and its lobes (as in the case of elephants)? Second, are peak locomotor pressures concentrated around the areas with the highest reported incidence of pathologies? Our results show a reduction of pressures around the fat pad and its lobes, which is potentially due to the material properties of the fat pad or a tendency to avoid or limit “heel” contact at impact. We also found an even and gradual concentration of foot pressures across all digits, which may be a by-product of the more horizontal foot roll-off during the stance phase. While our exploratory, descriptive sample precluded hypothesis testing, our study provides important new data on rhinoceros locomotion for future studies to build on, and thus impetus for improved implementation in the care of captive/managed rhinoceroses.
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Gigliucci, G., O. De Lucia, A. Fioravanti, F. Galluccio, S. Guiducci, A. Moretti, M. Matucci-Cerinic, et al. "AB0588 “ESORT” ITALIAN SOCIETY OF RHEUMATOLOGY (SIR) REGISTER ON OSTEOARTHRITIS (OA): PRELIMINARY DATA." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1331.1–1331. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1001.
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Background:In Italy Osteoarthritis (OA) is a widespread and disabling disease that affects an increasingly large number of patients in the population, representing one of the main causes of morbidity and disability with high socio-economic costs. The etiology of OA is multifactorial, even if the significant association with some modifiable risk factors like mechanical overload and obesity is now well demonstrated. Early diagnosis and treatment strategies in OA could reduce both patient morbidity and associated costs.Objectives:Promoted by the Italian Society of Rheumatology (SIR), The Early Symptomatic OsteoaRThritis (ESORT) registry has the aim to study the natural history of OA from the earliest stages (pre- radiographic) considering risk factors in the progression of the disease, and the influence of therapeutic factors on long-term disease outcomes. The ESORT register aims to describe the socio-demographic and clinical characteristics of patients affected by OA in Italy; evaluates the extent of symptoms, functional damage, comorbidities, the frequency of use of drugs currently indicated in our country, and differences related to clinical subsets according with comorbidities and geographical localization of the patient.Methods:Actually 8 Italian Rheumatology centers are involved in the online data entry data of the SIR registry (developed and validated by SIR Study Center), considering patients affected by OA. In particular, the electronic database collects information about main demographic variables, significant anamnestic elements (risk factors and comorbidities), localization of OA, laboratory data, clinimetric indices with WOMAC / FIHOA / VAS scales, radiographic instrumental data and therapy in act. These data are reported in specific forms in the register with annual reassessment.Results:Currently, 318 patients with OA are included in the “ESORT” registry with an extension of observation up to 48 months, 214 women and 104 men with an average age of 71 years and an average weight of 72 kg. About 14% of patients affected by knee OA show Kellgren and Lawrence radiological stage 0 in presence of painful symptoms at the knees. The most frequent localization of OA is the knee (63%), followed by the hip (41%), hand (36%), spine (34%), and other sites (16%). The Table 1 shows details of some parameters (average age, average weight, intake of NSAIDs, intake of opioids and intake of chondroprotectors) according to the localization of the disease. From the registry data, patients with OA results treated mainly with NSAIDs and chondroprotectors, and patients with knee OA are the most frequently treated with opioid analgesics (44%), less used in other OA locations.Conclusion:The “ESORT” register is a useful tool for epidemiological and clinical information relating to patients with OA and for monitoring the evolution of the disease and the response to therapy.Average age (years)Average weight (kg)Intake of NSAIDs (% of patients)Intake of opioids (% of patients)Intake of chondroprotectors (% of patients)OA hand706774%10%25-31%OA knee747585%44%53-59%OA hip697075%25%24-28%OA spine757576%14%19-28%OA other localization747369%13%15-35%Disclosure of Interests:Gianfranco Gigliucci: None declared., Orazio De Lucia: None declared., Antonella Fioravanti: None declared., Felice Galluccio: None declared., Serena Guiducci: None declared., Antimo Moretti: None declared., Marco Matucci-Cerinic Speakers bureau: Consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Grant/research support from: Consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Antonella Murgo: None declared., Simone Parisi Speakers bureau: Personal fees (as speaker and/or consultant) from NOVARTIS, BMS, LILLY, UCB, MSD, PFIZER, ABBVIE, BIOGEN, AMGEN, JANSENN CILAG, CHIESI and GRUNENTHAL outside the submitted work;, Consultant of: Personal fees (as speaker and/or consultant) from NOVARTIS, BMS, LILLY, UCB, MSD, PFIZER, ABBVIE, BIOGEN, AMGEN, JANSENN CILAG, CHIESI and GRUNENTHAL outside the submitted work;, Roberta Ramonda: None declared., Sara Tenti: None declared., Enrico Tirri: None declared., Alberto Migliore Speakers bureau: Grants from Abiogen,Lilly,Fidia,Jansen (outside the submitted work), Consultant of: Grants from Abiogen,Lilly,Fidia,Jansen (outside the submitted work), Grant/research support from: Grants from Abiogen,Lilly,Fidia,Jansen (outside the submitted work).
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Bollapragada, Mani Kumar, Manjula Shantaram, and Sunil Kumar R. "OBESITY: DEVELOPMENT, EPIDEMIOLOGY, FACTORS AFFECTING, QUANTITY, HEALTH HAZARDS, MANAGEMENT AND NATURAL TREATMENT-A REVIEW." International Journal of Pharmacy and Pharmaceutical Sciences 9, no. 2 (February 1, 2017): 12. http://dx.doi.org/10.22159/ijpps.2017v9i2.15049.
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<p>Due to the advancement in science, enhanced knowledge on the physiological aspects of almost all the tissues and the organs of the human body is gained. One of the most important prevalent topics needed for discussion is obesity and its effect on the metabolic changes leading to disorders in the human body such as diabetes, hypertension, cardiovascular diseases in addition to chronic diseases such as stroke, osteoarthritis, sleep apnea, some cancers, and inflammation-based pathologies. In recent years, obesity is a serious socioeconomic issue, which has become one of the major health problems all over the world, affecting people of all ages, sex, ethnicities and races. Obesity is a complex and multifactorial disease caused by the interaction of a myriad genetics, dietary, lifestyle and environmental factors and it is characterised by an excessive weight for height due to an enlarged fat deposition in the adipose tissue, which is due to a higher calorie intake than the energy expenditure. The pharmaceutical drugs are currently available to treat obesity but generally they have unpleasant side effects. Recent researches demonstrated the potential of natural products to counteract on obesity. Now the novel promising approach is the usage of dietary supplements and plant products and their bioactive compounds that could interfere on pancreatic lipase activity, food intake, lipid metabolism and adipocyte differentiation. In a similar way, hundreds of extracts are currently being isolated from plants, fungi, algae or bacteria and are screened for their potential inhibitions of activity against obesity. Natural products may have a synergistic activity that increases their bioavailability and action on multiple molecular targets.</p>
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Mählich, Daniela, Anne Glasmacher, Ilka Müller, Johannes Oppermann, David Grevenstein, Peer Eysel, Juliane Heilig, Brunhilde Wirth, Frank Zaucke, and Anja Niehoff. "Expression and Localization of Thrombospondins, Plastin 3, and STIM1 in Different Cartilage Compartments of the Osteoarthritic Varus Knee." International Journal of Molecular Sciences 22, no. 6 (March 17, 2021): 3073. http://dx.doi.org/10.3390/ijms22063073.
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Osteoarthritis (OA) is a multifactorial disease which is characterized by a change in the homeostasis of the extracellular matrix (ECM). The ECM is essential for the function of the articular cartilage and plays an important role in cartilage mechanotransduction. To provide a better understanding of the interaction between the ECM and the actin cytoskeleton, we investigated the localization and expression of the Ca2+-dependent proteins cartilage oligomeric matrix protein (COMP), thrombospondin-1 (TSP-1), plastin 3 (PLS3) and stromal interaction molecule 1 (STIM1). We investigated 16 patients who suffered from varus knee OA and performed a topographical analysis of the cartilage from the medial and lateral compartment of the proximal tibial plateau. In a varus knee, OA is more pronounced in the medial compared to the lateral compartment as a result of an overloading due to the malalignment. We detected a location-dependent staining of PLS3 and STIM1 in the articular cartilage tissue. The staining intensity for both proteins correlated with the degree of cartilage degeneration. The staining intensity of TSP-1 was clearly reduced in the cartilage of the more affected medial compartment, an observation that was confirmed in cartilage extracts by immunoblotting. The total amount of COMP was unchanged; however, slight changes were detected in the localization of the protein. Our results provide novel information on alterations in OA cartilage suggesting that Ca2+-dependent mechanotransduction between the ECM and the actin cytoskeleton might play an essential role in the pathomechanism of OA.
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Gudkevich, K., N. Martusevitch, and E. Dashkevich. "POS1377 SOME PARAMETERS OF ENDOTHELIAL FUNCTION IN PATIENTS WITH IDIOPATHIC AVASCLAR NECROSIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 970.2–971. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3699.
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Background:Avascular necrosis (AN) is a disease, which is the result of blood flow disturbance and necrosis of the bone tissue. It affects predominantly men of working age and steadily progresses to secondary osteoarthritis. AN is a multifactorial disease. In the context of vascular hypothesis it is of particular interest to evaluate homocysteine and its metabolism in patients with AN.Objectives:The aim of the present study was to evaluate some parameters of endothelial function in patients with AN of the femoral head or femoral condyles in order to determine possible treatment and prevention options.Methods:We included 53 patients with AN of the femoral head or femoral condyles into the study. The patients were aged 49 (35-62) years, 58,49% (n=31) were male. The inclusion criteria was diagnosis of AN confirmed by X-Ray, CT or MRI. The exclusion criteria were: traumatic AN, Legg-Calve-Pertes disease, connective tissue systemic diseases. We recruited 51 patients into the control group. The groups were comparable by age and gender. In order to analyse engothelial function in the groups we investigated the following serum parameters: homocysteine, vitamin B12, folate. In order to analyse the data obtained we used non-parametric statistics.Results:We determined a higher level of homocysteine in patients with AN (12,15 (7,55-14,60) vs. 8,18 (6,57-10,70) mcmol/l in the control group, p=0,04). Also we observed almost equal levels of vitamin B12 in patients with AN an in the control group (531,95 (340,80-793,55) vs. 532,75 (417,60-669,7) pg/ml, p=0,99). The level of folate was lower in the study group (5,66 (3,83-6,83) vs. 6,99 (5,02-10,38) ng/ml, p=0,01).Conclusion:The data obtained show that homocysteine level in patients with AN is higher. This can be a consequence of folate deficiency, which takes part in homocysteine metabolism. Therefore, homocysteine metabolism disturbances can lead to endothelial dysfunction, which results in cardiovascular events in the heart, brain, kidneys [1] as well as in the bone, according to the study results. Folate supplement is the possible way of AN treatment and prevention.References:[1]Nowroozpoor A, Gutterman D, Safdar B. Is microvascular dysfunction a systemic disorder with common biomarkers found in the heart, brain, and kidneys? - A scoping review. Microvasc Res. 2021 Mar;134:104123. doi: 10.1016/j.mvr.2020.104123. Epub 2020 Dec 15. PMID: 33333140.Disclosure of Interests:None declared
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Crepaldi, G., M. Voci, M. Saracco, A. Laezza, P. Santino, M. Marcato, G. Rovera, and C. Lomater. "AB0241 PREVALENCE OF ANXIOUS SYMPTOMS AND DEPRESSION IN A SAMPLE OF PATIENTS WITH RHEUMATOID ARTHRITIS (RA) AND OTHER CHRONIC RHEUMATIC DISEASES." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1420.2–1421. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2471.
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Background:Clinical practice with patients suffering from chronic diseases highlights the presence of psychological symptoms of discomfort fed by biological and non-biological mechanisms linked to disease and treatment. In rheumatic diseases, literature detects the presence of anxious symptoms and depressed mood of clinical and sub-clinical importance with a multifactorial genesis1.Objectives:To detect the impact on the state of health of anxious symptoms and depressed mood in a population suffering from RA and other rheumatic diseases in order to implement the effectiveness of psychological intervention through the selection of patients who present critical levels of discomfort.Methods:Patients afferent to the Rheumatology outpatient clinic of Mauriziano Hospital have been screened from May 2018 to July 2018 with two self-administered questionnaires: HADS-A and HADS-D (Hospital Anxiety and Depression Scale), specifically developed for the evaluation of anxious and depressive symptoms in medical pathologies, and HAQ (Health Assessment Questionnaire) to explore functional disability. Data about rheumatic diagnosis and socio-demographic characteristics were also collected. Data were analyzed with descriptive statistics; the Student Test and the ANOVA test were used to evaluate prevalence and to compare the presentation of symptoms in the different diseases and the Pearson correlation coefficient was used to evaluate the relationship between symptoms and disability.Results:A total of 427 subjects were screened (317 females and 110 males), aged between 19 and 90 years (mean 60 ± 14 yrs). 156 subjects (36.5%) had a diagnosis of RA, 76 (17.8%) of psoriatic arthritis, 42 (9.8%) of ankylosing spondylitis, 14 (3.3%) of systemic lupus erythematosus and 139 (32.6%) of other rheumatic diseases (including Sjogren, osteoarthritis, fibromyalgia).A high prevalence of anxious symptoms and depressed mood has been found and the number of subjects reporting scores indicating a clinically relevant uncomfortable situation (HADS ≥ 11) was also relevant (Table 1); an increased prevalence in female patients was observed. There were no differences in the presentation of symptoms between RA and the other included pathologies (Table 2).Table 1.Prevalence of anxiety and depression according to the HADS questionnaire in rheumatic diseasesMeanSDHADS-A7.564.63HADS-D7.124.59HADS-A ScoreN%0-722452.47-108419.711-2111927.9HADS-D ScoreN%0-723154.17-109221.511-2110424.4Table 2.Comparison between RA and other rheumatic diseases in anxiety and depression symptoms presentation (ANOVA test).NMeanSDSECIHADS-ARA1562.345.200.411.52PsA762.304.470.511.28AS421.513.190.490.51SLE141.773.741.00-0.38other1392.465.080.431.61HADS-DRA1561.743.510.281.19PsA762.034.210.481.07AS420.690.540.080.52SLE140.930.680.180.54other1391.683.790.321.04There was a positive and significant correlation between anxious symptoms or depressed mood and functional disability (0.49 and 0.60 respectively, p<0,01).Conclusion:The results show a significant presence of uncomfortable situations that could evolve in a psychopathological sense. The discomfort expressed through anxious and depressive symptoms is related to the level of functional disability. Recognizing the presence of psychological distress allows to orient the treatment plan and facilitate the patient’s adaptation to the disease condition.References:[1]Geenen R. et al. Best Pract Res Clin Rheumatol. 2012;26(3):305-19.Disclosure of Interests:Gloria Crepaldi Consultant of: Advisory board for Sanofi and Celgene, Speakers bureau: BMS, MSD, Mariarosaria Voci: None declared, Marta Saracco: None declared, Antonella Laezza: None declared, Paolo Santino: None declared, Maddalena Marcato: None declared, Guido Rovera: None declared, Claudia Lomater Consultant of: Advisory board for Sanofi, Novartis, Abbvie
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Lim, D. R., D. Farina, W. Huang, and J. Zhu. "A181 ENDOSCOPIC BALLOON DILATION IS EFFECTIVE AND SAFE IN THE MANAGEMENT OF NSAID-INDUCED NON-ULCERATIVE GASTRIC OUTLET OBSTRUCTION." Journal of the Canadian Association of Gastroenterology 3, Supplement_1 (February 2020): 48–50. http://dx.doi.org/10.1093/jcag/gwz047.180.
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Abstract Background We describe an unusual case of NSAID-induced gastric outlet obstruction (GOO) in the absence of malignancy or ulcers. This was successfully managed conservatively with drug withdrawal and serial endoscopic balloon dilation (EBD). Aims Case Report Methods Case Report and Literature Review Results A 58-year-old woman with 20-year history of daily Ketorolac use for osteoarthritis presented with iron deficiency anemia (IDA) of 58 g/L and post-prandial emesis for 2 months. There was no overt GI bleeding. Gastroscopy revealed severe erosive esophagitis and GOO with no ulcers. After a negative CT imaging ruled out extrinsic malignant compression, GOO was managed with EBD. Examination of the duodenum post-EBD revealed complete atrophy and scalloping. Focused biopsies reveal chronic gastritis, complete villous atrophy in the duodenum; ruled out H. Pylori, celiac disease, amyloidosis and dysplasia. EUS negative for infiltrative disease or regional adenopathy. Vitamin B12, anti-TTG I IgA, HLA DQ2/8 were normal. These findings made drug-induced enteropathy the top contender. PPI therapy was initiated and NSAID discontinued. Five serial EBD were performed over 4 months to 18mm. A pureed diet was tolerated after 2 dilations. Follow-up at 3 months showed partial recovery of enteropathy and pyloric stenosis. No adverse events were seen. The severe esophagitis was likely an erosive process secondary to reflux from GOO. Her IDA is likely multifactorial: Severe enteropathy and GOO may have led to chronic malabsorption; occult GI bleeding from erosions or ulcers that have healed may further contribute. Ketorolac could explain the enteropathy. COX-1 inhibition leads to decreased gastric cytoprotection. In rat models, COX-2 inhibition has been suggested to delay gastric healing and dysregulated immune response to food antigens in the small bowel [4–6]. NSAID-induced GOO almost always occur in the context of peptic ulcer disease [1,2]. A similar case [3] found pyloric stenosis in a 75-year old woman with esophagitis and ulcer-induced pyloric stenosis. They postulate that post ulcerative healing led to benign pyloric stenosis and explained the absence of ulcers. Historically, surgical intervention and stent placement have played a major role in the management of benign mechanical GOO. EBD has replaced surgical intervention as first line therapy [7] showing promising results beyond 3 months post EBD[8], sparing patients from surgery related morbidity. An algorithm has been suggested by us [Img 1] for the management of benign GOO. Conclusions We present an unusual case of NSAID-induced mechanical GOO and enteropathy. This case highlights these entities as rare but serious complications of chronic NSAID use. Management of benign mechanical GOO should be individualized. Prudence with prescribing NSAIDs to at risk populations is recommended. Funding Agencies None