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  • The Role of Platelet-Rich Plasma in Promoting Cartilage Integration and Chondrocyte Migration

    inBold\">Abstract

    Objectives: Current therapies for cartilage repair either do not result in regeneration of articular cartilage, or there is inadequate integration with the host tissue leading to failure of the repair. Thus, there is an interest in developing alternative approaches. The mechanisms of cartilage integration remain relatively unknown, however it is believed that chondrocyte migration is crucial to this process. Previously, we showed that platelet rich plasma (PRP) enhances in vitro cartilage tissue formation. We hypothesized that PRP will enhance the integration of bioengineered cartilage with native cartilage due to increased matrix accumulation at the interface and that PRP could promote chondrocyte migration.

    Methods: Isolated bovine chondrocytes were seeded on a porous bone substitute and grown in vitro to form osteochondral-like tissue. After 7 days the biphasic constructs were soaked in PRP for 30 minutes prior to implantation into the core of a ring-shaped osteochondral explant. Controls were not soaked in PRP. The resulting implant-explant construct was cultured in a stirring bioreactor for 2 weeks (contact model). Alternatively, the PRP soaked biphasic construct was placed 2mm away from a native cartilage/bone plug of equal dimensions to assess chondrocyte migration between the two tissues (non-contact model). The integration zone was visualized histologically. A push-out test was performed to assess the strength of integration. Matrix accumulation at the zone of integration was assessed biochemically and the gene expression of the cells in this region was assessed by RT-PCR. Cell migration was evaluated by video microscopy over 8 days. Significance (p<0.05) was determined by a χ2 test, a student\'s t-test or one-way ANOVA with tukey\'s post hoc.

    Conclusion: PRP soaked bioengineered cartilage implants showed improved integration with native cartilage compared to non-soaked implants perhaps due to increased matrix accumulation. Chondrocytes grew out from the in vitro formed tissue and migrated along fibers after PRP soaking. The contribution of these cells to integration requires further study.

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  • A Novel Treatment for Carpal Tunnel Syndrome?

    Abstract

    Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and is caused by chronic compression of the median nerve as it enters the carpal tunnel. Although the prevalence and incidence of CTS vary widely depending on the diagnostic criteria used, it is thought that, clinically, approximately 1 in 10 people have development of carpal tunnel syndrome. 1,2 At this time, there is no consensus for the treatment of mild to moderate carpal tunnel syndrome. The American Academy of Orthopedic Surgeons has stated that nonsurgical treatments, such as splinting of the wrist to a neutral position and local corticosteroid injections, are reasonable options for patients early in the course of symptoms when there is no evidence of median nerve denervation.

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  • Six-month Efficacy of Perineural Dextrose for Carpal Tunnel Syndrome

    Abstract

    Objective: To assess the 6-month effectiveness of ultrasound-guided perineural injection therapy (PIT) using 5% dextrose (D5W) in patients with mild-to-moderate carpal tunnel syndrome (CTS).

    Patients and Methods: A prospective, randomized, placebo-controlled, and double-blind study was conducted between May 1, 2016, through March 30, 2017. A total of 49 participants diagnosed with mild-to-moderate CTS were randomized into D5W and control groups. Participants in the D5W group received 1 session of ultrasound-guided PIT with 5 cc of D5W, and the control group received PIT with normal saline. The visual analog scale measured pain as a primary outcome. Secondary outcomes were Boston Carpal Tunnel Syndrome Questionnaire scores, the cross-sectional area of the median nerve, and electrophysiological measurement results. Assessment was performed before injection and at 1, 3, and 6 months post-injection.

    Results: All patients (data from 30 wrists in each group) completed the study. Compared with the control group, at all post-injection time points, the D5W group had a significant reduction in pain and disability, improvement on electrophysiological response measures, and decreased cross-sectional area of the median nerve.

    Conclusion: Our study reveals that ultrasound-guided PIT with D5W is an effective treatment for patients with mild-to-moderate CTS.

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  • Is osteoarthritis a metabolic disease?

    Abstract

    Obesity, together with aging and injury, is among the main risk factors for osteoarthritis. Obesity-related osteoarthritis can affect not only the weight-bearing joints, but also the hands, suggesting a role for circulating mediators released by the adipose tissue and known as adipokines. Thus, osteoarthritis may have a systemic metabolic component. Evidence from both epidemiological and biological studies support the concept of metabolic osteoarthritis, defined as a broad clinical phenotype that includes obesity-related osteoarthritis. Thus, osteoarthritis can be related to metabolic syndrome or to an accumulation of metabolic abnormalities. In addition, studies have demonstrated associations linking osteoarthritis to several components of the metabolic syndrome, such as hypertension and type 2 diabetes, independently from obesity or any of the other known risk factors for osteoarthritis. Both in vitro and in vitro findings indicate a deleterious effect of lipid and glucose abnormalities on cartilage homeostasis. Chronic low-grade inflammation is a feature shared by osteoarthritis and metabolic disorders and may contribute to the genesis of both. Thus, osteoarthritis is emerging as a disease that has a variety of phenotypes including a metabolic phenotype, in addition to the age-related and injury-related phenotypes.

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  • The effectiveness of platelet-rich plasma injections in gluteal tendinopathy - a randomised, double-blind controlled trial comparing a single platelet-rich plasma injection with a single corticosteroid injection.

    Abstract

    Importance: Gluteus medius/minimus tendinopathy is a common cause of lateral hip pain or greater trochanteric pain syndrome.

    Objective: There would be no difference in the modified Harris Hip score between a single Platelet-Rich-Plasma (PRP) injection compared to a corticosteroid injection (CSI) in the treatment of gluteal tendinopathy.

    Design: Randomised Controlled Clinical Trial; Level of evidence 1, recruitment 29 May 2013 to May 2015, follow-up September 2016. Treating/assessing clinicians and subjects were blinded to treatment. PARTICIPANTS: 228 consecutive patients referred with gluteal tendinopathy were screened to enrol 80 participants. 148 excluded (refusal 48, previous surgery 39, sciatica 28, osteoarthritis 17, full thickness tears tendons 17, other 22).

    Conclusion: Patients with chronic gluteal tendinopathy >4 months, diagnosed with both clinical and radiological examinations, achieved greater clinical improvement at 12 weeks when treated with a single PRP injection than those treated with a single corticosteroid injection.

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  • Comparison study between plasma rich in growth factors and platelet-rich plasma for osteoconduction in rat calvaria

    Abstract

    Objective: Plasma rich in growth factors (PRGF) and platelet-rich plasma (PRP) can be rapidly obtained from patient blood. They are a new and potentially useful adjunct in oral and maxillofacial bone repair or regenerative surgery. The aim of this study was to compare the possibility of new bone formation using PRGF and PRP.

    Methods: The osteogenic potential with transplantation of PRGF or PRP onto rat calvaria was evaluated by histologic examination and microCT. PRGF or PRP was prepared by centrifugation of rat whole blood (WB). First, the cells in the blood product were counted; there were no leukocytes in PRGF, and PRP included leukocytes. PRGF contained higher levels of TGF-β1 and PDGF-BB than PRP. Furthermore, PRGF or PRP was transplanted onto calvarial bone of rats.

    Results: MicroCT showed that PRGF promoted an increase in bone volume when compared to PRP. Histological observation demonstrated that the PRGF group showed newly formed bone in a wide range. In addition, the PRP group showed numerous inflammatory cells compared to the PRGF group in HE-stained specimens. This suggests that PRP might delay bone regeneration due to the inflammatory response.

    Conclusions: PRGF has more availability for bone regeneration than PRP, and PRGF may be useful in bone regeneration treatment.

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  • Ultrasound-guided platelet-rich plasma injections for the treatment of osteoarthritis of the hip

    Abstract

    Objective: To assess the safety and symptomatic changes of IA injections of platelet-rich plasma (PRP) in patients with OA of the hip.

    Methods: Forty patients affected by monolateral severe hip OA were included in the study. Each joint received three IA injections of PRP, which were administered once a week. The primary end point was meaningful pain relief, which was described as a reduction in pain intensity of at least 30% from baseline levels as evaluated by the WOMAC subscale at 6-months post-treatment. The visual analogue scale (VAS) and Harris hip score subscale for pain were used to verify the results. Secondary end points included changes in the level of disability of at least 30% and the percentage of positive responders, i.e. the number of patients that achieved a >30% reduction in pain and disability.

    Results: Statistically significant reductions in VAS, WOMAC and Harris hip subscores for pain and function were reported at 7 weeks and 6 months (P < 0.05). Twenty-three (57.5%) patients reported a clinically relevant reduction of pain (45%, range 30-71%) as assessed by the WOMAC subscale. Sixteen (40%) of these patients were classified as excellent responders who showed an early pain reduction at 6-7 weeks, which was sustained at 6 months, and a parallel reduction of disability. Side effects were negligible and were limited to a sensation of heaviness in the injection site.

    Conclusion: This preliminary non-controlled prospective study supported the safety, tolerability and efficacy of PRP injections for pain relief and improved function in a limited number of patients with OA of the hip.

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  • The contribution of leucocytes to the antimicrobial activity of platelet-rich plasma preparations: a systematic review

    Abstract

    The infection of a wound is one of the major contributors to delays in healing and tissue regeneration. As multi-drug resistance to antibiotics is becoming a serious threat, research in this field has focused on finding new agents and strategies to fight infection and additionally to reduce healing times. The topical use of autologous Platelet Rich Plasma (PRP) as a biological accelerator of the healing process, has been safely used as a form of treatment for wounds since the 1990s. Although the presence or absence of leucocytes in PRP preparation was previously neglected, in the last decade more attention has been paid to their role and several studies have been conducted to explore both their immuno-metabolic effects and their antimicrobial properties. In this review, we aim to summarise the literature on the contribution of leucocytes included in PRP preparations in terms of their antimicrobial properties. This should help to inform clinical practice and additional research in this promising field.

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  • Ultrasound-guided perineural injection with platelet-rich plasma improved the neurophysiological parameters of carpal tunnel syndrome: A case report

    Abstract

    Carpal tunnel syndrome (CTS) is a common and sometimes challenging condition, which causes pain; paresthesia; tingling of the thumb, index and long fingers; and even thenar weakness in the hands. The effectiveness of corticosteroid injections seems to be transient, and there is a lack of information around long-term effects in previous studies. In recent years, platelet-rich plasma (PRP) has proven to bean alternative as it encourages tissue regeneration. We hereby describe a patient with CTS showing significant improvements in electrophysiological parameters after receiving PRP injections. The results revealed significant improvements in the distal motor and sensory latencies as well as the sensory nerve action potential and compound muscle action potential amplitudes of the both median nerves. In summary, if patients are refractory to conservative treatments —such as splinting, oral medication, and corticosteroid injection —PRP may be used as an alternative before surgical intervention.

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  • High-resolution ultrasound and magnetic resonance imaging to document tissue repair after prolotherapy: a report of 3 cases

    Abstract

    High-resolution ultrasound imaging of musculoskeletal tissue is increasing in popularity because of patient tolerability, low cost, ability to visualize tissue in real-time motion, and superior resolution of highly organized tissue such as a tendon. Prolotherapy, defined as the injection of growth factors or growth factor production stimulants to grow normal cells or tissue, has been a controversial procedure for decades; it is currently gaining in popularity among physiatrists and other musculoskeletal physicians. This report describes imaging of tendons, ligaments, and medial meniscus disease (from trauma or degeneration). Although these tissues have been poorly responsive to nonsurgical treatment, it is proposed that tissue growth and repair after prolotherapy in these structures can be documented with ultrasound and confirmed with magnetic resonance imaging. Directions for future research application are discussed.

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  • Platelet-Rich Plasma Augmentation for Hip Arthroscopy

    Abstract

    Biological augmentation and therapeutics are being increasingly used in musculoskeletal and orthopaedic care. Platelet-rich plasma (PRP) is produced from centrifugation of peripheral blood, a process that concentrates platelets within autologous plasma. The process of PRP preparation is fundamental in controlling the contents, and it influences its therapeutic potential. Platelets contain alpha granules that store and release a variety of growth factors and other proteins that may augment the healing environment; PRP also has the added benefit of promoting postsurgical hemostasis. The purpose of this report was to detail our institutional preparation protocol and method of administration of PRP during hip arthroscopy.

    Biological augmentation and therapeutics are being increasingly used in musculoskeletal and orthopaedic care1,2,3 Platelet-rich plasma (PRP) has been used by orthopaedic surgeons and other health practitioners to enhance healing and modulate the environment of tendinopathy, surgical repair of tendons, ligament reconstruction, diffuse arthritis, and focal chondral defects4,5,6.

    PRP is produced from centrifugation of peripheral blood, a process that concentrates platelets within autologous plasma.2 Platelets contain alpha granules that store and release a variety of growth factors, such as cytokines and chemokines, as well as other proteins including insulin growth factor 1, transforming growth factor β1, and vascular endothelial growth factor.1 These biological factors can be modulated by the preparation method used to produce the PRP. For example, leukocyte-rich PRP may increase inflammation and catabolic pathways, whereas leukocyte-poor PRP may decrease inflammation and anabolic pathways.7, 8 In addition, PRP can be prepared as a fibrinous product with adhesive hemostatic properties through endogenous or exogenous activation. The PRP-fibrin preparation can enhance endothelial, epithelial, and epidermal regeneration, by stimulating angiogenesis, improving collagen synthesis, and decreasing scarring.9

    PRP has been historically described as \"a volume of plasma with a platelet count above baseline,\"10 but a more recent quantitative definition requires PRP to contain more than 1 million platelets per milliliter of serum or a 5-fold increase from the baseline platelet concentration.11 The preparation of PRP is essential in determining the therapeutic potential for biological augmentation. The purpose of this report was to detail our institutional PRP preparation protocol and method of administration during hip arthroscopy.

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  • Prolotherapy Induces an Inflammatory Response in Human Tenocytes In Vitro

    Abstract

    Background: Proliferative therapy, or prolotherapy, is a controversial treatment method for many connective tissue injuries and disorders. It involves the injection of a proliferant, or irritant solution, into the site of injury, which causes small-scale cell death. This therapeutic trauma is theorized to initiate the body\'s wound-healing cascade, perhaps leading to tissue repair. The immediate effects of many of these proliferants are poorly characterized, as are the cellular responses to them; here, we sought to evaluate the immediate effects of two common proliferants (dextrose and P2G, a combination of phenol, glucose, and glycerin) on the cellular response of human tenocytes, and begin to explicate the mechanisms with which each proliferant functions.

    QUESTIONS/PURPOSES: We asked: What are the effects of treating cultured tenocytes with proliferative treatment agents on their (1) cellular metabolic activity, (2) RNA expression, (3) protein secretion, and (4) cell migration?

    Methods: Using human hamstring and Achilles tendon cells, we attempted to answer our research questions. We used a colorimetric metabolic assay to assess the effect of dextrose and P2G proliferant treatment on cell mitochondrial activity compared with nontreated tenocytes. Next, using quantitative PCR, ELISA, and a reporter cell line, we assessed the expression of several key markers involved in tendon development and inflammation. In addition, we used a scratch wound-healing assay to evaluate the effect of proliferant treatment on tenocyte migration.

    Results: Results showed that exposure to both solutions led to decreased metabolic activity of tenocytes, with P2G having the more pronounced effect (75% ± 7% versus 95% ± 7% of untreated control cell metabolic levels) (ANOVA; p < 0.01; mean difference, 0.202; 95% CI, 0.052-0.35). Next, gene expression analysis confirmed that treatment led to the upregulation of key proinflammatory markers including interleukin-8 and cyclooxygenase-2 and downregulation of the matrix marker collagen type I. Furthermore, using a reporter cell line for transforming growth factor-β (TGF-β), a prominent antiinflammatory marker, we showed that treatments led to decreased TGF-β bioactivity. Analysis of soluble proteins using ELISA revealed elevated levels of soluble prostaglandin E2 (PGE2), a prominent inducer of inflammation. Finally, both solutions led to decreased cellular migration in the tenocytes.

    Conclusion: Taken together, these results suggest that prolotherapy, more so with P2G, may work by decreasing cellular function and eliciting an inflammatory response in tenocytes. Additional studies are needed to confirm the cellular signaling mechanisms involved and the resulting immediate response in vivo.

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  • Single Platelet-Rich Plasma Injection for Early Stage of Osteoarthritis of the Knee

    Abstract

    Purpose: The purpose of this study was to determine the safety efficacy and outcomes of platelet-rich plasma (PRP) intra-articular injections for early stages of knee osteoarthritis (OA).

    Methods: Twenty-five patients affected by grade I and II knee primary OA according to the Kellgren-Lawrence scale received a single intra-articular PRP injection. Patients were prospectively evaluated for 6 months. Visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee injury and Osteoarthritis Outcome Score (KOOS) scoring scales were used to evaluate clinical outcomes. Wilcoxon signed rank test was used to evaluate significance of improvement of WOMAC, KOOS, and VAS scores.

    Results: Twenty-one patients completed 6-months follow-up. The median WOMAC score improved from 29.1 points (range: 17.4-60.4; standard deviation [SD] = 13.0) at baseline to 42.41 (range: 24.3-71.2; SD = 12.5) at final follow-up. Improvements in median KOOS and VAS score have been also found, from 37.49 points and 64.2 mm before injection to 59.71 points and 42.8 mm, respectively. All these improvements were statistically significant (p < 0.05). No adverse reactions have been observed.

    Conclusion: Treating knee OA with PRP injection is safe. A single dose of PRP seems to be effective in managing pain and improving quality of life in patients with low-grade knee OA.

    Level of Evidence: Level IV, therapeutic case series.

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  • Dr Weglein and Dr Garcia teaching at TOBI ( the Orthobiologic institute)

    Dr Weglein and Dr Garcia teaching at TOBI ( the Orthobiologic institute)

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  • TOBI Faculty for 2017

    Abstract

    Over the years, TOBI has become best known for world-renowned faculty. TOBI annual events bring together field experts publishing the research in orthopedic biologics and regenerative medicine. This event has enjoyed consistent annual growth, as global thought-leaders return for annual updates and the year\'s best networking opportunities to collaborate on projects and advance the field. Newcomers to the field come to learn from the best.

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  • Effect of High-Volume Injection, Platelet-Rich Plasma, and Sham Treatment in Chronic Midportion Achilles Tendinopathy: A Randomized Double-Blinded Prospective Study

    Abstract

    Background: Injection therapies are often considered alongside exercise for chronic midportion Achilles tendinopathy (AT), although evidence of their efficacy is sparse.

    Purpose: To determine whether eccentric training in combination with high-volume injection (HVI) or platelet-rich plasma (PRP) injections improves outcomes in AT.

    Study Design: Randomized controlled trial; Level of evidence, 1.

    Methods: A total of 60 men (age, 18-59 years) with chronic (>3 months) AT were included and followed for 6 months (n = 57). All participants performed eccentric training combined with either (1) one HVI (steroid, saline, and local anesthetic), (2) four PRP injections each 14 days apart, or (3) placebo (a few drops of saline under the skin). Randomization was stratified for age, function, and symptom severity (Victorian Institute of Sports Assessment-Achilles [VISA-A]). Outcomes included function and symptoms (VISA-A), self-reported tendon pain during activity (visual analog pain scale [VAS]), tendon thickness and intratendinous vascularity (ultrasonographic imaging and Doppler signal), and muscle function (heel-rise test). Outcomes were assessed at baseline and at 6, 12, and 24 weeks of follow-up.

    Conclusion: Treatment with HVI or PRP in combination with eccentric training in chronic AT seems more effective in reducing pain, improving activity level, and reducing tendon thickness and intratendinous vascularity than eccentric training alone. HVI may be more effective in improving outcomes of chronic AT than PRP in the short term.

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  • Prolotherapy: An effective therapy for Tietze syndrome

    Abstract

    Purpose: To compare the short-term effect of prolotherapy and conservative terapy for the Tietze synrome.

    Patients And Methods: From 2013 to 2014, twenty-one patients underwent prolotherapy (group 1) and thirteen underwent conservative therapy with analgesics (group 2). A visual analogue score (VAS) was recorded for measurement of pain intensity in all patients before (Pre VAS) and after injection first day (VAS1), first week (VAS2) and fourth week (VAS3). Group 2 were received systemic nonsteroidal anti-inflammatory drug. VAS score was recorded similarly at the same times (Pre VAS, VAS1, VAS2, VAS3), and clinical affects were compared between the two groups.

    Results: The mean VAS score (mm) before prolotherapy was 7.10 in patients who received prolotherapy, and 7.14 mm in patients who treated nonsteroidal anti-inflammatory drug. The mean VAS after the fist injection was 2.19 mm and dropped to 1.52 mm after the third injection. The mean VAS after the nonsteroidal anti-inflammatory drug treatment dropped 2.62 mm and during the same scores to 3 weeks later. There was no significant difference between the group 1 and group 2 in the age, sex and comorbidity. Also there was no significant difference between the group 1 and group 2 in clinical and radiological evidence. The prolotherapy group showed a faster recovery, including significantly reduced clinic findings (p: 0.001). Third VAS is significant finding for the prolotherapy group.

    Conclusion: Prolotherapy could be performed safely and is a method with a favorable long term treatments for t he Tietze Syndrome. It may be the ideal procedure for patients with drugs side effects and advers events especially for those with limited liver and kidney reserve or significant comorbidities.

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  • Houston researchers use stem cells to treat traumatic brain injuries

    Abstract

    A Houston research team has uncovered a possible treatment for severe brain injuries that could dramatically improve the outlook for tens of thousands of trauma patients - from those injured on Houston highways, to soldiers wounded on faraway battlefields.

    About 275,000 people across the country each year are wheeled into emergency rooms with severe traumatic brain injuries; about a fourth don\'t survive. Those who do often suffer permanent disabilities, in part because swelling in the brain in the days and weeks after the injury cuts off blood flow, killing neurons.

    In a new clinical trial conducted at Memorial Hermann Hospital, researchers from UTHealth have shown it\'s possible to reduce brain inflammation by harvesting stem cells from a trauma patient\'s bone marrow and re-infusing them into the bloodstream within 48 hours of injury. The results are promising, said Dr. Charles Cox, who\'s been working on the experimental treatment for more than 15 years.

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  • Functional outcomes of platelet rich plasma injections in plantar fascitis

    Abstract

    Background: The study was conducted to analyse the clinical outcomes following a single injection of platelet rich plasma, produced using autologous blood by standard double centrifugation technique in patients with plantar fasciitis who have not had relief using conservative methods.

    Methods: Between June 2013 and June 2015, 26 consecutive patients (Mean age 45.92) (11 males/15 females) who had symptoms for a minimum of 3 months and had failed conservative management options such as rest, anti-inflammatories and physiotherapy were given a single injection of PRP in the medial calcaneal tubercle.

    Results: The outcomes were measured using Visual analogue scale and Foot function index at pre injection, and at 1, 6 and 12 months post injection and results tabulated. All patients reported an improvement in VAS and FFI scores consistently. One superficial infection was encountered.

    Conclusions: Single injection of platelet rich plasma improves pain and function in the foot in patients suffering from plantar fasciitis when conservative management has failed. The synergism between various autologous growth factors may play a role in tendon healing.

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  • Effect of Intraarticular injection of ozone on inflammatory cytokines in knee osteoarthritis

    Abstract

    Introduction: Knee Osteoarthrosis is one of the most debilitating diseases. Prolotherapy includes intraarticular injection of various drugs to decrease inflammation. Injection of Intradiscal O2-O3 has reduced pain and disability of patients with low back pain due to prolapsed lumbar disk.

    Objective: To compare the effect of intraarticular injection of Ozone and steroids in improvement of clinical and cellular healing of knee osteoarthritis.

    Methods:in a randomized clinical trial, 70 patients with knee osteoarthrosis were included in the study. In Ozone group, 5 ml (35 μg/ml) of Ozone and in steroid group 5ml (50 mg) Triamcinolone were injected intraarticular. At 1,2,and 6 month patients were followed for pain scale, disability index and IL-1β and TNF-α serum levels were measured.

    Results: At 1 month after injection pain scale and disability index and IL-1β and TNF-α were decreased in both groups. However, at 2 and 6 month pain scale and disability index were significantly lower in Ozone group compare to steroid group (p<0.05). Besides, serum level of IL-1β and TNF-α were also significantly lower at 2 and 6 month in Ozone group compare to steroid group (p<0.05).

    Conclusion: Intraarticular Ozone induces significantly longer improvement of pain and disability in knee osteoartherosis compare to steroid injection. In addition, serum inflammatory cytokines are also lower in Ozone group compared to steroid group along with clinical improvements.

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