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  1. #1
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    Default Polyacrylamide Hydrogel

    Has anyone injected their horses joint(s) with this and if so were you pleased with the results? I have very limited experience with injecting as I have never had a horse that had needed it but this was recommended to me for a mare with a bit of arthritic changes in her fetlocks. I would love to hear experiences. Thanks for any input!
    Cindy's Warmbloods
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  2. #2
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    Default

    I think that's a fairly recent invention--sort of a synthetic polysaccharide in the same family as the adequans/pentosans of the world. Why this product and not those, I wonder? There is precious little in the medical literature other than patent applications and in vitro stuff. One of those "medical devices" that is potentially in use without strictly being FDA approved, maybe? I don't know enough about it to say for sure but I'd love to hear why this product would be chosen above the many others out there.
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  3. #3
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    Default

    I am not sure. I bought a mare from a lady and her vet recommended it and really thought highly of it. Something about it can last years with just one treatment. I am just not familiar at all with the product at all so I wanted to hear more experiences.
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  4. #4
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    Default

    As a person who has helped develop hydrogels, this makes absolutely NO sense! It is a stable polymer (plastic) that does not degrade quickly. We use it for sheaths for neural regeneration and in places we want a SOLID construct in tissues (it depends on the level of polymerization). The general use are the particles used to hold water in soils for plant availability.

    In my experience, it is like an injection of sand into a joint. It will trash the cartilage surface, similar to polyethylene particles from implants used in joint replacement. From what I see, the inventors think that injecting a plastic into the joint will somehow heal the joint. It would be like injection polyethylene (used in buckets and milk bottles) directly in the joint rather than forming them into the joint surfaces used in joint replacement devices.

    I will ask our resident hydrogel guys though. There is no medical or scientific data published based on a search using Scirus.

    There is a European Patent Application from 2 years ago by Jens Petersen, Robert Lessel and Richard Schmidt of Denmark:

    Polyacrylamide hydrogel for use in the treatment of arthritis EP20100182169 20010825

    The invention concerns a hydrogel for use in the treatment of arthritis, said hydrogel obtainable by combining acrylamide and methylene bis-acrylamide in amounts so as to give about 0.5 to 25% by weight polyacrylamide, based on the total weight of the hydrogel; radical initiation; and washing with pyrogen-free water or saline solution. The preferred treatment is by injection of the hydrogel into the intra-articular cavity of a joint.

    Listed Claims:
    1. A hydrogel for use in the treatment of arthritis,
    said hydrogel obtainable by combining acrylamide and methylene bis-acrylamide in amounts so as to give about 0.5 to 25% by weight polyacrylamide, based on the total weight of the hydrogel; radical initiation; and washing with pyrogen-free water or saline solution.

    2. The hydrogel according to claim 1, wherein the hydrogel is administered by injection into the intra-articular cavity of a joint.

    3. The hydrogel according to claim 1, wherein the arthritis is in the knee joint, hip joint, the elbow, or metacarpal-phalangeal and interphalangeal joints in hands and feet.

    4. The hydrogel according to any one of the preceding claims, wherein the hydrogel has an elasticity module of from 10 to 700 Pa.

    5. The hydrogel according to any one of the preceding claims, wherein the hydrogel has an elasticity module of from 35 to 480 Pa.

    6. The hydrogel according to any one of the preceding claims, wherein the acrylamide and methylene bis-acrylamide are combined in a molar ratio of 150:1 to 1000:1.

    7. The hydrogel according to claim 6, wherein the acrylamide and methylene bis-acrylamide are combined in a molar ratio of 200:1 to 600:1.

    8. The hydrogel according to any one of the preceding claims comprising less than 15% by weight polyacrylamide.

    9. The hydrogel according to claim 8 comprising less than 7.5% by weight polyacrylamide.

    10. The hydrogel according to claim 9 comprising less than 3.5% by weight polyacrylamide.

    Here is a complete description: http://worldwide.espacenet.com/publi...=&locale=en_EP


    Jens Petersen seems to be a patent generator for this technology and has all sorts of patents for use of this in all sorts of tissues.

    I would be very wary of this.
    Last edited by RAyers; Feb. 6, 2013 at 11:59 PM.



  5. #5
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    Default

    Thanks Rayers, I appreciate the feedback. I am definitely wary of this product as I am not familiar with it but she said her vet had been having good results with it. Here is an online article I found, it is called Arthramid:

    http://www.voorjaarsdagen.org/index....horses&catid=5



    Here is the article I was sent, I removed the references at the bottom as they were quite extensive. Sorry the graphs didn't turn out either...

    Efficacy of a polyacrylamide hydrogel in horses with symptomatic osteoarthritis: An international multi-centre prospective study


    1. Take home message

    This prospective study has shown that a polyacrylamide hydrogel significantly alleviated lameness in symptomatic osteoarthritic joints in horses.

    2. Introduction

    Osteoarthritis (OA) is a common cause of lameness and poor performance in the horse. Lameness due to OA is the most common cause of early retirement of pleasure and performance horses.1,2 OA is an essentially non-inflammatory and painful disorder, characterized by degeneration and loss of articular cartilage and the development of new bone on joint surfaces and margins.3-5 As in people, equine OA is probably not a single disease but reflects a common response of joint tissues to a number of potential causes.6 The specific contributions and interactions of various mechanical and biological factors contributing to development of OA lesions remain unclear. Even though OA is a common chronic disease worldwide in humans and animals, its treatment remains a big challenge.
    In OA, the viscoelastic properties of synovial fluid are lower than in normal joints which contribute to the decreased mobility of the joint. The use of viscosupplementation and cushioning, like intra-articular injections of hyaluronic acid, has been implemented in recent years in the treatment of OA in humans7 as well as in animals, especially horses.8 The purpose of such treatment modality is to increase the viscoelastic properties of the synovial fluid and thus improve the lubricating effect of the joint. Since hyaluronic acid is degradable and rapidly destroyed, the duration of its protective effect is short,9 and repeated treatments are necessary. By protecting the joint by a buffer, the joint is allowed to move more freely without the sensation of pain, because the apposed joint surfaces like bone and cartilage will be protected by a cushioning effect.9,10
    Polyacrylamide hydrogela (PAAG) are polymers obtained by the polymerization of acrylamide and are considered nontoxic because of the inability to pass through biological membranes due to their large size.11 PAAG is a non-particulate homogenous gel similar to hyaluronic acid gel in overall structure and tissue compatibility,11 but with a longer-lasting viscous effect, as it is non-degradable.12 It consists of 97.5% sterile water and 2.5% polyacrylamide. It consists of an irreversibly and firmly bound backbone of polyacrylamide to which exchangeable water molecules are attached.13 PAAG is in constant equilibrium with the extracellular matrix of the surrounding tissue due to the high water content and the constant exchange of water molecules.13 The PAAG polymer backbone will, however, stay at the injection site and allow ingrowth of host vessels and cells via a fibrous network. After a few months the gel will be fully integrated within the tissue allowing the gel to maintain its filling effect for years.14 This gel has been used for years in the augmentation of connective tissue12,15-19 The filling effect from PAAG is achieved entirely by the gel itself, whereas other gel fillers need to produce a significant foreign body response in order to achieve the complete filling effect.20 Experimental studies supported by histo-pathological observations in the clinic have shown that PAAG exerts its effect by being integrated over time within the soft tissues through a combination of vessel in-growth and molecular water exchange.11,14,21,22 Vessel in-growth begins with host macrophages and foreign-body giant cells that enter the gel connect and eventually develop into a thin vessel-bearing fibrous network.14 A recent pilot study on rabbits compared the action of intra-articular PAAG with intra-articular hyaluronic acid hydrogel.23 This study showed that PAAG has a lasting effect on the joint capsule (femoro-patellar joint) at 1 year, by being incorporated into the soft tissue of normal joints. Another recent pilot study on an experimental OA model in goats has shown that PAAG was integrated into the synovial membranes of the injected joint injected, and significantly improved the lameness caused by OA.24
    The purpose of the present study was to investigate the effect of a PAAG in improving clinical signs of OA in the fetlock or carpus. PAAG is recently used to intra-articularly treat OA in horses; however, no prospective study on the efficacy of PAAG has been reported.

    3. Materials and methods

    Thirty three horses older than 2 years with a confirmed symptomatic OA in only one joint (fetlock or carpus) based on clinical evaluation, intra-articular anesthesia and imaging (radiography, MRI or arthroscopy) have been included in this clinical trial. We excluded from this study horses with lameness localized at more than one joint, horses with OA secondary to joint infection, horses that had surgery of this joint (including arthroscopy) within one month prior to treatment, and horses that had any other OA treatment administered to the affected joint within the previous 14 days before treatment. Horses were injected with 2 ml of PAAG in the affected joint and were followed up at 1, 3, and 6 months. At 1, 3 and 6 months, follow up data were obtained for 30, 19 and 33 horses respectively. Efficacy of the treatment was evaluated by clinical assessment of lameness in the affected joint. Data relating to case details, type of activity (show jumping, dressage, others (racing, pleasure, 3 day eventing, western riding and training for license)), joint (fetlock, carpus) and leg involved, lameness duration (1-6 months, > 6 months), previous joint treatment (yes, no), lameness scoring (AAEP lameness grading system: 0 to 5) at baseline and at 1, 3, and 6 months, joint effusion scoring (0: no distension, 1: mild, 2: moderate, 3: marked and 4: severe), radiographic scoring of OA (0: no lesion, 1: mild, 2: moderate and 3: marked), and owner assessment (1: not satisfied, 2: slightly satisfied, 3: satisfied and 4: very satisfied) were recorded. The radiographic scoring system used was similar to the one reported by van Hoogmoed et al. (2003). Safety assessment of the joint was also evaluated through recording of any adverse reaction following joint injection.
    Statistical analysis: The statistical variables used in this study are described in table 1.

    Table 1: The statistical variables included in the study.


    Categorical variables

    Age (years)
    Sex
    Breed
    Type of activity
    Time point (months)
    Joint involved
    Continuous
    Female, male, gelding
    Warmbloods, others
    Dressage, Jumping, others
    Baseline, 1, 3, 6
    Fetlock, Carpus










    Leg involved
    Front, Hind

    Previous treatment
    Lameness duration before treatment (months)
    Yes, No
    1 to 6; > 6

    Lameness scoring (AAEP system)
    0 to 5

    Joint effusion scoring
    0 to 4

    Radiographic scoring of OA
    0 to 3

    Owner assessment scoring
    1 to 4

    Random variables

    Horses
    33
    AAEP: American Association of Equine Practitioners

    Variables potentially associated with the outcome measure ”lameness scoring” were analyzed using generalized linear mixed model for ordinal regression with random effect of horse (Variance component: 5.25; Likelihood ratio: 27.51, with p < 0.0001). A P value of <0.05 was considered significant. It was hypothesized that PAAG would significantly decrease the lameness scoring in the OA affected joints.

    4. Results

    The study population included 25 (75.7 %) Warmbloods and 8 others (2 Thoroughbreds, 2 Trotters, and 4 miscellaneous breeds). There were 13 females, 13 geldings and 7 intact males. The age ranged between 2 and 16 years with an average age of 9.5 years (s.d. ± 4.3 years). The horse activities were: dressage (13), show jumping (10), and others (racing: 4, miscellaneous activities: 6). Lameness was localized in 21 (63.6%) front legs and 12 (36.4%) hind legs. Thirty one (94%) horses had a fetlock treated, whereas only 2 (6%) horses had a carpus treated. The lameness duration before treatment with PAAG was 1 to 6 months in 24 (72.7%) horses and more than 6 months in 9 (27.3%) horses. Twenty eight horses (84.8%) had previously received another anti-osteoarthritic treatment for the treated joint, 2 had no treatment and no information was obtained for 3 horses.
    Radiographic score of OA before the treatment was 1 (mild), 2 (moderate) and 3 (marked), in 13 (39.4%), 8 (24.3%) and 12 (36.3%) horses respectively. In addition to radiography, 17 of 33 horses (51.5%) underwent MRI or arthroscopy, or both modalities for the diagnosis of OA. Before treatment, the proportion of horses with lameness score 1, 2, 3 and 4 was 27.3%, 33.3%, 33.3% and 6.1% respectively.
    Table 2 shows that the estimated proportion of horses with lameness improvement at 1, 3, and 6 months was 81%, 88% and 87% respectively. The estimated proportion of sound horses at 1, 3 and 6 months was 53%, and 58% and 70% respectively.

    Table 2: Associated averaged conditional probabilities for the changes in lameness score from
    baseline to Time = 1, 3 or 6

    Time x
    (month)
    Change = Score (Time x) – Score (Baseline)
    Total

    -4
    -3
    -2
    -1
    0
    +1
    +2
    +3
    +4

    1
    0.0147
    0.1203
    0.3288
    0.3502
    0.1622
    0.0209
    0.0026
    0.0002
    0.0000
    1.00
    3
    0.0339
    0.1994
    0.3665
    0.2826
    0.1103
    0.0066
    0.0007
    0.0001
    0.0000
    1.00
    6
    0.0299
    0.1863
    0.3649
    0.2936
    0.1164
    0.0081
    0.0009
    0.0001
    0.0000
    1.00

    For the statistical model used, only the time point (p<0.0001) and the activity (p=0.0005) variables were significant. There was a statistically significant decrease in lameness score from baseline to 1 month, and from 1 to 3 months (Odds ratios= 214), but lameness score was constant from 3 to 6 months (Table 2).
    Lameness status at 6 months: At 6 months following the treatment, approximately 70 % of the horses were lame free, 87% improved their lameness score, whereas 15% had either no change or a worsening in their lameness score (Table 2). In horses with pre-treatment lameness score 1, eight of nine horses (89%) were lame free, and 1 horse had no change in the lameness score. Horses with pre-treatment lameness score 2 were lame free, improved, had no change or had a worse lameness score in 54.5%, 27.3%, 9.1% and 9.1% respectively. Horses with pre-treatment lameness score 3, were lame free, improved or had a worse lameness score in 81.8%, 9.1% and 9.1% respectively. One horse with pre-treatment lameness score 4 improved the lameness score and another one had a worse lameness score.
    At 6 months, 81.8% of the owners were satisfied or highly satisfied with the outcome of the treatment, whereas 18.2% of the owners were slightly satisfied or not satisfied with the outcome of the treatment. In addition, no side effect was observed in the treated joints.

    5. Discussion

    The inclusion criteria in the present study were strict in order to maximize the validity of the results. Cases with limb OA were only included if they had only 1 joint involved that showed a positive response to intra-articular anesthesia, and the osteoarthritic lesions were visualized based on radiography, MRI or arthroscopy or a combination of these imaging modalities.
    Our study population included a majority of Warmblood horses, mainly performing dressage or show jumping with an average age of 9.5 years. Fetlock OA was the predominantly (94%) treated condition in our series. Approximately two thirds of the treated joints were located at the front legs and one third at the hind legs, however there was no correlation between the OA location and the response to treatment. In addition, the majority of horses have previously received a non successful anti-osteorthritic treatment, and there was no association between such treatment and the outcome factor.
    A modified radiographic scoring system25 was used to grade typical changes of OA. The numerical scoring system used in this study was easily applied. The allocated scores were based on a subjective evaluation of the joints supporting a report,26 which showed that a verbal descriptive scale (mild/moderate/severe) is more accurate than a quantitative rating scale in assessing distal tarsal joint OA. In the present study, radiographic scoring of OA in the joints before treatment was assessed as mild (39.4%), moderate (24.3%) and marked (36.3%). Radiographic findings were predominantly ‘mild’ or ‘marked’, but no significant difference between the radiographic score could be noted in relationship to lameness improvement following treatment. In contrast to a reported study,27 the present study did not show an association between clinical lameness and severity of radiographic findings. Inconsistent lameness among horses with similar radiographic signs parallels the weak correlation between pain and lameness and the radiographic findings of early OA in people.28,29 Although radiography has some merit in characterizing changes in bone that accompany established OA, this imaging technique lacks unfortunately sensitivity and may not detect performance limiting lesions in horses.30,31 Another major disadvantage of radiography is that radiographic changes may not be present when early OA is characterized by cartilage degeneration. This may delay diagnosis and treatment and may consequently decrease the long term prognosis, hence the role of the other imaging modalities, including arthroscopy as well, in improving OA diagnosis. In the present study, in addition to radiography, approximately the half of horses (51.5%) underwent also MRI or arthroscopy, or both modalities for the diagnosis of OA, which may have reduced the disadvantages of radiography in these horses. However, even though there is a poor correlation between radiographic findings and clinical symptoms in OA, radiography remains the most frequently used method of diagnosis of OA.
    Most of the horses (72.7%) have been lame for 1 to 6 months, illustrating the chronic nature of this condition. There was no association between the duration and degree of lameness.
    Before treatment, the proportion of horses with lameness score 1, 2, 3 and 4 was 27.3%, 33.3%, 33.3% and 6.1% respectively. In contrast to a recent study,32 in distal tarsal OA, where cases with ‘moderate or severe’ radiographic changes tended to show a positive long-term response to treatment, the degree of lameness showed no association with response to treatment. In the present study, the lameness score was mild (score 1 or 2) in the majority of horses (60.6%), which is consistent with our clinical experience, whereas in a recent study of fetlock OA, 63.3% of the horses had a lameness score 3 before treatment.33
    A high proportion of horses with lameness improvement were seen at 1, 3, and 6 months. The estimated proportion of sound horses at 1, 3 and 6 months was 53%, and 58% and 70% respectively. This may be interpreted as a progressive improvement of the lameness from baseline to 6 months. However, at 3 months, only 19 from 33 horses could be followed up, which might probably have biased the result at that time point. In a recent study using lyophilized products from green-lipped mussel administered orally to treat fetlock OA in horses, 63.2% of the horses improved their lameness score, whereas only 10.5% were lame free after this treatment.33
    Horses with pre-treatment lameness score 1 and 3 showed a higher proportion of lame free horses than horses with pre-treatment lameness score 2. None of the 2 horses with pre-treatment lameness score 4 was lame free after treatment. However, there was no significant association between pre-treatment lameness score and response to treatment
    In addition, there was a statistically significant decrease in lameness score from baseline to 1 month, and from 1 to 3 months, but lameness score was constant from 3 to 6 months. This might suggest that the effect of PAAG on OA mainly occur during the first 3 months following the treatment. This speculation needs to be confirmed with further studies.
    In the current study, no adverse reaction following joint injection was observed. This is consistent with studies using PAAG intra-articularly in others species.23,24 At 6 months, the majority of the horse owners, approximately 82%, were satisfied or highly satisfied with the outcome of the treatment, whereas 18.2% of the owners were slightly satisfied or not satisfied.
    Although conventional concepts of OA emphasize the direct and predominant involvement of cartilage and bone in OA development, it is increasingly recognized that the synovium contributes to the central pathophysiological event of cartilage matrix depletion. Recently synoviocytes have been shown as rich source of a variety of inflammatory mediators and degradative enzymes implicated in cartilaginous degeneration, including prostaglandins,34 cytokines,35 and matrix metalloproteinases.36 However, precise characterization of the relative quantitative and temporal contributions of cartilage and synovium to OA lesion development has not yet been accomplished.
    Normal homeostasis within a joint cavity is a concert of two lubricating mechanisms that protect the joint and promote normal, pain free functions: weeping lubrication of water, and hyaluronic acid.37,38 Hyaluronic acid clings to the surface of the soft tissues of the interior of the joint, and, through its slippery nature, lubricates by minimizing friction of the interface of tissues because of the sliding of the hyaluronic acid layers, preventing the soft tissues of the interior of the joint from contacting opposite surfaces and creating friction.10 Inflammation within the joint, disrupts these lubricating mechanisms, eliminates their protection of the synovial lining and articular surfaces, accelerates wear on the joint, and creates pain.9 The boundary lubrication is very labile.38 Hyaluronic acid is rapidly destroyed, but this process is totally reversible as long as the synovial lining remains functional.9 Chronic synovial lining insult, such as in OA, eventually results in permanent loss of boundary lubrication capacity.37 Chronic inflammation, such as OA, has been reported to be more damaging.38,39 This emphasizes the role of viscosupplementation, and hence the improvement of lubrication within the joint, in protecting a joint suffering from OA, and reducing the resulting pain.
    Precise characterization of the mechanism of action of PAAG on OA joints has not yet been accomplished. However, a recent pilot study on rabbit compared the action of intra-articular PAAG with intra-articular hyaluronic acid hydrogel.23 This study showed that PAAG has a lasting effect on the joint capsule at 1 year, by being incorporated into the soft tissue of normal joints. Experimental studies in an experimental OA model in goats have shown that the intra-articular injection of PAAG, significantly reduced the clinical signs and the gross pathologic lesions in the treated joint in comparison with the control joint.24 Further work investigating the mechanism of action of PAAG in OA joints is highly required.
    Study limitations include, a low number of horses, a lack of comparison treatment, and a variety of clinicians performing the diagnostic. The statistical analysis of this study indicates a beneficial effect of PAAG, which, however, remains to be verified in a randomized clinical trial including a control group.
    Preliminary results of the present prospective study have shown that PAAG significantly alleviated lameness in OA affected joints, as assessed by standard veterinary lameness evaluation. No side effect was observed in the treated joints. PAAG is a promising treatment for symptomatic OA in horses; however its further evaluation is warranted.
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  6. #6
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    Default

    DH works in that industry... so I thought I'd ask him because I was just kind of curious, here's what he said.
    his response was combined with if you are not completely 100% assured of your supplier. Put very simply, Polyacrylamide production is easily going to contain acrylamide... quite a nice little neurotoxin. Is the supplier is someone that is going to do good quality control? DH knows first hand what a little stray acrylamide in the air can do, he sure wouldn't want any injected in his joints. A good supplier with good QC can have that problem taken care of. He actually kind of thought it sounded like an interesting idea.



  7. #7
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    Default

    I think some form of this is what is used for plastic surgery, no? Like injecting lips and chins to make them "plump"? If so, I doubt any major concerns re: neurotoxicity have been addressed ASSUMING it's FDA approved for that indication. One can never assume with the bioesthetic industry, however.

    Thank you for listing the citation, but if that's the only available evidence it is WAY too soon to put this product into use, IMO. Lack of evidence rarely stops it from being done, however.

    Here's one scary article . . .

    http://archfaci.jamanetwork.com/arti...ticleid=480223

    I think I would pass on what sounds like still-experimental treatment for a disease that has a number of other products to try first.
    Last edited by deltawave; Feb. 7, 2013 at 08:13 AM.
    Click here before you buy.



  8. #8
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    Default

    Thanks I think I will pass as well for now :-)
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