Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Superficial digital flexor tendinitis was induced in each forelimb of 8 horses by injecting 4,000 U of collagenase into the midmetacarpal region of the tendon. In each horse, each tendon was treated 24 and 96 hours after the collagenase injection with SC injections of sodium hyaluronate (treated limbs) or an equal volume of 0.9% NaCl solution (control limbs). Exercise was restricted for the first 3 weeks of the study, and a controlled exercise program was instituted for the remainder of the study. Horses were evaluated clinically for lameness, tendon swelling, and midmetacarpal limb circumference. Ultrasonographic examinations were performed regularly (11 examinations/horse) throughout the study, and all horses were euthanatized 12 weeks after collagenase injections. Tendons from 4 horses were harvested for biomechanical testing, and samples were obtained from tendons from the remaining 4 horses for biochemical analysis of collagen. Samples were obtained from all tendons for microscopic evaluation. Significant differences between treated and control tendons were not noticed in any of the variables examined in live horses, although trends toward less lameness in treated limbs and toward better healing on ultrasonographic examination in control limbs were recorded. Significant differences were not noticed in biomechanical or biochemical evaluations, and the only significant (P < 0.05) microscopic finding was more severe inflammation in tendons from treated limbs. This study did not reveal significant benefits of treatment with sodium hyaluronate outside a synovial sheath on tendon repair in collagenase-induced tendinitis.
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PMID:Effect of sodium hyaluronate in collagenase-induced superficial digital flexor tendinitis in horses. 147 24

The influence of regional nerve blocks on lameness resulting from tendon injury was studied in six horses. Tendonitis was induced in the midmetacarpal region of the Superficial Digital Flexor Tendon (SDF), Deep Digital Flexor Tendon (DDF) and the Suspensory Ligament (SL) through collagenase injections. The results were evaluated through sequential clinical examinations, ultrasonographic imaging and kinetic gait analysis (force plate) during a period of 144 days post injury and subsequently compared with gross and microscopic findings. The lameness corresponding to the SDF and DDF tendon lesions was completely abolished by a high palmar nerve block. The SL desmitis was partly abolished by high palmar nerve block and completely blocked with an additional ulnar nerve block. The ultrasonic evaluations showed the lesions, expanding until approximately 30 days post injection (p.i.) and subsequently decreasing. The texture of the lesion also improved markedly after 30 days p.i. The post-mortem macro- and microscopic evaluation revealed still considerable abnormalities at 145 days p.i. At that time the tendon lesions were no longer detectable ultrasonographically.
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PMID:The effect of regional nerve blocks on the lameness caused by collagenase induced tendonitis in the midmetacarpal region of the horse: a study using gait analysis, and ultrasonography to determine tendon healing. 149 64

Sodium hyaluronate reduces adhesions after tendon repair in rodents and dogs, and has been used in limited clinical trials in people. To evaluate its effect on tendon healing and adhesion formation in horses and to compare these effects with those of a compound of similar visco-elastic properties, a study was performed in horses, using a model of collagenase injection in the flexor tendons within the digital sheath. Eight clinically normal horses were randomly allotted to 2 groups. Adhesion formation between the deep digital flexor tendon and the tendon sheath at the pastern region was induced in the forelimbs of all horses. Using tenoscopic control, a 20-gauge needle was inserted into the deep digital flexor tendon of horses under general anesthesia and 0.2 ml of collagenase (2.5 mg/ml) was injected. The procedure was repeated proximally at 2 other sites, spaced 1.5 cm apart. A biopsy forceps was introduced, and a 5-mm tendon defect was created at each injection site. Group-A horses had 120 mg of sodium hyaluronate (NaHA) gel injected into the tendon sheath of one limb. Group-B horses had methylcellulose gel injected at the same sites. The contralateral limbs of horses in both groups served as surgical, but noninjected, controls. Horses were euthanatized after 8 weeks of stall rest. Ultrasonographic evaluation revealed improved tendon healing after NaHa injection, but no difference in peritendinous adhesion formation. Tendon sheath fluid volume and hyaluronic acid (HA) content were greater in NaHA-treated limbs. Gross pathologic examination revealed considerably fewer and smaller adhesions when limbs were treated with NaHA. However, significant difference in pull-out strengths was not evident between NaHA-treated and control limbs. Histologically, the deep digital flexor tendon from the NaHA-treated limbs had reduced inflammatory cell infiltration, improved tendon structure, and less intratendinous hemorrhage. Treatment with methylcullulose had no significant effect on tendon healing, adhesion size, quantity, or strength or on the volume and composition of the tendon sheath fluid. Sodium hyaluronate, administered intrathecally, appears to have a pharmaceutically beneficial action in this collagenase-induced tendinitis and adhesion model in horses.
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PMID:Effects of sodium hyaluronate on tendon healing and adhesion formation in horses. 185 4

To answer the question whether it is possible to differentiate, by means of a high plantar nerve block in the hind limb, flexor tendon lameness from a suspensory ligament lameness, mid-plantar tendinitis or desmitis was induced with collagenase in five Standardbred horses in two trials. Before the induction of lameness, and on the fourth (D4) and fourteenth day (D14) after the induction of lameness the horses were evaluated subjectively (clinical lameness score), objectively (ground reaction force (GRF) measurements), and ultrasonographically. Clinical evaluation and GRF measurements were also done on D4 and D14 after a high plantar nerve block. From the GRF measurements variables were selected and analysed and related to the clinical lameness score. The horses were significantly lame on D4; this lameness had decreased on D14. The clinical findings were supported by the GRF data. In the flexor tendon group, a high plantar nerve block resulted in soundness or lameness in the other hind limb, whereas in the suspensory ligament group the effect was less conclusive. The correlation between the subjective clinical lameness score and several objectively measured GRF variables proved to be moderate to high. The collagenase model proved to be useful to study the effect of a high plantar nerve block on lameness resulting from induced tendon/ligament lesion. However, a high plantar nerve block cannot be used to differentiate between flexor tendon and suspensory ligament lesions.
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PMID:Clinical and force plate evaluation of the effect of a high plantar nerve block in lameness caused by induced mid-metatarsal tendinitis. 780 6

Controversy exists with respect to the innervation of the suspensory ligament (SL) in the fore limb of the horse. It is uncertain whether this structure is exclusively innervated by branches of the ulnar nerve or also to some extent by median nerve branches. Ground Reaction Forces (GRF) were determined in horses before and after the induction of a tendonitis in the lateral branch of the SL by the injection of collagenase, and before and after a high palmar and an ulnar block respectively. The high palmar block succeeded in bringing all GRF variables back to their original values which the ulnar block did not. It is concluded that the SL is innervated by branches of both the ulnar and the median nerves, with the median nerve being relatively more important for the distal part of the SL.
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PMID:The effect of the high palmar nerve block and the ulnar nerve block on lameness provoked by a collagenase-induced tendonitis of the lateral branch of the suspensory ligament. 893 85

This study was designed to determine the effects of a single injection of a species-specific preparation of cytokines into rabbit patellar tendons and to compare the results with a known model of tendinitis, the collagenase-injection model. New Zealand White rabbits were divided into two groups and two time periods (4 and 16 weeks) and injected in the midsubstance of the right patellar tendon with either cytokines or collagenase under ultrasound guidance to confirm intratendinous needle placement. The left patellar tendon was injected with 0.025 ml of saline solution and served as a control. The rabbits were returned to cage activity after injection. At death, two rabbits in each group underwent histological analysis; the remaining eight animals in each time frame were evaluated biomechanically and then biochemically with use of the patella/whole patellar tendon/tibia complex. Histologic results at 4 weeks in the tendons injected with cytokines demonstrated increased cellularity, which was resolving by 16 weeks. The matrix appeared unchanged. The tendons injected with collagenase demonstrated increased angiogenesis of the matrix, hypercellularity, and fibrosis around the tendon at 4 weeks. At 16 weeks, myxoid changes, focal fibrosis, and collagen-bundle disarray with persistent increase in cellularity were noted. Biomechanically, a significant decrease in ultimate load at 16 weeks was seen in the tendons injected with cytokines but no change was seen in cross-sectional area. The tendons injected with collagenase demonstrated a significant increase in cross-sectional area at 4 and 16 weeks compared with those injected with cytokines. Biochemically, there was no significant difference in collagen content between the two groups at 4 or 16 weeks but the tendons injected with collagenase demonstrated a significant increase in crosslinking at 16 weeks. Our conclusion is that the tendons injected with the cytokine preparation represent a model of mild, seemingly reversible tendon injury. The cytokine preparation produces no matrix damage or evidence of collagen degradation and is species specific.
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PMID:Cytokine-induced tendinitis: a preliminary study in rabbits. 1022 32

Tendinitis is a painful soft tissue pathology that accounts for almost half of all occupational injuries in the United States. It is often caused by repeated movements and may result in loss of work and income. Current treatments for tendinitis are aimed at reducing inflammation, the major cause of the pain. Although anti-inflammatory drugs and various alternative therapies are capable of improving tendinitis, there are no quantitative scientific data available regarding their impact on inflammation. The objective of this study is to determine the time course for healing of rat tendinitis without intervention to be able to assess the efficacy of tendinitis treatments. We are interested in evaluating the therapeutic use of pulsed electromagnetic fields (PEMFs), a therapeutic modality that has been found to be beneficial for healing soft tissue injuries. Tendinitis was induced in Harlan Sprague Dawley rats by collagenase injections into the Achilles tendon, and tendons were collected for four weeks post-injury. To determine the amount of edema, we used caliper measurements of the rat ankles and quantified the tendon water content. To determine the extent of inflammation, we estimated the number of inflammatory cells on histological sections applying stereological methods. The data reveal that edema is maximal 24 hours after injury accompanied by a massive infiltration of inflammatory cells. Inflammatory cells are then gradually replaced by fibroblasts, which are responsible for correcting damage to the extracellular matrix. This natural time course of tendon healing will be used to evaluate the use of PEMFs as a possible therapeutic modality.
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PMID:Quantitative characterization of rat tendinitis to evaluate the efficacy of therapeutic interventions. 1208 95

In previous studies we established a rat model of acute tendinitis including functional and mechanical measures of healing. Achilles' tendinitis was induced by injection of collagenase, an enzyme that produces localized fiber digestion and edema formation. As quantitative measures of tissue inflammation, hypercellularity and edema were evaluated in injured tendons in comparison with controls. Using the rat tendinitis model, we have applied isotope-coded affinity tag analysis (ICAT) methodology to indicate localized tendon healing by quantitating protein expression. This novel proteomics method allows detection of subtle differences in protein levels that provide a detailed picture of tendinitis healing. The method involves a new class of chemical linkers used to differentially label cysteine residues from similar peptides in control and treated protein samples with heavy (deuterium off of backbone) and light (hydrogen off of backbone) ICAT reagents that are otherwise chemically identical. Proteins were extracted under liquid nitrogen from control untreated or injured Achilles' tendons 72 hours after collagenase-injection. These proteins were digested with endoproteinase Glu-C and trypsin and the resulting peptide mixtures were evaluated using reverse-phase C18 HPLC and Tristricine SDS-polyacrylamide gel electrophoresis. The two ICAT-modified peptide populations were mixed, affinity-purified and analyzed using microcapillary liquid chromatography and electrospray ionization tandem mass-spectroscopy. The process resulted in relative abundance and charge-to-mass ratio data used in conjunction with database searching to identify proteins expressed differentially in the two treatment groups. By analyzing different time periods in the healing process, an accurate model of the healing rat tendon can be made.
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PMID:Use of proteomics methodology to evaluate inflammatory protein expression in tendinitis. 1272 41

Although impaired wound healing associated with type 1 diabetes mellitus has been well studied in skin tissue, the influence of this metabolic disorder on tendon healing and recovery has not been extensively investigated. Because tendons are known to have limited repair potential, we studied the tendon-healing process by using a diabetic rat tendonitis model. We tested the hypothesis that diabetes influences the inflammatory response, cell proliferation, and angiogenesis in injured Achilles tendons. Diabetes was induced by injecting streptozotocin at 45 mg/kg body wt. Non-diabetic rats as well as diabetic and insulin-treated diabetic animals were then injected with collagenase. The accumulation of inflammatory cells was quantified in transversal sections of Achilles tendon by using immunohistochemical staining at days 0, 1, 3, 7, 14, and 28 posttrauma. The number of proliferative cells and the extent of neovascularization was also quantified in the paratenon and the core of the tendon at days 0, 3, 7, 14, and 28 posttrauma. Relative to nondiabetic and insulin-treated diabetic animals, the numbers of accumulated neutrophils and ED1(+) and ED2(+) macrophages in diabetic rats decreased by 46, 43, and 52%, respectively, in the first 3 days after injury compared with levels in nondiabetic and insulin-treated diabetic animals. The density of newly formed blood vessels decreased by 35 and 29% in the paratenon and the core of tendon, respectively, at days 3 and 7 after injury. Lastly, the concentration of proliferative cells decreased by 34% in the paratenon at day 7 posttrauma in injured tendons from diabetic rats relative to nondiabetic rats. These results indicate that alterations in inflammatory, angiogenic, and proliferative processes occurred in the diabetic state that might eventually perturb tendon healing and remodeling.
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PMID:Insulin-dependent diabetes impairs the inflammatory response and delays angiogenesis following Achilles tendon injury. 1471 91

Extracorporeal shock wave therapy (ESWT) is being used to treat desmitis and tendonitis in horses. This paper compares the clinical, ultrasonographic and histological characteristics of ESWT treated collagenase induced superficial digital flexor tendon (SDFT) lesions, versus untreated controls. This blinded study utilizes six mature, healthy horses where bilateral forelimb SDFT lesions were induced. One forelimb was treated while the other served as an untreated control. Three shock wave treatments were administered at three week intervals. At weekly intervals, ultrasonograms were used to measure: 1) percentage lesion at the maximum injury zone (MIZ), 2) the grey scale of the SDFT at the MIZ, 3) the percentage disruption of the longitudinal fibres at the MIZ. The data were also summed from 8-20 cm distal to the accessory carpal bone. Measurements of the external width of the SDFT were obtained through the study period. Examinations were performed on four occasions to evaluate heat, response to palpation, presence/character of swelling over the SDFT, and lameness. At the completion of the study all tendons were evaluated histologicalally. The lesion size, grey scale, and longitudinal fibre disruption at the MIZ, and sum of each variable changed significantly over time, however, there was no difference between treated and control groups. Histopathology showed increased neovascularization in treated tendons (p = 0.001). When compared to untreated controls, ESWT did not change the ultrasonographic appearance of the tendons. However, it did increase neovascularization.
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PMID:The evaluation of extracorporeal shock wave therapy on collagenase induced superficial digital flexor tendonitis. 1681 Mar 52


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