Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Peyronie's disease is an acquired benign condition without known systemic sequelae with presenting symptoms that include the presence of a plaque or induration of the penile shaft, penile curvature or deformity during erection, penile pain, and erectile dysfunction. This article reviews the natural history of the disease, discusses the disease's etiology (widely thought to involve minor penile trauma with subsequent aberrant wound healing), and outlines proper clinical evaluation of Peyronie's disease patients. Medical treatments can be systemic (colchicine, potassium aminobenzoate, vitamin E), intralesional (steroids, verapamil, collagenase, interferons), or topical. Surgical therapy for Peyronie's disease (plication, graft-based, and prosthetic techniques) should be reserved for the man who has failed conservative therapy and whose curvature, indentation, or erectile dysfunction precludes intercourse. Regardless of the surgical procedure, the patient should be made aware of the inherent risks of surgery.
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PMID:Peyronie's Disease: A Review. 1698 35

The essentially irreversible degradation of articular cartilage collagen represents a key, rate-limiting process in arthritic diseases. This process is typically initiated as a consequence of an inflammatory response, and if left unchecked ultimately leads to loss of joint function, pain, disability and a need for joint replacement surgery. Although we have identified the enzymes capable of effecting such destructive proteolysis, and considerable evidence indicates that tumour necrosis factor alpha and interleukin-1 are major pro-inflammatory mediators in joint destruction, we still know relatively little about how these mediators regulate collagenase gene expression in chondrocytes. Inflammatory arthritis has long been considered to be synovium-driven but compelling data now also implicate the chondrocyte, the sole cell type present in cartilage, as an active player in the destructive process. An understanding of how different cytokines interact, and how the pathways they activate cross-talk will not only provide important new insight into the mechanisms of joint destruction but also identify new targets for therapeutic intervention.
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PMID:Collagenase gene regulation by pro-inflammatory cytokines in cartilage. 1712 15

The debilitating destruction of joint tissues seen in osteoarthritis (OA) is due, in large part, to the degradative activity of metalloproteinase (MP) enzymes that target extracellular matrix (ECM) components within articular cartilage. Although successful in suppressing the pain and inflammation associated with this disease, conventional OA therapeutics do not inhibit the underlying tissue catabolism, allowing the disease to progress into irreversible ECM loss and chronic disability. Therapeutic inhibition of metalloproteinase activity is not a new concept, however, its transfer into clinical use has been frustrating. Disappointing results from clinical trials with small molecule inhibitors of metalloproteinases have highlighted the critical importance of inhibitor specificity, and the need to identify the individual metalloproteinases responsible for joint destruction. We discuss strategies of inhibition using small molecule inhibitors and tissue inhibitors of metalloproteinases (TIMPs) engineered to increase inhibitory specificity, and present new data using of new reagents such as ribozymes and inhibitory RNAs that repress expression of specific enzymes. Recent data has implicated the disease stage-dependent involvement of matrix metalloproteinase-1, -2, -3, -9, -13, ADAM-17/TACE (tumor-necrosis factor-alpha converting enzyme), and ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin 1 motifs) as major in vivo mediators of the ECM degradation seen in OA, and as such, they represent promising therapeutic targets. We conclude that the concept of molecular polypharmacy, in which the relevant enzymes are selectively targeted with multiple directed therapies, may offer a new therapeutic strategy that prevents joint destruction and minimizes toxicities.
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PMID:Molecular targets in osteoarthritis: metalloproteinases and their inhibitors. 1730 7

Peyronie's disease is a localised, fibrosing condition of the penis that occurs in up to 9% of men. Although its aetiology has not been elucidated, Peyronie's disease probably results from the presence of a predisposing genetic susceptibility combined with an inciting event, most probably trauma. Following appropriate clinical evaluation, initial treatment consists of a trial of oral and/or intralesional pharmacotherapy. Oral therapies most commonly employed include para-aminobenzoate (Potaba) and tocopherol (vitamin E), with colchicine, tamoxifen, propoleum and acetyl-L-carnitine being used less frequently. Placebo-controlled studies examining these agents have failed to show a consistent beneficial effect on Peyronie's disease, with the exception of para-aminobenzoate, which may decrease plaque size and curvature, and acetyl-L-carnitine, which may reduce erectile pain and inhibit disease progression. Intralesional injection therapy for Peyronie's disease is commonly used as a first-line therapy along with oral medications. The current standard of care involves injection with interferon-alpha-2a or -2b, verapamil or collagenase over 2-week intervals for a period of 5-6 months. Interferon-alpha-2b, in particular, has been documented in a large, multicentre, placebo-controlled study to be significantly more effective than placebo in decreasing penile curvature, plaque size, penile pain and plaque density. However, interferon treatment is also associated with significant adverse effects, including fever and other flu-like symptoms. Other available therapies that have not consistently shown efficacy in placebo-controlled studies include corticosteroids and orgotein. Surgery is considered in patients with Peyronie's disease who have not responded to a trial of conservative medical therapy for 1 year and who are precluded from sexual intercourse. Procedures commonly performed include the Nesbit procedure (or variations of the Nesbit), penile plaque incision/excision with or without grafting, and implantation of a penile prosthesis. Further basic scientific research in Peyronie's disease is likely to identify additional targets for future pharmacotherapy.
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PMID:Pharmacological Management of Peyronie's Disease. 1735 13

We evaluated the effects of buprenorphine (0.05 mg/kg intraperitoneally) after collagenase-induced intracerebral hemorrhage in Sprague-Dawley rats. Methods of evaluation included serum biochemistry, behavioral tests (neurologic exam and rotarod treadmill), and histopathology. Serum biochemistry parameters showed no change after surgery in controls and buprenorphine-treated animals. At 48 h after collagenase injections, the performance of treated rats on the rotarod treadmill test was not significantly different from that of untreated rats, but the neurologic exams of treated rats showed significantly improved performance. Although the volume of the hematoma was reduced with buprenorphine, the number of necrotic neurons in the penumbra was significantly increased. These data indicate that administration of buprenorphine led to neurologic and histopathologic differences in a rat model of intracerebral hemorrhage, and data from such studies should be interpreted carefully if an opioid analgesic is used to minimize pain.
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PMID:Effects of buprenorphine on intracerebral collagenase-induced hematoma in Sprague-Dawley rats. 1748 46

Prolotherapy is an alternative injection-based therapy for chronic musculoskeletal pain. Three different proliferants, D-glucose (dextrose), phenol-glucose-glycerine (P2G), and sodium morrhuate, used in prolotherapy are hypothesized to strengthen and reorganize chronically injured soft tissue and decrease pain through modulation of the inflammatory process. Our hypothesis is that commonly used prolotherapy solutions will induce inflammation (leukocyte and macrophage infiltration) in medial collateral ligaments (MCLs) compared to needlestick, saline injection, and no-injection controls. MCLs of 84 Sprague- Dawley rats were injected one time at both the tibial and femoral insertions. Immunohistochemistry (IHC) was used to determine the inflammatory response at three locations (tibial and femoral insertions and midsubstance) 6, 24, and 72 h after dextrose injection compared to saline- and no-injection controls and collagenase (positive control) (n = 4). qPCR was used to analyze gene expression 24 h postinjection (n = 4). Sodium morrhuate, P2G, and needlestick control were also investigated after 24 h (n = 4). In general, inflammation (CD43+, ED1+, and ED2+ cells) increased after prolotherapy injection compared to no-injection control but did not increase consistently compared to saline and needlestick control injections. This response varied by both location and proliferant. Inflammation was observed at 6 and 24 h postinjection but was resolved by 72 h compared to no-injection controls (p < 0.05). CD43+ leukocytes and ED2+ macrophages increased compared to needlestick and saline-injection control, respectively, 24 h postinjection (p < 0.05). Prolotherapy injections created an inflammatory response, but this response was variable and overall, not uniformly different from that caused by saline injections or needlestick procedures.
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PMID:Early inflammatory response of knee ligaments to prolotherapy in a rat model. 1824 Mar 27

The properties of dorsal root ganglion (DRG) neurons have been mostly investigated in culture of dissociated cells, and it is uncertain whether these cells maintain the electrophysiological properties of the intact DRG neurons. Few attempts have been made to record from DRG neurons in the intact ganglion using the patch clamp technique. In this study, rat DRGs were dissected and incubated for at least 1h at 37 degrees C in collagenase (10mg/ml). We used oblique epi-illumination to visualize DRG neurons and perform patch clamp recordings. All DRG neurons exhibited strong delayed rectifier potassium current and a high threshold for spike generation (-15 mV) that rendered the cells very weakly excitable, generating only one action potential upon strong current injection (>300 pA). It is therefore possible that cultured DRG neurons, commonly used in studies of pain processing, may be hyperexcitable because they acquired "neuropathic" properties due to the injury induced by their dissociation. Electrical stimulation of the attached root produced an antidromic spike in the soma that could be blocked by intracellular hyperpolarization or high frequency stimulation. Imaging intracellular calcium concentration with Oregon Green BAPTA-1 indicates that antidromic stimulation caused a long-lasting increase in intracellular calcium concentration mostly near the cell membrane. This study describes a simple approach to examine the electrophysiological and pharmacological properties and intracellular calcium signaling in DRG neurons in the intact ganglion where the effects of somatic spike invasion can be studied as well.
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PMID:An improved method for patch clamp recording and calcium imaging of neurons in the intact dorsal root ganglion in rats. 1858 15

Peyronie's disease (PD) is a wound-healing disorder in which a fibrotic plaque forms in the tunica albuginea layer of the penis. It clinically presents as any combination of penile pain, angulation, and erectile dysfunction. Recent studies indicate that PD has a prevalence of 3%-9% in adult men. Although the exact etiology has not been established, PD likely results from a predisposing genetic susceptibility combined with an inciting event such as microtrauma during intercourse. During the initial acute phase (6-18 months), the condition may progress, stabilize, or regress. For this reason authorities recommend a more conservative treatment approach, with a trial of oral and/or intralesional pharmacotherapy, before surgical reconstruction is considered. Oral therapies most commonly employed include tocopherol (vitamin E) and paraaminobenzoate (Potaba), with colchicine, tamoxifen, propoleum, and acetyl-L-carnitine being used less often. There are a limited number of long-term placebo-controlled studies with these oral agents, and for the most part, studies have failed to show a consistent beneficial effect. Intralesional injection therapy for PD is more commonly used as a first-line therapy. The current standard of care includes injection with interferon-alpha-2b, verapamil, or collagenase. Interferon-alpha-2b, in particular, has been documented in a large, multicenter, placebo-controlled study to show significant benefit over placebo in decreasing penile curvature, plaque size, penile pain, and plaque density. However, intralesional interferon is associated with posttreatment flu-like symptoms unless patients are premedicated with a nonsteroid anti-inflammatory agent. Other available therapies that have not consistently shown efficacy in placebo-controlled studies include corticosteroids, orgotein, radiation, and extracorporeal shockwave therapy. Surgery is considered when men with PD do not respond to conservative or medical therapy for approximately 1 year and cannot perform satisfactory sexual intercourse. Ongoing basic research in PD will likely identify future targets for medical exploitation.
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PMID:Medical management of Peyronie's disease. 1897 22

Chronic tendinopathy is characterized with longstanding activity-related pain with degenerative tendon injuries. An objective tool to measure painful responses in animal models is essential for the development of effective treatment for tendinopathy. Gait analysis has been developed to monitor the inflammatory pain in small animals. We reported the use of motion analysis to monitor gait changes in a rat model of degenerative tendon injury. Intratendinous injection of collagenase into the left patellar tendon of Sprague Dawley rat was used to induce degenerative tendon injury, while an equal volume of saline was injected in the control groups. Motion analyses with a high speed video camera were performed on all rats at pre-injury, 2, 4, 8, 12 or 16 weeks post injection. In the end-point study, the rats were sacrificed to obtain tendon samples for histological examination after motion analyses. In the follow-up study, repeated motion analyses were performed on another group of collagenase-treated and saline-treated rats. The results showed that rats with injured patellar tendon exhibited altered walking gait as compared to the controls. The change in double stance duration in the collagenase-treated rats was reversible by administration of buprenorphrine (p=0.029), it suggested that the detected gait changes were associated with pain. Comparisons of end-point and follow-up studies revealed the confounding effects of training, which led to higher gait velocities and probably a different adaptive response to tendon pain in the trained rats. The results showed that motion analysis could be used to measure activity-related chronic tendon pain.
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PMID:The use of motion analysis to measure pain-related behaviour in a rat model of degenerative tendon injuries. 1942 42

We evaluated the efficacy and safety of chemonucleolysis and intradiscal electrothermal therapy (IDET) on the basis of the data presented in recently published papers with respect to pain relief, function, and complication rates. Detailed searches for English and German articles published between 2003 and 2008 were performed in a number of electronic databases. Further publications were identified by manual search. For summarizing the evidence, we considered only systematic reviews and controlled studies. The internal validity of reviews and studies was judged by two authors independently. Data extraction was performed by one author, and the extracted data was checked for completeness and correctness by a second author. The evidence of the efficacy of chemonucleolysis using chymopapain or collagenase is summarized in two recent, high-quality systematic reviews. We found 5 controlled studies evaluating nucleolysis using an oxygen-ozone mixture (O (2)O (3)-nucleolysis). Some of those studies were of limited methodological quality, but all showed the efficacy of O (2)O (3)-nucleolysis in comparison to microdiscectomy or the use of alternative substances. There is hardly any data regarding O (2)O (3)-nucleolysis complications. Regarding IDET, the authors of the 6 identified systematic reviews come to different conclusions about the efficacy of the procedure. The results of the 3 included controlled IDET studies, of which 2 are of high methodological quality, are also conflicting. The complication rates range from 0 to 15 %. In summary, the evidence of efficacy is presently more compelling for chemonucleolysis than for IDET. This may also be because indications for chemonucleolysis are more firmly established. However, safety aspects should be better evaluated and presented in the literature.
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PMID:[Chemonucleolysis and intradiscal electrothermal therapy: what is the current evidence?]. 1978 5


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