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)

Tetracycline has anticollagenase activity in human and animal tissues. Recent evidence shows collagenase to be instrumental in the progression of infectious and noninfectious corneal ulceration. We investigated the effect of systemic tetracycline on the incidence of corneal perforation in Pseudomonas aeruginosa ulcerative keratitis in rabbits. Twenty rabbits were assigned randomly to two groups in a masked fashion. All corneas were inoculated with 10(6) P. aeruginosa organisms. Ten rabbits (20 eyes) received intramuscular tetracycline 50mg/kg/day in a saline vehicle (treatment group), and ten rabbits (20 eyes) received saline alone (control group) for ten days. The incidence of corneal perforation in the treatment group (45%) was significantly lower than that in the control group (80%, P less than .02). This appeared to be independent of any antimicrobial effect from tetracycline. Administration of tetracycline may be a useful adjunct in the treatment of P. aeruginosa corneal ulcers.
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PMID:Effect of systemic tetracycline on progression of Pseudomonas aeruginosa keratitis in the rabbit. 211 13

Corneal ulceration and perforation following a severe alkali burn occur as a consequence of collagen destruction by locally released enzymes. A thiol peptide, which recently was shown to be a potent inhibitor of corneal collagenase in vitro, was tested in alkali-burned rabbit corneas to determine its effectiveness in inhibiting corneal ulceration. Following a standard alkali burn to one eye of each rabbit, ten animals were treated topically six times daily and subconjunctivally one time daily with a 1 mM solution of the peptide for a period of 3 weeks. A control group of ten rabbits was administered vehicle only using the same regimen as the experimental group. Corneal ulceration occurred in ten out of ten of the control eyes and seven out of ten progressed to perforation. The experimental group demonstrated ulcerations in four out of nine animals, only one of which was deep (one of nine), and no perforations. There was no significant difference when comparing the onset of ulceration between the two groups, but the difference was significant when comparing the total number of ulcerations (0.02 less than P less than 0.05), deep ulcerations (0.01 less than P less than 0.02) and perforations (0.001 less than P less than 0.01) between the two groups. Histologic examination of the corneas after 3 weeks of treatment revealed that the experimental, thiol-treated corneas that did not ulcerate contained relatively few PMNs, whereas the control corneas demonstrated a marked inflammatory infiltrate in the form of PMNs, most notably at sites of corneal ulceration. These findings demonstrate that a synthetic thiol peptide inhibits alkali-induced corneal ulceration and perforation in vivo.
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PMID:Inhibition of alkali-induced corneal ulceration and perforation by a thiol peptide. 215 43

The effects of transforming growth factor-beta (TGF beta) and epidermal growth factor (EGF) on the synthesis of collagen and fibronectin, and on the proliferation of human corneal stromal fibroblasts in vitro, were evaluated. Human corneal stromal fibroblasts in culture were incubated for 48 hours with TGF beta or EGF in the absence of serum. Collagen and fibronectin in the culture media were measured by a collagenase-digestion assay and a competitive ELISA, respectively. The effects of the growth factors on proliferation were assessed by 3H-thymidine incorporation. Collagen synthesis was dose-dependently stimulated by TGF beta; at a concentration of 1 ng/ml of TGF beta, a 120% increase in collagen synthesis was seen over that of controls (p < 0.01). EGF, at a concentration of 10 ng/ml, induced a 40% increase in collagen synthesis over that of controls (p < 0.01). The maximum stimulation by TGF beta was greater than that by EGF (p < 0.05). Fibronectin synthesis was stimulated by TGF beta and EGF in a dose-dependent manner; 230% (p < 0.001) and 210% (p < 0.01) increases in fibronectin synthesis were caused by 10 ng/ml TGF beta and EGF, respectively. TGF beta and EGF dose-dependently stimulated 3H-thymidine incorporation. The maximum increases in 3H-thymidine incorporation reached 180% (p < 0.001) and 190% (p < 0.001) over that in controls, at 10 ng/ml concentrations of TGF beta and EGF, respectively. In conclusion, both TGF beta and EGF are potent stimulants of collagen and fibronectin synthesis and proliferation. Therefore, these two growth factors may be effective alternatives or additional choices for the treatment of corneal ulcer.
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PMID:Transforming growth factor-beta stimulates collagen and fibronectin synthesis by human corneal stromal fibroblasts in vitro. 822 30

We examined the effect of matrix metalloproteinase (MMP) inhibitor (CS-610) on experimental pseudomonal corneal ulceration by clinical and histological evaluation. Intrastromal injection of 3.5 microliters sterile culture broth of P. aeruginosa, IID-1117 (13.5 unit Type I collagenase equivalent proteinase activities), was done to induce corneal ulcers in guinea pigs. The animals were divided into two groups of 23 each. The CS-610 group received topical CS-610 (400 micrograms/ml) treatment at 2-hour intervals and the control group received only the vehicle of CS-610 at the same intervals. In the control group, corneas developed acute corneal damage following corneal ulcerations at 6-12 hours. In the CS-610 group, these corneal lesions were inhibited in most of the eyes (p < 0.01). In the late period, as inflammatory cells migrated into the cornea, some animals of the CS-610 group developed corneal ulcer. The results indicated that CS-610 had a potent inhibitory activity against pseudomonal proteinases in vivo. The results also suggested that the mechanism of the ulceration model involved not only pseudomonal proteinases but also endogenous responses.
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PMID:[Effect of matrix metalloproteinase inhibitor on experimental pseudomonal corneal ulceration]. 985 15

Previous studies in the laboratory have shown that platelet-activating factor (PAF), a potent inflammatory mediator that accumulates rapidly in the cornea after an injury, stimulates the expression of urokinase (uPA) and matrix metalloproteinase-1 (MMP-1) and -9 (MMP-9). Tissue inhibitors of MMPs (TIMPs) and plasminogen activator inhibitor (PAI-1) are produced in conjunction with these enzymes and are important regulators of their activity. Here, the authors investigated how PAF affects the expression of PAI-1, TIMP-1 and -2 relative to that of uPA, MMP-1, and -9 in rabbit corneal epithelial cells. Rabbit corneas were incubated in MEM medium containing 100 nM cPAF. To block the effects of PAF in some studies, corneas were preincubated for 1 hr in the presence of the PAF antagonist BN50730 (10 microM). At several time intervals, mRNA was extracted from epithelial cells and the levels of gene expression for the enzymes and their inhibitors were determined by real-time PCR. All quantitations were normalized to the 18s rRNA values (endogenous control) and changes in gene expression were reported as fold increase relative to untreated controls. PAF produced a 20-fold increase in the gene expression of PAI-1 at 8 hr, while similar fold increases in uPA mRNA expression occurred at 2 hr. PAF treatment also stimulated the expression of TIMP-1 and -2 genes, with a six-fold increase in TIMP-1 expression occurring at 36 hr and a four-fold increase in TIMP-2 expression at 24 hr. Maximal induction of MMP-1 and -9 mRNA, on the other hand, occurred at 4 and 8 hr, respectively. Induction of MMP-1 gene expression was similar to that of its inhibitors TIMP-1 and -2, while MMP-9 mRNA induction exceeded that of these inhibitors by 100-fold. The PAF-induced expression of PAI-1, TIMP-1 and -2 mRNAs was abolished by pre-treatment with BN50730. These data indicate that PAF activates the gene expression of TIMP-1, -2, and PAI-1 in corneal epithelium by a receptor-mediated mechanism. Furthermore, PAF induced overexpression of MMP-9 mRNA relative to that of TIMP-1 and -2, suggesting an imbalance between the expression of this proteolytic enzyme and its inhibitors, which may contribute to changes in the wound-healing process and ultimately lead to corneal ulcer development.
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PMID:Platelet-activating factor induces the gene expression of TIMP-1, -2, and PAI-1: imbalance between the gene expression of MMP-9 and TIMP-1 and -2. 1201 20