Thymosin-beta4 modulates corneal matrix metalloproteinase levels and polymorphonuclear cell infiltration after alkali injury. (57/274)

PURPOSE: Corneal alkali injury is highly caustic, and present clinical therapies are limited. The purpose of this study was to investigate the ability of thymosin-beta4 (Taubeta4) to promote healing in an alkali injury model and the mechanisms involved in that process. METHODS: Corneas of BALB/c mice were injured with NaOH, irrigated copiously with PBS, and treated topically with either Tbeta4 or PBS twice daily. At various time points after injury (PI), corneas from the Tbeta4- versus the PBS-treated group were examined for polymorphonuclear leukocyte (PMN) infiltration, chemokine, and matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) expression. RESULTS: Tbeta4-treated corneas demonstrated improved corneal clarity at day 7 PI. Whereas Tbeta4 decreased corneal MMP-2 and -9 and MT6-MMP levels after alkali injury, no change in TIMP-1 and -2 expression was detected. Tbeta4 treatment also decreased corneal KC (CXCL1) and macrophage inflammatory protein (MIP)-2 chemokine expression and PMN infiltration. Immunohistochemistry studies demonstrated MMP-9 expression at the leading edge of the epithelial wound, in the the limbus (containing stem cells), and in stromal PMNs. CONCLUSIONS: Tbeta4 treatment decreases corneal inflammation and modulates the MMP/TIMP balance and thereby promotes corneal wound repair and clarity after alkali injury. These results suggest that Tbeta4 may be useful clinically to treat severe inflammation-mediated corneal injuries.  (+info)

Effect of a metalloproteinase inhibitor on established corneal ulcers after an alkali burn. (58/274)

Proteinase inhibitors have been shown to prevent corneal ulceration and perforation when used immediately after an experimental alkali burn injury. To evaluate the clinical efficacy of a synthetic metalloproteinase inhibitor, HSCH2CH[CH2CH(CH3)2]CO-Phe-Ala-NH2(SIMP), treatment with inhibitor was withheld until corneal ulceration ensued after a standard alkali injury to the rabbit eye. When topical therapy with a 1 mmol/l solution of SIMP was initiated after corneal ulceration had progressed to a mid-stromal level (clinical score of 2), there was no significant difference in the progression of corneal ulceration between the treated vs. control group after 6 d of therapy. In the second study in which treatment was initiated earlier at the onset of superficial ulceration (clinical score of 1), there was a significant difference in clinical scores between the two groups after 1 day of treatment until termination of the experiment at 21 d (P less than 0.005). In the inhibitor-treated group, 88.9% of the corneas showed a reversal or cessation of progression of the ulceration process. Eighty-seven-and-a-half percent of the control corneas progressed to descemetocele formation or perforation by day 14 of treatment. This study suggests that SIMP may be used for effective treatment of corneal ulcers resulting from an alkali burn injury in the human eye. It also shows that early and aggressive initiation of therapy is critical.  (+info)

Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells. (59/274)

To examine whether transplantation of human mesenchymal stem cells (MSCs) could reconstruct the corneal damage and also whether grafted MSCs could differentiate into corneal epithelial cells, we isolated MSCs from healthy donors. After growth and expansion on amniotic membrane, cells were transplanted into rat corneas 7 days after chemical burns. Reconstruction of the damaged cornea and the rat vision were measured once a week by slit lamp and by an optokinetic head-tracking instrument, respectively. Corneas were then cut out, fixed, and imbedded for immunofluorescent study of the expression of keratin 3 and keratin-pan as epithelial cell markers. Expression of CD45, interleukin 2, and metalloproteinase-2 was also investigated for inflammation and inflammation-related angiogenesis. The data showed that transplantation of MSCs, like limbal epithelial stem cells, successfully reconstructed damaged rat corneal surface. Interestingly, the therapeutic effect of the transplantation may be associated with the inhibition of inflammation and angiogenesis after transplantation of MSCs rather than the epithelial differentiation from MSCs. This study provides the first line of evidence that MSCs can be used for reconstruction of damaged corneas, presenting a new source for autotransplantation in the treatment of corneal disorders.  (+info)

Improper disposal of hazardous substances and resulting injuries--selected States, January 2001-March 2005. (60/274)

Many consumer and industrial products, including fuels, solvents, fertilizers, pesticides, paints, and household cleaning disinfectants, contain hazardous substances. Improper disposal of these materials can lead to unexpected releases of toxins that are hazardous to humans and harmful to the environment. This report summarizes all known events involving improper disposal of hazardous substances reported to the Agency for Toxic Substances and Disease Registry (ATSDR) during January 2001-March 2005, describes four illustrative case reports, and provides recommendations for preventing injury resulting from improper disposal.  (+info)

Trapidil, an inhibitor for phosphodiesterase and platelet-derived-growth factor, ameliorates corrosive esophageal burn in rats. (61/274)

Corrosive esophageal burn is a common health problem in the pediatric age group and causes serious esophageal injuries. The medical treatment in acute phase of corrosive esophageal injury is of particular importance for prevention of esophageal stricture. We therefore aimed to investigate the possible beneficial effect of trapidil (triazolopyrimidine), an inhibitor for phosphodiesterase and platelet-derived-growth-factor, during acute phase of esophageal corrosive injury. Wistar albino rats were randomly allocated to untreated, treated, and sham-operated groups (n = 10 for each group). Corrosive esophageal burn was generated with 10% NaOH solution. The rats were left untreated (untreated group) or treated with trapidil as a single dose of 40 mg/kg intraperitoneally after one hour of the injury (treated group). Abdominal esophageal segment was isolated and tied in sham-control group. The studied esophageal segment was removed from each animal after 24 hours. Malondialdehyde (MDA) and nitric oxide (NO) levels were measured in the esophageal tissues. The ulcer depth was graded by histopathologic examination. MDA and NO levels were significantly higher in the untreated group than in the treated group. Namely, trapidil treatment significantly decreased MDA and NO levels in the injured tissues, the levels of which are similar to those in the tissues of control animals. The grades of ulcer depth were significantly improved in the treated group. These results indicate that the reactive oxygen radicals increase in the early phase of corrosive esophagitis and cause tissue damage. We suggest that trapidil treatment may be useful in acute phase of corrosive esophageal injury.  (+info)

Titanium tetrachloride burns to the eye. (62/274)

We present eight cases of chemical burns of the eyes from titanium tetrachloride, an acidic corrosive liquid. However it causes severe chemical burns which have a protracted course and features more akin to severe alkali burns. Injuries related to titanium tetrachloride should be treated seriously and accordingly appropriate management is suggested.  (+info)

Plasminogen kringle 5 inhibits alkali-burn-induced corneal neovascularization. (63/274)

PURPOSE: Plasminogen kringle 5 (K5) is a potent angiogenic inhibitor. The purpose of the present study was to evaluate the therapeutic effect of K5 on alkali-burn-induced corneal neovascularization (NV) and to investigate its mechanism of action. METHODS: Corneal NV was induced in rabbits by NaOH. The rabbits received eye drops containing K5 or vehicle alone, four times per day. Corneal NV and inflammation were monitored every other day with a slit lamp microscope, and the length of the vessels in the cornea and the area of NV were measured. Vascular endothelial growth factor (VEGF) was determined by immunohistochemical and Western blot analyses. The TUNEL assay was used to assess the apoptosis of endothelial cells. The effects of K5 on primary bovine aortic endothelial cells (BAECs) were determined by MTT assay, flow cytometry, transmission electron microscopy, and DNA fragmentation assay. RESULTS: Alkali-burn-induced progressive corneal NV and inflammation in the cornea. K5 delayed the onset of corneal NV (P < 0.05) and decreased NV areas (P < 0.05) in a dose-dependent manner. K5 treatment, after the formation of corneal NV, induced regression of newly formatted vessels in the cornea. K5 decreased the inflammatory index in the corneas at different time points after the alkali burn. Corneal VEGF levels were reduced by K5 treatment. K5 inhibits proliferation and induces apoptosis in BAECs. CONCLUSIONS: Topical application of K5 may have therapeutic potential for the chemical burn-induced corneal NV and inflammation. The inhibitory effect of K5 on corneal NV may be by downregulation of VEGF expression.  (+info)

Accelerated wound healing of alkali-burned corneas in MRL mice is associated with a reduced inflammatory signature. (64/274)

PURPOSE: The present study was conducted to investigate healing of alkali-burned corneas in MRL/MpJ (MRL) mice. METHODS: Gross, clinical, and histologic criteria were used to compare healing of alkali-burned corneas in MRL and control C57BL/6J (B6) mice. Effects of neutrophil depletion of B6 mice and allogeneic reconstitution of B6 mice with MRL bone marrow on wound healing were evaluated. Gene expression patterns in normal and wounded corneas were surveyed with array-based quantitative real-time RT-PCR (AQPCR). RESULTS: MRL mice showed accelerated reepithelialization and decreased corneal opacity compared with B6 mice after alkali wounding. Marked inflammatory cell infiltration and fibrosis were evident in the corneas and anterior chambers of B6 mice. MRL mice showed less severe lesions, except for stromal edema. Rapid reepithelialization and reduced keratitis/iritis were also observed in neutrophil-depleted B6 mice, but not in B6 mice reconstituted with MRL bone marrow. AQPCR showed transcriptional changes of fewer genes associated with inflammation and corneal tissue homeostasis in alkali-burned corneas from MRL mice. Increased expression of an anti-inflammatory gene, Socs1, and a gene associated with healing, Mmp1a, were evident in MRL corneas. CONCLUSIONS: Alkali-burned corneas heal faster and more completely in MRL mice than in B6 mice, by means of rapid reepithelialization, reduced inflammation, and reduced fibrosis. Reduced inflammation, including decreased neutrophil infiltrates and the lack of a robust proinflammatory gene expression signature correlates with the rapid healing. However, the rapid-healing phenotype is not intrinsic to MRL hematopoietic progenitor cells.  (+info)