Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many different infections with protozoan and helminthic parasites are common global health problems. Several protozoa are responsible for opportunistic infections in patients with AIDS. The newly developed drug, albendazole, has a strong activity against many nematode and cestode parasites. In the case of echinococcosis, it reduces the viability of protoscolices and cysts. Its hepatic metabolite, albendazole sulfoxide, is active against the larval cestodes. In the case of neurocysticercosis, administration of either the standard treatment, praziquantel, or the newly developed drug, albendazole, reduces or eliminates tapeworm cysts in 80-90% of patients. Patients with numerous cysts and those in whom neurologic symptoms or intracranial hypertension develops after therapy against cysticerci should receive adjunctive therapy with dexamethasone. Mass chemotherapy with single doses of albendazole or the older drug, mebendazole, is feasible for school-age children to treat the soil-transmitted helminthiases (ascariasis, hook-worm infection, and trichuriasis). The newly developed drug, ivermectin, is more effective against chronic strongyloidiasis than albendazole. It has been used most extensively against river blindness. It greatly reduces the number of microfilariae in the skin and eyes but has no effect on sclerosing keratitis or chorioretinitis. Both drugs are available in the US on a compassionate-use basis from their manufacturers. Field trials show that ivermectin is also effective against lymphatic filariasis and Mansonella ozzardi. Praziquantel is effective against many trematode and cestode infections. It is the drug of choice for schistosomiasis. Albendazole was effective against giardiasis in children in Bangladesh but ineffective in adult travelers returning from tropical areas. It appears to effect symptomatic improvement of intestinal microsporidial infections in patients with AIDS. The newly developed drug, fumagillin, can ameliorate ocular microsporidiosis. The newly developed drug, paromycin, treats cryptosporidiosis. Trimethoprim-sulfamethoxazole treats cyclosporiasis and isosporiasis.
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PMID:Antiparasitic drugs. 860 86

Ocular onchocerciasis results from immune recognition of parasite proteins released into the eye by degenerating microfilariae. Previous studies have shown that pathology similar to human ocular onchocerciasis can be induced in sensitized mice by intracorneal injection with Onchocerca volvulus antigens. In the current study, we used this murine model to map the segments of O. volvulus protein disulfide isomerase (OvPDI) associated with the development of corneal pathology. Subclones of OvPDI were constructed encompassing one or more predicted T cell epitopes. Keratitis was induced in BALB/c mice after subcutaneous immunizations with OvPDI, followed by intracorneal challenge of OvPDI constructs. Truncated OvPDI proteins containing amino acids 450-481 of OvPDI were found to induce keratitis, whereas constructs that did not include this region did not induce corneal pathology. Consistent with this observation, two peptides derived from the 450-481 region stimulated T cell proliferation to a greater degree than control carrier protein. DNA sequence analysis of cDNAs encoding OvPDI from blinding and non-blinding strains of O. volvulus indicated no differences in the primary amino acid sequence of the 450-481 domain. Immunization of animals with OvPDI induced antibodies recognizing a 55 kDa host protein, identical to the predicted molecular weight of the mouse PDI homologue. Together, these data implicate specific antigenic epitopes of OvPDI in the development of O. volvulus mediated corneal pathology.
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PMID:Identification of an epitope of a recombinant Onchocerca volvulus protein that induces corneal pathology. 929 6

Onchocercal keratitis (river blindness) is one of the leading worldwide causes of blindness. Light microscopic analysis of human specimens and corneal tissue from experimental models has implicated the eosinophil as an important cell in the inflammatory response. Our previous studies in experimental murine onchocercal keratitis have demonstrated that the inflammatory infiltrate is composed primarily of eosinophils displaying ring shaped or bilobed nuclei. However, a number of cells were not characterizable by light microscopy, presumably due to mechanical distortion. To more fully characterize the inflammatory cell infiltrate, we examined corneal specimens by transmission electron microscopy. In addition to typical eosinophils with bilobed and ring shaped nuclei, this approach revealed cells with variable nuclear morphology and cell shape which contained the dense cored granules characteristic of eosinophils. Hence, the degree of pleomorphism of eosinophils is broader than appreciated and underscores the importance of this cell in experimental murine onchocercal keratitis.
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PMID:Pleomorphism of stromal eosinophils in murine experimental onchocercal keratitis. 932 60

Invasion of the corneal stroma by neutrophils and eosinophils and subsequent degranulation disrupts corneal clarity and can result in permanent loss of vision. In the current study, we used a model of helminth-induced inflammation to demonstrate a novel role for Ab in mediating recruitment of these inflammatory cells to the central cornea. C57BL/6 and B cell-deficient (microMT) mice were immunized s. c. and injected intrastromally with Ags from the parasitic helminth Onchocerca volvulus (which causes river blindness). C57BL/6 mice developed pronounced corneal opacification, which was associated with an Ag-specific IL-5 response and peripheral eosinophilia, temporal recruitment of neutrophils and eosinophils from the limbal vessels to the peripheral cornea and subsequent migration to the central cornea. In contrast, the corneas of microMT mice failed to develop keratitis after intrastromal injection of parasite Ags unless Ags were injected with immune sera. Eosinophils were recruited from the limbal vessels to the peripheral cornea in microMT mice, but failed to migrate to the central cornea, whereas neutrophil recruitment was impaired at both stages. With the exception of IL-5, T cell responses and peripheral eosinophils were not significantly different between C57BL/6 and microMT mice. Taken together, these findings not only demonstrate that Ab is required for the development of keratitis, but also show that recruitment of neutrophils to the cornea is Ab-dependent, whereas eosinophil migration is only partially dependent upon Ab interactions.
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PMID:An essential role for antibody in neutrophil and eosinophil recruitment to the cornea: B cell-deficient (microMT) mice fail to develop Th2-dependent, helminth-mediated keratitis. 1052 1

River blindness is thought to occur as a result of the host response to degenerating microfilariae in the eye. Utilizing a murine model of corneal inflammation (keratitis) to investigate the immune and inflammatory responses associated with river blindness, we recently demonstrated an important role for endotoxin-like products from endosymbiotic bacteria and for activation of Toll-like receptor 4 (TLR4). These observations have led to a new understanding of the pathogenesis of this disease
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PMID:Immunopathogenesis of Onchocerca volvulus keratitis (river blindness): a novel role for endosymbiotic Wolbachia bacteria. 1259 65

Infection with the parasitic nematode Onchocerca volvulus is associated with inflammation of the skin and cornea that can lead to blindness. Corneal damage is thought to occur as a result of the host inflammatory responses to degenerating microfilariae in the eye. We have utilized a murine model of corneal inflammation (keratitis) to investigate the immune and inflammatory responses associated with river blindness. Soluble extracts of O. volvulus, a filarial species that contains the endosymbiont bacteria Wolbachia or Acanthocheilonema viteae (a nematode not naturally infected with the bacteria) were injected into mouse corneas. Inflammatory responses and corneal changes were measured. We demonstrated a major role for endosymbiont Wolbachia bacteria and Toll-like receptor 4 (TLR4) in the pathogenesis of ocular onchocerciasis.
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PMID:Immunopathogenesis of Onchocerca volvulus keratitis (river blindness): a novel role for TLR4 and endosymbiotic Wolbachia bacteria. 1473 27

In individuals with onchocerciasis, severe visual impairment (river blindness) occurs as a result of corneal inflammation induced by antigens released from dead and dying Onchocerca volvulus microfilariae. To characterize the underlying immune response, animal models have been developed that partially reproduce many of the clinical features of human onchocercal keratitis, Eric Pearlman here discusses how these studies have identified systemic and local immune responses associated with keratitis, including T helper-cell subset and cytokine responses.
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PMID:Experimental onchocercal keratitis. 1527 90

Onchocerciasis is caused by the parasitic worm Onchocerca volvulus, which releases millions of offspring (microfilariae). Microfilariae migrate through the skin and can enter the anterior or posterior regions of the eye. While alive, the microfilariae appear to cause little or no inflammation, being in the anterior chamber. However, when they die, either by natural attrition or after chemotherapy, the host response to degenerating worms can result in ocular inflammation (keratitis, uveitis, chorioretinitis, neuritis of the optic nerve) that causes progressive loss of vision and ultimately leads to blindness. With the use of a mouse model of corneal inflammation to study the pathogenesis of ocular onchocerciasis by injecting worm extracts directly into the corneal stroma, it was found that worms treated with the antibiotic doxycycline, which destroys Wolbachia, induced lower corneal stromal thickness and stromal haze (indicators of corneal oedema and opacity) and neutrophil infiltration compared with both untreated worms and worms that do not harbour Wolbachia. These data indicate that endosymbiotic Wolbachia bacteria in filarial parasites have a key role in the pathogenesis of river blindness. Worms recovered from patients treated for 6 weeks with doxycycline contained fewer Wolbachia bacteria and had abnormal embryogenesis, indicating a role for Wolbachia in the survival or fecundity of the worms. Antibiotic treatment may also reduce the severity of the inflammatory response in the cornea.
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PMID:[Ocular onchocerciasis: a key role for Wolbachia]. 1797 45