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

Wolbachia endosymbiotic bacteria have been implicated in the inflammatory pathogenesis of filariasis. Inflammation induced by Brugia malayi female worm extract (BMFE) is dependent on Toll-like receptors 2 and 6 (TLR2/6) with only a partial requirement for TLR1. Removal of Wolbachia, lipids, or proteins eliminates all inflammatory activity. Wolbachia bacteria contain the lipoprotein biosynthesis genes Ltg and LspA but not Lnt, suggesting Wolbachia proteins cannot be triacylated, accounting for recognition by TLR2/6. Lipoprotein databases revealed 3-11 potential lipoproteins from Wolbachia. Peptidoglycan-associated lipoprotein (PAL) and Type IV secretion system-VirB6 were consistently predicted, and B. malayi Wolbachia PAL (wBmPAL) was selected for functional characterization. Diacylated 20-mer peptides of wBmPAL (Diacyl Wolbachia lipopeptide (Diacyl WoLP)) showed a near identical TLR2/6 and TLR2/1 usage compared with BMFE and bound directly to TLR2. Diacyl WoLP induced systemic tumor necrosis factor-alpha and neutrophil-mediated keratitis in mice. Diacyl WoLP activated monocytes induce up-regulation of gp38 on human lymphatic endothelial cells and induced dendritic cell maturation and activation. Dendritic cells primed with BMFE generated a non-polarized Th1/Th2 CD4+ T cell profile, whereas priming with Wolbachia depleted extracts (following tetracycline treatment; BMFEtet) polarized to a Th2 profile that could be reversed by reconstitution with Diacyl WoLP. BMFE generated IgG1 and IgG2c antibody responses, whereas BMFEtet or inoculation of TLR2 or MyD88-/- mice produced defective IgG2c responses. Thus, in addition to innate inflammatory activation, Wolbachia lipoproteins drive interferon-gamma-dependent CD4+ T cell polarization and antibody switching.
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PMID:Wolbachia lipoprotein stimulates innate and adaptive immunity through Toll-like receptors 2 and 6 to induce disease manifestations of filariasis. 1945 89