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F Villegas R Angles R Barrientos G Barrios MA Valero K Hamed H Grueninger SK Ault A Montresor D Engels S Mas-Coma AF Gabrielli 《PLoS neglected tropical diseases》2012,6(8):e1720
Background
The Bolivian northern Altiplano is characterized by a high prevalence of Fasciola hepatica infection. In order to assess the feasibility, safety and efficacy of large-scale administration of triclabendazole as an appropriate public health measure to control morbidity associated with fascioliasis, a pilot intervention was implemented in 2008.Materials and Methods
Schoolchildren from an endemic community were screened for fascioliasis and treated with a single administration of triclabendazole (10 mg/kg). Interviews to assess the occurrence of adverse events were conducted on treatment day, one week later, and one month after treatment. Further parasitological screenings were performed three months after treatment and again two months later (following a further treatment) in order to evaluate the efficacy of the intervention.Results
Ninety infected children were administered triclabendazole. Adverse events were infrequent and mild. No serious adverse events were reported. Observed cure rates were 77.8% after one treatment and 97.8% after two treatments, while egg reduction rates ranged between 74% and 90.3% after one treatment, and between 84.2% and 99.9% after two treatments. The proportion of high-intensity infections (≥400 epg) decreased from 7.8% to 1.1% after one treatment and to 0% after two treatments.Conclusion
Administration of triclabendazole is a feasible, safe and efficacious public health intervention in an endemic community in the Bolivian Altiplano, suggesting that preventive chemotherapy can be applied to control of fascioliasis. Further investigations are needed to define the most appropriate frequency of treatment. 相似文献24.
Bleomycin (BLM) is a clastogenic compound, which due to the overdispersion in the cell distribution of induced dicentrics has been compared to the effect of high-LET radiation. Recently, it has been described that in fibroblast derived cell lines BLM induces incomplete chromosome elements more efficiently than any type of ionizing radiation. The objective of the present study was to evaluate in human lymphocytes the induction of dicentrics and incomplete chromosome elements by BLM. Peripheral blood samples have been treated with different concentrations of BLM. Two cytogenetic techniques were applied, fluorescence plus Giemsa (FPG) and FISH using pan-centromeric and pan-telomeric probes. The observed frequency of dicentric equivalents increases linearly with the BLM concentration, and for all BLM concentrations the distribution of dicentric equivalents was overdispersed. In the FISH study the ratio between total incomplete elements and multicentrics was 0.27. The overdispersion in the dicentric cell distribution, and the linear BLM-concentration dependence of dicentrics can be compared to the effect of high-LET radiation, on the contrary the ratio of incomplete elements and multicentrics is similar to the one induced by low-LET radiation (~0.40). The elevated proportion of interstitial deletions in relation to total acentric fragments, higher than any type of ionizing radiation could be a characteristic signature of the clastogenic effect of BLM. 相似文献
25.
It has been over 80 years since the antiarthritic properties of gold(I) complexes were first recognized. However, a detailed understanding of their mechanism of action has been slow to develop. One likely biological target of gold(I) is the cathepsin family of lysosomal cysteine proteases, enzymes involved in the inflammation and joint destruction that are hallmarks of rheumatoid arthritis (RA). We have previously shown that analogs of auranofin, a clinically available antiarthritic drug, inhibit cathepsin B. In this study, the extent to which the steric and electronic properties of the phosphine ligand can be modified to obtain enhanced potency against cathepsin B is investigated. 相似文献
26.
Shamila S. Gunatilleke Cesar Augusto F. de Oliveira J. Andrew McCammon Amy M. Barrios 《Journal of biological inorganic chemistry》2008,13(4):555-561
Gold(I) compounds have been used in the treatment of rheumatoid arthritis for over 80 years, but the biological targets and
the structure–activity relationships of these drugs are not well understood. Of particular interest is the molecular mechanism
behind the antiarthritic activity of the orally available drug triethylphosphine(2,3,4,6-tetra-O-acetyl-β-1-d-thiopyranosato-S) gold(I) (auranofin, Ridaura). The cathepsin family of lysosomal, cysteine-dependent enzymes is an attractive biological
target of Au(I) and is inhibited by auranofin and auranofin analogs with reasonable potency. Here we employ a combination
of experimental and computational investigations into the effect of changes in the phosphine ligand of auranofin on its in
vitro inhibition of cathepsin B. Sequential replacement of the ethyl substituents of triethylphosphine by phenyl groups leads
to increasing potency in the resultant Au(I) complexes, due in large part to favorable interactions of the more sterically
bulky Au(I)–PR3 fragments with the enzyme active site. 相似文献
27.
A significant challenge in the field of medicinal inorganic chemistry is the identification of biological targets of metal-based drugs and the characterization of the metal–biomolecule adducts. A classic example is Au(I), which has long been used to treat rheumatoid arthritis despite a poor understanding of its biological targets due to the lability, reactivity, and “spectroscopic silence” that are characteristic of Au(I). Here, we report two qualitative methods for characterizing Au(I)–protein adducts: a thiol-reactive probe that facilitates the identification of biological cysteine–Au(I) adducts and a photoreactive Au(I) complex that produces a covalent bond between the Au(I) complex and the biomolecule. 相似文献
28.
Thirteen reef areas of Colombian territories in the Southwestern Caribbean were surveyed during the last 10 years. Coral diseases have been recorded in all these areas since 1990 and some of them have increased progressively. Six types were differentiated in the region, of which black band disease (BBD), dark spots disease (DSD), white band disease (WBD) and white plague disease (WPD) are widespread and common. Yellow band disease (YBD) was observed only since April 1998 but has been found now in seven reef areas and eight coral species (most of them recorded here as new hosts). In total, 25 species of hard corals were observed with diseases in the region, of which Colpophyllia natans, Diploria labyrinthiformis, Montastraea annularis, M. faveolata, M. franksi and Acropora spp. appear to be highly susceptible. 相似文献
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Acetonitrile-based solvents: Their application in thin-layer chromatography of cyclic nucleotides, nucleosides, purine, and pyrimidines 总被引:1,自引:0,他引:1
Joseph F. Tomashefski Jr. Roberto J. Barrios Oscar Sudilovsky 《Analytical biochemistry》1974,60(2):589-595
Acetonitrile-based solvent mixtures have been applied to the separation of nucleotides, nucleosides, purines, pyrimidines, and cyclic nucleotides by thin-layer chromatography. The Rf's of over 35 compounds are presented. Development times with some of the systems were as low as 16 min. The use of acetonitrile-containing solvents in adenyl cyclase and cyclic phosphodiesterase assays and in the nucleotides and nucleic acid fields is discussed. 相似文献