Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regional limb perfusion (RLP) significantly decreases morbidity and mortality associated with distal limb injuries in horses. There is an urgent need for finding additional effective antimicrobial drugs for use in RLP. In this study, we tested the pharmacokinetics (PK) of chloramphenicol in RLP. Eight horses participated in the study, which was approved by the University Animal Care and Use Committee. The cephalic and the saphenous veins were used to perfuse the limbs. Synovial samples were collected from the metacarpo/metatarsophalangeal (MCP/MTP) joint. The Friedman Test was applied for assessing change in PK concentration over time, for all time points. The Wilcoxon Signed Ranks Test was used to test the difference between PK concentration in joint & serum as well as concentration in joint vs. MIC. The comparison of measurements between measurements taken on hind vs. front legs was carried out using the Mann-Whitney Test. A P-value of 5% or less was considered statistically significant. After RLP, the concentration of chloramphenicol in the synovial fluid of the MCP/MTP joint using either the cephalic or the saphenous vein was initially far above the minimal inhibitory concentration (MIC) of most susceptible pathogens and remained above the MIC for approximately 6 h. The results indicate that performing RLP using the cephalic and saphenous veins enables reaching concentrations of chloramphenicol in the MCP/MTP joint that are well above the MIC of most susceptible pathogens. The chloramphenicol concentrations achieved in the synovial fluid of the MCP/MTP joint in the current study were between 1.5 (MTP) and 7 (MCP) times the MIC of MRSA in horses. These results are encouraging since MRSA infections are becoming far more common, causing considerable morbidity. To the best of our knowledge, this is the first study to evaluate the pharmacokinetics of chloramphenicol following RLP in the horse and the results are positive.
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PMID:Evaluation of regional limb perfusion with chloramphenicol using the saphenous or cephalic vein in standing horses. 2507 20

Selenium is traditionally considered as an antioxidant element and selenium compounds are often discussed in the context of chemoprevention and therapy. Recent studies, however, have revealed a rather more colorful and diverse biological action of selenium-based compounds, including the modulation of the intracellular redox homeostasis and an often selective interference with regulatory cellular pathways. Our basic activity and mode of action studies with simple selenium and tellurium salts in different strains of Staphylococcus aureus (MRSA) and Saccharomyces cerevisiae indicate that such compounds are sometimes not particularly toxic on their own, yet enhance the antibacterial potential of known antibiotics, possibly via the bioreductive formation of insoluble elemental deposits. Whilst the selenium and tellurium compounds tested do not necessarily act via the generation of Reactive Oxygen Species (ROS), they seem to interfere with various cellular pathways, including a possible inhibition of the proteasome and hindrance of DNA repair. Here, organic selenides are considerably more active compared to simple salts. The interference of selenium (and tellurium) compounds with multiple targets could provide new avenues for the development of effective antibiotic and anticancer agents which may go well beyond the traditional notion of selenium as a simple antioxidant.
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PMID:Aspects of a Distinct Cytotoxicity of Selenium Salts and Organic Selenides in Living Cells with Possible Implications for Drug Design. 2626 63