FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4537230> ?p ?o ?g. }

• W4537230 endingPage "1059" @default.
• W4537230 startingPage "1059" @default.
• W4537230 abstract "To be of use in the control of tuberculosis, any new drug must be capable of shortening the duration of treatment by accelerating sterilizing activity, that is the rate at which Mycobacterium tuberculosis is killed in the lesions. The most difficult to kill are the extra-cellular bacilli in cavities. Persistence during therapy arises because there is a proportion of slowly metabolising bacilli (persisters) in the cavitary bacterial population at the start of treatment. Bacterial growth is slowed by low oxygen tension, quorum sensing and old age, but probably not by cellular immunity, since there are few professional phagocytic cells in cavities. The degree of phenotypic resistance to the bactericidal action of drugs can go through several stages: (i) the non-replicating stages 1 and 2 of micro-aerophilic adaptation, described by Wayne; (ii) a tolerant population that survives exposure to high rifampicin concentrations and is capable of growth in liquid medium but not on solid medium; and (iii) a population found in the sterile state of Cornell model mice which cannot grow initially in either liquid or solid medium but will eventually cause re-activation of tuberculosis. In all of these stages the bacilli are phenotypically resistant; there is no selection for genomic drug resistance. Rifampicin and pyrazinamide are the two drugs largely responsible for sterilizing activity during current treatment. Pyrazinamide is unique amongst anti-tuberculosis drugs in having no genomic site of action and having greater bactericidal activity as bacillary metabolism slows down; it is remarkably effective in human disease. The development of a new drug with a similar mode of activity might be very fruitful, especially if there were no need for an acid environment. Current methods advocated for drug development pass through a number of complex stages: choice of a genomic target, development of an in vitro assay, high throughput screening and identification of lead compounds, often with scaling up of synthesis of the molecule and preliminary studies of toxicity and animal pharmacology before tests are done for sterilizing activity. If the drug is not good at sterilizing, all of this initial work will be largely wasted as it would only have a very limited role in the treatment of MDR disease. One of the most important steps necessary is the development of rapid and simple tests to screen for sterilizing activity. Of tests currently available, none of those employing mice seem adequate, though a screen using a streptomycin dependent Mycobacterium tuberculosis seems the most hopeful. A set of in vitro tests is described. There is an urgent need to develop these tests further since the factors slowing growth are closer to those in tuberculous cavities than in mouse models. They have the advantages of simplicity and require only small amounts of a new molecule." @default.
• W4537230 created "2016-06-24" @default.
• W4537230 creator A5019940804 @default.
• W4537230 date "2004-01-01" @default.
• W4537230 modified "2023-09-23" @default.
• W4537230 title "The search for new sterilizing anti-tuberculosis drugs" @default.
• W4537230 cites W113437334 @default.
• W4537230 cites W1488891609 @default.
• W4537230 cites W1867075303 @default.
• W4537230 cites W1943619333 @default.
• W4537230 cites W1962278961 @default.
• W4537230 cites W1965280766 @default.
• W4537230 cites W2004753123 @default.
• W4537230 cites W2051025479 @default.
• W4537230 cites W2058610257 @default.
• W4537230 cites W2064290245 @default.
• W4537230 cites W2070278937 @default.
• W4537230 cites W2123084649 @default.
• W4537230 cites W2124001620 @default.
• W4537230 cites W2140571706 @default.
• W4537230 cites W2140999299 @default.
• W4537230 cites W2155360762 @default.
• W4537230 cites W2165885466 @default.
• W4537230 cites W2166758514 @default.
• W4537230 cites W2300029236 @default.
• W4537230 cites W233147817 @default.
• W4537230 cites W2408522819 @default.
• W4537230 cites W2412111353 @default.
• W4537230 cites W2474478755 @default.
• W4537230 cites W2914834773 @default.
• W4537230 cites W324835945 @default.
• W4537230 cites W94847999 @default.
• W4537230 doi "https://doi.org/10.2741/1293" @default.
• W4537230 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/14977529" @default.
• W4537230 hasPublicationYear "2004" @default.
• W4537230 type Work @default.
• W4537230 sameAs 4537230 @default.
• W4537230 citedByCount "83" @default.
• W4537230 countsByYear W45372302012 @default.
• W4537230 countsByYear W45372302013 @default.
• W4537230 countsByYear W45372302014 @default.
• W4537230 countsByYear W45372302015 @default.
• W4537230 countsByYear W45372302016 @default.
• W4537230 countsByYear W45372302017 @default.
• W4537230 countsByYear W45372302018 @default.
• W4537230 countsByYear W45372302019 @default.
• W4537230 countsByYear W45372302020 @default.
• W4537230 countsByYear W45372302021 @default.
• W4537230 countsByYear W45372302022 @default.
• W4537230 countsByYear W45372302023 @default.
• W4537230 crossrefType "journal-article" @default.
• W4537230 hasAuthorship W4537230A5019940804 @default.
• W4537230 hasBestOaLocation W45372301 @default.
• W4537230 hasConcept C114851261 @default.
• W4537230 hasConcept C142724271 @default.
• W4537230 hasConcept C185592680 @default.
• W4537230 hasConcept C203014093 @default.
• W4537230 hasConcept C2776870249 @default.
• W4537230 hasConcept C2777975735 @default.
• W4537230 hasConcept C2778607973 @default.
• W4537230 hasConcept C2780035454 @default.
• W4537230 hasConcept C2780459521 @default.
• W4537230 hasConcept C2780544761 @default.
• W4537230 hasConcept C2781069245 @default.
• W4537230 hasConcept C2908647359 @default.
• W4537230 hasConcept C501593827 @default.
• W4537230 hasConcept C523546767 @default.
• W4537230 hasConcept C54355233 @default.
• W4537230 hasConcept C71924100 @default.
• W4537230 hasConcept C86803240 @default.
• W4537230 hasConcept C89423630 @default.
• W4537230 hasConcept C98274493 @default.
• W4537230 hasConcept C99454951 @default.
• W4537230 hasConceptScore W4537230C114851261 @default.
• W4537230 hasConceptScore W4537230C142724271 @default.
• W4537230 hasConceptScore W4537230C185592680 @default.
• W4537230 hasConceptScore W4537230C203014093 @default.
• W4537230 hasConceptScore W4537230C2776870249 @default.
• W4537230 hasConceptScore W4537230C2777975735 @default.
• W4537230 hasConceptScore W4537230C2778607973 @default.
• W4537230 hasConceptScore W4537230C2780035454 @default.
• W4537230 hasConceptScore W4537230C2780459521 @default.
• W4537230 hasConceptScore W4537230C2780544761 @default.
• W4537230 hasConceptScore W4537230C2781069245 @default.
• W4537230 hasConceptScore W4537230C2908647359 @default.
• W4537230 hasConceptScore W4537230C501593827 @default.
• W4537230 hasConceptScore W4537230C523546767 @default.
• W4537230 hasConceptScore W4537230C54355233 @default.
• W4537230 hasConceptScore W4537230C71924100 @default.
• W4537230 hasConceptScore W4537230C86803240 @default.
• W4537230 hasConceptScore W4537230C89423630 @default.
• W4537230 hasConceptScore W4537230C98274493 @default.
• W4537230 hasConceptScore W4537230C99454951 @default.
• W4537230 hasIssue "1-3" @default.
• W4537230 hasLocation W45372301 @default.
• W4537230 hasLocation W45372302 @default.
• W4537230 hasOpenAccess W4537230 @default.
• W4537230 hasPrimaryLocation W45372301 @default.

• next