On the Action of Methotrexate and 6-Mercaptopurine on M. avium Subspecies paratuberculosis
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{"title"=>"On the action of methotrexate and 6-mercaptopurine on M. avium subspecies paratuberculosis", "type"=>"journal", "authors"=>[{"first_name"=>"Robert J.", "last_name"=>"Greenstein", "scopus_author_id"=>"7007022089"}, {"first_name"=>"Liya", "last_name"=>"Su", "scopus_author_id"=>"24544993100"}, {"first_name"=>"Vahram", "last_name"=>"Haroutunian", "scopus_author_id"=>"7006715762"}, {"first_name"=>"Azra", "last_name"=>"Shahidi", "scopus_author_id"=>"6604049141"}, {"first_name"=>"Sheldon T.", "last_name"=>"Brown", "scopus_author_id"=>"7501420431"}], "year"=>2007, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"17252054", "issn"=>"19326203", "pui"=>"352605968", "sgr"=>"34249986158", "scopus"=>"2-s2.0-34249986158", "doi"=>"10.1371/journal.pone.0000161", "isbn"=>"1932-6203 (Electronic)"}, "id"=>"00f1ee23-5cbb-322a-b2a6-61dbe0bf5b9b", "abstract"=>"BACKGROUND: Clinical improvement in inflammatory bowel disease (IBD) treated with methotrexate and 6-mercaptopurine (6-MP) is associated with a decrease in pro-inflammatory cytokines. This has been presumed to indicate the mechanism of action of methotrexate and 6-MP. Although controversial, there are increasingly compelling data that Mycobacterium avium subspecies paratuberculosis (MAP) may be an etiological agent in some or all of IBD. We hypothesized that the clinical efficacy of methotrexate and 6-MP in IBD may be to simply inhibit the growth of MAP.\\n\\nMETHODOLOGY: The effect on MAP growth kinetics by methotrexate and 6-MP were evaluated in cell culture of two strains each of MAP and M. avium using a radiometric ((14)CO(2) BACTEC detection system that quantifies mycobacterial growth as arbitrary \"growth index units\" (GI). Efficacy data are presented as \"percent decrease in cumulative GI\" (% -DeltacGI).\\n\\nPRINCIPAL FINDINGS: The positive control antibiotic (clarithromycin) has >or=85% -DeltacGI at a concentration of 0.5 microg/ml. The negative control (ampicillin) has minimal inhibition at 64 microg/ml. MAP ATCC 19698 shows >or=80% -DeltacGI for both agents by 4 microg/ml. With the other three isolates, although more effective than ampicillin, 6-MP is consistently less effective than methotrexate.\\n\\nCONCLUSIONS: We show that methotrexate and 6-MP inhibit MAP growth in vitro. Each of the four isolates manifests different % -DeltacGI. These data are compatible with the hypothesis that the clinical improvement in patients with IBD treated with methotrexate and 6-MP could be due to treating a MAP infection. The decrease in pro-inflammatory cytokines, thought to be the primary mechanism of action, may simply be a normal, secondary, physiological response. We conclude that henceforth, in clinical studies that evaluate the effect of anti-MAP agents in IBD, the use of methotrexate and 6-MP should be excluded from any control groups.", "link"=>"http://www.mendeley.com/research/action-methotrexate-6mercaptopurine-m-avium-subspecies-paratuberculosis", "reader_count"=>16, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>2, "Student > Master"=>2, "Other"=>2, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>2, "Student > Master"=>2, "Other"=>2, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>4, "Immunology and Microbiology"=>1, "Veterinary Science and Veterinary Medicine"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1, "Argentina"=>1, "United Kingdom"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/953434"], "description"=>"<p>A composite graph of the four bacterial strains studied. “0” is diluent control with an equal CFU inoculum and “00” is a 1∶10 dilution of the water control inoculum. Drug concentrations are indicated on the abscissa. For each isolate, drug dose was studied in singlicate. For all four bacteria, clarithromycin has achieved maximal inhibition by 1 µg/ml. For MAP ATCC 19698, replicating data presented in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000161#pone-0000161-g001\" target=\"_blank\">Figure 1</a>, both methotrexate and 6-MP %−<i>Δ</i>GI is the same as for clarithromycin by 4 µg/ml. Note that with the other MAP isolate (Dominic) and both <i>M. avium</i> isolates, methotrexate is more effective at a lower dose than is 6-MP. The lower cumulative GI (seen on the ordinate) for the <i>M. avium</i> isolates is ascribable to their more rapid growth and earlier reaching the off scale BACTEC GI values of “999.”</p>", "links"=>[], "tags"=>["microbiology/environmental microbiology", "microbiology/medical microbiology", "gastroenterology and hepatology/gastrointestinal infections", "gastroenterology and hepatology/inflammatory bowel disease", "infectious diseases/antimicrobials and drug resistance", "infectious diseases/bacterial infections", "infectious diseases/gastrointestinal infections", "public health and epidemiology/infectious diseases", "surgery/gastrointestinal surgery"], "article_id"=>623731, "categories"=>["Medicine", "Computational Biology", "Engineering", "Cancer", "Infectious Diseases", "Microbiology", "Virology"], "users"=>["Robert J. Greenstein", "Liya Su", "Vahram Haroutunian", "Azra Shahidi", "Sheldon T. Brown"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000161.g002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Figure_2_/623731", "title"=>"Figure 2", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 12:51:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/953313"], "description"=>"<p>Shown is a bar graph of the cumulative GI data evaluating MAP ATCC 19698. Each drug dilution was studied in duplicate. Error bars are SD. There are three control inoculations, labeled on the abscissa as “0, 00 & 000. The left hand “0” had an equal number of CFU's as in each drug studied. “00”  =  10 & “000”  =  100 fold dilutions. In each control the maximum concentration of diluent used for each agent (methanol for Clarithromycin, water for ampicillin and NaOH for methotrexate and 6-MP) was added. Clarithromycin is most effective and ampicillin is the least effective at decreasing MAP growth. Both methotrexate and 6-MP are as effective as clarithromycin in MAP %−<i>Δ</i>cGI at a dose of 4 µg/ml.</p>", "links"=>[], "tags"=>["microbiology/environmental microbiology", "microbiology/medical microbiology", "gastroenterology and hepatology/gastrointestinal infections", "gastroenterology and hepatology/inflammatory bowel disease", "infectious diseases/antimicrobials and drug resistance", "infectious diseases/bacterial infections", "infectious diseases/gastrointestinal infections", "public health and epidemiology/infectious diseases", "surgery/gastrointestinal surgery"], "article_id"=>623614, "categories"=>["Medicine", "Computational Biology", "Engineering", "Cancer", "Infectious Diseases", "Microbiology", "Virology"], "users"=>["Robert J. Greenstein", "Liya Su", "Vahram Haroutunian", "Azra Shahidi", "Sheldon T. Brown"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000161.g001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Figure_1_/623614", "title"=>"Figure 1", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 12:51:05"}

PMC Usage Stats | Further Information

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Relative Metric

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