title: Treatment with inhibitors of the NF-kappaB pathway improves whole body tension development in the mdx mouse.
abstract: The whole body tension (WBT) method was used to evaluate the hypothesis that long term treatment with NF-kappaB inhibitors improves the total forward pulling tension exerted by the limb musculature of the mdx mouse. Mdx mice exhibited significantly reduced WBT values and more profound weakening during the course of generating multiple forward pulling movements than age-matched nondystrophic mice. Long term treatment with the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) did not significantly reduce nuclear p65 activation in the costal diaphragm, but increased WBT by 12% in mature (12 month) mice. Daily treatment (30 days) of 1 month old mdx mice with the inhibitor ursodeoxycholic acid (UDCA) reduced costal diaphragm nuclear p65 activation by 40% and increased WBT by 21%. These results indicate that treatment with NF-kappaB inhibitors improves WBT in the mdx mouse and further establishes the utility of the WBT procedure in assessing therapeutic efficacy.
authors.affiliation: Dept. of Physiology, Kirksville College of Osteopathic Medicine, AT Still University, Kirksville, MO 63501, USA.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Siegel
authors.forename: Cathy
authors.initials: C
authors.lastname: Bledsoe
authors.forename: Jesse
authors.initials: J
authors.lastname: Lavin
authors.forename: Francesca
authors.initials: F
authors.lastname: Gatti
authors.forename: Jonas
authors.initials: J
authors.lastname: Berge
authors.forename: Gregory
authors.initials: G
authors.lastname: Millman
authors.forename: Eric
authors.initials: E
authors.lastname: Turin
authors.forename: W Tyler
authors.initials: WT
authors.lastname: Winders
authors.forename: John
authors.initials: J
authors.lastname: Rutter
authors.forename: Beniamino
authors.initials: B
authors.lastname: Palmeiri
authors.forename: C George
authors.initials: CG
authors.lastname: Carlson
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D052580:Muscle Stretching Exercises / Q000009:adverse effects; D009129:Muscle Tonus / Q000187:drug effects* / Q000502:physiology; D018908:Muscle Weakness / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013859:Thiocarbamates / Q000494:pharmacology* / Q000627:therapeutic use; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D002756:Cholagogues and Choleretics; D016328:NF-kappa B; D011759:Pyrrolidines; C498144:Rela protein, mouse; D013859:Thiocarbamates; D051996:Transcription Factor RelA; C020972:pyrrolidine dithiocarbamic acid; D014580:Ursodeoxycholic Acid