Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0030552 (
paresis
)
5,831
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Treatment of rats for 5 to 6 days with dithiobiuret (
DTB
, 1 mg/kg/day, ip) causes a flaccid, ascending neuromuscular weakness which is associated with a decreased end-plate potential (EPP) amplitude, quantal content, miniature end-plate potential (MEPP) frequency, and prolongation of MEPP and EPP rise and decay times. Whereas small daily doses of
DTB
reliably cause this
paresis
, a single large dose, approximating the LD50, and far in excess of the cumulative dose given chronically to induce paralysis, causes no apparent muscle weakness. It was of interest to determine whether subtle changes in neuromuscular transmission are produced by
DTB
under dosing conditions in which gross muscle weakness is not apparent. As such the present study had two goals: first, to determine whether a single large dose of
DTB
(25 mg/kg, ip) altered neuromuscular transmission at times when the animal did not exhibit
paresis
; and second, to determine whether bath application of
DTB
, at concentrations approximating those in the animal following a single large dose, altered junctional transmission at early exposure times. EPPs and MEPPs were recorded, from hemidiaphragms taken 1, 4, 8, or 24 hr following treatment of rats with a single dose of
DTB
or vehicle or from untreated rats which were exposed to 200 microM or 1.85 mM
DTB
by bath application. One hour after a single large dose of
DTB
, EPP amplitude and MEPP frequency and amplitude were all decreased. Rise and decay times for MEPPs were prolonged in muscles taken 4 hr after treatment. By 4, 8, and 24 hr after treatment, EPP amplitude, MEPP amplitude, and MEPP frequency returned toward control levels. Bath application of
DTB
initially increased EPP amplitude, MEPP amplitude, and MEPP frequency; however, with continued exposure EPP amplitude decreased to below control levels. Block of EPPs occurred after approximately 10 or 37 min of exposure to 1.85 mM or 200 microM
DTB
, respectively. MEPP frequency also decreased with continued exposure to
DTB
, yet remained above control levels for the duration of
DTB
exposure. Bath application of
DTB
caused a slowing of decay times of MEPPs similar to that observed following in vivo exposure. These results demonstrate that a single large dose of
DTB
initially induces neuromuscular effects similar to those observed in rats paralyzed following chronic treatment with
DTB
but these effects, with the exception of effects on rise and decay times of synaptic potentials, tend to reverse by 24 hr following exposure.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Acute alterations in murine neuromuscular transmission following exposure to a nonparalytic dose of dithiobiuret. 215 19
