piperidines and Contracture

Fibrosis of normal tissues often accompanies radiation treatment of cancer. Activation of the transforming growth factor-beta (TGF-beta) signaling pathway is thought to play a major role in radiation-induced fibrosis and has prompted the development and assessment of low molecular weight inhibitors of the pathway. Previous studies with halofuginone have shown it to inhibit TGF-beta signaling in vitro and protect mice from radiation-induced leg contraction (a model for soft tissue fibrosis). The current study confirms these findings for HaCaT cells stimulated with exogenous TGF-beta treatment. Reducing the halifuginone treatment from 7 days/week (used previously) to 5 days/week post-radiation exposure provided significant protection against radiation-induced leg contraction in mice 3 and 4 months post-radiation treatment. Halofuginone treatment was shown to attenuate TGF-beta signaling molecules taken from irradiated skin including TGF-betaRII, pSmad3, Smad7, and TSP1. The latter, TSP1, a co-activator of TGF-beta may serve as a suitable biomarker for monitoring the efficacy of halofuginone should it be evaluated in a clinical setting for protection against radiation-induced fibrosis.

Topics: Animals; Cell Line; Contracture; Female; Fibrosis; Humans; Leg; Mice; Mice, Inbred C3H; Piperidines; Protein Serine-Threonine Kinases; Quinazolinones; Radiotherapy; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; Signal Transduction; Transforming Growth Factor beta

The measurement of diastasis of the spinous processes and of muscular action potentials by means of bio-feedback equipment is a clinically valid means to evaluate the extent of reflex muscular contracture. The methods were used to study the relaxant effect of pridinol mesylate on the lumbar extensor muscles in subjects with acute low back pain. It was found that pridinol mesylate significantly reduced the contracture of the extensor lumbar muscles in low back pain when given per os or parenterally.

Topics: Action Potentials; Back Pain; Biofeedback, Psychology; Contracture; Electrophysiology; Humans; Muscle Relaxation; Muscles; Piperidines; Posture

Topics: Back Pain; Contracture; Flatfoot; Humans; Low Back Pain; Mesylates; Muscle Relaxants, Central; Piperidines