Repeated oral administration of a cathepsin K inhibitor significantly suppresses bone resorption in exercising horses with evidence of increased bone formation and maintained bone turnover.

Our investigations evaluated the effect of VEL-0230, a highly specific irreversible inhibitor of cathepsin K (CatK). The objectives of our study were to determine whether repeated dosing of a CatK inhibitor (CatKI) produced a desired inhibition of the bone resorption biomarker (CTX-1), and document the effect of repeated dosing on bone homeostasis, structure, and dynamics of bone resorption and formation in horses. Twelve young exercising horses were randomized in a prospective, controlled clinical trial and received 4 weekly doses of a CatKI or vehicle. Baseline and poststudy nuclear scintigraphy, blood sampling and analysis of plasma bone biomarkers (CTX-1 and osteocalcin), poststudy bone fluorescent labeling, and bone biopsy were performed. Bone specimens were further processed for microcomputed tomography and bone histomorphometry. Each dose of this CatKI transiently inhibited plasma CTX-1 (reflecting inhibition of bone collagen resorption) and increased bone plasma osteocalcin concentrations, with no detectable adverse effect on normal bone turnover in the face of exercise. Bone morphology, density, and formation rate were not different between control and treated group. Further investigation of CatK inhibition in abnormal bone turnover is required in animals with bone diseases.

Normobaric hyperoximia increases hypoxia-induced cerebral injury: DTI study in rats.

Perinatal hypoxia affects normal neurological development and can lead to motor, behavioral and cognitive deficits. A common acute treatment for perinatal hypoxia is oxygen resuscitation (hyperoximia), a controversial treatment. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), was performed in a P7 rat model of perinatal hypoxia to determine the effect of hyperoximia. These studies were performed on two groups of animals: 1) animals which were subjected to ischemia followed by hypoxia (HI), and 2) HI followed by hyperoximic treatment (HHI). Lesion volumes on high resolution MRI and DTI derived measures, fractional anisotropy (FA), mean diffusivity (MD), and axial and radial diffusivities (lambda(l) and lambda(t), respectively) were measured in vivo one day, one week, and three weeks after injury. Most significant differences in the MRI and DTI measures were found at three weeks after injury. Specifically, three weeks after HHI injury resulted in significantly larger hyperintense lesion volumes (95.26 +/- 50.42 mm(3)) compared to HI (22.25 +/- 17.62 mm(3)). The radial diffusivity lambda(t) of the genu of corpus callosum was significantly larger in HHI (681 +/- 330 x 10(-6) mm(2)/sec) than in HI (486 +/- 96 x 10(-6) mm(2)/sec). Over all, most significant differences in all the DTI metrics (FA, MD, lambda(t), lambda(l)) at all time points were found in the corpus callosum. Our results suggest that treatment of perinatal hypoxia with normobaric oxygen does not ameliorate, but exacerbates damage.

Evaluation of sedative effects of single and repeated doses of 50 mg and 150 mg tolperisone hydrochloride. Results of a prospective, randomized, double-blind, placebo-controlled trial.

Sedative effects of single and repeated doses of 50 mg and 150 mg tolperisone hydrochloride (Mydocalm), a centrally active muscle-relaxing agent, were evaluated in a placebo-controlled double-blind clinical trial. A total of 72 healthy young adults balanced by sex were randomized to receive 50 mg or 150 mg tolperisone hydrochloride or placebo t.i.d. for a period of 8 days. Control examinations were performed in the mornings of days 1 and 8 before intake of the morning dose and at 1.5, 4 and 6 hours postdose. The psychomotoric test battery used in this trial revealed no sedative effects of tolperisone hydrochloride in the given doses at any control examination. Subjective mood ratings quantified by the Welzel Colored Scales were not impaired either. The lack of differences in sedative potentials of tolperisone hydrochloride and placebo was confirmed by tests on differences and by tests on equivalence using 95% CI. The present study substantiates clinical experience and previous clinical trials demonstrating that tolperisone hydrochloride, though being a centrally active muscle relaxant, does not cause any sedation and does not impair reaction times.

Actualizing empowerment: a case in point.

A three-hour "think tank" session and continual revision have led to a creative reorganization of admissions procedures that successfully addressed a growing problem of "boarders." This has resulted in providing more comprehensive patient care, increased satisfaction for both family and caregivers and significant cost reductions.