Tibolone, a hormone replacement drug, protects postmenopausal women against osteoporosis and climacteric symptoms without inducing adverse effects on the endometrium and breast. Compared with other estrogens, little is known about the cardiovascular effects of tibolone. Because abnormal growth of smooth muscle cells (SMCs) is a prerequisite for coronary artery disease, here we investigated the effects of tibolone on SMC growth. We examined the effects of tibolone and its metabolites on human arterial SMC growth (DNA synthesis, cellular proliferation, cell migration, collagen synthesis) and MAPK expression. Fetal calf serum-induced SMC growth, phosphorylated MAPK expression, and platelet-derived growth factor-induced SMC-migration were concentration-dependently inhibited by tibolone and its endogenous estrogenic and progestogenic/androgenic metabolites in the following order of potency: Delta 4-tibolone>3 beta-OH-tibolone congruent with 3 alpha-OH-tibolone. The antimitogenic effects of tibolone were partially blocked by ER antagonist (ICI182780), progesterone receptor antagonist (RU486) but not by the androgen receptor antagonist (flutamide); moreover, RU486 was more potent than ICI182780. The antimitogenic effects of tibolone were completely blocked by RU486 plus ICI182780. In addition, the inhibitory effects of equimolar concentrations of the three tibolone metabolites summed up to the inhibitory effects of tibolone. In conclusion, tibolone inhibits SMC growth and MAPK phosphorylation via both its estrogenic and progestogenic metabolites, and these inhibitory effects involve both progesterone and ERs. Hence, tibolone may induce antivasoocclusive actions and protect women against coronary artery disease.
People with amputation may perceive phantom limb sensations or pain in the amputated body part when ipsilateral body-regions are stimulated. These body-regions are called receptive fields. This study assessed whether receptive fields change in size and position over the course of one month in people with trans-tibial amputation and whether electrical stimulation of these fields in synchrony with walking affects phantom sensations and variables of gait. Thirty-one subjects participated in this study. Receptive fields were mapped seven times over a one month period. Thereafter, the effect of electrical stimulation in synchrony with walking was compared to placebo stimulation in an acute setting with a randomized, single-blind gait analysis in 18 participants. Results showed that receptive field size and position presented an adequate degree of consistency (difference in point of first response position of 4.9 ± 4.8 cm and overlap of total receptive field area of 54.3 ± 35.0 %) for future use of electrical stimulation. Gait parameters for everyday activities (speed, gait width, % stance and swing phase) as well as perception of phantom pain were not altered to a clinically relevant degree by electrical stimulation and no negative effects were reported. In conclusion: Location and size of receptive fields are consistent enough for daily electrical stimulation without laborious daily assessment. If applied acutely, no significant effect on gait or pain could be detected. However, results are promising enough to test chronic application of electrical stimulation during gait in a long-term setting.
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