Calpain I inhibition prevents atrial structural remodeling in a canine model with atrial fibrillation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Atrial fibrillation (AF) is accompanied by atrial structural remodeling. Calpain activity is induced during AF. To test a causal relationship between calpain activation and atrial structural changes, N-acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor, was utilized in a canine AF model.</p><p><b>METHODS</b>Fifteen dogs were randomly divided into 3 groups: sham-operated group, control group and calpain inhibitor group; each with 5 dogs. Sustained AF was induced by rapid right atrium pacing at 600 beats per minute for 3 weeks. ALLM was administered at a dosage of 1.0 mg x kg(-1) x d(-1) in the calpain inhibitor group. Three weeks later, the proteolysis, protein expression of TnT and myosin, calpain I localization and expression and structural changes were examined in left atrial free walls, right atrial free walls and the interatrial septum respectively. Atrial size and contractile function were also measured by echocardiography.</p><p><b>RESULTS</b>Long-term rapid atrial pacing induced marked structural changes such as enlarged atrial volume, myolysis, degradation of TnT and myosin, accumulation of glycogen and changes in mitochondrial shape and size, which were paralleled by an increase in calpain activity. The positive correlation between calpain activity and the degree of myolysis (r(s) = 0.90 961, P < 0.0001) was demonstrated. In addition to structural abnormalities, pacing-induced atrial contractile dysfunction was observed in this study. The pacing-induced atrial structural alterations and loss of contractility were partially prevented by the calpain inhibitor ALLM.</p><p><b>CONCLUSIONS</b>Activation of calpain represents key features in the progression towards overt structural remodeling. Calpain inhibitor, ALLM, suppressed the increased calpain activity and reversed structural remodeling caused by sustained atrial fibrillation in the present model. Calpain inhibition may therefore provide a possibility for therapeutic intervention in AF.</p>

Effects of 40H-tamoxifen on the proliferation and apoptosis of prostate stromal cells / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of 4OH-Tamoxifen (OHT) on proliferation and apoptosis of primary cultured prostate stromal cells.</p><p><b>METHODS</b>Primarily cultured prostate stromal cells in vitro were treated with various concentrations (10(-8) mol/L - 10(-5) mol/L) of estradiol (E2), diethylstilbestrol (DES), OHT and the mixture of E2 (10(-8) mol/L - 10(-6) mol/L) with OHT (10(-7) mol/L) and then MTT and TUNEL were used to detect their proliferation and apoptosis respectively.</p><p><b>RESULTS</b>There was a significant difference (P < 0.05) between OHT and estrogens in the effects on the apoptosis and proliferation of the primarily cultured prostate stromal cells. OHT suppressed proliferation of the prostate stromal cells at the concentrations from 10(-7) mol/L to 10(-5) mol/L (P < 0.05), and this effect was concentration related (r = -0.383, P = 0.005); OHT (10(-7) mol/L) suppressed the proliferation stimulation effect of E2 at the concentrations from 10(-8) mol/L to 10(-6) mol/L (P < 0.05). OHT induced apoptosis at the concentrations from 10(-8) mol/L to 10(-5) mol/L (P < 0.05), and this effect was concentration related (r = 0.349, P = 0.012). The apoptosis induced by OHT could not be reversed by E2 at the concentrations from 10(-8) mol/L to 10(-5) mol/L (P > 0.05).</p><p><b>CONCLUSION</b>OHT can obviously suppressed the proliferation and promote the apoptosis of primarily cultured prostate stromal cells, which might not be totally attributed to the competitive inhibition of the estrogen receptor.</p>