Acne Scars

Pacing Clin Electrophysiol. 2009 Jul; 32(7): 851-861Pouliopoulos J, Thiagalingam A, Eipper VE, Campbell C, Ross DL, Kovoor PBackground: Myocardial refractoriness and repolarization is an important electrophysiological property that, when altered, increases the risk of arrhythmogenesis. These electrophysiological changes associated with chronic myocardial infarction (MI) have not been studied in detail. We assessed the influence of left ventricular (LV) scarring on local refractoriness, repolarization, and electrogram characteristics. Methods: MI was induced in five sheep by percutaneous left anterior descending artery occlusion for 3 hours. Mapping was performed at 19 +/- 6 weeks post-MI. A total of 20 quadripolar transmural needles were deployed at thoracotomy in the LV within and surrounding scar. Bipolar pacing was performed from each needle to assess the effective refractory period (ERP) of the subendocardium and subepicardium. The activation (AT) and repolarization (RT) times, and modified activation recovery interval (ARI(m)) were determined from endocardial unipolar electrograms recorded in sinus rhythm simultaneously from all needles. Scarring was quantified histologically and compared with electrophysiological characteristics. Results: Increased scarring corresponded with increased ERP (P < 0.01), decreased subendocardial electrogram amplitude (P < 0.001), and slope (P < 0.001). ERP did not differ between endocardium and epicardium (P > 0.05). The ARI(m) and RT were prolonged during early myocardial activation (P < 0.001). After adjusting for AT, the RT and ARI(m) were prolonged in areas of scarring (P < 0.001). After adjusting for electrogram amplitude, the ARI(m) was prolonged in dense scar (P < 0.05). Conclusions: We confirmed histologically that scarring contributes to prolongation of repolarization, increased refractoriness, and reductions in conduction and voltage post-MI. Prolongation of repolarization may be further augmented when local activation is earliest or electrogram voltage is decreased within scar.

Endocrinology. 2009 Jul 2; Lim P, Robson M, Spaliviero J, McTavish KJ, Jimenez M, Zajac JD, Handelsman DJ, Allan CMWe examined the biological importance of Sertoli cell androgen receptor (AR) genomic interaction, using a Cre-loxP approach to selectively disrupt the AR DNA-binding domain (AR-DBD). Sertoli cell (SC)-specific transgenic Abpa or AMH promoters targeted Cre-mediated inframe excision of mouse Ar exon-3, encoding the AR-DBD second zinc-finger (ZF2), generating SC-specific mutant AR(DeltaZF2) lines designated Abp.SCAR(DeltaZF2) and AMH.SCAR(DeltaZF2) respectively. Both SCAR(DeltaZF2) lines produced infertile males exhibiting spermatogenic arrest, despite normal SC numbers and immunolocalized SC nuclear AR. Adult homozygous TgCre((+/+)) SCAR(DeltaZF2) or double TgCre((+/-)) Abp/AMH.SCAR(DeltaZF2) males displayed equivalent small testes 30% of normal size, representing maximal Cre-loxP-disruption of Sertoli AR function. Hemizygous TgCre((+/-)) vs. homozygous TgCre((+/+)) Abp.SCAR(DeltaZF2) testes were larger (47% normal size) with more post-meiotic development, indicating dose-dependent Cre-mediated disruption of SC-specific AR-DBD activity. SCAR(DeltaZF2) males exhibited adult Leydig cell hypertrophy but normal serum testosterone levels. Sertoli cell-specific Rhox5 and Spinlw1 transcription, regulated by divergent or classical androgen-response elements respectively, were both decreased in postnatal SCAR(DeltaZF2) vs. control testes, demonstrating SC-specific AR-DBD function as early as postnatal day 5. However, Rhox5 expression declined dose-dependently, whereas Spinlw1 expression increased, in adult TgCre((+/-)) and TgCre((+/+)) SCAR(DeltaZF2) testes, revealing differential temporal control for distinct AR-regulated transcripts. Androgen-repressed Ngfr was not upregulated in SCAR(DeltaZF2) testes, suggesting maintenance of a non-classical mechanism independent of AR-DBD. Thus, our unique SCAR(DeltaZF2) paradigm provided dose-dependent Cre-mediated-disruption of testicular development and gene expression revealing that the AR-DBD is essential for SC function and post-meiotic spermatogenesis. Non-genomic or AR-DBD-independent pathways appear secondary, or play no major independent role in SC function.