Both topical nitrate treatments (ISMN and GTN) were effective for chronic anal fissures. The reduction of the anal pressure was slightly higher after ISMN treatment (28%) than the treatment with GTN (23%). However, the statistical difference was not significant (p>0.05).

No abstract

Neuroblastoma (NB) is the most common extracranial solid tumor of childhood and is a rapidly growing, highly-vascularized cancer. NBs frequently express angiogenic factors and high tumor angiogenesis has been associated with poor outcomes. Placental growth factor (PlGF) is an angiogenic protein belonging to the vascular endothelial growth factor (VEGF) family and is up-regulated mainly in pathologic conditions. Recently, PlGF was identified as a member of a gene expression signature characterizing highly malignant NB stem cells drawing attention as a potential therapeutic target in NB. In the present study, we sought to investigate the expression of PlGF in NB patients and the effect of PlGF inhibition on high-risk MYCN-non-amplified SK-N-AS NB xenografts. Human SK-N-AS cells, which are poorly differentiated and express PlGF and VEGF-A, were implanted subcutaneously in athymic nude mice. Treatment was done by intratumoral injection of replication-incompetent adenoviruses (Ad) expressing PlGF- or VEGF-specific short hairpin (sh)RNA, or soluble (s)VEGF receptor 2 (VEGFR2). The effect on tumor growth and angiogenesis was analyzed. High PlGF expression levels were observed in human advanced-stage NBs. Down-regulating PlGF significantly reduced NB growth in established NB xenografts by reducing cancer cell proliferation but did not suppress angiogenesis. In contrast, blocking VEGF by administration of Ad(sh)VEGF and Ad(s)VEGFR2 reduced tumor growth associated with decreased tumor vasculature. These findings suggest that PlGF and VEGF-A modulate MYCN-non-amplified NB tumors by different mechanisms and support a role for PlGF in NB biology.

Idiopathic dilated cardiomyopathy (DCM) is characterized by declined left ventricular ejection fraction, systolic and diastolic dysfunction, ventricular wall remodeling and an increased incidence of apoptosis. The early growth response gene Egr‐1 is a transcription factor containing zinc finger DNA‐binding motifs and domains which both activate and repress transcription from target promoters. In a targeted screen of gene expression levels in DCM cardiac tissue, we found that Egr‐1 expression is significantly increased in DCM patients. An associated increase in the expression levels of the pro‐apoptotic SIVA gene was observed and multiple high affinity and GC rich Egr‐1 binding sites in the promoter region were identified in silico. Adenoviral‐mediated Egr‐1 (AdEgr‐1) overexpression directly induced caspase‐dependent apoptosis in mixed cardiac cultures in vitro which was characterized by surface phosphatidylserine expression, development of a sub G0/G1 population in FACS analysis and the emergence of TUNEL positive nuclei. Induction of apoptosis was accompanied by upregulation of SIVA protein expression in vitro. Direct intracardial injection of AdEgr‐1 also induced rat cardiac apoptosis in vivo. These results indicate that sustained Egr‐1 expression induces a pro‐apoptotic transcriptional program in cardiac cells which may play a pivotal role in the development of DCM.