Cyclic GMP-selective phosphodiesterase type 5 (PDE5) has been traditionally thought to play little role in cardiac myocytes, yet recent studies using selective inhibitors such as sildenafil suggest it can potently modulate acute and chronic cardiac stress responses. To date, evidence for myocyte PDE5 expression and regulation has relied on small-molecule inhibitors and anti-sera, leaving open concerns regarding non-specific immune-reactivity, and off-target drug effects. To directly address both issues, we engineered a robust PDE5-gene silencing shRNA (inserted into miRNA-155 cassette) and DsRed-PDE5 fusion protein, both coupled to a CMV promoter and incorporated into adenoviral vectors. PDE5 mRNA and protein knockdown eliminated anti-sera positivity on immunoblots and fluorescent immuno-histochemistry in neonatal and adult cardiomyocytes, and suppressed PDE5 enzyme activity. Stimulation of myocyte hypertrophy by phenylephrine was blunted by PDE5 gene silencing in a protein kinase G dependent manner, and this effect was similar to that from sildenafil with no additive response by both combined. DsRed-PDE5 fusion protein expression showed normal z-band localization in adult myocytes but was diffuse in eNOS -/-myocytes; echoing reported findings with anti-sera. PDE5 over-expression increased enzyme activity and amplified natriuretic peptide gene expression from phenylephrine stimulation. These data confirm PDE5 expression, activity, and targeted inhibition by sildenafil in cardiomyocytes, as well as the role of this PDE in cardiomyocyte hypertrophy modulation.

Splenic rupture in the absence of major trauma is a rare occurrence, which may occur by idiopathic means or a specific pathologic process. One such condition, amyloidosis, involves the extracellular deposition of abnormally folded ‘amyloid’ protein, which can affect the spleen. Protein infiltration in the organ may cause splenomegaly and potentially capsular rupture in advanced cases. We describe a 68-year-old male with a history of end-stage renal disease status-post living donor renal transplant on chronic immunosuppression and Coumadin that presented with abdominal pain, weakness and hypotension. The patient was found to have hemoperitoneum secondary to splenic rupture and was emergently taken for exploratory laparotomy and splenectomy. The pathology of the spleen revealed AL amyloidosis. He was subsequently found to have advanced plasma cell neoplasm by bone marrow biopsy with numerous osseous lytic lesions, consistent with a monomorphic post-transplant lymphoproliferative disorder.

Twenty four specimens of holothuroids recently received from the South African Environmental and Observation Network (SAEON), collected from off the south and west coasts of South Africa, are herein recorded and/or described. The specimens comprise eight nominal and one indeterminate species and represent both shallow-water and deep-sea forms, distributed from Plettenberg Bay to just north of Lambert's Bay in the Western Cape Province. There are no new species but two new records for the South African region and extensions of horizontal and bathymetric distributions of the other species. Additions to the South African fauna are Zygothuria lactea (Théel, 1886) and Synallactes cf. challengeri (Théel, 1886). The paper also contains the first definite record of Thyone venusta Selenka, 1868, originally described from the Red Sea. Distribution ranges of the following species have been altered Synallactes viridilimus Cherbonnier, 1952; S. mollis Cherbonnier, 1952 and Psuedostichopus langeae Thandar, 2009.