Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

5′-CMP and 5′-UMP alleviate dexamethasone-induced muscular atrophy in C2C12 myotubes

Atrogin-1 and muscle RING finger 1 (MuRF1) are ubiquitin ligases specifically expressed during skeletal muscle atrophy and mediate muscle protein degradation. In contrast, PGC-1α (peroxisome proliferator-activated receptor γ coactivator 1α), which is a master regulator of mitochondrial biosynthesis, protects skeletal muscle from atrophy. Pyrimidine nucleoside 5′-monophosphates, such as cytidine 5′-monophosphate (5′-CMP) and uridine 5′-monophosphate (5′-UMP), induce PGC-1α expression and promote myotube formation in mouse C2C12 cells. In this study, we determined the effect of 5′-CMP and 5′-UMP on muscular atrophy in C2C12 myotube cells. 5′-UMP decreased Atrogin-1 and MuRF1 mRNA levels that were upregulated by dexamethasone treatment. 5′-CMP and 5′-UMP ameliorated dexamethasone-mediated atrophy in C2C12 myotubes. Furthermore, the combination of 5′-CMP and 5′-UMP further alleviated dexamethasone-mediated atrophy. In addition, cytidine and uridine, the precursors of 5′-CMP and 5′-UMP, markedly ameliorated dexamethasone-mediated atrophy. Considering nucleotide metabolism and absorption, the active metabolites underlying the observed effects of 5′-CMP and 5′-UMP appear to be cytidine and uridine. Our results indicate that 5′-CMP alleviates muscle atrophy by activating PGC-1α and differentiation, and 5′-UMP alleviates muscle atrophy by suppressing the activation of the myolytic system, whereas the combined use of both enhances the muscle atrophy inhibitory effect. 5′-CMP and 5′-UMP may be an effective and safe treatment for muscular atrophy

Pannus-Related Mechanical Valve Dysfunction Leading to Hemodynamic Shock

Mechanical prosthetic valve dysfunction caused by pannus formation is rare. Pannus restricts movement of prosthetic valve leaflets, resulting in severe aortic regurgitation. We describe the case of a 77-year-old woman who presented to the emergency room with increasing dyspnea, ischemia, and shock secondary to mechanical aortic valve dysfunction. Transesophageal echocardiography showed a blockade of the leaflets of the mechanical aortic valve, with severe aortic regurgitation. She underwent emergent cardiac surgery for aortic valve replacement. Pannus formation should be considered as a potential cause of acute severe aortic regurgitation in a patient with a small-sized mechanical aortic prosthesis in the supra-annular position. On a pathological exam, extensive pannus was found on the ventricular side of the prosthetic valve, extending from the ring into the central orifice. [Arch Clin Exp Surg 2012; 1(1.000): 50-53

The effects of health education on health science teachers’ intention to recommend adolescent HPV vaccine for female students in Japan

The Japanese government suspended proactive recommendation of human papillomavirus (HPV) vaccination due to several reports of adverse events related to it in 2013. After that, the immunization rate of HPV vaccine quickly declined in Japan. Health science teachers (HSTs) are qualified and licensed teachers in charge of health care and health education for students in Japanese schools. HSTs have not recommended HPV vaccination to female students, since active governmental recommendation for HPV vaccination was halted for 5 y. We conducted a primary survey targeting HSTs (N = 39) and university students taking the HST training course (N = 123). In each group, awareness regarding HPV vaccine and disease burden was evaluated and factors related to and barriers to HPV vaccine recommendation were identified. The primary survey found that many HSTs and university students recognized their insufficient knowledge regarding the HPV vaccine. Based on the primary survey’s results, infectious disease specialists, collaborating with Japanese HSTs, developed educational slide sets on HPV vaccine. A secondary survey was conducted before and after the lecture with HSTs (N = 162), where we evaluated their intelligibility and intention to recommend HPV vaccination for female students. In the post-lecture, secondary survey, the number of HSTs who recommended the HPV vaccine to their students had statistically increased from 76 before the lecture, to 103 (p < .05). An educational lecture using appropriate materials improved HSTs’ vaccine confidence and intention to recommend the HPV vaccine to their students, verifying the study’s hypothesis