Exposure to human blood inactivates swine ecto-5'-nucleotidase.

Ecto-5'-nucleotidase (E5'N) is an extracellular enzyme forming anti-inflammatory and immunosuppressive adenosine. We evaluated whether confrontation of pig heart and endothelial cells with human blood changes the activity of E5'N. Pig hearts were perfused ex vivo with fresh human blood for 4 h. Pig aortic endothelial cells (PAEC) were incubated in vitro with human plasma for 3 h. Ex vivo perfusion of pig heart with fresh human blood resulted in a decrease in E5'N activity to 62% and 61% of initial in wild-type and transgenic pig hearts, respectively. PAEC activity of E5'N decreased to 71% and 50% of initial after 3 h exposure to heat-inactivated and active complement human plasma, respectively, while it remained constant in controls. Pig heart activity of E5'N decreased following exposure to human blood, which may affect adenosine production and exacerbate hyperacute and vascular rejection

Hearing loss and PRPS1 mutations: Wide spectrum of phenotypes and potential therapy

Item does not contain fulltextOBJECTIVE: The purpose of this review was to evaluate the current literature on phosphoribosylpyrophosphate synthetase 1 (PRPS1)-related diseases and their consequences on hearing function. DESIGN: A literature search of peer-reviewed, published journal articles was conducted in online bibliographic databases. Study sample: Three databases for medical research were included in this review. RESULTS: Mutations in PRPS1 are associated with a spectrum of non-syndromic to syndromic hearing loss. Hearing loss in male patients with PRPS1 mutations is bilateral, moderate to profound, and can be prelingual or postlingual, progressive or non-progressive. Audiogram shapes associated with PRPS1 deafness are usually residual and flat. Female carriers can have unilateral or bilateral hearing impairment. Gain of function mutations in PRPS1 cause a superactivity of the PRS-I protein whereas the loss-of-function mutations result in X-linked nonsyndromic sensorineural deafness type 2 (DFN2), or in syndromic deafness including Arts syndrome and X-linked Charcot-Marie-Tooth disease-5 (CMTX5). CONCLUSIONS: Lower residual activity in PRS-I leads to a more severe clinical manifestation. Clinical and molecular findings suggest that the four PRPS1 disorders discovered to date belong to the same disease spectrum. Dietary supplementation with S-adenosylmethionine (SAM) appeared to alleviate the symptoms of Arts syndrome patients, suggesting that SAM could compensate for PRS-I deficiency