N-Octanoyl Dopamine, a Non-Hemodyanic Dopamine Derivative, for Cell Protection during Hypothermic Organ Preservation

BACKGROUND: Although donor dopamine treatment reduces the requirement for post transplantation dialysis in renal transplant recipients, implementation of dopamine in donor management is hampered by its hemodynamic side-effects. Therefore novel dopamine derivatives lacking any hemodynamic actions and yet are more efficacious in protecting tissue from cold preservation injury are warranted. We hypothesized that variation of the molecular structure would yield more efficacious compounds avoid of any hemodynamic effects. METHODOLOGY/PRINCIPAL FINDINGS: To this end, we assessed protection against cold preservation injury in HUVEC by the attenuation of lactate dehydrogenase (LDH) release. Modification of dopamine by an alkanoyl group increased cellular uptake and significantly improved efficacy of protection. Further variation revealed that only compounds bearing two hydroxy groups in ortho or para position at the benzene nucleus, i.e. strong reductants, were protective. However, other reducing agents like N-acetyl cysteine and ascorbate, or NADPH oxidase inhibition did not prevent cellular injury following cold storage. Unlike dopamine, a prototypic novel compound caused no hemodynamic side-effects. CONCLUSIONS/SIGNIFICANCE: In conclusion, we demonstrate that protection against cold preservation injury by catecholamines is exclusively governed by strong reducing capacity and sufficient lipophilicity. The novel dopamine derivatives might be of clinical relevance in donor pre-conditioning as they are completely devoid of hemodynamic action, their increased cellular uptake would reduce time of treatment and therefore also may have a potential use for non-heart beating donors

Role of deficits in pathogen recognition receptors in infection susceptibility

This work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014 to A.C. and SFRH/BPD/96176/2013 to C.C.

Supraspinatus tear—a mechanical outlet impingement lesion?

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>The etiology of degenerative supraspinatus tendon (SSP) tear is still subject to discussion.</jats:p> </jats:sec><jats:sec> <jats:title>Objectives</jats:title> <jats:p>Our objective was to correlate clinical, radiological, and intraoperative signs of mechanical outlet impingement in patients with degenerative SSP tears.</jats:p> </jats:sec><jats:sec> <jats:title>Materials and methods</jats:title> <jats:p>This prospective study included 100 patients with degenerative SSP tears that required surgery. Preoperatively, clinical impingement signs and radiological parameters (critical shoulder angle [CSA], acromion type according to Bigliani, acromion index [AI]) were recorded. Intraoperatively, the extent of the rupture and grinding marks on the bottom of the acromion were assessed.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Of the 100 patients, 59 had clinical impingement signs preoperatively; 90 patients had at least one positive radiological sign (CSA > 35°, AI > 0.67, acromion type II or III). In 23 patients a partial tear, in 55 patients a full thickness tear, and in 22 patients an additional infraspinatus tendon tear were found. In 10 cases no grinding marks at the bottom of the acromion during arthroscopy were found. In 75 cases moderate grinding marks and in 15 cases severe marks with bare bone at the bottom of the acromion were found. There was no statistically significant correlation between preoperative impingement signs and arthroscopic grinding marks (<jats:italic>p</jats:italic> = 0.83) or between clinical signs and radiological parameters (<jats:italic>p</jats:italic> = 0.44). There was no significant correlation between extent of the rupture, extent of grinding marks or radiological impingement parameters (<jats:italic>p</jats:italic> = 0.16; <jats:italic>p</jats:italic> = 0.26).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>We could not verify a correlation between clinical and radiological impingement sign and arthroscopic impingement parameters. Based on our study, degenerative SSP tear cannot be characterized as the result of a mechanical outlet impingement.</jats:p> </jats:sec&gt