Beta-Pro7Ang III is a novel highly selective angiotensn AT2 receptor agonist, which acts as a vasodepressor agent via the AT2 receptor in conscious SHR.
We have previously shown that individual b-amino acid substitution to Ang II reduced AT1R- but not AT2R-binding, and that the heptapeptide Ang III exhibited greater AT2R: AT1R selectivity than Ang II. Therefore, we hypothesised that β-amino acid substituted Ang III peptide analogues would yield highly selective AT2R ligands, which we have tested in binding and functional vascular assays. In competition binding experiments using either AT1R- or AT2R- transfected HEK-293 cells, novel β-substituted Ang III analogues lacked appreciable AT1R affinity while most compounds could fully displace [125I]-Sar1Ile8Ang II from AT2R. The rank order of affinity at AT2R was CGP42112> Ang III> b-Pro7-Ang III = Ang II> b-Tyr4-Ang III ≥ PD123319>> b-Phe8-Ang III>> b-Arg2-Ang III = b-val3-Ang III>> b-Ile5-Ang III. The novel analogue b-Pro7-Ang III was the most selectiveAT2R ligand tested, which was> 20,000-fold more selective for AT2R than AT1R. IC50 values at AT2R from binding studies correlated with maximum vasorelaxation in mouse aortic rings. Given that b-Pro7-Ang III was an AT2R agonist, we compared b-Pro7-Ang III and native Ang III for their ability to reduce blood pressure in separate groups of conscious spontaneously hypertensive rats. While Ang III alone increased mean arterial pressure (MAP), b-Pro7-Ang III had no effect. During low-level AT1R blockade, both Ang III and b-Pro7-Ang III, but not Ang II, lowered MAP (by ~30 mmHg) at equimolar infu...
Authors: Stange EF, Schroeder BO Abstract Introduction: Inflammatory bowel diseases (IBD) are on the rise worldwide. This review covers the current concepts of the etiology of Crohn´s disease and ulcerative colitis by focusing on an unbalanced interaction between the intestinal microbiota and the mucosal barrier. Understanding these issues is of paramount importance for the development of targeted therapies aiming at the disease cause. Area covered: Gut microbiota alterations and a dysfunctional intestinal mucosa are associated with IBD. Here we focus on specific defense structures of the mucosal barrier, nam...
ConclusionsOromotor exercises are more effective than incentive spirometry training in improving both pulmonary and oromotor functions in children with Down's syndrome.
Publication date: Available online 11 October 2019Source: Journal of Taibah University Medical SciencesAuthor(s): Beuy Joob, Viroj Wiwanitkit
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Publication date: Available online 11 October 2019Source: The SurgeonAuthor(s): Gregory L. Falk
ConclusionsPatients receiving perioperative gabapentin, acetaminophen, and NSAIDs under an ERAS protocol required significantly fewer narcotics and shorter length of stay. This protocol may merit consideration for use at other centers.
ConclusionsMore than half (51%) of women who underwent genetic counseling and received an uninformative negative genetic test result had a significantly elevated risk for the development of breast cancer. It is, therefore, imperative that women do not conclude that a negative genetic test result represents a lack of risk.
Publication date: Available online 11 October 2019Source: The American Journal of SurgeryAuthor(s): Dhruv J. Patel, Waseem Lutfi, Patrick Sweigert, Emanuel Eguia, Gerard Abood, Lawrence Knab, Paul C. Kuo, Marshall S. BakerAbstractBackgroundPrior studies of adjuvant systemic therapy in pancreatic acinar cell carcinoma have been underpowered.MethodsWe queried the National Cancer Data Base to identify patients presenting with resectable (clinical stage I and II) acinar cell carcinoma between 2004 and 2015. Multivariable Cox Regression was used to evaluate the association between overall survival and systemic therapy.Results29...
ConclusionOur pilot curriculum addresses a gap in resident education about surgical cost. Residents generally regard equipment standardization as either improving or not changing hospital metrics.