دورية أكاديمية
Identification and local delivery of vasodilators for the reduction of ureteral contractions.
العنوان: | Identification and local delivery of vasodilators for the reduction of ureteral contractions. |
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المؤلفون: | Lee CX; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Cheah JH; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Soule CK; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Ding H; The Barbara K. Ostrom (1978) Bioinformatics and Computing Facility in the Swanson Biotechnology Center, Massachusetts Institute of Technology, Cambridge, MA, USA., Whittaker CA; The Barbara K. Ostrom (1978) Bioinformatics and Computing Facility in the Swanson Biotechnology Center, Massachusetts Institute of Technology, Cambridge, MA, USA., Karhohs K; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA., Burds AA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Subramanyam KS; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Carpenter AE; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA., Eisner BH; Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Cima MJ; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA. mjcima@mit.edu.; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. mjcima@mit.edu.; Department of Material Science Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. mjcima@mit.edu. |
المصدر: | Nature biomedical engineering [Nat Biomed Eng] 2020 Jan; Vol. 4 (1), pp. 28-39. Date of Electronic Publication: 2019 Dec 02. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Springer Nature Country of Publication: England NLM ID: 101696896 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2157-846X (Electronic) Linking ISSN: 2157846X NLM ISO Abbreviation: Nat Biomed Eng Subsets: MEDLINE |
أسماء مطبوعة: | Publication: London : Springer Nature Original Publication: [London] : Macmillan Publishers Limited, [2016]- |
مواضيع طبية MeSH: | Muscle Contraction/*drug effects , Myocytes, Smooth Muscle/*drug effects , Ureter/*drug effects , Vasodilator Agents/*administration & dosage, Animals ; Cells, Cultured ; Drug Evaluation, Preclinical ; Humans ; Nifedipine/administration & dosage ; Protein Kinase Inhibitors/administration & dosage ; Sus scrofa |
مستخلص: | Kidney stones and ureteral stents can cause ureteral colic and pain. By decreasing contractions in the ureter, clinically prescribed oral vasodilators may improve spontaneous stone passage rates and reduce the pain caused by ureteral stenting. We hypothesized that ureteral relaxation can be improved via the local administration of vasodilators and other smooth muscle relaxants. Here, by examining 18 candidate small molecules in an automated screening assay to determine the extent of ureteral relaxation, we show that the calcium channel blocker nifedipine and the Rho-kinase inhibitor ROCKi significantly relax human ureteral smooth muscle cells. We also show, by using ex vivo porcine ureter segments and sedated pigs that, with respect to the administration of a placebo, the local delivery of a clinically deployable formulation of the two drugs reduced ureteral contraction amplitude and frequency by 90% and 50%, respectively. Finally, we show that standard oral vasodilator therapy reduced contraction amplitude by only 50% and had a minimal effect on contraction frequency. Locally delivered ureteral relaxants therefore may improve ureter-related conditions. |
التعليقات: | Comment in: J Urol. 2020 Dec;204(6):1385. (PMID: 32955979) |
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معلومات مُعتمدة: | P30 CA014051 United States CA NCI NIH HHS; R35 GM122547 United States GM NIGMS NIH HHS |
المشرفين على المادة: | 0 (Protein Kinase Inhibitors) 0 (Vasodilator Agents) I9ZF7L6G2L (Nifedipine) |
تواريخ الأحداث: | Date Created: 20191204 Date Completed: 20200505 Latest Revision: 20210616 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC7962136 |
DOI: | 10.1038/s41551-019-0482-4 |
PMID: | 31792422 |
قاعدة البيانات: | MEDLINE |
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