RESUMO
We have previously demonstrated that the Na-K-ATPase signaling-mediated oxidant amplification loop contributes to experimental uremic cardiomyopathy and anemia induced by 5/6th partial nephrectomy (PNx). This process can be ameliorated by systemic administration of the peptide pNaKtide, which was designed to block this oxidant amplification loop. The present study demonstrated that the PNx-induced anemia is characterized by marked decreases in red blood cell (RBC) survival as assessed by biotinylated RBC clearance and eryptosis as assessed by annexin V binding. No significant change in iron homeostasis was observed. Examination of plasma samples demonstrated that PNx induced significant increases in systemic oxidant stress as assessed by protein carbonylation, plasma erythropoietin concentration, and blood urea nitrogen. Systemic administration of pNaKtide, but not NaKtide (pNaKtide without the TAT leader sequence) and a scramble "pNaKtide" (sc-pNaKtide), led to the normalization of hematocrit, RBC survival, and plasma protein carbonylation. Administration of the three peptides had no significant effect on PNx-induced increases in plasma erythropoietin and blood urea nitrogen without notable changes in iron metabolism. These data indicate that blockage of the Na-K-ATPase signaling-mediated oxidant amplification loop ameliorates the anemia of experimental renal failure by increasing RBC survival.NEW & NOTEWORTHY The anemia of CKD is multifactorial, and the current treatment based primarily on stimulating bone marrow production of RBCs with erythropoietin or erythropoietin analogs is unsatisfactory. In a murine model of CKD that is complicated by anemia, blockade of Na-K-ATPase signaling with a specific peptide (pNaKtide) ameliorated the anemia primarily by increasing RBC survival. Should these results be confirmed in patients, this strategy may allow for novel and potentially additive strategies to treat the anemia of CKD.
Assuntos
Anemia , Eritropoetina , Insuficiência Renal Crônica , Anemia/tratamento farmacológico , Anemia/etiologia , Animais , Eritrócitos/metabolismo , Eritropoetina/metabolismo , Eritropoetina/farmacologia , Feminino , Meia-Vida , Humanos , Ferro/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nefrectomia , Oxidantes , Peptídeos/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
The development of the Prescription Drug Monitoring Program (PDMP) led to an innovation in the healthcare organization system (HCOs). The PDMP system has been utilized in different states at various organizational levels in an effort to achieve improved health outcomes, reduce the number of prescription drug overdoses, and lighten the economic burden that follows. However, during the implementation of PDMP, there were several barriers and limitations that were discovered. Those barriers impeded the process of utilization of PDMP, such as the complex user interface and lack of training for healthcare providers. The purpose of this paper was to examine the advances and limitations in the utilization and implementation of PDMP in the US healthcare industry and develop strategies for effective use of PDMP in West Virginia. The qualitative part of this paper was a literature review. The paper referred to several peer-reviewed studies and research articles from several reliable resources, which were reached by databases or Google Scholar. A total of 44 articles were reviewed for this study. The implementation of the PDMP was influenced by benefits and barriers. This article reviewed several studies in general that demonstrated positive outcomes from the implementation of PDMP, including a reduced number of prescription drug overdoses, coordinated care for patients, and improved health outcomes. However, the barriers and limitations were not neglected, which mainly include integration of PDMP into the electronic health record (EHR) system, lack of training for the providers, and lack of basic standards for the use of PDMP. Although the new health reforms encouraged the adaption of PDMP among providers, data reporting and data interpretation still remain major concerns for assessing the health outcomes of PDMP implementation.