Human MME(Neprilysin) ELISA Kit

Rationale: Lower NP (natriuretic peptide) levels may contribute to the development of cardiometabolic diseases. Blacks have lower NP levels than middle-aged and older white adults. A high-carbohydrate challenge causes an upregulation of a negative ANP regulator microRNA-425 (miR-425), which reduces ANP (atrial-NP) levels in whites. Objectives: We designed a prospective trial to study racial differences in (1) NP levels among young adults, (2) NP response to a high-carbohydrate challenge, and (3) explore underlying mechanisms for race-based differences. Methods and Results: Healthy self-identified blacks and whites received 3 days of study diet followed by a high-carbohydrate challenge. Gene expression from whole blood RNA was assessed in the trial participants. Additionally, atrial and ventricular tissue samples from the Myocardial Applied Genomics Network repository were examined for NP system gene expression. Among 72 healthy participants, we found that B-type-NP, NT-proBNP (N-terminal-pro-B-type NP), and MRproANP (midregional-pro-ANP) levels were 30%, 47%, and 18% lower in blacks compared with whites (P <= 0.01), respectively. The decrease in MRproANP levels in response to a high-carbohydrate challenge differed by race (blacks 23% [95% CI, 19%-27%] versus whites 34% [95% CI, 31%-38]; P-interaction<0.001), with no change in NT-proBNP levels. We did not observe any racial differences in expression of genes encoding for NPs (NPPA/NPPB) or NP signaling (NPR1) in atrial and ventricular tissues. NP processing (corin), clearance (NPR3), and regulation (miR-425) genes were approximate to 3.5-, approximate to 2.5-, and approximate to 2-fold higher in blacks than whites in atrial tissues, respectively. We also found a 2-and 8-fold higher whole blood RNA expression of gene encoding for Neprilysin (MME) and miR-425 among blacks than whites. Conclusions: Racial differences in NP levels are evident in young, healthy adults suggesting a state of NP deficiency exists in blacks. Impaired NP processing and clearance may contribute to race-based NP differences. Higher miR-425 levels in blacks motivate additional studies to understand differences in NP downregulation after physiological perturbations.

Introduction: Substance use and abuse may have the significant, but unanticipated, consequence of lessening the efficacy of opioid analgesics for acute pain management. We hypothesized that pre-injury substance use increases opioid analgesic consumption following traumatic injury. Methods: This retrospective multi-institutional pilot study included admitted patients to four level 1 trauma centers with vehicular trauma over four months (n = 176). We examined the effect of positive urine drug screen (UDS; 7-drug panel, examined individually and combined, yes/no) and positive blood alcohol content (BAC, >= 80 mg/dL) on pain management with opioid analgesics over the hospital stay. Average daily opioid consumption was examined using a repeated measures mixed model, by positive UDS and BAC findings, adjusting forage, injury severity score, andnon-opioid analgesia. Opioid analgesics were converted to milligram morphine equivalents (MME) and analyzed with a square-root transformation due to non-normality. Results: A positive drug or alcohol test was reported in 33.5% (59/176), including 12.5% (n = 22) with positive UDS and 26% (n = 45) with a positive BAC. There were no differences in gender, injury severity scores, Glasgow coma scores, or cause of vehicular trauma between substance users and non-users; only age was significantly different. Patients with a positive UDS consumed significantly more opioids compared to those with a negative UDS (34.7 MME vs. 24.7 MME, p = 0.04), after adjustment. Individually, detection of opiates, THC, cocaine, and amphetamines were associated with increased opioid consumption compared to their UDS negative counterparts; on the other hand, benzodiazepines and alcohol intoxication were associated with reduced opioid consumption during the course of hospitalization. However, none of the individual UDS results reached statistical significance. The largest effect of all the individual drugs was with opiates, which was associated with a borderline significant increase in opioid analgesic consumption (p = 0.06). Conclusions: Our preliminary data suggest drug use may significantly alter acute pain management following traumatic injury, corresponding to 40% increase in opioid analgesia for substance users than non-users. These results may have broad reaching implications because of the high prevalence of substance use in the trauma population. (C) 2019 Elsevier Ltd. All rights reserved.