Evidence map›Paper›PMID 29483619›Full record

ArticleScientific reports2018

Normalization of cell associated antiretroviral drug concentrations with a novel RPP30 droplet digital PCR assay.

Shetty Ravi Dyavar, Zhen Ye, Siddappa N Byrareddy, Kimberly K Scarsi, Lee C Winchester, Jonathan A Weinhold, Courtney V Fletcher, Anthony T Podany

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.9field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 32 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Shetty Ravi DyavarAntiviral Pharmacology Laboratory, Department of Pharmacy Practice, College of Pharmacy (COP), University of Nebraska Medical Center (UNMC), Omaha, NE, 68198, USA. shettyravi.dyavar@unmc.edu.
Zhen YeDepartment of Pharmaceutical Sciences, COP, UNMC, Omaha, NE, 68198, USA.
Siddappa N ByrareddyDepartment of Pharmacology and Experimental Neuroscience, College of Medicine, UNMC, Omaha, NE, 68198, USA.
Kimberly K ScarsiAntiviral Pharmacology Laboratory, Department of Pharmacy Practice, College of Pharmacy (COP), University of Nebraska Medical Center (UNMC), Omaha, NE, 68198, USA.
Lee C WinchesterAntiviral Pharmacology Laboratory, Department of Pharmacy Practice, College of Pharmacy (COP), University of Nebraska Medical Center (UNMC), Omaha, NE, 68198, USA.
Jonathan A WeinholdAntiviral Pharmacology Laboratory, Department of Pharmacy Practice, College of Pharmacy (COP), University of Nebraska Medical Center (UNMC), Omaha, NE, 68198, USA.
Courtney V FletcherAntiviral Pharmacology Laboratory, Department of Pharmacy Practice, College of Pharmacy (COP), University of Nebraska Medical Center (UNMC), Omaha, NE, 68198, USA. cfletcher@unmc.edu.
Anthony T PodanyAntiviral Pharmacology Laboratory, Department of Pharmacy Practice, College of Pharmacy (COP), University of Nebraska Medical Center (UNMC), Omaha, NE, 68198, USA. apodany@unmc.edu.
University of Nebraska Medical Center · US

Funding

Tracking and Evaluation CoreU54GM115458 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI ZHANG, YING · 2016 to 2025
$42.8M
Therapeutics Core (Page 286)P30MH062261 · NIMH · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI GENDELMAN, HOWARD E · 2000 to 2021
$37.7M
The Lymphoid Tissue Pharmacology of Antiretroviral DrugsR01AI124965 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI FLETCHER, COURTNEY V · 2016 to 2020
$3.7M
Limiting HIV establishment and maintenace by preserving intestinal immunityR01AI129745 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BYRAREDDY, SIDDAPPA N, PAIARDINI, MIRKO · 2017 to 2020
$3.3M
NIAID NIH HHS R01 AI124965NIAID NIH HHS R01 AI129745NIGMS NIH HHS U54 GM115458NIMH NIH HHS P30 MH062261
6 · The paper itself

Abstract

Quantification of antiretroviral (ARV) drug concentrations in peripheral blood mononuclear cells (PBMCs) and tissue isolated mononuclear cells (TIMCs) from lymph node (LNMC) and rectum (RMC) is an important measure of bio-distribution. Normalization of drug concentrations is critical to represent tissue drug concentrations and to analyze both intra-individual and inter-individual variability in drug distribution. However, a molecular method to normalize intracellular drug concentrations in PBMCs and TIMCs methanol extracts is currently unavailable. In this study, a novel droplet digital PCR (ddPCR) assay was designed to amplify RPP30 gene sequence conserved in human and non-human primates (NHP). Genomic DNA (gDNA) isolated from 70 percent methanol embedded PBMCs and TIMCs was used as ddPCR template to quantitate precise RPP30 copies to derive cell counts. The novel molecular method quantitated RPP30 copies in human and rhesus macaque gDNA templates with greater accuracy and precision than qPCR. RPP30 ddPCR derived cell counts are strongly correlated with automated cytometer based cell counts in PBMC (R = 0.90, p = 0.001 and n = 20); LNMC (R = 0.85 p = 0.0001 and n = 22) and RMC (R = 0.92, p = 0.0001 and n = 20) and achieved comparable normalized drug concentrations. Therefore, the RPP30 ddPCR assay is an important normalization method in drug bio-distribution and pharmacokinetic studies in humans and NHPs.

Indexed as

Anti-Retroviral AgentsAutoantigensCells, CulturedHumansLeukocytes, MononuclearLymph NodesReal-Time Polymerase Chain ReactionRectumReproducibility of ResultsRibonuclease PViral LoadAnti-Retroviral AgentsAutoantigensRibonuclease PRPP30 protein, human

Identifiers

PMID29483619
PMCPMC5827666
OpenAlexW2797381598

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.