Evidence map›Paper›PMID 32316887›Full record

ArticleCurrent pharmaceutical design2020

Pharmacokinetics of Inter-Alpha Inhibitor Proteins and Effects on Hemostasis After Hypoxic-Ischemic Brain Injury in Neonatal Rats.

Xiaodi Chen, Dawei Song, Sakura Nakada, Joseph Qiu, Karin Iwamoto, Ray H Chen, Yow-Pin Lim, William J Jusko, Barbara S Stonestreet

Open access · greenAbstract read
In one paragraph

Article in Current pharmaceutical design, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
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

9 authors at 3 institutions in 1 country.

Xiaodi ChenDepartment of Pediatrics, Women & Infants Hospital of Rhode Island, The Alpert Medical School of Brown University, Providence, RI, United States.
Dawei SongSchool of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, United States.
Sakura NakadaDepartment of Pediatrics, Women & Infants Hospital of Rhode Island, The Alpert Medical School of Brown University, Providence, RI, United States.
Joseph QiuProThera Biologics, Inc., Providence, RI, United States.
Karin IwamotoDepartment of Pediatrics, Women & Infants Hospital of Rhode Island, The Alpert Medical School of Brown University, Providence, RI, United States.
Ray H ChenDepartment of Pediatrics, Women & Infants Hospital of Rhode Island, The Alpert Medical School of Brown University, Providence, RI, United States.
Yow-Pin LimProThera Biologics, Inc., Providence, RI, United States.
William J JuskoSchool of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, United States.
Barbara S StonestreetDepartment of Pediatrics, Women & Infants Hospital of Rhode Island, The Alpert Medical School of Brown University, Providence, RI, United States.
Brown University · USProvidence College · USUniversity at Buffalo, State University of New York · US

Funding

CORTICOSTEROID PHARMACOKINETICS/DYNAMICSR01GM024211 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI JUSKO, WILLIAM J. · 1985 to 2018
$4.7M
Inter-alpha Inhibitors in Hypoxic-Ischemic Brain InjuryR44NS084575 · NINDS · PROTHERA BIOLOGICS, LLC · PI LIM, YOW-PIN · 2017 to 2023
$4.7M
Research CoreP30GM114750 · NIGMS · WOMEN AND INFANTS HOSPITAL-RHODE ISLAND · PI SHAW, SUNIL K · 2015 to 2019
$4.5M
Mechanistic Pharmacokinetics and PharmacodynamicsR35GM131800 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI JUSKO, WILLIAM J. · 2019 to 2023
$2.9M
Inter-alpha inhibitors: Novel neuroinflammatory modulator of neonatal brain injuryR21NS095130 · NINDS · WOMEN AND INFANTS HOSPITAL-RHODE ISLAND · PI STONESTREET, BARBARA S · 2016 to 2017
$441k
Beneficial Effects of Inter-alpha Inhibitors in Fetal Brain InjuryR21NS096525 · NINDS · WOMEN AND INFANTS HOSPITAL-RHODE ISLAND · PI STONESTREET, BARBARA S · 2016 to 2017
$441k
NIGMS NIH HHS P30 GM114750NIGMS NIH HHS R01 GM024211NIGMS NIH HHS R35 GM131800NINDS NIH HHS R21 NS095130NINDS NIH HHS R21 NS096525NINDS NIH HHS R44 NS084575
6 · The paper itself

Abstract

backgroundHypoxic-ischemic (HI) brain injury is a leading cause of long-term neurodevelopmental morbidities in neonates. Human plasma-derived Inter-Alpha Inhibitor Proteins (hIAIPs) are neuroprotective after HI brain injury in neonatal rats. The light chain (bikunin) of hIAIPs inhibits proteases involved in the coagulation of blood. Newborns exposed to HI can be at risk for significant bleeding in the brain and other organs.

objectiveThe objectives of the present study were to assess the pharmacokinetics (PK) and the duration of bleeding after intraperitoneal (IP) administration of hIAIPs in HI-exposed male and female neonatal rats.

methodsHI was induced with the Rice-Vannucci method in postnatal (P) day-7 rats. After the right common carotid artery ligation, rats were exposed to 90 min of 8% oxygen. hIAIPs (30 mg/kg, IP) were given immediately after Sham or HI exposure in the PK study and serum was collected 1, 6, 12, 24, or 36 h after the injections. Serum hIAIP concentrations were measured with a competitive ELISA. ADAPT5 software was used to fit the pooled PK data considering first-order absorption and disposition. hIAIPs (60 mg/kg, IP) were given in the bleeding time studies at 0, 24 and 48 h after HI with tail bleeding times measured 72 h after HI.

resultsIP administration yielded significant systemic exposure to hIAIPs with PK being affected markedly including primarily faster absorption and reduced elimination as a result of HI and modestly of sex-related differences. hIAIP administration did not affect bleeding times after HI.

conclusionThese results will help to inform hIAIP dosing regimen schedules in studies of neuroprotection in neonates exposed to HI.

Indexed as

Brain InjuriesHypoxia-Ischemia, BrainAnimalsAnimals, NewbornBrainFemaleHemostasisRatscoagulationhypoxic-ischemic brain injuryinter-alpha-inhibitor proteinsneonatesPharmacokineticssex.

Identifiers

PMID32316887
PMCPMC7545274
OpenAlexW3017367297

What OpenQuestion holds

Textmetadata
LicenceTDM
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.