Evidence map›Paper›PMID 25892862›Full record

ArticleWorld journal of gastroenterology2015

Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure.

Nicholas G Theodorakis, Yining N Wang, Vyacheslav A Korshunov, Mary A Maluccio, Nicholas J Skill

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in World journal of gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

1 citing paper in PubMed, 6 citations in OpenAlex.

  1. Article
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

5 authors at 1 institution in 2 countries.

Nicholas G TheodorakisNicholas G Theodorakis, Mary A Maluccio, Nicholas J Skill, Division of Transplant Surgery, Department of Surgery, School of Medicine, Indiana University, Indianapolis, IN 46202, United States.
Yining N WangNicholas G Theodorakis, Mary A Maluccio, Nicholas J Skill, Division of Transplant Surgery, Department of Surgery, School of Medicine, Indiana University, Indianapolis, IN 46202, United States.
Vyacheslav A KorshunovNicholas G Theodorakis, Mary A Maluccio, Nicholas J Skill, Division of Transplant Surgery, Department of Surgery, School of Medicine, Indiana University, Indianapolis, IN 46202, United States.
Mary A MaluccioNicholas G Theodorakis, Mary A Maluccio, Nicholas J Skill, Division of Transplant Surgery, Department of Surgery, School of Medicine, Indiana University, Indianapolis, IN 46202, United States.
Nicholas J SkillNicholas G Theodorakis, Mary A Maluccio, Nicholas J Skill, Division of Transplant Surgery, Department of Surgery, School of Medicine, Indiana University, Indianapolis, IN 46202, United States.
St Nicholas Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimPortal hypertension is a common complication of liver cirrhosis and significantly increases mortality and morbidity. Previous reports have suggested that the compound thalidomide attenuates portal hypertension (PHT). However, the mechanism for this action is not fully elucidated. One hypothesis is that thalidomide destabilizes tumor necrosis factor α (TNFα) mRNA and therefore diminishes TNFα induction of nitric oxide synthase (NOS) and the production of nitric oxide (NO). To examine this hypothesis, we utilized the murine partial portal vein ligation (PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout mice.

methodsWild type, inducible nitric oxide synthase (iNOS)(-/-) and endothelial nitric oxide synthase (eNOS)(-/-) mice received either PVL or sham surgery and were given either thalidomide or vehicle. Serum nitrate (total nitrate, NOx) was measured daily for 7 d as a surrogate of NO synthesis. Serum TNFα level was quantified by enzyme-linked immunosorbent assay. TNFα mRNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain reaction. PHT was determined by recording splenic pulp pressure (SPP) and abdominal aortic flow after 0-7 d. Response to thalidomide was determined by measurement of SPP and mean arterial pressure (MAP).

resultsSPP, abdominal aortic flow (Qao) and plasma NOx were increased in wild type and iNOS(-/-) PVL mice when compared to sham operated control mice. In contrast, SPP, Qao and plasma NOx were not increased in eNOS(-/-) PVL mice when compared to sham controls. Serum TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA used. Therefore, the effect of thalidomide on serum TNFα levels was undetermined in wild type, eNOS(-/-) or iNOS(-/-) mice. Thalidomide acutely increased plasma NOx in wild type and eNOS(-/-) mice but not iNOS(-/-) mice. Moreover, thalidomide temporarily (0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, eNOS(-/-) and iNOS(-/-) PVL mice, after which time levels returned to the respective baseline.

conclusionThalidomide does not reduce portal pressure in the murine PVL model by modulation of NO biosynthesis. Rather, thalidomide reduces PHT by decreasing MAP by an undetermined mechanism.

Indexed as

AnimalsAntihypertensive AgentsAorta, AbdominalArterial PressureBiomarkersBlood Flow VelocityDisease Models, AnimalHypertension, PortalMacrophagesMiceMice, Inbred C57BLMice, KnockoutNitratesNitric OxideNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIAntihypertensive AgentsBiomarkersNitratesNitric OxideNitric Oxide Synthase Type IINitric Oxide Synthase Type IIINos2 protein, mouseNos3 protein, mouseThalidomideTumor Necrosis Factor-alphaEndothelial nitric oxide synthaseInducible nitric oxide synthaseKnockout miceNitric oxidePortal hypertensionThalidomideTumor necrosis factor alpha

Identifiers

PMID25892862
PMCPMC4394073
OpenAlexW2088571644

What Socratic holds

Textmetadata
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 Socratic graph.