Evidence map›Paper›PMID 33434240›Full record

ArticlePloS one2021

Ultrasonography validation for early alteration of diaphragm echodensity and function in the mdx mouse model of Duchenne muscular dystrophy.

Antonietta Mele, Paola Mantuano, Adriano Fonzino, Francesco Rana, Roberta Francesca Capogrosso, Francesca Sanarica, Jean-Francois Rolland, Ornella Cappellari, Annamaria De Luca

Abstract read
In one paragraph

Article in PloS one, 2021. 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
–field-weighted citation impact
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.

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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

9 authors.

Antonietta MeleSection of Pharmacology, Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
Paola MantuanoSection of Pharmacology, Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
Adriano FonzinoSection of Pharmacology, Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
Francesco RanaSection of Pharmacology, Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
Roberta Francesca CapogrossoSection of Pharmacology, Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
Francesca SanaricaSection of Pharmacology, Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
Jean-Francois RollandAxxam, S.p.A, Bresso, Milan, Italy.
Ornella CappellariSection of Pharmacology, Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
Annamaria De LucaSection of Pharmacology, Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.ORCID 0000-0002-5652-7341

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The mdx mouse model of Duchenne muscular dystrophy is characterized by functional and structural alterations of the diaphragm since early stages of pathology, closely resembling patients' condition. In recent years, ultrasonography has been proposed as a useful longitudinal non-invasive technique to assess mdx diaphragm dysfunction and evaluate drug efficacy over time. To date, only a few preclinical studies have been conducted. Therefore, an independent validation of this method by different laboratories is needed to increase results reliability and reduce biases. Here, we performed diaphragm ultrasonography in 3- and 6-month-old mdx mice, the preferred age-window for pharmacology studies. The alteration of diaphragm function over time was measured as diaphragm ultrasound movement amplitude. At the same time points, a first-time assessment of diaphragm echodensity was performed, as an experimental index of progressive loss of contractile tissue. A parallel evaluation of other in vivo and ex vivo dystrophy-relevant readouts was carried out. Both 3- and 6-month-old mdx mice showed a significant decrease in diaphragm amplitude compared to wild type (wt) mice. This index was well-correlated either with in vivo running performance or ex vivo isometric tetanic force of isolated diaphragm. In addition, diaphragms from 6-month-old dystrophic mice were also highly susceptible to eccentric contraction ex vivo. Importantly, we disclosed an age-dependent increase in echodensity in mdx mice not observed in wt animals, which was independent from abdominal wall thickness. This was accompanied by a notable increase of pro-fibrotic TGF-β1 levels in the mdx diaphragm and of non-muscle tissue amount in diaphragm sections stained by hematoxylin & eosin. Our findings corroborate the usefulness of diaphragm ultrasonography in preclinical drug studies as a powerful tool to monitor mdx pathology progression since early stages.

Indexed as

AnimalsDiaphragmDisease Models, AnimalMaleMiceMice, Inbred C57BLMice, Inbred mdxMuscular Dystrophy, DuchenneTransforming Growth Factor beta1UltrasonographyTransforming Growth Factor beta1

Identifiers

PMID33434240
PMCPMC7802948

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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.