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Article ; Online: Comparison of amikacin lung delivery between AKITA® and eFlow rapid® nebulizers in healthy controls and patients with CF: A randomized cross-over trial.

Aubriot, Anne-Sophie / Maerckx, Guillaume / Leal, Teresinha / Gohy, Sophie / Reychler, Gregory

Respiratory medicine and research

2023 Volume 84, Page(s) 101038

Abstract: Introduction: Nebulization plays a key role in the treatment of cystic fibrosis. The Favorite function couple to jet nebulizers (AKITA®) emerged recently. The aim of this study was to assess the efficiency of the lung delivery by the AKITA® by comparing ...

Abstract	Introduction: Nebulization plays a key role in the treatment of cystic fibrosis. The Favorite function couple to jet nebulizers (AKITA®) emerged recently. The aim of this study was to assess the efficiency of the lung delivery by the AKITA® by comparing the urinary concentration of amikacin after nebulization with the AKITA® and the eFlow rapid®, in healthy subjects and patients with CF (PwCF). Method: The two samples (healthy subjects and PwCF) were randomized (cross-over 1:1) for two nebulizations (500 mg of amikacin diluted in 4 mL of normal saline solution), with the AKITA® and with the eFlow rapid®. The primary endpoint was the amount of urinary excretion of amikacin over 24 h. The constant of elimination (Ke) was calculated based on the maximal cumulative urinary amikacin excretion plotted over time. Results: The total amount of urinary amikacin excretion was greater when AKITA® was used in PwCF (11.7 mg (8.2-14.1) vs 6.1 mg (3.7-13.3); p = 0.02) but not different in healthy subjects (14.5 mg (11.7-18.5) vs 12.4 mg (8.0-17.1); p = 0.12). The duration of the nebulization was always shorter with eFlow rapid® than with AKITA® (PwCF: 6.5 ± 0.6 min vs 9.2 ± 1.8 min; p = 0.001 - Healthy: 4.7 ± 1.3 min vs 9.7 ± 1.6 min; p = 0.03). The constant of elimination was similar between the two modalities in CF subjects (0.153 (0.071-0.205) vs 0.149 (0.041-0.182); p = 0.26) and in healthy subjects (0.166 (0.130-0.218) vs 0.167 (0.119-0.210), p = 0.25). Conclusion: the Favorite inhalation is better to deliver a specific amount of drug than a mesh nebulizer (eFlow rapid®) in PwCF but not in healthy subjects.
MeSH term(s)	Humans ; Amikacin/urine ; Anti-Bacterial Agents ; Cross-Over Studies ; Respiratory Aerosols and Droplets ; Nebulizers and Vaporizers ; Lung
Chemical Substances	Amikacin (84319SGC3C) ; Anti-Bacterial Agents
Language	English
Publishing date	2023-07-04
Publishing country	France
Document type	Randomized Controlled Trial ; Journal Article
ISSN	2590-0412
ISSN (online)	2590-0412
DOI	10.1016/j.resmer.2023.101038
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Article ; Online: Nasal Potential Difference to Quantify Trans-epithelial Ion Transport in Mice.

Beka, Mathilde / Leal, Teresinha

Journal of visualized experiments : JoVE

2018 , Issue 137

Abstract: The nasal potential difference test has been used for almost three decades to assist in the diagnosis of cystic fibrosis (CF). It has proven to be helpful in cases of attenuated, oligo- or mono-symptomatic forms of CF usually diagnosed later in life, and ...

Abstract	The nasal potential difference test has been used for almost three decades to assist in the diagnosis of cystic fibrosis (CF). It has proven to be helpful in cases of attenuated, oligo- or mono-symptomatic forms of CF usually diagnosed later in life, and of CF-related disorders such as congenital bilateral absence of vas deferens, idiopathic chronic pancreatitis, allergic bronchopulmonary aspergillosis, and bronchiectasis. In both clinical and preclinical settings, the test has been used as a biomarker to quantify responses to targeted therapeutic strategies for CF. Adapting the test to a mouse is challenging and can entail an associated mortality. This paper describes the adequate depth of anesthesia required to maintain a nasal catheter in situ for continuous perfusion. It lists measures to avoid broncho-aspiration of solutions perfused in the nose. It also describes the animal care at the end of the test, including administration of a combination of antidotes of the anesthetic drugs, leading to rapidly reversing the anesthesia with full recovery of the animals. Representative data obtained from a CF and a wild-type mouse show that the test discriminates between CF and non-CF. Altogether, the protocol described here allows reliable measurements of the functional status of trans-epithelial chloride and sodium transporters in spontaneously breathing mice, as well as multiple tests in the same animal while reducing test-related mortality.
MeSH term(s)	Animals ; Ion Transport/physiology ; Male ; Mice ; Nasal Mucosa/metabolism
Language	English
Publishing date	2018-07-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/57934
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Article: On the Corner of Models and Cure: Gene Editing in Cystic Fibrosis.

Ensinck, Marjolein / Mottais, Angélique / Detry, Claire / Leal, Teresinha / Carlon, Marianne S

Frontiers in pharmacology

2021 Volume 12, Page(s) 662110

Abstract: Cystic fibrosis (CF) is a severe genetic disease for which curative treatment is still lacking. Next generation biotechnologies and more efficient cell-based ... ...

Abstract	Cystic fibrosis (CF) is a severe genetic disease for which curative treatment is still lacking. Next generation biotechnologies and more efficient cell-based and
Language	English
Publishing date	2021-04-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2021.662110
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Article ; Online: PDE5 Inhibitors As Potential Tools In The Treatment Of Cystic Fibrosis

TeresinhaLeal

Frontiers in Pharmacology, Vol

2012 Volume 3

Abstract: Despite great advances in the understanding of the genetics and pathophysiology of cystic fibrosis (CF), there is still no cure for the disease. Using phosphodiesterase type 5 (PDE5) inhibitors, we and others have provided evidence of rescued F508del- ... ...

Abstract	Despite great advances in the understanding of the genetics and pathophysiology of cystic fibrosis (CF), there is still no cure for the disease. Using phosphodiesterase type 5 (PDE5) inhibitors, we and others have provided evidence of rescued F508del-CFTR trafficking and corrected deficient chloride transport activity. Studies using PDE5 inhibitors in mice homozygous for the clinically relevant F508del mutation have been conducted with the aim of restoring F508del-CFTR protein function. We demonstrated, by measuring transepithelial nasal potential difference in F508del mice following intraperitoneal injection of sildenafil, vardenafil or taladafil at clinical doses are able to restore the decreased CFTR-dependent chloride transport across the nasal mucosa. Moreover, vardenafil, but not sildenafil, stimulates chloride transport through the normal CFTR protein. We developed a specific nebulizer setup for mice, with which we demonstrated, through a single inhalation of PDE5 inhibitors, local activation of CFTR protein in CF. Significant potential advantages of inhalation drug therapy over oral or intravenous routes include rapid onset of pharmacological action, reduced systemic secondary effects and reduced effective drug doses compared to the drug delivered orally; this underlines the relevance and impact of our work for translational science. More recently, we analyzed the bronchoalveolar lavage of CF and wild-type mice for cell infiltrates and expression of pro-inflammatory cytokines and chemokines; we found that the CFTR activating effect of vardenafil, selected as a representative long-lasting PDE5 inhibitor, breaks the vicious circle of lung inflammation which plays a major role in morbi-mortality in CF. Our data highlight the potential use of PDE5 inhibitors in CF. Therapeutic approaches using clinically approved PDE5 inhibitors to address F508del-CFTR defects could speed up the development of new therapies for CF.
Keywords	Cystic Fibrosis ; CFTR ; PDE5 inhibitors ; sildenafil ; vardenafil ; taladafil ; Therapeutics. Pharmacology ; RM1-950 ; Medicine ; R
Language	English
Publishing date	2012-09-01T00:00:00Z
Publisher	Frontiers
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sweat Proteomics in Cystic Fibrosis: Discovering Companion Biomarkers for Precision Medicine and Therapeutic Development.

Burat, Bastien / Reynaerts, Audrey / Baiwir, Dominique / Fléron, Maximilien / Gohy, Sophie / Eppe, Gauthier / Leal, Teresinha / Mazzucchelli, Gabriel

Cells

2022 Volume 11, Issue 15

Abstract: In clinical routine, the diagnosis of cystic fibrosis (CF) is still challenging regardless of international consensus on diagnosis guidelines and tests. For decades, the classical Gibson and Cooke test measuring sweat chloride concentration has been a ... ...

Abstract	In clinical routine, the diagnosis of cystic fibrosis (CF) is still challenging regardless of international consensus on diagnosis guidelines and tests. For decades, the classical Gibson and Cooke test measuring sweat chloride concentration has been a keystone, yet, it may provide normal or equivocal results. As of now, despite the combination of sweat testing,
MeSH term(s)	Biomarkers/metabolism ; Chlorides/metabolism ; Cystic Fibrosis/diagnosis ; Cystic Fibrosis/genetics ; Cystic Fibrosis/metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Glycosyltransferases/metabolism ; Humans ; Precision Medicine ; Proteome/metabolism ; Proteomics ; Sweat/metabolism
Chemical Substances	Biomarkers ; Chlorides ; Proteome ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Glycosyltransferases (EC 2.4.-) ; LFNG protein, human (EC 2.4.1.-)
Language	English
Publishing date	2022-07-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11152358
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Article ; Online: Characterization of the Human Eccrine Sweat Proteome-A Focus on the Biological Variability of Individual Sweat Protein Profiles.

Burat, Bastien / Reynaerts, Audrey / Baiwir, Dominique / Fléron, Maximilien / Eppe, Gauthier / Leal, Teresinha / Mazzucchelli, Gabriel

International journal of molecular sciences

2021 Volume 22, Issue 19

Abstract: The potential of eccrine sweat as a bio-fluid of interest for diagnosis and personalized therapy has not yet been fully evaluated, due to the lack of in-depth sweat characterization studies. Thanks to recent developments in omics, together with the ... ...

Abstract	The potential of eccrine sweat as a bio-fluid of interest for diagnosis and personalized therapy has not yet been fully evaluated, due to the lack of in-depth sweat characterization studies. Thanks to recent developments in omics, together with the availability of accredited sweat collection methods, the analysis of human sweat may now be envisioned as a standardized, non-invasive test for individualized monitoring and personalized medicine. Here, we characterized individual sweat samples, collected from 28 healthy adult volunteers under the most standardized sampling methodology, by applying optimized shotgun proteomics. The thorough characterization of the sweat proteome allowed the identification of 983 unique proteins from which 344 were identified across all samples. Annotation-wise, the study of the sweat proteome unveiled the over-representation of newly addressed actin dynamics, oxidative stress and proteasome-related functions, in addition to well-described proteolysis and anti-microbial immunity. The sweat proteome composition correlated with the inter-individual variability of sweat secretion parameters. In addition, both gender-exclusive proteins and gender-specific protein abundances were highlighted, despite the high similarity between human female and male sweat proteomes. In conclusion, standardized sample collection coupled with optimized shotgun proteomics significantly improved the depth of sweat proteome coverage, far beyond previous similar studies. The identified proteins were involved in many diverse biological processes and molecular functions, indicating the potential of this bio-fluid as a valuable biological matrix for further studies. Addressing sweat variability, our results prove the proteomic profiling of sweat to be a promising bio-fluid analysis for individualized, non-invasive monitoring and personalized medicine.
MeSH term(s)	Adult ; Aged ; Child ; Child, Preschool ; Eccrine Glands/metabolism ; Female ; Humans ; Male ; Middle Aged ; Proteome/analysis ; Proteome/metabolism ; Proteomics/methods ; Specimen Handling ; Sweat/chemistry ; Sweat/metabolism ; Young Adult
Chemical Substances	Proteome
Language	English
Publishing date	2021-10-08
Publishing country	Switzerland
Document type	Comparative Study ; Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms221910871
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Article ; Online: Characterization of the Human Eccrine Sweat Proteome—A Focus on the Biological Variability of Individual Sweat Protein Profiles

Bastien Burat / Audrey Reynaerts / Dominique Baiwir / Maximilien Fléron / Gauthier Eppe / Teresinha Leal / Gabriel Mazzucchelli

International Journal of Molecular Sciences, Vol 22, Iss 10871, p

2021 Volume 10871

Abstract	The potential of eccrine sweat as a bio-fluid of interest for diagnosis and personalized therapy has not yet been fully evaluated, due to the lack of in-depth sweat characterization studies. Thanks to recent developments in omics, together with the availability of accredited sweat collection methods, the analysis of human sweat may now be envisioned as a standardized, non-invasive test for individualized monitoring and personalized medicine. Here, we characterized individual sweat samples, collected from 28 healthy adult volunteers under the most standardized sampling methodology, by applying optimized shotgun proteomics. The thorough characterization of the sweat proteome allowed the identification of 983 unique proteins from which 344 were identified across all samples. Annotation-wise, the study of the sweat proteome unveiled the over-representation of newly addressed actin dynamics, oxidative stress and proteasome-related functions, in addition to well-described proteolysis and anti-microbial immunity. The sweat proteome composition correlated with the inter-individual variability of sweat secretion parameters. In addition, both gender-exclusive proteins and gender-specific protein abundances were highlighted, despite the high similarity between human female and male sweat proteomes. In conclusion, standardized sample collection coupled with optimized shotgun proteomics significantly improved the depth of sweat proteome coverage, far beyond previous similar studies. The identified proteins were involved in many diverse biological processes and molecular functions, indicating the potential of this bio-fluid as a valuable biological matrix for further studies. Addressing sweat variability, our results prove the proteomic profiling of sweat to be a promising bio-fluid analysis for individualized, non-invasive monitoring and personalized medicine.
Keywords	human eccrine sweat ; shotgun proteomics ; inter-individual variability ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	500
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Nasal potential difference to quantify trans-epithelial ion transport in mice

Beka, Mathilde / Leal, Teresinha

Journal of visualized experiments. 2018 July 04, , no. 137

2018

Abstract	The nasal potential difference test has been used for almost three decades to assist in the diagnosis of cystic fibrosis (CF). It has proven to be helpful in cases of attenuated, oligo- or mono-symptomatic forms of CF usually diagnosed later in life, and of CF-related disorders such as congenital bilateral absence of vas deferens, idiopathic chronic pancreatitis, allergic bronchopulmonary aspergillosis, and bronchiectasis. In both clinical and preclinical settings, the test has been used as a biomarker to quantify responses to targeted therapeutic strategies for CF. Adapting the test to a mouse is challenging and can entail an associated mortality. This paper describes the adequate depth of anesthesia required to maintain a nasal catheter in situ for continuous perfusion. It lists measures to avoid broncho-aspiration of solutions perfused in the nose. It also describes the animal care at the end of the test, including administration of a combination of antidotes of the anesthetic drugs, leading to rapidly reversing the anesthesia with full recovery of the animals. Representative data obtained from a CF and a wild-type mouse show that the test discriminates between CF and non-CF. Altogether, the protocol described here allows reliable measurements of the functional status of trans-epithelial chloride and sodium transporters in spontaneously breathing mice, as well as multiple tests in the same animal while reducing test-related mortality.
Keywords	anesthetics ; animal care ; antidotes ; aspergillosis ; biomarkers ; breathing ; catheters ; cystic fibrosis ; depth of anesthesia ; functional status ; mice ; mortality ; nose ; pancreatitis ; sodium ; transporters
Language	English
Dates of publication	2018-0704
Size	p. e57934.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/57934
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Sweat Proteomics in Cystic Fibrosis

Bastien Burat / Audrey Reynaerts / Dominique Baiwir / Maximilien Fléron / Sophie Gohy / Gauthier Eppe / Teresinha Leal / Gabriel Mazzucchelli

Cells, Vol 11, Iss 2358, p

Discovering Companion Biomarkers for Precision Medicine and Therapeutic Development

2022 Volume 2358

Abstract	In clinical routine, the diagnosis of cystic fibrosis (CF) is still challenging regardless of international consensus on diagnosis guidelines and tests. For decades, the classical Gibson and Cooke test measuring sweat chloride concentration has been a keystone, yet, it may provide normal or equivocal results. As of now, despite the combination of sweat testing, CFTR genotyping, and CFTR functional testing, a small fraction (1–2%) of inconclusive diagnoses are reported and justifies the search for new CF biomarkers. More importantly, in the context of precision medicine, with a view to early diagnosis, better prognosis, appropriate clinical follow-up, and new therapeutic development, discovering companion biomarkers of CF severity and phenotypic rescue are of utmost interest. To date, previous sweat proteomic studies have already documented disease-specific variations of sweat proteins (e.g., in schizophrenia and tuberculosis). In the current study, sweat samples from 28 healthy control subjects and 14 patients with CF were analyzed by nanoUHPLC-Q-Orbitrap-based shotgun proteomics, to look for CF-associated changes in sweat protein composition and abundance. A total of 1057 proteins were identified and quantified at an individual level, by a shotgun label-free approach. Notwithstanding similar proteome composition, enrichment, and functional annotations, control and CF samples featured distinct quantitative proteome profiles significantly correlated with CF, accounting for the respective inter-individual variabilities of control and CF sweat. All in all: (i) 402 sweat proteins were differentially abundant between controls and patients with CF, (ii) 68 proteins varied in abundance between F508del homozygous patients and patients with another genotype, (iii) 71 proteins were differentially abundant according to the pancreatic function, and iv) 54 proteins changed in abundance depending on the lung function. The functional annotation of pathophysiological biomarkers highlighted eccrine gland cell perturbations in: ...
Keywords	cystic fibrosis ; human eccrine sweat ; shotgun proteomics ; companion biomarkers ; actin cytoskeleton ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis: current perspectives.

Schmidt, Béla Z / Haaf, Jérémy B / Leal, Teresinha / Noel, Sabrina

Clinical pharmacology : advances and applications

2016 Volume 8, Page(s) 127–140

Abstract: Mutations of ... ...

Abstract	Mutations of the
Language	English
Publishing date	2016-09-21
Publishing country	New Zealand
Document type	Review ; Journal Article
ZDB-ID	2520726-X
ISSN	1179-1438
ISSN	1179-1438
DOI	10.2147/CPAA.S100759
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