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252 results on '"Pirro, Valentina"'

2. Glucose-Dependent Insulinotropic Polypeptide Receptor Signalling in Oligodendrocytes Increases the Weight Loss Action of GLP-1R Agonism

Author

Hansford, Robert, primary, Buller, Sophie, additional, Tsang, Anthony H., additional, Benoit, Simon, additional, Roberts, Anna, additional, Erskine, Emmy, additional, Pirro, Valentina, additional, Reimann, Frank, additional, Harada, Norio, additional, Inagaki, Nobuya, additional, Adrienssens, Alice, additional, Samms, Ricardo, additional, and Blouet, Clemence, additional

Published
2024
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10. GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice

Author

Samms, Ricardo J., Christe, Michael E., Collins, Kyla A.L., Pirro, Valentina, Droz, Brian A., Holland, Adrienne K., Friedrich, Jessica L., Wojnicki, Samantha, Konkol, Debra L., Cosgrove, Richard, Furber, Ellen P.S. Conceiqao, Ruan, Xiaoping, OFarrell, Libbey S., Long, Annie M., Dogra, Mridula, Willency, Jill A., Lin, Yanzhu, Ding, Liyun, Cheng, Christine C., Cabrera, Over, Briere, Daniel A., Alsina-Fernandez, Jorge, Gimeno, Ruth E., Moyers, Julie S., Coskun, Tamer, Coghlan, Matthew P., Sloop, Kyle W., and Roell, William C.

Subjects
Hormone antagonists -- Research, Obesity -- Drug therapy -- Models, Pharmacology, Experimental -- Usage, Gastrointestinal hormones -- Health aspects -- Physiological aspects, Insulin -- Physiological aspects, Hypoglycemic agents -- Research, Drug sensitization -- Research, Health care industry
Abstract

Tirzepatide (LY3298176), a dual GIP and GLP-1 receptor (GLP-1R) agonist, delivered superior glycemic control and weight loss compared with GLP-1R agonism in patients with type 2 diabetes. However, the mechanism by which tirzepatide improves efficacy and how GIP receptor (GIPR) agonism contributes is not fully understood. Here, we show that tirzepatide is an effective insulin sensitizer, improving insulin sensitivity in obese mice to a greater extent than GLP-1R agonism. To determine whether GIPR agonism contributes, we compared the effect of tirzepatide in obese WT and Glp-1r-null mice. In the absence of GLP-1R-induced weight loss, tirzepatide improved insulin sensitivity by enhancing glucose disposal in white adipose tissue (WAT). In support of this, a long-acting GIPR agonist (LAGIPRA) was found to enhance insulin sensitivity by augmenting glucose disposal in WAT. Interestingly, the effect of tirzepatide and LAGIPRA on insulin sensitivity was associated with reduced branched-chain amino acids (BCAAs) and ketoacids in the circulation. Insulin sensitization was associated with upregulation of genes associated with the catabolism of glucose, lipid, and BCAAs in brown adipose tissue. Together, our studies show that tirzepatide improved insulin sensitivity in a weight-dependent and -independent manner. These results highlight how GIPR agonism contributes to the therapeutic profile of dual- receptor agonism, offering mechanistic insights into the clinical efficacy of tirzepatide., Introduction Type 2 diabetes mellitus (T2DM) is a global pandemic, placing significant strain on healthcare systems world wide (1). Driven primarily by excess body weight, systemic insulin resistance (IR) is [...]

Published
2021
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14. Friedman Tongue Position and the Anthropometric Parameters in Adult Patients with Obstructive Sleep Apnea: An Observational Study

Author

Luzzi, Valeria, primary, Altieri, Federica, additional, Guaragna, Mariana, additional, Pirro, Valentina, additional, Marasca, Beatrice, additional, Cotticelli, Luisa, additional, Mazur, Marta, additional, Di Carlo, Gabriele, additional, Di Giacomo, Paola, additional, Di Paolo, Carlo, additional, Brunori, Marco, additional, Ierardo, Gaetano, additional, Piperno, Gabriele, additional, Magliulo, Giuseppe, additional, Pace, Annalisa, additional, Iannella, Giannicola, additional, Palange, Paolo, additional, Martini, Agnese, additional, Pietrafesa, Emma, additional, and Polimeni, Antonella, additional

Published
2023
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15. Evaluation of nasal airway resistance in a cohort of children with primary snoring and maxillary deficiency

Author

LUZZI, Valeria, primary, DE FILIPPO, Maria, additional, GUARNIERI, Rosanna, additional, FIORAVANTI, Miriam, additional, GUARAGNA, Mariana, additional, MARASCA, Beatrice, additional, PIRRO, Valentina, additional, ALTIERI, Federica, additional, VOZZA, Iole, additional, NDOKAJ, Artnora, additional, BRINDISI, Giulia, additional, BARBATO, Ersilia, additional, POLIMENI, Antonella, additional, and ZICARI, Anna Maria, additional

Published
2023
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21. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept

Author

Coskun, Tamer, primary, Urva, Shweta, additional, Roell, William C., additional, Qu, Hongchang, additional, Loghin, Corina, additional, Moyers, Julie S., additional, O’Farrell, Libbey S., additional, Briere, Daniel A., additional, Sloop, Kyle W., additional, Thomas, Melissa K., additional, Pirro, Valentina, additional, Wainscott, David B., additional, Willard, Francis S., additional, Abernathy, Matthew, additional, Morford, LaRonda, additional, Du, Yu, additional, Benson, Charles, additional, Gimeno, Ruth E., additional, Haupt, Axel, additional, and Milicevic, Zvonko, additional

Published
2022
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25. Correlations of Obstructive Sleep Apnea Syndrome and Daytime Sleepiness with the Risk of Car Accidents in Adult Working Population: A Systematic Review and Meta-Analysis with a Gender-Based Approach

Author

Luzzi, Valeria, primary, Mazur, Marta, additional, Guaragna, Mariana, additional, Di Carlo, Gabriele, additional, Cotticelli, Luisa, additional, Magliulo, Giuseppe, additional, Marasca, Beatrice, additional, Pirro, Valentina, additional, Di Giorgio, Gianni, additional, Ndokaj, Artnora, additional, Pasqualetti, Patrizio, additional, Simonelli, Ilaria, additional, Martini, Agnese, additional, Pietrafesa, Emma, additional, and Polimeni, Antonella, additional

Published
2022
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28. OSAS Severity and Occlusal Parameters: A Prospective Study among Adult Subjects with Comorbidities

Author

Luzzi, Valeria, primary, Altieri, Federica, additional, Di Carlo, Gabriele, additional, Guaragna, Mariana, additional, Pirro, Valentina, additional, Marasca, Beatrice, additional, Cotticelli, Luisa, additional, Mazur, Marta, additional, Di Giacomo, Paola, additional, Di Paolo, Carlo, additional, Brunori, Marco, additional, Piperno, Gabriele, additional, Magliulo, Giuseppe, additional, Martini, Agnese, additional, Pietrafesa, Emma, additional, and Polimeni, Antonella, additional

Published
2022
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35. Desorption Electrospray Ionization Mass Spectrometry Imaging: Recent Developments and Perspectives

Author

Ferreira, Christina, Alfaro, Clint M., Pirro, Valentina, and Cooks, R. Graham

Subjects
Scientific Session Abstracts
Abstract

Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) is an ambient ionization MS method utilized in over 730 peer-reviewed manuscripts. In this technique, a highly charged aerosol of microdroplets is sprayed onto a surface, desorbing and ionizing molecules which are then analyzed by MS. Since samples are analyzed in their native conditions with minimal to no sample preparation (e.g. without the need for separation or an organic matrix), chemicals, drugs, metabolites and lipids are rapidly detected and mapped in diverse types of samples. We focus on three recent DESI-MSI developments: (1) intraoperative brain cancer diagnostics, (2) developmental biology, and (3) high-throughput chemical reaction screening. For intraoperative brain cancer diagnostics, DESI-MS is being used in operating rooms for rapid tissue biopsy smear analysis to screen for diagnostic lipids and oncometabolites indicative of tumor type (e.g. glioma), grade and extent of tumor infiltration at surgical margins. Recently, isocitrate dehydrogenase (IDH) mutation status was determined intraoperatively by DESI in gliomas, offering new tumor management options which may impact extent of resection goals. In developmental biology, DESI-MSI was applied to whole body 2D and 3D swine fetus cryosections, and a range of lipids and metabolites specific to particular organs were spatially mapped and related to organogenesis. Finally, an autonomous system for high-throughput chemical reaction screening by DESI-MSI is an ongoing effort funded by the Defense Advanced Research Projects Agency (DARPA). This system takes advantage of the fact that chemical reactions are accelerated in DESI microdroplets to read over 1,000 unique reaction spots/hour and to explore the high dimensional chemical reaction space. To accomplish that, DESI-MS is integrated with four other commercial instruments all under computer control (a robotic pipetting robot, a robotic arm, a plate hoteling system and a precision solvent delivery system). In addition, future directions and perspectives for DESI-MSI will be presented.

Published
2019

40. Effects of Tirzepatide, a Dual GIP and GLP-1 RA, on Lipid and Metabolite Profiles in Subjects With Type 2 Diabetes.

Author

Pirro, Valentina, Roth, Kenneth D., Yanzhu Lin, Willency, Jill A., Milligan, Paul L., Wilson, Jonathan M., Ruotolo, Giacomo, Haupt, Axel, Newgard, Christopher B., and Duffin, Kevin L.

Subjects
TYPE 2 diabetes, BODY weight, HEMOGLOBINS
Abstract

Context: Tirzepatide substantially reduced hemoglobin A1c (HbA1c) and body weight in subjects with type 2 diabetes (T2D) compared with the glucagon-like peptide 1 receptor agonist dulaglutide. Improved glycemic control was associated with lower circulating triglycerides and lipoprotein markers and improved markers of beta-cell function and insulin resistance (IR), effects only partially attributable to weight loss. Objective: Assess plasma metabolome changes mediated by tirzepatide. Design: Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks. Post hoc exploratory metabolomics and lipidomics analyses were performed. Setting: Post hoc analysis. Participants: 259 subjects with T2D. Intervention(s): Tirzepatide (1, 5, 10, 15 mg), dulaglutide (1.5 mg), or placebo. Main Outcome Measure(s): Changes in metabolite levels in response to tirzepatide were assessed against baseline levels, dulaglutide, and placebo using multiplicity correction. Results: At 26 weeks, a higher dose tirzepatide modulated a cluster of metabolites and lipids associated with IR, obesity, and future T2D risk. Branched-chain amino acids, direct catabolic products glutamate, 3-hydroxyisobutyrate, branched-chain ketoacids, and indirect byproducts such as 2-hydroxybutyrate decreased compared to baseline and placebo. Changes were significantly larger with tirzepatide compared with dulaglutide and directly proportional to reductions of HbA1c, homeostatic model assessment 2-IR indices, and proinsulin levels. Proportional to metabolite changes, triglycerides and diglycerides were lowered significantly compared to baseline, dulaglutide, and placebo, with a bias toward shorter and highly saturated species. Conclusions: Tirzepatide reduces body weight and improves glycemic control and uniquely modulates metabolites associated with T2D risk and metabolic dysregulation in a direction consistent with improved metabolic health. [ABSTRACT FROM AUTHOR]

Published
2022
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50. Chemometric approach to open validation protocols: Prediction of validation parameters in multi-residue ultra-high performance liquid chromatography-tandem mass spectrometry methods

Author

Alladio, Eugenio, Pirro, Valentina, Salomone, Alberto, Vincenti, Marco, and Leardi, Riccardo

Subjects
Prediction of parameters, Chromatography, Chemometrics, Multi-residue analysis, Open validation, Partial least squares regression, Ultra-high performance liquid chromatography-tandem mass spectrometry, Chromatography, High Pressure Liquid, Humans, Hypnotics and Sedatives, Least-Squares Analysis, Limit of Detection, Lorazepam, Naloxone, Narcotic Antagonists, Street Drugs, Tandem Mass Spectrometry, Validation Studies as Topic, Biochemistry, Analytical Chemistry, Spectroscopy, Environmental Chemistry, Illicit Drugs, High Pressure Liquid
Abstract

The recent technological advancements of liquid chromatography-tandem mass spectrometry allow the simultaneous determination of tens, or even hundreds, of target analytes. In such cases, the traditional approach to quantitative method validation presents three major drawbacks: (i) it is extremely laborious, repetitive and rigid; (ii) it does not allow to introduce new target analytes without starting the validation from its very beginning and (iii) it is performed on spiked blank matrices, whose very nature is significantly modified by the addition of a large number of spiking substances, especially at high concentration. In the present study, several predictive chemometric models were developed from closed sets of analytes in order to estimate validation parameters on molecules of the same class, but not included in the original training set. Retention time, matrix effect, recovery, detection and quantification limits were predicted with partial least squares regression method. In particular, iterative stepwise elimination, iterative predictors weighting and genetic algorithms approaches were utilized and compared to achieve effective variables selection. These procedures were applied to data reported in our previously validated ultra-high performance liquid chromatography-tandem mass spectrometry multi-residue method for the determination of pharmaceutical and illicit drugs in oral fluid samples in accordance with national and international guidelines. Then, the partial least squares model was successfully tested on naloxone and lormetazepam, in order to introduce these new compounds in the oral fluid validated method, which adopts reverse-phase chromatography. Retention time, matrix effect, recovery, limit of detection and limit of quantification parameters for naloxone and lormetazepam were predicted by the model and then positively compared with their corresponding experimental values. The whole study represents a proof-of-concept of chemometrics potential to reduce the routine workload during multi-residue methods validation and suggests a rational alternative to ever-expanding procedures progressively drifting apart from real sample analysis.

Published
2014

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