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Book ; Online ; E-Book: Metabolomics and its impact on health and diseases

Ghini, Veronica / Stringer, Kathleen A. / Luchinat, Claudio

(Handbook of experimental pharmacology ; 277)

2023

Abstract: Preface -- Practical Aspects of NMR-Based Metabolomics -- Compound Identification in Mass Spectrometry-Based Metabolomics -- METABOLOMICS USING NMR – Avoiding the ‘Black-Box’ -- Natural products drug discovery: on silica or in silico?- Quantitative NMR ... ...

Author's details	Veronica Ghini, Kathleen A. Stringer, Claudio Luchinat editors
Series title	Handbook of experimental pharmacology ; 277
Collection
Abstract	Preface -- Practical Aspects of NMR-Based Metabolomics -- Compound Identification in Mass Spectrometry-Based Metabolomics -- METABOLOMICS USING NMR – Avoiding the ‘Black-Box’ -- Natural products drug discovery: on silica or in silico?- Quantitative NMR Methods in Metabolomics -- Advancements in pulsed stable isotope resolved metabolomics -- Metabolomics in Cell Biology -- NMR-based metabolomics to evaluate individual response to treatments -- Pharmacometabolomics of Asthma as a road map to Precision Medicine -- Prospective metabolomic studies in precision medicine -- Chemotherapy-induced Peripheral Neuropathy -- Metabolomics of Respiratory Diseases. This volume of the Handbook of Experimental Pharmacology, which celebrated its 100th anniversary in 2019, addresses the rapidly growing and evolving field of metabolomics. It has been compiled and designed to broaden and enrich your understanding as well as simplify a complicated picture of the diverse field of metabolomics. This is accomplished by chapters from experts in the field on basic principles as well as reviews and updates of analytical techniques. The variety and different perspectives of the NMR approaches are described in the chapters By David Wishart, Daniel Raftery and Ryan McKay, while mass spectrometry advances are covered by Charles R. Evans and Stefan Kempa. This book also reflects the state of the art in the application of metabolomics to cell biology (Marta Cascante and Ulrich Guenther) and chapters that share insights into the application of metabolomics in various diseases (Paola Turano and Claudio Luchinat, Rachel S. Kelly and Jessica Lasky-Su, Paige Lacy, and Angela Rogers. Relationships of metabolomics with drugs are highlighted by Robert Verpoorte (natural products drug discovery), by Oscar Millet and by Turano and Luchinat (perspectives in precision medicine) and by Daniel L. Hertz (drug-induced peripheral neuropathy). From the above list of diverse topics, we believe this book has interdisciplinary appeal and scholars with an interest in the role of metabolomics in achieving precision medicine will find it of particular or special interest.
Keywords	Pharmacology ; Biochemical markers ; Cytology ; Analytical biochemistry
Language	English
Size	1 Online-Ressource (VIII, 384 Seiten), Illustrationen
Publisher	Springer
Publishing place	Cham
Publishing country	Switzerland
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
HBZ-ID	HT021777394
ISBN	978-3-031-26859-5 ; 9783031268588 ; 3-031-26859-8 ; 303126858X
DOI	10.1007/978-3-031-26859-5
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: The gut microbiome in ARDS: from the "whether" and "what" to the "how".

Bongers, Kale S / Stringer, Kathleen A / Dickson, Robert P

The European respiratory journal

2023 Volume 61, Issue 2

MeSH term(s)	Animals ; Mice ; Gastrointestinal Microbiome ; Succinic Acid ; Acute Lung Injury ; Succinates ; Respiratory Distress Syndrome ; Ischemia
Chemical Substances	Succinic Acid (AB6MNQ6J6L) ; Succinates
Language	English
Publishing date	2023-02-16
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.02233-2022
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Zs.A 2322: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 292: Show issues

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Article: Clofazimine-Mediated, Age-Related Changes in Skeletal Muscle Mitochondrial Metabolites.

Diaz-Espinosa, Jennifer / Stringer, Kathleen A / Rosania, Gus R

Metabolites

2023 Volume 13, Issue 5

Abstract: Mitochondrial health declines with age, and older patients can demonstrate dysfunction in mitochondrial-rich tissues, such as cardiac and skeletal muscle. Aged mitochondria may make older adults more susceptible to adverse drug reactions (ADRs). We ... ...

Abstract	Mitochondrial health declines with age, and older patients can demonstrate dysfunction in mitochondrial-rich tissues, such as cardiac and skeletal muscle. Aged mitochondria may make older adults more susceptible to adverse drug reactions (ADRs). We assessed mitochondrial metabolic function by measuring two metabolites, l-carnitine and acetylcarnitine, to determine their effectiveness as candidate clinical biomarkers for age-related, drug-induced alterations in mitochondrial metabolism. To study age- and medication-related changes in mitochondrial metabolism, we administered the FDA-approved mitochondriotropic drug, clofazimine (CFZ), or vehicle for 8 weeks to young (4-week-old) and old (61-week-old) male C57BL/6J mice. At the end of treatment, whole blood and cardiac and skeletal muscle were analyzed for l-carnitine, acetylcarnitine, and CFZ levels; muscle function was measured via a treadmill test. No differences were found in blood or cardiac carnitine levels of CFZ-treated mice, but CFZ-treated mice displayed lost body mass and alterations in endurance and levels of skeletal muscle mitochondrial metabolites. These findings demonstrate the age-related susceptibility of the skeletal muscle to mitochondria drug toxicity. Since drug-induced alterations in mitochondrial metabolism in skeletal muscle were not reflected in the blood by l-carnitine or acetylcarnitine levels, drug-induced catabolism and changes in muscle function appear more relevant to stratifying individuals at increased risk for ADRs.
Language	English
Publishing date	2023-05-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo13050671
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Conference proceedings: Advances in the treatment of acute coronary syndromes

Stringer, Kathleen A.

focus on low-molecular-weight heparins ; based on the proceedings of a roundtable meeting

(Pharmacotherapy ; 19,9, Pt. 2)

1999

Author's details	guest ed. Kathleen A. Stringer
Series title	Pharmacotherapy ; 19,9, Pt. 2
Collection
Language	English
Size	S. 139S - 160S : Ill., graph. Darst.
Publisher	Pharmacotherapy Publ
Publishing place	Boston, MA
Publishing country	United States
Document type	Book ; Conference proceedings
HBZ-ID	HT011089233
Database	Catalogue ZB MED Medicine, Health

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Zs A 1738 -19,9,Pt.2-	not available for loan	Zeitschriften-Lesesaal

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Article: Distinguishing the Concentration- vs. Bioaccumulation-Dependent Immunological and Metabolic Effects of Clofazimine.

Willmer, Andrew R / Diaz-Espinosa, Jennifer / Zhou, Austin / Stringer, Kathleen A / Rosania, Gus R

Pharmaceutics

2023 Volume 15, Issue 9

Abstract: The antimycobacterial drug clofazimine (CFZ) is used as a single agent at high doses, to suppress the exaggerated inflammation associated with leprosy. Paradoxically, increasing doses of CFZ leads to bioaccumulation of CFZ in the spleen and other organs ... ...

Abstract	The antimycobacterial drug clofazimine (CFZ) is used as a single agent at high doses, to suppress the exaggerated inflammation associated with leprosy. Paradoxically, increasing doses of CFZ leads to bioaccumulation of CFZ in the spleen and other organs under physiologically relevant dosing regimens, without accompanying dose-dependent elevation in the concentrations of the circulating drug in the blood. In long-term oral dosing regimens, CFZ induces immunological and metabolic changes resulting in splenomegaly, while the mass of other organs decreases or remains unchanged. As an organ that extensively sequesters CFZ as insoluble drug precipitates, the spleen likely influences drug-induced inflammatory signaling. To probe the role of systemic drug concentrations vs. drug bioaccumulation in the spleen, healthy mice were treated with six different dosing regimens. A subgroup of these mice underwent surgical splenectomies prior to drug treatment to assess the bioaccumulation-dependent changes in immune system signaling and immune-system-mediated drug distribution. Under increasing drug loading, the spleen was observed to grow up to six times in size, sequestering over 10% of the total drug load. Interestingly, when the spleen was removed prior to CFZ administration, drug distribution in the rest of the organism was unaffected. However, there were profound cytokine elevations in the serum of asplenic CFZ-treated mice, indicating that the spleen is primarily involved in suppressing the inflammatory signaling mechanisms that are upregulated during CFZ bioaccumulation. Thus, beyond its role in drug sequestration, the spleen actively modulates the systemic effect of CFZ on the immune system, without impacting its blood concentrations or distribution to the rest of the organism.
Language	English
Publishing date	2023-09-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15092350
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Book ; Conference proceedings: The role of thrombolytics in acute myocardial infarction management

Stringer, Kathleen A.

where are we headed? ; Based on proceedings of a symposium presented during the American Society of Health-System Pharmacists Midyear Clinical Meeting, December 6, 1995 [Las Vegas]

(Pharmacotherapy ; 16,5, Pt. 2 = Suppl.)

1996

Event/congress	Midyear Clinical Meeting (1995, LasVegasNev.)
Author's details	guest ed. Kathleen A. Stringer
Series title	Pharmacotherapy ; 16,5, Pt. 2 = Suppl.
Collection
Keywords	Fibrinolytic Agents / therapeutic use / congresses ; Myocardial Infarction / drug therapy / congresses
Language	English
Size	S. 118S - 140S : Ill.
Publisher	Pharmacotherapy Publ
Publishing place	Boston, MA
Publishing country	United States
Document type	Book ; Conference proceedings
HBZ-ID	HT007490300
Database	Catalogue ZB MED Medicine, Health

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Zs A 1738 -16,5,Pt.2-	not available for loan	Zeitschriften-Lesesaal

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Article ; Online: Excluded Volume and Weak Interactions in Crowded Solutions Modulate Conformations and RNA Binding of an Intrinsically Disordered Tail.

Stringer, Madison A / Cubuk, Jasmine / Incicco, J Jeremías / Roy, Debjit / Hall, Kathleen B / Stuchell-Brereton, Melissa D / Soranno, Andrea

The journal of physical chemistry. B

2023 Volume 127, Issue 26, Page(s) 5837–5849

Abstract: The cellular milieu is a solution crowded with a significant concentration of different components (proteins, nucleic acids, metabolites, ...

Abstract	The cellular milieu is a solution crowded with a significant concentration of different components (proteins, nucleic acids, metabolites,
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Protein Conformation ; Polyethylene Glycols/chemistry ; RNA ; Nucleocapsid Proteins
Chemical Substances	Polyethylene Glycols (3WJQ0SDW1A) ; RNA (63231-63-0) ; Nucleocapsid Proteins
Language	English
Publishing date	2023-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1520-5207
ISSN (online)	1520-5207
DOI	10.1021/acs.jpcb.3c02356
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Kidney function as a key driver of the pharmacokinetic response to high-dose L-carnitine in septic shock.

Jennaro, Theodore S / Puskarich, Michael A / Flott, Thomas L / McLellan, Laura A / Jones, Alan E / Pai, Manjunath P / Stringer, Kathleen A

Pharmacotherapy

2023 Volume 43, Issue 12, Page(s) 1240–1250

Abstract: Study objective: Levocarnitine (L-carnitine) has shown promise as a metabolic-therapeutic for septic shock, where mortality approaches 40%. However, high-dose (≥ 6 grams) intravenous supplementation results in a broad range of serum concentrations. We ... ...

Abstract	Study objective: Levocarnitine (L-carnitine) has shown promise as a metabolic-therapeutic for septic shock, where mortality approaches 40%. However, high-dose (≥ 6 grams) intravenous supplementation results in a broad range of serum concentrations. We sought to describe the population pharmacokinetics (PK) of high-dose L-carnitine, test various estimates of kidney function, and assess the correlation of PK parameters with pre-treatment metabolites in describing drug response for patients with septic shock. Design: Population PK analysis was done with baseline normalized concentrations using nonlinear mixed effect models in the modeling platform Monolix. Various estimates of kidney function, patient demographics, dose received, and organ dysfunction were tested as population covariates. Data source: We leveraged serum samples and metabolomics data from a phase II trial of L-carnitine in vasopressor-dependent septic shock. Serum was collected at baseline (T0); end-of-infusion (T12); and 24, 48, and 72 h after treatment initiation. Patients and intervention: Patients were adaptively randomized to receive intravenous L-carnitine (6 grams, 12 grams, or 18 grams) or placebo. Measurements and main results: The final dataset included 542 serum samples from 130 patients randomized to L-carnitine. A two-compartment model with linear elimination and a fixed volume of distribution (17.1 liters) best described the data and served as a base structural model. Kidney function estimates as a covariate on the elimination rate constant (k) reliably improved model fit. Estimated glomerular filtration rate (eGFR), based on the 2021 Chronic Kidney Disease Epidemiology collaboration (CKD-EPI) equation with creatinine and cystatin C, outperformed creatinine clearance (Cockcroft-Gault) and older CKD-EPI equations that use an adjustment for self-identified race. Conclusions: High-dose L-carnitine supplementation is well-described by a two-compartment population PK model in patients with septic shock. Kidney function estimates that leverage cystatin C provided superior model fit. Future investigations into high-dose L-carnitine supplementation should consider baseline metabolic status and dose adjustments based on renal function over a fixed or weight-based dosing paradigm.
MeSH term(s)	Humans ; Cystatin C ; Carnitine ; Shock, Septic/drug therapy ; Creatinine ; Glomerular Filtration Rate/physiology ; Renal Insufficiency, Chronic ; Kidney
Chemical Substances	Cystatin C ; Carnitine (S7UI8SM58A) ; Creatinine (AYI8EX34EU)
Language	English
Publishing date	2023-10-11
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	603158-4
ISSN	1875-9114 ; 0277-0008
ISSN (online)	1875-9114
ISSN	0277-0008
DOI	10.1002/phar.2882
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Zs.A 1738: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 585: Show issues

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Article ; Online: Co-occurrence and metabolic biomarkers of sensory and motor subtypes of peripheral neuropathy from paclitaxel.

Chen, Ciao-Sin / Smith, Ellen M Lavoie / Stringer, Kathleen A / Henry, N Lynn / Hertz, Daniel L

Breast cancer research and treatment

2022 Volume 194, Issue 3, Page(s) 551–560

Abstract: Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is the major treatment-limiting toxicity of paclitaxel, which predominantly presents as sensory symptoms, with motor symptoms in some patients. Differentiating CIPN into subtypes has been ... ...

Abstract	Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is the major treatment-limiting toxicity of paclitaxel, which predominantly presents as sensory symptoms, with motor symptoms in some patients. Differentiating CIPN into subtypes has been recommended to direct CIPN research. The objective of this study was to investigate whether sensory and motor CIPN are distinct subtypes with different predictive biomarkers in patients with breast cancer receiving paclitaxel. Methods: Data were from a prospective cohort of 60 patients with breast cancer receiving up to 12 weekly infusions of 80 mg/m Results: More sensory than motor CIPN was found (CIPN Conclusion: Our findings suggest that sensory and motor CIPN co-occur and may not have differentiating metabolic biomarkers. These findings need to be validated in larger cohorts of patients treated with paclitaxel and other neurotoxic agents to determine the optimal approach to predict, prevent, and treat CIPN and improve patients' outcomes.
MeSH term(s)	Antineoplastic Agents/adverse effects ; Breast Neoplasms/drug therapy ; Female ; Humans ; Paclitaxel/adverse effects ; Peripheral Nervous System Diseases/chemically induced ; Prospective Studies ; Quality of Life
Chemical Substances	Antineoplastic Agents ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2022-06-28
Publishing country	Netherlands
Document type	Clinical Study ; Journal Article
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-022-06652-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Database screening as a strategy to identify endogenous candidate metabolites to probe and assess mitochondrial drug toxicity.

De la Rosa, Mery Vet George / Patel, Dipali / McCann, Marc R / Stringer, Kathleen A / Rosania, Gus R

Scientific reports

2023 Volume 13, Issue 1, Page(s) 22013

Abstract: Adverse drug reactions (ADRs) are considered an inherent risk of medication use, and some ADRs have been associated with off-target drug interactions with mitochondria. Metabolites that reflect mitochondrial function may help identify patients at risk of ...

Abstract	Adverse drug reactions (ADRs) are considered an inherent risk of medication use, and some ADRs have been associated with off-target drug interactions with mitochondria. Metabolites that reflect mitochondrial function may help identify patients at risk of mitochondrial toxicity. We employed a database strategy to identify candidate mitochondrial metabolites that could be clinically useful to identify individuals at increased risk of mitochondrial-related ADRs. This led to L-carnitine being identified as the candidate mitochondrial metabolite. L-carnitine, its acetylated metabolite, acetylcarnitine and other acylcarnitines are mitochondrial biomarkers used to detect inborn errors of metabolism. We hypothesized that changes in L-carnitine disposition, induced by a "challenge test" of intravenous L-carnitine, could identify mitochondrial-related ADRs by provoking variation in L-carnitine and/or acetylcarnitine blood levels. To test this hypothesis, we induced mitochondrial drug toxicity with clofazimine (CFZ) in a mouse model. Following CFZ treatment, mice received an L-carnitine "challenge test". CFZ-induced changes in weight were consistent with previous work and reflect CFZ-induced catabolism. L-carnitine induced differences in whole blood acetylcarnitine concentrations in a manner that was dependent on CFZ treatment. This supports the usefulness of a database strategy for the discovery of candidate metabolite biomarkers of drug toxicity and substantiates the potential of the L-carnitine "challenge test" as a "probe" to identify drug-related toxicological manifestations.
MeSH term(s)	Humans ; Mice ; Animals ; Acetylcarnitine/metabolism ; Carnitine/metabolism ; Mitochondria/metabolism ; Clofazimine/metabolism ; Drug-Related Side Effects and Adverse Reactions/metabolism ; Biomarkers/metabolism
Chemical Substances	Acetylcarnitine (6DH1W9VH8Q) ; Carnitine (S7UI8SM58A) ; Clofazimine (D959AE5USF) ; Biomarkers
Language	English
Publishing date	2023-12-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-49443-0
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