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  1. Article: The

    Fitzgerald, Hannah K / O'Rourke, Sinead A / Desmond, Eva / Neto, Nuno G B / Monaghan, Michael G / Tosetto, Miriam / Doherty, Jayne / Ryan, Elizabeth J / Doherty, Glen A / Nolan, Derek P / Fletcher, Jean M / Dunne, Aisling

    Antioxidants (Basel, Switzerland)

    2022  Volume 11, Issue 1

    Abstract: The extracellular parasite and causative agent of African sleeping ... ...

    Abstract The extracellular parasite and causative agent of African sleeping sickness
    Language English
    Publishing date 2022-01-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox11010164
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: An alternative view of the role of clinical pharmacology.

    Fitzgerald, J Desmond

    British journal of clinical pharmacology

    2011  Volume 71, Issue 3, Page(s) 471–472

    MeSH term(s) Curriculum/trends ; Education, Medical/trends ; Europe ; Humans ; Pharmacology, Clinical/education ; United Kingdom
    Language English
    Publishing date 2011-02-01
    Publishing country England
    Document type Letter
    ZDB-ID 188974-6
    ISSN 1365-2125 ; 0306-5251 ; 0264-3774
    ISSN (online) 1365-2125
    ISSN 0306-5251 ; 0264-3774
    DOI 10.1111/j.1365-2125.2010.03842.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Lack of Bioequivalence Among Low-dose, Enteric-coated Aspirin Preparations.

    Cox, Dermot / Fitzgerald, Desmond J

    Clinical pharmacology and therapeutics

    2017  Volume 103, Issue 6, Page(s) 1047–1051

    Abstract: Low-dose aspirin (75 mg or 81 mg) is considered to be the lowest effective dose for cardiovascular protection; however, the use of enteric preparations has created a source of variability in bioavailability. As part of regulatory requirements, we carried ...

    Abstract Low-dose aspirin (75 mg or 81 mg) is considered to be the lowest effective dose for cardiovascular protection; however, the use of enteric preparations has created a source of variability in bioavailability. As part of regulatory requirements, we carried out bioequivalence tests for two 75 mg enteric-coated aspirin preparations (Caprin and Protek) using Nu-Seals 75 mg aspirin as the comparator. The primary endpoint was serum thromboxane levels after 14 days of treatment. Protek failed to meet bioequivalence, as it was significantly less effective than Nu-Seals. In contrast, Caprin was not bioequivalent with Nu-Seals but as it was more effective it was granted approval. However, 75 mg plain aspirin was found to be more effective than Nu-Seals at inhibiting serum thromboxane production. Thus, there is significant variation in the ability of low-dose aspirin preparations to inhibit serum thromboxane production.
    MeSH term(s) Arachidonic Acid/metabolism ; Aspirin/administration & dosage ; Aspirin/pharmacokinetics ; Dose-Response Relationship, Drug ; Humans ; Peptide Fragments/metabolism ; Platelet Aggregation Inhibitors/administration & dosage ; Platelet Aggregation Inhibitors/pharmacokinetics ; Tablets, Enteric-Coated ; Therapeutic Equivalency ; Thromboxane A2/metabolism
    Chemical Substances Peptide Fragments ; Platelet Aggregation Inhibitors ; Tablets, Enteric-Coated ; thrombin receptor peptide SFLLRNP (145229-76-1) ; Arachidonic Acid (27YG812J1I) ; Thromboxane A2 (57576-52-0) ; Aspirin (R16CO5Y76E)
    Language English
    Publishing date 2017-10-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 123793-7
    ISSN 1532-6535 ; 0009-9236
    ISSN (online) 1532-6535
    ISSN 0009-9236
    DOI 10.1002/cpt.874
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: 15-Deoxy-Δ

    Marcone, Simone / Evans, Paul / Fitzgerald, Desmond J

    Frontiers in immunology

    2016  Volume 7, Page(s) 459

    Abstract: ... 15-Deoxy- ... ...

    Abstract 15-Deoxy-Δ
    Language English
    Publishing date 2016
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2016.00459
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  5. Article ; Online: Historical lessons in translational medicine: cyclooxygenase inhibition and P2Y12 antagonism.

    Fitzgerald, Desmond J / Fitzgerald, Garret A

    Circulation research

    2013  Volume 112, Issue 1, Page(s) 174–194

    Abstract: The development of drugs that inhibit platelets has been driven by a combination of clinical insights, fundamental science, and sheer luck. The process has evolved as the days of stumbling on therapeutic gems, such as aspirin, have long passed and have ... ...

    Abstract The development of drugs that inhibit platelets has been driven by a combination of clinical insights, fundamental science, and sheer luck. The process has evolved as the days of stumbling on therapeutic gems, such as aspirin, have long passed and have been replaced by an arduous process in which a drug is designed to target a specific protein implicated in a well-characterized pathophysiological process, or so we would like to believe. The development of antiplatelet therapy illustrates the importance of understanding the mechanisms of disease and the pharmacology of the compounds we develop, coupled with careful clinical experimentation and observation and, yes, still, a fair bit of luck.
    MeSH term(s) Animals ; Aspirin/therapeutic use ; Blood Platelets/drug effects ; Blood Platelets/enzymology ; Cardiovascular Diseases/blood ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/history ; Clopidogrel ; Cyclooxygenase Inhibitors/administration & dosage ; Cyclooxygenase Inhibitors/adverse effects ; Cyclooxygenase Inhibitors/history ; Cyclooxygenase Inhibitors/therapeutic use ; Dose-Response Relationship, Drug ; Drug Discovery/history ; Drug Resistance ; Evidence-Based Medicine ; History, 20th Century ; History, 21st Century ; Humans ; Pharmacogenetics ; Platelet Aggregation Inhibitors/administration & dosage ; Platelet Aggregation Inhibitors/adverse effects ; Platelet Aggregation Inhibitors/history ; Platelet Aggregation Inhibitors/therapeutic use ; Purinergic P2Y Receptor Antagonists/administration & dosage ; Purinergic P2Y Receptor Antagonists/adverse effects ; Purinergic P2Y Receptor Antagonists/history ; Purinergic P2Y Receptor Antagonists/therapeutic use ; Ticlopidine/analogs & derivatives ; Ticlopidine/therapeutic use ; Translational Medical Research/history
    Chemical Substances Cyclooxygenase Inhibitors ; Platelet Aggregation Inhibitors ; Purinergic P2Y Receptor Antagonists ; Clopidogrel (A74586SNO7) ; Ticlopidine (OM90ZUW7M1) ; Aspirin (R16CO5Y76E)
    Language English
    Publishing date 2013-01-03
    Publishing country United States
    Document type Historical Article ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.111.300271
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  6. Article ; Online: The Academic Facility Is Associated with Higher Utilization of Esophagectomy and Improved Overall Survival for Esophageal Carcinoma.

    Merritt, Robert E / Abdel-Rasoul, Mahmoud / Fitzgerald, Morgan / D'Souza, Desmond M / Kneuertz, Peter J

    Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract

    2020  Volume 25, Issue 7, Page(s) 1677–1689

    Abstract: Background: Operable esophageal carcinoma is potentially curable with surgical resection. The short-term outcomes and overall survival rate for operable esophageal carcinoma may be impacted by the healthcare facility type where patients receive care.: ...

    Abstract Background: Operable esophageal carcinoma is potentially curable with surgical resection. The short-term outcomes and overall survival rate for operable esophageal carcinoma may be impacted by the healthcare facility type where patients receive care.
    Methods: A total of 37, 271 cases with the American Joint Committee on Cancer clinical stage I, II, and III esophageal carcinoma that were reported to the National Cancer Data Base at over 12,721 facilities were analyzed. Healthcare facilities were dichotomized into the community and academic facility types. Marginal multivariable Cox proportional hazard models were used to evaluate differences in overall survival between facility types, which accounted for facility esophageal cancer volume. Propensity score methodology with inverse probability of treatment weighting was used to adjust for patient related baseline differences between facility types.
    Results: Patients with clinical stage I-III esophageal carcinoma who underwent esophagectomy at academic healthcare facilities had a significantly better overall survival compared with patients who underwent esophagectomy at community healthcare facilities [HR = 0.89: CI [0.84-0.95] (p = 0.0005)]. The rate of esophagectomy was significantly higher at the academic facilities (49.0% versus 26.5%; p < 0.0001). The 30-day and 90-day mortality rates for esophagectomy were significantly better for patients who underwent esophagectomy for esophageal cancer at the academic facility types.
    Conclusion: Patients with clinical stage I-III esophageal carcinoma who received care at academic facility types had significantly better overall survival compared with community facility types. The utilization of esophagectomy was significantly higher and the short-term surgical outcomes were better for patients treated at academic facility types.
    MeSH term(s) Carcinoma, Squamous Cell/surgery ; Esophageal Neoplasms/pathology ; Esophageal Neoplasms/surgery ; Esophagectomy ; Humans ; Neoplasm Staging ; Propensity Score ; Retrospective Studies ; Survival Rate ; Treatment Outcome
    Language English
    Publishing date 2020-10-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2012365-6
    ISSN 1873-4626 ; 1934-3213 ; 1091-255X
    ISSN (online) 1873-4626 ; 1934-3213
    ISSN 1091-255X
    DOI 10.1007/s11605-020-04817-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The Academic Facility Type Is Associated With Improved Overall Survival for Early-Stage Lung Cancer.

    Merritt, Robert E / Abdel-Rasoul, Mahmoud / Fitzgerald, Morgan / D'Souza, Desmond M / Kneuertz, Peter J

    The Annals of thoracic surgery

    2020  Volume 111, Issue 1, Page(s) 261–268

    Abstract: Background: Early-stage non-small cell lung cancer (NSCLC) is potentially curable with surgical resection. The overall survival rate for early-stage NSCLC may be determined by the healthcare facility type where patients receive their lung cancer ... ...

    Abstract Background: Early-stage non-small cell lung cancer (NSCLC) is potentially curable with surgical resection. The overall survival rate for early-stage NSCLC may be determined by the healthcare facility type where patients receive their lung cancer treatment.
    Methods: A total of 103,748 cases with the American Joint Committee on Cancer clinical stage I and II NSCLC that were reported to the National Cancer Database at over 1150 facilities were analyzed in this study. Healthcare facilities were dichotomized into the community and academic facility types. Marginal multivariable Cox proportional hazards models were used to evaluate differences in overall survival. Propensity score methodology with inverse probability of treatment weighting was used to adjust for facility volume and patient-related baseline differences between facility types.
    Results: Patients with early-stage NSCLC who were treated at academic facility types had a significantly better median overall survival (63.2 months) compared with patients who received care at community healthcare facilities (54.2 months) (hazard ratio, 0.86; 95% confidence interval, 0.82-0.91; P < .0001). The surgical quality outcomes for NSCLC surgery, including 30-day mortality, 90-day mortality, and the median number of lymph nodes removed were significantly better for patients treated at the academic facility types.
    Conclusions: Patients with early-stage NSCLC who were treated at academic facility types had a significantly higher overall median survival compared with patients treated at community facility types. The short-term surgical quality outcomes were significantly better for patients who underwent surgery for early-stage NSCLC at academic facility types.
    MeSH term(s) Aged ; Carcinoma, Non-Small-Cell Lung/mortality ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/surgery ; Female ; Health Facilities/classification ; Humans ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Lung Neoplasms/surgery ; Male ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Survival Rate
    Language English
    Publishing date 2020-06-29
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 211007-6
    ISSN 1552-6259 ; 0003-4975
    ISSN (online) 1552-6259
    ISSN 0003-4975
    DOI 10.1016/j.athoracsur.2020.05.051
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  8. Article ; Online: Nomograms for Predicting Overall and Recurrence-free Survival From Pathologic Stage IA and IB Lung Cancer After Lobectomy.

    Merritt, Robert E / Abdel-Rasoul, Mahmoud / Fitzgerald, Morgan / D'Souza, Desmond M / Kneuertz, Peter J

    Clinical lung cancer

    2020  Volume 22, Issue 4, Page(s) e574–e583

    Abstract: Background: Stage I non-small-cell lung cancer (NSCLC) is potentially curable with surgical resection. Significant proportions of patients may still experience recurrence and death despite undergoing curative surgery. This study describes predictive ... ...

    Abstract Background: Stage I non-small-cell lung cancer (NSCLC) is potentially curable with surgical resection. Significant proportions of patients may still experience recurrence and death despite undergoing curative surgery. This study describes predictive nomograms for recurrence-free (RFS) and overall survival (OS) after lobectomy.
    Patients and methods: A total of 301 patients with the American Joint Committee on Cancer pathologic stage IA and IB NSCLC who underwent open, thoracoscopic, or robotic lobectomy from January 2011 to April 2017 were analyzed. Multivariate Cox proportional hazards regression models were used to create nomograms for OS and RFS. Kaplan-Meier survival curves were calculated for OS and RFS comparing high-risk and low-risk cohorts based on nomogram scores.
    Results: Histology (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.10-0.56; P = .002), lymphovascular invasion (HR, 0.46; 95% CI, 0.29-0.74; P = .001), smoking status (HR, 3.46; 95% CI, 1.25-9.55: P = .02), and total lymph nodes removed (HR, 1.05; 95% CI, 1.01-1.10; P = .021) were significant predictors for OS in a multivariate model. Lymphovascular invasion (HR, 0.55; 95% CI, 0.36-0.83; P = .0040), smoking status (HR, 2.56; 95% CI, 1.16-5.62; P = .02), total lymph nodes removed (HR, 1.04; 95% CI, 1.00-1.08; P = .029), and tumor size (HR, 1.30; 95% CI, 1.30-1.68; P = .047) were significant predictors of RFS in a multivariate model.
    Conclusion: Nomograms can predict OS and RFS for pathologic stage IA and IB NSCLC after lobectomy regardless of operative approach. The risk for death and recurrence after stratification by the nomogram scores may provide guidance regarding adjuvant therapy and surveillance.
    MeSH term(s) Aged ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/surgery ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/pathology ; Lung Neoplasms/surgery ; Lymphatic Metastasis/pathology ; Male ; Middle Aged ; Neoplasm Staging ; Nomograms ; Pneumonectomy/methods ; Retrospective Studies ; Robotic Surgical Procedures/methods ; Survival Rate ; Thoracoscopy/methods
    Language English
    Publishing date 2020-10-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2145146-1
    ISSN 1938-0690 ; 1525-7304
    ISSN (online) 1938-0690
    ISSN 1525-7304
    DOI 10.1016/j.cllc.2020.10.009
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  9. Article ; Online: Milk-derived bioactive peptides and their health promoting effects: a potential role in atherosclerosis.

    Marcone, Simone / Belton, Orina / Fitzgerald, Desmond J

    British journal of clinical pharmacology

    2016  Volume 83, Issue 1, Page(s) 152–162

    Abstract: Bioactive peptides derived from milk proteins are food components that, in addition to their nutritional value, retain many biological properties and have therapeutic effects in several health disorders, including cardiovascular disease. Amongst these, ... ...

    Abstract Bioactive peptides derived from milk proteins are food components that, in addition to their nutritional value, retain many biological properties and have therapeutic effects in several health disorders, including cardiovascular disease. Amongst these, atherosclerosis is the underlying cause of heart attack and strokes. It is a progressive dyslipidaemic and inflammatory disease where accumulation of oxidized lipids and inflammatory cells leads to the formation of an atherosclerotic plaque in the vessel wall. Milk-derived bioactive peptides can be released during gastrointestinal digestion, food processing or by enzymatic and bacterial fermentation and are considered to promote diverse beneficial effects such as lipid lowering, antihypertensive, immnomodulating, anti-inflammatory and antithrombotic effects. In this review, an overview of the diverse biological effects of these compounds is given, particularly focusing on their beneficial properties on cardiovascular disease and proposing novel mechanisms of action responsible for their bioactivity. Attempts to prevent cardiovascular diseases target modifications of several risk factors such as high blood pressure, obesity, high blood concentrations of lipids or insulin resistance. Milk-derived bioactive peptides are a source of health-enhancing components and the potential health benefit of these compounds has a growing commercial potential. Consequently, they have been incorporated as ingredients in functional foods, as dietary supplements and as pharmaceuticals to promote health and reduce risk of chronic diseases.
    MeSH term(s) Atherosclerosis/prevention & control ; Dietary Supplements ; Fermentation ; Humans ; Milk Proteins/chemistry ; Peptides/administration & dosage ; Peptides/isolation & purification ; Peptides/pharmacology
    Chemical Substances Milk Proteins ; Peptides
    Language English
    Publishing date 2016-06-17
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 188974-6
    ISSN 1365-2125 ; 0306-5251 ; 0264-3774
    ISSN (online) 1365-2125
    ISSN 0306-5251 ; 0264-3774
    DOI 10.1111/bcp.13002
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  10. Article ; Online: Proteomic identification of the candidate target proteins of 15-deoxy-delta12,14-prostaglandin J2.

    Marcone, Simone / Fitzgerald, Desmond J

    Proteomics

    2013  Volume 13, Issue 14, Page(s) 2135–2139

    Abstract: 15-Deoxy-delta12, 14-prostaglandin J(2) (15d-PGJ(2)) is an endogenous anti-inflammatory lipid ...

    Abstract 15-Deoxy-delta12, 14-prostaglandin J(2) (15d-PGJ(2)) is an endogenous anti-inflammatory lipid derived from PGD(2). One potential mechanism for its activity is the covalent modification of cellular proteins, via a reactive α,β-unsaturated carbonyl group in its cyclopentenone ring, which in turn alters protein function. In order to identify the candidate target proteins covalently modified by 15d-PGJ(2) in human aortic endothelial cell (EC), EC was treated with biotinylated-15d-PGJ(2), the modified proteins extracted by Neutravidin affinity-purification and the proteins identified by LTQ Orbitrap mass spectrometer. Classification of the 358 identified proteins was performed using PANTHER classification system (www.pantherdb.org), showing that the proteins mapped to metabolic process, cellular process, and transport activity. This protein data set highlights the potential for 15d-PGJ(2) to covalently modify cellular proteins and provides a source of data that will aid further studies on the mechanism of action of this endogenous regulator of inflammation.
    MeSH term(s) Cell Line ; Chromatography, Reverse-Phase ; Endothelial Cells/chemistry ; Endothelial Cells/metabolism ; Humans ; Prostaglandin D2/analogs & derivatives ; Prostaglandin D2/chemistry ; Prostaglandin D2/metabolism ; Proteins/analysis ; Proteins/chemistry ; Proteins/classification ; Proteins/metabolism ; Proteome/analysis ; Proteome/chemistry ; Proteome/metabolism ; Proteomics/methods ; Tandem Mass Spectrometry
    Chemical Substances 15-deoxy-delta(12,14)-prostaglandin J2 ; Proteins ; Proteome ; Prostaglandin D2 (RXY07S6CZ2)
    Language English
    Publishing date 2013-07
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2032093-0
    ISSN 1615-9861 ; 1615-9853
    ISSN (online) 1615-9861
    ISSN 1615-9853
    DOI 10.1002/pmic.201200289
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