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Pharmaceuticals
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Biomarkers
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Biomarkers

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (30 November 2009) | Viewed by 51554

Special Issue Editors

Prof. Dr. Subodh Verma

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Guest Editor
Canada Research Chair in Atherosclerosis, Department of Surgery, University of Toronto Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, CanadaCanada
Interests: atherosclerosis; vasoactive factors; endothelial function; insulin resistance; vascular biology and diabetes
Dr. Hwee Teoh

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Guest Editor
Division of Cardiac Surgery, Terrence Donnelly Research Laboratories, Cardiometabolic Research Initiative, Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael\'s Hospital, Toronto, ON, Canada

Keywords

  • C-reactive protein
  • adipokines
  • endothelin
  • cholesterol
  • apolipoproteins

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Published Papers (4 papers)

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Research

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Article
Real Time Imaging of Biomarkers in the Parkinson's Brain Using Mini-Implantable Biosensors. II. Pharmaceutical Therapy with Bromocriptine
by Patricia A. Broderick and Edwin H. Kolodny
Pharmaceuticals 2009, 2(3), 236-249; https://doi.org/10.3390/ph2030236 - 22 Dec 2009
Cited by 5 | Viewed by 10963
Abstract
We used Neuromolecular Imaging (NMI) and trademarked BRODERICK PROBE® mini-implantable biosensors, to selectively and separately detect neurotransmitters in vivo, on line, within seconds in the dorsal striatal brain of the Parkinson’s Disease (PD) animal model. We directly compared our results derived [...] Read more.
We used Neuromolecular Imaging (NMI) and trademarked BRODERICK PROBE® mini-implantable biosensors, to selectively and separately detect neurotransmitters in vivo, on line, within seconds in the dorsal striatal brain of the Parkinson’s Disease (PD) animal model. We directly compared our results derived from PD to the normal striatal brain of the non-Parkinson’s Disease (non-PD) animal. This advanced biotechnology enabled the imaging of dopamine (DA), serotonin (5-HT), homovanillic acid (HVA) a metabolite of DA, L-tryptophan (L-TP) a precursor to 5-HT and peptides, dynorphin A 1-17 (Dyn A) and somatostatin (somatostatin releasing inhibitory factor) (SRIF). Each neurotransmitter and neurochemical was imaged at a signature electroactive oxidation/half-wave potential in dorsal striatum of the PD as compared with the non-PD animal. Both endogenous and bromocriptine-treated neurochemical profiles in PD and non-PD were imaged using the same experimental paradigm and detection sensitivities. Results showed that we have found significant neurotransmitter peptide biomarkers in the dorsal striatal brain of endogenous and bromocriptine-treated PD animals. The peptide biomarkers were not imaged in dorsal striatal brain of non-PD animals, either endogenously or bromocriptine-treated. These findings provide new pharmacotherapeutic strategies for PD patients. Thus, our findings are highly applicable to the clinical treatment of PD. Full article
(This article belongs to the Special Issue Biomarkers)
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Review

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Review
Lp-PLA2 Inhibition—The Atherosclerosis Panacea?
by Mahir Karakas and Wolfgang Koenig
Pharmaceuticals 2010, 3(5), 1360-1373; https://doi.org/10.3390/ph3051360 - 29 Apr 2010
Cited by 16 | Viewed by 15688
Abstract
Based on the complex pathophysiology of atherosclerosis, a large number of biomarkers that relate to lipids, inflammation, immunity, thrombosis and hemostasis, have been investigated experimentally, in epidemiologic studies and in clinical trials. Interest focuses on their potential role to aid in risk stratification, [...] Read more.
Based on the complex pathophysiology of atherosclerosis, a large number of biomarkers that relate to lipids, inflammation, immunity, thrombosis and hemostasis, have been investigated experimentally, in epidemiologic studies and in clinical trials. Interest focuses on their potential role to aid in risk stratification, as possible surrogate markers of atherosclerosis, and potential targets for therapy. More recently, one lipid associated biomarker, lipoprotein-associated phospholipase A2 (Lp-PLA2), has gained considerable interest. In addition to a plausible pathophysiological role by generating pro-inflammatory and pro-atherogenic compounds from oxidized LDL in the vessel wall, there is a large, fairly consistent epidemiological database indicating that increased levels of Lp-PLA2 mass or activity are associated with increased risk for cardiovascular outcomes; such data further suggest that it might improve risk stratification. In addition, clinical studies indicate that increased Lp-PLA2 levels are associated with endothelial dysfunction. Moreover, it may also serve as an interesting therapeutic target, since a specific inhibitor of the enzyme is available with promising animal data and initial positive data in humans. Recent experimental data from a hyperlipidemic diabetic pig model strongly suggest that increased Lp-PLA2 in the vessel wall is associated with a more vulnerable plaque phenotype which can be modulated by inhibiting Lp-PLA2 activity. A biomarker study in more than 1,000 patients with CHD over three months has demonstrated a positive effect on various inflammatory molecules. In addition, an imaging study using IVUS based modalities (greyscale, virtual histology, and palpography) together with a panel of biomarkers (IBIS-2) has been done in more than 300 patients with CHD treated over 12 months and results indicate that the progression of the necrotic core of the plaque can be retarded. Inhibition of the pro-atherogenic and pro-inflammatory effects of Lp-PLA2 may therefore contribute to decrease the residual risk in high risk patients already on polypharmacotherapy. This hypothesis is now being tested in two large phase 3 clinical trials. Thus, Lp-PLA2 indeed may represent a biomarker and a promising target for intervention. Full article
(This article belongs to the Special Issue Biomarkers)
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2256 KiB  
Review
Molecular Model of Plasma PAF Acetylhydrolase-Lipoprotein Association: Insights from the Structure
by Prabhavathi Srinivasan and Brian J. Bahnson
Pharmaceuticals 2010, 3(3), 541-557; https://doi.org/10.3390/ph3030541 - 8 Mar 2010
Cited by 11 | Viewed by 13964
Abstract
Plasma platelet-activating factor acetylhydrolase (PAF-AH), also called lipoprotein-associated phospholipase A2 (Lp-PLA2), is a group VIIA PLA2 enzyme that catalyzes the hydrolysis of PAF and certain oxidized phospholipids. Although the role of PAF-AH as a pro- or anti-atherosclerotic enzyme is [...] Read more.
Plasma platelet-activating factor acetylhydrolase (PAF-AH), also called lipoprotein-associated phospholipase A2 (Lp-PLA2), is a group VIIA PLA2 enzyme that catalyzes the hydrolysis of PAF and certain oxidized phospholipids. Although the role of PAF-AH as a pro- or anti-atherosclerotic enzyme is highly debated, several studies have shown it to be an independent marker of cardiovascular diseases. In humans the majority of plasma PAF-AH is bound to LDL and a smaller portion to HDL; the majority of the enzyme being associated with small dense LDL and VHDL-1 subclasses. Several studies suggest that the anti- or pro-atherosclerotic tendency of PAF-AH might be dependent on the type of lipoprotein it is associated with. Amino acid residues in PAF-AH necessary for binding to LDL and HDL have been identified. However our understanding of the interaction of PAF-AH with LDL and HDL is still incomplete. In this review we present an overview of what is already known about the interaction of PAF-AH with lipoprotein particles, and we pose questions that are yet to be answered. The recently solved crystal structure of PAF-AH, along with functional work done by others is used as a guide to develop a model of interaction of PAF-AH with lipoprotein particles. Full article
(This article belongs to the Special Issue Biomarkers)
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349 KiB  
Review
Functional Consequences of Mutations and Polymorphisms in the Coding Region of the PAF Acetylhydrolase (PAF-AH) Gene
by Diana M. Stafforini
Pharmaceuticals 2009, 2(3), 94-117; https://doi.org/10.3390/ph2030094 - 20 Nov 2009
Cited by 18 | Viewed by 10455
Abstract
In the past several years a number of alterations in the PAFAH/PLA2G7/LpPLA2 gene have been described. These include inactivating mutations, polymorphisms in the coding region, and other genetic changes located in promoter and intronic regions of the gene. The consequences [...] Read more.
In the past several years a number of alterations in the PAFAH/PLA2G7/LpPLA2 gene have been described. These include inactivating mutations, polymorphisms in the coding region, and other genetic changes located in promoter and intronic regions of the gene. The consequences associated with these genetic variations have been evaluated from different perspectives, including in vitro biochemical and molecular studies and clinical analyses in human subjects. This review highlights the current state of the field and suggests new approaches that can be used to evaluate functional consequences associated with mutations and polymorphisms in the PAF-AH gene. Full article
(This article belongs to the Special Issue Biomarkers)
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