ISSN (Print): 1381-6128
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Volume 24, 46 Issues, 2018
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ISSN (Print): 1381-6128
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Special Issue Submission
Thanks a lot for your continued support in publishing our article in various Bentham Journals. I believe, it is now around 3-4 years that Bentham has given me this opportunity and continued support in publishing my research and review articles.
13 Abstract Ahead of Print are available electronically
97 Articles Ahead of Print are available electronically
It has been absolute honor to serve as a guest editor for this special issue of Current Pharmaceutical Design. Inflammation is the common
pathological basis for age-related diseases such as cancer, neurodegenerative diseases, cardiovascular diseases, and diabetes. Life expectancy
is estimated to dramatically increase in the upcoming decades, and despite it should be a great accomplishment for our societies, the increase
of longevity is a significant challenge for the global economy because this increase leads to an enhance in the incidence of age-related diseases.
There is great interest by pharmaceutical/biotechnology industries to focus on drug development strategies for inflammatory-related
pathologies. Nowadays, anti-inflammatory therapeutics market is the major part of global pharmaceutical industries and is expected to grow.
The pharmaceutical industries are benefiting of academic inflammation research, and are adopting novel approaches in drug designing as key
strategies to gain additional market share. In fact, according with Allied Market Research report, the global anti-inflammatory market is expected
to garner $106.1 billion by 2020. However, still the challenge is to design new anti- inflammatory drug with lesser side effects.
This special issue will cover several inflammatory research areas. For example, a growing number of researchers have discovered various
signaling pathways that are associated with the initiation and progression of inflammation. An excellent manuscript by Yeung and Colleagues
 focus on classical inflammatory pathways: p38 MAPK, IL-6/JAK/STAT3 and PI3K; and a non-classical inflammatory pathway, the
Hippo. The molecular mechanisms, associated pathologies, selected drugs of these signaling pathways and limitations and potential risks of
anti-inflammatory drugs will be summarized. The central nervous system may be the target of several chronic inflammatory-related pathologies
where the inflammatory component acts either as a primary cause of the disease or as a secondary outcome of the tissue damage. An
outstanding manuscript by Degan and colleagues  summarize current data on Alzheimer’s disease, Parkinson’s disease, Huntington’s disease,
Amyotrophic Lateral Sclerosis, stroke and traumatic brain diseases and discuss the potential anti-inflammatory therapeutic approaches
acting at different levels and stages of the diseases.
Alcohol consumption causes comprehensive liver disorders, designated as Alcoholic Liver Disease (ALD). In an interesting manuscript
Lu and Cederbaum  summarize the consequences of liver damage, the relationship of CYP2E1/CYP2A5 and ALD development, the
mechanisms involved and recent advances, some unpublished data of cytochrome P450 enzymes dysregulation in inflammatory disease
states. Mucositis or inflammation of the mucosa that occurs throughout the alimentary tract from the mouth to anus, is a side effect associated
with the use of chemotherapy. Mahendran and colleagues  in an excellent reviews focus the pathobiology of chemotherapy-induced oral
and gastrointestinal mucositis and recent research examining the role of agents with anti-inflammatory activity in treatment and prevention of
the condition. The skin is the largest organ in the human body which function is to protect the body from external hazards. Skin inflammation
leads to skin aging that can eventually promote cellular damage and the development of cancer. An interesting manuscript by Kim and Lee
 summarize some proteins and signaling pathways involving in skin inflammation, which can be modulated by phytochemicals with the
purpose to attenuate skin inflammation.
Considerable progress has been made in the understanding of inflammatory mechanisms which may open new avenues for preparation of
novel anti-inflammatory drugs. Medicinal plants are promising sources for preparation of such novel drugs. Taking into consideration the
anti-inflammatory activities of a large group of medicinal plants, Kazemi and colleagues  remarkably describe recent advances in progresses
in understanding the molecular basis of inflammation, and presents the most important medicinal plants with anti-inflammatory activity.
Melatonin is an indolamine synthesized and secreted by the pineal gland and other extrapineal sources including immune system cells,
brain, skin and the gastrointestinal tract. Carrascal and colleagues  present very timely manuscript evaluating the use of melatonin in the
control of inflammation underlying the Alzheimer, Amiotrophic lateral, Multiple Sclerosis, Huntigton´s disease and ulcerative colitis. The
authors propose that these actions of melatonin are mediated through their receptors but also with their direct antioxidant action and melatonin's
ability to break the vicious cycle of ROS-inflammation.
The use of nanomedicine, nanoscale structures for drug delivery, exhibits a really high therapeutic potential in the field of neuroinflammation
therapy. In an excellent manuscript Cayero-Otero and colleagues  analyzes a wide variety of compounds as possible candidates to
cross the Blood-Brain Barrier (BBB) and reach the brain in sufficient concentration to be able to exert its effect. The authors also describe
PLGA nanoparticles as one of the most versatile drug delivery nanosystems, and other strategies, as direct intranasal administration (nose-tobrain),
novel viral vectors and novel implanted catheters. Computational biology approaches could be useful to design novel drugs for inflammation
treatment. Virtual screening involves applying computational methods to discover new ligands for biological structures from the
formation of large libraries composed of a large number of compounds. In an interesting manuscript Scotti and colleagues  illustrate different
studies employing a variety of virtual screening approaches to find molecules that have actions on important, diverse targets implicated in
Drug Delivery Systems and Drug Targeting
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Antibodies and Immunotherapeutics
In this special issue of Current Pharmaceutical Design, entitled: “Antimicrobial peptides as mediators of innate immunity”, the major
features of Antimicrobial Peptides (AMPs) are outlined. In particular, their classification, cellular sources, and biological properties in health
and disease are described. Finally, clinical applications of AMPs, as novel therapeutics in the course of infections caused by antibioticresistant
bacteria, fungi, protozoa and viruses as well as in cancer, are discussed.
Magrone et al.  at first review the phylogenic sources of AMPs as well as their anti-inflammatory and immunomodulating activities.
Moreover, lantibiotics, as new potential anti-infective drugs, are described. Authors also point out the ability of dietary bioactive principles
and food supplements to induce AMP production.
Pizzo et al.  place emphasis on the exploitation of structure, function and mechanisms of action exerted by AMPs in drug targeting. In
this review, cryptic AMPs are introduced as proteins hidden in their primary structure and, then, released by the host and/or bacterium proteases.
Their discovery has enlarged the spectrum of known AMPs, also allowing investigation of new functions and applications.
Drago-Serrano et al.  describe the role of Lactoferrin (LF) and lactoferricins (Lfcins) in the control of pathogens also in virtue of their
immune regulatory properties. LF and Lfcins are molecules of pharmacological interest and native LF and its N-terminus peptides seem to
have potential applications as adjunctive anti-infectious agents. Finally, these compounds have the property to retard tumor growth and attenuate
Chieosilapatham et al.  review the role played by human cathelicidin LL-37 in the modulation of innate immune response. Particularly,
LL-37 exerts pro- and anti-inflammatory activities, also inducing maturation, proliferation and regulation of apoptosis. Finally, according to
its anatomical distribution, LL-37 seems to play different roles in the regulation of innate immunity.
Kiatsurayanon et al.  illustrate the role of human beta-defensins (hBDs) in the maintenance of skin barriers. They exert a broad spectrum
of microbicidal activities also displaying several immunoregulatory activities in the course of skin infections and inflammation. A better
knowledge of hBD physiology may contribute to develop new therapeutic remedies in the course of skin barrier impairment, such as atopic
dermatitis and psoriasis.
Skovbakke et al.  outline the property of Formyl Peptide Receptors (FPRs) in mediating the immunomodulatory activities of AMPs
and peptidomimetics. In this framework, for their function neutrophils express FPRs which behave as targets of AMPs. On these bases, peptidomimetics
represent new molecules able to modulate neutrophil activities.
Adolph et al.  describe the function of intestinal Paneth cells as producers of AMPs finalized to the homeostatic control of microbiota.
Emphasis is placed on the alteration of Paneth cell function in inflammatory disease and, especially, in the course of ulcerative colitis and
Khurshid et al.  point out the unique structure of human defensins based on amino acid sequences bearing disulphide bridges which
allow their synthesis or natural production with the help of bacteria. In particular, in this review, the role exerted by oral defensins in health
and disease is stressed out.
Rivas-Santiago and Torres-Juarez  highlight the ability of AMPs to kill mycobacteria both in vitro and in vivo. Then, AMPs can be
used as an adjunctive therapy in the course of human tuberculosis. However, to avoid collateral effects depending on the multiple activities
exerted by AMPs, Authors suggest that certain features, such as comorbidity, family history and risk factors in patients with tuberculosis
should be taken into consideration prior to AMP therapy start.
Magrone et al.  emphasize the concept that AMPs in comparison to antibiotics possess a larger spectrum of antimicrobial activities
without inducing bacterial resistance. Therefore, their use in different clinical settings, even including septic shock is discussed. Finally, a
series of novel compounds derived from AMPs for their potential capacity to reinforce the immune response are illustrated.
Approximately 15 million babies are born preterm each year and one million die of complications of prematurity. As of the close of 2016,
the latest year for which data are available, the preterm birth rate rose for the second year in a row in the United States, and now stands at
9.8%. This setback in the US is likely tied to major lifestyle and environmental factors that have negatively impacted other health outcomes
Recent data indicate that increased obesity and oxidative stress lead to dysregulation of the immune response, which, in turn, leads to
disease. Inflammation, resulting from immune dysregulation, has been linked to cardiovascular, neurodegenerative and oncologic disorders.
Inflammation, in the absence or presence of microorganisms, is also the single most common driving force behind spontaneous preterm birth.
In this second volume of our “hot topics” issue focused on emerging pharmacotherapy for preterm birth (PTB), we move into the realm of
investigative approaches at the cutting edge of the field that target immune dysregulation. Recognizing that toll-like receptor 4 (TLR4) lies at
the crossroads of both infectious and sterile inflammatory pathways, Sarah Robertson et al. review the evidence supporting the targeting of
toll-like receptor 4 (TLR4) to prevent preterm labour . The authors review the role of TLR4 in both normal parturition and preterm birth as
well as how this receptor interacts with both pathogen-derived and endogenous ligands. Finally, the authors summarize recent exciting data
supporting the use of specific TLR4 antagonists to prevent PTB, including (+)-naloxone.
In a comprehensive review on the topic, Carlos Salomon et al. propose that preterm birth may be triggered by extracellular membrane
vesicles involved in the regulation of signaling cascades during pregnancy and parturition, known as exosomes . These highly stable
nanovesicles, serving as transporters of mRNA, miRNA, DNA, lipid, cell-surface receptor and protein mediators, communicate between the
maternal and fetal compartments in pregnancy. The authors present the provocative proposal that exosomes carry the signals for the initiation
Kiersten Giusto and Charles Ashby point to the role of the sphingosine kinase/endothelin-1 pathway as a novel putative target of prevent
PTB . The data summarized in their review provide solid evidence for the dual role of this pathway in PTB, which mediates both a proinflammatory
response as well as uterine contraction. The fact that this pathway is regulated by positive feedback underlines its explosive
role in inflammation-driven PTB.
Samir Gorasiya et al. describe an exciting new class of cytokine suppressive anti-inflammatory drugs, based on the accidental discovery
that N,N-dimethylacetamide, a common pharmaceutical excipient, rescues timed pregnant mice from lipopolysaccharide induced preterm
birth . These molecules represent a novel group of nuclear factor kappa B (NF-κB) inhibitors. As NF-κB is implicated in so many disorders,
these new drugs may have broad clinical impact.
Finally, Nicole Olgun of the Centers for Disease Control and Prevention reviews the special considerations related to viral infection in
pregnancy and Ebola virus in particular . Dr. Olgun reminds us of the devastating toll viral infections exert on neonatal health. Her review
emphasizes the value of preparedness as unexpected epidemics emerge.
The development of pharmacotherapy to prevent preterm birth presents a special challenge because of the vulnerability of the developing
fetus. Even agents proven to be safe in other clinical settings that show potential tocolytic activity can not simply be repurposed for the prevention
of preterm labor without being carefully vetted for teratogenic effects. The successful approach to this far-reaching clinical problem
will come from collaborative efforts among investigators with different perspectives and expertise. This issue, the second of a two volume
series on this topic, brings together insightful reviews written by experts from around the globe.
Infections caused by microorganisms are one of the most common issues and a serious threat to patients in the clinic. These microbial
infections often result in disease progression and surgical failure. To address this problem, many efforts have been made to exploit various
biomaterials and medical devices with antibacterial properties.
Currently, various materials, namely antibiotics, inorganic nanomaterials, polymers, and Antimicrobial Peptides (AMPs), have been
widely investigated and used as antimicrobial agents. The morphologies, molecular structures, or release behaviors of these materials may
significantly affect their functionality. Meanwhile, the antibacterial mechanisms of these materials have also gained much attention and may
direct the design of advanced antibacterial materials or medical devices. In this theme issue, ten reviews from researchers in differing fields
were collected together with a primary focus on the design of antibacterial materials and their applications.
Hydrogels, an important biomaterial, have been widely used in biomedical fields. Weiguo Xu et al. gave a review on the recent development
of antimicrobial hydrogels and discussed their potential prospects . Polymers with antibacterial functions have also been investigated.
Cansu Ergene and Edmund F. Palermo introduced a wide range of antimicrobial polymers and gave a review on state-of-the-art methods employed
to optimize macromolecular structures for high antibacterial activity . Diego and his colleagues gave a comprehensive introduction
on antibacterial coatings with different molecules, and the striking developments of chitosan-based functional coatings for pharmaceutical and
biomedical applications were well reviewed .
Besides polymers, inorganic materials also made a significant impact in antibacterial fields. Zhou Chen et al. evaluated recent developments
regarding bioactive glass, graphene-based antibacterial materials, as well as metal ion coatings . The antibacterial mechanisms of
nanoparticles have been well investigated by Scott and his colleagues as they summarized the challenges metal oxide antibacterial materials
face and presented novel methods to evaluate the antibacterial potency and efficiency of these nanoparticles .
AMPs are another promising therapeutic agents to combat infectious diseases. However, the applications of AMP are limited due to insufficient
sources, instability, toxicity, and bioavailability. In this theme issue, Huping Jiao’s group provided a review on the design and modification
of AMPs, and summarized both chemical and biological methods to adjust the properties of AMPs .
The controlled release of antibiotics is an efficient method to prevent or treat implant-associated infections. Liqun Xu et al. provided a
summary on the carrier platforms used for loading antibiotics and their drug release behaviors were also highlighted . Layer-by-layer
(LBL) is also a versatile method to construct functional surfaces and films. Lan Liao and coauthors gave a brief introduction and summarized
the applications of LBL to construct antibacterial surfaces or films .
Antibacterial agents play an important role in the wound healing process. Zhengwen Li and Menno Knetsch gave a review on current
antibacterial strategies of wound dressings, the wound infection process, antibacterial agents, and a controlled drug delivery system .
The real-time monitoring of bacterial infections and drug evaluation are also important topics. Xiwen Wang and his colleagues provide a
review about bacterial luciferase gene cassette as a real-time bioreporter for infection model and drug evaluation .
This special issue covers various fields of antibacterial materials. The guest editors and all the authors hope this theme issue may help
readers discover advanced ideas and guidance, while simultaneously motivating readers to contribute to researches on antibacterial materials.
Abstract: In the field of inflammation/infection imaging, nuclear medicine techniques offer non-invasive tools to detect early pathophysiological
changes before the development of anatomical changes detected by radiological procedures and, often, before clinical onset
of symptoms. This field has been recently developed with several new radiopharmaceuticals for SPECT and PET used to define new
strategies for imaging immune cells as well as pathogens.
In particular, we count now several dozens of new radiopharmaceuticals designed for bacterial imaging and new peptides and antibodies
for imaging neutrophils, T-cells, B-cells and macrophages.
These may have important applications not only for diagnostic purposes but also for prognostic purposes, therapy decision making and
for early follow-up of therapy efficacy, thus allowing us to define specific therapies for each individual patient.
Inflammatory disorders, infections and cancer, have a tangible impact for health and social costs. For this reason, it is advisable to establish,
in each hospital, a multi-disciplinary team of experts for the management of patients with chronic inflammatory/infectious diseases, as
well as for cancer patients, to optimize diagnostic protocols, therapy decision and follow-up. Nowadays, among the several imaging modalities
available, nuclear medicine techniques play a secondary role after radiation-free methods such as ultrasound (US) and Magnetic Resonance
Imaging (MRI). Nevertheless, a multidisciplinary approach combining radiology and nuclear medicine often represents a suitable diagnostic,
prognostic, and monitoring tool in patient management. Nuclear medicine techniques, in particular, offer non-invasive tools to detect
early pathophysiological changes before the development of anatomical changes detected by radiological procedures and often before clinical
onset of symptoms.
Hence, this monographic issue is well-timed for providing clinicians current knowledge on molecular imaging in inflammatory disorders
and infections, since an early and accurate diagnosis represents an important step to prevent serious or long-lasting complications as well as to
monitor therapeutic responses.
Functional imaging with radiopharmaceuticals has been shown to detect inflammatory processes with high sensitivity and specificity and
constitute the basis of molecular imaging with Positron Emission Tomography (PET) or Single-Photon Emission Computed Tomography
These techniques are also of great importance for therapy decision making and in monitoring response to therapy. Thanks to the possibility
of deeply understanding the nature of an inflammatory process and what cells or cytokines are present in the inflamed site we are now able
to decide the most appropriate therapy and to verify its efficacy.
As an example, I could mention the role of 99mTc-anti-TNFα antibodies [1-5] or 99mTc-anti-CD20 antibodies [6, 7] or 99mTc-octreotide [8,
9] in patients with rheumatic diseases, or the role of 99mTc-Interleukin-2 in patients with Type 1 diabetes [10, 11], or the role of 99mTc-labelled
antibiotics in defining the nature of pathogen causative of an infection , or other radiopharmaceuticals in neuro-inflammation  and
heart inflammation .
Along this line, many other radiopharmaceuticals have been developed and studied including those for targeting chemotaxis, cell recruitment,
matrix metalloproteinase production, macrophage metabolism, angiogenesis, and several other specific against cells and soluble antigens
involved in inflammatory and infective diseases as reviewed in this issue by Signore et al.  and Sollini et al. . The approach of
specific imaging of bacteria has been reviewed by Ebenhan et al.  whereas the new radiopharmaceuticals labelled with 68Ga for PET imaging
have been reviewed by Vorster et al. .
It must be clarified, however, that in some pathological condition it is not so relevant to use a highly specific radiopharmaceutical, being
more relevant its high sensitivity or even the strategy used for image acquisition that could improve the disease specificity of a non-highly
specific radiopharmaceutical as clearly explained by S. Skehan and M. Peters in early 2000 [19, 20] and others .
The understanding of the properties of radiopharmaceuticals and of the most appropriate image acquisition modality, relies on the success
of the use of radiolabelled neutrophils [22-24] and on the use of 18F-FDG is certain specific pathological conditions [25-27] as also reviewed
by Ankrah et al. in case of fungal infections in children  or as described by Keidar in case of diabetic infections  or by Palestro et al.
in case of fever of unknown origin .
Colchicine has been used for over two thousand years. Recently research studies have shed light on potential new indications. While colchicine
is in fact an ancient drug, there is a lack of “big” data on its utilization in modern medicine.
Tsoucalas et al.  searches back in ancient Greek and Byzantine sources for documentation of colchicine utilization. While initially
considered as an effective poison to “kill a rebellious slave, or a rival nobleman”, later on Late Greek antiquity its potential therapeutic aspects
were recognised . Karamanou M et al.  unveils the modern historical course of colchicine from distribution through empiric physicians
(charlatans) in the 15th century to the contemporary pharmacopeia of the 19th century.
Colchicine exploits a plethora of pathophysophysiological pathways and is in general characterized by a relatively safe profile. Side effects
are mainly of gastrointestinal origin, while toxicity is associated to doses multiple of the common therapeutic regimens. Angelidis C.
et al. , review pharmacokinetics, mechanisms of action and side effects of colchicine.
Drosos E. et al.  reviews potential indications of colchicine in the fields of low-back pain, gliomas and stroke from the viewpoint of
neurosurgery. Tsivgoulis G. et al.  review available data and ongoing studies in utilization of colchicine’s anti-inflammatory properties for
prevention cerebral atherosclerotic events.
Marinaki S et al.  provide an overview of colchicine employment in a series of entities affecting the kidneys (fibrotic disorders, diabetic
neuropathy, familial Mediterranean fever and amyloidosis, renal transplantation, hypertensive kidney disease, autosomal dominant
polycystic kidney disease, focal segmental glomerulosclerosis).
Colchicine as a treatment for gout, a classic indication, is comprehensively reviewed by Parcart T and Richette P . Further, Lantinioti
G. et al.  present current perspectives on indications of colchicine in autoinflammatory disorders (Familial Mediterranean Fever, Periodic
fever with aphthous stomatitis, pharyngitis and adenitis, Behcet’s disease, Idiopathic recurrent acute pericarditis).
Finally, colchicine has been suggested as a means of primary prevention for post-operative atrial fibrillation. A series of randomized studies
and meta-analyses have lately been available and are presented in detail by Vrachatis D. et al. . Last, but not least, a “traditional” indication
of colchicine, pericardial syndromes, is thoroughly reviewed by Lazaros G. et al. .
Heart diseases are the world’s leading cause of morbidity and mortality. For a broad spectrum of heart diseases, though each has its own unique features in pathogenesis and disease evolution, the inflammatory processes are commonly shared among them. The initial inflammatory reaction is a cardioprotective response to triggers such as ischemia, tissue injury and infection. However, prolonged inflammation, can damage normal tissue, cause cardiac dysfunction, result in adverse cardiac remodeling including myocyte hypertrophy and necrosis, fibrosis, and at last contribute to a poor prognosis. Recent findings suggest that regulation of inflammation is a potential target for development of therapies for heart diseases. In the purpose of facilitating further management of heart diseases, this issue will systemically review recent studies focusing inflammation in heart diseases. The issue contains 12 papers that summarize inflammatory pathways and potential therapeutic targets for heart diseases.
Lifestyle modifications and diet therapy are two of the most important tools in prevention and treatment of cardiovascular risk factors, cancer and other chronic diseases. In keeping to this, increasing epidemiological data support the concept that diet rich in fruit and vegetables promotes health and attenuate, or delay, the onset of various diseases, including heart disease, hypertension, cancer and certain age-related degenerative disorders. Over the past decades increasing research interest has been addressed to the potential health benefits of polyphenols. According to this, it has been suggested that the health benefits from fruit and vegetables can be partially linked to their content of a certain group of polyphenols, the flavonoids. A large body of evidence supports that dietary intake of polyphenols (particularly flavonoids and the specific class of flavonoids named flavanols largely contained in red wine, cocoa, tea, fruits and vegetables) might exert some beneficial vascular effects, reduce the risk of cardiovascular morbidity and mortality and contribute to the prevention of other chronic diseases. Among phytochemicals, polyphenols constitute one of the most numerous and widely distributed groups of substances in the plant kingdom, with more than 8000 phenolic structures. They occurred in a variety of fruits, vegetables, seeds, flowers, beverages and even some manufactured food as a component of the natural ingredients used.
These bioactive compounds typically occur in small quantities in foods. They are being intensively studied to evaluate their effects on health. The impetus sparking this scientific inquiry was the result of many epidemiologic studies that have shown protective effects of plant-based diets on cardiovascular disease and cancer. According to this, growing interest has been addresed to many bioactive compounds. These compounds vary widely in chemical structure and function and are grouped accordingly.
Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research.
Adequate nutrition is one of the pillars of public health. Before developing and implementing effective intervention programmes to improve nutrition at the population level, it is important to know the nutritional situation of the target group.
Therefore, the time lapse for hidden progression of pathological process may take years and even decades. During this time, both the person at risk and physician remain unaware of the existing premorbid pathological condition. As a result, no preventive measures are undertaken to reduce the individual risk of the development of the overt disease.
Polyphenols are abundant nutraceutical micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases is emerging.
The WHO estimated that the costs of not engaging in prevention and therapy will be fastly growing in the next years, with a more severe impact in developing countries. Several natural nutraceutical from our diet and ingredients marketed for use in dietary supplements address such risk factors. The ability of nutraceuticals to favorably influence cardiovascular risk factors and atherosclerotic vascular disease as well as a number of different chronic disease should be recognized as an enormous opportunity for the prevention or treatment of this common condition.