scholarly journals Focus on the Lymphatic Route to Optimize Drug Delivery in Cardiovascular Medicine

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1200
Author(s):  
Nolwenn Tessier ◽  
Fatma Moawad ◽  
Nada Amri ◽  
Davide Brambilla ◽  
Catherine Martel
Keyword(s):  
Cardiovascular Disease ◽  
Drug Delivery ◽  
New Technologies ◽  
Vascular System ◽  
Current Knowledge ◽  
Lymphatic Vessels ◽  
Oral Agents ◽  
Lymphatic Network ◽  
New Generation ◽  
Lymphatic Route

While oral agents have been the gold standard for cardiovascular disease therapy, the new generation of treatments is switching to other administration options that offer reduced dosing frequency and more efficacy. The lymphatic network is a unidirectional and low-pressure vascular system that is responsible for the absorption of interstitial fluids, molecules, and cells from the peripheral tissue, including the skin and the intestines. Targeting the lymphatic route for drug delivery employing traditional or new technologies and drug formulations is exponentially gaining attention in the quest to avoid the hepatic first-pass effect. The present review will give an overview of the current knowledge on the involvement of the lymphatic vessels in drug delivery in the context of cardiovascular disease.

scholarly journals Molecular Mechanisms Controlling Lymphatic Endothelial Junction Integrity

2021 ◽  
Vol 8 ◽  
Author(s):  
Pieter R. Norden ◽  
Tsutomu Kume
Keyword(s):  
Molecular Mechanisms ◽  
Vascular System ◽  
Current Knowledge ◽  
Lymphatic Vessels ◽  
Circulatory System ◽  
Lymphatic Endothelial Cell ◽  
Basement Membranes ◽  
Cell Junctions ◽  
Lipid Absorption ◽  
Tissue Fluid

The lymphatic system is essential for lipid absorption/transport from the digestive system, maintenance of tissue fluid and protein homeostasis, and immune surveillance. Despite recent progress toward understanding the cellular and molecular mechanisms underlying the formation of the lymphatic vascular system, the nature of lymphatic vessel abnormalities and disease in humans is complex and poorly understood. The mature lymphatic vasculature forms a hierarchical network in which lymphatic endothelial cells (LECs) are joined by functionally specialized cell-cell junctions to maintain the integrity of lymphatic vessels. Blind-ended and highly permeable lymphatic capillaries drain interstitial fluid via discontinuous, button-like LEC junctions, whereas collecting lymphatic vessels, surrounded by intact basement membranes and lymphatic smooth muscle cells, have continuous, zipper-like LEC junctions to transport lymph to the blood circulatory system without leakage. In this review, we discuss the recent advances in our understanding of the mechanisms by which lymphatic button- and zipper-like junctions play critical roles in lymphatic permeability and function in a tissue- and organ-specific manner, including lacteals of the small intestine. We also provide current knowledge related to key pathways and factors such as VEGF and RhoA/ROCK signaling that control lymphatic endothelial cell junctional integrity.

Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Disease

2020 ◽  
Vol 26 (43) ◽  
pp. 5617-5627
Author(s):  
Mirjana Stojković ◽  
Miloš Žarković
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Cardiac Electrophysiology ◽  
Vascular System ◽  
Density Lipoprotein ◽  
Thyroid Stimulating Hormone ◽  
Normal Limits ◽  
Developing Heart ◽  
Treatment Indications ◽  
Increased Risk

The prevalence of subclinical hypothyroidism (SH) is 3-10%. The prevalence of subclinical hyperthyroidism (SHr) is 0.7-9.7%. Thyroid hormones affect cardiac electrophysiology, contractility, and vasculature. SH is associated with an increased risk of coronary heart disease (CHD), especially in subjects under 65. SHr seems to be associated with a slightly increased risk of CHD and an increase in CHD-related mortality. Both SH and SHr carry an increased risk of developing heart failure (HF), especially in those under 65. Both SH and SHr are associated with worse prognoses in patients with existing HF. SH is probably not associated with atrial fibrillation (AF). SHr, low normal thyroid-stimulating hormone (TSH) and high normal free thyroxine (FT4) are all associated with the increased risk of AF. An association between endothelial dysfunction and SH seems to exist. Data regarding the influence of SHr on the peripheral vascular system are conflicting. SH is a risk factor for stroke in subjects under 65. SHr does not increase the risk of stroke. Both SH and SHr have an unfavourable effect on cardiovascular disease (CVD) and all-cause mortality. There is a U-shaped curve of mortality in relation to TSH concentrations. A major factor that modifies the relation between subclinical thyroid disease (SCTD) and mortality is age. SH increases blood pressure (BP). SHr has no significant effect on BP. Lipids are increased in patients with SH. In SHr, high-density lipoprotein cholesterol and lipoprotein( a) are increased. SCTD should be treated when TSH is over 10 mU/l or under 0.1 mU/l. Treatment indications are less clear when TSH is between normal limits and 0.1 or 10 mU/L. The current state of knowledge supports the understanding of SCTD’s role as a risk factor for CVD development. Age is a significant confounding factor, probably due to age-associated changes in the TSH reference levels.

Biosurfactants as a Novel Additive in Pharmaceutical Formulations: Current Trends and Future Implications

2020 ◽  
Vol 21 (11) ◽  
pp. 885-901
Author(s):  
Shubham Thakur ◽  
Amrinder Singh ◽  
Ritika Sharma ◽  
Rohan Aurora ◽  
Subheet Kumar Jain
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Toxicity Testing ◽  
Pharmaceutical Formulations ◽  
Delivery Systems ◽  
Surface Active Agents ◽  
Regulatory Status ◽  
Different Temperatures ◽  
High Production Cost ◽  
New Generation

Background: Surfactants are an important category of additives that are used widely in most of the formulations as solubilizers, stabilizers, and emulsifiers. Current drug delivery systems comprise of numerous synthetic surfactants (such as Cremophor EL, polysorbate 80, Transcutol-P), which are associated with several side effects though used in many formulations. Therefore, to attenuate the problems associated with conventional surfactants, a new generation of surface-active agents is obtained from the metabolites of fungi, yeast, and bacteria, which are termed as biosurfactants. Objectives: In this article, we critically analyze the different types of biosurfactants, their origin along with their chemical and physical properties, advantages, drawbacks, regulatory status, and detailed pharmaceutical applications. Methods: 243 papers were reviewed and included in this review. Results: Briefly, Biosurfactants are classified as glycolipids, rhamnolipids, sophorolipids, trehalolipids, surfactin, lipopeptides & lipoproteins, lichenysin, fatty acids, phospholipids, and polymeric biosurfactants. These are amphiphilic biomolecules with lipophilic and hydrophilic ends and are used as drug delivery vehicles (foaming, solubilizer, detergent, and emulsifier) in the pharmaceutical industry. Despite additives, they have some biological activity as well (anti-cancer, anti-viral, anti-microbial, P-gp inhibition, etc.). These biomolecules possess better safety profiles and are biocompatible, biodegradable, and specific at different temperatures. Conclusion: Biosurfactants exhibit good biomedicine and additive properties that can be used in developing novel drug delivery systems. However, more research should be driven due to the lack of comprehensive toxicity testing and high production cost which limits their use.

The Potential of Milk-derived Exosomes for Drug Delivery

2020 ◽  
Vol 17 ◽  
Author(s):  
Shuyuan Li ◽  
Yue Tang ◽  
Yushun Dou
Keyword(s):  
Drug Delivery ◽  
Oral Delivery ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Drug Loading ◽  
Drug Carriers ◽  
Current Application ◽  
Therapeutic Benefits ◽  
Loading Methods

Background: Exosomes, one of the extracellular vesicles, are widely present in all biological fluids and play an important role in intercellular communication. Because of its hydrophobic lipid bilayer and aqueous hydrophilic core structure, it is considered a possible alternative to liposome drug delivery systems. Not only do they protect the cargo like liposomes during delivery, they are less toxic and better tolerated. However, due to the lack of sources and methods for obtaining enough exosomes, the therapeutic application of exosomes as drug carriers is limited. Methods: A literature search was performed using the ScienceDirect and PubMed electronic databases to obtain information from published literature on milk exosomes related to drug delivery. Results: Here, we briefly reviewed the current knowledge of exosomes, expounded the advantages of milk-derived exosomes over other delivery vectors, including a higher yield, the oral delivery characteristic and additional therapeutic benefits. The purification and drug loading methods of milk exosomes, and the current application of milk exosomes were also introduced. Conclusion: The emergence of milk-derived exosomes is expected to break through the limitations of exosomes as therapeutic carriers of drugs. We hope to raise awareness of the therapeutic potential of milk-derived exosomes as a new drug delivery system.

scholarly journals Vascular endothelial cell specification in health and disease

Angiogenesis ◽  
2021 ◽  
Author(s):  
Corina Marziano ◽  
Gael Genet ◽  
Karen K. Hirschi
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Current Knowledge ◽  
Vascular Malformations ◽  
Immune Surveillance ◽  
Vascular Endothelial Cell ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cell ◽  
The Body ◽  
Vascular Networks

AbstractThere are two vascular networks in mammals that coordinately function as the main supply and drainage systems of the body. The blood vasculature carries oxygen, nutrients, circulating cells, and soluble factors to and from every tissue. The lymphatic vasculature maintains interstitial fluid homeostasis, transports hematopoietic cells for immune surveillance, and absorbs fat from the gastrointestinal tract. These vascular systems consist of highly organized networks of specialized vessels including arteries, veins, capillaries, and lymphatic vessels that exhibit different structures and cellular composition enabling distinct functions. All vessels are composed of an inner layer of endothelial cells that are in direct contact with the circulating fluid; therefore, they are the first responders to circulating factors. However, endothelial cells are not homogenous; rather, they are a heterogenous population of specialized cells perfectly designed for the physiological demands of the vessel they constitute. This review provides an overview of the current knowledge of the specification of arterial, venous, capillary, and lymphatic endothelial cell identities during vascular development. We also discuss how the dysregulation of these processes can lead to vascular malformations, and therapeutic approaches that have been developed for their treatment.

scholarly journals Phony peach disease: past and present impact on the peach industry in the southeastern U.S.A

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Kendall A. Johnson ◽  
Clive H. Bock ◽  
Phillip M. Brannen
Keyword(s):  
New Technologies ◽  
Current Knowledge ◽  
Future Research ◽  
Management Options ◽  
Disease Epidemiology ◽  
Pathogen Diversity ◽  
Foundational Research ◽  
Global Threat ◽  
And Control ◽  
The Impact

Abstract Background Phony peach disease (PPD) is caused by the plant pathogenic bacterium Xylella fastidiosa subsp. multiplex (Xfm). Historically, the disease has caused severe yield loss in Georgia and elsewhere in the southeastern United States, with millions of PPD trees being removed from peach orchards over the last century. The disease remains a production constraint, and management options are few. Limited research has been conducted on PPD since the 1980s, but the advent of new technologies offers the opportunity for new, foundational research to form a basis for informed management of PPD in the U.S. Furthermore, considering the global threat of Xylella to many plant species, preventing import of Xfm to other regions, particularly where peach is grown, should be considered an important phytosanitary endeavor. Main topics We review PPD, its history and impact on peach production, and the eradication efforts that were conducted for 42 years. Additionally, we review the current knowledge of the pathogen, Xfm, and how that knowledge relates to our understanding of the peach—Xylella pathosystem, including the epidemiology of the disease and consideration of the vectors. Methods used to detect the pathogen in peach are discussed, and ramifications of detection in relation to management and control of PPD are considered. Control options for PPD are limited. Our current knowledge of the pathogen diversity and disease epidemiology are described, and based on this, some potential areas for future research are also considered. Conclusion There is a lack of recent foundational research on PPD and the associated strain of Xfm. More research is needed to reduce the impact of this pathogen on peach production in the southeastern U.S., and, should it spread internationally, wherever peaches are grown.

scholarly journals Review of Current Spinal Robotic Orthoses

Healthcare ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 70
Author(s):  
Siu Kei David Mak ◽  
Dino Accoto
Keyword(s):  
New Technologies ◽  
Current Knowledge ◽  
Axial Loading ◽  
Early Mobilization ◽  
Bed Rest ◽  
Field Application ◽  
Symptomatic Management ◽  
Spinal Brace ◽  
Potential Improvement ◽  
Spinal Orthosis

Osteoporotic spine fractures (OSF) are common sequelae of osteoporosis. OSF are directly correlated with increasing age and incidence of osteoporosis. OSF are treated conservatively or surgically. Associated acute pain, chronic disabilities, and progressive deformities are well documented. Conservative measures include a combination of initial bed rest, analgesia, early physiotherapy, and a spinal brace (orthosis), with the aim for early rehabilitation to prevent complications of immobile state. Spinal bracing is commonly used for symptomatic management of OSF. While traditional spinal braces aim to maintain the neutral spinal alignment and reduce the axial loading on the fractured vertebrae, they are well known for complications including discomfort with reduced compliance, atrophy of paraspinal muscles, and restriction of chest expansion leading to chest infections. Exoskeletons have been developed to passively assist and actively augment human movements with different types of actuators. Flexible, versatile spinal exoskeletons are designed to better support the spine. As new technologies enable the development of motorized wearable exoskeletons, several types have been introduced into the medical field application. We have provided a thorough review of the current spinal robotic technologies in this paper. The shortcomings in the current spinal exoskeletons were identified. Their limitations on the use for patients with OSF with potential improvement strategies were discussed. With our current knowledge of spinal orthosis for conservatively managed OSF, a semi-rigid backpack style thoracolumbar spinal robotic orthosis will reduce spinal bone stress and improve back muscle support. This will lead to back pain reduction, improved posture, and overall mobility. Early mobilization is an important part of management of patients with OSF as it reduces the chance of developing complications related to their immobile state for patients with OSF, which will be helpful for their recovery.

scholarly journals Dietary Fiber, Atherosclerosis, and Cardiovascular Disease

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1155 ◽  
Author(s):  
Ghada A. Soliman
Keyword(s):  
Cardiovascular Disease ◽  
Dietary Fiber ◽  
Water Solubility ◽  
Disease Risk ◽  
Current Knowledge ◽  
Digestive Enzyme ◽  
Water Soluble ◽  
Blood Cholesterol ◽  
Fiber Intake ◽  
Intestinal Transit Time

Observational studies have shown that dietary fiber intake is associated with decreased risk of cardiovascular disease. Dietary fiber is a non-digestible form of carbohydrates, due to the lack of the digestive enzyme in humans required to digest fiber. Dietary fibers and lignin are intrinsic to plants and are classified according to their water solubility properties as either soluble or insoluble fibers. Water-soluble fibers include pectin, gums, mucilage, fructans, and some resistant starches. They are present in some fruits, vegetables, oats, and barley. Soluble fibers have been shown to lower blood cholesterol by several mechanisms. On the other hand, water-insoluble fibers mainly include lignin, cellulose, and hemicellulose; whole-grain foods, bran, nuts, and seeds are rich in these fibers. Water-insoluble fibers have rapid gastric emptying, and as such may decrease the intestinal transit time and increase fecal bulk, thus promoting digestive regularity. In addition to dietary fiber, isolated and extracted fibers are known as functional fiber and have been shown to induce beneficial health effects when added to food during processing. The recommended daily allowances (RDAs) for total fiber intake for men and women aged 19–50 are 38 gram/day and 25 gram/day, respectively. It is worth noting that the RDA recommendations are for healthy people and do not apply to individuals with some chronic diseases. Studies have shown that most Americans do not consume the recommended intake of fiber. This review will summarize the current knowledge regarding dietary fiber, sources of food containing fiber, atherosclerosis, and heart disease risk reduction.

scholarly journals Mast cell–derived particles deliver peripheral signals to remote lymph nodes

2009 ◽  
Vol 206 (11) ◽  
pp. 2455-2467 ◽  
Author(s):  
Christian A. Kunder ◽  
Ashley L. St. John ◽  
Guojie Li ◽  
Kam W. Leong ◽  
Brent Berwin ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mast Cell ◽  
Mast Cells ◽  
Tumor Necrosis Factor ◽  
Lymph Nodes ◽  
Tumor Necrosis ◽  
Lymphatic Vessels ◽  
Lymphoid Tissues ◽  
Draining Lymph Nodes ◽  
Necrosis Factor

During infection, signals from the periphery are known to reach draining lymph nodes (DLNs), but how these molecules, such as inflammatory cytokines, traverse the significant distances involved without dilution or degradation remains unclear. We show that peripheral mast cells, upon activation, release stable submicrometer heparin-based particles containing tumor necrosis factor and other proteins. These complexes enter lymphatic vessels and rapidly traffic to the DLNs. This physiological drug delivery system facilitates communication between peripheral sites of inflammation and remote secondary lymphoid tissues.

Future directions for the discovery of antibiotics from actinomycete bacteria

2017 ◽  
Vol 1 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Rebecca Devine ◽  
Matthew I. Hutchings ◽  
Neil A. Holmes
Keyword(s):  
New Technologies ◽  
Gene Clusters ◽  
Biosynthetic Gene Clusters ◽  
Future Directions ◽  
Streptomyces Species ◽  
Genus Streptomyces ◽  
New Antibiotics ◽  
The Uk ◽  
Almost All ◽  
New Generation

Antimicrobial resistance (AMR) is a growing societal problem, and without new anti-infective drugs, the UK government-commissioned O'Neil report has predicted that infectious disease will claim the lives of an additional 10 million people a year worldwide by 2050. Almost all the antibiotics currently in clinical use are derived from the secondary metabolites of a group of filamentous soil bacteria called actinomycetes, most notably in the genus Streptomyces. Unfortunately, the discovery of these strains and their natural products (NPs) peaked in the 1950s and was then largely abandoned, partly due to the repeated rediscovery of known strains and compounds. Attention turned instead to rational target-based drug design, but this was largely unsuccessful and few new antibiotics have made it to clinic in the last 60 years. In the early 2000s, however, genome sequencing of the first Streptomyces species reinvigorated interest in NP discovery because it revealed the presence of numerous cryptic NP biosynthetic gene clusters that are not expressed in the laboratory. Here, we describe how the use of new technologies, including improved culture-dependent and -independent techniques, combined with searching underexplored environments, promises to identify a new generation of NP antibiotics from actinomycete bacteria.

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