Thursday, April 16, 2015
Oral infections are the most common diseases of mankind and are also a key risk factor for heart disease, which is the leading cause of death worldwide. In a review article published in Trends in Endocrinology and Metabolism on April 16, researchers summarize the latest clinical evidence supporting a link between oral infections, which are caused by the bacteria in our mouth, and heart disease, and they emphasize the important role of inflammation in both of these conditions.
"Given the high prevalence of oral infections, any risk they contribute to future cardiovascular disease is important to public health," says senior author Thomas Van Dyke of the Forsyth Institute. "Unravelling the role of the oral microbiome and inflammation in cardiovascular disease will likely lead to new preventive and treatment approaches." The (oral) microbiome refers to the totality of microorganisms in a body part-in this case the mouth--that we all co-exist with.
The most common oral infections are cavities and periodontal diseases such as gingivitis and periodontitis, which are chronic inflammatory diseases that slowly and steadily destroy the supporting structures of multiple teeth. Significant epidemiological evidence supports an association between oral infections, particularly periodontitis, and stroke, especially among men and younger individuals.
Inflammation plays a major role both in oral infections such as periodontitis and in cardiovascular disease. However, over-the-counter nonsteroidal anti-inflammatory drugs such as ibuprofen can produce significant cardiovascular side effects, which means it is crucial that we consider alternative therapies. A high dose of a commonly prescribed cholesterol-lowering medication, atorvastatin, which boosts blood levels of anti-inflammatory molecules called lipoxins and resolvins, prevents both periodontal and cardiovascular inflammation and reverses existing disease in humans. This is exciting and promising because lipoxins and resolvins also have the advantage of naturally controlling inflammation without suppressing the immune system.
"New discoveries of natural pathways that resolve inflammation have offered many opportunities for revealing insights into disease pathogenesis and for developing new pharmacologic targets for the treatment of both oral infections and cardiovascular disease," Van Dyke says.
In future studies, it will be important to compare the effectiveness of these inflammation-reducing molecules, which we produce naturally, and other interventions that could potentially prevent or reverse periodontitis and cardiovascular disease. Another open question is whether there is a reverse relationship between these conditions: what if the onset of cardiovascular disease influences the presence or progression of periodontal disease? Or what are some of the common genetic mechanisms underlying periodontitis and cardiovascular disease?
In the meantime, Van Dyke recommends that people take better care of their teeth to potentially lower their risk of cardiovascular disease and other health problems. "The majority of diseases and conditions of aging, including obesity and type 2 diabetes, have a major inflammatory component that can be made worse by the presence of periodontitis," he says. "Periodontitis is not just a dental disease, and it should not be ignored, as it is a modifiable risk factor."
Trends in Endocrinology & Metabolism, Kholy et al.:"Oral infections and cardiovascular disease" http://dx.doi.org/10.1016/j.tem.2015.03.001
Tuesday, April 14, 2015
A new study from the Forsyth Institute is helping to shed more light on the important connection between the mouth and heart. According to research recently published online by the American Heart Association, scientists at Forsyth and Boston University have demonstrated that using an oral topical remedy to reduce inflammation associated with periodontitis, more commonly known as gum disease, also results in the prevention of vascular inflammation and can lower the risk of heart attack.
This study is the first time researchers anywhere have demonstrated the ability of an oral treatment for gum disease to also reduce inflammation in the artery wall. The active ingredient is an inflammation resolving molecule, known as Resolvin E1. This discovery further underscores the increasing body of evidence showcasing how problems in the mouth - and how they are treated - can have life changing influences on other key systems in the body, such as the heart in this case.
"Our research is helping to underscore the very real link between oral health and heart disease," said Lead Investigator Hatice Hasturk, DDS, PhD, an associate member of Forsyth's Department of Applied Oral Sciences and director of Forsyth's Center for Clinical and Translational Research. "The general public understands the connection between heart health and overall wellness, and often takes appropriate steps to prevent heart disease. More education is needed to elevate oral wellness into the same category in light of proven connections to major health conditions."
According to the CDC, heart disease accounts for one in four deaths in the United States, and the rate continues to rise. Forsyth's findings suggest a need to expand the public's understanding of risk factors beyond cholesterol, smoking, hypertension and diabetes to include a focus on oral health. With support from the scientific community, Forsyth aims to generate greater awareness of gum disease (affecting 64.7 million American adults according to the CDC) as a critical risk factor for heart disease, independent from diet and lifestyle.
The study, titled, "Resolvin E1 Prevents Atheromatous Plaque Formation," will be published in print in the May issue of Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB), a journal of the American Heart Association. It is the first paper to show a rabbit model of accelerated heart disease, demonstrating a range of atherosclerotic plaque stages that more closely resemble those in humans without genetic modification of the animal. This research is authored by Hatice Hasturk, Rima Abdallah, Alpdogan Kantarci, Daniel Nguyen, Nicholas Giordano, James Hamilton and Thomas E. Van Dyke.
Wednesday, April 1, 2015
Therapeutic agents intended to reduce dental plaque and prevent tooth decay are often removed by saliva and the act of swallowing before they can take effect. But a team of researchers has developed a way to keep the drugs from being washed away.
Dental plaque is made up of bacteria enmeshed in a sticky matrix of polymers--a polymeric matrix--that is firmly attached to teeth. The researchers, led by Danielle Benoit at the University of Rochester and Hyun Koo at the University of Pennsylvania's School of Dental Medicine, found a new way to deliver an antibacterial agent within the plaque, despite the presence of saliva.
Their findings have been published in the journal ACS Nano.
"We had two specific challenges," said Benoit, an assistant professor of biomedical engineering. "We had to figure out how to deliver the anti-bacterial agent to the teeth and keep it there, and also how to release the agent into the targeted sites."
To deliver the agent--known as farnesol--to the targeted sites, the researchers created a spherical mass of particles, referred to as a nanoparticle carrier. They constructed the outer layer out of cationic--or positively charged--segments of the polymers. For inside the carrier, they secured the drug with hydrophobic and pH-responsive polymers.
The positively-charged outer layer of the carrier is able to stay in place at the surface of the teeth because the enamel is made up, in part, of HA (hydroxyapatite), which is negatively charged. Just as oppositely charged magnets are attracted to each other, the same is true of the nanoparticles and HA. Because teeth are coated with saliva, the researchers weren't certain the nanoparticles would adhere. But not only did the particles stay in place, they were also able to bind with the polymeric matrix and stick to dental plaque.
Since the nanoparticles could bind both to saliva-coated teeth and within plaque, Benoit and colleagues used them to carry an anti-bacterial agent to the targeted sites. The researchers then needed to figure out how to effectively release the agent into the plaque.
A key trait of the inner carrier material is that it destabilizes at acidic--or low pH--levels, such as 4.5, allowing the drug to escape more rapidly. And that's exactly what happens to the pH level in plaque when it's exposed to glucose, sucrose, starch, and other food products that cause tooth decay. In other words, the nanoparticles release the drug when exposed to cavity-causing eating habits--precisely when it is most needed to quickly stop acid-producing bacteria.
The researchers tested the product in rats that were infected with Streptococcus mutans--a microbe that causes tooth decay. "We applied the test solutions to rats' mouths twice daily for 30 seconds, simulating what a person might do using a mouth rinse morning and night," said Hyun Koo, a professor in the Department of Orthodontics and co-senior author of the work. "When the drug was administered without the nanoparticle carriers, there was no effect on the number of cavities and only a very small reduction in their severity. But when it was delivered by the nanoparticle carriers, both the number and severity of the cavities were reduced."
Plaque formation and tooth decay are chronic conditions that need to be monitored through regular visits to the dental office. The researchers hope their results will someday lead to better--and perhaps permanent--treatments for dental plaque and tooth decay, as well as other biofilm-related diseases.