For children with autism, adjusting the environment to be more soothing could eliminate the need for general anesthesia to cope with routine dental cleanings

Going to the dentist might have just gotten a little less scary for the estimated 1 in 68 U.S. children with autism spectrum disorder as well as children with dental anxiety, thanks to new research from USC.

In an article published on May 1 by the Journal of Autism and Developmental Disorders, researchers from USC and Children's Hospital Los Angeles (CHLA) examined the feasibility of adapting dental environments to be more calming for children with autism spectrum disorder.

"The regular dental environment can be quite frightening for children with autism who, not knowing how to react, tend to be completely averse to whatever we're trying to do," said one of the study's authors, José Polido DDS, head of dentistry at CHLA and assistant professor at the Herman Ostrow School of Dentistry of USC.

Children with autism spectrum disorders -- as well as some typically developing children -- often show heightened responses to sensory input and find these sensations uncomfortable. As such, the dental office, with its bright lights, loud sounds from the dental equipment, and touch of children in and around the mouth, present particular challenges for such children.

In the study, 44 CHLA patients -- 22 with autism and 22 "typically developing" (defined as children not on the autism spectrum)--underwent two professional dental cleanings. One cleaning took place in a regular dental environment, the other in a sensory adapted dental environment. During each session, the child's physiological anxiety, behavioral distress and pain intensity were measured.

"I've talked to several parents who have said, 'We really put off taking our child to the dentist because we know how hard it is and we know he's going to scream and cry,'" said Sharon Cermak, the study's lead author and professor at the USC Mrs. T.H. Chan Division of Occupational Science and Occupational Therapy, as well as professor of pediatrics at the Keck School of Medicine of USC.

To help combat that reaction, researchers adapted the dental environments by turning off overhead office lights and headlamps, projecting slow-moving visual effects onto the ceiling and playing soothing music.

Instead of using traditional means to secure the child in the dental chair, practitioners used a seat cover that looked like a gigantic butterfly whose wings wrapped around the child and provided a comforting, deep-pressure hug.

The research team found that both children who are typically developing as well as those with autism spectrum disorders exhibited decreased psychological anxiety and reported lower pain and sensory discomfort in the sensory-adapted dental environment.

The study -- which represents a unique collaboration between pediatric dentists and occupational therapists--could help improve oral health care for children with autism -- a group reported to suffer from poor oral health, research shows.

The findings could also represent a cost savings to the health care system, with fewer insurance reimbursements paid to dental offices for the additional staff members and general anesthesia often necessary for children with autism.

Next up for the researchers is to increase their sample size -- they'll be using 110 children in each group -- to determine which factors (e.g. age, anxiety, sensory over-responsitivity) best predict which children respond best to the intervention.

"One of our long-term goals with this study is to help dentists develop protocols for their own dental clinics to see how sensory components are contributing to behavioral issues," Cermak said. "I think these protocols can then be translated across the globe."

Arginine, amino acid, could improve oral health

Arginine, a common amino acid found naturally in foods, breaks down dental plaque, which could help millions of people avoid cavities and gum disease, researchers at the University of Michigan and Newcastle University have discovered.

Alexander Rickard, assistant professor of epidemiology at the U-M School of Public Health, and colleagues, discovered that in the lab L-arginine -- found in red meat, poultry, fish and dairy products, and is already used in dental products for tooth sensitivity--stopped the formation of dental plaque.

"This is important as bacteria like to aggregate on surfaces to form biofilms. Dental plaque is a biofilm," Rickard said. "Biofilms account for more than 50 percent of all hospital infections. Dental plaque biofilms contribute to the billions of dollars of dental treatments and office visits every year in the United States."

Dental biofilms are the culprits in the formation of dental caries (cavities), gingivitis and periodontal disease. Surveys indicate that nearly 24 percent of adults in the United States have untreated dental caries, and about 39 percent have moderate-to-severe periodontitis, a number that rises to 64 percent for those over age 65.

Most methods for dental plaque control involve use of antimicrobial agents, such as chlorhexidine, which are chemicals aimed at killing plaque bacteria, but they can affect sense of taste and stain teeth. Antimicrobial treatments have been the subject of debate about overuse in recent years.

Pending further clinical trials to verify their lab findings, the researchers said L-arginine could take the place of the current plaque-controlling biocide substances including chlorhexidine and other antimicrobials.

"At present, around 10-to-15 percent of adults in the Western world have advanced periodontitis, which can lead to loose teeth and even the loss of teeth. Therefore, there is a clear need for better methods to control dental plaque," said Nick Jakubovics, a lecturer at Newcastle University's School of Dental Sciences.

Their findings are reported in the current issue of PLOS ONE.

The mechanism for how L-arginine causes the disintegration of the biofilms needs further study, the researchers said. It appears arginine can change how cells stick together, and can trigger bacteria within biofilms to alter how they behave so that they no longer stick to surfaces, they said.

In conducting their research, team members used a model system they introduced in 2013 that mimics the oral cavity. The researchers were able to grow together the numerous bacterial species found in dental plaque in the laboratory, using natural human saliva.

"Other laboratory model systems use one or a small panel of species," Rickard said. "Dental plaque biofilms can contain tens to hundreds of species, hence our model better mimics what occurs in the mouth, giving us great research insight."

Treating gum disease reduces prostate symptoms

Treating gum disease reduced symptoms of prostate inflammation, called prostatitis, report researchers from Case Western Reserve University School of Dental Medicine and the Departments of Urology and Pathology at University Hospitals Case Medical Center.

Previous studies have found a link between gum disease and prostatitis, a disease that inflames the gland that produces semen. Inflammation can make urination difficult.

"This study shows that if we treat the gum disease, it can improve the symptoms of prostatitis and the quality of life for those who have the disease," said Nabil Bissada, chair of Case Western Reserve's Department of Periodontics and the new study's corresponding author.

The researchers reported their findings in the Dentistry article, "Periodontal Treatment Improves Prostate Symptoms and Lowers Serum PSA in Men with High PSA and Chronic Periodontitis." Naif Alwithanani, a graduate student in the dental school, led the investigation as part of his residency in periodontics.

Bissada explained that gum disease not only affects the mouth, but is a system-wide condition that can cause inflammation in various parts of the body. The dental school has previously found a link between gum disease and fetal deaths, rheumatoid arthritis and heart disease.

The new prostate study

Researchers studied 27 men, 21 years old and older. Each had had a needle biopsy within the past year that confirmed inflammation of the prostate gland, and a blood test that showed elevated prostate specific antigen (PSA) levels--possible signs of inflammation and cancer.

The men were assessed for symptoms of prostate disease by answering questions on the International-Prostate Symptom Score (IPSS) test about their quality of life and possible urination issues.

Researchers found 21 of the 27 participants had no or mild inflammation, but 15 had biopsy-confirmed malignancies. Two had both inflammation and a malignancy.

The men also had to have at least 18 teeth and were examined for signs of gum disease, such as increased levels of inflammation and bleeding and/or loose teeth due to attachment and bone loss.

All the men had moderate to severe gum disease, for which they received treatment. They were tested again for periodontal disease four to eight weeks later and showed significant improvement.

During the periodontal care, the men received no treatment for their prostate conditions. But even without prostate treatment, 21 of the 27 men showed decreased levels of PSA. Those with the highest levels of inflammation benefited the most from the periodontal treatment. Six participants showed no changes.

Symptom scores on the IPSS test also showed improvement.

Bissada is now conducting follow-up research to support the first study's findings. He hopes to make periodontal treatment a standard part of treating prostate disease, much like cardiac patients are often encouraged to visit their dentist before undergoing heart procedures and a dental checkup is advised for women who are pregnant or considering pregnancy.

The connection between mouth bacteria and inflammation in heart disease

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."

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Trends in Endocrinology & Metabolism, Kholy et al.:"Oral infections and cardiovascular disease" http://dx.doi.org/10.1016/j.tem.2015.03.001

How gum disease treatment can prevent heart disease

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.

A novel way to apply drugs to dental plaque

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.

Inflammation in mouth, joints in rheumatoid arthritis

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At the 93rd General Session and Exhibition of the International Association for Dental Research, researcher Sheila Arvikar, Massachusetts General Hospital, Boston, USA, will present a study titled "Inflammation in the Mouth and Joints in Rheumatoid Arthritis." The IADR General Session is being held in conjunction with the 44th Annual Meeting of the American Association for Dental Research and the 39th Annual Meeting of the Canadian Association for Dental Research.

Periodontitis shares pathogenic mechanisms with rheumatoid arthritis (RA) and may trigger its onset. In this study, researchers performed joint and dental examinations, determined Porphyromonas gingivalis (P. gingivalis) antibodies, and examined inflammatory microenvironments in early and chronic RA patients.

Twenty-three RA patients, (15 new-onset disease, eight chronic) and 20 age/gender-matched healthy subjects (HS) without periodontitis/RA were enrolled in this study. Serum P. gingivalis IgG antibodies were measured by ELISA. Twenty inflammatory mediators were measured in serum, saliva, gingival crevicular fluid (GCF), and joint fluid by Luminex.

The 23 patients (87% female) received routine dental care, except for one; none currently smoked. Of the 23 RA patients, 10 had gingivitis and nine had periodontitis. RA patients exhibited increased pocket depth, clinical attachment loss, bleeding on probing and GCF volume compared with HS. Six of 23 patients had P. gingivalis antibodies, and all six had periodontitis.
RA patients showed a marked inflammatory profile in all microenvironments, including oral, despite routine dental care. P. gingivalis antibodies can be considered as biomarkers for rheumatologists in identifying those who may benefit from periodontal treatment.