Tag: Dentistry

A disease-causing bacterium found in the mouth needs manganese, a trace mineral, in order to cause a serious heart infection, according to a preclinical study led by researchers at Virginia Commonwealth University Philips Institute for Oral Health Research in the School of Dentistry. The findings, which may solve a longstanding mystery of why some bacteria need manganese to cause disease, provide possible new targets for antibiotics. Researchers from VCU and MIT have been studying the bacterium Streptococcus sanguinis, which lives in the mouth, to understand its role in infective endocarditis, a heart valve disease. The infection is hard to treat and can be deadly — killing more than 20 percent of the people who contract it. Researchers have known for some time that several types of bacteria responsible for serious infections — including S. sanguinis — need more manganese than others to grow normally. In joint studies published this week in the Journal of Biological Chemistry, researchers showed that an enzyme that provides the building blocks needed for making DNA requires manganese to do its job. When the VCU team eliminated that enzyme or a second protein that attaches the manganese to the enzyme, then the bacterium could no longer cause endocarditis, nor survive within the animal model. The MIT team carefully examined the activity of the purified enzymes and determined the function of each. The VCU-MIT study is the first of its kind to test the importance of these enzymes for causing any disease.

Understanding the importance of manganese in the cell has been key to learning the best way to target the bacterium and stop it from causing disease, according to corresponding author Todd Kitten, Ph.D., associate professor at the Phillips Institute for Oral Health Research at the VCU School of Dentistry. “The best antibiotics attack parts of a bacterium that are critical for bacterial survival, but are not found in human cells,” Kitten said. “The manganese-requiring enzyme meets both requirements because these bacteria need it to survive and humans use a very different, iron-containing enzyme to make DNA building blocks. It is the manganese requirement that makes the bacterial proteins good targets,” he said. Kitten added that humans have very little manganese in their bodies, so these bacteria require specialized systems to take in enough manganese to survive. These uptake systems are not found in humans. The team is in the early stages of a collaboration with Glen Kellogg, Ph.D., associate professor in the Department of Medicinal Chemistry at the VCU School of Pharmacy, to create designer drugs to attack the manganese uptake system in these bacteria. Down the road, it could be possible to target several other disease-causing bacteria that also have this enzyme and likely need it to cause disease, including MRSA; the flesh-eating bacterium, Streptococcus pyogenes; and the bacterium that causes anthrax.

http://www.sciencedaily.com/ Science Daily

March 18, 2014

http://www.sciencedaily.com/releases/2014/03/140305125245.htm Original web page at Science Daily

Researchers may have uncovered new evidence of ancient dentistry in the form of a 6,500-year-old human jaw bone with a tooth showing traces of beeswax filling, as reported Sept. 19 in the open access journal PLOS ONE. The researchers, led by Federico Bernardini and Claudio Tuniz of the Abdus Salam International Centre for Theoretical Physics in Italy in cooperation with Sincrotrone Trieste and other institutions, write that the beeswax was applied around the time of the individual’s death, but cannot confirm whether it was shortly before or after. If it was before death, however, they write that it was likely intended to reduce pain and sensitivity from a vertical crack in the enamel and dentin layers of the tooth. According to Tuniz, the severe wear of the tooth “is probably also due to its use in non-alimentary activities, possibly such as weaving, generally performed by Neolithic females.” Evidence of prehistoric dentistry is sparse, so this new specimen, found in Slovenia near Trieste, may help provide insight into early dental practices. “This finding is perhaps the most ancient evidence of pre-historic dentistry in Europe and the earliest known direct example of therapeutic-palliative dental filling so far,” says Bernardini.

Science Daily
October 2, 2012

Original web page at Science Daily

A Chinese research team, led by Anhui Medical University and BGI, has found strong genetic evidence of a link between mutations of the mevalonate kinase gene (MVK) and disseminated superficial actinic porokeratosis (DSAP). It is a major step toward discovering the genetic pathogenesis of DSAP, and sheds light on its further molecular diagnosis and treatment. The latest study was published online in Nature Genetics. DSAP is a rare, non-cancerous, non-contagious skin disorder that causes dry, itchy lesions on the arms and legs. It usually begins to develop in adolescents and reach near-complete penetrance by the third or fourth decade of life. The accumulated sun exposure is a risk factor for DSAP. DSAP is a chronic disorder; it can be treated, but it cannot be cured. In this study, Chinese researchers performed exome sequencing in two affected and one unaffected individuals who belong to a DSAP family. Through variants analysis and data filtering, they supposed that MVK gene emerged as the only candidate gene located in previously defined linkage region linked to DSAP. Then they confirmed the co-segregation between the identified novel deleterious mutation and DSAP phenotype within the family.

To further identify novel MVK mutations, researchers conducted Sanger sequencing in other DSAP cases, which identified additional novel deleterious mutations. And none of which was detected in 676 unrelated and ethnically matched controls. It provided strong evidence that these novel mutations were not polymorphisms. They did not find MVK mutations in other clinical subtypes of Porokeratosis, suggesting that MVK mutations may be specific to DSAP patients. Mevalonate kinase, the protein encoded by MVK, is an important enzyme in the mevalonate pathway that is vital for multiple cellular processes by providing cells with essential bioactive molecules. In the investigation of the impact of MVK expression on the biological activities of keratinocytes, researchers indicated that MVK plays a role in regulating calcium-induced keratinocytes differentiation and the MVK expression could protect keratinocytes from UVA-caused apoptosis. Tao Jiang, senior scientist of this project at BGI, said, “Considering the high genetic heterogeneity of DSAP, it is fortunate for us to find the causative gene MVK by sequencing only three exomes and using previous genome-wide linkage results. Our study provides new insights into the pathogenesis of DSAP, and the identified MVK mutations offer the best candidate targets for gene diagnosis and clinical treatment of the disease.” Xuejun Zhang, corresponding author of this study, President of Anhui Medical University, said, “The exome sequencing is an effective method for identifying disease gene of monogenetic diseases in recent years. In this study, the Chinese scientists found disease gene MVK for DSAP using exome sequencing plus functional study. It not only indicates China has step into the most advanced level in searching the disease genes for monogenetic disease in the world, but also provides scientific basis for revealing DSAP pathogenesis, genetic counseling, risk prediction, prenatal diagnosis, new drug development, clinical diagnosis and treatment.”

Science Daily
October 2, 2012

Original web page at Science Daily

Scientists using nanotechology at the University of Maryland School of Dentistry have created the first cavity-filling composite that kills harmful bacteria and regenerates tooth structure lost to bacterial decay. Rather than just limiting decay with conventional fillings, the new composite is a revolutionary dental weapon to control harmful bacteria, which co-exist in the natural colony of microorganisms in the mouth, says professor Huakun (Hockin) Xu, PhD, MS. “Tooth decay means that the mineral content in the tooth has been dissolved by the organic acids secreted by bacteria residing in biofilms or plaques on the tooth surface. These organisms convert carbohydrates to acids that decrease the minerals in the tooth structure,” says Xu, director of the Division of Biomaterials and Tissue Engineering in the School’s Department of Endodontics, Prosthodontics and Operative Dentistry.

After a dentist drills out a decayed tooth, the cavity still contains residual bacteria. Xu says it is not possible for a dentist to remove all the damaged tissue, so it’s important to neutralize the harmful effects of the bacteria, which is just what the new nanocomposites are able to do. The researchers also have built antibacterial agents into primer used first by dentists to prepare a drilled-out cavity and into adhesives that dentists spread into the cavity to make a filling stick tight to the tissue of the tooth. “The reason we want to get the antibacterial agents also into primers and adhesives is that these are the first things that cover the internal surfaces of the tooth cavity and flow into tiny dental tubules inside the tooth,” says Xu. The main reason for failures in tooth restorations, says Xu, is secondary caries or decay at the restoration margins. Applying the new primer and adhesive will kill the residual bacteria, he says. Fillings made from the School of Dentistry’s new nanocomposite, with antibacterial primer and antibacterial adhesive, should last longer than the typical five to 10 years, though the scientists have not thoroughly tested longevity. Xu says a key component of the new nanocomposite and nano-structured adhesive is calcium phosphate nanoparticles that regenerate tooth minerals. The antibacterial component has a base of quaternary ammonium and silver nanoparticles along with a high pH. The alkaline pH limits acid production by tooth bacteria. “The bottom line is we are continuing to improve these materials and making them stronger in their antibacterial and remineralizing capacities as well as increasing their longevity,” Xu says.

Science Daily
May 15, 2012

Original web page at Science Daily

Stripping some mouth bacteria of their access key to gangs of other pathogenic oral bacteria could help prevent gum disease and tooth loss. The study, published in the journal Microbiology suggests that this bacterial access key could be a drug target for people who are at high risk of developing gum disease. Oral bacteria called Treponema denticola frequently gang up in communities with other pathogenic oral bacteria to produce destructive dental plaque. This plaque, made up of bacteria, saliva and food debris, is a major cause of bleeding gums and gum disease. Later in life this can lead to periodontitis and loss of teeth. It is this interaction between different oral pathogens that is thought to be crucial to the development of periodontal disease. Researchers from the University of Bristol have discovered that a molecule on the surface of Treponema called CTLP acts as the key pass that grants the bacterium access to the community, by allowing it to latch onto other oral bacteria. Once incorporated, CTLP in conjunction with other bacterial molecules can start to wreak havoc by inhibiting blood clotting (leading to continued bleeding of the gums) and causing tissue destruction.

Professor Howard Jenkinson, who led the study, said that periodontal disease and bleeding gums are common ailments, affecting many groups of people, including the elderly, pregnant women and diabetics. “Devising new means to control these infections requires deeper understanding of the microbes involved, their interactions, and how they are able to become incorporated into dental plaque,” he said. The study shows that CTLP could be a good target from which novel therapies could be developed. “CTLP gives Treponema access to other periodontal communities, allowing the bacteria to grow and survive. Inhibiting CTLP would deny Treponema access to the bacterial communities responsible for dental plaque, which in turn would reduce bleeding gums and slow down the onset of periodontal disease and tooth loss.” The team is now working to find a compound that will inhibit CTLP. “If a drug could be developed to target this factor, it could be used in people who are at higher risk from developing gum disease,” explained Professor Jenkinson. The latest study backs up previous work in Professor Jenkinson’s lab on the workings of harmful oral bacteria. “The overarching message from our latest study as well as previous work is that regular tooth brushing and maintaining a healthy mouth is vitally important to keep harmful mouth bacteria at bay,” he stressed.

Science Daily
February 21, 2012

Original web page at Science Daily

The Groningen professors Bauke Dijkstra and Lubbert Dijkhuizen have deciphered the structure and functional mechanism of the glucansucrase enzyme that is responsible for dental plaque sticking to teeth. This knowledge will stimulate the identification of substances that inhibit the enzyme. Just add that substance to toothpaste, or even sweets, and caries will be a thing of the past. The University of Groningen researchers analysed glucansucrase from the lactic acid bacterium Lactobacillus reuteri, which is present in the human mouth and digestive tract. The bacteria use the glucansucrase enzyme to convert sugar from food into long, sticky sugar chains. They use this glue to attach themselves to tooth enamel. The main cause of tooth decay, the bacterium Streptococcus mutans, also uses this enzyme. Once attached to tooth enamel, these bacteria ferment sugars releasing acids that dissolve the calcium in teeth. This is how caries develops. The results of the research have been published this week in the journal Proceedings of the National Academy of Sciences (PNAS).

Using protein crystallography, the researchers were able to elucidate the three dimensional (3D) structure of the enzyme. The Groningen researchers are the first to succeed in crystallizing glucansucrase. The crystal structure has revealed that the folding mechanism of the protein is unique. The various domains of the enzyme are not formed from a single, linear amino acid chain but from two parts that assemble via a U-shaped structure of the chain; this is the first report on such a folding mechanism in the literature. The unravelling of the 3D structure provided the researchers with detailed insight into the functional mechanism of the enzyme. The enzyme splits sucrose into fructose and glucose and then adds the glucose molecule to a growing sugar chain. Thus far the scientific community assumed that both processes were performed by different parts of the enzyme. However, the model created by the Groningen researchers has revealed that both activities occur in the same active site of the enzyme.

Dijkhuizen expects that specific inhibitors for the glucansucrase enzyme may help to prevent attachment of the bacteria to the tooth enamel. Information about the structure and functional mechanism of the enzyme is crucial for developing such inhibitors. Thus far, such research has not been successful, states Dijkhuizen: ‘The various inhibitors studied not only blocked the glucansucrase, but also the digestive enzyme amylase in our saliva, which is needed to degrade starch.’ The crystal structure also provides an explanation for this double inhibition. The data published by the Groningen scientists shows that glucansucrase proteins most likely evolved from amylase enzymes that degrade starch. ‘We already knew that the two enzymes were similar’, says Dijkhuizen, ‘but the crystal structure revealed that the active sites are virtually identical. Future inhibitors thus need to be directed towards very specific targets because both enzymes are evolutionary closely related.’ Dijkhuizen points out that in future glucansucrase inhibitors may be added to toothpaste and mouthwash. ‘But it may even be possible to add them to sweets’, he suggests. ‘An inhibitor might prevent that sugars released in the mouth cause damage.’ However, Dijkhuizen doesn’t expect that toothbrushes have had their day: ‘it will always be necessary to clean your teeth.’

Science Daily
December 21, 2010

Original web page at Science Daily

Plasma jets capable of obliterating tooth decay-causing bacteria could be an effective and less painful alternative to the dentist’s drill, according to a new study published in the February issue of the Journal of Medical Microbiology. Firing low temperature plasma beams at dentin – the fibrous tooth structure underneath the enamel coating – was found to reduce the amount of dental bacteria by up to 10,000-fold. The findings could mean plasma technology is used to remove infected tissue in tooth cavities – a practice that conventionally involves drilling into the tooth. Scientists at the Leibniz-Institute of Surface Modifications, Leipzig and dentists from the Saarland University, Homburg, Germany, tested the effectiveness of plasma against common oral pathogens including Streptococcus mutans and Lactobacillus casei. These bacteria form films on the surface of teeth and are capable of eroding tooth enamel and the dentin below it to cause cavities. If left untreated it can lead to pain, tooth loss and sometimes severe gum infections. In this study, the researchers infected dentin from extracted human molars with four strains of bacteria and then exposed it to plasma jets for 6, 12 or 18 seconds. The longer the dentin was exposed to the plasma the greater the amount of bacteria that were eliminated.

Plasmas are known as the fourth state of matter after solids, liquids and gases and have an increasing number of technical and medical applications. Plasmas are common everywhere in the cosmos, and are produced when high-energy processes strip atoms of one or more of their electrons. This forms high-temperature reactive oxygen species that are capable of destroying microbes. These hot plasmas are already used to disinfect surgical instruments. Dr Stefan Rupf from Saarland University who led the research said that the recent development of cold plasmas that have temperatures of around 40 degrees Celsius showed great promise for use in dentistry. “The low temperature means they can kill the microbes while preserving the tooth. The dental pulp at the centre of the tooth, underneath the dentin, is linked to the blood supply and nerves and heat damage to it must be avoided at all costs.” Dr Rupf said using plasma technology to disinfect tooth cavities would be welcomed by patients as well as dentists. “Drilling is a very uncomfortable and sometimes painful experience. Cold plasma, in contrast, is a completely contact-free method that is highly effective. Presently, there is huge progress being made in the field of plasma medicine and a clinical treatment for dental cavities can be expected within 3 to 5 years.”

EurekAlert! Medicine
February 9, 2010

Original web page at EurekAlert! Medicine

The next person who reminds you to floss might be your cardiologist instead of your dentist. Scientists have known for some time that a protein associated with inflammation (CRP) is elevated in people who are at risk for heart disease. But where’s the inflammation coming from? A new research study by Italian and U.K. scientists published online in The FASEB Journal shows that infected gums may be one place. Indeed, proper dental hygiene should reduce the risk of atherosclerosis, stroke and heart disease independently of other measures, such as managing cholesterol. “It has been long suspected that atherosclerosis is an inflammatory process, and that periodontal disease plays a role in atherosclerosis,” said Mario Clerici, M.D., a senior researcher on the study. “Our study suggests that this is the case, and indicates that something as simple as taking good care of your teeth and gums can greatly reduce your risk of developing serious diseases.”

To reach this conclusion, the scientists examined the carotid arteries of 35 otherwise healthy people (median age 46) with mild to moderate periodontal disease before and after having their periodontal disease treated. One year after treatment, the scientists observed a reduction in oral bacteria, immune inflammation and the thickening of the blood vessels associated with atherosclerosis. “Because many Americans have some form of gum disease, this research can’t be brushed aside,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “As it turns out, the health of our blood vessels could be hanging by the proverbial thread: dental floss.”

The FASEB Journal
January 13, 2009

Original web page at The FASEB Journal

Individuals reporting a history of periodontal disease were more likely to have increased levels of inflammation, a risk factor for heart disease, compared to those who reported no history of periodontal disease, according to an American Journal of Cardiology report available online. Led by investigators from Columbia University Medical Center and NewYork-Presbyterian Hospital, the findings suggest persons with increased levels of inflammatory markers associated with a higher risk of cardiovascular disease might be identified by asking about oral health history. This group might not be detected by traditional cardiovascular risk screening. Inflammation has been associated with cardiovascular disease and has been suggested to be a potential link between periodontal disease and cardiovascular disease. To examine whether oral health history and inflammatory markers associated with cardiovascular disease were linked, the investigators followed participants in the National Heart, Lung and Blood Institute (NHLBI) Family Intervention Trial for Heart Health (F.I.T. Heart), an ongoing national trial led by principal investigator Lori Mosca, M.D., M.P.H., Ph.D., professor of medicine at Columbia University College of Physicians and Surgeons and director of preventive cardiology at NewYork-Presbyterian Hospital/Columbia University Medical Center.

The NHLBI Family Intervention Trial for Heart Health aims to study family members of patients hospitalized with heart disease because they may be at increased risk themselves due to shared genetic and/or lifestyle factors. Dr. Mosca and her research team recruited family members or co-habitants of patients hospitalized for such cardiac events as a heart attack or narrowed arteries that required bypass surgery or an angioplasty procedure. Previous research has shown that family members of cardiovascular disease patients may be at increased risk for the disease due to the genes and lifestyle habits they share. In this study, 421 individuals who were blood related to and/or living with a person recently hospitalized due to cardiovascular disease were screened for traditional cardiovascular risk factors (such as elevated blood pressure and abnormal cholesterol levels), inflammatory markers associated with disease risk (high-sensitivity c-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2)). They were also asked standardized questions about their oral health status, including whether they had ever been diagnosed with periodontal (gum) disease, whether they had ever been treated for periodontal disease, whether they used partial or complete removable dentures, and the date of their last teeth cleaning. The oral health history was then correlated with standard markers of inflammation.

Results found that among participants who did not have traditional cardiovascular disease risk factors (such as high blood pressure, high cholesterol, and overweight/obese status), almost one in four were found to have a personal history of periodontal disease and higher levels of Lp-PLA2, an inflammatory marker which has been found present in inflamed rupture prone plaque in heart arteries/valves. It is important to note that it is not possible to determine from this study that poor oral health causes cardiovascular disease risk or that any therapy based on oral health status would be effective in preventing cardiovascular disease. However, Dr. Mosca says, “Our finding is novel because it suggests the dentist and oral health exam may be the latest weapon in identifying persons at risk of cardiovascular disease, our nation’s number one killer.” “Many people don’t realize how oral health is often a predictor of one’s overall health,” says co-author John T. Grbic, DMD, MS, MMSc, professor of clinical dental medicine at the Columbia University College of Dental Medicine. “Symptoms for many life-threatening illnesses, such as diabetes and heart disease, first appear in the mouth. For this reason, it’s vitally important for people to have routine dental check-ups and have an ongoing dialogue with their dentist about their oral health. Patients may also benefit from seeing dentists affiliated with an academic medical center, where they are tapped into deep referral networks to appropriate clinicians.”

EurekAlert! Medicine
December 9, 2008

Original web page at EurekAlert! Medicine

Researchers at the University of Southern California School of Dentistry say they have improved upon a surgical procedure developed by periodontist Tom Wilcko that rapidly straightens teeth, delivering a healthy bite and attractive smile in months instead of years. Led by Hessam Nowzari DDS, PhD, Director of the USC School of Dentistry and Advanced Education in Periodontology program, the researchers have published the first case study of the successful use of a patient’s own bone material for the grafting necessary in the accelerated orthodontic surgical procedure. The report appears in the May 2008 issue of the Compendium of Continuing Education in Dentistry. Accelerated orthodontics is gaining popularity as a way for patients, particularly adults with mature bones, to speed up the time it takes to straighten misaligned bites and fix crowded teeth. Wilcko, who operates a practice in Erie, Penn., offers courses in the procedure, trademarked as “Wilckodontics.”

USC dentists used a procedure known as PAOO, short for Periodontally Accelerated Osteogenic Orthodontics. With this technique, a periodontist or oral surgeon uses special instruments to score the bone that holds the teeth in place and then applies bone graft material over the grooves. The procedure is done under local anesthetic in the dental office operatory. As the bone begins to heal, it softens slightly, allowing teeth to be moved into alignment with dental braces in a matter of months, rather than the years required with traditional orthodontics. The cost for accelerated orthodontics typically ranges from $10,000 to $15,000, depending on the course of treatment. Prior to the USC study, the bone graft material used for this procedure was bovine bone and bioactive glass particles to help the bone strengthen as it healed. Nowzari says that his team believed they could improve the technique by using the patient’s own bone instead of the artificial or bovine graft. “Given a choice for grafts, nothing is better than a patient’s own tissue,” Nowzari explains. “It encourages new, healthy bone formation in the grafted area. It’s very safe and eliminates the risk of any disease transmission.”

Science Daily
July 8, 2008

Original web page at Science Daily

Good dental hygiene and health may be crucial in preventing heart valve infection, according to research reported in Circulation: Journal of the American Heart Association. In a study of 290 dental patients, researchers investigated several measures of bacteremia (bacteria released into the bloodstream) during three different dental activities — tooth brushing, a single tooth extraction with a preventive antibiotic and a single tooth extraction with a placebo. As expected, researchers found bacteria in the blood more often with the two extraction groups than with the brushing group. However, the incidence of bacteremia from brushing was closer to an extraction than expected. “This suggests that bacteria get into the bloodstream hundreds of times a year, not only from tooth brushing, but also from other routine daily activities like chewing food,” said the study’s lead author Peter Lockhart, D.D.S.

In 2007, the American Heart Association modified its recommendation that preventive antibiotics be used prior to most dental procedures for the great majority of those at risk for infective endocarditis (IE) — a rare but life-threatening infection of the lining of the heart or heart valve that can occur when bacteria enter the bloodstream. The association now recommends preventive antibiotics only for patients at the highest risk for a bad outcome from IE. In this double-blind, placebo-controlled study, researchers sought to determine if daily dental activities like tooth brushing posed as much risk for IE as major dental procedures (e.g., tooth extractions) for which preventive antibiotics might be prescribed. Researchers drew blood from each patient a total of six times — before, during and after these interventions — and analyzed the samples for bacterial species that are associated with IE. They found that bacteria enter the bloodstream in most patients early on during a dental extraction or tooth brushing, and that bacteria can still be found in the blood as long as an hour after these procedures in a small number of cases.

“While the likelihood of bacteremia is lower with brushing, these routine daily activities likely pose a greater risk for IE simply due to frequency: that is, bacteremia from brushing twice a day for 365 days a year versus once or twice a year for dental office visits involving teeth cleaning, or fillings and other procedures,” said Lockhart, chair of the Department of Oral Medicine at the Carolinas Medical Center, Charlotte, N.C. “For people who are not at risk for infections such as IE, the short-term bacteremia is nothing to worry about,” he said. If you stop oral hygiene measures, the amount of disease in your mouth goes up considerably and progressively and you’ll have far worse oral disease,” Lockhart said. “It’s the gingival (gum) disease and dental caries (decay), that lead to chronic and acute infections such as abscesses. It’s that sort of thing that puts you at risk for frequent bacteremia and presumably endocarditis if you have a heart or other medical condition that puts you at risk.”

“The incidence of IE-related bacteremia from all blood draws was 23 percent in the tooth-brushing group, 33 percent in the extraction plus antibiotic group, and 60 percent for the extraction-placebo group,” Lockhart said. The researchers therefore found that amoxicillin significantly decreased the incidence of bacteremia from an extraction but did not eliminate it altogether. The highest incidence of positive IE-related bacterial cultures occurred within five minutes of all three procedures, with the majority (93 percent) of patients with bacteria in the blood experiencing the condition for less than 20 minutes after the procedures. Only 5 percent of the extraction-placebo group and 2 percent of the brushing group still had bacteria in the blood at one hour. “The human mouth is colonized by a larger variety of bacteria than any other body area, and many of the bacterial species in the mouth that cause disease are found in the periodontal pocket (below the gum line) adjacent to the teeth,” said Lockhart, adding that some of those species have been associated with IE. “Bacteria commonly gain entrance to the circulation through ulcerated gingival (gum) tissue surrounding the teeth, but oral hygiene reduces gingival disease and reduces that risk.” Patients in this study came to an urgent care clinic in need of tooth extractions. So it’s likely they had a higher level of dental disease and poorer oral hygiene than the general population.

The researchers are analyzing additional data from this study to determine if there is a direct correlation between the level of dental disease and the likelihood of IE bacteria getting into the bloodstream. According to the American Heart Association, those at highest risk for adverse outcomes from IE are 1) patients with a prosthetic cardiac valve or prosthetic material used for cardiac valve repair; 2) previous endocarditis; 3) cardiac transplantation recipients who develop cardiac valve abnormalities; and 4) congenital heart disease for unrepaired cyanotic congenital heart disease, including palliative shunts and conduits; completely repaired congenital heart defect with prosthetic material or device, during the first six months after the procedure; or repaired congenital heart disease with persisting leaks or abnormal flow at the site or adjacent to the site of a prosthetic patch or prosthetic device.

Science Daily
June 24, 2008

Original web page at Science Daily

Researchers at Columbia University, including Jeremy Mao of the Columbia College of Dental Medicine, have demonstrated a novel way of using porous structures as a drug-delivery vehicle that can help boost the integration of host tissue with surgically implanted titanium. Instead of being acted upon by the body as an impenetrable foreign object, the synthetic bone replacement — currently being tested in rabbits — features a porous material that allows for the delivery of “microencapsulated bioactive cues” that speed up the growth of host tissue at the site and allow for the growth of new bone. A critical finding is that the drug dose needed for host tissue integration by this controlled-release approach is about 1/10 of that by the traditional technique of simple adsorption of the growth factor.

The approach could bring to orthopedics and dentistry a treatment that has wrought much interest and success in the field of cardiology with the development of drug-eluting stents, which take what is ordinarily an inert tube, and infuse it with drugs to make the placement of what is essentially a man-made, foreign object more compatible with the patient’s body, and at the same time, actively promoting healing of injured tissue. After just four weeks, the porous implants that Mao and his team are using showed a 96 percent increase in bone-to-implant contact and a 50 percent increase in the growth of new bone over placebos. Since stem cells play a vital role in the growth of new bone, Mao and his team have focused on impregnating the titanium implants with a factor that “homes” the bodies’ own regenerating cells to the potential growth site to create and build on a platform for new bone.

The new approach may in the future obviate the need to harvest bone from a non-injured site in the body for grafting into the site of injury, as commonly performed now. This strategy, although often effective, creates additional wounds. The work of Mao and his team suggests that it should be possible to harnesses the body’s natural tissue regeneration capacity to recruit the right cells to the site where new bone tissue is needed. Implants that naturally attract the mesenchymal stem cells that can readily differentiate into bone, fat, cartilage and other types of cells could be the way of the future, Mao says. “In comparison with donor site morbidity and pain in association with autologous tissue grafting, synthetic materials have the advantage of ready and endless supply without any sacrifice of donor tissue,” he says. The approach also overcomes a practical obstacle confronting many orthopedic surgeons.

“This is a hybrid approach releasing biological cues from existing orthopedic and dental implants to recruit the body’s own stem cells. It’s unrealistic, at least from what we know now, to build a cell culture room next to every operating room,” Mao added. “Using these types of porous implants doesn’t require physicians to deliver stems cells so much as it allows the patient’s body to send its own cells to the right place.”

Science Daily
February 19, 2008

Original web page at Science Daily

Bacteria that eat sugar and release cavity-causing acid onto teeth may soon be made dramatically more vulnerable to their own acid. Researchers have identified key genes and proteins that, if interfered with, can take away the ability of a key bacterial species to thrive as its acidic waste builds up in the mouth. The ability of Streptococcus mutans (S. mutans) to survive in acid is one reason that the species is the main driver of tooth decay worldwide. Past research has shown that this ability has several components including a bacterial enzyme called fatty acid biosynthase M (FabM), which when shut down, makes S. mutans almost precisely 10,000 times more vulnerable to acid damage. In addition, early work suggests that FabM or one of its relatives may also help all Streptococci (strep) and Staphylococci (staph) infections to resist the human body’s defenses, which include immune cells that subject bacteria to acid. Between them, “strep” and “staph” bacteria are responsible for meningitis, pneumonia, sepsis, methicillin-resistant staph aureus, the “flesh-eating” infection (fasciitis), as well as infections on heart valves and around stents.

While FabM represents a major target for the design of new drugs, the focus of the next round of work is to identify and rank every one of the 2,000 known S. mutans genes that contributes to its “fitness” (ability to survive, out-compete other strains and cause disease). A research team at the University of Rochester Medical Center announced that it has received a $3.6 million fitness profiling grant from the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health (NIH). Grant-funded projects will seek to create a catalogue of proteins that, along with FabM, can serve as targets for a multi-pronged attack on bacteria that tend to evolve around single-thrust treatments. “Our first goal is to force the major bacterium behind tooth decay to destroy itself with its own acid as soon as it eats sugar,” said Robert G. Quivey, Ph.D., professor of Microbiology & Immunology at the University of Rochester Medical Center and principal investigator for the grant. “After that, this line of work could help lead to new anti-bacterial combination therapies for many infections that have become resistant to antibiotics.”

Science Daily
January 22, 2008

Original web page at Science Daily

High-tech dental lasers used mainly to prepare cavities for restoration now can help eliminate bacteria in root canals, according to research published in the July issue of The Journal of the American Dental Association (JADA). The study, conducted by researchers in Austria, credits the development of miniaturized, flexible fiber tips for allowing the laser to be used in endodontic (root canal) treatment. Dr. Ulrich Schoop and a team of researchers in the dental school at the University of Vienna used 60 extracted human teeth with one root each to test the effects of laser irradiation on root canals using an erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser. Dr. Schoop and colleagues inoculated the root canals with one of two types of bacteria (Enterococcus faecalis and Escherichia coli) and then irradiated the canals using either a 1- or 1.5-watt power setting. The team found that the laser reduced the amount of E. coli at the lower power setting and reduced it to below the detection level at the higher setting. It also was effective in eliminating E. faecalis.

Researchers found, too, that the laser removed the smear layer and debris from the root canal walls and that the temperature rise during irradiation was within safe borders. The authors concluded that the Er,Cr:YSGG laser may be suitable for cleaning and disinfecting root canals and that it can be used safely if the common precautions for using lasers are observed and the energy levels and irradiation times are within the proposed range. They also suggested that clinical studies are needed to confirm their laboratory findings. In a related article in July JADA, Dr. Roy H. Stevens and colleagues at the Kornberg School of Dentistry, Temple University, describe their study of an Er,Cr:YSGG laser with a new tip that emits radiation radially. Dr. Stevens and colleagues examined the efficiency of this new laser tip in disinfecting root canal dentin walls infected with E. faecalis. They found that it significantly reduced the amount of E. faecalis in contaminated root canals.

Science Daily
August 21, 2007

Original web page at Science Daily

More than 92 percent of Illinois dentists provide oral cancer examinations for their patients, but many are not performing the procedures thoroughly or at optimum intervals, according to a new University of Illinois at Chicago study. With an incomplete understanding of the nature of pre-malignant lesions and of proper examination techniques, some dentists in Illinois “are not doing all they should be doing to detect oral cancers in their patients,” said Charles LeHew of the UIC Cancer Center’s Center for Population Health and Health Disparities and the Institute for Health Research and Policy. More than 500 dentists in 19 Illinois counties responded to the 38-item questionnaire that was used to gauge the extent of their knowledge of oral cancer prevention and early detection. A greater than 60 percent response rate indicated that Illinois dentists “take seriously their important role in addressing the state’s oral cancer burden,” said LeHew, who was the lead researcher of the study.

According to LeHew, the majority of dentists correctly identified squamous cell carcinoma, the most common form of oral cancer, as well as the most common sites for oral cancer and the most-common types of early lesions. Many, however, were not able to answer those questions correctly. Moreover, dentists lacked knowledge needed for risk assessment and counseling. For example, when asked which of several risk factors is least important, the most frequent answer was age — which is actually an important factor, LeHew said. “Some dentists incorrectly identified tobacco or alcohol as the least important risk factor, when in fact they are the two most important,” he said. Two-thirds of the dentists had had oral cancer continuing education; however, 40 percent had trained more than two years prior to the survey. And training in risk counseling was rare, LeHew said. “There is a clear need for additional training and for greater vigilance.”

Approximately 31,000 Americans will be diagnosed with oral or pharyngeal cancer this year; it will cause more than 8,000 deaths. Of the newly diagnosed patients, only half will be alive in five years, according to the Oral Cancer Foundation. Survival has not significantly improved in decades. The death rate for oral cancer is higher than for cervical cancer; Hodgkin’s disease; and cancer of the brain, liver, testes, kidney or skin (malignant melanoma). Early detection is essential in increasing the survival rate for oral cancer. Symptoms include a mouth sore that fails to heal or that bleeds easily; a white or red patch in the mouth that may not be painful but will not go away; a lump, thickening or soreness in the mouth, throat or tongue; and difficulty chewing or swallowing food. “Illinois dentists face many barriers to providing early detection and risk counseling services to their patients,” said Dr. Linda Kaste, associate professor of prevention and public health sciences who co-authored the study. “Lack of proper training and adequate time appear to be chief among them.”

To increase awareness of the disease, UIC has been working with organizations in several Illinois counties that have high incidences of oral cancer to develop and distribute public health education materials, Kaste said. Oral cancer screenings are also provided to the underserved populations. The counties are located in northeast, central, western, and southwestern Illinois. LeHew said the findings of the study were similar to studies in other states. Illinois dentists are performing at levels similar to dentists in other parts of the country, he said. “Dentists are not going to diagnosis cancer,” he said. “They are going to find potentially dangerous lesions and refer the patient to an oral surgeon. Because dentists are intimately familiar with the oral cavity, they can take a look around while they are examining a patient. “The expectations are not clear for what dentists should do in regards to oral cancer. We need to identify what the best practices are. There is still a lot of work to be done to get there.”

Science Daily Health & Medicine
June 12, 2007

Original web page at Science Daily Health & Medicine

The mouth is a tough environment–which is why dentists do not give lifetime guarantees. Despite their best efforts, a filling may eventually crack under the stress of biting, chewing and teeth grinding, or secondary decay may develop where the filling binds to the tooth. Fully 70 percent of all dental procedures involve replacements to existing repairs, at a cost of $5 billion per year in the United States alone. Now, however, scientists at the American Dental Association’s Paffenbarger Research Center, a joint research program at the National Institute of Standards and Technology (NIST), have shown that nanotechnology has the potential to lessen that toll by producing tooth restorations that are both stronger than any decay-fighting fillings available today, and more effective at preventing secondary decay. They report their findings in a recent issue of The Journal of Dental Research.

The researchers’ new technique solves a problem with the standard composite resin filling, a natural-looking restoration that is the method of choice when appearance is an issue. A dentist creates the filling by mixing the pure liquid resin with a powder that contains coloring, reinforcement and other materials, packing the resulting paste into the cavity, and illuminating the tooth with a light that causes the paste to polymerize and harden. For decay-fighting composite fillings, the problem arises from an additive that is included in the powder to provide a steady release of calcium and phosphate ions. These ions are essential to the long-term success of the filling because they not only strengthen the crystal structure of the tooth itself, but buffer it against the decay-causing acid produced by bacteria in the mouth. Yet the available ion-releasing compounds are structurally quite weak, to the point where they weaken the filling as a whole.

To get around this conundrum, the Paffenbarger researchers have devised a spray-drying technique that yields particles of several such compounds, one of which being dicalcium phosphate anhydrous, or DCPA, that are about 50 nanometers across–20 times smaller than the 1-micrometer particles in a conventional DCPA powder. Because these nanoscale particles have a much higher surface to volume ratio, they are much more effective at releasing ions, which means that much less of the material is required to produce the same effect. That, in turn, leaves more room in the resin for reinforcing fibers that strengthen the final filling. To exploit that opportunity, the Paffenbarger researchers also have developed nanoscale silica-fused fibers that produce a composite resin nearly twice as strong as the currently available commercial variety.

Science Daily
May 15, 2007

Original web page at Science Daily

Who would have guessed that when the Star Trek medical diagnostic tool known as the tricorder makes its appearance in real life, the first user might be . . . your dentist. According to a paper in the March 27 issue of PNAS (the Proceedings of the National Academy of Sciences), a recently completed pilot study conducted with the University of Michigan shows that a Sandia National Laboratories handheld device determined in minutes — from a tiny sample of saliva alone — not only if a patient has gum disease but quantitatively how advanced the disease is. “The gold standard for any medical test is when instruments are used to examine human patients,” says Sandia researcher Amy Herr. “The pilot study allowed us to compare our results to accepted clinical measurements. Then we could statistically validate both the periodontal disease biomarker and the new microfluidic instrument.

“We achieved faster and more reproducible results because we combined steps that ordinarily require time-consuming manual handling by many people, into a single automated device.” Because the amount of sample fluid needed for testing is so small, Herr sees further applications in other disease areas — including potentially improved diagnosis of prostate and breast cancer — as well as rapid measurements of serum in animal models employed in vaccine development research. Says Sandia researcher Anup Singh, “This technology also has great promise for Sandia’s efforts in homeland defense. We have on-going efforts to use the diagnostic platform to detect biotoxins and other markers in bodily fluids to be able to diagnose exposure to a biological agent.” “We’ve filed patents and technical advances to protect the work,” Herr says. “The study has sparked commercial and university interest in our inventions. Our team — an interdisciplinary group of internal and external collaborators — believes Sandia’s contributions in this area could advance personalized medicine. So we’re motivated to extend the limits of Sandia’s lab-on-a-chip tools.”

A “lab on a chip” refers to an entire laboratory on an area the size of a computer chip, requiring only minute amounts of material to perform automated chemical analysis. While components of the saliva-detection technique were reported earlier by Sandia, this is the first comprehensive study of Sandia’s integrated clinical method. The basic principle? “Biomedical researchers have suspected that changes in the amount or type of proteins present may be useful as biological markers in disease diagnosis,” says Herr. “Our current work with a particular enzyme in saliva supports that hypothesis regarding periodontal disease.”Aiding dental practitioners, the pocket-sized device measures the state of biomarkers to determine how much the disease has been set back. Its progress may be cloaked, silently advancing or retreating without showing any signs.

“Periodontitis can be episodic in nature,” says Herr. “You need to know the stage of disease progression to diagnose and treat the illness most effectively. The enzyme [biomarker] that we monitored decreased or stabilized if the treatment was working well.” Often, owing to the time and expense involved, practitioners formerly had not been able to perform extensive biochemical investigations. The work, funded by the National Institute of Dental and Craniofacial Research (NIDCR) — one of 20 institutes in the National Institutes of Health — is the first application using microliters of saliva, a painlessly and easily secured fluid. The real-life alternative for the most part has been quasi-subjective physiological measurements, such as gum recession and gum bleeding on probing, to diagnose periodontitis.

Unlike Sandia’s MicroChemLab — its patented version of a lab on a chip — which reports multiple protein signatures in fluids of interest, the clinical diagnostic instrument described in PNAS is a lab on a chip designed to quantify the amount of a specific protein (or panel of proteins) present in particular biological fluids. Monitoring quantities of specific proteins makes the tool useful as a clinical diagnostic. Using a disposable lab-on-a-chip cartridge, the device makes use of a molecular sieve made out of a polyacrylamide gel. The location of the sieve in the microfluidic chips is determined using photo-lithographical methods adapted from the semiconductor industry. The gel is porous, with very small openings. A low electrical current (measured in micro-amps) is passed through the gel and a process called electrophoresis moves charged proteins through it. The gel has a gelatin-like consistency and, by permitting the easy passage of smaller molecules and slowing the passage of larger ones, quickly separates proteins contained in the saliva. Prior to this separation, the proteins are brought into contact with specific antibodies chosen on their ability to bind to the biomarkers. The antibodies are pre-labeled with fluorescent molecules attached to them. Interrogation by laser of these combined molecules — fluorescent antibody and fluorescent antibody bound to the biomarker — determines the amount of biomarker present, indicating the degree of periodontitis.

Science Daily
April 17, 2007

Original web page at Science Daily

Tooth decay often goes undetected until too late. Early signs of damage are usually hidden from sight and it is unhealthy to take too many X-rays. Now researchers working for the National Institutes of Health (NIH) in the US have discovered that infrared light – with a wavelength of 1310 nanometres – can pass straight through a tooth, providing a safe and simple way to probe for hidden decay. Most light frequencies bounce off enamel, meaning they cannot probe below the surface. But the NIH research found that, for a narrow band of infrared, reflection is 30 times less than normal. An infrared diode shines light through a tooth and a Charge-Coupled Device (CCD) sensor on the other side measures the light that passes through. Any decay inside the tooth creates small pores that scatter the infrared light, causing a dark shadow to appear in the resulting image. The image quality could be further improved by polarising the infrared light before sending it through a tooth, the researchers suggest. This is because any hidden pores should also depolarise this light, making for better image contrast. Tests show that an infrared diode can shine light through 5 millimetres of enamel, providing an image as clear as an X-ray, but without exposing the patient to harmful radiation.

New Scientist
December 5, 2006

Original web page at New Scientist

The immune system may contribute to tooth loss associated with the gum disease periodontitis, according to a new study in the American Journal of Pathology. By comparing markers in diseased gum tissue samples to samples from healthy patients, the authors found that B-cells and T-cells in gum lesions were producing a key protein known to stimulate bone loss. This paper “elevates the importance of lymphocytes in periodontal lesions,” said Denis Kinane from the University of Louisville’s School of Dentistry, who was not affiliated with the study.

Both gingivitis and periodontitis are characterized by inflamed gum tissue. In advanced periodontitis, however, the gums develop lesions that are packed with immune cells and can damage the bone that supports teeth. For approximately 30 years, scientists have struggled to identify the molecular basis for advanced periodontitis and the role immune cells play in pathogenesis. One protein, called RANKL (receptor activator of nuclear factor-KB ligand) may be a key player. Previous studies have suggested RANKL stimulates the differentiation and activation of osteoclasts, or cells that digest bone, in bone resorption diseases, such as osteoporosis and rheumatoid arthritis. Research has also shown RANKL is present in periodontal lesions.

“We just wanted to take the next step and see if we could connect the immune cells with RANKL,” coauthor of the study Toshihisa Kawai of the Forsyth Institute told The Scientist. Using confocal microscopy, Kawai and his colleagues found that, among the many cell types identified in the lesions, only T-cells and B-cells expressed RANKL. In addition, ELISA assays showed RANKL is expressed mainly in diseased tissue samples, not healthy samples, adding further evidence that RANKL is a key player in pathogenesis. To test if the amount of RANKL was enough to cause cellular differentiation, the researchers performed an in vitro assay that demonstrated increased RANKL expression was sufficient to induce osteoclast differentiation.

Still, these findings do not show that RANKL triggers the bone resorption in advanced periodontitis, according to Thomas Van Dyke of Boston University, who was not involved with the study. “RANKL may be elevated from these cells, but many other molecules are elevated also,” he told The Scientist in an Email. A subsequent experiment should interrupt the RANKL-pathway to prove that it is vital for periodontal bone resorption, Van Dyke noted. Kinane said he is also “not truly 100% sure that [RANKL] is the most pivotal molecule” in the pathogenesis of periodontitis. Though it was a well argued and an interesting paper, he told The Scientist, more data are required to prove that RANKL is the key to bone loss in gum disease.

Kawai said he and his group are indeed planning to interrupt the RANKL pathway to confirm their hypothesis that RANKL is important for osteoclast activation and differentiation. These findings could also answer some outstanding questions, Kawai noted, such as why many lymphocytes are recruited to gum lesions. Further experiments will also investigate the underlying difference between protein expression levels in healthy versus diseased tissues. “We just don’t know how [periodontal disease] happens yet,” Kawai said.

The Scientist
September 26, 2006

Original web page at The Scientist