A team of scientists from The Forsyth Institute, the University of Connecticut Health Center, the CDC and the Wadsworth Center, have used state-of-the-art technology to elucidate the molecular architecture of Treponema pallidum, the bacterium which causes syphilis. The previously unknown detailed structure of the bacteria can now be shown in three dimensions. This provides the first real image of the pathogen and reveals previously unknown features, which may help fight the spread of syphilis.

Cryo-electron tomography (CET) is a type of microscope that is used to obtain a three-dimensional reconstruction of a sample from two dimensional images at extremely low temperatures. Using CET, the research team has clarified the fundamental differences between Treponema pallidum and other gram-negative bacteria.

This research will be featured as the cover story in the December 15th issue of the Journal of Bacteriology. (http://jb.asm.org/content/vol191/issue24/cover.dtl)According to lead author Jacques Izard, Ph.D., this work provides a clear snapshot of a cell in real time. Added Izard, “This changes how we study this bacterium. Having an accurate architecture of the cell provides important insight for understanding how it becomes invasive in the human body. With this information we may learn how to stop disease progression.”

After a sharp decrease in the rate of primary and secondary syphilis cases in the 90s, since the year 2000 the CDC has observed a steady increase in prevalence. The over 36,000 cases recorded annually affect both men and women as well as newborns with congenital syphilis.

Project Summary

Over a decade ago, the publication of the Treponema pallidum genome sequence provided a much needed parts list for the bacterium. However, scientists have learned very little about how these components are organized to create this extremely virulent and immuno-evasive pathogen. CET has emerged as a powerful tool for bridging the knowledge gap. With this technique, thin films of cells are frozen to preserve cell structure in a close-to-native state, avoiding degradation caused by preparation for traditional microscopy. A series of images acquired as the sample is progressively tilted in an electron microscope are used to generate a 3D image.

With CET T. pallidum cells appeared to form flat waves and did not contain an outer coat. This highly motile organism can attach to human cells by its tip. The present work has shown that the tip of this bacteria has a unique structure among pathogens, which improved the understanding of cell attachment and tissue penetration. Additionally, novel structural evidence explains how those bacteria mysteriously move with the flagella inside their cell body.

This work was supported by grants from the National Institutes of Health and the National Center for Research Resources.

Jacques Izard, Ph.D., is an Assistant Member of the Staff in the Department of Molecular Genetics at The Forsyth Institute. His laboratory is working to understand the role of oral pathogens in oral disease and their influence on systemic disease progression. Dr. Izard and his team focus on bacterial cell biology and the host response. To learn more about his work visit http://www.forsyth.org/research/scientists/profiles/jizard.html.

The Forsyth Institute is the world’s leading independent organization dedicated to scientific research and education in oral health and related biomedical sciences. Established in 1910, Forsyth’s goal is to lead the discovery, communication and application of breakthroughs in oral health and disease prevention that will significantly improve the health and wellbeing of the nation and the world. For more information about Forsyth visit its Web site at www.forsyth.org.

July 8, 2009

A scientific team from The Forsyth Institute has discovered new links between certain oral bacteria and obesity. In a recent study, the researchers demonstrated that the salivary bacterial composition of overweight women differs from non-overweight women. This preliminary work may provide clues to interactions between oral bacteria and the pathology of obesity. This research may help investigators learn new avenues for fighting the obesity epidemic.

This work will be published in the Journal of Dental Research, and is available online today at http://jdr.sagepub.com/cgi/content/full/88/6/519.“There has been a world-wide explosion of obesity, with many contributing factors,” said Dr. J. Max Goodson, senior author of the study. “However, the inflammatory nature of the disease is also recognized. This led me to question potential unknown contributing causes of obesity. Could it be an epidemic involving an infectious agent?” “It is exciting to image the possibilities if oral bacteria are contributing to some types of obesity,” added Goodson.

Summary of Study

In order to measure the salivary bacterial populations of overweight women, samples were collected from 313 women with a body mass index between 27 and 32 (classifying them as overweight). Using DNA analysis, the researchers measured the bacterial populations of this group and compared it with historical data from 232 individuals that were not overweight. Significant differences in seven of the 40 species studied occurred in the salivary bacteria of subjects in the overweight group. In addition, more than 98 percent of the overweight women could be identified by the presence of a single bacterial species, called Selenomanas noxia, at levels greater than 1.05 percent of the total salivary bacteria. These data suggest that the composition of salivary bacteria changes in overweight women. It seems likely that these bacterial species could serve as indicators of a developing overweight condition and possibly be related to the underlying causation.

Dr. Goodson noted that the reasons for a relationship between obesity and oral bacteria are likely complex. The observed relationship may be circumstantial as being related to diet or opportunistic due to metabolic changes. In the next phase of this research, Dr. Goodson plans to further examine this relationship by initially conducting a controlled cohort study to see if this initial observation can be reproduced. In addition, he hopes to conduct longitudinal studies in children to see if oral infection relates to weight gain. Ultimately, the development of strategies to eliminate specific oral bacteria would be required to provide definitive evidence that certain oral bacteria may be responsible for weight gain.

J. Max Goodson, DDS, PhD, is a Senior Member of the Staff at The Forsyth Institute and heads up The Forsyth Clinical Research Collaborative (CRC). . Principal research personnel associated with the CRC include scientists that conduct clinical and health care delivery research.

This work was supported in part by Interleukin Genetics of Waltham, MA and by a grant from the National Institute of Dental and Craniofacial Research. The Forsyth Institute is the world’s leading independent organization dedicated to scientific research and education in oral health and related biomedical sciences.

www.forsyth.org

ScienceDaily (Jan. 2, 2009) — Researchers at the University Of Southern California, School Of Dentistry release results of clinical data that links oral bisphosphonates to increased jaw necrosis. The study is among the first to acknowledge that even short-term use of common oral osteoporosis drugs may leave the jaw vulnerable to devastating necrosis, according to a new report.

DT: With the increasing popularity and predictability of implant treatment, will endodontics become obsolete?

Dr. Koch: It’s a good question. It is also a question that was initially broached to us 8 years ago by the president of a leading European endodontic company. His concern was, “Are implants going to totally replace endodontics?” What created his concern at that time was that many European clinicians were placing dental implants instead of performing root canals. A further contributing factor (at that point in time) was that some countries had decent reimbursement for surgical procedures but very little for nonsurgical endodontics. Additionally, the endodontic skill of the average European dentist at that time was not at the quality level it is today. Consequently, there was an existing concern about the endodontic failure rate, which was viewed as being greater than with implants.
Interestingly enough, as the quality of European endodontics has dramatically improved, the tendency to place implants (particularly in necrotic cases) has reversed itself. Patients now want to save their natural teeth, if at all possible. Consequently, as the result of better endodontic care, patients are now taking the opportunity to save their natural teeth and are choosing endodontic procedures over implant placement.
Nonetheless, this issue of endodontics becoming obsolete is a very good question, and it has more application today than ever before in North America. But why is this such a hot topic, and how can we resolve this dilemma? To address this issue fully, we need to look at this from multiple perspectives.

Dr. Brave: Recently, the University of Minnesota completed a study that compared 196 single-tooth implants with 196 nonsurgical endodontic procedures. The conclusion was that restored endodontically treated teeth and single-tooth implants had similar failure rates (6.1%), although the implant group displayed a longer time to function and an increased incidence of postoperative complications. This study did not address the financial differential that exists between the 2 treatment modalities. It is our opinion (and the opinion, we believe, of the majority of dentists) that when viewed in a nonbiased manner, indications exist for both treatment modalities. The key is that whichever treatment modality you choose, perform the procedure in such a manner that you enhance the long-term retention of the tooth (or implant).
But we must ask ourselves another question, “Why have implants suddenly become so popular?” There are probably a number of reasons for this gain in popularity, but one that stands out is that many endodontically treated teeth have had excessive coronal enlargement, which compromises their structural integrity and long-term prognosis. When the coronal third of the radicular dentin has been cored out, the long-term prognosis of that tooth is significantly reduced, and an implant may be the better choice. It certainly is interesting that if you ask most dentists today whether they are seeing more fractured endodontically treated teeth than in the past, the answer is yes. The key is not to destroy the structural integrity of the tooth while performing a root canal procedure. Shaping should achieve the intended biologic goals of cleaning and debridement without compromising the tooth.
Our main emphasis at Real World Endo is to do endodontics (whatever system you use) in such a fashion that you address the biologic requirements of doing a root canal but do it in such a manner that you do not overly weaken the tooth. Endodontics done in such a manner will have a long-term retention rate equal to or better than that of implants.

DT: What is the most immediate challenge facing organized endodontics today?

Dr. Koch: Education. The AAE (American Association of Endodontics), and endodontics in general, must make a concerted effort to educate dentists about the benefits of good root canal therapy. The concept of having general dentists learn more about endodontics is not a threat to the specialty. Implants also are not a threat to the specialty. What is a threat is not educating general practitioners on good endodontics and how it may benefit their patients. This issue of endodontic education is particularly critical in undergraduate dental curricula where students (in some schools) seem to be getting less clinical experience than ever before. It is very common now to meet recent dental graduates who endodontically treated only 2 or 3 teeth during their undergraduate experience.
Also, part of this challenge is for all those involved in endodontics to take the time to teach and demonstrate to general practitioners which procedures they should be doing. With appropriate case selection, correct philosophy, and good technique many procedures should be performed by the general practitioner. We’ve had a good 10 to 15 years of endodontic commentary on the immense complexity of the root canal system. Some, in fact, have even attempted to discourage general dentists from doing endodontics because it is so complicated. Well, maybe that worked years ago when there was no viable option to doing a root canal. But now there is an option: simply extract the tooth and place an implant. Dentists should not be frightened by endodontics. They must understand how good-quality endodontics can benefit their patients.
The truth is that we have had high success rates in endodontics prior to this discourse on complexity. Now, we have all types of adjunctive procedures and products that do everything from opening up lateral canals to removing biofilm. This is fine, but the real questions are these: How necessary are these additional procedures, and are they removing an excessive amount of tooth structure, which may weaken the tooth and compromise its long-term retention? The failures that we now see in endodontics are more commonly coronal in nature, not apical. Additionally, we have even witnessed some endodontic programs taking apical preparations in mesial-buccal canals of molars to a minimum size 55. Hold on here folks… We cannot render a tooth sterile regardless of how much tooth structure we remove or how many medicaments we place into the system. Without question, we absolutely can satisfy all the biologic requirements of doing a root canal and do it in such a manner that we do not compromise the structural integrity and long-term retention of the tooth.

Dr. Brave: Endodontics should be taught (and performed) in such a manner that it allows the greatest majority of dentists to achieve excellent results. Simplicity, predictability, and efficiency will be the key to teaching future endodontics. Endodontic education will not be productive if it allows only 10% to 15% of clinicians to get great results. And please do not confuse any of the above with a lack of quality.

DT: Can you elaborate on your last statement of not confusing simplicity with poor or mediocre results?

Dr. Brave: We need to understand the difference between quick and efficient to get a handle on this issue. Quick has nothing to do with quality, and, in most cases, when a sophisticated procedure is done quickly, something is often compromised. Efficient has everything to do with quality and, in fact, specifically addresses quality in its definition. Efficiency has no meaning unless measured against a known outcome. The outcome must be the same or better for the word efficient to have any meaning at all. The outcome of any procedure that is less than what it is being measured against cannot be defined as efficient. Something done poorly and quickly is just that…poor and quick. A good outcome (the same or better) achieved predictably and consistently through better technology and techniques can truly be said to be efficient. This is what Real World Endo is all about. Predict-able, consistent, and reproducible results achievable by the majority of clinicians who choose to use our techniques.

DT: What are the most significant changes anticipated in endodontics over the next 3 years?

Dr. Koch: We believe that the near future will see an increased concentration on what we call the Endo-Restorative Continuum. Think about it for a second. The general dentist placing a post in a root canal is in the same space as the clinician who did the endodontics. In fact, a strong case can be made that the best post drill is an endodontic rotary file. It must be established that there exists an intimate connection between doing endodontics in a nondestructive fashion and the long-term prognosis of the tooth.
We further anticipate that there will be a continued effort to reduce the width of the coronal portion of the overall endodontic preparation. Accordingly, we fully expect to see more practitioners perform a constant .04 taper preparation (orifice to apex) rather than a constant .06 preparation or a variable taper technique. In addition to minimizing the loss of tooth structure, the constant .04 taper preparation meets all the requirements of thorough irrigation as well as permits the use of heated gutta-percha obturation techniques. However, a .04 taper preparation is a lot kinder to the tooth.
Real World Endo has been talking about this need to reduce coronal enlargement for nearly 2 years, and we are now sensing an increasing wave of acceptance. Certainly, while we would like all dentists to use our system, this is at its essence a generic story. Do root canal therapy (whatever system) in such a way that it is not merely endodontics, but more importantly, is part of an Endo-Restorative Continuum. We must say this again. If you do a root canal but destroy the tooth in the process, then nothing really has been accomplished.

DT: Do you foresee any dramatic long-term changes in the way endo-dontics is performed?

Dr. Brave: In the long term we do see some significant changes from the way endodontics is currently performed. While we can anticipate new alloys and materials on the instrumentation side, we really expect the big changes to occur on the obturation front. It is very reasonable to expect that in the next decade we will see endodontics performed where the entire root canal space is filled with a cement-like substance. This material may be a Portland cement-like substance, a bone cement, or possibly even a bioceramic material. Regardless of the specific material utilized with such a technique, there will be a decided interest in filling root canals in such a manner. But why will this technique gain acceptance?

Dr. Koch: First, we must ask ourselves, “Do we fill a root canal to get the best possible seal or do we obturate a root canal to make it retreatable?” As we move into the future, we see the world of endodontic retreatment diminishing.
If an endodontic case fails in the future, some practitioners may choose to do an implant (or apical surgery). Thus, complete obturation of the root canal space (with a cement-like substance) will become a technique that must be user-friendly as well as one that will produce excellent sealing ability and simultaneously strengthen the tooth. While we recognize this is a significant departure from current protocol, we see any widely accepted obturation technique of the future being one that will favor ease of use and better sealing ability over retreatability.

DT: What will be the role of the endodontic specialist in the future?

Dr. Brave: Endodontics is not going away! In fact, the role of the endodontist will become greater and more important than ever before. In addition to being an education resource for the general dentist, future endodontists will be more intimately involved in the overall treatment planning process. Who better than the endodontist to help in the decision-making process of root canal or implant? Consequently, in addition to providing excellent endodontic skills, the future endodontist must also be well-versed in conservative surgical procedures. This expanded surgical knowledge will include the indications of use for both dental implants and crown lengthening.
While we are not proponents of most endodontists placing dental implants, we do believe that there is a need for endodontists to perform crown lengthening and tooth extrusion. Part of this rationale is based on the current lack of these procedures being performed, when in reality, in many cases they are just what the doctor should be doing rather than an implant.
Finally, let us restate that it is absolutely critical that the future endodontic specialist understand the intimate connection that exists between a well-done root canal and the restoration of the tooth. Endodontics must be done in such a way as to enhance the long-term retention of the tooth. Real World Endo is resolute in our confidence that endodontics will remain a robust specialty, and one that will continue to be a critical component of the dental team.