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Gum disease bacteria selectively disarm immune system, study finds PDF Print E-mail

The human body is comprised of roughly 10 times more bacterial cells than human cells. In healthy people, these bacteria are typically harmless and often helpful, keeping disease-causing microbes at bay. But, when disturbances knock these bacterial populations out of balance, illnesses can arise. Periodontitis, a severe form of gum disease, is one example.

In a new study, University of Pennsylvania researchers show that bacteria responsible for many cases of periodontitis cause this imbalance, known as dysbiosis, with a sophisticated, two-prong manipulation of the human immune system.

Their findings, reported in the journal Cell Host & Microbe, lay out the mechanism, revealing that the periodontal bacterium Porphyromonas gingivalis acts on two molecular pathways to simultaneously block immune cells' killing ability while preserving the cells' ability to cause inflammation. The selective strategy protects "bystander" gum bacteria from immune system clearance, promoting dysbiosis and leading to the bone loss and inflammation that characterizes periodontitis. At the same time, breakdown products produced by inflammation provide essential nutrients that "feed" the dysbiotic microbial community. The result is a vicious cycle in which inflammation and dysbiosis reinforce one another, exacerbating periodontitis.

George Hajishengallis, a professor in the Penn School of Dental Medicine's Department of Microbiology, was the senior author on the paper, collaborating with co-senior author John Lambris, the Dr. Ralph and Sallie Weaver Professor of Research Medicine in the Department of Pathology and Laboratory Medicine in Penn's Perelman School of Medicine. Collaborators included Tomoki Maekawa and Toshiharu Abe of Penn Dental Medicine.

Work by Hajishengallis's group and collaborators had previously identified P. gingivalis as a "keystone pathogen." Drawing an analogy from the field of ecology, in which a species such as a grizzly bear is thought of as a keystone species because of the influence it has over a number of other species in the community, the idea suggests that, although P. gingivalis may be relatively few in number in the mouth, their presence exerts an outsized pull on the overall microbial ecosystem. Indeed, the team has shown that, although P. gingivalis is responsible for instigating the process that leads to periodontitis, it can't cause the disease by itself.

"Scientists are beginning to suspect that keystone pathogens might be playing a role in irritable bowel disease, colon cancer and other inflammatory diseases," Hajishengallis said. "They're bugs that can't mediate the disease on their own; they need other, normally non-pathogenic bacteria to cause the inflammation."

In this study, they wanted to more fully understand the molecules involved in the process by which P. gingivalis caused disease.

"We asked the question, how could bacteria evade killing without shutting off inflammation, which they need to obtain their food," Hajishengallis said.

The researchers focused on neutrophils, which shoulder the bulk of responsibility of responding to periodontal insults. Based on the findings of previous studies, they examined the role of two protein receptors: C5aR and Toll-like receptor-2, or TLR2.

Inoculating mice with P. gingivalis, they found that animals that lacked either of these receptors as well as animals that were treated with drugs that blocked these receptors had lower levels of bacteria than untreated, normal mice. Blocking either of these receptors on human neutrophils in culture also significantly enhanced the cells' ability to kill the bacteria. Microscopy revealed that P. gingivalis causes TLR2 and C5aR to physically come together.

"These findings suggest that there is some crosstalk between TLR2 and C5aR," Hajishengallis said. "Without either one, the bacteria weren't as effective at colonizing the gums."

Further experiments in mice and in cultured human neutrophils helped the researchers identify additional elements of how P. gingivalis operates to subvert the immune system. They found that the TLR2-C5aR crosstalk leads to degradation of the protein MyD88, which normally helps clear infection. And in a separate pathway from MyD88, they discovered that P. gingivalis activates the enzyme PI3K through C5aR-TLR2 crosstalk, promoting inflammation and inhibiting neutrophils' ability to phagocytose, or "eat," invading bacteria.

Inhibiting the activity of either PI3K or a molecule that acted upstream of PI3K called Mal restored the neutrophils' ability to clear P. gingivalis from the gums.

"P. gingivalis uses this connection between C5aR and TLR2 to disarm and dissociate the MyD88 pathway, which normally protects the host from infection, from the proinflammatory and immune-evasive pathway mediated by Mal and PI3K," Hajishengallis said.

Not only does the team's discovery open up new targets for periodontitis treatment, it also suggests a bacterial strategy that could be at play in other diseases involving dysbiosis.

http://feeds.sciencedaily.com/~r/sciencedaily/health_medicine/dentistry/~3/sEhCj91C18E/140611132044.htm

 
Framework for monitoring oral cancer developed PDF Print E-mail

Each year, approximately 22,000 Americans are diagnosed with oral cancer. The five-year survival rate of 40% in the U.S. is one of the lowest of the major cancers, and it has not improved in the past 40 years. More people die each year in the U.S. from oral cancer than from melanoma, cervical, or ovarian cancer. Worldwide, the incidence of oral cancer is increasing, particularly among young people and women, with an estimated 350,000 -- 400,000 new cases diagnosed each year.

"The major risk factors, tobacco and alcohol use, alone cannot explain the changes in incidence, because oral cancer also commonly occurs in patients without a history of tobacco or alcohol exposure," said Dr. Brian Schmidt, professor of oral and maxillofacial surgery and director of the Bluestone Center for Clinical Research at the NYU College of Dentistry (NYUCD)

Changes in the microbial community are commonly associated with dental diseases such as periodontal disease, which is most likely a poly-microbial disease characterized by outgrowth of certain pathologic organisms, and chronic periodontitis has been reported to be a risk factor for oral premalignant lesions and cancers.

"We know that other cancers, including gallbladder, colon, lung and prostate, have been associated with particular bacterial infections, so we hypothesized that shifts in the composition of the normal oral cavity microbiome could be promoters or causes of oral cancer," said Dr. Albertson.

Drs. Schmidt and Albertson and their team profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. The team's findings, "Changes in abundance of oral microbiota associated with oral cancer," published on-line in the journal PLOS ONE (June 2, 2014), begin to develop a framework for exploiting the oral microbiome for monitoring oral cancer development, progression and recurrence.

In cancer samples from both a discovery (n=5) and a subsequent confirmation cohort (n=10), abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient. Significant decreases in abundance of these phyla were observed for pre-cancers, but not when comparing samples from contralateral sites (tongue and floor of mouth) from healthy individuals. Using differences in abundance of the genera Actinomyces, Rothia, Streptococcus and Fusobacterium, the team was able to separate most cancer samples from pre-cancer and normal samples.

"The oral cavity offers a relatively unique opportunity to screen at risk individuals for (oral) cancer, because the lesions can be seen, and as we found, the shift in the microbiome of the cancer and pre‑cancer lesions compared to anatomically matched clinically normal tissue from the same individual can be detected in non‑invasively collected swab samples." said Dr. Schmidt.

Non‑invasively sampling the microbiome of oral lesions and corresponding normal tissue opens the possibility to not only detect cancer‑associated changes at one time point, but the relative stability of the adult oral microbiome also offers the opportunity to monitor shifts in bacterial communities over time.

"Here we observed changes in the microbiome, which, in future larger studies, may be confirmed as a potential biomarker of oral cancers or pre‑cancers, and may even have utility to discriminate patients with lymph node metastases," notes Dr. Albertson. "In addition, there are other challenges in clinical management of oral cancers that would benefit from better diagnostic tools."

Oral cancer patients are also at risk of second primary cancers and recurrences. The microbiome may provide signatures that can be used as a biomarker for monitoring field changes associated with the high rate of second primary oral cancers and recurrences. The team also notes the possibility of medically modulating the oral microbiome for treatment of oral pre-cancers and damaged fields (field cancerization).

Story Source:

The above story is based on materials provided by New York University. Note: Materials may be edited for content and length.

http://feeds.sciencedaily.com/~r/sciencedaily/health_medicine/dentistry/~3/cqNQp5HiEAg/140610152741.htm

 
Framework for monitoring oral cancer developed PDF Print E-mail

Each year, approximately 22,000 Americans are diagnosed with oral cancer. The five-year survival rate of 40% in the U.S. is one of the lowest of the major cancers, and it has not improved in the past 40 years. More people die each year in the U.S. from oral cancer than from melanoma, cervical, or ovarian cancer. Worldwide, the incidence of oral cancer is increasing, particularly among young people and women, with an estimated 350,000 -- 400,000 new cases diagnosed each year.

"The major risk factors, tobacco and alcohol use, alone cannot explain the changes in incidence, because oral cancer also commonly occurs in patients without a history of tobacco or alcohol exposure," said Dr. Brian Schmidt, professor of oral and maxillofacial surgery and director of the Bluestone Center for Clinical Research at the NYU College of Dentistry (NYUCD)

Changes in the microbial community are commonly associated with dental diseases such as periodontal disease, which is most likely a poly-microbial disease characterized by outgrowth of certain pathologic organisms, and chronic periodontitis has been reported to be a risk factor for oral premalignant lesions and cancers.

"We know that other cancers, including gallbladder, colon, lung and prostate, have been associated with particular bacterial infections, so we hypothesized that shifts in the composition of the normal oral cavity microbiome could be promoters or causes of oral cancer," said Dr. Albertson.

Drs. Schmidt and Albertson and their team profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. The team's findings, "Changes in abundance of oral microbiota associated with oral cancer," published on-line in the journal PLOS ONE (June 2, 2014), begin to develop a framework for exploiting the oral microbiome for monitoring oral cancer development, progression and recurrence.

In cancer samples from both a discovery (n=5) and a subsequent confirmation cohort (n=10), abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient. Significant decreases in abundance of these phyla were observed for pre-cancers, but not when comparing samples from contralateral sites (tongue and floor of mouth) from healthy individuals. Using differences in abundance of the genera Actinomyces, Rothia, Streptococcus and Fusobacterium, the team was able to separate most cancer samples from pre-cancer and normal samples.

"The oral cavity offers a relatively unique opportunity to screen at risk individuals for (oral) cancer, because the lesions can be seen, and as we found, the shift in the microbiome of the cancer and pre‑cancer lesions compared to anatomically matched clinically normal tissue from the same individual can be detected in non‑invasively collected swab samples." said Dr. Schmidt.

Non‑invasively sampling the microbiome of oral lesions and corresponding normal tissue opens the possibility to not only detect cancer‑associated changes at one time point, but the relative stability of the adult oral microbiome also offers the opportunity to monitor shifts in bacterial communities over time.

"Here we observed changes in the microbiome, which, in future larger studies, may be confirmed as a potential biomarker of oral cancers or pre‑cancers, and may even have utility to discriminate patients with lymph node metastases," notes Dr. Albertson. "In addition, there are other challenges in clinical management of oral cancers that would benefit from better diagnostic tools."

Oral cancer patients are also at risk of second primary cancers and recurrences. The microbiome may provide signatures that can be used as a biomarker for monitoring field changes associated with the high rate of second primary oral cancers and recurrences. The team also notes the possibility of medically modulating the oral microbiome for treatment of oral pre-cancers and damaged fields (field cancerization).

Story Source:

The above story is based on materials provided by New York University. Note: Materials may be edited for content and length.

http://feeds.sciencedaily.com/~r/sciencedaily/health_medicine/dentistry/~3/cqNQp5HiEAg/140610152741.htm

 
Shellac: Fabricating the Trial Denture Base PDF Print E-mail
Here's a helpful video that can help you practice fabricating a Trial Denture Base using Shellac Baseplate Material. (From The University of Michigan Youtube Channel)

http://dentistboards.blogspot.com/2014/06/shellac-fabricating-trial-denture-base.html

 
PFM Crown Preparation for an Anterior Tooth (11) PDF Print E-mail
Here's a helpful video that can help you practice preparing an anterior tooth for a porcelain fused to metal crown. (From youtube)

http://dentistboards.blogspot.com/2014/06/pfm-crown-preparation-for-anterior.html

 
Dental pulp stem cells may lead to heat stroke treatment PDF Print E-mail
Scientists in Taiwan have found that intravenous injections of stem cells derived from human exfoliated deciduous tooth pulp (SHED) have a protective effect against brain damage from heat stroke in...

http://www.medicalnewstoday.com/releases/277886.php

 
SCFDS Completes and Turns Over a Full Dental Client for Victims of Typhoon Haiyan PDF Print E-mail
In November 8, 2013, Typhoon Haiyan, the largest typhoon that ever hit land devastated the island of Leyte in the Philippines. The eye of the typhoon directly passed over the capital city of Tacloban destroying everything in its path. As many as 7000 people died and millions were left homeless without food, water and shelter. […]

http://www.scfds.org/news/scfds-completes-turns-full-dental-client-victims-typhoon-haiyan/

 
SCFDS Completes and Turns Over a Full Dental Clinic for Victims of Typhoon Haiyan PDF Print E-mail
In November 8, 2013, Typhoon Haiyan, the largest typhoon that ever hit land devastated the island of Leyte in the Philippines. The eye of the typhoon directly passed over the capital city of Tacloban destroying everything in its path. As many as 7000 people died and millions were left homeless without food, water and shelter. […]

http://www.scfds.org/news/scfds-completes-and-turns-over-a-full-dental-clinic-for-victims-of-typhoon-haiyan/

 
Covington Who's Who Selects Dr. Lawrence S. Lipkin as an Honored Member of the Executive and... PDF Print E-mail
The selection recognizes Lawrence S. Lipkin's commitment to excellence in Dentistry and Higher Education.
 
Treatment outcomes for preventive oral health services delivered to young children by non-dental... PDF Print E-mail
The International and American Associations for Dental Research (IADR/AADR) have published a paper titled "Preventive Services by Medical and Dental Providers and Treatment Outcomes.

http://www.medicalnewstoday.com/releases/277745.php

 
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