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Yale researchers have uncovered the molecular tricks used by bacteria to fight the effects of fluoride, which is commonly used in toothpaste and mouthwash to combat tooth decay.
In the Dec. 22 online issue of the journal Science Express, the researchers report that sections of RNA messages called riboswitches -- which control the expression of genes -- detect the build-up of fluoride and activate the defenses of bacteria, including those that contribute to tooth decay.
"These riboswitches are detectors made specifically to see fluoride," said Ronald Breaker, the Henry Ford II Professor and chair of the Department of Molecular, Cellular and Developmental Biology and senior author of the study.
Fluoride in over-the-counter and prescription toothpastes is widely credited with the large reduction in dental cavities seen since these products were made available beginning in the 1950s. This effect is largely caused by fluoride bonding to the enamel of our teeth, which hardens them against the acids produced by bacteria in our mouths. However, it has been known for many decades that fluoride at high concentrations also is toxic to bacteria, causing some researchers to propose that this antibacterial activity also may help prevent cavities.
The riboswitches work to counteract fluoride's effect on bacteria. "If fluoride builds up to toxic levels in the cell, a fluoride riboswitch grabs the fluoride and then turns on genes that can overcome its effects," said Breaker.
Since both fluoride and some RNA sensor molecules are negatively charged, they should not be able to bind, he notes.
"We were stunned when we uncovered fluoride-sensing riboswitches" said Breaker. "Scientists would argue that RNA is the worst molecule to use as a sensor for fluoride, and yet we have found more than 2000 of these strange RNAs in many organisms."
By tracking fluoride riboswitches in numerous species, the research team concluded that these RNAs are ancient -- meaning many organisms have had to overcome toxic levels of fluoride throughout their history. Organisms from at least two branches of the tree of life are using fluoride riboswitches, and the proteins used to combat fluoride toxicity are present in many species from all three branches.
"Cells have had to contend with fluoride toxicity for billions of years, and so they have evolved precise sensors and defense mechanisms to do battle with this ion," said Breaker, who is also an investigator with the Howard Hughes Medical Institute. Now that these sensors and defense mechanisms are known, Breaker said, it may be possible to manipulate these mechanisms and make fluoride even more toxic to bacteria. Fluoride riboswitches and proteins common in bacteria are lacking in humans, and so these fluoride defense systems could be targeted by drugs. For example, the Yale team discovered protein channels that flush fluoride out of cells. Blocking these channels with another molecule would cause fluoride to accumulate in bacteria, making it more effective as a cavity fighter.
Fluoride is the 13th most common element in Earth's crust, and it is naturally present in high concentrations throughout the United States and elsewhere. Its use in toothpaste and its addition to city water supplies across the United States sparked a controversy 60 years ago, and the dispute continues to this day. In the United Kingdom, and in other European Union countries, fluoride is used to a much lesser extent due to fierce public opposition.
The new findings from Yale only reveal how microbes overcome fluoride toxicity. The means by which humans contend with high fluoride levels remains unknown, Breaker notes. He adds that the use of fluoride has had clear benefits for dental health and that these new findings do not indicate that fluoride is unsafe as currently used.
Tuesday, December 27, 2011
Saturday, December 17, 2011
Addition of Mannitol Increases Effectiveness of Dental Nerve Block Anesthesia
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Allowing a patient to be comfortable and pain-free during surgical and restorative dental procedures is an essential part of the process. The most commonly used local anesthetic injection for lower teeth is the inferior alveolar nerve (IAN) block. However, failure rates ranging from 10 to 39 percent have been reported.
Allowing a patient to be comfortable and pain-free during surgical and restorative dental procedures is an essential part of the process. The most commonly used local anesthetic injection for lower teeth is the inferior alveolar nerve (IAN) block. However, failure rates ranging from 10 to 39 percent have been reported.
The current issue of the journal Anesthesia Progress presents a study testing the efficacy of adding a solution of mannitol to the anesthetic typically used in IAN blocks. Forty adult subjects participated in the study, receiving an IAN block at each of three separate appointments at least one week apart.
The study compared the effectiveness of the standard anesthetic, lidocaine with epinephrine, to the effectiveness of two different volumes of lidocaine with epinephrine plus 0.5 M mannitol. Mannitol is a sugar alcohol that occurs naturally in fruits and vegetables. It is rapidly excreted by the kidneys.
Though its impact is short-lived, mannitol has the positive effect of opening the perineurial membrane. It is believed that, in cases of IAN block failure, the perineurial barrier around the nerve does not allow complete diffusion of the anesthetic into the nerve trunk. The addition of mannitol apparently allows enhanced permeability, increasing the success of an IAN block when administered concurrently.
After injections of the IAN block solutions, subjects’ pain levels were measured by an electric pulp test of their mandibular teeth at 4-minute intervals for 60 minutes. The study concluded that the addition of mannitol to lidocaine with epinephrine significantly increased the effectiveness of the anesthesia.
About Anesthesia Progress
Anesthesia Progress is the official publication of the American Dental Society of Anesthesiology (ADSA). The quarterly journal is dedicated to providing a better understanding of the advances being made in the science of pain and anxiety control in dentistry. The journal invites submissions of review articles, reports on clinical techniques, case reports, and conference summaries. To learn more about the ADSA, visit:
Oral Bacteria Enables Breaking Bond On Blood Vessels to Allow Invaders in
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A common oral bacteria, Fusobacterium nucleatum, acts like a key to open a door in human blood vessels and leads the way for it and other bacteria like Escherichia coli to invade the body through the blood and make people sick, according to dental researchers at Case Western Reserve University.
Yiping Han, professor of periodontics at the Case Western Reserve School of Dental Medicine, made the discovery in her continued work with the Fusobacterium nucleatum bacterium, one of the most prevalent of the more than 700 bacteria in the mouth.
She found the gram-negative anaerobe has a novel adhesin or bonding agent she's named FadA that triggers a cascade of signals that break the junctures in an interlocking sheath of endothelial cells on blood vessel's surface just enough to allow F. nucleatum and other bacteria into the blood.
A description of bond-breaking process was described in the Molecular Microbiology article, "Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity."
The microbiologist at the dental school has studied the oral bacteria over the past decade and was the first to find direct evidence that linked it to preterm labor and fetal death. But its presence is found in other infections and abscesses in the brain, lungs, liver, spleen and joints.
After finding and genetically matching the oral bacteria in the fetal death, she began to unravel the mystery of how an oral bacterium can be found throughout the body and jumps the blood-brain and placental barriers that usually block disease-causing agents.
Through years of lab work, her research led to the vascular endothelial (VE)-cadherin, cell-cell junctures that link the endothelial vascular cells together on the blood vessels.
These junctures are like a hook and loop connection, but for some unknown reason when F. nucleatum invades the body through breaks in the mucous membranes of the mouth, due to injuries or periodontal disease, this particular bacterium triggers a cascade of signals that causes the hook to recede back into the endothelial cell. The oral bacterium leads the way with any other harmful invaders following along.
This "deceding" was observed by confocal microscopy when Han used cells from human umbilical cord. The researchers introduced F. nucleatum and demonstrated the VE-cadherins break on bonds on the endothelial cells and creating enough space in the endothelium for the invaders to move in.
Lab tests included introducing F. nucleatum with and without other bacteria. When E. coli alone was introduced, the bond did not break. But when F. nucleatum was introduced first, the bond broke, and the E. coli bacteria were able to move through the otherwise intact cell layers.
"This cascade knocks out the guard on duty and allows the bacteria to enter the blood and travel like a bus loaded with riders throughout the system. Whenever the F. nucleatum wants to get off the bus at the liver, brain, spleen, or another place, it does," Han said.
When it disembarks from its ride through the blood, it begins to colonize. The colony of bacteria induces an inflammatory reaction that has a range of consequences from necrosis of tissue to fetal death.
A common oral bacteria, Fusobacterium nucleatum, acts like a key to open a door in human blood vessels and leads the way for it and other bacteria like Escherichia coli to invade the body through the blood and make people sick, according to dental researchers at Case Western Reserve University.
Yiping Han, professor of periodontics at the Case Western Reserve School of Dental Medicine, made the discovery in her continued work with the Fusobacterium nucleatum bacterium, one of the most prevalent of the more than 700 bacteria in the mouth.
She found the gram-negative anaerobe has a novel adhesin or bonding agent she's named FadA that triggers a cascade of signals that break the junctures in an interlocking sheath of endothelial cells on blood vessel's surface just enough to allow F. nucleatum and other bacteria into the blood.
A description of bond-breaking process was described in the Molecular Microbiology article, "Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity."
The microbiologist at the dental school has studied the oral bacteria over the past decade and was the first to find direct evidence that linked it to preterm labor and fetal death. But its presence is found in other infections and abscesses in the brain, lungs, liver, spleen and joints.
After finding and genetically matching the oral bacteria in the fetal death, she began to unravel the mystery of how an oral bacterium can be found throughout the body and jumps the blood-brain and placental barriers that usually block disease-causing agents.
Through years of lab work, her research led to the vascular endothelial (VE)-cadherin, cell-cell junctures that link the endothelial vascular cells together on the blood vessels.
These junctures are like a hook and loop connection, but for some unknown reason when F. nucleatum invades the body through breaks in the mucous membranes of the mouth, due to injuries or periodontal disease, this particular bacterium triggers a cascade of signals that causes the hook to recede back into the endothelial cell. The oral bacterium leads the way with any other harmful invaders following along.
This "deceding" was observed by confocal microscopy when Han used cells from human umbilical cord. The researchers introduced F. nucleatum and demonstrated the VE-cadherins break on bonds on the endothelial cells and creating enough space in the endothelium for the invaders to move in.
Lab tests included introducing F. nucleatum with and without other bacteria. When E. coli alone was introduced, the bond did not break. But when F. nucleatum was introduced first, the bond broke, and the E. coli bacteria were able to move through the otherwise intact cell layers.
"This cascade knocks out the guard on duty and allows the bacteria to enter the blood and travel like a bus loaded with riders throughout the system. Whenever the F. nucleatum wants to get off the bus at the liver, brain, spleen, or another place, it does," Han said.
When it disembarks from its ride through the blood, it begins to colonize. The colony of bacteria induces an inflammatory reaction that has a range of consequences from necrosis of tissue to fetal death.
Wednesday, December 14, 2011
Oral Surgery Protocol to Control Bleeding for Heart Patients Shows Positive Results
Cardiac patients that take anticoagulant medications and need a tooth extraction face an increased risk of bleeding that must be addressed by the treating clinician. Therefore, a protocol for heart patients is needed that will avoid significant bleeding after dental extractions without suspending anticoagulant therapy.
A study reported in the current issue of the Journal of Oral Implantology evaluated the use of leukocyte- and platelet-rich fibrin biomaterial. This material is commonly used in dentistry to improve healing and tissue regeneration. It was tested as a safe filling and hemostatic material after dental extractions in 50 heart patients undergoing oral anticoagulant therapy.
These heart patients had mechanical valve substitutions, and then were placed on anticoagulant oral therapy with warfarin. It is not recommended that the anticoagulant be suspended and replaced with heparin before a minor surgery, although this substitution may control the risk of postoperative bleeding.
One method of controlling bleeding without suspending the anticoagulant is the use of platelet-rich plasma gel placed in postextraction tooth sockets. Although this protocol has been successful, there are barriers to its daily use. The platelet concentrates are expensive and take a long time to prepare.
Platelet-rich fibrin offers an alternative biomaterial that is simple and inexpensive to prepare. Blood is collected in tubes without anticoagulant and centrifuged. It divides into three layers, creating a strong platelet-rich fibrin clot in the middle layer. Platelet-rich fibrin has proved useful in daily dental practice as filling material for regeneration in order to place implants.
In this study, 50 heart patients following an anticoagulant therapy were treated with leukocyte- and platelet-rich fibrin clots placed into postextraction sockets. Complications of bleeding were reported in only two of these patients, and 10 had mild bleeding. All complications were resolved within a few hours after the oral surgery.
Additionally, the study reported no painful events, quick healing of soft tissue, and complete wound closure within one week after oral surgery. Leukocyte- and platelet-rich fibrin offers an excellent option for use in heart patients on an anticoagulant regimen.
Full text of the article, “Prevention of Hemorrhagic Complications After Dental Extractions Into Open Heart Surgery Patients Under Anticoagulant Therapy: The Use of Leukocyte- and Platelet-Rich Fibrin ,” Journal of Oral Implantology, Vol. 37, No. 6, 2011, is available at http://www.joionline.org/ .
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About Journal of Oral Implantology
The Journal of Oral Implantology is the official publication of the American Academy of Implant Dentistry and of the American Academy of Implant Prosthodontics. It is dedicated to providing valuable information to general dentists, oral surgeons, prosthodontists, periodontists, scientists, clinicians, laboratory owners and technicians, manufacturers, and educators. The JOI distinguishes itself as the first and oldest journal in the world devoted exclusively to implant dentistry. For more information about the journal or society, please visit: http://www.aaid-implant.org/index.html
Tuesday, December 6, 2011
Dental X-rays can predict fractures
It is now possible to use dental X-rays to predict who is at risk of fractures, reveals a new study from researchers at the Sahlgrenska Academy reported in the journal Nature Reviews Endocrinology.
In a previous study, researchers from the University of Gothenburg's Sahlgrenska Academy and Region Västra Götaland demonstrated that a sparse bone structure in the trabecular bone in the lower jaw is linked to a greater chance of having previously had fractures in other parts of the body.
X-rays investigates bone structure
The Gothenburg researchers have now taken this a step further with a new study that shows that it is possible to use dental X-rays to investigate the bone structure in the lower jaw, and so predict who is at greater risk of fractures in the future. Published in the journal Bone, the results were also mentioned in both Nature Reviews Endocrinology and the Wall Street Journal.
Linked to risk of fractures
"We've seen that sparse bone structure in the lower jaw in mid-life is directly linked to the risk of fractures in other parts of the body, later in life,"says Lauren Lissner, a researcher at the Institute of Medicine at the Sahlgrenska Academy.
Study started 1968
The study draws on data from the Prospective Population Study of Women in Gothenburg started in 1968. Given that this has now been running for over 40 years, the material is globally unique. The study included 731 women, who have been examined on several occasions since 1968, when they were 38-60 years old. X-ray images of their jaw bone were analysed in 1968 and 1980 and the results related to the incidence of subsequent fractures.
For the first 12 years fractures were self-reported during followup examinations. It is only since the 1980s that it has been possible to use medical registers to identify fractures. A total of 222 fractures were identified during the whole observation period.
One out of five in higher risk
The study shows that the bone structure of the jaw was sparse in around 20% of the women aged 38-54 when the first examination was carried out, and that these women were at significantly greater risk of fractures.
The study also shows that the older the person, the stronger the link between sparse bone structure in the jaw and fractures in other parts of the body.
Applies for both sexes
Although the study was carried out on women, the researchers believe that the link also applies for men.
"Dental X-rays contain lots of information on bone structure," says Grethe Jonasson, the researcher at the Research Centre of the Public Dental Service in Västra Götaland who initiated the fractures study. "By analysing these images, dentists can identify people who are at greater risk of fractures long before the first fracture occurs."
In a previous study, researchers from the University of Gothenburg's Sahlgrenska Academy and Region Västra Götaland demonstrated that a sparse bone structure in the trabecular bone in the lower jaw is linked to a greater chance of having previously had fractures in other parts of the body.
X-rays investigates bone structure
The Gothenburg researchers have now taken this a step further with a new study that shows that it is possible to use dental X-rays to investigate the bone structure in the lower jaw, and so predict who is at greater risk of fractures in the future. Published in the journal Bone, the results were also mentioned in both Nature Reviews Endocrinology and the Wall Street Journal.
Linked to risk of fractures
"We've seen that sparse bone structure in the lower jaw in mid-life is directly linked to the risk of fractures in other parts of the body, later in life,"says Lauren Lissner, a researcher at the Institute of Medicine at the Sahlgrenska Academy.
Study started 1968
The study draws on data from the Prospective Population Study of Women in Gothenburg started in 1968. Given that this has now been running for over 40 years, the material is globally unique. The study included 731 women, who have been examined on several occasions since 1968, when they were 38-60 years old. X-ray images of their jaw bone were analysed in 1968 and 1980 and the results related to the incidence of subsequent fractures.
For the first 12 years fractures were self-reported during followup examinations. It is only since the 1980s that it has been possible to use medical registers to identify fractures. A total of 222 fractures were identified during the whole observation period.
One out of five in higher risk
The study shows that the bone structure of the jaw was sparse in around 20% of the women aged 38-54 when the first examination was carried out, and that these women were at significantly greater risk of fractures.
The study also shows that the older the person, the stronger the link between sparse bone structure in the jaw and fractures in other parts of the body.
Applies for both sexes
Although the study was carried out on women, the researchers believe that the link also applies for men.
"Dental X-rays contain lots of information on bone structure," says Grethe Jonasson, the researcher at the Research Centre of the Public Dental Service in Västra Götaland who initiated the fractures study. "By analysing these images, dentists can identify people who are at greater risk of fractures long before the first fracture occurs."
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