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Antibiotics Destroy ‘Good Bacteria’ And Worsen Oral Infection

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New research shows that the body’s own microbes are effective in maintaining immune cells and killing certain oral infections.

A team of Case Western Reserve University researchers found that antibiotics actually kill the “good” bacteria keeping infection and inflammation at bay.

Scientists have long known that overuse of antibiotics can do more harm than good. For example, overuse can cause antibiotic resistance. But research into this phenomenon in oral health was uncharted territory.

Pushpa Pandiyan, an assistant professor of biological sciences in the School of Dental Medicine, led a team of researchers to examine “resident” bacteria, their fatty acids and their effect on certain types of white blood cells that combat infections in the mouth.

Specifically, researchers looked at the “short-term maintenance” of Tregs and Th-17 cells in fighting fungal infections, such as Candida, in a laboratory setting.

They found that those natural defenses were very effective in reducing infection and unwanted inflammation — and antibiotics can prevent such natural defenses. Their work was recently published in Frontiers in Microbiology.

“We set out to find out what happens when you don’t have bacteria to fight a fungal infection,” Pandiyan said.

“What we found was that antibiotics can kill short-chain fatty acids produced by body’s own good bacteria.”

“We have good bacteria doing good work every day, why kill them?” Pandiyan added.

“As is the case with many infections, if you leave them alone, they will leave on their own.”

“Of course, antibiotics are still needed for life threatening infections. No question about that. Our bodies have many natural defenses that we shouldn’t meddle with,” she said.

However, needless overuse of antibiotics is not helpful, she said.

“Also, we know there is a definite link between oral health and overall health,” she added.

Pandiyan said the study could have broader implications on protective effects of “resident microbiota” in other types of infections.

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Regrowing Dental Tissue With Stem Cells From Baby Teeth

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Sometimes kids trip and fall, and their teeth take the hit. Nearly half of children suffer some injury to a tooth during childhood. When that trauma affects an immature permanent tooth, it can hinder blood supply and root development, resulting in what is essentially a “dead” tooth.

Until now, the standard of care has entailed a procedure called apexification that encourages further root development, but it does not replace the lost tissue from the injury and, even in a best-case scenario, causes root development to proceed abnormally.

New results of a clinical trial, jointly led by Songtao Shi of the University of Pennsylvania and Yan Jin, Kun Xuan, and Bei Li of the Fourth Military Medicine University in Xi’an, China, suggest that there is a more promising path for children with these types of injuries: Using stem cells extracted from the patient’s baby teeth. The work was published in the journal Science Translational Medicine.

“This treatment gives patients sensation back in their teeth. If you give them a warm or cold stimulation, they can feel it; they have living teeth again,” says Shi, professor and chair in the Department of Anatomy and Cell Biology in Penn’s School of Dental Medicine.

“So far we have follow-up data for two, two and a half, even three years and have shown it’s a safe and effective therapy.”

Shi has been working for a decade to test the possibilities of dental stem cells after discovering them in his daughter’s baby tooth. He and colleagues have learned more about how these dental stem cells, officially called human deciduous pulp stem cells (hDPSC), work and how they could be safely employed to regrow dental tissue, known as pulp.

The Phase I trial, conducted in China, which has a research track for clinical trials, enrolled 40 children who had each injured one of their permanent incisors and still had baby teeth. Thirty were assigned to hDPSC treatment and 10 to the control treatment, apexification.

Those that received hDPSC treatment had tissue extracted from a healthy baby tooth. The stem cells from this pulp were allowed to reproduce in a laboratory culture, and the resulting cells were implanted into the injured tooth.

Upon follow-up, the researchers found that patients who received hDPSCs had more signs than the control group of healthy root development and thicker dentin, the hard part of a tooth beneath the enamel. Blood flow increased as well.

At the time the patients were initially seen, all had little sensation in the tissue of their injured teeth. A year following the procedure, only those who received hDPSCs had regained some sensation. Examining a variety of immune-system components, the team found no evidence of safety concerns.

As further support of the treatment’s efficacy, the researchers had the opportunity to directly examine the tissue of a treated tooth when the patient reinjured it and had to have it extracted. They found that the implanted stem cells regenerated different components of dental pulp, including the cells that produce dentin, connective tissue, and blood vessels.

“For me the results are very exciting,” Shi says.

“To see something we discovered take a step forward to potentially become a routine therapy in the clinic is gratifying.”

It is, however, just a first step. While using a patient’s own stem cells reduces the chances of immune rejection, it’s not possible in adult patients who have lost all of their baby teeth. Shi and colleagues are beginning to test the use of allogenic stem cells, or cells donated from another person, to regenerate dental tissue in adults. They are also hoping to secure FDA approval to conduct clinical trials using hDPSCs in the United States.

Eventually, they see even broader applications of hDPSCs for treating systemic disease, such as lupus, which Shi has worked on before.

“We’re really eager to see what we can do in the dental field,” Shi says, “and then building on that to open up channels for systemic disease therapy.”

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New Findings On Chronic Pain Syndrome In The Mouth

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The picture is becoming clearer regarding the chronic oral pain condition known as Burning Mouth Syndrome, or BMS, which mainly affects women who are middle-aged and older. In a dissertation at Sahlgrenska Academy, additional steps are being taken toward better diagnosis and treatment.

“Our hope is that the new findings will contribute to the development of objective diagnostic criteria and effective individualized treatment both that are currently lacking,” says Shikha Acharya, who has a PhD in oral microbiology and immunology at the Institute of Odontology.

Burning Mouth Syndrome (BMS) is a chronic pain syndrome in the oral cavity that affects approximately 4% of the Swedish population. This chronic condition mainly affects middle-aged and elderly women.

The pain is experienced as burning or stinging. The tongue is most often afflicted, but the palate, lips and gums also may be affected. Other common symptoms include dry mouth and altered taste sensation, such as a bitter or metallic taste in the mouth.

BMS is a challenge for health care providers, particularly in dental care, and a debilitating condition for many of the patients. When they estimate their problem on a visual analogue scale (VAS) where 0 is “not at all difficult” and 100 is “unbearable,” the average response is 66, the dissertation indicates. The findings came from 56 women with BMS.

In her work Shikha Acharya also connected clinical findings and self-reported reported findings from questionnaires from patients with BMS about their symptoms and background (other diseases, use of medications, etc.) along with saliva-related factors. The results have been compared with a gender- and age-matched control group.

It turns out that 45 percent of the BMS patients reported to have altered taste sensations. A total of 73 percent experienced pain that was burning or stinging or a combination of the two, but stinging and numbness also occurred.

In addition to BMS, they have a higher incidence of other types of diseases, use more medications, are more prone to grinding their teeth and report more allergies than the control group. However, more advanced analyses show that BMS was strongly associated to self-reported skin diseases and subjective oral dryness.

The fact that the BMS patients, compared with people in the control group, report that they suffer considerably more from skin diseases and skin problems is a new discovery. Similarly, that the mucin proteins in BMS patients’ saliva are altered and contain lower amounts of carbohydrate structures that affect the oral cavity’s immune system.

Analysis of inflammatory constituents in saliva shows complex relationship between BMS and background inflammation, with some of the BMS patients having higher levels of inflammation than the control group while others had lower.

The dissertation work is part of a larger project aimed at finding a model for BMS that can facilitate diagnosis and treatment in the future. The new pieces of the puzzle are helping to characterize the disease and the persistent mouth pain associated with it.

“It’s important because the afflicted patients often feel that their surroundings and health care professionals doubt their ailment,” says Shikha.

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Novel Nanoparticle-Based Approach Detects And Treats Oral Plaque Without Drugs

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When the good and bad bacteria in our mouth become imbalanced, the bad bacteria form a biofilm (aka plaque), which can cause cavities, and if left untreated over time, can lead to cardiovascular and other inflammatory diseases like diabetes and bacterial pneumonia.

A team of researchers from the University of Illinois has recently devised a practical nanotechnology-based method for detecting and treating the harmful bacteria that cause plaque and lead to tooth decay and other detrimental conditions.

Bioengineering Associate Professor Dipanjan Pan (seated) and doctoral student Fatemeh Ostadhossein have demonstrated a drug-free, nanotechnology-based method for detecting and destroying the bacteria that causes dental plaque.

Oral plaque is invisible to the eye so dentists currently visualize it with disclosing agents, which they administer to patients in the form of a dissolvable tablet or brush-on swab. While useful in helping patients see the extent of their plaque, these methods are unable to identify the difference between good and bad bacteria.

“Presently in the clinic, detection of dental plaque is highly subjective and only depends on the dentist’s visual evaluation,” said Bioengineering Associate Professor Dipanjan Pan, head of the research team.

“We have demonstrated for the first time that early detection of dental plaque in the clinic is possible using the regular intraoral X-ray machine which can seek out harmful bacteria populations.”

In order to accomplish this, Fatemeh Ostadhossein, a Bioengineering graduate student in Pan’s group, developed a plaque detection probe that works in conjunction with common X-ray technology and which is capable of finding specific harmful bacteria known as Streptococcus mutans (S. mutans) in a complex biofilm network. Additionally, they also demonstrated that by tweaking the chemical composition of the probe, it can be used to target and destroy the S. mutans bacteria.

The probe is made up of nanoparticles made of hafnium oxide (HfO2), a non-toxic metal that is currently under clinical trial for internal use in humans. In their study, the team demonstrated the efficacy of the probe to identify biochemical markers present at the surface of the bacterial biofilm and simultaneously destroy S. mutans. They conducted their study on Sprague Dawley rats.

In practice, Pan envisions a dentist applying the probe on the patient’s teeth and using the X-ray machine to accurately visualize the extent of the biofilm plaque. If the plaque is deemed severe, then the dentist would follow up with the administering of the therapeutic HfO2 nanoparticles in the form of a dental paste.

In their study, the team compared the therapeutic ability of their nanoparticles with Chlorhexidine, a chemical currently used by dentists to eradicate biofilm. “Our HfO2 nanoparticles are far more efficient at killing the bacteria and reducing the biofilm burden both in cell cultures of bacteria and in [infected] rats,” said Ostadhossein, noting that their new technology is also much safer than conventional treatment.

The nanoparticles’ therapeutic effect is due, said Pan, to their unique surface chemistry, which provides a latch and kill mechanism.

“This mechanism sets our work apart from previously pursued nanoparticle-based approaches where the medicinal effect comes from anti-biotics encapsulated in the particles,” said Pan, also a faculty member of the Carle Illinois College of Medicine and the Beckman Institute for Advanced Science and Technology.

“This is good because our approach avoids anti-biotic resistance issues and it’s safe and highly scalable, making it well-suited for eventual clinical translation.”

In addition to Pan and Ostadhossein, other members of the research team include bioengineering post-doctoral researcher Santosh Misra, visiting scholar Indu Tripathi, undergraduate Valeriya Kravchuk, visiting scholar Gururaja Vulugundam; and Veterinary Medicine clinical assistant professor Denae LoBato and adjunct assistant professor Laura Selmic.

Their work is described in the paper, “Dual purpose hafnium oxide nanoparticles offer imaging Streptococcus mutans dental biofilm and fight it In vivo via a drug free approach,” published online on July 30, 2018, in the journal Biomaterials. The research was funded by the University of Illinois at Urbana-Champaign Children’s Discovery Institute and the American Heart Association.

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