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Can This Type of Protein Affect The Movement of Teeth?

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A frequent problem in orthodontic practice is that the teeth do not remain in their new positions. Can a protein prevent teeth from moving in the mouth?

In the body, some proteins work as small keys that unlock cells and tell them to perform a specific task. Now, research at the Faculty of Dentistry shows that the protein, adiponectin can perhaps affect how a tooth shifts in the mouth. Fellow Sigrid Haugen and co-workers have investigated this phenomenon.

Adiponectin – An important protein
Signal molecules that serve as keys to initiate processes in our bodies are called hormones. Hormones are produced in many parts of the body. For example, the pancreas produces insulin, which is important for blood sugar regulation. The ovaries and testicles produce sex hormones, and the thyroid gland produces two growth hormones. It is common knowledge that the glands, bone marrow and some areas of the brain produce hormones. However, the fact that fat tissue produces hormones, and is, therefore, an endocrine organ, is not equally known. Fat tissue actually produces many different hormones. The first to be described was leptin and adiponectin.

Adiponectin is shown to play an important role in the metabolism of sugar and fats, but may also have other important functions in the body and, in some contexts, it can help reduce inflammation, e.g. in cardiovascular disease.

“We knew that adiponectin is secreted by fat cells and circulates in high concentrations in the blood of young and healthy people,” explains Professor Janne Reseland.

“We did not know, however, whether this hormone is produced in other cells and tissues of the body.”

In 2004, Reseland and coworkers discovered that adiponectin is present in bone cells, not only in osteoblasts, the cells that synthesize bone but also in osteoclasts, the cells that break down bone tissue. Both cell types help to maintain bone mass and bone strength.

Movement of teeth
In orthodontic tooth movement, the goal is to move teeth into the correct position.. When a tooth moves in the mouth, it moves in the jawbone by the help of the bone cells? In simple terms, teeth are pulled by the osteoclasts that break down bone on one side and pushed in the same direction by the osteoblasts, the bone-building cells, on the other.

A question emerged; “Can adiponectin affect the movement of teeth”?

A rat model
A rat model was used to look into this question. The research team used 24 rats, each of which had braces fitted on the same tooth and at the same location in the mouth. Then the rats were divided into three groups. While one group received a low dose of adiponectin injected in front of the moving tooth,, another group received a high dose of adiponectin at the same location. The last group was the control group and these rats were injected with saline solution.

“In orthodontics we seek to move the tooth in a certain direction,” explains Sigrid Haugen, a doctoral research fellow at the Institute for Clinical Dentistry.

“This was successful in the control rats that were injected with saline solution, not adiponectin”, she explains.

The research team discovered that, in rats injected with adiponectin, the tooth moved less than in the control group. In the group that received a high dose of adiponectin, the tooth did not move at all, and in the group that received a low dose of adiponectin, the tooth had moved far less than the control group.

This meant that something had occurred in the bone cells to prevent the teeth from moving.

A local effect

“Another interesting discovery was that we did not find changes in adiponectin levels in plasma,” says Haugen.

“This suggests that the adiponectin, administered in front of the moving tooth probably had a local effect, indicating that the procedure did not affect other parts of the body.”

The fact that the active substance only has a local effect is important if we intend to use it in orthodontics or dentistry in the future.

Exciting new direction

“We have not determined the mechanisms by which adiponectin anchors teeth or how long the effects of the injection last. These aspects remains to be investigated” explains Haugen.

The interesting thing is that the research shows that it is possible to influence tooth movement in these model and the findings suggest that possibly in the future we will be able to use injectable substances to regulate the speed of tooth movement.

“As with all new research, more studies are requiered before we can reach any firm conclusion. Nevertheless, the results of our research into the adiponectin protein lead us in a new and exciting direction,” says Haugen.

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The Effectiveness Of Chlorhexidine Is Limited In Preventing Infections In Oral Procedures

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The human oral cavity is colonised by a huge variety of bacteria. When surgical procedures such as a tooth extraction are carried out, the bacteria can pass into the bloodstream causing bacteraemia that is generally transient. What is not yet clear is how significant this presence of bacteria in the blood is in terms of the origin and evolution of infectious processes such as endocarditis of the heart valves, prosthetic valves, hip and knee joint replacements generally, and in local infection.

Numerous studies have shown that a mouthwash containing chlorhexidine has a powerful antimicrobial effect on saliva microflora and bacterial plaque.

“On the basis of this hypothesis we can assume that antimicrobial mouthwashes used before the dental procedure should reduce the number of micro-organisms that pass into the patient’s bloodstream, yet this is a hotly debated issue,” said the members of the UPV/EHU’s research group.

In 1997 the American Heart Association (AHA) suggested that patients at risk of infectious endocarditis should use an antimicrobial mouthwash before a dental procedure. In 2006, the British Society for Antimicrobial Chemotherapy (BSAC) recommended a single mouthwash with 0.2% chlorhexidine (CHX) (10 ml for 1 minute) before the carrying out of dental procedures associated with bacteraemia in patients at risk. Yet in 2007 the AHA recommended against adopting any antiseptic prophylaxis protocol.

In an effort to shed scientific light on this issue, the UPV/EHU research group comprising Iciar Arteagoitia, Carlos Rodriguez-Andrés and Eva Ramos decided to conduct a systematic review and meta-analysis of random controlled trials (RCT), following the PRISMA Statement. The aim was to assess the effectiveness of chlorhexidine in preventing bacteraemia following a tooth extraction. The research was conducted in collaboration with the UPV/EHU’s Department of Epidemiology and was published in Plos One.

In the study that included 8 clinical trials with 523 patients there were 267 in the group treated with chlorhexidine, in which 145 cases of bacteraemia were recorded, and 256 in the control group, in which there were 156 cases of bacteraemia. The results of the research therefore indicate that the percentage of cases of bacteraemia that can be prevented if a population undergoes chlorhexidine-based prevention is 12%. The NNT, the number of patients that need to be treated to prevent bacteraemia, is 16.

The results point to the relative and not particularly significant effectiveness of the use of chlorhexidine when it comes to preventing the bacteria present in the mouth from passing into the bloodstream when dental extraction is carried out.

“Yet, given its low cost and the absence of adverse reactions and complications, we would recommend a mouthwash with chlorhexidine before a procedure of this type is carried out,” concluded the UPV/EHU’s research group.

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Effective Diagnosis Of Persistent Facial Pain Will Benefit Patients And Save Money

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Patients with persistent facial pain are costing the economy more than £3,000 each per year, new research has revealed.

Experts at Newcastle University, UK, say introducing an electronic referral system to speed up diagnosis and treatment is likely to improve quality of life and save money.

The team has assessed the hidden costs of people suffering from long-term face and mouth pain that wasn’t caused by toothache.

Findings, published today in the Journal of Dental Research, show patients’ out-of-pocket costs are more than £650 a year, including prescription charges and travel expenses to and from appointments.

Meanwhile, costs to employers can be almost £2,500 every 12 months, due to aspects such as absenteeism and workers’ loss of productivity as a result of dealing with pain.

Screening patients

This research adds weight to growing evidence that there is a need to screen patients with a Graded Chronic Pain Scale (GCPS) to ensure those most severely affected receive specialist care quickly.

A previous study, by the same team at Newcastle University, showed that a well-established graded pain scale could help reduce costs by providing a better structured system of care.

Justin Durham, Professor of Orofacial Pain and Deputy Dean of Clinical Medicine, at Newcastle University, led the two-year study which was funded by the National Institute for Health Research.

He said: “Our research shows that people have to go around the proverbial ‘mulberry bush’, visiting lots of different healthcare professionals to even get close to obtaining a diagnosis never mind beginning treatment for their condition.

“A better and more defined care pathway would improve care for those with persistent facial pain and help reduce their costs and those to the economy.”

It is estimated that 7% of the population have Persistent Orofacial Pain (POFP), including temporomandibular disorders, phantom tooth pain, burning mouth syndrome, trigeminal neuralgia and atypical facial pain.

This research has revealed how patients attend a large number of appointments with different healthcare professionals but fail to obtain effective diagnosis or treatment plan quickly.

Professor Durham added: “Persistent facial pain is like having toothache every day of the week and, therefore, understandably has a profound and debilitating impact on people’s lives, and our research has highlighted the hidden costs of this condition.”

Data collected

Experts asked 200 patients suffering long-term face and or mouth pain to complete questionnaires every six months for two years to assess how individuals used the NHS for their pain.

The team collected the costs of the care patients received, such as what the NHS paid to provide medication, surgery or other treatments, how much patients paid out of their own pockets and how their condition affected their ability to work.

Within a six month period, participants reported an average of nine healthcare appointments, and those employed reported missing almost two days off work. This absenteeism equates to an average employer cost of £174 per person per six-months.

While the findings suggest that most study participants were unlikely to have a large number of days off work because of their pain, they did report experiencing pain while working for nearly 35 days in a six-month period, during which they noted a decrease in their productivity whilst at work that could cost employers more than £1,000.

Professor Durham said: “We’re calling for the introduction of an electronic referral system which uses a Graded Chronic Pain Scale — a simple seven item questionnaire.

“This scale would be a reliable way to determine who to fast-track to specialists and who should begin care immediately at their dentists or GP, meaning direct referrals would be made electronically to the best service local to the patient rather than relying on healthcare professionals’ knowledge of who manages persistent facial pain in their locality.”

Further research is expected to focus on how care pathways can be designed to better meet the needs of patients.

In partnership with the British Dental Association, the Newcastle University team is helping dentists and GPs manage persistent facial pain by setting up study days for next year.

Peter Dyer, Chair of the British Dental Association’s Central Committee for Hospital Dental Staff, said: “Dentists working in hospitals will have seen patients who have failed to get priority, some on the verge of suicide in the face of unmanageable pain.

“This important research is a timely reminder that facial pain carries a huge personal and financial cost, and patients need not face barriers securing care.

“When so many people have been laid low by this condition GPs and high street dentists need a clear pathway to ensure patients can get the right treatment, when they need it.”

Patient’s story

Father-of-two Joe Buckham’s life was turned upside down when he began to get severe facial pain a decade ago.

The extraction of a wisdom tooth left the former school teacher in agony as he suffered a fractured jaw during the procedure and a subsequent bone infection.

Mr Buckham was pushed from pillar to post as healthcare professionals struggled to identify the problem despite extensive tests, scans and investigations.

He spent a lot of money on hospital trips, including return train fares to a specialist in Oldham up to eight times, and private treatment, such as acupuncture and sports massage therapy.

It was not until he was referred to Professor Justin Durham, an Honorary Consultant Oral Surgeon at Newcastle upon Tyne Hospitals NHS Foundation Trust, that his problem was unearthed.

The 52-year-old has received treatment at Newcastle Hospitals’ orofacial pain referral service and is on medication to help him deal with the pain.

The foster carer, of Rowlands Gill, Gateshead, said: “I believe had I been given the correct treatment quicker than I was, then I would have continued to work as a teacher.

“Sadly I had to retire because I couldn’t do the job due to the seriousness of the pain — even things such as heat and antibiotics make it much worse.

“The pain I get in my face is severe and it can be very debilitating, sometimes it’s so bad I just want to lie in a darkened room.

“Persistent facial pain is a hidden condition as no-one can see the problem and people don’t understand it’s so serious that it can ruin lives and you’re stuck with it forever.

“The specialist service in Newcastle is fantastic and the research being done into facial pain is very much welcomed to help raise awareness of the condition.

“I feel that if medical healthcare professionals were able to use a Graded Chronic Pain Scale it would help ensure patients like me got the best treatment as soon as possible.”

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Researchers Are First To Sequence Rare Bacteria That Causes Rampant Tooth Decay

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The most prevalent chronic disease in both children and adults, tooth decay occurs when the good and bad bacteria in our mouth become imbalanced. The bad bacteria, Streptococcus mutans, forms a biofilm (aka tartar), then takes the sugars we eat and ferments them into acid, which decalcifies our teeth and causes cavities.

Scientists know, though, that there is a second harmful bacteria called Streptococcus sobrinus that accelerates tooth decay in some people, but very little is known about this microbe. This will soon change because a team of Illinois Bioengineering researchers led by Assistant Professor Paul Jensen has successfully sequenced the complete genomes of three strains of S. sobrinus.

According to Jensen, S. sobrinus is difficult to work with in the lab and it is not present in all people, so researchers have instead focused their efforts over the years on understanding the more stable and prevalent S. mutans, which was sequenced in 2002.

“Although it is rare, S. sobrinus produces acid more quickly and is associated with the poorest clinical outcomes, especially among children,” noted Jensen, a researcher at the Carl R. Woese Institute for Genomic Biology on campus.

“If S. sobrinus is present along with S. mutans, you’re at risk for rampant tooth decay, which means there’s some level of communication or synergy between the two that we don’t understand yet.”

Now that the S. sobrinus sequencing is complete, Jensen and his students are building computational models to better understand how the two bacteria interact and why S. sobrinus can cause such potent tooth decay when combined with S. mutans.

Already they have confirmed, for example, that S. sobrinus lacks complete pathways for quorum sensing, which is the ability bacteria have to sense and react to nearby bacteria, and ultimately proliferate.

According to Jensen, S. mutans bacteria send out feelers in the form of a peptide to find out how many other S. mutans cells are nearby. Once the S. mutans cells reach a certain threshold, they attack and create an imbalance in a person’s mouth between good and bad bacteria, which leads to rapid cavity formation.

S. sobrinus doesn’t have a complete system to do this,” said Jensen.

“We’re really curious to explore this further and find out what is missing and why.”

Interestingly, the entire S. sobrinus genome sequencing was completed by a team of Bioengineering undergraduates and students enrolled in the one-year Master of Engineering (M.Eng.) program, rather than doctoral candidates who typically conduct this type of research over several years.

“For the S. sobrinus field, this is groundbreaking work because the field was plagued by a lack of information,” said Jensen.

“In 2018, it is surprising that we had a whole species [of bacteria] that causes disease and no complete genome of it. Yet, an ambitious team of undergrads and M.Eng. students completed the sequencing in a year.”

Mia Sales, who graduated with her bachelor’s degree this past May, completed the assemblies of two of the species of S. sobrinus. Sales also built the computer that other team members used to do the initial genome assemblies.

Fellow undergraduate Will Herbert worked on the annotation part of the project, finding genes in the strings of approximately 2 million adenine (A), cytosine (C), guanine (G), and thymine (T) nucleotides that make up the S. sobrinus genomes.

Other contributors to the research include M.Eng. students Yuting Du, Amitha Sandur, and Naaman Stanley.

“This work exemplifies the students’ ability to synthesize their learning experience with a completely new insight, resulting in an original research publication,” said Professor Dipanjan Pan, director of the M.Eng. program.

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