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An Overview of the Derivation and Function of Multinucleated Giant Cells and Their Role in Pathologic Processes

July 25th, 2019

Monocyte lineage cells play important roles in health and disease. Their differentiation into macrophages is crucial for a broad array of immunologic processes that regulate inflammation, neoplasia, and infection. In certain pathologic conditions, such as foreign body reactions and peripheral inflammatory lesions, monocytes fuse to form large, multinucleated giant cells (MGCs). Currently, our knowledge of the fusion mechanisms of monocytes and the regulation of MGC formation and function in discrete pathologies is limited. Herein, we consider the types and function of MGCs in disease and assess the mechanisms by which monocyte fusion contributes to the formation of MGCs. An improved understanding of the cellular origins and metabolic functions of MGCs will facilitate their identification and ultimately the treatment of diseases and disorders that involve MGCs.

Certain healthy tissues, including skeletal muscle, placenta, and bone, contain populations of multinucleated cells.1 In contrast, the presence of multinucleated cells in other tissues is considered pathologic. Multinucleated giant cells (MGCs), which are polykaryons of monocytic origin, are often spatially associated with foreign bodies (ie, introduced exogenous materials) or comprise part of a tissue response to infection. MGCs also appear in autoimmune, neoplastic, and genetic disorders. Histologically, MGCs are morphologically similar to one another, despite their appearance in various discrete pathologies. Currently, the characterization of the various types of MGCs by histology alone is of limited value as the molecular determinants that specify the formation and function of these cells are not defined.

For the rest of this journal article please find it here! 


June 26th, 2019

The following information was taken from the Ontario Dental Association website https://www.oda.ca

Oral health is one factor that contributes to a healthy lifestyle. Here are some tips to help you look after your oral health.

  • Schedule regular visits to your dentist.
  • Brush at least twice a day and floss at least once a day.
  • Eat a well-balanced diet.
  • Check your mouth regularly to become familiar with what is normal for you. This will help you recognize when something in your mouth looks or feels different or abnormal.
  • Avoid activities that might harm your mouth or teeth such as smokingoral piercings and recreational drugs.
  • Try to reduce the impact stress has on your oral and overall health.
  • Alert your dentist to any herbal remedies, over-the-counter or prescription drugs you are taking.
  • Wear a mouthguard to protect your teeth when you are playing sports. Read more about mouthguards.

What should my mouth look like on the inside?
Between dental visits check your mouth for warning signs of gum disease and oral cancer.

Warning signs of gum disease may include:

  • puffy, red, sore, shiny or sensitive gums
  • bleeding when you brush or floss
  • bad breath that won’t go away

Warning signs of oral cancer may include:

  • numbness and tingling
  • open sores that don’t go away within a week to 10 days
  • unexplained bleeding
  • lumps or thickening on the bottom or sides of your tongue, cheeks, or roof of your mouth.

If you notice any of these signs, or have any concerns, call your dentist immediately.

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People may overlook the effect stress has on our oral health. However, our mouths can be just as affected by stress as the rest of our bodies are. Stress can have real consequences for our oral health as well as overall well-being.

Stress can make people neglect their oral-health routines. They may not brush or floss as often as they should or miss dental appointments. People under stress sometimes make poor lifestyle choices – smoking, consuming too much alcohol and eating more sugary foods – which can lead to serious issues including oral cancer, gum disease or tooth decay.

Stress is a contributing factor to other serious oral-health conditions, including:

  • Bruxism, or teeth grinding. People under stress may clench or grind their teeth, especially during sleep. Over a long period of time, bruxism can wear down tooth surfaces. Teeth can also become painful or loose from severe grinding or prone to fractures.
  • Temporomandibular disorder (TMD) affects the jaws joints and groups of muscles that let us chew, swallow, speak and yawn. Symptoms include tender or sore jaw muscles, headaches and problems opening or closing your mouth. Bruxism is a major cause of TMD – clenching your jaw muscles can cause them to ache.
  • Periodontal (gum) disease. Research has shown that stress affects our immune systems, increasing our susceptibility to infections, including the bacteria that cause gum disease.
  • Xerostomia, or dry mouth, can also be caused by medications to treat stress. Saliva is vital to keep your mouth moist, wash away food and neutralize the acids that are produced by plaque. Left untreated, dry mouth can damage your teeth.

It may be impossible to eliminate all stress from your life, but you can take simple steps to reduce its impact on your health.

  • Find relaxation techniques or exercises to help you cope with stress.
  • Brush at least twice a day and floss daily.
  • Schedule and keep regular appointments with your dentist.
  • Talk to your dentist about getting a custom-fitted nightguard to protect your teeth while you sleep.
  • Eat a balanced diet, with plenty of fruits and vegetables.
  • Stay active. If you don't have time to exercise, a 30-minute walk every day is a good start.
  • Get plenty of sleep.

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It’s important to know that all types of tobacco including cigarettes, cigars and chewing tobacco are harmful for your oral health. In addition to containing nicotine — which is addictive — they have been all been known to cause:

  • gum disease
  • tooth loss
  • oral cancer (cancer of the lip, tongue)
  • cancer of the esophagus and voice box
  • pancreatic, esophagal, colon and bladder cancer
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Almost 75% of gum disease in adults is caused by smoking. Also, your gums may recede as a result of smoking. This may lead to tooth decay and an increased sensitivity to hot and cold food and drinks.

Find out more about tobacco cessation and how your dentist can help.

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Oral Piercings
If you are considering an oral piercing, it’s important to know the potential side-effects. Here are some of the complications that may occur:

  • Your mouth contains a lot of bacteria. Oral piercing may lead to infection
  • Your piercing may result in pain, swelling or gum tissue damage
  • Your piercing may cause chipped or cracked teeth
  • A pierced blood vessel may cause uncontrollable bleeding
  • In some cases, your swollen tongue can actually block your airway and inhibit your breathing

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Recreational Drugs
Did you know that there are consequences for your oral health when you decide to use recreational drugs? It’s true! Here are some examples:

  • Tooth loss: Using tobacco, ecstasy, amphetamines and methamphetamines, can lead to the constriction of the capillaries in your gums. This affects the attachment of the bone to the tissue of your teeth and may lead to tooth loss.
  • Dry mouth: Marijuana, ecstasy, amphetamines, methamphetamines, heroin and replacement therapies may decrease the saliva production that occurs in your mouth. This will in turn, increase your risk for gum disease and tooth decay.
  • Erosion and tooth decay: Ecstasy raises your body temperature and you will want to consume sugary liquids. Marijuana and heroin also cause sugar cravings. Frequent consumption of sugary drinks and sweets will weaken your tooth enamel. Vomiting after alcohol consumption may also erode your teeth.

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Prescription Drugs
It’s important to be aware of how prescriptions and over-the counter-drugs may affect your oral health. For example:

  • Asthma inhalers that are high in acid can dissolve tooth enamel when used frequently
  • Cough syrups that have a high sugar content may result in tooth decay
  • Antihistamines may cause dry mouth
  • Aspirins, blood thinners and some herbal remedies may affect the ability of the blood to clot normally

The following medications may cause damage to your gums:

  • oral contraceptives
  • immunosuppressive drugs
  • chemotherapy drugs
  • anti-hypertensives
  • antihistamines

Talk to your dentist about how the prescription drugs you are taking might affect your oral health.

Oral Health Research: Neutrophils Break Down Dentin and Cured Composite Resin

June 20th, 2019

Following decades of research indicating that bacteria are responsible for tooth decay, the need for fillings and restorations, a new study, conducted by a number of University of Toronto oral health researchers and titled Human neutrophils degrade methacrylate resin composites and tooth dentin, is now pointing to a long-ignored culprit: neutrophils.

A type of white blood cell, neutrophils have up until now been best known for fighting inflammation. However, the research team has shown that the body’s immune system itself may be causing tooth decay and failing composite and other restorations.

The Research

Building on a theory proposed 50-years ago by John Gabrovsek, in the Cleveland Clinic, and published in the Journal of Dental Research (1970), the research team used neutrophils isolated from blood to coat parts of extracted teeth and cured composite resin. Within the body, neutrophils reach the mouth via the gums and roots of the teeth. Then, they measured the level of teeth degradation at intervals of 2, 4, 24, and 48 hours and the degradation of cured composite resin degradation at intervals of 48 and 96 hours.

Within a few hours, researchers found dentin and the cured composite resin had sustained damage.

According to the study co-author, Dr. Michael Glogauer, “We can actually see them breaking down using electron microscopy.”

The team’s research also confirms the breakdown of by-products can only come from neutrophils. The reason? When bacteria is present in the mouth, neutrophils are activated and release “attack” enzymes. These enzymes attack mouth bacteria creating acids that degrade teeth and resins in the process.

Study co-author, Dr. Yoav Finer, explained that “On their own, neutrophils are incapable of causing damage to the teeth. They [neutrophils] don’t have acid, so they can’t do much to mineralized tooth structures.”

What’s Next?

Today, the team is setting their sights on isolating the type of enzymes that damage teeth and finding ways to control or limit the damage caused by neutrophils, for example using mouth rinse.

Read the article or learn more about this research.

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Until next time!

CDA Oasis Team

Fibrosis research at the Faculty of Dentistry receives major funding boost

June 13th, 2019

The Faculty of Dentistry was awarded ~$10 million in research funds from the CFI Innovation Fund and Ontario Research Fund. The award – largest in the Faculty’s history – will create Canada’s first comprehensive state-of-the-art research hub: “The Fibrosis Network”. The Network is founded on the bedrock of pioneering multi-disciplinary research, long-standing multi-sector partnerships, and the innovative vision of Dentistry’s Chris McCulloch. McCulloch led the initiative along with Dentistry’s Michael Glogauer and Boris Hinz and involved seven additional top-notch scientists and clinicians at U of T’s Faculty of Arts and Science, Ted Rogers Centre for Heart Research, St. Michael’s Hospital, and Toronto Western Research Institute. Farah Thong, Dentistry’s Research and Business Development Manager was instrumental in the success of the application by coordinating this multi-centre application and by providing strategic writing of the proposal.

Fibrosis, simply put is a pathological “stiffening” of once agile vital organs such as heart and lung, affects more than 2 billion people, costs more than $2.5 billion in global health care resources annually and is a major burden on families and society. It is a major cause of organ failure and there is currently no cure and its early diagnosis that can circumvent organ transplantation is not possible. The CFI/ORF award will fund new cutting-edge research infrastructure that will be needed to conduct world-class human-centric fibrosis research across three major themes: Mechanisms of Fibrosis, Biomarker Discovery and Diagnostics, and Fibrosis Therapies that will lead to the discovery of new drug targets and biomarkers, non-invasive in vivo diagnostics to facilitate early diagnosis, and new treatment strategies. “By virtue of using this equipment, we’re able to conduct experiments we’d otherwise never be able to do,” says leader McCulloch, who holds a Tier 1 Canada Research Chair in Matrix Dynamics.

The Fibrosis Network dovetails nicely with the Global Fibrosis Network established through a recent $250,000 award from U of T’s Connaught Global Challenge Fund to IBBME and Dentistry’s cross-appointed Craig Simmons. The award, which included co-applicant Chris McCulloch and researchers at U of T’s affiliated hospitals, will fund international fibrosis research networking events to enhance local and global collaborations and establish a global community of trainees and provide them with multi-sectoral and global perspectives on fibrosis research and technology. Soror Sharifpoor, Research Program Manager at U of T’s Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, was key in writing the winning proposal.

Boris Hinz, a Distinguished Professor of Tissue Repair and Regeneration in Dentistry, received $3.17 million over seven years from the Canadian Institutes of Health Research as one of few recipients of a highly competitive Foundation grant. Hinz will continue his research on myofibroblasts, which are cells involved in tissue repair. “The issue with these cells is that they keep on repairing the tissue. They don’t know when to stop,” says Hinz. When they go overboard, they leave disease-causing fibrosis behind.

These timely awards will provide significant resources to transform fibrosis research, build mutual capacity across sectors, and train the next generation of researchers. These initiatives will help the researchers achieve a level of basic and clinical research capacity unmatched in Canada that will have significant impact on patient care and establish Canada as a global leader in fibrosis research. “This remarkable combined success has now created a powerful hub to eventually make a real difference to fibrosis patients. Faculty of Dentistry researchers are playing a critical role in this multidisciplinary team effort. This is a big step in the right direction for us,” says the Faculty’s Vice-Dean Research, Bernhard Ganss.


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