New Biomimetic Controlled-Release Capsules Foster Healing And Regrowth Of Gum Tissue Damaged By Periodontal Disease

Scientists are trying to open a new front in the battle against gum disease, the leading cause of tooth loss in adults and sometimes termed the most serious oral health problem of the 21st century. They described another treatment approach for the condition in a report at the 244th National Meeting & Exposition of the American Chemical Society, the world's largest scientific society.


"Our technology uses controlled-release capsules filled with a protein that would be injected in the pockets between the gums and the teeth," said Steven Little, Ph.D., who reported on the research. "That's ground-zero for periodontal disease - 'gum disease' - the place where bacteria breed and inflammation occurs. The capsules dissolve over time, releasing a protein that acts as a homing beacon. It guides immune cells to the diseased area, reducing inflammation, creating an environment that fights the disease process and even could create conditions favorable for gum tissue to regrow."


Little and colleagues, who are with the University of Pittsburgh, have evidence from laboratory experiments with mice - stand-ins for humans in early research of this kind that cannot be done with actual patients - that the approach does foster healing and regrowth of gum tissue damaged by periodontal disease.

A bacterial infection causes periodontal disease. It first appears as mild tenderness and bleeding of the gums. It leads to inflammation and, if left untreated, can damage the gums so that they recede and lose their attachment to the teeth. It may progress even further and damage bone and other tissues that hold teeth firmly in place. Surprisingly, gum disease has a number of deleterious effects outside the mouth, with some studies linking inflammation in the gums to an increased risk of heart disease, stroke and preterm delivery in pregnant women.

Treatment includes scaling, root planing and other procedures to remove the plaque and bacteria that have accumulated in pockets between the teeth and gums. Dentists may combine this with antibiotics to fight the bacteria involved in gum disease.

Many scientists are seeking alternative treatments that kill the bacteria. Little's group is taking an entirely different approach. They are targeting the inflammation process. "Although bacteria start the disease, inflammation is what keeps it going and causes progressive damage," Little explained.

To reduce inflammation at the gums, Little and colleagues designed injectable controlled-release capsules containing a protein encased inside a plastic-like polymer material. The polymer is already used in medicine in dissolvable sutures. After the capsules are injected, the polymer slowly breaks down, releasing the protein encapsulated inside. The protein, termed a chemokine, is already produced by the body's existing cells in order to summon specialized white blood cells to a specific site. Scientists previously tried to keep those cells, termed lymphocytes, away from the gums so as to block inflammation from occurring in the first place.

"It seems counterintuitive to lure in a lymphocyte, which is traditionally thought of as an inflammatory cell, if there's inflammation," Little pointed out. "But remember that a certain level of natural inflammation is required to fight off an infection. Inflammation is inherently a good thing, but too much of it is a bad thing. That's why we aim to restore the immune balance, or homeostasis."

Little's team injected the capsules into mice and discovered evidence that disease symptoms are dramatically reduced and that proteins and other substances involved in regrowth of gum tissue had appeared. Little said that this finding offers encouragement that the treatment could not only rebalance the immune system, but also prompt regrowth of lost gum and bone tissue in the mouth.

Nanocrystals Make Dentures Shine

The hardest substance in the human body is moved by its strongest muscles: When we heartily bite into an apple or a hotdog, enormous strengths are working on the surface of our teeth.

"What the natural tooth enamel has to endure also goes for dentures, inlays or bridges," glass chemist Prof. Dr. Christian Rüssel of the Friedrich Schiller University Jena (Germany) says. After all, these are worn as much as healthy teeth. Ceramic materials used so far are not very suitable for bridges, as their strengths are mostly not high enough. Now Prof. Rüssel and his colleagues of the Otto-Schott-Institute for Glass Chemistry succeeded in producing a new kind of glass ceramic with a nanocrystalline structure, which seems to be well suited to be used in dentistry due to their high strength and its optical characteristics. The glass chemists of Jena University recently published their research results in the online-edition of the science magazine Journal of Biomedical Materials Research.

Glass-ceramics on the basis of magnesium-, aluminium-, and silicon oxide are distinguished by their enormous strength. "We achieve a strength five times higher than with comparable denture ceramics available today," Prof. Rüssel explains. The Jena glass chemists have been working for a while on high density ceramics, but so far only for utilisation in other fields, for instance as the basis of new efficient computer hard drives. "In combination with new optical characteristics an additional field of application is opening up for these materials in dentistry," Prof. Rüssel is convinced.

Materials, to be considered as dentures are not supposed to be optically different from natural teeth. At the same time not only the right colour shade is important. "The enamel is partly translucent, which the ceramic is also supposed to be," Prof. Rüssel says.

To achieve these characteristics, the glass ceramics are produced according to an exactly specified temperature scheme: First of all the basic materials are melted at about 1.500 °C, then cooled down and finely cut up. Then the glass is melted again and cooled down again. Finally, nanocrystals are generated by controlled heating to about 1,000 °C. "This procedure determines the crystallisation crucial for the strength of the product," the glass chemist Rüssel explains. But this was a technical tightrope walk. Because a too strongly crystallised material disperses the light, becomes opaque and looks like plaster. The secret of the Jena glass ceramic lies in its consistence of nanocrystals. The size of these is at most 100 nanometers in general. "They are too small to strongly disperse light and therefore the ceramic looks translucent, like a natural tooth," Prof. Rüssel says.

A lot of developing work is necessary until the materials from the Jena Otto-Schott-Institute will be able to be used as dentures. But the groundwork is done. Prof. Rüssel is sure of it.

DNA Vaccines Show Promise in Preventing Dental Caries

In a report on a preclinical investigation titled "Flagellin Enhances Saliva Ig A Response and Protection of Anti-caries DNA Vaccine," lead author Wei Shi, Wuhan Institute of Virology, Chinese Academy of Sciences, and his team of researchers demonstrate that anti-caries DNA vaccines, including pGJA-P/VAX, are promising for preventing dental caries. However, challenges remain because of the low immunogenicity of DNA vaccines.

This study is published in the Journal of Dental Research, the official publication of the International and American Associations for Dental Research (IADR/AADR).

In this study, Shi and team used recombinant flagellin protein derived from Salmonella as mucosal adjuvant for anti-caries DNA vaccine (pGJA-P/VAX) and analyzed the effects of Salmonella protein on the serum surface protein immunoglobulin G and saliva surface protein immunoglobulin A antibody responses, the colonization of Streptococcus mutans (S. mutans) on rodent teeth, and the formation of caries lesions. The results showed that Salmonella promoted the production of surface protein immunoglobulin G in serum and secretory immunoglobulin A in saliva of animals by intranasal immunization with pGJA-P/VAX plus Salmonella.

Furthermore, Shi found that enhanced surface protein immunoglobulin A responses in saliva were associated with inhibition of S. mutans colonization of tooth surfaces and endowed better protection with significant less carious lesions. In conclusion, the study demonstrates that recombinant Salmonella could enhance specific immunoglobulin A responses in saliva and protective ability of pGJA-P/VAX, providing an effective mucosal adjuvant candidate for intranasal immunization of an anti-caries DNA vaccine.

Daniel Smith, The Forsyth Institute, wrote a corresponding perspective article in response to the Shi et al report titled "Prospects in Caries Vaccine Development." In it, he states that DNA vaccine approaches for dental caries have had a history of success in animal models. Dental caries vaccines, directed to key components of S. mutans colonization and enhanced by safe and effective adjuvants and optimal delivery vehicles, are likely to be forthcoming.

"These papers highlight the exciting potential of using vaccines to protect against dental caries," said JDR Editor-in-Chief William Giannobile. "This research is promising and provides optimism to help promote public health of caries-susceptible individuals."

Effect of Thyrotoxicosis on bone : A Review Article

BY : DR. GAURAV ARORA

Introduction:
Thyrotoxicosis, a clinical syndrome characterized by manifestation of excess thyroid hormone, is one of the commonly-recognised conditions of the thyroid gland. It is a hypermetabolic condition associated with elevated levels of thyroxine (T4) and/or triiodothyronine (T3).

Thyrotoxicosis causes acceleration of bone remodelling and one of the known risk factors for osteoporosis. Studies have shown that thyroid hormones have effects on bone, both in vitro and in vivo. Treatment of thyrotoxicosis leads to reversal of bone loss and metabolic alterations, and decreases the fracture risk.

Clinical presentation of thyrotoxicosis :
Thyrotoxicosis leads to an apparent increase in sympathetic nervous system symptoms.

Younger patients exhibit symptoms of more sympathetic activation, such as anxiety, hyperactivity, palpitations, sweating and tremor, while older patients have more cardiovascular symptoms, including dyspnoea, atrial fibrillation and unexplained weight loss.

One of the first reports of hyperthyroid bone disease was found in 1891 when von Recklinghausen described the "worm eaten" appearance of the long bones of a young woman who died from hyperthyroidism.

Mechanism:
Thyroid hormone directly stimulates bone resorption. This action may be mediated by a nuclear triiodothyronine (T3) receptor which has been found in rat and human osteoblast cell lines and in osteoclasts derived from an osteoclastoma . Thus, thyroid hormone may affect bone calcium metabolism either by a direct action on osteoclasts, or by acting on osteoblasts which in turn mediate osteoclastic bone resorption . Experimental studies in mice lacking either the thyroid receptor- α or -β, suggest that bone loss is mediated by thyroid receptor. Thyroid stimulating hormone (TSH) may also have a direct effect on bone formation and bone resorption, mediated via the TSH receptor on osteoblast and osteoclast precursors. However, bone loss appeared independent of TSH levels in the experiments with mice lacking specific TR isoforms.

Increased serum interleukin-6 (IL-6) concentrations in hyperthyroid patients may also play a role in thyroid hormone-stimulated bone loss. Interleukin-6 stimulates osteoclast production and may be an effector of the action of parathyroid hormone (PTH) on bone.

Biochemical markers: Biochemical markers of bone and mineral metabolism are also affected. The serum concentrations of alkaline phosphatase, osteocalcin, and osteoprotegerin , and fibroblast growth factor-23 (FGF-23) are increased in hyperthyroidism and may remain high for months after treatment, presumably due to a persistent increase in osteoblastic activity . Urinary excretion of bone collagen-derived pyridinium cross-links is increased, and falls to normal shortly after treatment

Prevention and Treatment of Reduced Bone Density:
With the introduction of antithyroid drugs and radioiodine in the 1940s, clinically apparent hyperthyroid bone disease became less common. However, bone density measurements during the last decade have demonstrated that bone loss is common in patients with overt hyperthyroidism and to a lesser extent in those with subclinical hyperthyroidism, whether caused by nodular goitre or excessive doses of thyroid hormone.

There are several measures that may prevent loss of bone density, such as titration of suppressive therapy to maintain a slightly low serum TSH concentration (e.g. between 0.1-0.5 mU/l), calcium supplementation, estrogen replacement therapy while keeping an eye on the adverse effect, and inhibitors of bone resorption (bisphosphonates or calcitonin). Guo et al, demonstrated the benefit of titrating T4 dose in patients on replacement/ suppressive dose of T4. Both lumbar and femoral bone density increased, and serum osteocalcin and urinary excretion of bone collagen-derived pyridinium cross-links decreased when the T4 dose was reduced in post-menopausal women whose initial serum TSH concentration was low.

Adequate dietary calcium intake is essential to ameliorate the adverse effects of thyroid hormone on bone. In a study of 46 post-menopausal women taking suppressive doses of T4, those taking placebo had 5 to 8 per cent reductions in bone density over a two-year period, while those given 1000 mg of calcium daily had no measurable bone loss

Conclusion
Loss of bone density and elevation of markers of bone resorption is common in thyrotoxicosis. After control of thyrotoxicosis partial recovery takes place. Treatment with anti-resorptive agents results in a better recovery. Similar phenomenon is seen during replacement therapy of patients with overt and subclinical hypothyroidism. Even euthyroid with inhibitors of bone resorption may be useful in patients with continuing bone loss. In short-term studies pamidronate reduced thyroid hormone-mediated increase in measures of bone turnover. Calcitonin reduced urinary hydroxyproline excretion and serum calcium in patients with overt patients with lower TSH values has been shown to have a lower bone density than those with high normal TSH.




References:




Meunier PJ, S-Bianchi GG, Edouard CM. Bony manifestations of thyrotoxicosis. Orthop Clin North Am 1972; 3 : 745-74.

Mundy GR, Shapiro JL, Bandelin JG. Direct stimulation of bone resorption by thyroid hormones. J Clin Invest 1976; 58



Udayakumar N, Chandrasekaran M, Rashid M H, Suresh R V, Sivaprakash S. Evaluation of bone mineral density in thyrotoxicosis. Singapore Med J 2006; 47 : 947-50.

Dhanwal DK, Kochupillai N, Gupta N, Cooper C, Dennison EM. Hypovitaminosis D and bone mineral metabolism and bone density in hyperthyroidism. J Clin Densitom 2010; 13: 462-6.

Reddy PA, Harinarayan CV, Sachan A, Suresh V, Rajagopal G. Bone disease in thyrotoxicosis. Indian J Med Res 2012; 135:277-86


Toh SH, Brown PH. Bone mineral content in hypothyroid male patients with hormone replacement: A 3 year study. J Bone Miner Res1990; 5 : 463-7.

Vestergaard P, Rejnmark L, Weeke J, Mosekilde L. Fracture risk in patients treated for hyperthyroidism. Thyroid 2000; 10: 341-8.

Grant DJ, McMurdo MET, Mole PA, Paterson CR. Is previous hyperthyroidism still a risk factor for osteoporosis in post-menopausal women? Clin Endocrinol 1995; 43: 339-45.

Britto JM, Fenton AJ, Holloway WR, Nicholson GC. Osteoblasts mediate thyroid hormone stimulation of osteoclastic bone resorption. Endocrinology 1994; 134: 169-76.

Lakatos P, Foldes J, Horvath C. Serum interleukin-6 and bone metabolism in patients with thyroid function disorders. J Clin Endocrinol Metab 1997; 82: 78-81.

Newly Identified Oral Bacterium Linked to Heart Disease and Meningitis

A novel bacterium, thought to be a common inhabitant of the oral cavity, has the potential to cause serious disease if it enters the bloodstream, according to a study in theInternational Journal of Systematic and Evolutionary Microbiology. Its identification will allow scientists to work out how it causes disease and evaluate the risk that it poses.

The similarity of S. tigurinus to other related bacteria has meant that it has existed up until now without being identified. Its recent identification is clinically important, explained Dr Andrea Zbinden who led the study. "Accurate identification of this bacterium is essential to be able to track its spread. Further research must now be done to understand the strategies S. tigurinus uses to successfully cause disease. This will allow infected patients to be treated quickly and with the right drug."The bacterium was identified by researchers at the Institute of Medical Microbiology of the University of Zurich and has been named Streptococcus tigurinus after the region of Zurich where it was first recognised. S. tigurinus was isolated from blood of patients suffering from endocarditis, meningitis and spondylodiscitis (inflammation of the spine). It bears a close resemblance to other Streptococcus strains that colonise the mouth. Bleeding gums represent a possible route of entry for oral bacteria into the bloodstream.

Dr Zbinden said that while the discovery of the bacterium is no cause for alarm, it is important that it is recognised and the risk is quantified. "This bacterium seems to have a natural potential to cause severe disease and so it's important that clinicians and microbiologists are aware of it," she said. "The next step is to work out exactly how common this bacterium is in the oral cavity and what risk it poses. Immunosuppression, abnormal heart valves, dental surgeries or chronic diseases are common predisposing factors for blood infections by this group of bacteria. However, the specific risk factors for S. tigurinus remain to be determined."

Dental Fillings That Kill Bacteria and Re-Mineralize the Tooth

Scientists using nanotechology at the University of Maryland School of Dentistry have created the first cavity-filling composite that kills harmful bacteria and regenerates tooth structure lost to bacterial decay.


Rather than just limiting decay with conventional fillings, the new composite is a revolutionary dental weapon to control harmful bacteria, which co-exist in the natural colony of microorganisms in the mouth, says professor Huakun (Hockin) Xu, PhD, MS.

"Tooth decay means that the mineral content in the tooth has been dissolved by the organic acids secreted by bacteria residing in biofilms or plaques on the tooth surface. These organisms convert carbohydrates to acids that decrease the minerals in the tooth structure," says Xu, director of the Division of Biomaterials and Tissue Engineering in the School's Department of Endodontics, Prosthodontics and Operative Dentistry.

After a dentist drills out a decayed tooth, the cavity still contains residual bacteria. Xu says it is not possible for a dentist to remove all the damaged tissue, so it's important to neutralize the harmful effects of the bacteria, which is just what the new nanocomposites are able to do.

The researchers also have built antibacterial agents into primer used first by dentists to prepare a drilled-out cavity and into adhesives that dentists spread into the cavity to make a filling stick tight to the tissue of the tooth. "The reason we want to get the antibacterial agents also into primers and adhesives is that these are the first things that cover the internal surfaces of the tooth cavity and flow into tiny dental tubules inside the tooth," says Xu. The main reason for failures in tooth restorations, says Xu, is secondary caries or decay at the restoration margins. Applying the new primer and adhesive will kill the residual bacteria, he says.

Fillings made from the School of Dentistry's new nanocomposite, with antibacterial primer and antibacterial adhesive, should last longer than the typical five to 10 years, though the scientists have not thoroughly tested longevity. Xu says a key component of the new nanocomposite and nano-structured adhesive is calcium phosphate nanoparticles that regenerate tooth minerals. The antibacterial component has a base of quaternary ammonium and silver nanoparticles along with a high pH. The alkaline pH limits acid production by tooth bacteria.

"The bottom line is we are continuing to improve these materials and making them stronger in their antibacterial and remineralizing capacities as well as increasing their longevity," Xu says.

The new products have been laboratory tested using biofilms from saliva of volunteers. The Xu team is planning to next test its products in animal teeth and in human volunteers in collaboration with the Federal University of Ceara in Brazil.

The University of Maryland has patents pending on the nanocomposite and the primer and adhesive technologies, according to Nancy Cowger, PhD, licensing officer with the University's Office of Technology Transfer (OTT).

Oral Cancer Detection Could Dramatically Increase With Saliva Test

A Michigan State University surgeon is teaming up with a Lansing-area dental benefits firm on a clinical trial to create a simple, cost-effective saliva test to detect oral cancer, a breakthrough that would drastically improve screening and result in fewer people dying of the world's sixth most common cancer.

Barry Wenig, a professor in the College of Human Medicine's Department of Surgery and lead investigator on the project, is working with Delta Dental of Michigan's Research and Data Institute to compile study data and recruit dentists. The study will enroll 100-120 patients with white lesions or growths in their mouths and tonsil areas to test as part of the clinical trial.

Wenig and his team will be looking for certain biomarkers previously identified by researchers at UCLA; the biomarkers have been shown in studies to confirm the presence of oral cancer. By creating a simple saliva test which could identify the biomarker's presence, physicians and dentists would know which patients need treatment and which ones could avoid needless and invasive biopsies.

"Most white lesions are benign, so a majority of people who develop them are getting biopsies that are not needed," Wenig said. "Conversely, a simple test would allow us to identify those patients with malignant lesions and get them into treatment quicker."

Oral cancer has a poor survival rate linked to late detection, Wenig said: Only 60 percent of patients live beyond five years after diagnosis. Among black males, the survival rate is less than 38 percent.

"The key challenge to reduce the mortality and morbidity of oral cancer is to develop strategies to identify and detect the disease when it is at a very early stage," he said.

In addition to Delta Dental's Research and Data Institute, which works with researchers from leading universities to monitor advances in science, Wenig is collaborating with PeriRx, a Pennsylvania company that will sponsor upcoming trials with the Food and Drug Administration.

"The results of this trial could be life changing for many people," said Jed Jacobson, chief science officer at Delta Dental and a licensed dentist. "It is a tremendous opportunity for the dental community to participate in what could be a groundbreaking research project."

Wenig and members of his team recently returned from southern California, where they met with UCLA colleagues, who are working to develop saliva diagnostic tests for other cancers as well.

"These tests are as noninvasive as it gets; patients simply need to spit into a cup," Wenig said. "The ease of the test will greatly expand our ability to effectively screen for the cancerous lesions.

"Right now, there are no early screenings available for most head and neck cancers."

The test also has the potential to accelerate health care savings, he added, since the number of biopsies can be dramatically reduced.

TEETH WHITENING ADS  REALLY WORK ????

Many people buy so-called "Teeth Whitening" toothpaste hoping to get whiter teeth. For many people, these toothpastes do not provide whiter teeth. Is this a form of false advertising? Actually, it's not.

The confusion lies in the definition of teeth whitening. Teeth whitening in its strictest sense means to whiten the teeth to their natural shade. Teeth bleaching, on the other hand means to whiten your teethbeyond their natural shade.

The reason there is so much confusion is because the phrase teeth bleaching isn't very attractive. So, companies that offer teeth bleaching, have started to refer to it as teeth whitening to make it more attractive to the average consumer.

In order for a toothpaste, mouthwash, or gum to be certified by the ADA as tooth whitening, it simply has to be able to remove surface stains off of your teeth.

How Teeth Get Stained
When our permanent teeth come in, they are a shiny white color. However, as we grow older (and eat lots of teeth-staining foods), our teeth get more and more yellowish-brown. Teeth Whitening toothpaste can remove tobacco stains, coffee stains, and other stains that we get as we go through our everyday lives.

Unfortunately, tooth whitening toothpastes can only return our teeth back to their original color. The toothpaste contains very gentle abrasives that rub against the stain and gradually remove it.

Why Teeth Whitening Toothpaste May Not Whiten Your Teeth
If you don't drink coffee much or chew tobacco, there's a good chance that your teeth aren't stained at all. In this case, if you use tooth whitening toothpaste, you probably won't notice a difference in how white your teeth are.

Also, in the last ten years, it seems that all toothpastes are "teeth whitening". Chance are, you've already been brushing with "tooth whitening" toothpaste. Continuing to brush with "tooth whitening" toothpaste isn't going to make your teeth any whiter since you've already removed the stains with previous tubes of "teeth whitening" toothpaste.

How to Whiten Your Teeth
If you truly want whiter teeth, you will probably want to use a form of teeth bleaching. Teeth bleaching is designed to whiten your teeth beyond their natural shade.

You should talk to your dentist about teeth whitening options such as in-office gels, Zoom teeth whitening, and take-home teeth whitening gels.

A Drug used to Treat Osteoporosis may Help Reverse Inflammatory Gums and Teeth



In a post on intelihealth.com, the News ReviewFrom Harvard Medical School has released an article stating that a drug call teriparatide (Forteo) may actually help bone repair for those suffering from periodontitis.

What is periodontitis? Well, most of us know its precursor, gingivitis. Gingivitis symptoms include red, swollen gums that bleed easily.

Periodontitis is when the gum disease has been left untreated as gingivitis and has become more severe. Periodontitis can lead to bone loss under teeth as well as teeth themselves. Symptoms of periodontitis include pus between teeth and gums, gums pulling away from teeth and permanent teeth that are becoming loose.

Teriparatide is currently used to help build bone in people suffering from osteoporosis. According to intelihealth.com, “It [teriparatide] actually stimulates new bone formation. But doctors also know that this drug, if given for more than two years, might increase the risk of developing bone tumors.” Thus, it is not the most commonly prescribed drug to help with osteoporosis.

However, in terms of people with periodontitis, teriparatide might really help, as it “did seem to help stimulate bone growth in the mouth.”

There are plans for more testing with periodontitis suffers. As intelihealth.com states, “We clearly need larger studies of this drug in the treatment of periodontitis. I think we also will see trials of this drug in the treatment of osteonecrosis of the jaw and of other areas of bone.”

While there may be a new treatment for periodontitis on the horizon, the best thing you can do is to not let the disease get to this stage. If you notice that your gums are red or bleeding, the best thing to do is to maintain a health oral care regimen: brush, floss and rinse at least two times per day. A healthy diet can also aid in beating gingivitis. And make sure you see your dentist regularly. He or she can always offer the best course of treatment for any dental issue.

There are products out there specifically designed to treat your gums and keep them healthy, so that may be something worth trying out. Remember, if you do have gingivitis, it is completely reversible. Just put the time and love into taking care of your mouth — after all, it’s the only one you’ve got.

Can Oral Care for Babies Prevent Future Cavities?

New parents have one more reason to pay attention to the oral health of their toothless babies. A recent University of Illinois study confirms the presence of bacteria associated with early childhood caries (ECC) in infant saliva.

ECC is a virulent form of caries, more commonly known as tooth decay or a cavity. Cavities are the most prevalent infectious disease in U.S. children, according to the Centers for Disease Control and Prevention.

"By the time a child reaches kindergarten, 40 percent have dental cavities," said Kelly Swanson, lead researcher and U of I professor of animal science. "In addition, populations who are of low socioeconomic status, who consume a diet high in sugar, and whose mothers have low education levels are 32 times more likely to have this disease."

Swanson's novel study focused on infants before teeth erupted, compared to most studies focused on children already in preschool or kindergarten -- after many children already have dental cavities.

"We now recognize that the "window of infectivity," which was thought to occur between 19 and 33 months of age years ago, really occurs at a much younger age," he said. "Minimizing snacks and drinks with fermentable sugars and wiping the gums of babies without teeth, as suggested by the American Academy of Pediatric Dentistry, are important practices for new parents to follow to help prevent future cavities."

In addition, his team used high-throughput molecular techniques to characterize the entire community of oral microbiota, rather than focusing on identification of a few individual bacteria.

"Improved DNA technologies allow us to examine the whole population of bacteria, which gives us a more holistic perspective," Swanson said. "Like many other diseases, dental cavities are a result of many bacteria in a community, not just one pathogen."

Through 454 pyrosequencing, researchers learned that the oral bacterial community in infants without teeth was much more diverse than expected and identified hundreds of species. This demonstration that many members of the bacterial community that cause biofilm formation or are associated with ECC are already present in infant saliva justifies more research on the evolution of the infant oral bacterial community, Swanson said.

Could manipulating the bacterial community in infants before tooth eruption help prevent this disease in the future?

"The soft tissues in the mouth appear to serve as reservoirs for potential pathogens prior to tooth eruption," he said. "We want to characterize the microbial evolution that occurs in the oral cavity between birth and tooth eruption, as teeth erupt, and as dietary changes occur such as breastfeeding vs. formula feeding, liquid to solid food, and changes in nutrient profile."

Swanson said educating parents-to-be on oral hygiene and dietary habits is the most important strategy for prevention of dental cavities.

Good Decision by Indian Health Ministry.....

"Indian Medical Graduates who go to foreign lands for higher studies will have to give an undertaking/bond that after their higher studies they will come back to Motherland India and serve society here if they want NOC from India.... And if they don't India reserves the right to write to the Foreign Govt. that these students shouldn't be allowed to practice there till they honour their agreement"... Best part is foreign governments are supportive....
GREAT DECISION.... IF YOU USE INDIA'S RESOURCES TO BECOME A GRADUATE, THEN YOU HAVE A MORAL AND NATIONAL OBLIGATION TO SERVE INDIA :)

Risk Of Blood-Vessel Constriction Linked To Gum Disease May Be Increased By Specific Protein :

A protein involved in cellular inflammation may increase the risk of plaque containing blood vessels associated with inflammatory gum disease, according to research presented at the American Heart Association's Arteriosclerosis, Thrombosis and Vascular Biology 2012 Scientific Sessions in Chicago.

The protein, CD36, is found in blood cells, as well as many other cell types. Research has shown that CD36 may increase the harmful effects of "bad cholesterol," or low-density lipoprotein (LDL).

Investigators "knocked out," or deleted, the gene responsible for CD36 production, then induced plaque in blood vessels by feeding mice a high fat diet. Some animals were also infected with the bacteria associated with gum disease.

More fatty plaque accumulation occurred in the blood vessels of the animals that were infected with gum disease. In the animals with the deleted CD36 gene, however, vessels remained free of new plaque even when oral inflammation occurred.

The Decay-Preventive Sweetener

By California Dental Association:

1.What is xylitol?

Xylitol is a natural sugar alcohol that helps prevents cavities. You may recognize other sugar alcohols used in sugarless products, such as mannitol and sorbitol. Xylitol is the sugar alcohol that shows the greatest promise for cavity prevention. It is equal in sweetness and volume to sugar and the granular form can be used in many of the ways that sugar is used, including to sweeten cereals and hot beverages and for baking (except when sugar is needed for yeast to rise).

2.How does xylitol prevent cavities?
Xylitol inhibits the growth of the bacteria that cause cavities. It does this because these bacteria (Streptococcus mutans) cannot utilize xylitol to grow. Over time with xylitol use, the quality of the bacteria in the mouth changes and fewer and fewer decay-causing bacteria survive on tooth surfaces. Less plaque forms and the level of acids attacking the tooth surface is lowered.

3.Studies show that Streptococcus mutans is passed from parents to their newborn children, thus beginning the growth of these decay-producing bacteria in the child. Regular use of xylitol by mothers has been demonstrated to significantly reduce this bacterial transmission, resulting in fewer cavities for the child.

4.What products contain xylitol and how do I find them?
Xylitol is found most often in chewing gum and mints. You must look at the list of ingredients to know if a product contains xylitol. Generally, for the amount of xylitol to be at decay-preventing levels, it must be listed as the first ingredient. Health food stores can be a good resource for xylitol containing products. Additionally, several companies provide xylitol products for distribution over the Internet.

5.How often must I use xylitol for it to be effective?
Xylitol gum or mints used 3-5 times daily, for a total intake of 5 grams, is considered optimal. Because frequency and duration of exposure is important, gum should be chewed for approximately 5 minutes and mints should be allowed to dissolve. As xylitol is digested slowly in the large intestine, it acts much like fiber and large amounts can lead to soft stools or have a laxative effect. However, the amounts suggested for cavity reduction are far lower than those typically producing unwelcome results.

6.Has xylitol been evaluated for safety?
Xylitol has been approved for safety by a number of agencies, including the U.S. Food and Drug Administration, the World Health Organization’s Joint Expert Committee on Food Additives and the European Union’s Scientific Committee for Food.

Xylitol has been shown to have decay-preventive qualities, especially for people at moderate to high risk for decay, when used as part of an overall strategy for decay reduction that also includes a healthy diet and good home care. Consult your CDA member dentist to help you determine if xylitol use would be beneficial for you.

TEETH WHITENING ADDS REALLY WORK ????


Many people buy so-called "Teeth Whitening" toothpaste hoping to get whiter teeth. For many people, these toothpastes do not provide whiter teeth. Is this a form of false advertising? Actually, it's not.

The confusion lies in the definition of teeth whitening. Teeth whitening in its strictest sense means to whiten the teeth to their natural shade. Teeth bleaching, on the other hand means to whiten your teethbeyond their natural shade.

The reason there is so much confusion is because the phrase teeth bleaching isn't very attractive. So, companies that offer teeth bleaching, have started to refer to it as teeth whitening to make it more attractive to the average consumer.

In order for a toothpaste, mouthwash, or gum to be certified by the ADA as tooth whitening, it simply has to be able to remove surface stains off of your teeth.

How Teeth Get Stained

When our permanent teeth come in, they are a shiny white color. However, as we grow older (and eat lots of teeth-staining foods), our teeth get more and more yellowish-brown. Teeth Whitening toothpaste can remove tobacco stains, coffee stains, and other stains that we get as we go through our everyday lives.

Unfortunately, tooth whitening toothpastes can only return our teeth back to their original color. The toothpaste contains very gentle abrasives that rub against the stain and gradually remove it.

Why Teeth Whitening Toothpaste May Not Whiten Your Teeth

If you don't drink coffee much or chew tobacco, there's a good chance that your teeth aren't stained at all. In this case, if you use tooth whitening toothpaste, you probably won't notice a difference in how white your teeth are.

Also, in the last ten years, it seems that all toothpastes are "teeth whitening". Chance are, you've already been brushing with "tooth whitening" toothpaste. Continuing to brush with "tooth whitening" toothpaste isn't going to make your teeth any whiter since you've already removed the stains with previous tubes of "teeth whitening" toothpaste.

How to Whiten Your Teeth

If you truly want whiter teeth, you will probably want to use a form of teeth bleaching. Teeth bleaching is designed to whiten your teeth beyond their natural shade.

You should talk to your dentist about teeth whitening options such as in-office gels, Zoom teeth whitening, and take-home teeth whitening gels.

Why Gums Suffer With Age !!!!!!

New research from Queen Mary, University of London in collaboration with research groups in the USA sheds light on why gum disease can become more common with old age.

The study, published in Nature Immunology, reveals that the deterioration in gum health which often occurs with increasing age is associated with a drop in the level of a chemical called Del-1.

The researchers say that understanding more about Del-1 and its effects on the body's immune system could help in the treatment or prevention of serious gum disease.

Periodontitis is a disease of the gums which causes bleeding and bone loss which can, over time, lead to loss of teeth. It affects about 20 per cent of the UK population and is caused by an over-active immune response to bacteria that grow in the mouth.

As people age they are more likely to suffer from inflammatory diseases, including gum disease.

The new research investigated gum disease in young and old mice and found that an increase in gum disease in the older animals was accompanied by a drop in the level of Del-1. This protein is known to restrain the immune system by stopping white blood cells from sticking to and attacking mouth tissue.

Mice that had no Del-1 developed severe gum disease and elevated bone loss and researchers found unusually high levels of white blood cells in the gum tissue.

When they treated the gums of the mice with Del-1, the number of white blood cells dropped, and gum disease and bone loss were reduced.

The researchers say their findings could be the basis for a new treatment or prevention of gum disease.

Mike Curtis is Professor of Microbiology at Queen Mary, University of London, Director of the Blizard Institute and the lead on the microbiological studies in the research. He said: "Periodontitis is an extremely common problem and we know that the disease tends to be more common as we get older.

"This research sheds some light on why ageing makes us more susceptible and understanding this mechanism is the first step to an effective treatment."

Plasma Torch Toothbrush Successfully Used In Human Mouth :

Attentive followers of dentistry developments that we are, we've been following the story of theplasma brush for awhile now. And it seems like it's making some serious progress: human clinical trials are supposed to begin in early 2012, and there's also a video (below) of the World's Bravest Dentist shooting a plasma beam into his own mouth.


Some background, for anyone who doesn't subscribe to Dentistry Illustrated Weekly: the plasma brush isn't a toothbrush, but actually a tool dentists are hoping to use for two primary situations. The first is breaking up plaque; the plasma torch, though it's no hotter than room temperature, is excellent at breaking the bonds that adhere plaque to a tooth. The second is as a sort of primer for filling cavities.


There are certain kinds of cavities, according to Hao Li, associate professor of mechanical and aerospace engineering in the Missouri University University of Missouri College of Engineering, that need to be refilled every five or seven years using current technology--and they can only be refilled a few times before having to be pulled. The plasma brush can prime a cavity for filling in sort of the same way pavers create those divots in roads before filling them in with new asphalt: it provides more surface area for the filling to stick to, and the research team claims plasma-assisted fillings could be 60% stronger than traditional fillings.

TISSUE ENGINEERING

BIOLOGIC MODIFIERS IN PERIODONTAL REGENERATION

OVERVIEW

Periodontal diseases result in destruction of periodontal tissues, including cementum, bone, and periodontal ligament (PDL), with eventual tooth loss if left untreated. Studies targeted at understanding the disease at the cellular and Molecular level as well as clinical investigations have resulted in improved therapies for arrest of disease progression. Moreover, beyond areas of disease progression, substantial evidence exists indicating that regeneration of periodontal tissues is a viable treatment for select situation. There is a need, however, to improve the predictability of regenerative therapies. This need has led to increased efforts, among clinical and basic science researchers, to establish the specific cells, factors, delivery systems, flap design, and host responses required for enhancing the outcome of regenerative therapies.

Although significant advances have been made toward understanding the complexities involved im promoting periodontal regeneration, much remains to be elucidated including questions regarding placement of factors (e.g., within a barrier membrane? In conjuction with resorabable or nonresorbable membranes? Directly into the defect? Coating onto the root surface?). What cells should these factors be targeted to, and what activities are attractive in promotion and inhibition by these factors.

This article is limited to discussions on potential and known biologic modifiers for use in regeneration of periodontal tissues. To maintain a central theme, nonendogenous factors, such bisphosphonates and antibiotics, are excluded because these are discussed elsewhere in this issue.

For clarity, it is important first to define biologic modifiers as interpreted. Biologic modifiers are materials or proteins and factors that have the potential to alter the host tissue so as to stimulate or regulate the wound healing process. Classic examples of biologic modifiers are growth factors. These agents can act through a systematic route(e.g., hormones)or act at the local site(e.g., many polypeptide cytokines and growth factors). This article centers around biologic modifiers that may have the potential to promote regeneration of periodontal tissues(i.e., new bone, new cementum, and new connective tissue attachment) through a variety of cell-tissue interactions, including promoting (1) cell migration, (2) attachment and subsequent spreading of cells at the local site, (3) cell proliferation, (4) cell differentiation, and (5) matrix synthesis.

RATIONALE FOR USE IN DENTISTRY

The concept that biologic modifiers may serve role in promoting wound healing is not unique to dentistry. With enhancement in cellular and molecular technologies, great have been made in understanding the activities of these modifiers and also in preparing large quantities of recombinant materials.

The interdisciplinary approach to developing new agents and materials for improving tissue function has resulted in substantial progress toward restoring tissues subsequent to disease. In particular, dental procedures rank as one of the most frequent techniques used to enhance tissue deficiencies.³⁵ Other areas that rank high are procedures to promote skin healing (e.g., burn patients and bone procedures. In the development of strategies advancing regeneration of periodontium, the periodontal field has taken advantage of approaches used for establishing directions to improve regenerative therapies for other tissues. A key factor for enhancing the predictability of regenerative therapies is an understanding of cellular and molecular events required to regenerate periodontal tissues. It is now recognized that an important link, although not exact, to understanding the requirements for regeneration of tissues is to acquire knowledge as to mechanisms involved in development of tissues. Figure I diagrams regulating events, cells, and proteins currently believed to be involved in regulating development of or regeneration of periodontal tissues. Information gained from studies targeted at understanding the mechanisms and factors controlling development of periodontal structures may p rove important for use in regeneration of such tissues, subsequent to disease. For example, data exist suggesting that dental follicle cells ( mesenchymal cells surrounding the tooth before root and PDL development) have the capacity to differentiate into osteoblasts, cementoblasts, or PDL cells, when triggered appropriately.^56,57,85 Thus, it is possible that factors and proteins identified as required for development and regeneration. In fact, as discussed later, this seems to be the case for some putative biologic modifiers.

Contrasting periodontal development with periodontal regeneration, it is apparent that some common principles exist as well as some concepts that are clearly different between the two processes. Events required for regeneration of periodontal tissues are analogous with those required for normal wound healing and, for the most part, are similar to those events required for development of the periodontium. In contrast to developmental stages, however, in both wound healing and regeneration, the early events include recruitment of marrow cells and release of cell cytokines and growth factors at the healing sites. During development, it is now recognized that specific growth factors and morphogens trigger differentiation of epithelial and mesenchymal derived cells during tooth formation. The importance of these growth factors (e.g., bone morphogenetic proteins [BMPs] (see review by Thesleff and Sahlberg) for regeneration of periodontal tissues as well as the function of endogenous factors present at wound sites is currently being examined in in vivo and in vitro models. Another event considered critical for both priate cells to the site of repair or development. Once at the site, the become biologically active. That is, such cells must differentiate into osteoblasts, cementoblasts, or PDL cells must differentiate into matrix required for formation of hard and soft connective tissues. To synthesize sufficient matrix, the appropriate cells must be stimulated to proliferate at the local site. Thus, it is reasonable to imagine that many of the molecules involved in triggering dsevelopment of periodontal tissues may prove to be effective in promoting regeneration of periodontal tissues.

This article first discusses basic principles of biologic modifiers. Next, specific biologic modifiers that may have activity in regenerative therapies are presented. This is followed by a section covering results to date using biologic modifiers to regenerate periodontal tissue in vivo and in vitro models. Last, trends and emerging therapies targeted at tissue regeneration are discussed.

BASIS OF ACTION OF BIOLOGIC MODIFIERS

Mode of Action

The overall scheme of how growth factors act depends on their mode of action. To evoke a biologic effect, a growth factor must be synthesized by an originating cell, travel to its target receptor, interact with the target receptor or binding protein, and activate second messengers or terminal effectors. The mode of action is the way the biologic modifier is meant to interact with its target receptor. Hormones traditionally act in an endocrine manner whereby they are secreted by one type and travel in the bloodstream to a distant target cell to exert their actions. Examples of hormone, and luteinizing hormone. These factors have the potential for widespread effects because of their circuation in the bloodstream and availability to many different cell types and subsequently are regulated not only by their blood levels, but also by the cells that bear receptors. Local modes of action are more traditionally associated with the term growth factor and involve paracrine autocrine, juxtal line, and intracrine modes. Paracrine action involves the production of a factor by one cell, with receptors present on another cell in the local microenvironment. The biologic modifier is secreted from the first cell in a soluble manner and binds to receptors on the target cell to evoke its effects. Examples of this are the growth factors platelet-derived growth factor (PDGF) and transforming growth factor-b (TGF-b), which are produced by platelets and act on target cells such as lymphocytes and osteoblasts. Autocrine factors are those that are synthesized by one cell, secreted in a soluble form outside the cell, then bind to surface receptors on the same cell to evoke an effect. Examples of autocrine factors are TGF-a, which is produced and acts on epithelial cells, and the BMPs, which are produced and act on osteoblastic cells. Less commonly described are juxtacrine effects, which are similar to paracrine effects except that the factor produced by the cell of original cell surface bound and required cell contact by the target cell to evoke a response. An example of juxtacrine mode of action is stem cell factor. Finally, another form of autocrine action is intracrine, whereby a factor is produced by one cell and not secreted but acts intracellularly to facilitate its effects. An example of this mode of action is parathyroid harmone-related protein (PTHrP) in which a portion of the protein has been shown to translocate to the nucleus to inhibit apoptosis. Transcription factors also fit into this category.

Receptors

For a biologic modifier to exert an effect, its designated receptor must be present in sufficient quantity, orientation, and functional activity to transmit the appropriate stimuli. Growth factor receptors can be divided broadly into two categories cell surface receptors and intracellular receptors. The most common prototype growth factor receptor is the cell surface receptor, which can be further divided into three categories: (1) G-protein linked, (2) receptor tyrosine kinases, mainly bind peptide factors that are soluble in water but not easily transported across the lipophilic cell membrane. Examples of the ligands for these cell surface receptors are outlined in Figure 3. The intracellular receptors are commonly described for steroids such as vitamin D_3, estrogen, and glucocorticoids. Steroid receptors have been described in both the cytoplasm and the nucleus of target cells. Additionally, intracellular receptors or binding proteins for factors that act in an intracrine manner are located within the nucleus.

Once a cell surface receptor has been bound and activated, a series of second messengers are responsible for taking the next step in evoking a biologic activity. Four main second messengers are outlined in Figure 4. Adenylyl cyclase (AC) is an enzyme activated by G-proteins in the cell membrane is response to activation of G-protein—linked receptors such as the parathyroid harmone(PTH)/PTHrP receptor. AC catalyzes the reaction of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP), which activates protein kinase A to cause protein phosphorylation. G-protein-linked receptors also couple to membrane bound phospholipase C with activation of protein kinase C to evoke protein phosphorylation. The receptor tyrosine kinases and serine threonine kinases are also responsible for p hosphorylating their target proteins. Protein phosphorylation is a key component of growth factor activity and is responsible for mediating changes in cell proliferation and differentiation, which are the hallmarks of growth factor activity.

Cell Proliferation

The most fundamental proceses of tissue growth and development begin with cell proliferation. Cell growth and division is a prerequisite for regeneration and repair. In cell division, duplication of the cell occurs such that every daughter cell receives an identical copy of genetic material. Cells from different tissues grow and divide at quite different rates. For example, cells of the junctional epithelium typically have a turnover rate of 20 times days. Despite this difference, cells undergo a similar pattern of cell gele events that characterize their process of cell division . There we four main phases of the cell cycle. The two G phases represent gap phases G₁ (first gap) and G₂ (second gap) between the S and M phases. The cell is not actively in the cycle (i.e., it is terminally differentiate of at rest), it is considered to be in the G₀ phase (exited from the cell cycle). For a ell to reenter the cell cycle from the resting G phase and hence initiate cell division, a stimulus designated as a competence factor required. Competence factors are necessary but not sufficient for the cell to enter into the cell cycle. An example of a competence factor is PDGF. After the cell has been rendered competent to undergo cell division it requires a progression factor. Progression factors are sufficient for the cells are rendered competent to progress through the cell cycle example of a progression factor is insulinlike growth factor I (IGF-I). Since a cell has progressed to the S phase, it is committed to undergo cell division, although there are growth factors that may at later stages to delay o’ block cells in the G₂ phase. Progressing through the cell cycle is an obvious prerequisite for cells to multiply,.forming the basis for development and regeneration of tissues. Biologic modifiers are key regulators of this process of cell proliferation via their action at different stages of the cell cycle.

Cell Differentiation

The process of cell differentiation is also a critical component of tissue regeneration. Beyond cell proliferation, differentiation of cells into mature cells bearing the respective phenotypic and functional characteristics composing the tissue type is necessary (e.g., bone, PDL , epithelium). The process of cell differentiation has been outlined for most cell arise from a common progenitor cell, which is an undifferentiated mesenchymal cell. This cell may progress and differentiate into multiple cell types, including osteoblast, fibroblasts, adipocytes, or muscle cells with thee appropriate signals. Biologic modifiers act in this regard to stimulate or inhabit cell differentiation along the designated pathways. Certain factors may act independently at one or more stages or in concert with other biologic mediator. During development, this process of cell differentiation is exquisitely regulated; hence, the challenge with regeneration is to recreate the appropriate organization of proliferation and differentiation to result in formation of functional tissues. Table 1 lists the most common biologic modifiers, their major source(s), and primary actions.

SPECIFIC AGENTS

Platelet-Derived Growth Factor (AA, AB, BB)

PDGF, one of the first growth factors to be described, was originally isolated from platelets and found to have mitogenic activity in smooth muscle. PDGF consists of two disulfide-bonded polypeptide chains that are encoded by two different genes, PDGF-A and PDGF-B. Consequently, PDGF can exist as a heterodimer (AB) or a homodimer (AA,BB). These three subtypes can bind to the PDGF receptor that is encoded by two separate genes. Several cell types produce PDGF, including degranulation platelets, smooth muscle, fibroblasts, endothelial cells, macrophages, and keratinocytes. PDGF plays a significant role in wound healing by stimulating connective tissue growth via its mitogenic and chemotactic activities.

Insulinlike Growth Factors (I, II)

IGFs are important regulators of proliferation and differentiation in a variety of cells. IGF-I and IGF-II have 65% amino acid sequence homology and similar biologic activities; however, their synthesis is under different regulating influences. Bone cells produce and respond to IGFs, and bone is a storage house for IGFs in their inactive forms. IGFs have pleotropic effects on their target cells, including an increase in transport of glucose and amino acids into osteoblasts, an increase in breakdown. IGFs stimulate cell replication as a progression factor and are required but not limiting factors for DNA synthesis in osteoblasts. IGFs also stimulate differentiation of mesenchymal cells and enhance matrix production, including the synthesis of collagens and proteoglycans. IGFs have distrinct receptors and also have a series of binding proteins (IGFBPs), which regulate the half-lives and distribution of IGFs.

Transforming Growth Factors (a,b)

The transforming growth factors (TGFs) were first named for their ability to stimulate anchorage-independent growth of fibroblasts in monolayer. TGF-a shares structural homology with epidermal growth factor (EGF), such that they bind to the same receptor and evoke a similar biologic activity of stimulating epidermal basal cell proliferation. TGF-a shares structural homology with epidermal growth factor (EGF), such that they bind to the same receptor and evoke a similar biologic activity of stimulating epidermal basal cell proliferation. TGF-b has been the subject of wide investigation in relation to its effects on bone and other cells of mesenchymal origin. TGF-b was originally isolated as a PDGF and later was found in the largest amounts stored in bone in an inactive form. TGF-b has immunosuppressive characteristics and has also been investigated for its ability to include cartilage and new bone growth in vivo.

Fibroblast Growth Factors (Acidic, Basic)

The two major members of thee fibroblast growth factors (FGFs) are acidic FGF(aFGF or FGF-I) and basic FGF (bFGF or FGF-2). Both FGFs are heparin binding proteins and have potent mitogenic effects on cells of meodermal and neuroectodermal origin. FGFs enhance bone formation and are also angiogenic. bFGF is considered to be more potent than bFGF and may act via the stimulation o other growth factors because it has been found to stimulate TGF-b.

Bone Morphogenetic Proteins (1-15)

The BMPs have been the subject of intense investigation for more than two decades. Urist⁸⁹ in 1965 reported that protein extracts from bone implanted into animals at no bone sites induced the formaton of new cartilage and bone tissue. This protein extract contained multiple factors that stimulate bone formation and was termed bone morphogenetic protein. At least 15 BMPs have been identified to date, and they are part of the TGF-b superfamily. The BMPs most widely studied include BMP-2, BMP-3a, (osteogenin), BMP-4, and BMP-7 (osteogenic protein -1 [OP-1] ).

Interleukins (1-12)

Interleukins were originally defined as factors are involved in immune cell interactions, but this definition has been extended because many of the interleukins have effects on connective tissue and other nonimmune cell types. At least 12 interleukins have been described; and the most commonly studied are interleukin-1 (IL-1), IL -2, IL -3, IL -4, and IL -6. IL -1 is produced by many cell types, including keratinocytes, macrophages, and endothelial cells. IL -1a and b bind to the same receptor and have the same biologic activities. IL -1 has also been termed endogenous pyrogen for its ability to induce fever in vivo. IL -1 induces neutrophilia, induces antiproliferative effects against certain tumor cells, and stimulates bone resorption. IL -2, also known as T-cell induces neutrophilia, induces antiproliferative effects against certain tumor cells,and stimulates bone resorption. IL -2, also known as T-cell growth factor, is produced by activated T lymphocytes and stimulates T-cell prloliferation. IL-3 is considered a colony-stimulating factor (CSF) for its ability to promote development of multipotential hematopoietic stem cells and progenitors of the granulocyte, macrophage, erythrocyte, eosinophil, megakaryocyte, mast cell, and basophil lineage. IL-4 is also known as B–cell growth, T-cell activation, and platelet production. IL-6 also stimulates bone resorption and has been implicated as a contributing factor in osteoporosis.

Colony-Stimulating Factors (G, GM, and M)

The CSFs were named for their ability to induce the development of distinct cell lineages. As described previously, IL – 3 is a CSF known as multi-CSF. IL-3 stimulates the formation of all nonlymphocyte blood cells. Granulocyte-macrophage-CSF (GM-CSF) and granulocyte-CSF (G-CSF) more specifically promote the differentiation of macrophages and granulocyes. Erythropoietin is a

cytokine produced by the kidney that stimulaes proliferation and differentiation of erythroid cells into erythrocytes. Erythropoietin was the first CSF commercially available for clinical use.

Parathyroid Hormone-Related Protein

PTHrP is a peptide growth factor with limited homology to the endocrine hormone PTH. Many cell and tissue types produce PTHrP, including keratinocytes, lactating mammary gland, and fetal parathyroid glands. PTHrP, including keratinocytes, lacting mammary gland, and fetal parathyroid glands. PTHrP has potent proliferative and differentiating characteristics and has been found to play a critical role in cartilage, mammary gland, and tooth development. PTHrP has both anabolic and catabolic effects in bone.

Epidermal Growth Factor

EGF is a keratinocyte-stimulating growth factor. Originally derived from saliva, EGF has been reported to have profound effects on tooth development. EGF is present in most biologic fluids (saliva, urine, plasma, sweat, and semen). As discussed earlier, EGF and TGF-a both bind to the same receptor and have the same biologic activity.

Adhesion Factors (Fibronectin, Osteopontin Bone Sialoprotein)

Adhesion and attachment factors are becoming increasingly important for their ability to stimulate growth and differentiation. Fibronectin is a noncollagenous glycoprotein that is a major component of serum and contains a sequence of amino acids (arginine-glycine-aspartic acid ; RGD, a domain in associated with cell adhesion. Fibronectin contains additional domains associate with cell binding. Fibronectin promotes the attachment of bone cells and likely contributes to their differentiation. Fibronectin binds to cells and to fibrin, heparin, gelatin, and collagen. Osteopontin, aslo termed Spp, BSP –1, and eta-1, is a sialoprotein component of the bone matrix. Osteopontin is thought to play a role in bone development but also in cellular transformation and metastasis. Osteopontin contains an RGD sequence and promotes the attachment of several cell types, including attachment of osteoclasts to bone surfaces. Bone sialoprotein also contains an RGD sequence and promotes cell attachment but has a more limited pattern of expression than that of osteopontin. Although the precise role for bone sialoprotein and marks a lage stage of osteoblastic differentiation and an early stage of matrix mineralization. Osteopontin, bone sialoprotein, and fibronectin are also found in odontoblasts and cementoblasts.

FUTURE PERSPECTIVES

Delivery Systems

Although the use of biologic modifiers to treat periodontal diseases has not reached the level of development necessary to ensure predictable results, knowledge of the biology involved surpassed knowledge of how to deliver these agents for optimal results. Studies focused on the biology are important; at the same time, however, studies focused on the biology are important; at the same time, however, studies to determine the mode of administration are critical and are currently under intense investigation. Items to consider regarding these materials include their biocompatibility, toxicity, ease of handling , release kinetics, and resorb ability or retrievability. Osseous grafts have been use for decades to treat periodontal defects and are a valuable source of biologic mediators. Type I collagen gels have been extensively investitgated for their space-filling properties as well as for their ability to resorb and release putative biologic mediators in wound healing situations. Collagen-based sutures and hemostatic spnges have been used extensively in medicine and dentistry. Resorbable collagen barriers have been used clinically for guided tissue regeneration procedures; however, their combination with biologic modifiers has not been explore. Another are of interest is in combination with biologic modifiers because they can be prepared reprople, a polymer of glycolic acid, is a normal product of metabolism. PGA suture material, and as implants for bone fracture fixation. The ability to impregnate these materials with biologically active factors and to control release of factors holds promise for treating periodontal defects. Polylactic acid (PLA) is more hydrophobic than PGA and is more soluble in organic solvents.copolymers of PGA and PLA have been used for many types of biomaterials, including sutures (Vicry1). Other synthetic materials are under active investigation sucha as poly (e-caprolactone), polydioxanone, and trimethylrny carbonate (for a comprehensive review see Hutmacher et al³⁴).

Gene Therapy

The term gene therapy originally referred to the treatment of a disease by means of genetic manipulation. According to Strayer gene therapy may involve (1) supplying or increasing the expression of a mutant gene that is insufficiently expressed (e.g., to treat genetic enzymatic deficiencies); (2) blocking a gene that is detrimental (e.g., using antisense constructs to inhibit tumor proliferation); or (3) adding a foreign gene to treat a situation beyond the capability of the normal genome (e.g., introduce an enzyme into a cell or tissue that allows the tissue to become more sensitive to the effects of a pharmacologic agent). Much of the initial interest in gene thrapy centered on its potential for treating genetic diseases, such as cystic fibrosis and familial hypercholesterolemia. More recently, the potentials for gene therapy have expanded to include gene therapy for defects at local sites (e.g., bone and salivary glands).

A major consideration in evaluating the potential for gene therapy for use in periodontal regeneration is the design and construction of the targeting vectors. DNA can be transferred via (1) naked DNA, which depends on physical and chemical methods to insure uptake into cells, or (2) virus-mediated vector, which rely on viral sequences as with retroviral vectors or adenoviral vectors to infect cells with the DNA of interest. The DNA of interest is typically driven via promoter from the viral vector, for example, to result in transcription of the gene of interest. Often, the DNA is driven by a promoter that is specific to the tissue of interest to ensure expression in a designated are versus a widespread manner. For example, a keratin promoter driving a gene of interest would target expression to epithelium and not to connective tissue. Obviously, this becomes increasingly difficult when considering regeneration of the periodontium and the multiple tissue types present. It is questionable whether bone-specific promoters, such as osteocalcin and bone sialoprotein, are truly bone specific, and there are no known cementum-specific promoters to target gene expression to the cementum. Although gene therapy offers many promosing prospects for the future, developing the strategies continues to be a challenging proposition.

Cell-Based Therapy

Cell-based therapies are most commonly associated with bone marrow transplantation strategies. Bone marrow transplantation has been successfully used to treat a multitude of conditions, including genetic disorders, immune disorders, and tumors. More recently, interest has focused on marrow stromal cells as stem cells for tissues of mesenchymal origin. Hematopoietic stem cells in the bone marrow provide a continuous source of progenitors for blood cells but additionally contain cells that are stem cells for constractive tissue. Bone marrow stromal cells can differntiate in culture with osteoblasts, chondrocytes, adipocytes, or myoblasts and may also be a more natural source of biologic modifiers in the wound environment. These cells present an intriguing resource for their potential use in periodontal regeneration and are currently being explored on a basic scene level. Clinically, a significant challenge is the source of cells and the stringency of maintaining cells ex vivo before replacement in the statement site. The actual use of cell seeding in a periodontal application has been limited to a pilot report using PDL fibroblasts in beagle dogs. Althouh attractive results were presented, including complete covertase of seeded roots with cementoblasts, the study population was small, and extensive characterization would be necessary before this technique could become a clinical reality.

SUMMARY

The specific objectives of this article was to update the reader on biologic modifiers being tried or suggested for use in therapies directed at regenerating periodontal tissues. As indicated from the studies presented here , many of these biologic modifiers have significant influences on cell behaviour and show great promise for use in regenerative therapies. As discussed here, however, additional investigations are required both at the molecular level therapies. With active investigations directed toward understanding the biology of the healing site, including identifying appropriate cells to target, coupled with designing delivery systems that can control release of agents at the local site, establishing the required environment for regeneration of periodontal tissues should be feasible.

Changes in Life Support ( CPR , AED)

Care Technique	Previous Recommendations	New Recommendations
Initial assessment	Check for responsiveness , then open the airway and check for normal breathing	Check for responsiveness  and simultaneously look for normal breathing
CPR technique	Give 2 breaths before beginning chest compressions ( ABC)	Begin CPR immediately with chest compressions( CAB)
Depth of compressions	1 ½ to 2 inches in adult , 1/3 to ½ the depth of the chest in an infant of child	At least 2 inches in an adult , at least 1/3 the depth of the chest in an infant ( about 1 1 ½ inches) or child ( about 2 inches)
Rate of compressions	100 per minute	At least 100 per minute
AED for infants and children	Use AED with paediatric pads for child ages 1 to 8 yrs	Use AED with pediatric pads for both infants and children uo to age 8

Focus on how to provide high quality CPR

1)    Chest compressions          

a.     Push hard and push fast

                                                              i.      At least 100 per minute ( vs. Approx 100/ minute)

                                                            ii.      Compression depth at least 2 inches in adult

  1.     2 inches in children ( = 1/3 AP diameter)

  2.     1 ½ inches in infants (= 1/3 AP diameter)

                                                          iii.      Allow complete recoil of the chest after each compression

                                                         iv.      Maximize the number of compressions per minute

  1.     Minimize interruptions

                                                           v.      Compression – ventilation ratio of 30:2