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.




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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).