References

Credibility and Trust

The following is a list of statements by prominent physicians who have scientifically studied and used the aMMP-8 biomarker technology in daily practice and have gained practical experience with it. That the technology stands for quality has been repeatedly proven hundreds of times over. More than just a theory, the biomarker has been validated in practice.

If you would like to send us a statement describing your practical experience with aMMP-8 technology, please write to us. We look forward to hearing from you.

”The novel aMMP-8 test method is one of the first commercially

available tests which opens up the possibility to optimize therapy and

prevention of periodontal disease.” March 2010

Prof. Dr. Ulrich Schlagenhauf
Head of the Department of Periodontology, University of Würzburg,
President of the German Society for Periodontology (DGP)

”Regarding cardiovascular diseases, pathologically excessive MMP-8 has

been implicated in atherosclerotic plaque

destabilization and rupture through its capacity to thin the protecting

collagenous fibrous cap.“ March 2010

Prof. Timo Sorsa PhD
Department of Cell Biology of Oral Diseases,
Institute of Dentistry, University of Helsinki, Helsinki, Finland

”From a cardiological point of view, the careful consideration

of the dental status becomes more important. The MMP-8 rapid test is an important

‘link’ for interdisciplinary communication.” May 2010

OA PD Dr. med. Heinrich Körtke
Head of the Institute for Applied Telemedicine, Clinic for Thoracic and Cardiovascular Surgery,
Heart and Diabetes Center, Bad Oeynhausen

“Active-aMMP-8 is an ideal test which is quantitative, highly sensitive

and specific, reproducible, and easy to perform.” August 2010

Maria Emanuel Ryan, D.D.S., Ph.D.
Professor of Oral Biology and Pathology, Associate Dean for Strategic Planning and External Affairs,
Medical Staff University Hospital, Practice Limited to Periodontics, Stony Brook University

“In my opinion, health communication can be optimized.

Enlightening the population regarding the connection between periodontitis

and overall health could help in this effort.” March 2010

Laurenz Meyer
Economist, CDU politician, Bundestag member ret.,
CDU General Secretary ret., CDU Economic Policy Spokesman ret., Berlin

“In order to ensure high quality in medicine, a stringent

diagnosis, therapy and aftercare concept is necessary – an interdisciplinary

approach is desirable in this context.” December 2010

Dr. med. dent., oec. med. Björn Eggert
Dentist, health economist and quality manager, Director of the goDentisDKV Academy

MMP-8 as a point-of-care biomarker of periodontitis, periimplantitis, and cardiovascular systemic diseases

Neutrophil collagenase or collagenase-2 (matrix metalloproteinase

[MMP] -8) belongs to collagenase subgroup of

MMP super family. MMP-8 is catalytically most competent

enzyme to initiate type I collagen and extracellular matrix

degradation associated to periodontal and peri-implant

tissue destruction leading to tooth and dental implant loss.

Regarding cardiovascular diseases pathologically excessive

MMP-8 has been implicated to atherosclerotic plaque

destabilization and rupture through its capacity to thin

the protecting collagenous fibrous cap. During the initiation

and course of inflammatory responses in periodontal,

peri-implant and cardiovascular diseases proinflammatory

mediators including especially MMP-8 are up-regulated

not only in affected tissues but also in secreted diseaseaffected

oral fluids (gingival crevicular fluid [GCF], periimplant

sulcular fluid [PSF], mouth-rinse and saliva) as

well as in serum (Sorsa et al. Oral Dis 2004, Sorsa et al. Ann

Med 2006, Tuomainen et al. ATVB 2007).

Regarding periodontitis, peri-implantitis and cardiovascular

diseases oral fluid and serum MMP-8 analysis has proved

to an objective biomarker that has been evaluated and confirmed

as an indicator of health, pathologic processes and

pharmacologic response to therapeutic intervention (Sorsa

et al. Oral Dis 2004, Sorsa et al. Ann Med 2006, Tuomainen

et al. ATVB 2007, Reinhardt et al. J Periodontol 2010). Oral

fluids i.e. GCF, PISF, mouth-rinse and saliva, are easily and

non-invasively collected for the site and patient-specific

diagnostic analysis in periodontitis and peri-implantitis

(Sorsa et al. 2004, 2006).

For diagnosis and monitoring of cardiovascular diseases

plasma and or serum sample collection is required (Tuomainen

et al. ATVB 2007, 2008). Research has consequently

been conforted with a need for development for innovative

point-of-care diagnostic tests for MMP-8 (Sorsa et al. Oral

Dis 2010, Gursoy et al. J Clin Periodontol 2010, Leppilahti

et al. Oral Dis 2010).

Prof. Timo Sorsa, PhD

Helsinki, Finland, March 2010

Prof. Timo Sorsa PhD
Department of Cell Biology of Oral Diseases,
Institute of Dentistry, University of Helsinki, Helsinki, Finland

aMMP-8 as a tool for precise diagnostics and improved follow-up therapy in all medical disciplines

At the Institute for Applied Telemedicine (IFAT) at the Heart and

Diabetes Center NRW of Ruhr-University Bochum

more than 1,600 patients are treated telemedically every year

in order to perform good pre- and postoperative follow-up.

The treatment guideline, “Move the information

and not the patient”, is our motto and

ensures that the quality of patient care will continue to increase”.

As an NRW center of excellence for telemedical

cardiodiagnostics and care, we take

a leading telemedical role and focus on the

best possible interdisciplinary and differential therapeutic

approach.

The IFAT is primed to develop targeted telemedical

home monitoring of patients with high cardiovascular

risk factors in order to develop the area of ​​prevention

further so as to benefit patients. From the cardiological point of view

, therefore, careful consideration

of the condition of the teeth also gains in importance.

The periodontal status of affected patients prior to cardiological

/cardiac surgery would be useful from my point of view.

By means of the new MMP-8 rapid test

, we are able to obtain a picture of the oral situation

within minutes and, if necessary, with the colleagues from the field of

periodontics and dentistry, ensure that the

oral area is free from inflammation,

which is needed to go ahead with cardiological treatment.

International studies show very clearly that stroke and heart attacks

are strongly influenced by periodontal disease.

A timely diagnosis

can significantly reduce the risk to patients. In addition,

a US study by Aetna shows that cardiac

treatment costs for periodontal treatment patients

may possibly be reduced. Thus, in addition to the

medical necessity of early diagnosis

and therapy, there is important economic evidence for the linkage

of periodontal and cardiological diagnostics.

The MMP-8 rapid test is an important link

for our interdisciplinary communication.

OA PD Dr. med. Heinrich Körtke

Bad Oeynhausen, May 2010

OA PD Dr. med. Heinrich Körtke
Head of the Institute for Applied Telemedicine, Clinic for Thoracic and Cardiovascular Surgery,
Heart and Diabetes Center, Bad Oeynhausen

Technology transfer makes the identification of oral inflammation possible for dentists, physicians and other health care professionals

Research conducted over the past decade has led to an increased

awareness of the systemic consequences of chronic

inflammation among dentists, physicians and other health care

professionals. The public has been alerted to the impact

of chronic inflammation on its overall health. The fact

is that the most common chronic inflammatory condition

known to mankind is periodontal disease. The research

has supported a link between periodontitis and many other

disease states such as diabetes, stroke, rheumatoid arthritis

and heart disease, as well as adverse pregnancy outcomes.

The problem has been that periodontal disease is often

a silent condition that can progress over the years if left

unchecked by a healthcare provider. Recent studies have

also indicated that dental implants often used to replace

natural teeth, can become diseased as well, generating a

significant inflammatory response that may exceed the

inflammation that has been associated with natural teeth

experiencing the same clinical level of disease. Current

methods of diagnosis for both teeth and implants are based

on clinical observations by the dental professional of pocketing,

attachment loss around teeth, radiographic evidence

of bone loss, redness, swelling, bleeding and suppuration.

In addition, once identified, periodontitis is known to have

periods of exacerbation and remission. The development

of biochemical diagnostic tests to aid in the identification of

disease and to determine levels of disease activity can help

in establishing a more accurate diagnosis and prognosis. A

biochemical marker allows for optimal treatment planning

and follow-up for both natural teeth and dental implants.

Based on numerous studies it appears that the matrix metalloproteinases

are ideal biochemical markers, particularly

active-MMP-8.

Due to the known impact of untreated periodontitis on

overall health and well-being, there has been a transition

toward the interdisciplinary management of patients so

as to provide the most comprehensive treatment possible.

Screening for oral inflammation can now easily be conducted

using the a-MMP-8 marker, prompting a physician

referral to the dental care professional for a thorough oral

examination. Once a referral is made, the source of the

a-MMP-8 can be identified and the appropriate treatment

can be provided. The source of a-MMP-8 can then be

monitored until the levels of a-MMP-8 are reduced and the

inflammatory process is resolved.

Maria Emanuel Ryan, D.D.S., Ph.D.

Professor of Oral Biology and Pathology

Associate Dean for Strategic Planning and External Affairs

Medical Staff University Hospital

Practice Limited to Periodontics

Stony Brook University

Evidenced-based practice would say that reducing the

inflammatory burden to our patients, whatever the source

of inflammation, is a winning strategy. Active-MMP-8 is an

ideal test which is quantitative, highly sensitive and specific,

reproducible, and easy to perform. The adoption of this test

into the medical and dental communities will help to facilitate

a new interdisciplinary approach to the management

of diseases.

Maria Emanuel Ryan, D.D.S., Ph.D.

New York, August 2010

Maria Emanuel Ryan, D.D.S., Ph.D.
Professor of Oral Biology and Pathology, Associate Dean for Strategic Planning and External Affairs,
Medical Staff University Hospital, Practice Limited to Periodontics, Stony Brook University

The aMMP-8 test optimizes the treatment and prevention of periodontal diseases

The occurrence of periodontal inflammation is closely

related to the presence of specific micro-organisms in the area around the

gingival sulcus or periodontal pockets.

Therefore, it is not surprising that the focus of periodontal

research efforts in the past mostly

focused on the detailed analysis of presumed bacterial virulence mechanisms which were deemed to be the culprits

in the onset

of the disease.

A multitude of clinical-experimental data has meanwhile

shown that periodontal diseases

are not transmissible bacterial infections in

the sense of the Kochian postulates, but rather

are regarded as opportunistic infections which arise chiefly

due to the faulty regulation of

the oral immune system. Implementing

consistent plaque control is, under clinical-practical aspects, nevertheless still the means of

choice for minimizing the intensity of periodontal inflammatory

inflammatory

processes.

However, the documentation of even optimal, plaque-free dental conditions

is, according to the current understanding of the etiology, not sufficient

by itself

in order to wholly prevent any onset of illness or

a relapse. However, when it comes to a correct risk assessment

– in addition to the absolutely necessary evaluation of the fitness of the oral

immune system – to date there have been no concepts which have been

unequivocally substantiated and widely accepted

on the basis of clinical studies.

The novel BioMarker test method is designed to determine

the activity of tissue-destroying matrix metalloproteinases

in the sulcus fluid or saliva, and is among

the first commercially available tests that also permits the evaluation

of a central part of the host reaction of periodontal

and peri-implant inflammation on an objective

basis and thus provides additional opportunities to optimize

the therapy and prevention of periodontal

disease.

Prof. Dr. Ulrich Schlagenhauf

Würzburg, March 2010

Prof. Dr. Ulrich Schlagenhauf
Head of the Department of Periodontology, University of Würzburg,
President of the German Society for Periodontology (DGP)

Interdisciplinary cooperation gains in importance from an economic point of view as well

As can be seen from numerous statements by researchers and scientists

, 70% of all Germans are unaware that they suffer from

health problems of the oral

cavity. Interactions between common medical diseases

and periodontal disease are becoming increasingly apparent.

The are massive personal and national negative consequences for those affected and

for society

as a whole.

This presents medical professionals and dentists

with challenges for which they may not be

adequately prepared in their studies.

The Interdisciplinary Diagnostic Initiative for the Early Detection of Periodontal Disease

is concerned with the topic of “pathogenic

enzymatic activity” and shows once more the extent to which there is a close

link between dental health and general health.

The interactions of periodontal diseases and

for example, diabetes and cardiovascular

diseases are scientifically proven.

Interdisciplinary collaboration is thus

of crucial importance: diseases can be detected early

, mitigated and allayed.

The study by US company Aetna indicates that there is a potential to reduce the costs associated with the cardiological treatment

of patients

undergoing periodontal treatment. Thus,

in my opinion the Aetna study offers important

economic evidence for the relevance of interdisciplinary

cooperation. In this case, the principle of

“prevention is better than cure” is always applicable.

Laurenz Meyer

Berlin, April 2010

Laurenz Meyer
Economist, CDU politician, Bundestag member ret.,
CDU General Secretary ret., CDU Economic Policy Spokesman ret., Berlin

“In order to ensure high quality in medicine, a stringent diagnosis, therapy and aftercare concept is necessary – an interdisciplinary approach is desirable in this context.” December 2010

Early diagnosis and patient-oriented therapy

at a definitively high quality level – these are certainly objective goals which every dental practitioner can make use of

for his or her practice.

This, combined with a preventive treatment concept,

ensures our patients the best possible care

and guarantees a high level of satisfaction, thus providing the basis for

the economic success of the dental practice. This

type of treatment is medically successful while

remaining affordable.

Still, we’re all familiar with the new patient, who, after years of treatment elsewhere just happens

to show up at our clinic.

Our results indicate the dental enamel has been adequately cared for with high-quality

treatment, and that his or her oral hygiene

is acceptable The results of the PSI come back as a surprise,

and in explaining

the horizontal bone loss on the current X-ray, the patient asks: “But I

had regular checkups and had my teeth professionally

cleaned every year. Why didn’t my dentist see this this?”

These types of patient cases repeatedly emphasize

the need for stringent diagnosis, therapy and

follow-up concepts, risk-oriented prevention measures,

and a high level of qualification and motivation on the part

of the dental treatment team, including assistants,

especially if it

performs delegable services. Naturally, this includes the willingness

for interdisciplinary cooperation with

all specialist fields.

Quality must be lived. Have we really already reached this goal?

Dr. med. dent., oec. med. Björn Eggert
Dentist, health economist and quality manager
Director of the goDentisDKV Academy