Background and introduction
It is a well-known fact that titanium particles deriving from dental titanium implants (DTI) dissolve into the surrounding bone. Although titanium (TI) is regarded as a ...compatible implant material, increasing concern is coming up that the dissolved titanium particles induce inflammatory reactions around the implant. Specifically, the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) is expressed in the adjacent bone. The transition from TNF-α-induced local inflammation following insertion of DTI surgery to a chronic stage of “silent inflammation” could be a neglected cause of unexplained medical conditions.
Material and methods
The signaling pathways involved in the induction of cytokine release were analyzed by multiplex analysis. We examined samples of jawbone (JB) for seven cytokines in two groups: specimens from 14 patients were analyzed in areas of DTI for particle-mediated release of cytokines. Each of the adjacent to DTI tissue samples showed clinically fatty degenerated and osteonecrotic medullary changes in the JB (FDOJ). Specimens from 19 patients were of healthy JB. In five cases, we measured the concentration of dissolved Ti particles by spectrometry
All DTI-FDOJ samples showed RANTES/CCL5 (R/C) as the only extremely overexpressed cytokine. DTI-FDOJ cohort showed a 30-fold mean overexpression of R/C as compared with a control cohort of 19 healthy JB samples. Concentration of dissolved Ti particles in DTI-FDOJ was 30-fold higher than an estimated maximum of 1.000 μg/kg.
As R/C is discussed in the literature as a possible contributor to inflammatory diseases, the here-presented research examines the question of whether common DTI may provoke the development of chronic inflammation in the jawbone in an impaired state of healing. Such changes in areas of the JB may lead to hyperactivated signaling pathways of TNF-α induced R/C overexpression, and result in unrecognized sources of silent inflammation. This may contribute to disease patterns like rheumatic arthritis, multiple sclerosis, and other systemic-inflammatory diseases, which is widely discussed in scientific papers.
From a systemic perspective, we recommend that more attention be paid to the cytokine cross-talk that is provoked by dissolved Ti particles from DTI in medicine and dentistry. This may contribute to further development of personalized strategies in preventive medicine.
Background: This case report demonstrates the value of ultrasound measurements, and immunological and toxicological diagnostics in addition to current x-ray imaging procedures to diagnose hidden oral ...and maxillofacial infections. Using a clear scheme shows the procedure of the authors' steps. The positive impact on the patient's dermatological clinical picture is shown. Functional regeneration using metal-free ceramic implants and autologous bone augmentation is demonstrated. After a healing period, a postoperative control took place. Question: Are chronic inflammatory and chronic toxic stressors from the oral region affecting the patient's state of health and dermatological symptoms? Patients and Methods: A 52 year old female suffering from neurodermatitis, who had been therapy-resistant for several years, was rehabilitated by oral surgery and prosthetics. Radiological examinations with orthopantomogram (OPG) and three-dimensional imaging (DVT/CBCT) were inconclusive for possible jawbone inflammatory sites. Immunological, toxicological diagnostics and trans-alveolar bone densitometry with ultrasound (TAU), were able to show immunological and toxicological stressors and areas of reduced bone density. Bone densitometry with ultrasound raised the suspicion of silent inflammations in the jawbone with potentially increased cytokine levels. Results: For the patient incompatible materials, teeth with increased toxin exposure and surrounding softened, fatty, ischaemic bone was removed. Histologies and cytokine profiles were obtained. The resulting defects were functionally regenerated using ceramic implants and autologous augmentation. The cytokine profiles showed significantly elevated RANTES/CCL5, confirming the need for surgical intervention. The patient's atopic dermatitis improved significantly in this case. Summary: Individualized immunological and toxicological diagnostics and trans-alveolar bone density bone densitometry with ultrasound (TAU) identified immunological and toxicological stressors as well as reduced bone density with increased cytokine levels. A therapy-resistant neurodermatitis improved significantly after treatment. Conclusion: This case report illustrates the need for patient-specific and individualized examinations that link dentistry more closely with other medical conditions in order to clarify possible interactions. Keywords: atopic dermatitis, CCL5/RANTES, osteoimmunology, ceramic implants, autologous augmentation, silent inflammation, FDOJ, trans alveolar ultrasonography
Cytokines, especially chemokines, are of increasing interest in immunology. This study characterizes the little-known phenomenon of "bone marrow defects of the jawbone" (BMDJ) with known ...overexpression of the chemokine RANTES/CCL5 (R/C).
Our investigation clarifies why BMDJ and the intensity of local R/C overexpression are challenging to detect, as examined in patients with seven different systemic immunological diseases. Specifically, we investigate whether R/C overexpression is specific to certain disease groups or if it represents a type of signal disruption found in all systemic immunological diseases.
In a total of 301 patients, BMDJ was surgically repaired during clinical practice to reduce "silent inflammation" associated with the presence of jaw-related pathologies. In each case of BMDJ, bone density was measured preoperatively (in Hounsfield units HU), while R/C expression was measured postoperatively. Each of the 301 patients suffered from allergies, atypical facial and trigeminal pain, or were diagnosed with neurodegenerative diseases, tumors, rheumatism, chronic fatigue syndrome, or parasympathetic disorders.
In all BMDJ cases, strongly negative HU values indicated decreased bone density or osteolysis. Consistently, all cases of BMDJ showed elevated R/C expression. These findings were consistently observed in every disease group.
BMDJ was confirmed in all patients, as verified by the HU measurements and laboratory results related to R/C expression. The hypothesis that a specific subset of the seven disease groups could be distinguished either based on the increased presence of BMDJ and by the overexpression of R/C could not be confirmed. A brief literature review confirms the importance of R/C in the etiology of each of the seven disease groups.
In this research, the crucial role played by BMDJ and the chemokine R/C in inﬂammatory and immune diseases is discussed for seven groups of patients. Each specific immune disease can be influenced or propelled by BMDJ-derived R/C inflammatory signaling pathways.
A common pathomechanism involved in many degenerative manifestations of non-communicable diseases is nitrosative stress, giving rise to a chronic insidious inflammation causing silent inflammation at ...a cellular level. The release of nitric oxide inhibits multiple enzyme reactions with reduced oxidative phosphorylation and mitochondrial ATP depletion.
We hypothesized that enzyme-inhibition can be alleviated by micronutrient supply, and studied laboratory parameters associated with nitrosative stress (nitrotyrosine, mitochondrial activity) after a micronutrient supplementation (a multivitamin mineral and trace element formulation as verum: LaVita®) and a placebo in healthy volunteers (n=150) for six months.
Mean nitrotyrosine levels dropped significantly after 3 month in the verum and placebo group, whereas mitochondrial activity increased after three month in the verum group (p=0,087), but not in the placebo group (p=0,990). Ubiquinone - an essential ingredient for mitochondrial function- increased after six months in the verum group, but not after placebo consumption (p=0,001). Serum zinc and cellular zinc increased steadily after 3 and 6 month verum intake (p<0,001). As the enzyme superoxide dismutase (SOD) is mainly involved in the formation of nitrosative stress (peroxides) we measured the activity, and found significant differences in the placebo and verum group after 3 and 6 month (p=0,050 and p=0,003 respectively).
We conclude that a balanced combination of vital nutrients may reduce nitrosative stress and silent inflammation, and consequently the risk for various forms of degenerative diseases.
Of the definitions listed in the International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10), two disease descriptions can be found together: "idiopathic ...aseptic bone necrosis" and "avascular bone necrosis." The relevant literature on both the conditions abbreviates both as "aseptic ischemic osteonecrosis in the jawbone" (AIOJ). To shed light on the clinical details of this condition, osteolytic jawbone samples of 24 patients with different systemic immunological diseases were examined using four steps: presurgical dental X-ray, postsurgical histology, polymerase chain reaction DNA analysis (PCR DNA) of bacteria, and RANTES/CCL5 (R/C) expression. These four steps showed that neither X-ray nor histology delivered unambiguous results with respect to inflammatory processes; furthermore, the PCR results did not show evidence of any microbial load within the jaw samples. However, there is a striking, coherent overexpression of chemokine R/C in the AIOJ samples. This study proved the aseptic existence of "silent inflammation" within the jawbone. The ICD-10 (AIOJ) definition, which is hard to interpret, can now be substantiated with clinical evidence, while the cytokine expressions described in this report can explain the systemic immunological effects observed within the group of examined patients.
Den Zahn- und Kieferherden müssen in der Ganzheitsmedizin v.a. in der Regulationsmedizin, zu welcher auch die Osteopathie zählt, mehr Bedeutung geschenkt werden. Die Diagnose solcher Herde ist nicht ...immer einfach und erfordert eine enge interdisziplinäre Zusammenarbeit. Hier sind gerade wir Osteopathen gefordert, da uns Menschen oft mit Dysfunktionen bis hin zu chronischen Beschwerdebildern aufsuchen.
In diesem Zusammenhang ist es unbedingt notwendig, daran zu denken, dass diese Herde unsere Arbeit behindern und zu schwerwiegenden Krankheiten führen können, die unseren Patienten einen enormen Leidensweg bescheren. Gerade in der Osteopathie, die den Anspruch auf Ganzheitlichkeit stellt, ist es daher dringend notwendig, über den Tellerrand hinweg zu sehen und sich auch andere diagnostische Hilfsmittel anzueignen.
In the holistic or rather regulatory medicine, like ostheopathy is, we have to care more about the dysfunctions in the field of the teeth and the jawbone. The diagnosis of such dysfunction is not always easy and we have to work in multidisciplinary teams. Just osteopaths have a special rule, because patients visiting us are suffering from body dysfunction up to chronic deseases. Therefore it is absolutely necessary to attach importance to these problems which can restrain our treatment and lead to serous medical conditions which results in a life of suffering for our patients. Especially in osteopathy, which claims to be holistic, it is therefore necessary to think outside the box and to acquire other diagnostic additives.
There is a need to clarify the extent to which the most common diagnostic tool in dentistry - two-dimensional panoramic tomography (2D-OPG) - is suitable for identifying fatty degenerative osteolysis ...of jawbone (FDOJ).
To obtain a qualitative assessment of edentulous jawbone sections, the results from 2D-OPG with a defined X-ray density (XrDn), expression of the cytokine RANTES (regulated on activation, normal T-cell expressed and secreted), and a transalveolar ultrasound system for measuring jawbone density were compared.
The difference in the XrDn of healthy jawbone and FDOJ are minimal, whereas RANTES is up to 25-fold higher in FDOJ. In contrast to 2D-OPG, transalveolar ultrasound showed coincidental findings in FDOJ areas.
Comparisons of the data revealed a discrepancy between the XrDn of 2D-OPGs and the medullary osteopathies in the jawbone like FDOJ.
The data suggest that there is a critical attitude toward the use of 2D-OPG as a sole imaging diagnostic tool for assessing chronic inflammatory processes in the jawbone. Specifically, 2D-OPG is objectively not suitable for depicting FDOJ.
Elastase–inhibitor complex was assessed by immunoassay in the seminal plasma of 312 men attending the outpatient infertility clinic. Using receiver operating characteristic (ROC) curve analysis, ...elastase at the cut-off value of ≥290 ng/ml was shown to be efficient (sensitivity 79.5%, specificity 74.4%) in the detection of genital tract inflammation as defined by leukocytospermia (>1×106 leukocytes/ml). The prevalence of increased elastase in 292 infertile men was significantly higher (34%) as compared with that (5%) observed in 20 fertile men (P = 0.02). Moreover, high elastase concentration (≥290 ng/ml) was observed in 66 of the 264 men (25%) without leukocytospermia. A significant positive correlation was found between elastase concentration and patient age (r = 0.202, P < 0.0001) and the number of leukocytes (r = 0.330, P < 0.0001). A negative correlation was found between elastase concentration and semen volume (r = –0.146, P = 0.01) and the percentage of spermatozoa with single-stranded DNA (r = –0.194, P = 0.024), but there was no correlation between elastase and sperm reactive oxygen species production. A higher seminal elastase concentration was significantly associated with tubal damage in female partners (P < 0.001). After norfloxacine antibiotic therapy, decrease in elastase concentration was observed in 15 (25%) of the 60 treated patients. Tubal damage in the partner negatively affected the response to antibiotic therapy. In conclusion, granulocyte elastase is a reliable screening test for silent genital tract inflammation of the couple. The elastase–inhibitor complex may have a protective effect in reducing sperm DNA denaturation.
Obesity and type 2 diabetes are strongly associated with increased inflammation. As the inflammation in adipose tissue increases, this becomes a strong driving force for the development of increased ...systemic inflammation that results in metabolic syndrome, eventually followed by the development of overt type 2 diabetes. The potential reversal of both conditions can be achieved by reducing the levels of inflammation through the use of an anti-inflammatory diet. The composition of such a diet and its molecular mode of action will be discussed.