Bärbel Miehe

Masticatory musculature under altered occlusal relationships--a model study with experimental animals.

In a study with experimental animals, the occlusal relationships of male Wistar rats were altered by the bilateral extraction of lateral teeth; the bolus function was eliminated by feeding a soft diet. Both steps led to relief of strain on the temporomandibular joint and thus also in the muscular system itself. The masticatory muscles adapted to the new experimental conditions. We observed a reduction in muscle dry weight and a shift in muscle fiber composition in favour of the IIb fibers, which indicates that less masticatory strength was required. Adaptation thus occurred equally on the macroscopic and microscopic levels.

Increased epidermal functioning wild-type p53 expression in vitiligo

Abstract:  Despite the lack of protective melanin and increased oxidative stress due to mM concentrations of epidermal H2O2 in vitiligo, there is no significantly increased risk for chronic actinic damage and non‐melanoma skin cancer. Therefore the question arises, which protective mechanisms could be involved in the skin of these patients preventing the initiation of these cancers. Recently an overexpression of p53 has been shown in vitiligo. Unfortunately there was no further characterization of this elevated p53. Employing a functional colour yeast assay, the study presented herein demonstrates for the first time the overexpression of a functioning wild‐type p53 protein in both depigmented and ‘normal’ pigmented epidermis of patients with vitiligo compared with healthy controls. Surprisingly long‐term narrowband UVB (311 nm) treatment does not alter this expression. Moreover, MDM‐2, PCNA and p21 protein expression remain unchanged compared with healthy controls. This increased epidermal p53 in vitiligo coincides with decreased thioredoxin reductase (TR) protein levels in both depigmented and pigmented skin whereas mRNA expression is unaffected. Because TR is one transcriptional target of p53, these results support a wild‐type functionality, which was further supported by the specific p53 FASAY yeast test. To our knowledge this is the first example of persistent elevated functioning wild‐type p53 in humans. Based on our results we hypothesize that the low incidence for actinic damage, basal cell and squamous cell carcinoma as documented in vitiligo could well reside in a protective function of up‐regulated wild‐type p53.

Delay of tympanic membrane wound healing in rats with topical application of a tyrosine kinase inhibitor.

An animal model of chronic tympanic membrane (TM) perforation is needed for experiments on supporting wound healing of TM perforations. The epidermal growth factor receptor (EGFR) has been implicated in the regulation of wound healing. The object of this study was to investigate the efficacy of topical EGFR‐inhibitor (erlotinib) to arrest wound healing of experimental TM perforation in rats. Bilateral instrumental myringotomies were performed in 13 male rats. A solution of erlotinib (10 mg/mL) was applied to one TM of each animal and vehicle only (control group) to the other side. The application procedure was repeated on both sides daily for 12 consecutive days. Thereafter, tympanic membranes were observed weekly for a total of 30 days. The mean healing period was found to be 12.1 days in the group with erlotinib and 6.4 days in the control group. The difference was significant. We observed differences in the histologic parameters between erlotinib group and control group. The inhibition of EGFR by topical application of erlotinib did delay the healing rate of myringotomies but seems not to be suitable to create a chronic TM perforation in rat.

The influence of altered occlusion on the condylar cartilage of the mandible and on the growth of the entire skull

The effect of the loss of the suspensory zones of the upper jaw on the cartilage of the mandibular condyles and on the growth of both the viscerocranium and the neurocranium was examined after tooth crowns had been reduced in Wistar rats. We measured the thickness of the individual layers of the condylar cartilage and its total thickness. Alterations in the developmental processes involving the condylar cartilage expressed themselves as accelerated maturation, particularly in the centrally compressed areas of the cartilage. Alterations in occlusion influenced the development of the viscerocranium, whereas no influence on the growth of the neurocranium was detected.

Topical application of transforming growth factor-β1 in acute traumatic tympanic membrane perforations: an experimental study in rats

High transforming growth factor‐β1 (TGF‐β1) expression in combination with fibrotic scar was observed in human tympanic membranes containing a chronic perforation. The purpose of this study was to investigate whether application of exogenous TGF‐β1 to experimentally created tympanic membrane perforations might induce a nonhealing tympanic membrane perforation. Bilateral myringotomies were performed in 20 rats. In 10 animals, a single dose of TGF‐β1 (0.1 μg) was topically applied to the left tympanic membrane after perforation. In the second part of the study with 10 animals, repeated applications of TGF‐β1 at a higher concentration were tested. In both groups, the opposite ears received vehicle alone. Tympanic membranes were observed for a total of 5 weeks. The effect of TGF‐β1 on the healing of the tympanic membranes was evaluated by closure rates and histology. In the single application group, the healing process was not delayed. Repeated applications of TGF‐β1 did cause a faster perforation closure and a thicker tympanic membrane. Topical TGF‐β1 applied to a traumatic tympanic membrane perforation does not create a chronic perforation at the concentrations and modes of application used in this study.

The influence of inhibition of the epidermal growth factor receptor on tympanic membrane wound healing in rats

Recently, a report on a bilateral tympanic membrane (TM) perforation in a patient after long-term treatment with erlotinib was published. The object of this study was to investigate the destructive potential of topical applied epidermal growth factor receptor (EGFR) inhibitors on wound healing of experimental TM perforation in rats by evaluating closure rates and histology. In 12 rats, erlotinib (10 mg/ml) was applied to one TM of each animal and cetuximab (5 mg/ml) to the other side daily for 12 consecutive days. Both the erlotinib group (11.8 days) and cetuximab group (9 days) had prolonged healing latencies compared to a reference value (7 days). We observed differences in the histologic parameters between both groups. Our results suggest that in normal TM, the inhibition of EGFR does not lead to a persistent perforation. However, in case of preexisting TM pathology, a spontaneous perforation in patients under long-term treatment of EGFR inhibitors seems to be possible.

Influence of glycemic control on tympanic membrane healing in diabetic rats

It is generally assumed that glycemic control in diabetic patients is important in optimizing wound healing. The goal of this study was to examine tympanic membrane (TM) wound healing in spontaneously diabetic rats depending on the diabetic metabolic state compared to nondiabetic control animals.

Functional conditions of the mandible: theory and physiology

The functional conditions of the mandible are differentiated according to the number of kinematic degrees of freedom assigned to each mandibular movement. One degree of freedom: pro- and retrusive occlusal border movement. The interplay of the TMJs with the occluding teeth determines a compulsory course which corresponds to a 4-bar-chain guidance. 2 degrees of freedom: free sagittal mouth movement without tooth contact. Using graphic recordings of cyclic mandibular movements, the mobile hinge axis is identified as a mandibularly fixed line which is not directly categorized as a part of an anatomical structure. In the maxillary coordinate system, its movement describes a cylinder; sagittally, it describes a circle. The mandibular positions are clearly identifiable with 2 angles. The in vivo measurements show that neuromuscularly healthy systems supply the mandible with anticipatory guidance. 3 degrees of freedom: bolus function. The articular space in the TMJ is utilized.

Alteration of the functional condition of the mandible during clinical treatment

Free mandibular movements and their neuromuscular guidance were measured with an ultrasonic device and analyzed with computer software developed by the authors. In all patients examined, we found maxillarly- and mandibularly-fixed axes which maintain a constant distance. This guidance system is named a neuromuscularly-determined dimeric link chain. The position of the mandible is defined by the 2 rotational angles (mu, alpha) around the axes of the dimeric link chain. This dimeric link chain of free movements normally functions according to the principle of least action. The angular velocities around the 2 axes show a constant ratio during the different segments of motion. In the mu-alpha-diagrams, the segments of movements of the mandible are represented by straight lines, the shortest path between 2 positions. Individual cases and statistical data show that the structure of mandibular movements of patients with skeletal mandibular retrognathism combined with dental class-II-relationship without craniomandibular pain significantly differs from the structure in patients with neutral alignment. Mandibular retrognathism and class-II-relationship are accompanied by marked coordination disturbances of rotations around the maxillary and mandibular neuromuscular axes. Following orthodontic-surgical treatment that restored ideal alignment of the occlusal, articular, and skeletal structures, the patients examined showed a similar pattern in the structure of mandibular movements to that of patients with neutral skeletal and dental relationships. Thus, combined orthodontic-surgical treatment leads to measurable functional harmonization not only of the skeletal and dental structures, but also of the neuromuscular guidance system.