The general aim of this thesis was to broaden our knowledge of the signs and symptoms, genetics, and outcomes of dental implant treatment in individuals with oligodontia or ectodermal dysplasia. Article I is a population-based study in three Swedish counties of 162 individuals with oligodontia, which was a prevalence of 0.09%. The intent was to explore ways for dentists to assess symptoms from other ectodermal structures than teeth through a clinical interview and chair-side analyses. Thirty per cent had low salivary secretion rates while only 11% with no known syndrome reported symptoms from hair, nails, or sweat glands. These are, together with teeth, the ectodermal structures on which it is proposed that a clinical diagnosis of ectodermal dysplasia (ED) be based. Article II screened 93 probands with oligodontia for mutations in six genes known to cause oligodontia and hypohidrotic ED. Sequence alterations predicted to be damaging or potentially damaging were revealed in the AXIN2, MSX1, PAX9, and EDARADD genes in 14 (15%) of the probands. All mutations but one were novel. For the first time, EDARADD mutations were shown to cause isolated oligodontia. No individual who had reported ectodermal symptoms from hair, nails, or sweat glands had a mutation. Article III assessed orofacial function in individuals with different types of EDs using the Nordic Orofacial Test-Screening (NOT-S) protocol. Individuals with ED scored significantly higher in orofacial dysfunction than a healthy reference sample, especially in the Chewing and swallowing, Dryness of the mouth, and Speech domains. Article IV surveyed treatment outcome of dental implants in Swedish children up to age 16 years. In a 20-year period, only 26 patients were treated, 5 of whom had hypohidrotic ED and anodontia of the mandible. Individuals with ED had 64% failed implants compared to 6% among subjects with teeth missing due to trauma or agenesis. The main conclusions of this thesis were that (i) a check of whether one or more permanent incisors are missing will identify 65% of individuals with oligodontia and 84% of individuals missing nine teeth or more, (ii) evaluation of salivary secretion is indicated in children with oligodontia, (iii) a majority of individuals with oligodontia did not report other abnormal ectodermal organ function besides teeth, (iv) no clinical indicator discriminated between individuals with and without mutations in the tested genes, and more unidentified genes are involved in tooth morphogenesis, (v) EDARADD mutations are associated with isolated oligodontia, (vi) evaluation of orofacial function is indicated in individuals with ED, and many individuals with ED would benefit from orofacial skills training, (vii) dental implant placement is a rare treatment modality in children, (viii) individuals with hypohidrotic ED seem to present special challenges due to structural as well as direct effects of the mutations on bone, which seem to compromise osseointegration, (ix) central registers on signs and symptoms in individuals with rare disorders would help establish prevalences of various diagnoses and define treatment needs, and (x) quality registers for monitoring treatment outcomes of dental implants would promote early detection of risks and side-effects in individuals with rare disorders.

Objective: To determine if significant differences exist in timings and rates of Peak Mandibular Growth (PMG) and mandibular projections of subjects with vertical, average and horizontal facial growth patterns. Methods: Sixty-three Caucasian orthognathic subjects with cephalograms (9 to 18 years) available from the Burlington Growth Centre were categorized into average, vertical and horizontal growth pattern groups based on their change in Y axis from age 10 to 16 years. PMG timing and rates were determined and mandibular projections measured. Comparisons were made by ANOVA. Results: Inter-group differences of PMG timing or rate were not statistically significant. Although not statistically significant, PMG of vertically growing females was 14 month earlier than all other subgroups. Horizontal mandibular projection differences approached significance in older children. Conclusions: No statistically significant differences were found in the timing or rate of PMG in different facial growth patterns. Differences in horizontal mandibular projections approached significance with growth.

Molecular defects in the p63 gene give rise to severe physiological abnormalities in patients with ectodermal dysplasia, however the mechanisms by which p63 mutations disrupt p63 function are unknown. In this study we examined four ΔNp63α mutants; Ectrodactyly-Ectodermal Dysplasia with Clefting (EEC) R204W, R304W and Ankyloblepharon-Ectodermal Dysplasia with Clefting (AEC) mutants, L514F and G530V, and characterized DNA binding, transcription factor activity, oligomerization with wild-type p63 and changes in protein stability/nuclear localization. We also investigated the putative OD-SAM interaction in p63 and p73. We demonstrated that both the EEC and AEC mutants cannot transcriptionally activate the PERP promoter and can hetero-oligomerize forming dominant negative complexes with wild-type p63. We show that both EEC mutants and AEC L514F mutants are more stable which is not due to aberrant degradation by the E3 ligase Itch. Finally, we discovered that a novel interaction between the p73 OD and SAM domain is absent in p63.

Objective: To determine if significant differences exist in timings and rates of Peak Mandibular Growth (PMG) and mandibular projections of subjects with vertical, average and horizontal facial growth patterns. Methods: Sixty-three Caucasian orthognathic subjects with cephalograms (9 to 18 years) available from the Burlington Growth Centre were categorized into average, vertical and horizontal growth pattern groups based on their change in Y axis from age 10 to 16 years. PMG timing and rates were determined and mandibular projections measured. Comparisons were made by ANOVA. Results: Inter-group differences of PMG timing or rate were not statistically significant. Although not statistically significant, PMG of vertically growing females was 14 month earlier than all other subgroups. Horizontal mandibular projection differences approached significance in older children. Conclusions: No statistically significant differences were found in the timing or rate of PMG in different facial growth patterns. Differences in horizontal mandibular projections approached significance with growth.

Molecular defects in the p63 gene give rise to severe physiological abnormalities in patients with ectodermal dysplasia, however the mechanisms by which p63 mutations disrupt p63 function are unknown. In this study we examined four ΔNp63α mutants; Ectrodactyly-Ectodermal Dysplasia with Clefting (EEC) R204W, R304W and Ankyloblepharon-Ectodermal Dysplasia with Clefting (AEC) mutants, L514F and G530V, and characterized DNA binding, transcription factor activity, oligomerization with wild-type p63 and changes in protein stability/nuclear localization. We also investigated the putative OD-SAM interaction in p63 and p73. We demonstrated that both the EEC and AEC mutants cannot transcriptionally activate the PERP promoter and can hetero-oligomerize forming dominant negative complexes with wild-type p63. We show that both EEC mutants and AEC L514F mutants are more stable which is not due to aberrant degradation by the E3 ligase Itch. Finally, we discovered that a novel interaction between the p73 OD and SAM domain is absent in p63.

<p>The redistribution of incident light into scattered fields ultimately limits the ability to image into biological media. However, these scattered fields also contain information about the structure and distribution of protein complexes, organelles, cells and whole tissues that can be used to assess the health of tissue or to enhance imaging contrast by excluding confounding signals. The interpretation of scattered fields depends on a detailed understanding of the scattering process as well as sophisticated measurement systems. In this work, the development of new instruments based on low coherence interferometry (LCI) is presented in order to perform precise, depth-resolved measurements of scattered fields. Combined with LCI, the application of new light scattering models based on both analytic and numerical methods is presented in order to interpret scattered field measurements in terms of scatterer geometry and tissue health. </p><p>The first portion of this work discusses the application of a new light scattering model to the measurement recorded with an existing technique, Angle Resolved Low Coherence Interferometry (a/LCI). In the a/LCI technique, biological samples are interrogated with collimated light and the energy per scattering angle at each depth in the volume is recorded interferometrically. A light scattering model is then used to invert the scattering measurements and measure the geometry of cell nuclei. A new light scattering model is presented that can recover information about the size, refractive index, and for the first time, shape of cell nuclei. This model is validated and then applied to the study of cell biology in a series of experiments measuring cell swelling, cell deformation, and finally detecting the onset of apoptosis.</p><p>The second portion of this work introduces an improved version of a/LCI based on two dimension angle resolved measurement (2D a/LCI) and Fourier domain low coherence interferometry (FD-LCI). Several systems are presenting for high speed and polarization-resolved measurements of scattered fields. An improved light scattering model based on fully polarization and solid angle resolved measurements is presented, and then efficiently implemented using distributed computing techniques. The combined system is validated with phantoms and is shown to be able to uniquely determine the size and shape of scattering particles using a single measurement.</p><p>The third portion of this work develops the use of angle-resolved interferometry for imaging through highly scattering media by exploiting the tendency of scatterers to forward scatter light. A new interferometers is developed that can image through very large numbers of scattering events with acceptable resolution. A computational model capable of reproducing experimental measurements is developed and used to understand the performance of the technique.</p><p>The final portion of the work develops a method for processing 2D angle resolved measurements using optical autocorrelation. In this method, measurements over a range of angles are fused into a single depth scan that incorporates the component of scattered light only from certain spatial scales. The utility of the technique is demonstrated using a gene knockout model of retinal degeneration in mice. Optical autocorrelation is shown to be a potentially useful biomarker of tissue disease.</p> / Dissertation

No description available.

Mucoadhesive drug delivery systems which are being used from 1980’s to avoid first pass metabolism of drugs, commercially exist for only systemic drug delivery with fast erosion times (15-60 min), that may not be appropriate for local oral disorders. The goal of this research was to develop and characterize mucoadhesive films with flexibility of carrying different drugs and proteins and provide sustained release for local treatment of oral disorders. Mucoadhesive films composed of polyvinylpyrrolidone (PVP) and carboxymethlycellulose (CMC) were formulated with imiquimod, an immune response modifier. Problems such as solubilization of imiquimod to increase drug loading, uniformity in films and total amount of drug released into supernatants were addressed by use of acetate buffer after investigating multiple methods. Subsequently, other relevant properties of mucoadhesive systems, such as adhesion (shear, pull-off), tensile properties, swelling profiles, transport kinetics, and subsequent changes in release profiles as a function of film composition were characterized. The potential of the system for local retention of imiquimod, determined in oral mucosa of hamsters showed time dependent decrease in imiquimod amount through 12 hours, with no traces of drug in blood. Further testing in humans revealed that the residence time of the mucoadhesive films depended on the application site, increasing in the order of tongue < cheek < gingiva. In parallel, mucoadhesive films loaded with epidermal growth factor (EGF) were developed to promote treatment of oral mucosal wounds. Bioactivity was tested in vitro on buccal tissues by creating a wound followed by application of films. Although EGF-loaded films did not accelerate wound healing, but rather elicited a hyperparakeratotic response. In vitro buccal tissues may not be appropriate for testing the effects of EGF in wound healing without incorporation of other biochemical factors. Overall, a mucoadhesive system capable of delivering bioactive small molecules and proteins in sustained manner was developed in this work. A thorough understanding of the system properties was achieved to further tune for future applications. In vitro studies and in vivo studies in hamsters and humans clearly showed the potential and usefulness of the system to translate in to clinic for treatment of oral precancerous lesions.

Andreas Starke Quantifizierung und Klassifizierung der kaninen Ellbogeninkongruenz auf Grundlage einer standardisierten Röntgen- und Messmethode Klinik für Kleintiere der Veterinärmedizinischen Fakultät der Universität Leipzig (79 Seiten, 27 Abbildungen, 8 Tabellen, 132 Literaturangaben) Zielstellung: Ziel der vorliegenden Arbeit war die objektive Quantifizierung der knöchernen Konformation des Ellbogengelenkes gesunder und erkrankter Hunde unter standardisierten Bedingungen. Dazu sollte eine Methode entwickelt werden mit der Röntgenaufnahmen von Ellbogen unter Belastung angefertigt und anhand von Messungen an markanten Knochenstrukturen evaluiert werden können. Diese standardisierte Röntgen- und Messmethode sollte an einer Kontrollgruppe getestet werden, um die Eignung der Methodik zu untersuchen und Referenzwerte zu erstellen. Besonderer Schwerpunkt war die Überprüfung der Reliabilität der Messungen in Abhängigkeit von Lagerungsartefakten und Messwiederholungen. Danach sollten Ellbogengelenke klinisch erkrankter Hunde untersucht und mit den Ergebnissen der Kontrollgruppe verglichen werden, um herauszufinden, ob sich die Messergebnisse signifikant von gesunden Gelenken unterscheiden. Zudem wurde die Hypothese aufgestellt, dass sich die dysplastischen Ellbogengelenke anhand der röntgenologischen Messparameter in unterschiedliche Formen der humeroulnaren und humeroradialen Inkongruenz unterteilen lassen. Material und Methode: Bei 27 lahmheitsfreien Hunden wurden von 47 Ellbogengelenken Röntgenaufnahmen mit und ohne Belastung (mediolateral, kraniokaudal; Aufnahmen am liegenden, narkotisierten Tier) sowie Aufnahmen im Stehen (kraniokaudal) untersucht. Digital gemessen wurden subchondrale Gelenkspaltenabstände, subchondrale Knochenabstände und ein Winkel. Anschließend wurden 149 Hunde mit ED der Röntgen- und Messmethode unterzogen und mit den Ergebnissen der Kontrollgruppe verglichen. Anhand von gehäuft auftretenden Messwertabweichungen wurden die 149 Hunde in Untergruppen eingeteilt und erneut mit der Kontrollgruppe verglichen. Danach wurden 4 Gruppen mit jeweils unterschiedlicher Osteotomie an Radius bzw. Ulna zur zwei- und dreidimensionalen Gelenkumstellung erstellt (euthanasierte Hunde ohne Ellbogenerkrankung), der gleichen Röntgen- und Messprozedur unterzogen und mit der Kontrollgruppe und den Gruppen der kranken Hunde verglichen. Ergebnisse: Eine standardisierte und reliable Lagerung sowie Längen- und Winkelmessungen an definierten Knochenpunkten konnten mit und ohne Belastung bei gesunden und kranken Hunden etabliert werden. Mittels Normalisierung der Parameter der Längenmessungen gelang eine Vergleichbarkeit zwischen unterschiedlichen Gelenken und Projektionsebenen herzustellen. Messwerte von Aufnahmen im Stehen zeigten viele Lagerungsartefakte und eine geringe Reliabilität. Von den einzelnen Messparametern der Aufnahmen mit und ohne Belastung konnten aufgrund ihrer geringen Streuung Normwerte von der Kontrollgruppe abgeleitet werden. Eine deutliche Abgrenzung auf Grundlage signifikanter Unterschiede führte zur Bildung der Untergruppen Typ I (n=60), Typ II (n=40) und indiff (n=49) innerhalb der 149 Hunde mit ED. Unterscheidungskriterien für die Einteilung eines kranken Ellbogengelenkes in Typ I, Typ II und indiff waren 3 subchondrale Gelenkspaltenabstände (mp3, mp4, mp6), 3 aus Gelenkspaltenabständen errechnete Indizes (LI 3, LI 4, LI 6) und ein Winkel. Diese Parameter wiesen in der Kontrollgruppe eine hohe Reliabilität auf. Durch die Osteotomiemodelle konnten Parallelen zwischen Typ I und einer short ulna sowie zwischen Typ II und einem short radius ermittelt werden. Schlussfolgerungen: Röntgenaufnahmen am stehenden Hund sind nicht praktikabel, nur bedingt auswertbar und daher nicht geeignet. Anhand von Röntgenbildern mit und ohne Belastung lassen sich dagegen die Knochenverhältnisse im Gelenk beschreiben und Normwerte erstellen. Die untersuchte Methodik ist geeignet 67% erkrankter Tiere einem Inkongruenztyp (Typ I oder Typ II) zuzuordnen. Die Ergebnisse der dreidimensionalen Ulnaverkürzung und dreidimensionalen Radiusverkürzung weisen auf dreidimensionale Bewegungen der Knochenoberflächen bei Typ I bzw. Typ II im und am Gelenk hin. Ob Ellbogengelenke des Typ I (40%) von einer dreidimensionalen Osteotomie der proximalen Ulna und Ellbogengelenke des Typ II (27%) von einer Radiuselongation profitieren würden, müssen weitere Untersuchungen zeigen. Die Inkongruenz selbst konnte nicht näher quantifiziert werden. / Andreas Starke Quantification and classification of canine elbow incongruency using a standardized method for radiography and measurement Department of Small Animal Medicine, Faculty of Veterinary Medicine, Universitiy of Leipzig (79 pages, 27 Figures, Tables, 132 references) Objective: Goal of this paper was the objective quantification of elbowjoint conformation for healthy and diseased dogs under standardized conditions. Therefor we developed a method for taking x-rays of the elbow joint under load to facilitate measurements using bone-landmarks. For this we aimed to test a standardized X-ray- and measurement methodology on a control group for evaluation of the developed methodology and to compile reference values. Emphasis has been placed on the validation of the reliability of the taken measurements especially were positioning artefacts and repeat measurements were concerned. Subsequently we examined elbow joints of clinically affected dogs and compared the results to that of the control group to determine whether signifikant differences can be found in the measurements compared to those taken in joints of healthy dogs. Additionally we formulated the hypothesis that displastic Elbow joints can be grouped into humero-ulnar and humero-radial incongruencies using the developed method of measurement. Material and methods: Plain x-rays and standardized stressed x-rays (medio-lateral, cranio-caudal taken under sedation; cranio-caudal views taken while standing) of 47 elbow-joints of 27 lameness free dogs were examined. We digitally measured subchondral jointgaps, subchondral bone gaps and an angle. Afterwards 149 dogs with ED were examined using our standardized X-ray method and we compared the results to the control group. The 149 dogs were divided into subgroups using frequent measurement deviances and the subgroups again compared to the control group. Afterwards we created 4 groups based on the kind of radial or ulnar osteotomy for two- and three- dimensional joint adjustment, took measurements based on our standardized X-ray method and compared the results to the control group and ED group. Results: A reliable standardized X-ray methodology as well as length and angle measurement on defined bone landmarks with and without load could be established on healthy dogs and those with ED. Using normalization of length-measurements we were able to establish comparability between different joints and projections. Measurements from x-rays taken in a standing position showed a lot of positioning related artefacts and low reliability. We were able to compile standard values from x-rays of the control group taken with- and without load due to the low deviation of the norm values. Due to marked delination based on significant differences we were able to establish subgroups Typ I (n=60), Typ II (n=40) and Group indiff (n=49) in the ED Group. Distinction Criterions to classify an ED elbow joint in Types I, II or indiff were 3 subchondral jointgaps (mp3, mp4, mp6), three indices calculated out of joint gaps (LI 3, LI 4 and LI 6) and an angle. In the control group these parameters showed a high reliability. Using an osteotomy model we were able to draw parallels between Typ I and a short Ulna, as well as Typ II and a short radius. Conclusions: X-rays taken in a standing position are not feasible. Using x-rays taken with and without load we were able to adequately describe bone-marker relations and could compile norm values. Using our developed method we have been able to assign 67% of the examined diseased joints to a type of incongruency (Type I or II). The results of three dimensional ulna and radius shortening indicate three dimensional movement of the bone surface in Typ I or II in the joint. Whether elbow joints of Typ I (40%) benefit of a three dimensional proximal ulna-osteotomy or joints of Typ II (27%) would benefit of a radial elongation needs to be shown in further studies.

Santrauka Baigiamojo darbo tema Šunų klubo sąnario displazija genetiniai aspektai Baigiamasis darbas atliktas 2012 - 2014 metais Biologiniu sistemų ir genetinių tyrimų institute, K. Janušausko gyvūnų genetikos laboratorijoje. Baigiamojo darbo kiekis 53 puslapių, 15 paveikslėlių , 8 lentelės. Darbo objektas ir uždaviniai. Išanalizuoti šunų klubo sąnario displazijos paveldimumą . Uždaviniai: išanalizuoti literatūrą apie šunų klubo sąnario displazijos genetinius aspektus , klinikinius požymius , diagnostikos ir gydymo metodus , priežastis, paveldėjimą , įvairių veislių šunų displazijos paplitimą, įvertinti genetinių veiksnių - veislės, amžiaus ir lyties įtaką - šunų klubo sąnario displazijos atsiradimui. Mokslinių tyrimų metodologija. Surinkti ir išanalizuoti literatūrą apie šunų klubo sąnario displazijos paplitimą " Jokovo veterinarijos centras" smulkių gyvūnų klinikoje. Rezultatai ir išvados. 2009 - 2013 metais buvo ištirta 638 šunų, iš kurių 169 nustatyta KDS, tai sudaro 26,5% visų ištirtų šunų. Dažniausiai KDS sirgo Amerikiečių stafordšyro terjerai (66,6%), Bordo dogai (66,6 %), Kaukazo aviganiai (57,1%), Anatolijos Karabašai (50%), Korsikos šuo (50%), Leonbergeriai (50%) ir Rytų Europos aviganiai (50%). Rečiausiai sirgo - Sibiro haskiai (7,1%), Amerikiečių akita (10%), samojedai (10%) ir dobermanai (11,1%). Dažniau KSD pasireikšdavo patelėms (31,5%) nei patinams (26,3%). Pagal pasaulinės organizacijos OFA duomenis, atliktus 1974 - 2012 metais Bordo dogai, senbernarai ir... [toliau žr. visą tekstą] / Summary Topic of Final study thesis Canine hip dysplasia genetic aspects Final work accomplished in the year 2012 – 2014 in Institute of Biology Systems and Genetics, K. Janušauskas Laboratory of Animal Genetics. Volume of Final work 53 page original, 15 pictures, 8 tables. Object and tasks of work. Analyse heredity of canine hip dysplasia. Tasks: analyse literature about canine hip dysplasia genetic aspects, clinical signs, diagnosis and treatment methods, causes, inheritances, prevalence of dysplasia in different breeds of dogs; evaluate influence of genetic factors - breed, age and sex – to occurrence of canine hip dysplasia. Research methodology. Gathering and analysing literature about canine hip dysplasia prevalence in “Jokov veterinary center”. Results and conclusions. During 2009 – 2013 years were examined 638 dogs for hip dysplasia manifestation, of which 169 established HD, accounting for 26,5% of the tested dogs. Mostly HD had the American Staffordshire Terrier (66.6%) Dogue de Bordeaux (66.6%), Caucasian shepherd (57.1%), the Anatolian Shepherd Dog (50%), the Corsican dog (50%), Leonberger (50%) and East European shepherd (50%). Least amount of HD were in - Siberian Huskies (7.1%), American akita (10%), Samoyed (10%) and a Dobermans (11.1%). More often CHD were fixed in bitches (31,5%) than in male dogs (26,3%). Up to 18 months age, hip dysplasia established 26,6%, and over 18 months – 31,8%. According to the global organization of OPA made researches in 1974 - 2... [to full text]