During development, tooth germs undergo various morphological changes resulting from interactions between the oral epithelium and ectomesenchyme. These processes are influenced by the extracellular matrix, the composition of which, along with cell adhesion and signaling, is regulated by metalloproteinases. Notably, these include matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs), and a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs). Our analysis of previously published scRNAseq datasets highlight that these metalloproteinases show dynamic expression patterns during tooth development, with expression in a wide range of cell types, suggesting multiple roles in tooth morphogenesis. To investigate this, Marimastat, a broad-spectrum inhibitor of MMPs, ADAMs, and ADAMTSs, was applied to ex vivo cultures of mouse molar tooth germs. The treated samples exhibited significant changes in tooth germ size and morphology, including an overall reduction in size and an inversion of the typical bell shape. The cervical loop failed to extend, and the central area of the inner enamel epithelium protruded. Marimastat treatment also disrupted proliferation, cell polarization, and organization compared with control tooth germs. In addition, a decrease in laminin expression was observed, leading to a disruption in continuity of the basement membrane at the epithelial-mesenchymal junction. Elevated hypoxia-inducible factor 1-alpha gene (Hif-1α) expression correlated with a disruption to blood vessel development around the tooth germs. These results reveal the crucial role of metalloproteinases in tooth growth, shape, cervical loop elongation, and the regulation of blood vessel formation during prenatal tooth development.NEW & NOTEWORTHY Inhibition of metalloproteinases during tooth development had a wide-ranging impact on molar growth affecting proliferation, cell migration, and vascularization, highlighting the diverse role of these proteins in controlling development.

• MeSH
• Hypoxia-Inducible Factor 1, alpha Subunit metabolism   genetics   MeSH
• Matrix Metalloproteinase Inhibitors pharmacology   MeSH
• Hydroxamic Acids pharmacology   MeSH
• Metalloproteases metabolism   genetics   MeSH
• Molar embryology   growth & development   metabolism   enzymology   MeSH
• Morphogenesis MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Odontogenesis * MeSH
• Cell Proliferation * MeSH
• Gene Expression Regulation, Developmental MeSH
• Tooth Germ embryology   metabolism   enzymology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Řeč, pohyb, správný ontogenetický vývoj jedince, kognice, emoce, schopnost učit se, paměť – a s výčtem bychom mohly pokračovat. To vše je přímo závislé na rovnováze, za kterou stojí rytmus realizovaný v optimálním tempu s dostatečnou intenzitou a v pravidelně se opakujících, časově dobře volených intervalech. Často si, vlivem zautomatizovaných činností, neuvědomujeme, s jakou pravidelností, plánováním a organizovaností vykonáváme základní motorické vzorce, které se intuitivně a naprosto přirozeně učíme prostřednictvím dostatečně intenzivních intervalových rytmických aktivit. A právě terapie v logopedické praxi vedená intenzivně a intervalově napomáhá u dětí a žáků příznivě ovlivňovat prognózu jejich řečového vývoje, bez ohledu na to, zda využíváme direktivní, nebo nedirektivní přístup. To je mimo jiné potvrzeno také v závěru uvedeným stručným kazuistickým příkladem klientky se závažnou myofunkční poruchou.

Speech, movement, proper ontogenetic development of the individual, cognition, emotions, ability to learn, memory and the list could go on. All of these are directly dependent on balance, which is based on the rhythm realised at an optimal pace with sufficient intensity and in regularly recurring intervals of well-chosen timing. Often, due to automated activities, we are not aware of the regularity, planning and organisation with which we perform the basic motor patterns that we intuitively and quite naturally learn through sufficiently intense interval rhythmic activities. And it is precisely the therapy in Speech Therapy practice conducted intensively and at intervals, that helps to positively influence the prognosis of children and pupils in their speech development, regardless of whether we use a directive or non-directive approach. This is confirmed, among other things, by the brief case example of a client with a severe myofunctional disorder, presented in the end of the paper.

• MeSH
• Dysarthria etiology   therapy   MeSH
• Language Disorders diagnosis   etiology   therapy   MeSH
• Language Tests MeSH
• Humans MeSH
• Malocclusion MeSH
• Nervous System growth & development   MeSH
• Speech Disorders * diagnosis   etiology   therapy   MeSH
• Speech Therapy methods   MeSH
• Learning physiology   MeSH
• Child Development MeSH
• Check Tag
• Humans MeSH

Úvod: V důsledku metabolických dějů dochází v živých strukturách k endogenní produkci chemiluminiscence, kterou také označujeme jako biologickou autochemiluminiscenci (BAL). Generování BAL je úzce spojeno s oxidačními procesy, tvorbou volných radikálů a obecně oxidačně-redukční homeostázou zkoumaného biologického materiálu. BAL byla již dříve studována v savčích buněčných modelech a tkáních. Doposud ovšem nebyl tento jev popsán v případě struktur zubní tkáně. Kromě endogenně generované BAL lze BAL indukovat i exogenně, a to jak fyzikálními (UV záření, mechanické poškození, teplo), tak i chemickými (oxidační činidla, např. H2O2) a biotickými (patogeny) faktory. Metodika: V předložené práci byla zkoumána endogenně produkovaná i exogenně indukovaná BAL v povrchových a vnitřních strukturách semiretinovaných a retinovaných třetích molárů, které byly indikovány k extrakci zubním lékařem pro jejich nevhodné uložení v čelisti u dvou pacientů (žena, 21 let, muž, 22 let). Detekce BAL byla provedena po mechanickém odstranění zubního plaku rotačním kartáčkem. Pomocí piezoelektrické pily byly připraveny podélné řezy vedené tak, aby došlo k odhalení všech vnitřních částí zubu. Takto připravené vzorky – celého vnitřního řezu a vnější části celého zubu – byly podrobeny detekci BAL ve světlotěsné komoře za použití fotonásobičového modulu. Následně byly vzorky ošetřeny roztokem oxidačního činidla 3% H2O2 a redukčního činidla 10 mM TCEP (tris(karboxyethyl)fosfin). Výsledky: U obou vzorků zubu bylo prokázáno, že produkují BAL. Produkce endogenní chemiluminiscence byla pozorována ve vnitřních strukturách zubu (18 600 pulzů/600 s), která byla přibližně 2,7krát vyšší než BAL detekovaná na povrchových strukturách zubu (6 900 pulzů/600 s). Po ošetření H2O2 došlo k významnému (až 14násobnému) nárůstu BAL pro vnitřní struktury zubu ve srovnání s bazální intenzitou endogenně produkované BAL. Aplikace TCEP (negativní kontrola) vedla k mírnému potlačení produkce BAL. Závěr: Výsledky této pilotní studie ukazují, že BAL může být produkována nejenom měkkými tkáněmi, ale i tvrdou zubní tkání. Získané výsledky by mohly být využity k výzkumu metabolické aktivity a reaktivity vnitřních i vnějších částí zubu, a to především v kontextu výzkumu oxidačněredukční homeostázy. Detekce BAL by také mohla být aplikována pro vývoj nových zobrazovacích technik.

Introduction: As a result of metabolic processes, the endogenous production of chemiluminescence occurs in living biological structures, which we also refer to as biological autochemiluminescence (BAL). The generation of BAL is closely connected with oxidation processes, the formation of free radicals, and in general the redox homeostasis of the investigated biological material. BAL has previously been studied in mammalian cells and tissues. So far, however, this phenomenon has not been described in dental tissue structures. In addition to endogenously generated BAL, BAL can be exogenously induced by physical (UV radiation, mechanical damage, heat), chemical (oxidizing agents, e.g. H2O2) or biotic (pathogens) factors. Methods: Endogenously and exogenously induced BAL were investigated on the surface and internal structures of semi-impacted and impacted third molars, which were indicated for extraction by a dentist due to their inappropriate placement in the jaw in two patients (a 21-year-old woman and a 22-year-old man). BAL detection was performed with samples after dental plaque was mechanically removed with a rotating brush. Using a piezosurgery unit with a saw headpiece, longitudinal sections were made to reveal all internal parts of the tooth. The samples prepared in this way – the entire internal section and the external part of the entire tooth – were subjected to BAL detection in a dark chamber using H7360-01 PMT photomultiplier. Subsequently, the samples were treated with a solution of the oxidizing agent 3% H2O2 or the reducing agent 10 mM TCEP (tris(carboxyethyl)phosphine). Results: Both tooth samples were shown to produce BAL. Endogenous chemiluminescence production was observed in the internal structures of the tooth (18,600 counts/600 s), which was 2.7-fold higher than the BAL detected on the tooth outer surfaces (6,900 counts/600 s). After H2O2 treatment, there was a significant (up to 14-fold) increase in BAL for internal tooth structures compared to the basal intensity of endogenously produced BAL. The application of TCEP (negative control) resulted in a residual suppression of BAL production. Conclusion: The results of this pilot study show that BAL can be produced not only by soft tissues but also by hard dental tissue. The obtained results could be used for further research of the metabolic activity and reactivity of the inner and outer parts of the tooth, especially in the context of redox biology research. BAL detection could also be applied in the development of new imaging techniques.

• MeSH
• Humans MeSH
• Luminescence * MeSH
• Luminescent Measurements MeSH
• Molar MeSH
• Oxidative Stress MeSH
• Hydrogen Peroxide chemistry   MeSH
• Pilot Projects MeSH
• Tooth Components MeSH
• Check Tag
• Humans MeSH

Development of dentition is a commonly studied process as a representative of the development of ectodermal derivates. A key step is the formation of a signaling center called the enamel knot (EK), which organizes tooth crown formation. In the mouse lower jaw, the anterior part of the tooth-forming region undergoes a series of complex events before the first molar primary EK can form more posteriorly and the tooth can progress through the cap stage. Although much is known about the molecular factors involved in tooth development, disentangling their specific roles is difficult. In this study, we circumvented this problem by isolating the posterior part of the tooth-forming region at embryonic day 13.5 and cultivating it in vitro. By treating them with molecules activating or inhibiting Sonic hedgehog (Shh) and fibroblast growth factor (Fgf) pathways, we demonstrate that Shh plays the role of an inhibitor of EK formation, and we suggest that the FGF pathways may have both positive and negative roles, as seen in hair. By RNA-sequencing of the cultivated isolates after 0, 16, or 24 h in vitro, respectively, we screened for genes whose expression varies with EK and cap formation and pointed to Cdkn2b and Sema3b as 2 promising candidates in this process.

• MeSH
• Fibroblast Growth Factors physiology   MeSH
• Molar embryology   MeSH
• Mice MeSH
• Odontogenesis * physiology   genetics   MeSH
• Hedgehog Proteins physiology   metabolism   MeSH
• Signal Transduction MeSH
• Gene Expression Regulation, Developmental MeSH
• Tooth Crown * embryology   MeSH
• Dental Enamel * embryology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Cílem článku je podělit se o naše zkušenosti se zhotovováním 3D modelů autotransplantovaných zubů a jejich vlastním použitím při výkonu. Zhotovení 3D repliky zubu pro chirurgické využití má tři fáze: tvorba virtuálního modelu repliky, výroba pomocí 3D tiskárny a sterilizace. Na naše oddělení byla doporučena 37letá zdravá pacientka k návrhu řešení stavu zubů ve II. kvadrantu. Po posouzení klinického stavu, zhodnocení CBCT (cone beam computed tomography) a po domluvě s pacientkou jsme se rozhodli pro extrakce zubů 26, 27 a následně autotransplantaci zubu 28 do místa 26. Na základě dat z CBCT jsme vytvořili dva 3D modely autotransplantovaného zubu a provedli jejich sterilizaci. Po extrakci zubů 26 a 27 jsme extrakční ránu 26 upravili za pomoci vytvořených 3D modelů a provedli autotransplantaci, přičemž extraalveorální čas zubu 28 byl pouze 21 vteřin. Hojení proběhlo bez komplikací a pacientka je s výsledkem spokojená. Autotransplantace je jednou z možností volby při řešení ageneze nebo ztráty zubu. Využití 3D modelu při operačním zákroku vede k výraznému zkrácení extraalveolárního času autotransplantátu a ke snížení nebezpečí poškození buněk periodontálního ligamenta opakovaným vkládáním autotransplantátu do připravované štoly.

The aim of this study is to show the experience with autotransplanted 3D model development and its use during surgery. The development of a 3D model has undergone three phases: building the virtual model, 3D printing and finally sterilisation. A 37-year-old female patient was recommended to our department for treatment of the 2nd quadrant. After planning the extraction of 26, 27 and consequently autotransplantation of tooth 28 was decided. According to CBCT data, two 3D models of the autotransplanted tooth were built and plasma sterilisation was done. After extraction of 26 and 27, a tooth cavity was prepared for the 3D model phantom and the autotransplantation was finished; extra alveolar time of tooth 28 was only 21 seconds. Healing period had no adverse problems and the patient was very satisfied with the result. Autotransplantation is one of the possible choices when treating malformation or tooth loss. The use of a 3D phantom during surgery leads to shortening of surgery time, thus lowering the risk of periodontal tissue damage by repeated testing of the right size of the tooth position and size.

• MeSH
• Printing, Three-Dimensional * MeSH
• Autografts classification   transplantation   MeSH
• Transplantation, Autologous * methods   MeSH
• Adult MeSH
• Tooth Extraction methods   MeSH
• Humans MeSH
• Molar transplantation   MeSH
• Cone-Beam Computed Tomography methods   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH

Infekce postihující kořenový kanálek zubu je nejčastější příčinou vzniku apikální periodontitidy (AP). Chronický zánět v periodonciu může vést k rozvoji radikulární cysty (RC), která patří k zánětlivým odontogenním cystám (OC). Další skupinu tvoří OC vývojové, k nimž se mimojiné řadí cysta folikulární (FC) a odontogenní keratocysta (OKC). Pro optimální volbu terapie a manažment pacientů je klasifikace OC, která reflektuje jejich etiopatogenezi a zahrnuje genetické faktory, zásadní. Cílem projektu je determinace rizikových faktorů rozvoje OC a zlepšení jejich diagnostiky. Projekt zahrnuje studii mikrobiomu kořenového kanálku zubu a OC zánětlivého původu, genetické asociační studie se zaměřením na imunitní profil pacientů a geny zapojené do odontogeneze, komparativní studie expresních profilů genů v různých typech OC, a studie vybraných molekulárních drah v patogenezi OC na animálním modelu. Na základě získaných výsledků se pokusíme navrhnout panel markerů pro predikci vzniku OC a jejich diferenciální diagnostiku.; Infections affecting the root canal of the tooth are the most common cause of apical periodontitis (AP). Chronic inflammation in the periodontium may lead to the development of a radicular cyst (RC), a type of inflammatory odontogenic cyst (OC). OC of developmental origin also includes dentigerous cysts (DC) and odontogenic keratocysts (OKC). Correct classification of OCs reflecting their etiopathogenesis including genetic factors is crucial for choosing an optimum therapy and patient management. The aim of the project is to identify risk factors of OC development and improve their diagnosis. The project includes study of microbiome present in the root canal, genetic association studies focused on patients ́immune profiling and influence of genes envolved in odontogenesis, comparative studies of gene expression profiles in various types of odontogenic cysts, and study of selected molecular pathways in OC pathogenesis in an animal model. Based on the obtained results we will propose a panel of markers for prediction of OC development and differential diagnosis of OC types.

• Keywords
• Genetická predispozice, Genetic predisposition, sequencing, Nanočástice, imunogenetika, nanoparticle, sekvenování, immunogenetics, apical periodontitis, orální mikrobiom, oral microbiome, SHH signalizace, in vivo animální model, odontogenní cysta, apikální periodontitida, SHH signaling, in vivo animal model, odontogenic cyst,

• NML Publication type
• závěrečné zprávy o řešení grantu AZV MZ ČR

• MeSH
• Child MeSH
• Upper Extremity diagnostic imaging   MeSH
• Correlation of Data MeSH
• Humans MeSH
• Adolescent MeSH
• Radiography, Panoramic MeSH
• Statistics as Topic MeSH
• Age Determination by Skeleton methods   statistics & numerical data   MeSH
• Age Determination by Teeth * methods   MeSH
• Age Factors MeSH
• Child Development MeSH
• Tooth growth & development   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Clinical Study MeSH

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy caused by a 1.5 Mb tandem duplication of chromosome 17 harbouring the PMP22 gene. This dose-dependent overexpression of PMP22 results in disrupted Schwann cell myelination of peripheral nerves. To obtain better insights into the underlying pathogenic mechanisms in CMT1A, we investigated the role of PMP22 duplication in cellular homeostasis in CMT1A mouse models and in patient-derived induced pluripotent stem cells differentiated into Schwann cell precursors (iPSC-SCPs). We performed lipidomic profiling and bulk RNA sequencing (RNA-seq) on sciatic nerves of two developing CMT1A mouse models and on CMT1A patient-derived iPSC-SCPs. For the sciatic nerves of the CMT1A mice, cholesterol and lipid metabolism was downregulated in a dose-dependent manner throughout development. For the CMT1A iPSC-SCPs, transcriptional analysis unveiled a strong suppression of genes related to autophagy and lipid metabolism. Gene ontology enrichment analysis identified disturbances in pathways related to plasma membrane components and cell receptor signalling. Lipidomic analysis confirmed the severe dysregulation in plasma membrane lipids, particularly sphingolipids, in CMT1A iPSC-SCPs. Furthermore, we identified reduced lipid raft dynamics, disturbed plasma membrane fluidity and impaired cholesterol incorporation and storage, all of which could result from altered lipid storage homeostasis in the patient-derived CMT1A iPSC-SCPs. Importantly, this phenotype could be rescued by stimulating autophagy and lipolysis. We conclude that PMP22 duplication disturbs intracellular lipid storage and leads to a more disordered plasma membrane owing to an alteration in the lipid composition, which might ultimately lead to impaired axo-glial interactions. Moreover, targeting lipid handling and metabolism could hold promise for the treatment of patients with CMT1A.

• MeSH
• Cell Membrane * metabolism   MeSH
• Charcot-Marie-Tooth Disease * genetics   metabolism   pathology   MeSH
• Gene Duplication MeSH
• Homeostasis * physiology   MeSH
• Induced Pluripotent Stem Cells * metabolism   MeSH
• Humans MeSH
• Lipid Metabolism * physiology   MeSH
• Myelin Proteins * metabolism   genetics   MeSH
• Mice MeSH
• Sciatic Nerve metabolism   MeSH
• Schwann Cells * metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: This 20-year retrospective study aimed to evaluate the treatment methods used in patients with impacted maxillary permanent canines and to determine the occurrence of ankylotic and resorptive processes and their association with potential risk factors. METHODS: The cohort consisted of 351 consecutive Caucasian patients (120 males and 231 females, mean age 18.4 and 19.9 years, respectively) with 420 impacted maxillary permanent canines. CT and CBCT findings were subsequently confirmed during surgery. Statistical analyses were performed by the generalized linear models, Pearson x2 and Fisher exact tests using the statistical programs R and Statistica v. 14. RESULTS: A total of 273 (65.0%) impacted canines were aligned in the dental arch by orthodontic traction after surgical exposure, this treatment was predominant in patients under 20 years of age. Surgical extraction was performed in 115 (27.2%) impacted canines and was more common in older patients. Ankylotic changes were recorded in 61 (14.5%) impacted canines. The probability of ankylosis increased with age, particularly after the patient's 20th year of life (p < 0.001). Patients were 1.2% likely to develop ankylosis at age 15 years, 4.3% at age 20 years, 14.1% at age 25 years, and 96.8% at age 45 years. Invasive cervical root resorption (ICRR) was found in 8 (1.9%) canines. In 4 canines (1.0%), root ankylosis in addition to ICRR was observed. In contrast to ankylosis, whose frequency of occurrence increased with age, the occurrence of ICRR resulting from PDL damage during surgery was more typical in younger patients. Canines in a high position above the root apices of the adjacent teeth, with a horizontal inclination of the longitudinal axis, with the crown located deep in the center of the alveolar bone and with labiopalatal position, should be considered critically impacted canines with a high risk to failure of orthodontic traction. CONCLUSION: In conclusion, the treatment of impacted canines depends mainly on the age of the patient, and the position and inclination of the longitudinal axis of the impacted tooth. To select an adequate treatment method, we recommend CBCT examination, which allows a precise analysis of the position of impacted canines.

• MeSH
• Child MeSH
• Adult MeSH
• Tooth Extraction MeSH
• Cohort Studies MeSH
• Humans MeSH
• Maxilla * surgery   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Orthodontic Extrusion methods   MeSH
• Tomography, X-Ray Computed MeSH
• Cone-Beam Computed Tomography * MeSH
• Root Resorption diagnostic imaging   etiology   MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Cuspid * diagnostic imaging   MeSH
• Age Factors MeSH
• Tooth, Impacted * surgery   diagnostic imaging   MeSH
• Tooth Ankylosis * diagnostic imaging   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Rozštěpové vady obličeje se řadí mezi nejčastější vrozené vývojové vady. Mají vliv na vzhled celého obličeje a zároveň funkční důsledky závislé na rozsahu rozštěpu. Terapie je vzhledem ke komplexnosti vady multidisciplinární, časově náročná a probíhá dlouhodobě, protože pacient s rozštěpovou vadou vyžaduje péči týmu odborníků od narození až do dospělosti. Autoři článku přináší v první části přehled etiologie, klasifikace, diagnostiky a základních principů multidisciplinární péče rozštěpových vad v České republice, které se v jednotlivých dílčích krocích mohou lišit dle zvyklostí jednotlivých pracovišť, základní postupy se však v principu neliší. V druhé části představují průběh perioperační péče o novorozence po rekonstrukci rozštěpu rtu a nosu v časném neonatálním období včetně charakteristiky souboru pacientů ošetřených ve FN Motol v období posledních 5 let.

Cleft facial defects are among the most common congenital craniofacial defects. They not only affect the appearance of the entire face, but also have multiple functional consequences depending on the extent of the cleft. Total clefts have a major impact on the newborn's ability to breastfeed by complicating adequate latching. They also affect the development of the upper jaw, speech and dentition, children are more prone to tooth decay and upper respiratory tract infections, and almost all affected patients show dysfunction of the Eustachian tube with the subsequent development of secretory otitis media. Due to the complexity of the cleft facial defects, therapy is usually multidisciplinary and time-consuming, as the patient requires care from birth to adulthood. In the first part, the authors of the article provide an overview of the etiology, classification, diagnosis and basic principles of multidisciplinary care for cleft defects in the Czech Republic. In the second part, they describe the course of perioperative care for newborns after reconstruction of a cleft facial defect in the early neonatal period, including the characteristics of the group of patients treated at the Motol University Hospital in the past 5 years.

• MeSH
• Stomatognathic System Abnormalities * diagnosis   etiology   classification   therapy   MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Face * surgery   pathology   MeSH
• Orthognathic Surgical Procedures methods   statistics & numerical data   MeSH
• Perioperative Care methods   nursing   MeSH
• Patient Care Team MeSH
• Plastic Surgery Procedures methods   statistics & numerical data   MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH
• Publication type
• Review MeSH