– The aim of this study was to investigate pre‐injury factors, causes of dental injuries and healing complications after traumatic injuries to permanent teeth. The analysed sample comprised 889 ...permanent teeth of 384 patients, who were treated in the Dentistry Department in Faculty Hospital in Pilsen. Enamel‐dentin fractures 233 teeth (26.2%) and lateral luxations 207 teeth (23.3%) were the most frequent injuries. The age of the patients at the time of injury varied between 7 and 65 years. Predominantly, children were affected 587 injured teeth (66.0%). The most frequent causes of injuries in patients older than 11 years were various sport activities, predominantly bicycling. Pulp necrosis was observed in 239 teeth (26.9%). It was the most frequent post‐traumatic complication in all types of dental traumas. Teeth with a completed root formation demonstrated a higher prevalence of pulp necrosis than teeth with an incomplete root formation in all types of luxation injuries. External root resorption was observed in 144 teeth. The rate of inflammatory resorption differed between the various types of luxation injuries (extrusive luxation 5.6%, lateral luxation 11.6%, intrusive luxation 33.3%). Following avulsion and replantation, active inflammatory resorptions were diagnosed in 13 (26.5%) of 49 replanted teeth and ankylosis/replacement resorptions were observed in 21 (42.9%) of 49 replanted teeth. After avulsion, primarily, immature teeth were affected by these complications. Within the observation period of 5 years, 39 teeth (4.4%) had to be removed (16 teeth with root fractures, 19 avulsed and replanted teeth, 3 luxated teeth, 1 tooth with crown‐root fracture).
The aim of this study is to evaluate the results of dentigerous cysts enucleation with preservation of cyst-associated teeth as a single procedure in a group of children and preadolescents. A ...retrospective case series of seven patients with 15 unerupted developing teeth associated with or adjacent to dentigerous cysts was conducted. Patients were treated using the uniform surgical protocol (cystectomy, preservation of cyst-associated teeth, without use of orthodontic traction, primary wound closure). The metric analysis of the cysts and unerupted teeth on CBCT and an evaluation of the state of involved teeth after the treatment was performed. The mean age of patients was 9.0 ± 2.1 years (range 5–12 years, median = 9 years). All teeth erupted spontaneously. No serious postoperative complications or recurrences of lesions were detected. The mean follow-up was 53.1 ± 15.7 months (range 25–71 months, median = 52 months). The cystectomy of dentigerous cysts with preservation of associated teeth may be considered an alternative to marsupialization in children and preadolescents.
– The aim of this study was to find out the causes that lead to dental avulsion in children, to analyze the effectiveness of our treatment and the response of the adults when such incidents occur ...and finally to determine the occurrence of posttraumatic complications some time after the injury, especially the resorption of the affected teeth root. We analyzed the documentations of a sample of patients containing 57 children who had a total of 90 avulsed teeth and were treated in Dentistry Department of Medical Faculty in Pilsen, Czech Republic, in the years between 1995 and 2005. We discovered that most frequently the children experience dental avulsion in the age between 8 and 11 years old, the most affected teeth are the upper central incisors and the most frequent causes are sports and games which are very common in these ages, in various environments, like schools, sport fields and home. The majority of the children were transferred to the Dentistry Department either quite long after the avulsion incident and without the avulsed teeth, or with the avulsed teeth which were carried in an inappropriate transport medium, indicating that there is insufficient knowledge of adult people, especially the ones who are in daily contact with children, on how to provide first aid in cases of dental avulsion.
This study is focused on the contemporary possibilities of the treatment of the teeth with internal root resorption. The aim was to find out the most frequent etiological factors, anamnestic ...information, clinical findings and forms of the pathogenesis of internal root resorption and also to determine the most convenient way of treatment of the affected teeth, including the way of definite root canal filling. Clinical part of this study included a retrospective study of 25 cases (14 men and 11 women) of teeth with internal resorption that they were diagnosed and treated in our department, in the period between 1985-2005. Most of internal root resorption cases (84%) were located in the frontal region of the oral cavity. The most frequent teeth afflicted with internal resorption (total of 8 teeth) were upper lateral incisors. The youngest among patients was 17 years old, the oldest was 55 years old and the average age of all patients was 34,6 years. The most frequent localization of internal resorption (13 out of 25 cases) was in the gingival root third, then in middle root third (7 out of 25 cases) and finally in apical root third (3 out of 25 cases). Two times we diagnosed internal resorption in the crown part of pulp cavity. In our study group, acute trauma was the most frequent cause of occurrence...
The aim of this study is to evaluate the possibility of achieving more effective and prolonged sedation in pigs by the oral administration of increased doses of azaperone and to evaluate its safety. ...This was performed through a prospective randomised and double blinded study. A total of 32 weaned piglets were divided into 4 groups (8 in each group). Group A was given 1 ml of saline orally and served as the control group. Group B received azaperone orally at a dose of 4 mg/kg b.w. Group C received azaperone orally at a dose of 8 mg/kg b.w. Group D was given azaperone orally at a dose of 12 mg/kg b.w. The response to the defined stimulus, movement level, degree of salivation, body temperature, respiratory frequency, blood plasma azaperone concentration and biochemical variables were included in the trial. We found that by increasing the dose of the orally administered azaperone, the onset of the sedation is faster, the end of the sedation starts later and the sedation time is longer. However, the use of higher doses of oral azaperone is not suitable for piglets because the doses negatively affect the respiratory rate, body temperature, some biochemical parameters and cause the immobility of the piglets.
Although numerous pathogenic mutations have been identified in various subunits of N-methyl-D-aspartate receptors (NMDARs), ionotropic glutamate receptors that are central to glutamatergic ...neurotransmission, the functional effects of these mutations are often unknown. Here, we combined in silico modelling with microscopy, biochemistry, and electrophysiology in cultured HEK293 cells and hippocampal neurons to examine how the pathogenic missense mutation S688Y in the GluN1 NMDAR subunit affects receptor function and trafficking. We found that the S688Y mutation significantly increases the EC
of both glycine and D-serine in GluN1/GluN2A and GluN1/GluN2B receptors, and significantly slows desensitisation of GluN1/GluN3A receptors. Moreover, the S688Y mutation reduces the surface expression of GluN3A-containing NMDARs in cultured hippocampal neurons, but does not affect the trafficking of GluN2-containing receptors. Finally, we found that the S688Y mutation reduces Ca
influx through NMDARs and reduces NMDA-induced excitotoxicity in cultured hippocampal neurons. These findings provide key insights into the molecular mechanisms that underlie the regulation of NMDAR subtypes containing pathogenic mutations.
NMDA receptors (NMDARs) are ionotropic glutamate receptors that play a key role in excitatory neurotransmission. The number and subtype of surface NMDARs are regulated at several levels, including ...their externalization, internalization, and lateral diffusion between the synaptic and extrasynaptic regions. Here, we used novel anti-GFP (green fluorescent protein) nanobodies conjugated to either the smallest commercially available quantum dot 525 (QD525) or the several nanometer larger (and thus brighter) QD605 (referred to as nanoGFP-QD525 and nanoGFP-QD605, respectively). Targeting the yellow fluorescent protein-tagged GluN1 subunit in rat hippocampal neurons, we compared these two probes to a previously established larger probe, a rabbit anti-GFP IgG together with a secondary IgG conjugated to QD605 (referred to as antiGFP-QD605). The nanoGFP-based probes allowed faster lateral diffusion of the NMDARs, with several-fold increased median values of the diffusion coefficient (
). Using thresholded tdTomato-Homer1c signals to mark synaptic regions, we found that the nanoprobe-based
values sharply increased at distances over 100 nm from the synaptic edge, while
values for antiGFP-QD605 probe remained unchanged up to a 400 nm distance. Using the nanoGFP-QD605 probe in hippocampal neurons expressing the GFP-GluN2A, GFP-GluN2B, or GFP-GluN3A subunits, we detected subunit-dependent differences in the synaptic localization of NMDARs,
value, synaptic residence time, and synaptic-extrasynaptic exchange rate. Finally, we confirmed the applicability of the nanoGFP-QD605 probe to study differences in the distribution of synaptic NMDARs by comparing to data obtained with nanoGFPs conjugated to organic fluorophores, using universal point accumulation imaging in nanoscale topography and direct stochastic optical reconstruction microscopy.
Our study systematically compared the localization and mobility of surface NMDARs containing GFP-GluN2A, GFP-GluN2B, or GFP-GluN3A subunits expressed in rodent hippocampal neurons, using anti-green fluorescent protein (GFP) nanobodies conjugated to the quantum dot 605 (nanoGFP-QD605), as well as nanoGFP probes conjugated with small organic fluorophores. Our comprehensive analysis showed that the method used to delineate the synaptic region plays an important role in the study of synaptic and extrasynaptic pools of NMDARs. In addition, we showed that the nanoGFP-QD605 probe has optimal parameters for studying the mobility of NMDARs because of its high localization accuracy comparable to direct stochastic optical reconstruction microscopy and longer scan time compared with universal point accumulation imaging in nanoscale topography. The developed approaches are readily applicable to the study of any GFP-labeled membrane receptors expressed in mammalian neurons.
Tacrine (THA), a long withdrawn drug, is still a popular scaffold used in medicinal chemistry, mainly for its good reactivity and multi-targeted effect. However, THA-associated hepatotoxicity is ...still an issue and must be considered in drug discovery based on the THA scaffold. Following our previously identified hit compound 7-phenoxytacrine (7-PhO-THA), we systematically explored the chemical space with 30 novel derivatives, with a focus on low hepatotoxicity, anticholinesterase action, and antagonism at the GluN1/GluN2B subtype of the NMDA receptor. Applying the down-selection process based on in vitro and in vivo pharmacokinetic data, two candidates, I-52 and II-52, selective GluN1/GluN2B inhibitors thanks to the interaction with the ifenprodil-binding site, have entered in vivo pharmacodynamic studies. Finally, compound I-52, showing only minor affinity to AChE, was identified as a lead candidate with favorable behavioral and neuroprotective effects using open-field and prepulse inhibition tests, along with scopolamine-based behavioral and NMDA-induced hippocampal lesion models. Our data show that compound I-52 exhibits low toxicity often associated with NMDA receptor ligands, and low hepatotoxicity, often related to THA-based compounds.
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•A series of 30 7-phenoxytacrine derivatives were designed, synthesized and screened.•Interaction with AChE and GluN1/GluN2B via ifenprodil-binding site was confirmed.•Compound I-52 is a lead candidate with favorable behavioral and neuroprotective effects under various in vivo models.•Compound I-52 is low hepatotoxic as demonstrated by the biotransformation study.
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