RESUMEN

OBJECTIVE: To observe the necessity and usefulness of follow-up Magnetic Resonance Imaging (MRI) and Computed Tomography Imaging (CTI) after RFA of osteoid osteoma. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Department of Radiology, Sisli Etfal Training and Research Hospital, Istanbul, Turkey, between May 2015 and January 2020. METHODOLOGY: Patients, who underwent CT-guided RFA for osteoid osteoma treatment, were followed-up both clinically and radiologically. MRI was recommended between the third and sixth months and CTI at 12th month or later for follow-up. All the pre and post-treatment radiological images were evaluated retrospectively. Radiological recovery was noted in three categories as complete/almost-complete, partial, and minimal-no recovery according to the healing of pre-treatment radiological findings. RESULTS: One-hundred and thirty-one patients with at least one follow-up CT or MRI were included. All had technically and clinically successful RFA treatments. Of 131 patients, 64.1% had CTI and 82.4% had MRI follow-up. In follow-up images, complete/almost-complete-recovery was observed in 70.2%, partial recovery in 26.7%, and minimal recovery in 3.1% of the cases. Re-ablation therapies were applied in 2 cases in this study due to pain recurrence after three months of successful treatments. CONCLUSION: Radiological follow-up is beneficial for the evaluation of outcome after RFA of osteoid-osteoma. At least one follow-up MRI may be helpful for the assessment of healing or recurrence. Follow-up CTI may not be needed unless planning a re-ablation. KEY WORDS: Osteoma osteoid, Radiofrequency ablation, Tomography, Magnetic resonance imaging.

Asunto(s)

Neoplasias Óseas , Ablación por Catéter , Osteoma Osteoide , Radiología , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Ablación por Catéter/métodos , Humanos , Osteoma Osteoide/diagnóstico por imagen , Osteoma Osteoide/patología , Osteoma Osteoide/cirugía , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento

RESUMEN

We identify a set of common phenotypic modifiers that interact with five independent autism gene orthologs (RIMS1, CHD8, CHD2, WDFY3, ASH1L) causing a common failure of presynaptic homeostatic plasticity (PHP) in Drosophila. Heterozygous null mutations in each autism gene are demonstrated to have normal baseline neurotransmission and PHP. However, PHP is sensitized and rendered prone to failure. A subsequent electrophysiology-based genetic screen identifies the first known heterozygous mutations that commonly genetically interact with multiple ASD gene orthologs, causing PHP to fail. Two phenotypic modifiers identified in the screen, PDPK1 and PPP2R5D, are characterized. Finally, transcriptomic, ultrastructural and electrophysiological analyses define one mechanism by which PHP fails; an unexpected, maladaptive up-regulation of CREG, a conserved, neuronally expressed, stress response gene and a novel repressor of PHP. Thus, we define a novel genetic landscape by which diverse, unrelated autism risk genes may converge to commonly affect the robustness of synaptic transmission.

Asunto(s)

Trastorno Autístico/genética , Plasticidad Neuronal/genética , Animales , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Genes/genética , Predisposición Genética a la Enfermedad/genética , Homeostasis/genética , Humanos , Mutación/genética , Factores de Riesgo , Transmisión Sináptica/genética

RESUMEN

Presynaptic homeostatic plasticity (PHP) is an evolutionarily conserved form of adaptive neuromodulation and is observed at both central and peripheral synapses. In this work, we make several fundamental advances by interrogating the synapse specificity of PHP. We define how PHP remains robust to acute versus long-term neurotransmitter receptor perturbation. We describe a general PHP property that includes global induction and synapse-specific expression mechanisms. Finally, we detail a novel synapse-specific PHP expression mechanism that enables the conversion from short- to long-term PHP expression. If our data can be extended to other systems, including the mammalian central nervous system, they suggest that PHP can be broadly induced and expressed to sustain the function of complex neural circuitry.

Asunto(s)

Plasticidad Neuronal/fisiología , Terminales Presinápticos/fisiología , Animales , Calcio/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Potenciales Postsinápticos Excitadores/fisiología , Homeostasis/fisiología , Neurotransmisores/fisiología , Terminales Presinápticos/metabolismo , Sinapsis/fisiología , Transmisión Sináptica/fisiología , Vesículas Sinápticas/metabolismo

RESUMEN

Presynaptic homeostatic plasticity (PHP) compensates for impaired postsynaptic neurotransmitter receptor function through a rapid, persistent adjustment of neurotransmitter release, an effect that can exceed 200%. An unexplained property of PHP is the preservation of short-term plasticity (STP), thereby stabilizing activity-dependent synaptic information transfer. We demonstrate that the dramatic potentiation of presynaptic release during PHP is achieved while simultaneously maintaining a constant ratio of primed to super-primed synaptic vesicles, thereby preserving STP. Mechanistically, genetic, biochemical and electrophysiological evidence argue that a constant ratio of primed to super-primed synaptic vesicles is achieved by the concerted action of three proteins: Unc18, Syntaxin1A and RIM. Our data support a model based on the regulated availability of Unc18 at the presynaptic active zone, a process that is restrained by Syntaxin1A and facilitated by RIM. As such, regulated vesicle priming/super-priming enables PHP to stabilize both synaptic gain and the activity-dependent transfer of information at a synapse.

Asunto(s)

Plasticidad Neuronal , Neurotransmisores/metabolismo , Terminales Presinápticos/metabolismo , Animales , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Proteínas del Tejido Nervioso/metabolismo , Vesículas Sinápticas/metabolismo , Sintaxina 1/metabolismo , Proteínas de Unión al GTP rab3/metabolismo

RESUMEN

Presynaptic homeostatic plasticity (PHP) controls synaptic transmission in organisms from Drosophila to human and is hypothesized to be relevant to the cause of human disease. However, the underlying molecular mechanisms of PHP are just emerging and direct disease associations remain obscure. In a forward genetic screen for mutations that block PHP we identified mctp (Multiple C2 Domain Proteins with Two Transmembrane Regions). Here we show that MCTP localizes to the membranes of the endoplasmic reticulum (ER) that elaborate throughout the soma, dendrites, axon and presynaptic terminal. Then, we demonstrate that MCTP functions downstream of presynaptic calcium influx with separable activities to stabilize baseline transmission, short-term release dynamics and PHP. Notably, PHP specifically requires the calcium coordinating residues in each of the three C2 domains of MCTP. Thus, we propose MCTP as a novel, ER-localized calcium sensor and a source of calcium-dependent feedback for the homeostatic stabilization of neurotransmission.

Asunto(s)

Calcio/metabolismo , Plasticidad Neuronal , Neuronas/fisiología , Transmisión Sináptica , Animales , Línea Celular , Drosophila

RESUMEN

Here we define activities of RIM-binding protein (RBP) that are essential for baseline neurotransmission and presynaptic homeostatic plasticity. At baseline, rbp mutants have a ∼10-fold decrease in the apparent Ca(2+) sensitivity of release that we attribute to (1) impaired presynaptic Ca(2+) influx, (2) looser coupling of vesicles to Ca(2+) influx, and (3) limited access to the readily releasable vesicle pool (RRP). During homeostatic plasticity, RBP is necessary for the potentiation of Ca(2+) influx and the expansion of the RRP. Remarkably, rbp mutants also reveal a rate-limiting stage required for the replenishment of high release probability (p) vesicles following vesicle depletion. This rate slows ∼4-fold at baseline and nearly 7-fold during homeostatic signaling in rbp. These effects are independent of altered Ca(2+) influx and RRP size. We propose that RBP stabilizes synaptic efficacy and homeostatic plasticity through coordinated control of presynaptic Ca(2+) influx and the dynamics of a high-p vesicle pool.

Asunto(s)

Calcio/metabolismo , Proteínas de Drosophila/metabolismo , Homeostasis/fisiología , Sinapsis/metabolismo , Vesículas Sinápticas/metabolismo , Proteínas de Unión al GTP rab3/metabolismo , Animales , Animales Modificados Genéticamente , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Drosophila , Proteínas de Drosophila/genética , Probabilidad , Sinapsis/genética , Potenciales Sinápticos/fisiología , Vesículas Sinápticas/genética , Proteínas de Unión al GTP rab3/genética

RESUMEN

Transmitter release at synapses is regulated by preceding neuronal activity, which can give rise to short-term enhancement of release like post-tetanic potentiation (PTP). Diacylglycerol (DAG) and Protein-kinase C (PKC) signaling in the nerve terminal have been widely implicated in the short-term modulation of transmitter release, but the target protein of PKC phosphorylation during short-term enhancement has remained unknown. Here, we use a gene-replacement strategy at the calyx of Held, a large CNS model synapse that expresses robust PTP, to study the molecular mechanisms of PTP. We find that two PKC phosphorylation sites of Munc18-1 are critically important for PTP, which identifies the presynaptic target protein for the action of PKC during PTP. Pharmacological experiments show that a phosphatase normally limits the duration of PTP, and that PTP is initiated by the action of a 'conventional' PKC isoform. Thus, a dynamic PKC phosphorylation/de-phosphorylation cycle of Munc18-1 drives short-term enhancement of transmitter release during PTP. DOI: http://dx.doi.org/10.7554/eLife.01715.001.

Asunto(s)

Proteínas Munc18/metabolismo , Neurotransmisores/metabolismo , Proteína Quinasa C/metabolismo , Sinapsis/metabolismo , Animales , Ratones

RESUMEN

This study evaluated the effect of different amounts of dentin powder (DP) mixed in Clearfil SE Bond (CSB) or Single Bond (SB) on adhesion to dentin. Human third molars (n=96) were sectioned to expose the mid-coronal dentin and divided into eight experimental groups (n=12 per group), namely, Group 1: CSB, Group 2: CSB+1.5 mg DP, Group 3: CSB+3 mg DP, Group 4: CSB+4.5 mg DP, Group 5: SB, Group 6: SB+1.5 mg DP, Group 7: SB+3 mg DP, and Group 8: SB+4.5 mg DP. Filtek Z250 composite was bonded onto dentin, and all specimens were subjected to shear bond strength test at a crosshead speed of 1 mm/min. Highest bond strength was obtained in Groups 1, 2, and 3 (15.1, 13.5, and 16.4 MPa respectively; p>0.05) and the lowest in Groups 6, 7, and 8 (5.5, 5.6, 4 MPa; p>0.05). DP addition, regardless of amount, adversely affected the bond strength of SB. Bond strength of CSB was not affected when 1.5 or 3 mg of DP was added.

Asunto(s)

Recubrimiento Dental Adhesivo , Recubrimientos Dentinarios/química , Dentina , Grabado Ácido Dental/métodos , Adhesividad , Bisfenol A Glicidil Metacrilato/química , Resinas Compuestas/química , Análisis del Estrés Dental/instrumentación , Dentina/ultraestructura , Humanos , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Ácidos Fosfóricos/química , Cementos de Resina/química , Resistencia al Corte , Estrés Mecánico , Propiedades de Superficie

RESUMEN

α-Synuclein (α-syn) is a presynaptic protein present at most nerve terminals, but its function remains largely unknown. The familial forms of Parkinson's disease associated with multiplications of the α-syn gene locus indicate that overabundance of this protein might have a detrimental effect on dopaminergic transmission. To investigate this hypothesis, we use adeno-associated viral (AAV) vectors to overexpress human α-syn in the rat substantia nigra. Moderate overexpression of either wild-type (WT) or A30P α-syn differs in the motor phenotypes induced, with only the WT form generating hemiparkinsonian impairments. Wild-type α-syn causes a reduction of dopamine release in the striatum that exceeds the loss of dopaminergic neurons, axonal fibers, and the reduction in total dopamine. At the ultrastructural level, the reduced dopamine release corresponds to a decreased density of dopaminergic vesicles and synaptic contacts in striatal terminals. Interestingly, the membrane-binding-deficient A30P mutant does neither notably reduce dopamine release nor it cause ultrastructural changes in dopaminergic axons, showing that α-syn's membrane-binding properties are critically involved in the presynaptic defects. To further determine if the affinity of the protein for membranes determines the extent of motor defects, we compare three forms of α-syn in conditions leading to pronounced degeneration. While membrane-binding α-syns (wild-type and A53T) induce severe motor impairments, an N-terminal deleted form with attenuated affinity for membranes is inefficient in inducing motor defects. Overall, these results demonstrate that α-syn overabundance is detrimental to dopamine neurotransmission at early stages of the degeneration of nigrostriatal dopaminergic axons.

Asunto(s)

Cuerpo Estriado/metabolismo , Dopamina/deficiencia , Proteínas de Filamentos Intermediarios/metabolismo , Actividad Motora/fisiología , Sustancia Negra/metabolismo , Vesículas Sinápticas/metabolismo , Ácido 3,4-Dihidroxifenilacético/metabolismo , Anfetamina/farmacología , Análisis de Varianza , Animales , Apomorfina/farmacología , Cromatografía Líquida de Alta Presión/métodos , Cuerpo Estriado/efectos de los fármacos , Agonistas de Dopamina/farmacología , Inhibidores de Captación de Dopamina/farmacología , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/ultraestructura , Electroquímica , Ensayo de Inmunoadsorción Enzimática/métodos , Conducta Exploratoria/efectos de los fármacos , Conducta Exploratoria/fisiología , Femenino , Lateralidad Funcional , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Vectores Genéticos/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Ácido Homovanílico/metabolismo , Humanos , Técnicas In Vitro , Proteínas de Filamentos Intermediarios/genética , Proteínas de Filamentos Intermediarios/ultraestructura , Microscopía Electrónica de Transmisión , Actividad Motora/efectos de los fármacos , Mutación/genética , Potasio/farmacología , Ratas , Ratas Sprague-Dawley , Sustancia Negra/efectos de los fármacos , Sustancia Negra/ultraestructura , Vesículas Sinápticas/ultraestructura , Factores de Tiempo , Transducción Genética , Proteínas de Transporte Vesicular de Monoaminas/metabolismo

RESUMEN

OBJECTIVE: The aim of this study was to investigate the ability of two NiTi rotary apical preparation techniques used with an electronic apex locator-integrated endodontic motor and a manual technique to create an apical stop at a predetermined level (0.5 mm short of the apical foramen) in teeth with disrupted apical constriction, and to evaluate microleakage following obturation in such prepared teeth. MATERIAL AND METHODS: 85 intact human mandibular permanent incisors with single root canal were accessed and the apical constriction was disrupted using a #25 K-file. The teeth were embedded in alginate and instrumented to #40 using rotary Lightspeed or S-Apex techniques or stainless-steel K-files. Distance between the apical foramen and the created apical stop was measured to an accuracy of 0.01 mm. In another set of instrumented teeth, root canals were obturated using gutta-percha and sealer, and leakage was tested at 1 week and 3 months using a fluid filtration device. RESULTS: All techniques performed slightly short of the predetermined level. Closest preparation to the predetermined level was with the manual technique and the farthest was with S-Apex. A significant difference was found between the performances of these two techniques (p<0.05). Lightspeed ranked in between. Leakage was similar for all techniques at either period. However, all groups leaked significantly more at 3 months compared to 1 week (p<0.05). CONCLUSIONS: Despite statistically significant differences found among the techniques, deviations from the predetermined level were small and clinically acceptable for all techniques. Leakage following obturation was comparable in all groups.

Asunto(s)

Humanos , Instrumentos Dentales , Filtración Dental , Odontometría/instrumentación , Obturación del Conducto Radicular/instrumentación , Preparación del Conducto Radicular/instrumentación , Ápice del Diente/anatomía & histología , Aleaciones Dentales , Diseño de Equipo , Ensayo de Materiales , Níquel , Reproducibilidad de los Resultados , Materiales de Obturación del Conducto Radicular/química , Obturación del Conducto Radicular/métodos , Preparación del Conducto Radicular/métodos , Acero Inoxidable , Factores de Tiempo , Titanio

RESUMEN

OBJECTIVE: The aim of this study was to investigate the ability of two NiTi rotary apical preparation techniques used with an electronic apex locator-integrated endodontic motor and a manual technique to create an apical stop at a predetermined level (0.5 mm short of the apical foramen) in teeth with disrupted apical constriction, and to evaluate microleakage following obturation in such prepared teeth. MATERIAL AND METHODS: 85 intact human mandibular permanent incisors with single root canal were accessed and the apical constriction was disrupted using a #25 K-file. The teeth were embedded in alginate and instrumented to #40 using rotary Lightspeed or S-Apex techniques or stainless-steel K-files. Distance between the apical foramen and the created apical stop was measured to an accuracy of 0.01 mm. In another set of instrumented teeth, root canals were obturated using gutta-percha and sealer, and leakage was tested at 1 week and 3 months using a fluid filtration device. RESULTS: All techniques performed slightly short of the predetermined level. Closest preparation to the predetermined level was with the manual technique and the farthest was with S-Apex. A significant difference was found between the performances of these two techniques (p<0.05). Lightspeed ranked in between. Leakage was similar for all techniques at either period. However, all groups leaked significantly more at 3 months compared to 1 week (p<0.05). CONCLUSIONS: Despite statistically significant differences found among the techniques, deviations from the predetermined level were small and clinically acceptable for all techniques. Leakage following obturation was comparable in all groups.

Asunto(s)

Instrumentos Dentales , Filtración Dental , Odontometría/instrumentación , Obturación del Conducto Radicular/instrumentación , Preparación del Conducto Radicular/instrumentación , Ápice del Diente/anatomía & histología , Aleaciones Dentales , Diseño de Equipo , Humanos , Ensayo de Materiales , Níquel , Reproducibilidad de los Resultados , Materiales de Obturación del Conducto Radicular/química , Obturación del Conducto Radicular/métodos , Preparación del Conducto Radicular/métodos , Acero Inoxidable , Factores de Tiempo , Titanio

RESUMEN

The aim of this study was to investigate whether the use of operating microscope in combination with ultrasonics increased the rate of second mesiobuccal (MB2) canal detection in permanent maxillary first molar teeth. A hundred extracted human maxillary first molars were assessed. After location of the main canals, the MB2 canal was sought in all teeth first without microscopy, then with the aid of the operating microscope and finally with the combined use of the operating microscope and ultrasonics. With these techniques, the MB2 canal was detected in 62%, 67% and 74% of the teeth, respectively. The combination of the operating microscope and ultrasonics detected significantly more MB2 canals than when no microscopy was utilized (P < 0.05). Sectioning of the roots disclosed the presence of the MB2 canal in 82% of the teeth. Twenty-nine per cent of the teeth had a separate MB2 canal orifice and separate apical foramina. The results of this study suggested that the combined use of the operating microscope and ultrasonics increased the detection of MB2 canals in maxillary first permanent molars.

Asunto(s)

Instrumentos Dentales , Cavidad Pulpar/anatomía & histología , Microscopía/instrumentación , Preparación del Conducto Radicular/instrumentación , Humanos , Diente Molar , Preparación del Conducto Radicular/métodos , Ultrasonido

RESUMEN

OBJECTIVE: The aim of this study was to compare the fracture resistance of roots obturated with different materials. STUDY DESIGN: Sixty root canals were instrumented and divided into 4 equal groups (n = 15 each). The root canals in group 1 were filled with AH26 sealer and gutta-percha, in group 2 with Resilon and Epiphany, and in group 3 with Ketac-Endo Aplicap and gutta-percha. Fifteen root canals had no obturation. The force required to fracture was recorded. The data was analyzed with analysis of variance and Duncan test. RESULTS: The mean force of fracture for group 1 was significantly higher than for the other 3 groups (P < .05). There was significant difference between group 2 and group 3 (P < .05). Group 2 and group 3 were not significantly different from the control group (P > .05). CONCLUSION: The use of AH26 + gutta-percha increased the fracture resistance of instrumented root canals compared with Resilon + Epiphany and Ketac-Endo Aplicap + gutta-percha.

Asunto(s)

Materiales de Obturación del Conducto Radicular/química , Obturación del Conducto Radicular/métodos , Fracturas de los Dientes/prevención & control , Raíz del Diente/química , Análisis de Varianza , Humanos