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Desenvolvimento e avaliação de cimentos reparadores experimentais à base de silicatos

Wed, 01 Jan 2025 00:00:00 GMT

Título: Desenvolvimento e avaliação de cimentos reparadores experimentais à base de silicatos Autor(es): Dias, Mirlyn de Souza Abstract: Complex endodontic procedures such as direct pulp capping, perforation sealing, revascularization, and apexification require the use of biomaterials with suitable physicochemical and biological properties. Mineral Trioxide Aggregate (MTA) and Biodentine have been widely used for this purpose due to their bioactivity and ability to induce mineralization, but they present limitations such as high solubility, risk of discoloration, and high cost. In this context, the present study aimed to prepare experimental calcium silicate–based repair cements (ERCs) incorporating zirconium (calcium zirconium silicate – Ca₃ZrSi₂O₉; CZS) or replacing it with strontium (strontium phosphate silicate – Sr₅(PO₄)₂SiO₄; SPS), in combination with auxiliary substances, in order to evaluate their physicochemical properties. The silicates were synthesized by solid-state reaction and used in the formulation of ERCs that were compared with the commercial cements MTA-Angelus (white and gray) and Biodentine. The following parameters were evaluated: setting time (initial and final) and radiopacity (ISO 6876/2012 and ASTM C266), volumetric solubility (micro-CT), pH (pH meter), and calcium/strontium ion release (atomic absorption and inductively coupled plasma optical emission spectrometry). The results showed that the experimental formulations presented initial setting times of 11 min (SPS) and 6 min (CZS), with significant differences between them (p < 0.05). Regarding final setting time, SPS (49 min) presented a significantly higher value compared with all other groups (p < 0.05). Radiopacity remained above the minimum requirement (> 3.0 mm Al), with emphasis on CZS (4.58 mm Al). Solubility was controlled, although CZS exhibited the highest value (3.09%). The pH remained alkaline, with peaks of 10.04 (SPS) and 9.70 (CZS) at 24 h, followed by a decline to 8.31 (SPS) and 7.80 (CZS) at 168 h. In the ion release analysis, a sustained pattern was observed for both cements; CZS showed intermediate release (peak of 25.96 mg/L at 3 h), whereas SPS exhibited lower values (peak of 10.95 mg/L at 168 h), with no significant difference compared with white MTA-Angelus (p < 0.05). Within the limitations of the present study, it can be concluded that the developed cements exhibited physicochemical properties that suggest promising potential for future clinical applications. Tipo: Dissertação

Fotobiomodulação com led versus laser no manejo da mucosite oral em pacientes com câncer de cabeça e pescoço e os fatores limitantes da terapia fotodinâmica contra Candida albicans

Wed, 01 Jan 2025 00:00:00 GMT

Título: Fotobiomodulação com led versus laser no manejo da mucosite oral em pacientes com câncer de cabeça e pescoço e os fatores limitantes da terapia fotodinâmica contra Candida albicans Autor(es): Nascimento, Matheus Vieira Abstract: Oral mucositis (OM) is a debilitating complication of chemoradiotherapy (CRT) in head and neck cancer (HNC) patients, severely impacting quality of life. Intraoral photobiomodulation (PBM) is an effective therapy in this context, primarily utilizing low-level laser. However, the literature still lacks studies using light-emitting diodes (LED) for this purpose, which may be a more accessible and adaptable tool. Furthermore, patients with HNC and OM are more susceptible to oral infections by opportunistic microorganisms, such as Candida albicans (C. albicans), requiring a different therapeutic approach. Antimicrobial photodynamic therapy (aPDT) is effective against a broad spectrum of microorganisms but faces challenges in eradicating infections caused by C. albicans. This thesis contains four chapters aimed at summarizing the literature on the efficacy of PBM in OM management, as well as comparing OM management with LED versus laser in patients undergoing CRT. The susceptibility of a C. albicans strain devoid of superoxide dismutases (SODs 4, 5, and 6) to methylene blue (MB)-mediated aPDT was also investigated, measuring the generation of reactive oxygen species (ROS). Methodologically, an overview of systematic reviews on the use of PBM in OM management in patients undergoing CRT for HNC treatment was conducted. Additionally, a triple-blind randomized clinical trial was performed with 37 patients who received PBM with laser (660 nm) or LED (635 nm), both with a fluence of 6.2 J/cm², three times a week. Primary outcomes were OM incidence, severity, duration, and pain. C. albicans biofilms with and without SODs were cultured for 24 h and subjected to aPDT (50 μM methylene blue and 73 J/cm² at 660 nm), quantified by colony-forming unit counts. ROS generation was measured by the degradation of anthracene exposed to toluidine blue (TBO) and MB under red light (193 J/cm² at 636 nm and 125 J/cm² at 660 nm, respectively). Results indicated 16 systematic reviews favorable to PBM. In the clinical trial, there was no statistically significant difference in OM incidence (31.6% Laser vs. 44.4% LED; p=0.50), severity, and duration (p>0.05). The LED group showed a statistical difference regarding pain (p=0.006), although the mean VAS value (4.4 ± 2.5) remained within that observed in similar studies. There was no difference between C. albicans strains with and without SODs (p>0.99) in susceptibility to aPDT. Higher ROS generation was observed at moderate photosensitizer concentrations (40 μM for TBO and 10 μM for MB). It is concluded that PBM is an effective strategy in OM management, and intraoral PBM with LED is clinically comparable to laser, representing a viable alternative. The absence of SODs in C. albicans did not make it more susceptible to aPDT, suggesting other evasion mechanisms. Increasing dye concentration for greater aPDT effectiveness should be viewed with caution, as ROS production may decrease. Tipo: Tese

Modelo de xenoenxerto derivado de paciente com células CAL27 em língua de camundongos NOD/SCID

Wed, 01 Jan 2025 00:00:00 GMT

Título: Modelo de xenoenxerto derivado de paciente com células CAL27 em língua de camundongos NOD/SCID Autor(es): Santos, Alana Lima dos Abstract: Oral cancer has a high incidence, with squamous cell carcinoma (SCC) being the most frequent subtype, and the tongue as the preferred site, often resulting in mutilating and unsatisfactory treatments, as well as a high recurrence rate. Therefore, the continuous search for new therapeutic targets and preclinical pharmacological tests is necessary. Patient-derived xenografts (PDX), using tongue SCC cell lines, have been employed in several studies. However, the methodologies differ in terms of animal lineage, cell amount and inoculation site, necessitating the standardization of a reproducible and rapid model that resembles SCC seen in humans. The aim of this study is to establish a model and characterize the tumor formed from PDX of CAL27 cells in the tongue of NOD/SCID mice, creating a reproducible, effective, and rapid protocol for future studies. To this end, CAL27 cells, derived from human SCC, were cultured and inoculated into the left lateral border of the tongue of male NOD/SCID mice, divided into three groups: G1 – eight mice that received 2x10⁶ CAL27 cells; G2 – eight mice that received 5x10⁶ CAL27 cells; G3 (negative control) – eight mice that received 50 µL of phosphate-saline solution. Tumor development was assessed daily by measuring tumor volume, as well as the animals' health by measuring their weight. After 31 days, the animals were euthanized and their tongues and organs (esophagus, lungs, and liver) were removed. Tumor implantation was confirmed by histological analysis of the tongues with hematoxylin and eosin (HE) and by Tissue Micro Array (TMA) with histochemistry (PAS with diastase) and immunohistochemistry (p63, Ki-67, and CK7). The other organs were analyzed using HE staining to verify the occurrence of metastasis. Data were expressed as mean ± standard error and analyzed using the Kolmogorov-Smirnov test, 2-way ANOVA, Bonferroni test, or Student's t-test (SPSS, p<0.05). The tumor on the tongue was visible from the third day. At the end of the experiment, the average tumor size per group was G1=11.91±1.44mm3 and G2=16.94±4.91mm3. G3 animals did not develop a tumor. Histopathological analysis revealed the development of SCC, with adenosquamous variation, presence of ductal formation, and signet ring cells. PAS-d was positive for the material contained within the ductal structures. In G1 and G2, there was strong staining for p63 (>90%) and Ki-67 (±70%). CK7 expression was observed in the ductal lining epithelium and in some signet ring cells. There was no tumor growth in other organs. The protocol used in G1 showed advantages due to the use of fewer cells and lower animal loss. This study successfully demonstrated the establishment of an PDX model, reproducing the histopathological characteristics of the original tumor, consolidating itself as a tool in the study of tumor biology. A rapid model was established, which presents clinical, macroscopic, and microscopic similarities with human tongue tumors, constituting an excellent resource for in vivo studies. Tipo: Dissertação

Influência da fotobiomodulação em lesões induzidas por aplicação tópica de 4-nitroquinolina-n-óxido em língua de camundongos swiss

Wed, 01 Jan 2025 00:00:00 GMT

Título: Influência da fotobiomodulação em lesões induzidas por aplicação tópica de 4-nitroquinolina-n-óxido em língua de camundongos swiss Autor(es): Moreira, Manuela da Silva Abstract: Oral cancer has a high incidence, with squamous cell carcinoma (SCC) being the most common type. Photobiomodulation (PBM) is recognized for its anti-inflammatory and tissue repair effects, but its influence on malignant lesions remains controversial. This study evaluated the impact of PBM with red and infrared lasers in an oral carcinogenesis model induced by 4-nitroquinoline 1-oxide (4-NQO). For this purpose, 60 Swiss mice were subjected to topical application of 1% 4-NQO on the dorsal surface of the tongue daily for 20 weeks. In the negative control group (NCG), only propylene glycol and dimethyl sulfoxide (DMSO) were used, while a positive control group (PCG) received 1% 4-NQO, and four experimental groups (TG) were treated with 4-NQO and irradiated three times a week with PBM [red laser (RL) and infrared laser (IRL)]. In TG1, RL was used, and in TG2, IRL, both groups starting in the last 6 weeks of 4-NQO application. In TG3, RL was applied, and in TG4, IRL, when lesions became clinically visible in the form of erythema, white plaques, ulcers, or elevations, continuing until lesion regression or until the animal showed visible signs of distress. Animals from the PCG, NCG, TG1, and TG2 groups were euthanized in the 20th week, while TG3 and TG4 animals were euthanized in the 22nd week. The tongues were surgically removed and processed for histological analysis of cellular and architectural alterations. Body weight data were expressed as mean ± standard error of the mean (SEM) and analyzed using two-way ANOVA with Bonferroni post-test, while histopathological findings were assessed using Pearson’s chi-square test. From the 17th week onwards, the groups subjected to PBM showed a significant reduction in body mass compared to the controls (p < 0.001). Histologically, all 4-NQO-irradiated groups exhibited epithelial alterations ranging from mild dysplasia to squamous cell carcinoma, with no statistical differences among the irradiated groups (p = 0.106). It was concluded that, under the evaluated conditions, PBM demonstrated limited oncological safety, with no significant impact on tumor progression or clinically visible lesions, highlighting the need for further studies to elucidate its safety in oral carcinogenesis contexts. Tipo: Dissertação