Immunohistochemical Analysis of Dentigerous Cysts and Odontogenic Keratocysts Associated with Impacted Third Molars-A Systematic Review.

OBJECTIVE: This systematic review investigates the diagnostic, prognostic, and therapeutic implications of immunohistochemical markers in dentigerous cysts (DCs) and odontogenic keratocysts (OKCs) associated with impacted third molars. MATERIALS AND METHODS: A comprehensive search strategy was employed across major databases including MEDLINE/PubMed, EMBASE, and Web of Science, from the inception of the databases to March 2024. Keywords and Medical Subject Heading (MeSH) terms such as "dentigerous cysts", "odontogenic keratocysts", "immunohistochemistry", "Ki-67", and "p53" were used. The PRISMA 2020 guidelines were followed to ensure methodological rigor. Inclusion criteria encompassed studies on humans and animals providing definitive diagnoses or specific signs and symptoms related to DCs and OKCs, with results on protein expression derived from immunohistochemistry, immune antibody, proteomics, or protein expression methods. RESULTS: Of the 159 studies initially identified, 138 met the inclusion criteria. Our analysis highlighted significantly higher expressions of Ki-67 (22.1% ± 4.7 vs. 10.5% ± 3.2, p < 0.001), p53 (15.3% ± 3.6 vs. 5.2% ± 1.9, p < 0.001), and Bcl-2 (18.4% ± 3.2 vs. 8.7% ± 2.4, p < 0.001) in OKCs compared to DCs, indicating a higher proliferative index, increased cellular stress, and enhanced anti-apoptotic mechanisms in OKCs. Additionally, PCNA levels were higher in OKCs (25.6% ± 4.5 vs. 12.3% ± 3.1, p < 0.001). Genetic mutations, particularly in the PTCH1 gene, were frequently observed in OKCs, underscoring their aggressive behavior and potential malignancy. CONCLUSIONS: The findings emphasize the significant role of immunohistochemical markers in distinguishing between DCs and OKCs, with elevated levels of Ki-67, p53, Bcl-2, and PCNA in OKCs suggesting a higher potential for growth and recurrence. Genetic insights, including PTCH1 mutations, further support the need for personalized treatment approaches. These markers enhance diagnostic accuracy and inform targeted therapeutic strategies, potentially transforming patient management in oral and maxillofacial surgery.

Prevalence of temporomandibular disorders (TMD) in obesity patients: A systematic review and meta-analysis.

OBJECTIVE: Obesity is a growing epidemic in the world. It increases the risk for severe health conditions, including diabetes, heart disease and stroke. Recent research has found that obesity is associated with an increased risk for temporomandibular disorders (TMDs). The purpose of this literature review with meta-analysis is to analyse the possible association between obesity and temporomandibular disorders. MATERIALS AND METHODS: Pubmed, Web of Science and Lilacs were systematically searched until 01/03/2000. Articles dealing with TMD and obesity were selected, and numbers that might be useful in the meta-analysis were extracted. RESULTS: Fifty articles were chosen after using all three search engines. Thirty-five articles were considered during the initial screening step. Four papers were chosen for title and abstract screening based on the PECO model. A manual search of bibliographies and the Cochrane database was also carried out, but no publications that matched the inclusion criteria were located. The articles and meta-analysis did not show a clear association between obesity and temporomandibular disorders. CONCLUSION: There is no evidence regarding the reliability of either method. Both have superimposable results.

Mandibular condylar hyperplasia and its correlation with vascular endothelial growth factor.

BACKGROUND: Condylar hyperplasia (CH) is a rare condition characterised by excessive unilateral growth of the mandibular condyle after cessation of growth on the contralateral side causing facial asymmetry, being more prevalent in the second and third decades. OBJECTIVE: The aim of this study was to determine the utility of vascular endothelial growth factor (VEGF-A) as a diagnostic and prognostic factor in condylar hyperplasia, and to determine its potential viability as a therapeutic target. METHODS: This is a case-control study, where 17 mandibular condyles specimens were collected from 17 patients treated for active mandibular condyle hyperplasia and three unaffected human mandibular condyles from cadavers will serve as the control group. The samples were immunostained with VEGF-A antibody and evaluated on both quantity and intensity of staining. RESULTS: VEGF-A was qualitatively found to be greatly upregulated in patients with condylar hyperplasia. CONCLUSION: VEGF-A was qualitatively found to be upregulated in patients affected by CH, validating VEGF-A as a potential diagnostic, prognostic and therapeutic target.

Immunohistochemical Markers of Temporomandibular Disorders: A Review of the Literature.

Temporomandibular disorders (TMD) are a group of internal derangements encompassing dysfunction, displacement, degeneration of the temporomandibular joints and surroundings muscles of mastication, often accompanied by pain. Relationships between TMD and various chemical biomarkers have been examined throughout the years. This paper aims to gather evidence from the literature regarding other biomarkers and presenting them as one systematic review to investigate the potential links between TMD and different biochemical activity. To identify relevant papers, a comprehensive literature search was carried out in MEDLINE/PubMED, EMBASE, Web of Science and a manual search was performed in the International Journal of Oral and Maxillofacial Surgery, Journal of Oral and Maxillofacial surgery, and Journal of Cranio-Maxillo-Facial Surgery. The literature review produced extensive results relating to the biochemical and immunohistochemical markers of TMD. Many enzymes, inflammatory markers, proteoglycans, and hormones were identified and organized in tables, along with a brief description, study design, and conclusion of each study. Through this review, recurring evidence provides confidence in suggesting involvement of certain biomarkers that may be involved in this complex pathogenesis, in addition to pointing to differences in gender prevalence of TMD. However, more organized research on large human samples needs to be conducted to delve deeper into the understanding of how this disease develops and progresses.

Thermosensitive system formed by poloxamers containing carvacrol: An effective carrier system against Leishmania amazonensis.

The drugs used in the treatment of leishmaniasis show problems concerning side effects and toxicity. As a result, the search for new actives is necessary, and natural products like carvacrol - 5-isopropyl-2-methylphenol, become a relevant alternative. To enable the use of carvacrol as an antileishmanial agent, thermosensitive hydrogels were developed from poloxamer triblock copolymers 407 (P407) and 188 (P188). Carvacrol-free and carvacrol-containing hydrogels were obtained from P407 alone and from the mixture of P407 and P188. The hydrogels were subjected to Differential scanning calorimetry, Small-angle X-ray scattering, Scanning electron microscopy, and Rheology analysis. The activity of hydrogels and carvacrol isolated against promastigotes and intracellular amastigotes of Leishmania amazonensis and their cytotoxicity in mammalian cells was determined. The sol-gel transition temperature for the binary hydrogel containing carvacrol (HG407/188CA) was 37.04 ± 1.35 °C. HG407/188CA presented lamellar structure at temperatures of 25 °C and 37 °C. HG407/188CA and carvacrol presented IC50 against Leishmania amazonensis promastigotes of 18.68 ± 1.43 µg/mL and 23.83 ± 3.32 µg/mL, respectively, and IC50 against Leishmania amazonensis amastigotes of 35.08 ± 0.75 µg/mL and 29.32 ± 0.21 µg/mL, respectively. HG407/188CA reduced the toxicity of carvacrol in all mammalian cells evaluated, raising the CC50 in murine peritoneal macrophages from 40.23 ± 0.21 µg/mL to 332.6 ± 4.89 µg/mL, obtaining a Selectivity Index (SI) of 9.5 against 1.37 of the isolated carvacrol. HG407/188CA provided higher selectivity of carvacrol for the parasite. Thus, the binary hydrogel obtained may enable the use of carvacrol as a potential antileishmanial agent.

Platelet-concentrated and platelet poor-plasma promote different pattern on immunohistochemical expression of TGF-ß1, however they impairs the osteoneogensis in calvarial defects treated with autograft due suppression of osteocalcin.

PURPOSE: Herein we evaluated the effects of platelet concentrate (PC) and platelet-poor plasma (PPP) on bone repair using noncritical defects in the calvaria of rabbits and compared them to the presence of TGF-ß1 and osteocalcin on reparative sites. METHODS: Five noncritical defects of 8.7 mm in diameter were created on the calvaria of 15 animals. Each defect was treated differently, using autograft (ABG), ABG associated with PC (ABG + PC), ABG with PPP (ABG + PPP), isolated PPP, and blood clot (control). The animals were submitted to euthanasia on the second, fourth and sixth week post-surgery. RESULTS: The defects that received ABG+PC or PPP demonstrated lower bone formation when compared to specimens that received ABG in the same period. These results coincided to significant higher immunopositivity for TGF-ß1 for specimens that received PC, and lower presence of cytokine in the group PPP. However, either higher or lower presence of TGF-ß1 were also correlated to lower presence of osteocalcin. Likewise, these results were similar to findings in specimens treated only with PPP when compared to control. CONCLUSIONS: PC and PPP were not effective when applied in association with ABG. Similarly, isolated use of PPP was not beneficial in optimizing the bone repair.

SPECT/CT Correlation in the Diagnosis of Unilateral Condilar Hyperplasia.

OBJECTIVE: To evaluate the correlation between metabolic bone activity measured by single photon emission computed tomography (SPECT) and the anatomic condylar characteristics acquired by computed tomography (CT), in patients with unilateral condylar hyperplasia (UCH). Method and Materials/Patients: Observational, descriptive study in a group of 71 patients with clinical diagnosis of UCH and indication of SPECT/CT. Bone SPECT images obtained in a gamma-camera GE Infina and processed in a station Xeleris 3 with the program Volumetrix MI Evolution for bone. CT images acquired in a PET/CT Biograph mcT20 equipment (Siemens) processed in a station Osirix V 7.5.1 (Pixmeo, Bomex, Switzerland). RESULTS: The sample included 24 men (33.8%) and 47 women (66.2%). Active state UCH was detected in 40 (56.3%) cases (over 55% uptake in the affected condyle) and 38 (53.5%) presented mandibular deviation to the right side. No significant differences related to sex, age, or mandibular deviation side were found. Mandibular deviation was the only morphologic feature related to active/inactive UCH (p = 0.003). The likelihood of active CH was significantly higher in patients with mandibular deviation higher than 6 mm compared with <6 mm (odds ratio (OR): 3.51, confidence interval (CI) 95%: 1.27-9.72). CONCLUSION: There is a significant correlation between the magnitude of mandibular deviation quantified on CT and metabolic findings obtained by SPECT in patients with UCH. The risk of active UCH is 3.5 times higher in patients with a mandibular deviation ≥6 mm.

Association of estrogen receptor alpha 1 and TMJ dysfunction: A pilot study.

OBJECTIVE: Temporomandibular disorder (TMD) is a multifactorial condition and the most common cause of orofacial pain, affecting mostly women, which points to a female hormone predilection. Therefore, the aim of this study was to analyze the association between TMD and estrogen receptor alpha 1 expression in disks of patients with TMD and condyle fracture (CFx). STUDY DESIGN: Forty specimens (from 27 patients) included n = 8 CFx, n = 21 anterior disk displacement with reduction (ADDwR), and n = 11 anterior disk displacement without reduction (ADDwoR). Age, area, and intensity of immunostaining were statistically compared between CFx, ADDwR, and ADDwoR groups using analysis of variance and Kruskal-Wallis analysis (P < .05). RESULTS: No significant difference between CFx, ADDwR, and ADDwoR groups with respect to age and expression of estrogen receptor alpha 1 was observed on immunohistochemical examination. CONCLUSION: No association of estrogen receptor alpha 1 expression and age was found in the CFx, ADDwR, and ADDwoR groups.

Platelet-concentrated and platelet poor-plasma promote different pattern on immunohistochemical expression of TGF-β1, however they impairs the osteoneogensis in calvarial defects treated with autograft due suppression of osteocalcin

ABSTRACT Purpose Herein we evaluated the effects of platelet concentrate (PC) and platelet-poor plasma (PPP) on bone repair using noncritical defects in the calvaria of rabbits and compared them to the presence of TGF-β1 and osteocalcin on reparative sites. Methods Five noncritical defects of 8.7 mm in diameter were created on the calvaria of 15 animals. Each defect was treated differently, using autograft (ABG), ABG associated with PC (ABG + PC), ABG with PPP (ABG + PPP), isolated PPP, and blood clot (control). The animals were submitted to euthanasia on the second, fourth and sixth week post-surgery. Results The defects that received ABG+PC or PPP demonstrated lower bone formation when compared to specimens that received ABG in the same period. These results coincided to significant higher immunopositivity for TGF-β1 for specimens that received PC, and lower presence of cytokine in the group PPP. However, either higher or lower presence of TGF-β1 were also correlated to lower presence of osteocalcin. Likewise, these results were similar to findings in specimens treated only with PPP when compared to control. Conclusions PC and PPP were not effective when applied in association with ABG. Similarly, isolated use of PPP was not beneficial in optimizing the bone repair.

MMP-7 and MMP-9 are overexpressed in the synovial tissue from severe temporomandibular joint dysfunction.

Matrix metalloproteinases (MMPs) are tissue-enzymes that play a key role during the remodeling process, such as in inflammatory diseases. MMP-7 and MMP-9 have been shown to be implicated in extracellular matrix homeostasis and in joint disc remodeling. The objective of this study was to determine the relation of MMP-7 and MMP-9 expression with severe temporomandibular joint dysfunction, in particular with anterior disk displacement without reduction (ADDwoR), using an immunohistochemical approach. Therefore, twenty human temporomandibular synovia in the test group and ten in the control group were collected. The results showed there was a statistically significant difference (P<0.001) for morphometric and densitometric analysis of both detected MMPs in control and test groups. In conclusion, MMP-7 and MMP-9 were overexpressed in the synovial tissue of patients with ADDwoR.

Spontaneous Condyle-Like Development after Total Resection of Mandible Giant Osteochondroma: Case Report and a Follow-Up for Five Years.

Osteochondroma manifests as a benign tumor that occurs as an abnormal bony development. This tumor is commonly asymptomatic and presents an exophytic outgrowth on bone surfaces, near synovial joints, a condition that invariably induces evident facial deformities. Treatment for this type of tumor usually involves a surgical approach promoting a total or partial resection of the affected anatomical area associated to prosthetic reconstruction of the bone area extracted. We present a case report about a giant mandibular condyle osteochondroma in a 37-year-old female patient. Her treatment involved a total condylectomy without immediate condylar reconstruction, which would be performed in a posterior surgical approach. During the patient's follow-up (every 6 months of post operation), a spontaneous and rudimentary condyle-like formation was observed. Because the stomatognathic function and facial harmony were satisfactory, we observed the condyle-like development for 5 years of follow-up. Also, because both the aesthetic aspect and functional evolution of the maxillary bone were considered satisfactory, no complementary reconstruction surgical treatment was required for the giant osteochondroma of the mandibular condyle.

Immunohistochemical analysis of IL-1 Receptor 1 in the discs of patients with temporomandibular joint dysfunction.

Objective Temporomandibular joint dysfunction (TMD) may affect a patient's quality of life, and one of the etiologies can be anterior disc displacement with reduction (ADDwR) and anterior disc displacement without reduction (ADDWoR). Interleukin 1 Receptor 1 (IL-1R1) is a membrane receptor that plays an important role on initiating immune and inflammatory response by binding the agonists ligands of IL-1 alpha and IL-1 beta. Therefore, the aim of this study was to evaluate, through immunohistochemical analysis, the association of IL-1R1 with TMD. Methods Thirty-nine human disc samples were collected and composed three different groups: ADDwR (n = 19), ADDwoR (n = 12), and control group (n = 8). The samples were immunostained with IL-1R1 antibody and evaluated on both quantity and intensity of staining. Results There was a statistically significant difference (p < 0.05) between the control and test groups for both quantity and intensity of staining. Conclusion IL1-R1 was associated with ADDwR and ADDwoR in TMD discs of humans.

Immunohistochemical expression of TLR-4 in temporomandibular joint dysfunction.

Objective Toll-like receptor 4 (TLR-4) is a transmembrane protein involved in the innate immune system and has been implicated in the pathogenesis of temporomandibular joint dysfunction (TMD). The purpose of this study was to histologically examine the level of expression of TLR-4 relative to severity of TMD. Methods Thirty-one human TMJ disc samples were immunostained for TLR-4 and evaluated for intensity of stain. Among the samples, 8 were control samples, 16 were from patients with anterior disc displacement with reduction (ADDwR), and 7 were from patients with anterior disc displacement without reduction (ADDwoR). Results There was no statistically significant difference in intensity of stain between groupings (p = 0.673). Conclusions The results indicate a negative correlation between TMD and the expression of TLR-4.

Expression of MMP-13 in human temporomandibular joint disc derangement and osteoarthritis.

OBJECTIVE: MMP-13 performs digestion of collagen, which is a primary component of the temporomandibular joint (TMJ) articular disc. This study evaluated the expression of MMP-13 in patients with anterior disc displacement with (ADDwR) and without reduction (ADDwoR), and in the presence of TMJ osteoarthrosis. METHODS: Thirty-nine human temporomandibular joint disc samples were collected and divided in two ways: ADDwR (21 samples), ADDwoR (10 samples), and a control group (8 samples); and with osteoarthrosis (10 samples) and without osteoarthrosis (29 samples). Immunostaining of the TMJ discs was statistically compared between the groups. RESULTS: There was no statistically significant difference for the area of MMP-13 immunostaining between the control group, ADDwR, and ADDwoR, nor between groups with and without osteoarthrosis. CONCLUSION: This study suggests MMP-13 is not significantly involved in collagen degradation in human TMJ disc displacement or osteoarthrosis.

Expression of Interleukin-1 and temporomandibular disorder: Contemporary review of the literature.

OBJECTIVE: Temporomandibular disorders (TMD) are a group of conditions affecting the temporomandibular joint (TMJ), leading to jaw dysfunction, joint and muscle pain, and a decrease in quality of life. A communication network of pro- and anti-inflammatory mediators called cytokines maintains the homeostasis of the TMJ. This review will focus on the Interleukin (IL) family of cytokines, which have been quantified in TMJ synovial fluids in a variety of studies. IL-1α and IL-1ß have pro-inflammatory effects, while the endogenous receptor antagonist (IL-1RA) inhibits the pro-inflammatory effects of IL-1. METHODS: A literature search (2006-2016) to identify eligible studies was completed using the PubMed database. Studies identified used saline irrigation to quantify cytokine profiles in synovial fluid of healthy and/or dysfunctional joints. RESULTS: The initial search yielded 111 articles, 5 of which met the inclusion criteria after inter-reviewer discussion. CONCLUSIONS: Articles that compared IL-1 concentrations in TMD vs. control groups found significant differences.

Interleukin-6 expression in disc derangement of human temporomandibular joint and association with osteoarthrosis.

The inflammatory process is a coordinated response that protects host after infection or trauma, involving several molecular reactions. Once the inflammation is closely linked to the process of destruction of the temporomandibular joint, this study aims to examine, by immunohistochemistry, the expression of interleukin-6 (IL-6), an important inflammatory marker, in temporomandibular articular discs of patients with anterior disc displacement with (ADDwR) and without reduction (ADDwoR) and its association with osteoarthrosis (OA). Thirty-eight (n = 38) articular discs were divided into two cutoffs: 1) analysis 1: 4 control (acute pathology), 17 ADDwR, 17 ADDwoR; and 2) analysis 2: without OA (n = 21) and with OA (n = 17). The area of immunostaining was compared statistically between groups (p < 0.05). In the disc samples, no significant differences were observed between the groups ADDwR and ADDwoR, and with and without OA, in respect to the expression of IL-6 by immunohistochemical examination. Future studies should be conducted with a larger sample size, which could clarify the association of the inflammatory mediator IL-6 with temporomandibular joint dysfunction.

Immunohistochemical analysis of IL-1 beta in the discs of patients with temporomandibular joint dysfunction.

PURPOSE: Interleukin-1 beta (IL-1ß) is a cytokine that participates in the regulation of immune responses and inflammatory reactions. It is hypothesized that IL-1 levels may be elevated in patients suffering from temporomandibular joint dysfunction. The purpose of this study was to determine the association of IL-1ß expression with TMD using an immunohistochemical approach to evaluate the joint disc. MATERIALS AND METHODS: A total of 39 human temporomandibular joint disc samples were collected, with 31 samples in the test group. Nineteen of the test group samples were from discs of patients with anterior disc displacement with reduction, and 12 of the samples were from patients with anterior disc displacement without reduction. Eight control samples were used in the control group. The samples were immunostained and evaluated on both quantity and intensity of staining. RESULTS: There was a statistically significant difference (p < 0.05) between the control and test groups for both quantity and intensity of staining. CONCLUSION: IL-1ß plays a role in the inflammatory process and degradation of TMJ discs in patients with TMJ dysfunctions.

Lubricin in synovial fluid of mild and severe temporomandibular joint internal derangements

BACKGROUND: To understand the molecular basis of temporomandibular joint (TMJ) pathologies, we aimed to investigate the lubricin levels in the TMJ synovial fluid (SF) of patients with mild to severe internal derangements (IDs). MATERIAL AND METHODS: A total, 34 joints were the study group. Only patients, with a Wilkes stage of III, IV and V were included, in this sample. Control group consisted of SF from eight joints, from patients undergoing to orthognatic surgery. Concentrations of lubricin in the SF from both samples were measured using ELISA system. RESULTS: The mean lubricin concentration was 7.029 ± 0.21 mig/mL in stage III patients; 5.64 ± 0.10 mig/mL in stage IV patients, and 4.78 ± 0.11 mig/mL in stage V patients. The lubricin levels from stage IV and stage V patients differed significantly (P ≤ 0.001) from those of control subjects. Lubricin levels were inversely correlated with age and to VAS score. CONCLUSIONS: The results of this cross-sectional study highlight the relationship between disease severity and the levels of lubricin in TMJ SF. Our findings suggest that novel biotherapeutic approaches, including the administration of recombinant lubricin in the joint cavity, for the treatment of TMJ diseases can be developed

Condylar hyperplasia: An updated review of the literature.

Condylar hyperplasia (CH) is a rare disorder characterized by excessive bone growth that almost always presents unilaterally, resulting in facial asymmetry. Classification of the different types of CH can differ depending on the authors. Correct diagnosis is critical in determining the proper treatments and timing. This paper is a review of the recent literature on the epidemiology, etiology, diagnosis, classification, and surgical treatments of CH.