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1.
Proc Natl Acad Sci U S A ; 119(3)2022 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-35012988

RESUMEN

Early diagnosis of oral squamous cell carcinoma (OSCC) remains an unmet clinical need. Therefore, elucidating the initial events of OSCC preceding tumor development could benefit OSCC prognosis. Here, we define the Langerhans cells (LCs) of the tongue and demonstrate that LCs protect the epithelium from carcinogen-induced OSCC by rapidly priming αßT cells capable of eliminating γH2AX+ epithelial cells, whereas γδT and natural killer cells are dispensable. The carcinogen, however, dysregulates the epithelial resident mononuclear phagocytes, reducing LC frequencies, while dendritic cells (DCs), macrophages, and plasmacytoid DCs (pDCs) populate the epithelium. Single-cell RNA-sequencing analysis indicates that these newly differentiated cells display an immunosuppressive phenotype accompanied by an expansion of T regulatory (Treg) cells. Accumulation of the Treg cells was regulated, in part, by pDCs and precedes the formation of visible tumors. This suggests LCs play an early protective role during OSCC, yet the capacity of the carcinogen to dysregulate the differentiation of mononuclear phagocytes facilitates oral carcinogenesis.


Asunto(s)
Antineoplásicos/metabolismo , Carcinógenos/toxicidad , Células de Langerhans/metabolismo , 4-Nitroquinolina-1-Óxido/toxicidad , Línea Celular Tumoral , Células Dendríticas/efectos de los fármacos , Células Dendríticas/patología , Células Epiteliales/metabolismo , Epitelio/efectos de los fármacos , Epitelio/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/patología , Histonas/metabolismo , Humanos , Inmunidad/efectos de los fármacos , Células de Langerhans/efectos de los fármacos , Fagocitos/efectos de los fármacos , Fagocitos/metabolismo , Fagocitos/patología , Quinolonas/toxicidad , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Lengua/patología , Transcriptoma/genética
2.
Immunity ; 43(2): 369-81, 2015 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-26231115

RESUMEN

Langerhans cells (LCs) populate the mucosal epithelium, a major entry portal for pathogens, yet their ontogeny remains unclear. We found that, in contrast to skin LCs originating from self-renewing radioresistant embryonic precursors, oral mucosal LCs derive from circulating radiosensitive precursors. Mucosal LCs can be segregated into CD103(+)CD11b(lo) (CD103(+)) and CD11b(+)CD103(-) (CD11b(+)) subsets. We further demonstrated that similar to non-lymphoid dendritic cells (DCs), CD103(+) LCs originate from pre-DCs, whereas CD11b(+) LCs differentiate from both pre-DCs and monocytic precursors. Despite this ontogenetic discrepancy between skin and mucosal LCs, the transcriptomic signature and immunological function of oral LCs highly resemble those of skin LCs but not DCs. These findings, along with the epithelial position, morphology, and expression of the LC-associated phenotype strongly suggest that oral mucosal LCs are genuine LCs. Collectively, in a tissue-dependent manner, murine LCs differentiate from at least three distinct precursors (embryonic, pre-DC, and monocytic) in steady state.


Asunto(s)
Diferenciación Celular , Células Dendríticas/inmunología , Células de Langerhans/inmunología , Monocitos/inmunología , Mucosa Bucal/inmunología , Animales , Antígenos CD/metabolismo , Antígenos de Superficie/genética , Antígenos de Superficie/metabolismo , Circulación Sanguínea , Antígeno CD11b/metabolismo , Células Cultivadas , Epitelio/inmunología , Cadenas alfa de Integrinas/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Lectinas de Unión a Manosa/genética , Lectinas de Unión a Manosa/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Especificidad de Órganos , Piel/inmunología , Transcriptoma/inmunología
3.
Clin Oral Investig ; 28(3): 200, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38453790

RESUMEN

OBJECTIVES: To compare long-term results of different treatment modalities in central giant cell granuloma of the maxillofacial-skeleton. Primary resection may result in major defects. Alternative treatments include pharmacological agents. As yet there has been no consensus on the use of the variety of treatment options, and few studies have reported clarifying long-term results. MATERIALS AND METHODS: This retrospective study on 22 patients with 25 lesions evaluated clinical, radiological and histological features, treatment preformed and lesion recurrence. Success was defined as regression/calcification and failure as recurrence, progression or un-responsiveness. RESULTS: Of the presenting patients, 77% were under age 40. Lesion prevalence was higher in the anterior mandible and left posterior maxilla. Most cases exhibited pain, tooth-mobility or mucosal-expansion. The appearance was predominantly unilocular in the maxilla and multilocular in the mandible, which also exhibited higher prevalence of cortical perforation. Up to 80% of lesions were classified as aggressive. Intralesional steroids/calcitonin were used in 7 cases. Mean follow-up was 39.8 months. Two cases showed recurrence. In 71% of the cases treated pharmacologically, calcification/regression were observed. CONCLUSIONS: Our analysis indicates better outcomes using a combined approach, including both pharmacological and surgical treatments in large aggressive lesions. Pharmacological treatment resulted in decreased size or well-defined lesions, thus reducing the need for extensive bone resection. Dual treatment with corticosteroids and calcitonin showed no superior outcomes, but a larger cohort should be assessed. CLINICAL RELEVANCE: There are several protocols for treatment of central-giant-cell-granuloma lesions, but most are not fully established. It is important to report results that contribute to the establishment of proven protocols. This report attempts to establish the relevance of the combined approach: pharmacological treatment followed by surgical resection.


Asunto(s)
Conservadores de la Densidad Ósea , Granuloma de Células Gigantes , Enfermedades Mandibulares , Humanos , Adulto , Calcitonina/uso terapéutico , Granuloma de Células Gigantes/diagnóstico por imagen , Granuloma de Células Gigantes/tratamiento farmacológico , Granuloma de Células Gigantes/cirugía , Estudios Retrospectivos , Enfermedades Mandibulares/cirugía , Conservadores de la Densidad Ósea/uso terapéutico , Mandíbula/patología
4.
J Clin Pediatr Dent ; 47(6): 30-37, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37997232

RESUMEN

To evaluate parental reports of postoperative pain, improvement and satisfaction following frenectomy with scalpel versus carbon dioxide (CO2) laser treatment. Forty-nine patients aged 2-6 years with a short labial or lingual frenulum who required frenectomy were randomly assigned to undergo CO2 laser or scalpel treatment. They were divided into a labial and a lingual frenulum group based on the severity of attachment. Frenectomy was performed using a scalpel or Pixel CO2 10,600 nm laser (Alma Lasers Company, Caesarea, Israel). Postoperative follow-up was conducted via a mobile application where pain was evaluated daily using the visual analog scale (VAS) in the first 72 hours, and painkiller use was recorded. Improvement and satisfaction were evaluated at 1-month post-surgery and compared among the groups. Our results showed significant differences between the degree of clinical attachment of the frenulum, one-month postoperative improvement and satisfaction based on VAS scores (p < 0.001). Although the use of scalpel was associated with lower postoperative pain scores than the CO2 groups, VAS scores of improvement and satisfaction after 1 month were higher in the CO2 groups (p < 0.05). This study showed that although laser was associated with more postoperative pain, it showed greater improvement and higher satisfaction among patients' parents at 1 month post-surgery compared with scalpel.


Asunto(s)
Dióxido de Carbono , Terapia por Láser , Niño , Humanos , Terapia por Láser/métodos , Rayos Láser , Dolor Postoperatorio/etiología , Lengua , Preescolar
5.
J Oral Maxillofac Surg ; 80(8): 1371-1381, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35533719

RESUMEN

PURPOSE: Identify associations between preoperative radiographic measurements and clinical findings of zygomatic arch fractures and postoperative radiographic measurements. Based on those findings, propose a comprehensive treatment algorithm for the solitary zygomatic arch fracture and combined zygomatic arch-zygomatic complex fracture. METHODS: Retrospective cohort study with patients referred to our department for zygomatic arch fractures between 2013 and 2018. Data analyzed included patient demographics, clinical evaluation, and radiographic information. Predictor variables were preoperative morphometric measurements: the initial latero-lateral (LL) defect was determined by the difference between the preoperative LL distances of the fractured and the healthy arches, LL distance was measured from the midsagittal plane in the cranium to the inner cortex of the most displaced arch segment, initial arch coronoid distances were measured from the medial part of the most dislocated arch fragment to the lateral aspect of the coronoid, and the anterior-posterior telescoping was measured as the distance between the 2 points in the arch that lost continuity and overlapped as a result of the fracture. The outcome was defined as the residual defect. It was calculated as the ratio between the postoperative remaining LL distance and the initial LL defect. RESULTS: A total of 179 cases were enrolled, all involving head residual defects. Statistical analysis was performed only on 149 medially displaced fractures. Results show that an initial LL defect larger than 3.5 mm has an 86.3% chance of remaining with a better residual defect (<84.1%), P = .001. Cases with antero-posterior (AP) telescoping > 1.45 mm showed a 72.4% chance of remaining with a poor residual defect >84% (P = .003). Arch-coronoid initial distance showed little effect on the chance of remaining with a large remining defect (P = .417, CI = 95%) CONCLUSION: Based on our results, we found that morphometric measurements can be used to predict the reduction results and can assist the clinician in choosing the optimal reduction method and thus increasing the success rate.


Asunto(s)
Fracturas Craneales , Fracturas Cigomáticas , Fijación de Fractura/métodos , Humanos , Estudios Retrospectivos , Cigoma/diagnóstico por imagen , Cigoma/cirugía , Fracturas Cigomáticas/diagnóstico por imagen , Fracturas Cigomáticas/cirugía
6.
J Craniofac Surg ; 33(4): 1032-1036, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-34608010

RESUMEN

ABSTRACT: Titanium plats are the gold-standard for fracture fixation. Titanium is considered biocompatible, corrosion resistant with an elasticity-modulus closest to bone. Nonetheless, titanium plates are not always as inherent as hoped. The authors investigated morbidity associated with titanium plates in mandibular fractures. A retrospective study of mandibular fractures treated between 2000 and 2018 using internal-fixation was conducted. Data included age, gender, complications, and location. Predictor-variable was location. Outcome-variable was plate removal. A total of 571 patients were included, 107 resulted in plate removal (18.7%). Body was the most prevalent location of fracture (29.3%). Symphysis/para-sym-physis showed the highest removal rate (24.1%), followed by body and angle (21.3/19.8%). A total of 23.4% of double-plating cases resulted in plate removal, upper-border in 15% and lower-border in 8.8%, all reconstruction-plates. Exposure was the most frequent complication leading to removal. Although titanium plates are the gold standard, almost every fifth patient returns for plate removal. Age-distribution emphasizing 41 to 50 with decrease towards extremities may imply better healing in the young and soft-tissue elasticity and less complaints in the elderly. Significantly more complications in double-plating compared to lower border suggests proximity to the oral-cavity as a risk-factor for removal. Complication rates and patterns are not negligible and perhaps should encourage clinicians to consider using biodegradable-systems for upper-border plates.


Asunto(s)
Fracturas Mandibulares , Anciano , Placas Óseas , Fijación Interna de Fracturas/métodos , Humanos , Mandíbula/cirugía , Fracturas Mandibulares/cirugía , Estudios Retrospectivos , Titanio
7.
Artículo en Inglés | MEDLINE | ID: mdl-34656509

RESUMEN

PURPOSE: Zygomatic arch fractures are commonly treated by closed reduction. This kind of treatment is highly influenced by the treating surgeon and type of fracture. Thus, it is important to choose the optimal treatment for different fractures. Current treatment schemes for zygomatic arch fractures reduction are based on subjective assessments. We believe this approach should be refined. Create a new treatment algorithm for the solitary and combined zygomatic arch fractures based on radiological morphometric measurements. This will assist the clinician in tailoring a suitable treatment for each case and avoiding pitfalls, thus achieving best possible results. METHODS: A total of 179 radiologic images of patients treated in our department for zygomatic arch fractures were morphometrically measured and analyzed. RESULTS: Three variables showed a capacity to predict a large remaining defect; The presence of a preoperative esthetic defect and a large initial latero-lateral (LL) defect reduced the probability of a large remaining defect (OR = 0.289, P= .019; (OR = 0.78, P= .008; respectively). Patients with initial LL defect < 3.5 mm presented postoperative residual defect 3-times greater than patients with initial LL defect > 3.5 mm A large antero-posterior telescoping increased the probability of a large remaining defect (OR = 1.27 P= .003). Cases that had antero-posterior telescoping > 1.45 mm had a 72.4% probability of remaining with a poor residual defect > 84.1% (P= .003). CONCLUSIONS: Based on our results we believe that the use of morphometric measurements is important when assessing zygomatic arch fractures. We found that there are measurements that can be used to predict esthetic and functional defects, as well as probability of resolving them. Morphometric measurements can be used to predict the reduction difficulty and can assist the clinician in choosing the optimal reduction method and thus increasing the success rate.

8.
J Oral Maxillofac Surg ; 79(7): 1482-1491, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33617788

RESUMEN

PURPOSE: Mucormycosis is an uncommon aggressive, opportunistic infection that can produce widespread orofacial tissue necrosis. This primarily affects immunocompromised individuals. It is the deadliest and most rapidly progressing type of human-affecting fungal infection. The aim of the study is to investigate the diagnostic criteria and treatment approach in 10 cases of mucormycosis in the author's institute from 2008 to 2019. Moreover, a review of the English literature presents all cases of mucormycosis after tooth extraction. MATERIALS AND METHODS: Ten patients at our institute have been treated. They were evaluated and discussed as per their diagnostic criteria, surgical treatment, and mortality rates. RESULTS: All 10 immunocompromised patients had a primary hematologic malignancy. The criteria for a positive diagnosis were clinical symptoms and a biopsy for microbiological culture and histologic analysis. Each patient was subjected to vigorous surgical resection and underwent antifungal treatment. Seven patients died because of their main disease. Owing to the unregulated spread of mucormycosis, 2 patients died. Four cases were diagnosed after maxillary tooth extraction. CONCLUSIONS: The most important factor for patient survival tends to be the management of the underlying disease with early detection and active surgical and antifungal action. Four of 10 cases diagnosed with mucormycosis appeared after tooth extraction, a relatively high number compared with the literature. Therefore, it is the dental profession's obligation to be familiar with the possibility of the potentially severe and possibly fatal complication.


Asunto(s)
Neoplasias Hematológicas , Mucormicosis , Antifúngicos/uso terapéutico , Atención Odontológica , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Huésped Inmunocomprometido , Mucormicosis/tratamiento farmacológico , Mucormicosis/terapia
9.
Proc Natl Acad Sci U S A ; 115(25): E5736-E5745, 2018 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-29871951

RESUMEN

AXL, a member of the TYRO3, AXL, and MERTK (TAM) receptor tyrosine kinase family, has been shown to play a role in the differentiation and activation of epidermal Langerhans cells (LCs). Here, we demonstrate that growth arrest-specific 6 (GAS6) protein, the predominant ligand of AXL, has no impact on LC differentiation and homeostasis. We thus examined the role of protein S (PROS1), the other TAM ligand acting primarily via TYRO3 and MERTK, in LC function. Genetic ablation of PROS1 in keratinocytes resulted in a typical postnatal differentiation of LCs; however, a significant reduction in LC frequencies was observed in adult mice due to increased apoptosis. This was attributed to altered expression of cytokines involved in LC development and tissue homeostasis within keratinocytes. PROS1 was then excised in LysM+ cells to target LCs at early embryonic developmental stages, as well as in adult monocytes that also give rise to LCs. Differentiation and homeostasis of LCs derived from embryonic precursors was not affected following Pros1 ablation. However, differentiation of LCs from bone marrow (BM) precursors in vitro was accelerated, as was their capability to reconstitute epidermal LCs in vivo. These reveal an inhibitory role for PROS1 on BM-derived LCs. Collectively, this study highlights a cell-specific regulation of LC differentiation and homeostasis by TAM signaling.


Asunto(s)
Proteínas Portadoras/metabolismo , Epidermis/metabolismo , Células de Langerhans/metabolismo , Proteína S/metabolismo , Animales , Médula Ósea/metabolismo , Proteínas de Unión al Calcio , Diferenciación Celular/fisiología , Homeostasis/fisiología , Queratinocitos/metabolismo , Ratones , Ratones Endogámicos C57BL , Monocitos/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Transducción de Señal/fisiología , Tirosina Quinasa c-Mer/metabolismo
10.
Proc Natl Acad Sci U S A ; 114(3): E337-E346, 2017 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-28049839

RESUMEN

The oral epithelium contributes to innate immunity and oral mucosal homeostasis, which is critical for preventing local inflammation and the associated adverse systemic conditions. Nevertheless, the mechanisms by which the oral epithelium maintains homeostasis are poorly understood. Here, we studied the role of growth arrest specific 6 (GAS6), a ligand of the TYRO3-AXL-MERTK (TAM) receptor family, in regulating oral mucosal homeostasis. Expression of GAS6 was restricted to the outer layers of the oral epithelium. In contrast to protein S, the other TAM ligand, which was constitutively expressed postnatally, expression of GAS6 initiated only 3-4 wk after birth. Further analysis revealed that GAS6 expression was induced by the oral microbiota in a myeloid differentiation primary response gene 88 (MyD88)-dependent fashion. Mice lacking GAS6 presented higher levels of inflammatory cytokines, elevated frequencies of neutrophils, and up-regulated activity of enzymes, generating reactive nitrogen species. We also found an imbalance in Th17/Treg ratio known to control tissue homeostasis, as Gas6-deficient dendritic cells preferentially secreted IL-6 and induced Th17 cells. As a result of this immunological shift, a significant microbial dysbiosis was observed in Gas6-/- mice, because anaerobic bacteria largely expanded by using inflammatory byproducts for anaerobic respiration. Using chimeric mice, we found a critical role for GAS6 in epithelial cells in maintaining oral homeostasis, whereas its absence in hematopoietic cells synergized the level of dysbiosis. We thus propose GAS6 as a key immunological regulator of host-commensal interactions in the oral epithelium.


Asunto(s)
Homeostasis/fisiología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Mucosa Bucal/metabolismo , Animales , Disbiosis/metabolismo , Células Epiteliales/metabolismo , Inmunidad Innata/inmunología , Inflamación/metabolismo , Interleucina-6 , Ratones , Ratones Endogámicos C57BL , Células Mieloides/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Neutrófilos/metabolismo , Proteína S/metabolismo , Especies de Nitrógeno Reactivo/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Tirosina Quinasa c-Mer/metabolismo
12.
J Craniofac Surg ; 30(7): 2065-2068, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31490441

RESUMEN

The research aimed at investigating potential correlations between craniofacial morphological measurements and mandibular pericondylar fractures, based on a retrospective study of 380 mandible fractures treated in our department, during 2010 to 2017. Predictors included morphological measurements and features. Primary outcome was presence of pericondylar fracture; 133 pericondylar fractures were found, including subcondylar, condylar neck, and condylar head fractures. Condylar neck fractures showed negative correlations with condylar neck width (5.7 mm versus 6.7 mm sagittaly, and 6.1 mm versus 6.8 mm coronally, respectively). Gonial angle (117.3 degrees versus 128.7), and mandibular length 106.2 mm versus 110.4 mm, respectively) showed negative correlation with all pericondylar fractures. Ramus height correlated positively with pericondylar fractures (53.6 mm versus 51.2 mm, respectively). Thus, our results showed condylar neck width was a predictor for condylar neck fractures. In addition, individuals suffering from pericondylar fractures had significantly smaller gonial angles, longer ramus height, and shorter mandibular length. These morphologic features are characteristic of individuals with decreased anterior facial height. Our results corroborated a previous study we had conducted, which suggested that increased anterior vertical growth correlates with angle fractures.


Asunto(s)
Mandíbula/diagnóstico por imagen , Fracturas Mandibulares/diagnóstico por imagen , Adolescente , Adulto , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Adulto Joven
13.
Stem Cells ; 35(3): 679-693, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27753164

RESUMEN

Neurons are continuously produced in brains of adult mammalian organisms throughout life-a process tightly regulated to ensure a balanced homeostasis. In the adult brain, quiescent Neural Stem Cells (NSCs) residing in distinct niches engage in proliferation, to self-renew and to give rise to differentiated neurons and astrocytes. The mechanisms governing the intricate regulation of NSC quiescence and neuronal differentiation are not completely understood. Here, we report the expression of Protein S (PROS1) in adult NSCs, and show that genetic ablation of Pros1 in neural progenitors increased hippocampal NSC proliferation by 47%. We show that PROS1 regulates the balance of NSC quiescence and proliferation, also affecting daughter cell fate. We identified the PROS1-dependent downregulation of Notch1 signaling to correlate with NSC exit from quiescence. Notch1 and Hes5 mRNA levels were rescued by reintroducing Pros1 into NCS or by supplementation with purified PROS1, suggesting the regulation of Notch pathway by PROS1. Although Pros1-ablated NSCs show multilineage differentiation, we observed a 36% decrease in neurogenesis, coupled with a similar increase in astrogenesis, suggesting PROS1 is instructive for neurogenesis, and plays a role in fate determination, also seen in aged mice. Rescue experiments indicate PROS1 is secreted by NSCs and functions by a NSC-endogenous mechanism. Our study identifies a duple role for PROS1 in stem-cell quiescence and as a pro-neurogenic factor, and highlights a unique segregation of increased stem cell proliferation from enhanced neuronal differentiation, providing important insight into the regulation and control of NSC quiescence and differentiation. Stem Cells 2017;35:679-693.


Asunto(s)
Proteínas Portadoras/metabolismo , Ciclo Celular , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , Neurogénesis , Proteína S/metabolismo , Células Madre Adultas/citología , Células Madre Adultas/metabolismo , Animales , Astrocitos/citología , Astrocitos/metabolismo , Proteínas de Unión al Calcio , Diferenciación Celular , Linaje de la Célula , Proliferación Celular , Eliminación de Gen , Hipocampo/citología , Ratones , Receptores Notch/metabolismo , Transducción de Señal
14.
J Immunol ; 192(4): 1395-403, 2014 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-24420922

RESUMEN

In vivo studies questioned the ability of Langerhans cells (LCs) to mediate CD8(+) T cell priming. To address this issue, we used intradermal immunization with plasmid DNA, a system in which activation of CD8(+) T cells depends on delayed kinetics of Ag presentation. We found that dendritic cells (DCs) located in the skin at the time of immunization have limited ability to activate CD8(+) T cells. This activity was mediated by a second generation of DCs that differentiated in the skin several days after immunization, as well as by lymph node-resident DCs. Intriguingly, CD8(+) T cell responses were not affected following treatment with clodronate liposomes, immunization of CCR2(-/-) mice, or local neutralization of CCL20. This suggests that local, rather than blood-derived, DC precursors mediate CD8(+) T cell priming. Analysis of DC differentiation in the immunized skin revealed a gradual increase in the number of CD11c(+) cells, which reached their maximum 2 wk after immunization. A similar differentiation kinetics was observed for LCs, with the majority of differentiating LCs proliferating in situ from epidermal precursors. By using B6/Langerin-diphtheria toxin receptor chimeric mice and LC ablation, we demonstrated that epidermal LCs were crucial for the elicitation of CD8(+) T cell responses in vivo. Furthermore, LCs isolated from lymph nodes 2 wk after immunization contained the immunization plasmid and directly activated Ag-specific CD8(+) T cells ex vivo. Thus, these results indicate that second-generation Ag-expressing LCs differentiating from epidermal precursors directly prime CD8(+) T cells and are essential for optimal cellular immune responses following immunization with plasmid DNA.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Células Gigantes de Langhans/inmunología , Activación de Linfocitos/inmunología , Animales , Antígeno CD11c/metabolismo , Diferenciación Celular/inmunología , Quimiocina CCL20/inmunología , Ácido Clodrónico , Células Dendríticas/metabolismo , Factor de Crecimiento Similar a EGF de Unión a Heparina , Péptidos y Proteínas de Señalización Intercelular/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Plásmidos/genética , Receptores CCR2/deficiencia , Receptores CCR2/genética , Receptores CCR2/inmunología , Piel/citología , Piel/inmunología
16.
Plast Reconstr Surg Glob Open ; 12(3): e5645, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38510331

RESUMEN

Background: Comminuted fractures of the jaws are complex injuries requiring special attention. In the past, treatment included closed reduction using maxillomandibular fixation. With advancements in technology and fixation systems, open reduction became a prevalent option. These fractures are difficult to reconstruct during the primary treatment phase, thus resulting in higher complication rates. The introduction of three-dimensional (3D) planning and printing brought about superior outcomes, yet these focus on secondary reconstruction due to the need for outsourcing planning and titanium printing. Methods: In this report, we describe real-time in-house 3D planning and printing using computer-assisted design software and a 3D-fused deposition printer for virtual reduction of the comminuted fractures and printing of the reconstructed mandible. Results: Following virtual 3D reduction, the newly created mandibles were 3D printed. The model was then used to preband a reconstruction plate, which in turn was used as a template during surgery for reducing the segments. The process of virtual reduction and printing should take a couple of hours at most. The results of five cases showed good alignment and proper function. Conclusion: Three-dimensional technology can be applied in the everyday primary care treatment protocol of comminuted fractures as an in-house tool which greatly improves both functional and aesthetic outcomes.

17.
J Craniomaxillofac Surg ; 52(4): 491-502, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38388230

RESUMEN

To compare the reconstruction of orbital fractures using patient-specific implants (PSI) and conventional pre-formed titanium mesh; to develop a method of three-dimensional (3D) superimposition and analysis of the reconstructed orbits; and to present the pitfalls in 3D planning of orbital PSI and how to avoid them. This was a retrospective study of patients with orbital fractures who were treated in our institution between the years 2022 and 2023 using PSI or conservative prefabricated titanium mesh. Three different methods for virtual reconstruction of orbital fractures were used and are detailed with advantages, disadvantages and indications. Data acquired included age, gender, method of reconstruction, functional outcomes and aesthetic outcomes. 3D analysis for accuracy of reconstruction was performed. A total of 23 patients were included; 12 were treated using PSI and 11 using prefabricated titanium meshes. There were 8 male and 4 female patients in the PSI group comparted to 5 and 6 in the prefabricated group. All three virtual methods for reconstruction were used successfully, each with the proper indications. When comparing PSI reconstruction to conventional mesh, a significant difference in accuracy was observed; PSI cases showed an inaccuracy of 0.58 mm compared to 1.54 mm with the conventional method. Complications are presented, and tips for avoiding them are detailed. Three different methods for virtual reconstruction were used successfully; automated computerized reconstruction is used for small defects, repositioning is the superior method for non-comminuted cases while mirroring is the method of choice in comminuted fractures. 3D analysis can be performed using a novel method detailed in this report. PSI reconstruction showed superior results, indicating it should be the method of choice when possible. Pitfalls are presented and approaches to prevent them are discussed. Orbital reconstruction is a very important entity in maxillofacial surgery with crucial functional and esthetical implications, and one should use virtual planning and PSI implants, as they significantly improve outcomes.


Asunto(s)
Implantes Dentales , Fracturas Orbitales , Procedimientos de Cirugía Plástica , Humanos , Masculino , Femenino , Titanio , Fracturas Orbitales/diagnóstico por imagen , Fracturas Orbitales/cirugía , Fracturas Orbitales/complicaciones , Mallas Quirúrgicas , Estudios Retrospectivos , Estética Dental , Órbita/cirugía
18.
Plast Reconstr Surg Glob Open ; 11(8): e5150, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37547354

RESUMEN

We aimed to compare the clinical and histological secondary healing effectiveness of various types of high-level laser versus scalpel excision in mucosa frenectomy. Methods: Forty-five Sprague Dawley rats were used in this study. These rats were divided into two laser intervention groups (CO2, n = 15; diode, n = 15) and one control group with scalpel excision (n = 15). The effectiveness of therapy has been assessed based on the comparison of intraoperative, postoperative, and histological parameters on days 7, 21, and 35, and postoperative weight changes as pain indicator. Results: Both laser groups demonstrated significantly (P < 0.05) less bleeding than did the control group during the intraoperative stage, whereas the CO2 laser showed more precise cutting compared with the diode laser (P < 0.05). The highest healing score was reported in the CO2 and scalpel groups on the first week of healing than in the diode group (P < 0.05). However, no significant difference was observed between the groups on days 21 and 35. Weight loss was significantly (P < 0.05) demonstrated in the diode group compared to the scalpel and CO2 groups till day 7. Both laser groups demonstrated delayed healing process compared with the scalpel. Nevertheless, the CO2 group followed the scalpel trends after day 7. Conclusion: Scalpel and CO2 laser yielded a superior clinical outcome compared with the diode excision of oral mucosa, whereby the CO2 has been proposed as the most effective laser type at the end of the first postoperative month.

19.
Plast Reconstr Surg Glob Open ; 11(9): e5255, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37736071

RESUMEN

Background: Facial asymmetry includes several etiologies, among them trauma to the condylar area during early childhood and congenital malformations such as hemifacial microsomia. This article describes the management of facial asymmetry in adolescents and young adults using a mandible first approach by distraction osteogenesis, followed by maxillary Le-Fort I as a second stage. Methods: Eighteen patients 14-25 years of age presented with unilateral hypoplasia of the jaws which manifested clinically by deviation of the chin and canting of the occlusal plane. Etiology included hemifacial microsomia and trauma injuries at early childhood.All patients underwent orthodontic treatment and two phases of surgical treatment. Surgical treatment included unilateral mandibular distraction followed by Le-Fort I osteotomy for alignment of the maxilla. Additional bone graft in the affected side and sliding genioplasty were done as required. Results: Marked ramal elongation of 18.94 mm concomitant with mandibular forward traction of 12.5 mm was noted while achieving symmetry. In all cases, the maxilla was centered to the midline in proper occlusion. Post distraction, posteroanterior cephalometric radiographs demonstrated elongation of the affected ramus, improvement in facial symmetry, and correction of the occlusal canting. Relapse was minimal based on long-term follow-ups of 47.4 months. Conclusions: The two-stage surgical approach that includes elongation of the mandible as a first stage followed by adaptation of the maxilla is useful in correcting facial asymmetry. Using this protocol at the correct age (14-18) is very stable, as demonstrated by our results, yet one should always remember the transverse deficiency in the gonial angle requires additional bone grafting or patient specific implants.

20.
Plast Reconstr Surg Glob Open ; 10(6): e4359, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35685746

RESUMEN

Extremely atrophic mandibles are difficult to treat. Most patients choose to live with removable dentures. However, what if the atrophy is so extreme that spontaneous fractures occur? The objective of this report is to offer a single-stage augmentation method, which uses patient-specific crib-shaped implants (PSI) combined with autogenous free bone grafts. PSI were planned using three-dimensional (3D) segmentation and 3D virtual-planning software. Implants were designed according to the patient's mandible with a mesh-like structure and included large holes for allowing blood supply recovery. During surgery, the PSI fitted perfectly. In cases exhibiting malposition of the mandibular fragments, repositioning was performed using 3D virtual planning. When repositioning mandibular segments, the PSI served as a guide for the correct positioning. Iliac-crest bone graft was harvested and fixed as an onlay over the residual mandibular basal bone. External approach was used to avoid contamination. Six months following surgery, fixation wires were removed, and dental implants were positioned in the newly formed bone. The PSI allowed for rigid fixation, thus leading to optimal incorporation of the iliac-crest bone graft. No further augmentation was required. Bony continuity for future stability and secession of the spontaneous fractures was achieved. Dental implants were placed effortlessly. Treating extremely atrophic mandibles is an entity of its own and is considered one of the most challenging in craniofacial reconstruction. It mostly requires multiple operations with high rates of failure. We offer a novel method of 3D mandibular reconstruction, both vertically and horizontally, showing promising results and achieving enough bone for further dental rehabilitation.

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