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1.
J Cutan Pathol ; 51(3): 209-213, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38084767

RESUMO

Syphilis can mimic, clinically and microscopically, many other diseases. By microscopy, typically syphilis presents with plasma cell infiltration, admixed with lymphocytes and macrophages, in lichenoid and/or perivascular/perineural distribution pattern. When exuberant, this inflammatory infiltrate can mimic a lymphoproliferative disorder (LPD), notably plasma cell neoplasia or lymphoma. To date, about 12 cases of secondary syphilis, all but one in extraoral location, suggesting initially a LPD, have been published. Here, to our knowledge, we report an unusual case of intraoral primary syphilis initially suggesting LPD, notably lymphoid hyperplasia (pseudolymphoma); however, mucosa-associated lymphoid tissue (MALT) lymphoma and follicular lymphoma could not be disregarded. Polyclonality of plasma cells on immunohistochemistry, in strict clinical correlation, was essential to arrive at the correct diagnosis.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Transtornos Linfoproliferativos , Sífilis , Humanos , Sífilis/diagnóstico , Sífilis/patologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfócitos/patologia , Diagnóstico Diferencial
2.
J Cutan Pathol ; 51(5): 348-352, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38380692

RESUMO

Several cases of elastofibromatous lesion affecting the oral mucosa have been reported. Clinically, these lesions may appear as small exophytic lesions or less often as white lesions. Therefore, fibrous hyperplasia and leukoplakia are not uncommonly considered in clinical differential diagnosis. Microscopically, elastic and fibrous connective tissue deposition is seen. Rarely, elastofibromatous changes can be detected when assessing intraoral lesions, including cysts, salivary gland neoplasms, and epithelial dysplasia. Here we report two oral lesions showing elastofibromatous changes, expanding their clinicopathological spectrum. The first case was a 46-year-old man with a history of asymptomatic nodular lesion on the palate 1 year ago, diagnosed as giant cell fibroma with elastofibromatous changes. The second case was a 79-year-old woman who presented a pigmented and mildly symptomatic lesion on the mandibular alveolar mucosa several months ago, diagnosed as amalgam tattoo associated with elastofibromatous changes.


Assuntos
Fibroma , Transtornos da Pigmentação , Tatuagem , Masculino , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Transtornos da Pigmentação/patologia , Mucosa Bucal/patologia , Fibroma/diagnóstico , Fibroma/patologia , Células Gigantes/patologia
3.
Eur J Appl Physiol ; 124(6): 1835-1843, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38216723

RESUMO

PURPOSE: To examine the association of the single nucleotide polymorphism A1470T in the SLC16A1 gene with blood lactate accumulation during a graded exercise test and its associated metaboreflex. METHODS: Forty-six Latin-American men (Age: 27 ± 6 years; Body fat: 17.5 ± 4.7%) performed a graded exercise test on a treadmill for the assessment of maximal oxygen uptake (VO2max), lactate threshold (LT), ventilatory threshold (VT) and the exercise intensity corresponding to maximal fat oxidation rate (FATmax), via capillary blood samples and indirect calorimetry. Genomic DNA was extracted from a peripheral blood sample. Genotyping assay was carried out by real-time polymerase chain reaction to identify the A1470T polymorphism (rs1049434). RESULTS: Genotypes distribution were in Hardy-Weinberg equilibrium (X2 = 5.6, p > 0.05), observing allele frequencies of 0.47 and 0.53 for the A and T alleles, respectively. No difference in VO2max, body composition nor FATmax were observed across genotypes, whereas carriers of the TT genotype showed a higher LT (24.5 ± 2.2 vs. 15.6 ± 1.7 mL kg-1 min-1, p < 0.01) and VT in comparison to carriers of the AA + AT genotypes (32.5 ± 3.3 vs. 21.7 ± 1.5 mL kg-1 min-1, p < 0.01). Both, VO2max and the A1470T polymorphism were positively associated to the LT (R2 = 0.50, p < 0.01) and VT (R2 = 0.55, p < 0.01). Only VO2max was associated to FATmax (R2 = 0.39, p < 0.01). CONCLUSION: Independently of cardiorespiratory fitness, the A1470T polymorphism is associated to blood lactate accumulation and its associated ventilatory response during submaximal intensity exercise. However, the A1470 polymorphism does not influence fat oxidation capacity during exercise in young men.


Assuntos
Ácido Láctico , Transportadores de Ácidos Monocarboxílicos , Polimorfismo de Nucleotídeo Único , Simportadores , Humanos , Masculino , Adulto , Ácido Láctico/sangue , Simportadores/genética , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Consumo de Oxigênio/genética , Consumo de Oxigênio/fisiologia , Oxirredução , Teste de Esforço , Genótipo , Limiar Anaeróbio/genética , Limiar Anaeróbio/fisiologia , Exercício Físico/fisiologia , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia
4.
Int Orthop ; 48(7): 1677-1688, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38502335

RESUMO

PURPOSE: Bone and joint infections, complicated by the burgeoning challenge of antimicrobial resistance (AMR), pose significant public health threats by amplifying the disease burden globally. We leveraged results from the 2019 Global Burden of Disease Study (GBD) to explore the impact of AMR attributed to bone and joint infections in terms of disability-adjusted life years (DALYs), elucidating the contemporary status and temporal trends. METHODS: Utilizing GBD 2019 data, we summarized the burden of bone and joint infections attributed to AMR across 195 countries and territories in the 30 years from 1990 to 2019. We review the epidemiology of AMR in terms of age-standardized rates, the estimated DALYs, comprising years of life lost (YLLs) and years lived with disability (YLDs), as well as associations between DALYs and socio-demographic indices. RESULTS: The GBD revealed that DALYs attributed to bone and joint infections associated with AMR have risen discernibly between 1990 and 2019 globally. Significant geographical disparities and a positive correlation with socio-demographic indicators were observed. Staphylococcus aureus infections, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter-related bone and joint infections were associated with the highest DALYs because of a high proportion of antimicrobial resistance. Countries with limited access to healthcare, suboptimal sanitary conditions, and inconsistent antibiotic stewardship were markedly impacted. CONCLUSIONS: The GBD underscores the escalating burden of bone and joint infections exacerbated by AMR, necessitating urgent, multi-faceted interventions. Strategies to mitigate the progression and impact of AMR should emphasize prudent antimicrobial usage and robust infection prevention and control measures, coupled with advancements in diagnostic and therapeutic modalities.


Assuntos
Anos de Vida Ajustados por Deficiência , Carga Global da Doença , Humanos , Farmacorresistência Bacteriana , Antibacterianos/uso terapêutico , Masculino , Saúde Global , Artrite Infecciosa/epidemiologia , Artrite Infecciosa/microbiologia , Artrite Infecciosa/tratamento farmacológico , Feminino , Doenças Ósseas Infecciosas/microbiologia , Doenças Ósseas Infecciosas/epidemiologia , Doenças Ósseas Infecciosas/tratamento farmacológico , Anos de Vida Ajustados por Qualidade de Vida
5.
Immunology ; 168(1): 96-109, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36056642

RESUMO

Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) are oral potentially malignant disorders (OPMDs) that microscopically show no or varying degrees of dysplasia. Even sharing clinical and microscopic aspects, PVL shows a more aggressive clinical behaviour, with a malignant transformation rate greater than 40%. Inflammatory infiltrate associated with dysplastic lesions may favour malignant transformation of OPMDs. This study aimed to evaluate the density of T cells and cytokines in dysplastic lesions from OL and PVL patients. Additionally, we evaluated whether soluble products produced in vitro by dysplastic keratinocytes are capable of modulating apoptosis rates and Th phenotype (Th1, Th2, Th17 and Treg) of peripheral blood mononuclear cells. The density of CD3, CD4 and CD8 T cells was assessed by immunohistochemistry. Cytokines and chemokines profile from frozen tissue samples were analysed using the LUMINEX system. Apoptosis rates and Th phenotype modulation were evaluated by flow cytometry. Our results showed an increase in the number of CD8 T cell in the subepithelial region from PVL dysplastic lesions in relation to OL samples. PVL showed increased levels of IL-5 and a decrease in IL-1ß and IFN-γ levels compared to OL. Soluble products of PVL and oral carcinoma cell cultures were able to reduce apoptosis rate and promote an imbalance of Th1/Th2 and Th17/Treg. The high-subepithelial density of CD8 T cells and immune imbalance of T lymphocytes subsets probably play an important role in the pathogenesis of PVL and may explain its more aggressive behaviour in relation to OL.


Assuntos
Neoplasias Bucais , Lesões Pré-Cancerosas , Humanos , Leucócitos Mononucleares/patologia , Leucoplasia Oral/patologia , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Linfócitos T CD8-Positivos/patologia , Citocinas , Transformação Celular Neoplásica
6.
Lab Invest ; 103(10): 100222, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37507024

RESUMO

Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant transformation. This study aimed to investigate the proteomic profile of PVL in tissue and saliva samples to identify potential diagnostic biomarkers with therapeutic implications. Tissue and saliva samples obtained from patients with PVL were compared with those from patients with oral OL and controls. Label-free liquid chromatography with tandem mass spectrometry was employed, followed by qualitative and quantitative analyses, to identify differentially expressed proteins. Potential biomarkers were identified and further validated using immunohistochemistry. Staining intensity scan analyses were performed on tissue samples from patients with PVL, patients with OL, and controls from Brazil, Spain, and Finland. The study revealed differences in the immune system, cell cycle, DNA regulation, apoptosis pathways, and the whole proteome of PVL samples. In addition, liquid chromatography with tandem mass spectrometry analyses showed that calreticulin (CALR), receptor of activated protein C kinase 1 (RACK1), and 14-3-3 Tau-protein (YWHAQ) were highly expressed in PVL samples. Immunohistochemistry validation confirmed increased CARL expression in PVL compared with OL. Conversely, RACK1 and YWHA were highly expressed in oral potentially malignant disorder compared to the control group. Furthermore, significant differences in CALR and RACK1 expression were observed in the OL group when comparing samples with and without oral epithelial dysplasia, unlike the PVL. This research provides insights into the molecular mechanisms underlying these conditions and highlights potential targets for future diagnostic and therapeutic approaches.


Assuntos
Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Proteômica , Espectrometria de Massas em Tandem , Leucoplasia Oral/diagnóstico , Leucoplasia Oral/patologia , Leucoplasia Oral/terapia , Biomarcadores , Cromatografia Líquida , Transformação Celular Neoplásica/patologia
7.
Am J Dermatopathol ; 45(5): 326-329, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36939130

RESUMO

ABSTRACT: Lymphomatoid papulosis (LyP) belongs to the spectrum of primary cutaneous CD30 + lymphoproliferative disorders, characterized by chronic, recurrent, self-healing papules, small nodules, or ulcers. The clinicopathological features of LyP can mimic overt lymphomas. To date, about 27 intraoral LyP cases have been reported. Of them, only 2 cases were diagnosed as angioinvasive LyP (type E). Herein, we report a 24-year-old Brazilian man who presented a large ulcerated lesion on the hard palate with rapid evolution. Remarkably, there was no involvement of the skin or other mucous membranes. Microscopy revealed a lymphoid infiltrate constituted by medium-sized to large atypical cells, with angiocentric and angiodestructive features. The atypical cells showed immunopositivity for CD3, CD8, CD30, CD56, granzyme B, perforin, and focally for MUM1/IRF4. Ki-67 highlighted almost all atypical lymphoid cells, whereas EBER1/2 was negative. After 2 months of follow-up, the lesion healed completely. Although rare, LyP type E should be included in the differential diagnosis of oral ulcers.


Assuntos
Papulose Linfomatoide , Neoplasias Cutâneas , Masculino , Humanos , Adulto Jovem , Adulto , Papulose Linfomatoide/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Diagnóstico Diferencial , Palato/patologia
8.
Clin Oral Investig ; 27(1): 345-352, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36260168

RESUMO

OBJECTIVES: To assess the influence of estrogen deficiency on tooth eruption rate (TER) and gene expression of estrogen receptor alpha and beta (ERα and ERß) in the odontogenic region of teeth with continuous formation in a rat model. MATERIALS AND METHODS: Ovariectomies (OVX; n = 25) and sham surgeries (SHAM; n = 25) were performed in female Wistar rats when animals were 25 days old. The TER of the lower incisors, both in impeded (hyperfunction condition) and unimpeded (trimmed incisal edge-hypofunction condition) conditions, was evaluated using standardized digital photographs acquired every 48-72 h for 3 weeks (35th-53rd day of life), using a camera coupled to a stereomicroscope. Quantitative real-time PCR was performed to evaluate the relative gene expression of ERα and ERß in the odontogenic region. RESULTS: The OVX group showed a significant reduction in TER when compared to the SHAM group, only in the impeded condition (p = 0.03). There was no statistically significant difference between the groups in ERα gene expression (p = 0.33). ERß showed a significantly higher gene expression in the OVX group (p ≤ 0.05). CONCLUSIONS: Estrogen deficiency decreases TER in teeth under impeded condition. Estrogen deficiency also increases ERß gene expression in the odontogenic region of teeth with continuous formation. CLINICAL RELEVANCE: Hormonal disturbances affecting estrogen levels can cause alterations in dental formation and teeth eruption.


Assuntos
Anormalidades Dentárias , Erupção Dentária , Ratos , Animais , Feminino , Humanos , Erupção Dentária/fisiologia , Ratos Wistar , Receptor alfa de Estrogênio , Incisivo , Receptor beta de Estrogênio/genética , Estrogênios , Receptores de Estrogênio , Ovariectomia
9.
Int J Mol Sci ; 24(6)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36982316

RESUMO

This study aimed to evaluate the density of the dendritic cells (DCs) and macrophages in oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) by immunohistochemical analysis. We analysed paraffined tissue samples of PVL (n = 27), OL (n = 20), and inflammatory fibrous hyperplasia (n = 20) as the control group using the immunomarkers for DCs (CD1a, CD207, CD83, CD208 and CD123) and macrophages (CD68, CD163, FXIIIa and CD209). A quantitative analysis of positive cells in the epithelial and subepithelial areas was determined. Our results showed a reduction in CD208+ cells in the subepithelial area of the OL and PVL compared to the control. Additionally, we found a higher density of FXIIIa+ and CD163+ cells in the subepithelial area in PVL compared to the OL and control. Four-way MANOVA revealed a relationship between increased CD123+ cell density in the subepithelial area of "high-risk" samples regardless of disease. Macrophages provide the first line of defence against PVL antigens, suggesting a distinct pattern of innate immune system activation in PVL compared to OL, which may contribute to the complexity and the high rate of malignant transformation in the PVL.


Assuntos
Fator XIIIa , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Subunidade alfa de Receptor de Interleucina-3 , Leucoplasia Oral , Macrófagos/patologia , Transformação Celular Neoplásica/patologia
10.
J Cutan Pathol ; 49(6): 560-564, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35001425

RESUMO

The primary cutaneous (PC) CD8+ T-cell lymphoproliferative disorders (LPDs) comprise clinically and histopathologically heterogeneous entities including mycosis fungoides, lymphomatoid papulosis, hydroa-vacciniforme-like LPD, subcutaneous panniculitis-like T-cell lymphoma (TCL), PC acral CD8+ TCL, PC CD8+ aggressive epidermotropic cytotoxic TCL, and PC peripheral TCL, not otherwise specified (PTCL-NOS). We describe a 33-year-old man who presented with progressive facial swelling and lower lip involvement 1 year ago. Microscopy revealed an atypical small to medium-sized lymphoid proliferation exhibiting perivascular accentuation, adnexotropism, and apoptotic cell debris, without surface epithelium involvement. The tumor cells were positive for CD3, CD8, granzyme B, perforin, MUM1/IRF4, and TCR-BF1. The Ki-67 labeling index was 48%. EBER1/2 was negative. Additional studies confirmed localized disease. The diagnosis favored PC-PTCL-NOS. Two months after completing chemotherapy, right-sided facial nerve palsy was diagnosed. CD8+ T-cell LPDs should be considered in the differential diagnosis when assessing facial swelling with intraoral involvement.


Assuntos
Antineoplásicos , Linfoma Cutâneo de Células T , Papulose Linfomatoide , Neoplasias Cutâneas , Adulto , Antineoplásicos/uso terapêutico , Linfócitos T CD8-Positivos/patologia , Nervo Facial/metabolismo , Nervo Facial/patologia , Humanos , Imuno-Histoquímica , Linfoma Cutâneo de Células T/patologia , Papulose Linfomatoide/patologia , Masculino , Paralisia/tratamento farmacológico , Neoplasias Cutâneas/patologia
11.
Rheumatol Int ; 42(8): 1411-1421, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34283264

RESUMO

Focal lymphocytic sialadenitis (FLS), an important diagnostic criterion for Sjögren's syndrome (SS) diagnosis, can also be observed when assessing minor salivary gland (mSG) biopsies from healthy asymptomatic individuals (non-SS patients). Fifty cases of primary SS (pSS group) and 31 cases of oral reactive lesions (non-SS non-sicca group) containing also typical FLS features, were assessed by morphological and immunohistochemical (CD10, CD23 and Bcl-6) analysis, aiming at the detection of GCs. All pSS cases showed FLS with focus score (FS) ≥ 1. In the non-SS non-sicca group, 12, 10 and 9 cases showed FLS with FS ≥ 1, FLS with FS < 1 and FLS associated with chronic sclerosing sialadenitis with FS < 1, respectively. The morphological analysis revealed similar frequency of GCs in pSS (20%) and non-SS non-sicca group (19%). The area (p = 0.052) and largest diameter (p = 0.245) of GCs were higher in pSS than non-SS non-sicca group. The FS and number of foci were significantly higher in pSS than non-SS non-sicca group with FS < 1. Immunohistochemistry confirmed all morphological findings (GCs showing CD23 and Bcl-6 positivity, with variable CD10 expression) and additionally in 3 and 1 cases of the pSS and non-SS non-sicca group, respectively. Moreover, another 6 and 2 cases of the pSS and non-SS non-sicca group with FS ≥ 1, respectively, showed positivity only for CD23. FLS can also be observed when assessing oral reactive lesions, which showed similar frequency of GCs with those found in pSS patients. Further studies, including functional analysis of lymphocytic populations and GCs in FLS, are encouraged.


Assuntos
Sialadenite , Síndrome de Sjogren , Biópsia , Centro Germinativo , Humanos , Linfócitos/metabolismo , Sialadenite/complicações , Sialadenite/patologia , Síndrome de Sjogren/complicações
12.
Molecules ; 27(13)2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35807429

RESUMO

5-Hydroxymethylfurfural (5-HMF) has been described as one of the 12 key platform molecules derived from biomass by the US Department of Energy, and its hydrogenation reaction produces versatile liquid biofuels such as 2,5-dimethylfuran (2,5-DMF). Catalytic hydrogenation from 5-HMF to 2,5-DMF was thoroughly studied on the metal nickel catalysts supported on Al2O3-TiO2-ZrO2 (Ni/ATZ) mixed oxides using isopropanol and formic acid (FA) as hydrogen donors to find the best conditions of the reaction and hydrogen donor. The influence of metal content (wt%), Ni particle size (nm), Nickel Ni0, Ni0/NiO and NiO species, metal active sites and acid-based sites on the catalyst surface, and the effect of the hydrogen donor (isopropanol and formic acid) were systematically studied. The structural characteristics of the materials were studied using different physicochemical methods, including N2 physisorption, XRD, Raman, DRS UV-Vis, FT-IR, SEM, FT-IR Pyad, H2-TPD, CO2-TPD, H2-TPR, TEM and XPS. Second-generation 2,5-DMF biofuel and 5-HMF conversion by-products were analyzed and elucidated using 1H NMR. It was found that the Ni0NiO/ATZ3WI catalyst synthesized by the impregnation method (WI) generated a good synergistic effect between the species, showing the best catalytic hydrogenation of 5-HMF to 2,5-DMF using formic acid as a hydrogen donor for 24 h of reaction and temperature of 210 °C with 20 bar pressure of Argon (Ar).


Assuntos
Hidrogênio , Níquel , 2-Propanol , Biocombustíveis , Furaldeído/análogos & derivados , Furanos , Hidrogênio/química , Hidrogenação , Níquel/química , Espectroscopia de Infravermelho com Transformada de Fourier , Titânio
13.
Nanotechnology ; 32(8): 085602, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33166942

RESUMO

Functionalized carbon nanospheres have been synthesized in situ via a facile chemical vapor deposition strategy, fabricated by the pyrolysis of toluene/ethanol mixtures at different percentages (0, 1, 2, 3, 4, and 5 wt% of ethanol). The as-grown nanospheres have been characterized using transmission electron microscopy, scanning electron microscopy, Raman and Fourier transform infrared spectroscopy, x-ray diffraction, nitrogen adsorption, zeta potential measurements and x-ray photoelectron spectroscopy. Results indicate that the incorporation of ethanol in the precursor solution reflected in the presence of oxygen and hydrogen functional groups, the highest functionalized nanospheres without compromising the morphology of the sample were yielded at 3 wt% concentration. These in situ added functional groups rendered the carbon nanostructures enhancedly dispersible and stable in water, avoiding post-synthesis and harsh chemicals processing; envisaging thus applications of the nanospheres in the biomedical field where hydrophilicity of the nanomaterials is mandatory.

14.
Dermatol Online J ; 27(8)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34755968

RESUMO

Oral pigmented lesions can be physiological or pathological, exogenous or endogenous, as well as focal, multifocal, or diffuse. Among them, the oral melanotic macule (OMM) is a small, well-delimited brown-to-black macule, often affecting the lip and gingiva. Amalgam tattoo (AT) is a grey or black area of discoloration on the oral mucosa as a result of entry of dental amalgam into the soft tissues, commonly gingiva and alveolar ridge. Herein, we present a patient with gingival pigmentation with features of both OMM and AT in the same location.


Assuntos
Amálgama Dentário/efeitos adversos , Antagonistas de Estrogênios/efeitos adversos , Doenças da Gengiva/etiologia , Transtornos da Pigmentação/etiologia , Tamoxifeno/efeitos adversos , Adulto , Feminino , Gengiva/patologia , Doenças da Gengiva/patologia , Humanos , Doenças da Boca/etiologia , Mucosa Bucal/patologia , Transtornos da Pigmentação/patologia
15.
Scand J Immunol ; 92(6): e12950, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32738155

RESUMO

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia commonly affecting children with frequent somatic mutations in MAPK pathway genes including BRAFV600E and MAP2K1. Some studies suggest that LCH cells can recruit and modulate inflammatory cells, which could provide reciprocal survival signals. To characterize the immune profile of infiltrating inflammatory cells, and to clarify their participation in LCH pathogenesis, a detailed immunohistochemical analysis was performed. Fifteen (10 children, 5 adults) LCH cases were assessed through macrophage (CD68 and CD163), mature dendritic cell (mDC; CD83 and CD208), regulatory T cell (Treg; CD4, CD25 and FOXP3) and cytotoxic lymphocyte (CL; CD56, CD57, perforin and granzyme B) immunomarkers. Moreover, lymphocytic and LCH markers were also analysed. All cases were S100, CD1a, CD207 and CD4-positive. Bcl-2 and cyclin D1 expression was observed in 13 of 15 cases. In the immune microenvironment, M2-polarized macrophages and Tregs were the predominant cell populations, followed by significantly (P < .005) smaller levels of mDCs and CLs. Additionally, the number of CD3 + cells was significantly higher than that of CD20 + cells. In the CD3 + cell population, there were a significantly higher number of CD4 + cells than CD8 + cells. While there were no differences when comparing the paediatric and adult populations, FOXP3 + cells were significantly higher in patients with multisystem involvement and treated with chemotherapy, than single-site cases and those without chemotherapy. Our results suggest that M2-polarized macrophages and Treg infiltration can promote LCH development and survival, probably through pro-tumoral, immunosuppressive and/or cytokine-mediated mechanisms. This work highlights the need for further exploration of immune-targeted therapy for LCH.


Assuntos
Histiocitose de Células de Langerhans/metabolismo , Células de Langerhans/fisiologia , Macrófagos/metabolismo , Linfócitos T Reguladores/metabolismo , Adulto , Antígenos CD/metabolismo , Diferenciação Celular , Microambiente Celular , Criança , Pré-Escolar , Citocinas/metabolismo , Células Dendríticas/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imuno-Histoquímica/métodos , Lactente , Macrófagos/imunologia , Masculino , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Reguladores/imunologia , Células Th2/imunologia
16.
Am J Med Genet A ; 182(5): 1223-1229, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32022998

RESUMO

We report a female patient with craniofrontonasal syndrome (CFNS) who in addition showed other cranial and extracranial midline defects including partial corpus callosum agenesis, ocular melanocytosis, pigmentary glaucoma, duplex collecting system, uterus didelphys, and septate vagina. She was found to have a novel pathogenic variant in exon 5 of EFNB1, c.646G>T (p.Glu216*) predicted to cause premature protein truncation. From our review, we found at least 39 published CFNS patients with extracranial midline defects, comprising congenital diaphragmatic hernia, congenital heart defects, umbilical hernia, hypospadias, and less frequently, sacrococcygeal teratomas, and internal genital anomalies in females. These findings support that the EFNB1 mutations have systemic consequences disrupting morphogenetic events at the extracranial midline. Though these are not rigorously included as midline defects, we found at least 10 CFNS patients with congenital anomalies of the kidney and urinary tract, all females. Additionally, uterus didelphys and ocular melanocytosis observed in our patient are proposed also as a previously unreported EFNB1-related midline defects. In addition, this case may be useful for considering the intentional search for genitourinary anomalies in future patients with CFNS, which will be helpful to define their frequency in this entity.


Assuntos
Agenesia do Corpo Caloso/genética , Anormalidades Craniofaciais/genética , Efrina-B1/genética , Hérnias Diafragmáticas Congênitas/genética , Agenesia do Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/patologia , Criança , Pré-Escolar , Anormalidades Craniofaciais/diagnóstico por imagem , Anormalidades Craniofaciais/patologia , Éxons/genética , Feminino , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Hérnias Diafragmáticas Congênitas/patologia , Heterozigoto , Humanos , Lactente , Masculino , Mutação/genética , Crânio/diagnóstico por imagem , Crânio/patologia
17.
J Periodontal Res ; 55(3): 374-380, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31876956

RESUMO

BACKGROUND AND OBJECTIVE: Some studies suggest that regulatory T cells (Tregs) have suppressive effects on inflammatory osteolysis. The aim of this study was to evaluate Treg immunomarkers in periodontitis-affected tissues from patients with periodontitis and clinically healthy gingiva (control). MATERIAL AND METHODS: The presence and distribution of positive cells for CD4, CD25 and FOXP3 (Treg immunomarkers) in periodontitis-affected tissues (epithelium and lamina propria) of 30 patients (ten per group) with a diagnosis of stage IV, grade C periodontitis (IV-C), stage III, grade B periodontitis (III-B) and the control were evaluated. A two-way ANOVA followed by Fisher's LSD test was used to demonstrate differences between the groups and immunomarkers; Student's t test was used to demonstrate differences between the epithelium and the lamina propria. RESULTS: Both IV-C and III-B periodontitis presented a significantly high proportion of immune-stained cells for all immunomarkers when compared to the control group. Notably, CD25+ and FOXP3+ cells were detected in a significantly higher number in III-B than IV-C periodontitis (P < .05). CONCLUSION: Our results suggest the participation of Tregs on the osteoimmunological mechanisms in IV-C and III-B periodontitis patients, notably contributing to strategies for alveolar bone regeneration in clinical treatment decisions.


Assuntos
Periodontite/imunologia , Linfócitos T Reguladores/citologia , Biomarcadores , Estudos de Casos e Controles , Fatores de Transcrição Forkhead , Gengiva , Humanos , Subunidade alfa de Receptor de Interleucina-2 , Periodontite/classificação
18.
Orthod Craniofac Res ; 23(3): 342-350, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32246880

RESUMO

OBJECTIVE: The role of oestrogen in craniofacial growth still remains unclear. Therefore, the present study aimed to assess the effect of oestrogen deficiency on maxilla and mandible dimensions. SETTING AND SAMPLE POPULATION: The study was conducted at the Department of Pediatric Dentistry at the School of Dentistry of Ribeirão Preto, University of São Paulo, and used forty female Wistar rats. MATERIAL AND METHODS: Ovariectomy (OVX) and placebo surgery (Sham) were performed when animals were twenty-one days old (prepubertal stage). Dimensions of the maxilla and mandible were assessed by craniometric analysis using radiographs, during and after puberty of the animals (45 and 63 days old, respectively). Quantitative real-time PCR and immunohistochemical analyses were performed to determine the expression and localization, respectively, of oestrogen receptor alpha (ERα) and oestrogen receptor beta (ERß) in different growth sites of the evaluated structures at puberty. The differences between the groups for each outcome were evaluated using the t test with an established alpha error of 5%. RESULTS: There were significant differences between the OVX and Sham groups for horizontal and vertical linear measurements in the maxilla and the mandible at both pubertal and post-pubertal stages (P < .05). The ovariectomized rats showed significantly greater measures for all dimensions assessed. No differences in gene expression of ERα and ERß were identified at the different growth sites between the OVX and Sham groups (P > .05). Immunohistochemical analyses revealed the presence of both oestrogen receptors in osteoblasts and chondrocytes in the midpalatal suture and mandibular condyle, respectively, in the OVX and Sham groups. CONCLUSION: Our results suggest that oestrogen deficiency from the prepubertal stage might increase the growth of the maxilla and mandible in female rats.


Assuntos
Maxila , Maturidade Sexual , Animais , Criança , Feminino , Humanos , Mandíbula , Ovariectomia , Ratos , Ratos Wistar
19.
Pediatr Dermatol ; 37(4): 721-723, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32372427

RESUMO

We report a case of atypical oral hairy leukoplakia (OHL) in a 9-year-old immunocompetent girl treated with fluticasone propionate nasal spray for allergic rhinitis. The OHL in childhood is uncommon and should be included in a differential diagnosis of white lesions in the oral mucosa.


Assuntos
Leucoplasia Pilosa , Sprays Nasais , Corticosteroides , Criança , Feminino , Fluticasona/efeitos adversos , Humanos , Leucoplasia Oral , Mucosa Bucal
20.
Am J Otolaryngol ; 41(2): 102321, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31787356

RESUMO

OBJECTIVE: To characterize inflammatory cells in Recurrent Respiratory Papillomatosis (RRP) and to correlate it with severity using the Derkay laryngoscopic scale. MATERIALS AND METHODS: The data and biopsies from 36 patients with Juvenile (JRRP) and 56 patients with Adult (ARRP) were collected and analyzed under light microscopy. The patients were separated into groups according to the Derkay index: ≥20 for the most severe and < 20 for the less severe cases. Immunohistochemical analysis using CD3, CD4, CD8, CD15, CD20, CD68, FoxP3 and MUM-1 antibodies was performed, and the inflammatory cells were quantified. All the clinicopathological characteristics and the results of the immunohistochemical analysis were compared among the groups proposed using the Chi-Square test and correlated through the Spearman correlation test. RESULTS: The ARRP showed significantly higher quantities of CD3+, CD8+ and MUM1+ cells (p < .05) than the JRRP samples. The presence of CD15+ cells showed positive correlation with the Derkay index (p < .05), while the MUM-1+ cells showed an inverse correlation (p = .01). CONCLUSION: There are differences between the inflammatory cells population in the juvenile and adult groups and it can be related to disease severity.


Assuntos
Papiloma/patologia , Neoplasias do Sistema Respiratório/patologia , Adulto , Autoanticorpos , Complexo CD3 , Antígenos CD4 , Antígenos CD8 , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Inflamação , Fatores Reguladores de Interferon/imunologia , Laringoscopia , Antígenos CD15 , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Papiloma/metabolismo , Papiloma/virologia , Papillomaviridae , Neoplasias do Sistema Respiratório/metabolismo , Neoplasias do Sistema Respiratório/virologia , Índice de Gravidade de Doença
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