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1.
Int J Nanomedicine ; 15: 4001-4020, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606661

RESUMO

Background: Simvastatin (SMV), a hypocholesterolemic agent, suffers from very low bioavailability due to its poor aqueous solubility and extensive first-pass metabolism. Methods: Two SMV carrier systems, namely, polymeric drug inclusion complex (IC) and mixed micelles (MM) nanoparticles, were developed and loaded into mucoadhesive buccal films to enhance SMV bioavailability. The two carrier systems were characterized and their permeation across human oral epithelial cells (OEC) was studied. The effect of IC to MM ratio (X1) and the mucoadhesive polymer concentration (X2) on the cumulative percent of drug released, elongation percent and the mucoadhesive strength, from the prepared mucoadhesive films, were optimized. Ex vivo permeation across bovine mucosal tissue was investigated. The permeation parameters for the in vitro and ex vivo release data were calculated. Results: Complexation of SMV with hydroxypropyl beta-cyclodextrin (HP ß-CD) was superior to all other polymers as revealed by the equilibrium saturation solubility, stability constant, complexation efficiency and thermodynamic potential. SMV-HP ß-CD IC was utilized to develop a saturated polymeric drug solution. Both carrier systems showed enhanced permeation across OEC when compared to pure drug. X1 and X2 were significantly affecting the characteristics of the prepared films. The optimized mucoadhesive buccal film formulation loaded with SMV IC and drug MM nanoparticles demonstrated superior ex vivo permeation when compared to the corresponding pure drug buccal film, and the calculated permeation parameters confirmed this finding. Conclusion: Mucoadhesive buccal films containing SMV IC and drug MM can be used to improve drug bioavailability; however, additional pharmacokinetic and pharmacodynamic studies are required.


Assuntos
Portadores de Fármacos/química , Liberação Controlada de Fármacos , Mucosa Bucal/efeitos dos fármacos , Muco/química , Sinvastatina/farmacologia , 2-Hidroxipropil-beta-Ciclodextrina/química , Adesividade , Animais , Varredura Diferencial de Calorimetria , Bovinos , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas/química , Nanopartículas/ultraestrutura , Permeabilidade , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
2.
J Cancer Res Ther ; 16(3): 458-462, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719251

RESUMO

Background: Oral mucositis is a common and debilitating painful side effect of many forms of chemotherapy and radiation therapy. Mucositis may lead to dose reductions and unplanned interruptions of chemotherapy and/or radiotherapy (RT) and often affects patients' quality of life. Aim: The objective of the study was to assess the efficacy of the ayurvedic preparation in decreasing the severity of mucositis in head-and-neck cancer patients receiving concomitant chemoradiotherapy. Materials and Methods: In this prospective randomized study, the patients were divided into three groups. Group 1 patients received conventional mucositis treatment, whereas Group 2 patients received ayurvedic preparation Yashtimadhu in addition to conventional treatment. Group 3 patients received honey for local application in oral cavity as well as one tea spoon of honey twice daily orally in addition to routine conventional treatment. All the patients were assessed for mucositis at the end of every week during the RT for a period of 6 weeks. Results: A significant difference was observed between the groups at each time point. Nearly 42.85% of patients in conventional treatment arm developed Grade 3 mucositis, 20% of patients developed Grade 3 mucositis in group where honey was given, and only 15.5% of patients developed Grade 3 mucositis in Yastimadhu group. Unplanned treatment breaks and hospitalization of patients were reduced with the use of yashtimadhu as compared to other two groups. Conclusion: Yashtimadhu was observed to be effective and delayed the development of severe form of mucositis. The drug appeared to be more efficient in the management of radiation-induced mucositis.


Assuntos
Produtos Biológicos/farmacologia , Quimiorradioterapia/efeitos adversos , Glycyrrhiza/química , Neoplasias de Cabeça e Pescoço/radioterapia , Mucosa Bucal/efeitos dos fármacos , Lesões por Radiação/tratamento farmacológico , Estomatite/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Mucosa Bucal/efeitos da radiação , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Estomatite/etiologia , Estomatite/patologia , Adulto Jovem
3.
PLoS One ; 15(5): e0231588, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32421698

RESUMO

We have recently established a protocol to grow wildtype human oral mucosa organoids. These three-dimensional structures can be maintained in culture long-term, do not require immortalization, and recapitulate the multilayered composition of the epithelial lining of the oral mucosa. Here, we validate the use of this model to study the effect of Leucovorin (LV) on Methotrexate (MTX)-induced toxicity. MTX is a chemotherapeutic agent used in the treatment of pediatric acute lymphoblastic leukemia. Although effective, the use of MTX often results in severe side-effects, including oral mucositis, which is characterized by epithelial cell death. Here, we show that organoids are sensitive to MTX, and that the addition of LV reduces MTX toxicity, in both a concentration- and timing-dependent manner. Additionally, we show that a 24 hour 'pretreatment' with LV reduces MTX-induced cell death, suggesting that such a pretreatment could decrease mucositis in patients. Taken together, we provide the first in vitro model to study the effect of MTX on wildtype oral mucosa cells. Our findings underscore the relevance of the clinically applied LV regimen and highlight the potential of this model to further optimize modifications in dosing and timing of Leucovorin on oral mucosa cells.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Apoptose/efeitos dos fármacos , Mucosa Bucal/efeitos dos fármacos , Organoides/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estomatite/patologia , Adolescente , Criança , Humanos , Técnicas In Vitro , Leucovorina/administração & dosagem , Metotrexato/administração & dosagem , Mucosa Bucal/patologia , Técnicas de Cultura de Órgãos , Organoides/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Estomatite/induzido quimicamente
4.
Mutat Res ; 852: 503159, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32265039

RESUMO

Dental technicians may be chronically exposed to methyl methacrylate (MMA), used in the production of dental prostheses. We have studied whether occupational exposure to MMA affects genotoxicity biomarkers such as 8-OHdG formation, comet assay, and buccal micronucleus frequency. MMA exposure was assessed via ambient air analysis. Although no significant differences between exposed and non-exposed individuals were seen with respect to blood genotoxicity measurements, we found a higher level of buccal-cell anomalies in the exposed group.


Assuntos
Cimentos para Ossos/toxicidade , Técnicos em Prótese Dentária , Metilmetacrilato/toxicidade , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Mucosa Bucal/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina/sangue , Adulto , Estudos de Casos e Controles , Ensaio Cometa , Dano ao DNA , Feminino , Humanos , Masculino , Testes para Micronúcleos , Mucosa Bucal/citologia , Exposição Ocupacional/análise
5.
Acta Cytol ; 64(5): 471-476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32316006

RESUMO

BACKGROUND/AIM: Cytogenetic biomarkers such as micronuclei (MN) are used for the evaluation of exposure to carcinogens and genotoxic effects in oral epithelial cells. Tobacco is one of the strongest carcinogens responsible for the development of cancer in oral mucosa. The aim of this study was to compare the genotoxic effect of waterpipe smoking with that of cigarette smoking. METHODS: This case-control study was performed on 30 waterpipe smokers, 30 cigarette smokers, and 30 nonsmokers. Buccal exfoliated cells were prepared using cytobrushes and stained with the Papanicolaou technique. The cytologic slides were examined under a light microscope for counting the number of MN and the number of cells with MN per 1,000 epithelial cells. RESULTS: The mean number ± standard deviation (SD) of MN in waterpipe smokers, cigarette smokers, and nonsmokers was 7.55 ± 5.530, 4.95 ± 5.633, and 2.00 ± 2.406, respectively. The mean number ± SD of cells with MN in waterpipe smokers, cigarette smokers, and nonsmokers was 6.20 ± 4.830, 3.50 ± 3.832, and 1.45 ± 1.701, respectively. Numbers of cells with MN differed significantly between waterpipe smokers and cigarette smokers (p = 0.04) and between waterpipe smokers and nonsmokers (p < 0.001). Numbers of MN differed significantly between waterpipe smokers and nonsmokers (p < 0.001). Numbers of MN did not differ significantly between waterpipe smokers and cigarette smokers (p = 0.10). Numbers of MN and of cells with MN did not differ significantly between cigarette smokers and nonsmokers (p = 0.06 and p = 0.052, respectively). CONCLUSIONS: Waterpipe smoking is associated with a significantly higher frequency of MN, and it seems that waterpipe smoking has a greater genotoxic effect than cigarette smoking.


Assuntos
Fumar Cigarros/efeitos adversos , Dano ao DNA , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Mucosa Bucal/patologia , não Fumantes/estatística & dados numéricos , Fumantes/estatística & dados numéricos , Fumar Cachimbo de Água/efeitos adversos , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Mucosa Bucal/efeitos dos fármacos , Adulto Jovem
6.
Food Chem ; 318: 126468, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32126464

RESUMO

The mechanism leading to aroma persistence during eating is not fully described. This study aims at better understanding the role of the oral mucosa in this phenomenon. Release of 14 volatile compounds from different chemical classes was studied after exposure to in vitro models of oral mucosa, at equilibrium by Gas-Chromatography-Flame Ionization Detection (GC-FID) and in dynamic conditions by Proton Transfer Reaction- Mass Spectrometry (PTR-MS). Measurements at equilibrium showed that mucosal hydration reduced the release of only two compounds, pentan-2-one and linalool (p < 0.05), and suggested that cells could metabolize aroma compounds from different chemical families (penta-2,3-dione, trans-2-hexen-1-al, ethyl hexanoate, nonan- and decan-2-one). Dynamic analyses for pentan-2-one and octan-2-one evidenced that the constituents of the mucosal pellicle influenced release kinetics differently depending on molecule hydrophobicity. This work suggests that mucosal cells can metabolize aroma compounds and that non-covalent interactions occur between aroma compounds and oral mucosa depending on aroma chemical structure.


Assuntos
Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Odorantes , Compostos Orgânicos Voláteis/análise , Monoterpenos Acíclicos/análise , Monoterpenos Acíclicos/metabolismo , Ingestão de Alimentos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Odorantes/análise , Pentanonas/análise , Pentanonas/metabolismo , Saliva
7.
J Appl Oral Sci ; 28: e20190382, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049136

RESUMO

OBJECTIVE: This study aimed to investigate the effects of Maras powder (a type of smokeless tobacco obtained from Nicotiana rustica Linn and mixed with the ashes of wood, especially from oak, walnut or grapevine) on the microRNA (miRNA) deregulation of oral mucosa, and it compares these effects with those of smoking. METHODOLOGY: Oral mucosal samples were collected from 74 patients, consisting of 16 nonusers, 26 smokers, and 32 Maras powder users. Genes associated with oral cancer were selected and 90 microRNAs targeting these genes were identified. MicroRNA were isolated and purified using the microRNA isolation kit. MicroRNA were expressed using Fluidigm RT-PCR. RESULTS: A positive correlation between the duration of Maras powder use with miR-31 expression levels, and a negative correlation between the Maras powder chewing time and miR-372 expression levels was found. In addition, there is a negative correlation between the amount of Maras powder consumed and expression levels of miR-375, miR-378a, miR-145, and miR-10b; moreover, another negative correlation is observed between the number of cigarettes consumed and the expression levels of miR-23a, miR-23b, miR-203a, miR-200b, and miR-375. However, miR-200b and miR-92a levels were downregulated significantly more in Maras powder users when compared with smokers and nonusers (p<0.05). CONCLUSION: The results show both chewing Maras powder and smoking have an effect on deregulation of miR-200b and miR-92a expressions. This leads to the belief that assessing the expression of these two miRNAs is a promising noninvasive method of analysis, especially in mutagen exposures. Finally, large-scale and high-throughput studies may help to identify an extensive miRNA expression profile associated with tobacco use and improve the understanding of oral malignancies.


Assuntos
MicroRNAs/efeitos dos fármacos , Mucosa Bucal/efeitos dos fármacos , Tabaco sem Fumaça/efeitos adversos , Adolescente , Adulto , Idoso , Análise de Variância , Estudos Transversais , Regulação para Baixo , Feminino , Expressão Gênica , Humanos , Masculino , MicroRNAs/análise , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Pós , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Fatores de Tempo , Adulto Jovem
8.
Medicina (Kaunas) ; 56(2)2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31991568

RESUMO

BACKGROUND AND OBJECTIVES: Bisphosphonates (BPs) are selective inhibitors of osteoclasts, used for the treatment of bone disorders. The objective of this study is to investigate the possible effects of BPs on the tongue's mucosa. MATERIALS AND METHODS: Specimens of the tongue of 20 female 12-month old Wistar rats were taken. Ten were used as control group, while in the remaining alendronate (Fosamax, Merck) was administered per os from 13 weeks. Observation of the harvested samples was made by Transmission Electron Microscopy (TEM). RESULTS: In the experimental group, focal alterations were observed to various extent in all specimens. The basement membrane was intact. Furthermore, an increase at the intercellular space was observed, predominantly at the middle layer, and the desmosomes were disorganized. In the lamina propria focal edema was observed. CONCLUSIONS: Investigation on the effect of BPs on the tongue's mucosa through TEM hasn't been documented in the past. According to our results, BPs seem to cause mild mucosal lesions on the tongue.


Assuntos
Difosfonatos/efeitos adversos , Mucosa Bucal/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Animais , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Modelos Animais de Doenças , Feminino , Microscopia Eletrônica/métodos , Mucosa Bucal/patologia , Mucosa Bucal/fisiopatologia , Osteoporose/prevenção & controle , Ratos , Ratos Wistar , Língua/efeitos dos fármacos , Língua/patologia , Língua/fisiopatologia
9.
Biochim Biophys Acta Biomembr ; 1862(2): 183133, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31785236

RESUMO

Food polyphenols in fruits juices, tea, coffee, wine and beer confer sensory properties such as colour, astringency and bitterness. The development of functional healthy drinks without the unpleasant sensory feeling is boosting research for a clearer understanding on the interactions of polyphenols within the oral mucosa. In this study we investigated the interaction of astringent polyphenols, namely ECG, EGCG, procyanidin B4 and PGG, with lipids in model membranes by spectroscopic techniques. The membrane model was built varying the cholesterol content to mimic mouth regions and experiments were conducted at pH 5 to mimic the pH drop at the moment of beverage (e.g. green tea, red wine) intake. Fluorescence quenching results conducted on LUVs with cholesterol molar fractions ranging between 0.34 < χchol < 0.74 and similar size distributions (122.9 ± 3.7 nm) showed that interaction of polyphenols is structure- and concentration-dependent. Also, the decrease of partition constants (Kp) with increasing cholesterol content (χchol) suggest that the affinity of polyphenols is weaker in cholesterol-rich liposomes. STD results revealed that the interaction of EGCG and PGG with membrane lipids involved mainly galloyl residues. Overall, spectroscopic data show that polyphenols interact to higher extent with more polar regions found in buccal, flour of the mouth and gingiva regions than with more hydrophobic regions located in the palate and tongue supporting that lipid microenvironments play a role in oral sensory perception.


Assuntos
Catequina/análogos & derivados , Lipossomos/química , Paladar , Catequina/química , Catequina/farmacologia , Lipídeos de Membrana/química , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo
10.
J Invest Surg ; 33(1): 49-58, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29856665

RESUMO

Aim: The aim of this study was to evaluate the effect of Hypericum perforatum (HP) oil on wound-healing process in rabbit palatal mucosa. Materials and Methods: Thirty-six New Zealand albino rabbits were randomly allocated to following groups; (1) HP oil (test, n = 18) and (2) olive oil (control, n = 18). Palatinal excisional wounds were created and the oils were topically applied (0.1 ml, 30 s, twice a day). Gingival biopsies were excised, and analyzed for re-epithelialization (RE) and granulation tissue maturation (GTM) on days 3, 7, and 14 after surgery. Levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) were assessed using the immunohistochemical method. Apoptotic cells (ACs) were evaluated using TUNEL staining. Enzyme-linked immunosorbent assay was used to assess tissue catalase (CAT) and malondialdehyde (MDA) levels. Results: RE and GTM were completed earlier in the HP oil group than in the control group. The number of positively stained cells/vessels was higher in olive oil than in the test group on day 3 for FGF-2 and on days 3 and 7 for VEGF (p < 0.05). In contrast, on day 14, a higher number of vessels was observed in the HP oil group than in the control group. HP oil treatment reduced the number of ACs compared to olive oil (p < 0.05), but the difference during the healing period did not reach significance. Tissue CAT and MDA levels between groups were not different, and also the results were the same when the levels were analyzed by the evaluated time periods (p > 0.05). Conclusions: The results of this study demonstrated that topical HP oil treatment did not provide an additional benefit to its base, olive oil, in the early phase of secondary wound healing.


Assuntos
Hypericum/química , Mucosa Bucal/efeitos dos fármacos , Óleos Vegetais/administração & dosagem , Reepitelização/efeitos dos fármacos , Ferida Cirúrgica/tratamento farmacológico , Administração Tópica , Animais , Biópsia , Modelos Animais de Doenças , Gengiva/efeitos dos fármacos , Gengiva/patologia , Gengiva/cirurgia , Humanos , Masculino , Mucosa Bucal/cirurgia , Palato/efeitos dos fármacos , Palato/patologia , Palato/cirurgia , Coelhos
11.
Phytother Res ; 34(4): 886-895, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31846135

RESUMO

Dental caries, candidiasis, and periodontal disease are the most common oral infections affecting a wide range of the population worldwide. The present study investigated the effects of two tart cherry (Prunus cerasus L.) fractions on important oral pathogens, including Candida albicans, Streptococcus mutans, and Fusobacterium nucleatum, as well as on the barrier function of oral epithelial cells. Procyanidins and quercetin and its derivatives were the most important constituents found in the tart cherry fractions. Although the fractions showed poor antimicrobial activity, they inhibited biofilm formation by the three oral pathogens in a dose-dependent manner. The tart cherry fractions also attenuated the adherence of C. albicans and S. mutans to a hydroxylapatite surface as well as the adherence of F. nucleatum to oral epithelial cells. Treating oral epithelial cells with the tart cherry fractions significantly enhanced the barrier function as determined by monitoring the transepithelial electrical resistance. In conclusion, this study showed that the tart cherry fractions and their bioactive constituents could be promising antiplaque compounds by targeting biofilm formation and adherence properties of oral pathogens. Furthermore, its property of increasing the epithelial barrier function may protect against microbial invasion of the underlying connective tissue.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Mucosa Bucal/efeitos dos fármacos , Boca/microbiologia , Extratos Vegetais/farmacologia , Prunus/química , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Células Cultivadas , Fracionamento Químico , Cárie Dentária/microbiologia , Frutas/química , Fusobacterium nucleatum/efeitos dos fármacos , Fusobacterium nucleatum/fisiologia , Humanos , Mucosa Bucal/metabolismo , Mucosa Bucal/microbiologia , Mucosa Bucal/fisiologia , Permeabilidade/efeitos dos fármacos , Extratos Vegetais/química , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/fisiologia
13.
PLoS One ; 14(12): e0226343, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31869348

RESUMO

The oral, cervical, and genital mucosa, covered by stratified squamous epithelia with polarized organization and strong tight and adherens junctions, play a critical role in preventing transmission of viral pathogens, including human immunodeficiency virus (HIV). HIV-1 interaction with mucosal epithelial cells may depolarize epithelia and disrupt their tight and adherens junctions; however, the molecular mechanism of HIV-induced epithelial disruption has not been completely understood. We showed that prolonged interaction of cell-free HIV-1 virions, and viral envelope and transactivator proteins gp120 and tat, respectively, with tonsil, cervical, and foreskin epithelial cells induces an epithelial-mesenchymal transition (EMT). EMT is an epigenetic process leading to the disruption of mucosal epithelia and allowing the paracellular spread of viral and other pathogens. Interaction of cell-free virions and gp120 and tat proteins with epithelial cells substantially reduced E-cadherin expression and activated vimentin and N-cadherin expression, which are well-known mesenchymal markers. HIV gp120- and tat-induced EMT was mediated by SMAD2 phosphorylation and activation of transcription factors Slug, Snail, Twist1 and ZEB1. Activation of TGF-ß and MAPK signaling by gp120, tat, and cell-free HIV virions revealed the critical roles of these signaling pathways in EMT induction. gp120- and tat-induced EMT cells were highly migratory via collagen-coated membranes, which is one of the main features of mesenchymal cells. Inhibitors of TGF-ß1 and MAPK signaling reduced HIV-induced EMT, suggesting that inactivation of these signaling pathways may restore the normal barrier function of mucosal epithelia.


Assuntos
Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Genitália/citologia , Proteína gp120 do Envelope de HIV/farmacologia , Mucosa Bucal/efeitos dos fármacos , Produtos do Gene tat do Vírus da Imunodeficiência Humana/farmacologia , Células Cultivadas , Pré-Escolar , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Feminino , Genitália/virologia , Células HEK293 , Proteína gp120 do Envelope de HIV/metabolismo , HIV-1/metabolismo , Humanos , Lactente , Recém-Nascido , Queratinócitos/efeitos dos fármacos , Queratinócitos/fisiologia , Masculino , Mucosa Bucal/fisiologia , Membrana Mucosa/citologia , Membrana Mucosa/efeitos dos fármacos
14.
World J Surg Oncol ; 17(1): 219, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842892

RESUMO

BACKGROUND: Transformation and progression of lymphoma after treatment is well known; however, since the advent of chemotherapy and radiotherapy, progression in untreated lymphoma is seldom seen. We present a case which was misdiagnosed and treated as abdominal tuberculosis later presented with progression and involvement of oral cavity. CASE PRESENTATION: A 41-year-old male who presented with urinary symptoms and abdominal pain was diagnosed as abdominal tuberculosis and treated. Two years later, he presented with B symptoms and oral cavity lesion that was diagnosed as diffuse large B cell lymphoma. The patient was treated with R-CHOP chemotherapy with complete regression of the lesion. CONCLUSION: Involvement of extranodal sites in predominantly nodal disease does occur; however, involvement of oral cavity is rare. Though primary extranodal lymphoma is reported to occur in oral cavity and oropharynx, natural progression in untreated disease is seldom documented.


Assuntos
Linfoma Difuso de Grandes Células B/patologia , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Progressão da Doença , Doxorrubicina/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Mucosa Bucal/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Prednisona/uso terapêutico , Prognóstico , Rituximab/uso terapêutico , Vincristina/uso terapêutico
15.
ACS Appl Mater Interfaces ; 11(50): 46591-46603, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31742377

RESUMO

Oral candidiasis as a highly prevalent and recurrent infection in medically compromised individuals is mainly caused by the opportunistic fungal pathogen Candida albicans. This epithelial infection, if not controlled effectively, can progress to life-threatening systemic conditions and complications. The efficacy of current frontline antifungals is limited due to their poor bioavailability and systemic toxicity. As such, an efficient intervention is essential for controlling disease progression and recurrence. Herein, a theranostic nanoplatform (CD-Gu+-AmB) was developed to track the penetration of antifungals and perturb the invasion of C. albicans at oral epithelial tissues, via decorating the homemade red-emissive carbon dots (CD) with positively charged guanidine groups (Gu+) followed by conjugation with antifungal polyene (amphotericin B, AmB) in a reacting site-controllable manner. The generated CD-Gu+-AmB favorably gathered within the Candida cells and exhibited potent antifungal effects in both planktonic and biofilm forms. It selectively accumulated in the nuclei of human oral keratinocytes and exhibited undetectable toxicity to the host cells. Moreover, we reported for the first time the penetration and exfoliation profiles of CD in a three-dimensional organotypic model of human oral epithelial tissues, demonstrating that the extra- and intracellular accumulation of CD-Gu+-AmB effectively resisted the invasion of C. albicans by forming a "shielding" layer throughout the entire tissue. This study establishes a multifunctional CD-based theranostic nanoplatform functioning as a traceable and topically applied antifungal to arm oral epithelia, thereby shedding light on early intervention of mucosal candidiasis for oral and general health.


Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Candidíase/tratamento farmacológico , Infecções Fúngicas Invasivas/tratamento farmacológico , Anfotericina B/química , Antifúngicos/química , Biofilmes/efeitos dos fármacos , Disponibilidade Biológica , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Candidíase/microbiologia , Carbono/química , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/microbiologia , Guanosina Monofosfato/química , Humanos , Infecções Fúngicas Invasivas/microbiologia , Queratinócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/microbiologia , Polienos/química , Polienos/farmacologia , Pontos Quânticos/química
16.
J Photochem Photobiol B ; 201: 111633, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31726378

RESUMO

In the present study, we assessed the oral mucosal irritation potential of antimicrobial chemotherapy involving hydrogen peroxide (H2O2) photolysis with a 405-nm laser device at an output power of ≥100 mW in hamsters. Twenty-four cheek pouches from 12 male Syrian hamsters received 7-min treatment with pure water (PW), 3% H2O2, laser irradiation of PW at 100 mW, laser irradiation of 3% H2O2 at 100 mW, laser irradiation of PW at 200 mW, or laser irradiation of 3% H2O2 at 200 mW (n = 4 each). The diameter of the irradiation area was set at 3 mm; accordingly, the calculated irradiances (optical power densities) of the 100- and 200-mW laser lights were approximately 1400 and 2800 mW/cm2, respectively. In addition, 12 cheek pouches from six animals received laser irradiation of 3% H2O2 at 100 mW for 1, 3, or 5 min (n = 4 each). Each treatment was repeated three times at 1-h intervals. Macroscopic and histological changes were evaluated 24 h after the last treatment. In addition, in vitro bactericidal activity of the treatment against periodontal pathogens was evaluated. We found that 405-nm laser irradiation of 3% H2O2 caused moderate to severe oral mucosal irritation when performed at powers of 100 and 200 mW for ≥3 min, while the same treatment performed at 100 mW for 1 min resulted in mild irritation. Moreover, 1-min H2O2 photolysis at 100 mW caused a >4-log decrease in viable bacterial counts. These findings suggest that 1-min H2O2 photolysis, which can effectively kill periodontal pathogens, may be acceptable when a 405-nm laser device is used at 100 mW. However, use of the laser at a lower power would be preferable for the prevention of unnecessary oral mucosal irritation.


Assuntos
Anti-Infecciosos/farmacologia , Peróxido de Hidrogênio/farmacologia , Lasers , Mucosa Bucal/efeitos dos fármacos , Fotólise/efeitos dos fármacos , Células 3T3-L1 , Animais , Anti-Infecciosos/química , Anti-Infecciosos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Cricetinae , Espectroscopia de Ressonância de Spin Eletrônica , Masculino , Camundongos , Mucosa Bucal/metabolismo , Mucosa Bucal/efeitos da radiação , Periodontite/tratamento farmacológico , Fotólise/efeitos da radiação , Porphyromonas gingivalis/efeitos dos fármacos , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , Streptococcus mutans/efeitos dos fármacos
17.
In Vivo ; 33(6): 1807-1811, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662506

RESUMO

BACKGROUND/AIM: Car painting is considered an occupational exposure job with high risk for cancer development, due to the association with harmful chemicals and mutagens. This study aimed to profile car painters occupationally exposed and determine its association with DNA damage and genomic instability. MATERIALS AND METHODS: We collected a questionnaire and buccal cells of 74 individuals (37 car painters and 37 non-exposed workers) paired by age, alcohol and smoking habits. The number of pyknotic cells, karyolitic cells, karyorrhetic cells, condensed chromatin, binucleated cells, basal cells, differentiated cells (DIFF), micronucleated cells and nuclear buds were evaluated using the Buccal Micronucleus Cytome Assay protocol. RESULTS: A statistically significant increase was observed in all parameters (p<0.05) in the exposed group, but DIFF showed a statistically significant decrease (p<0.001), compared to the control group. CONCLUSION: In association with the poor work environment and lack of personal and collective protective equipment, occupational exposure of car painters leads to high DNA damage, genomic instability and alterations in cellular kinetics.


Assuntos
Citocinese/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Instabilidade Genômica/efeitos dos fármacos , Mutagênicos/efeitos adversos , Exposição Ocupacional/efeitos adversos , Pintura/efeitos adversos , Adulto , Automóveis , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/genética , Citocinese/genética , Dano ao DNA/genética , Humanos , Masculino , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Testes para Micronúcleos/métodos , Mucosa Bucal/efeitos dos fármacos , Neoplasias/induzido quimicamente , Neoplasias/genética
18.
Methods Mol Biol ; 2031: 147-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31473959

RESUMO

The micronucleus (MN) assay, applied in different surrogate tissues, is one of the best validated cytogenetic techniques for evaluating chromosomal damage in humans. The cytokinesis-block micronucleus cytome assay in peripheral blood lymphocytes (L-CBMNcyt) is the most frequently used method in biomonitoring human populations to evaluate DNA damage caused by exposure to genotoxic agents, micronutrient deficiency or excess and genetic instability. Furthermore, recent scientific evidence suggests an association between an increased MN frequency in lymphocytes and risk of cancer and other age-related degenerative diseases. The micronucleus cytome assay applied in buccal exfoliated cells (BMNCyt), provides a complementary method for measuring DNA damage and cytotoxic effects in an easily accessible tissue not requiring ex vivo/in vitro culture. The protocol for L-CBMNcyt described here, refers to the use of ex vivo whole blood method, involving 72 h of culture with the block of cytokinesis starting at 44 h. BMNCyt protocol reports the established method for sample collection, processing, slide preparation and scoring.


Assuntos
Linfócitos/efeitos dos fármacos , Testes para Micronúcleos/métodos , Mucosa Bucal/efeitos dos fármacos , Mutagênicos/toxicidade , Técnicas de Cultura de Células/métodos , Células Cultivadas , Aberrações Cromossômicas/induzido quimicamente , Citocinese/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Humanos , Linfócitos/citologia , Linfócitos/metabolismo , Mucosa Bucal/citologia , Mucosa Bucal/metabolismo , Coloração e Rotulagem/métodos
19.
Clin Adv Periodontics ; 9(1): 24-28, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31490034

RESUMO

INTRODUCTION: Pemphigus vulgaris (PV) is a relatively rare, potentially life-threatening autoimmune disease that, in most cases, has an unknown etiology. Medications for hypertension have been linked to the onset and exacerbation of PV-like symptoms. The diagnosis of medication-related PV can be challenging because it has an identical appearance to the clinical and histologic appearance of idiopathic PV and cases may not resolve after discontinuation of the drug. CASE PRESENTATION: We present a case of an elderly patient with gingival and cutaneous erosions, who underwent several medical and dental consultations without an appropriate diagnosis. After biopsy and a thorough review of her medical history, metoprolol was suspected as the offending agent. After consulting with her cardiologist, metoprolol was discontinued, and a complete resolution of all lesions resulted. CONCLUSIONS: To our knowledge, the current case is the first reported case of metoprolol-induced PV in the English-language literature. As such, it highlights the potential of medication involvement in some immune-mediated diseases. Because the oral mucosa is often the first site of involvement in PV, knowledge of drug-related PV is crucial in the diagnosis, treatment, and management of dental patients.


Assuntos
Anti-Hipertensivos , Metoprolol , Pênfigo , Idoso , Anti-Hipertensivos/efeitos adversos , Biópsia , Feminino , Humanos , Metoprolol/efeitos adversos , Mucosa Bucal/efeitos dos fármacos , Pênfigo/induzido quimicamente
20.
Mutat Res ; 781: 11-29, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31416572

RESUMO

A biomarker-based approach using micronucleus (MN) (extranuclear DNA-containing bodies) frequencies in buccal cells has been proposed to monitor workers exposed to aero-digestive carcinogens for early detection of occupational cancer. To assess this non-invasive MN approach, we sought to understand: (A) What is the extent of MN frequency increase in occupationally exposed over non-exposed populations across studies published in the scientific literature for buccal cells; and (B) Which types of occupational exposures give relevant summary MN ratios across studies published in the scientific literature. A systematic literature review was performed, and the MN frequency ratios for buccal cells were calculated for each occupational study. Meta-analytic techniques were applied using the confidence interval or a standard error on the log-transformed ratio. Exposure categories were developed based on similar occupational exposures or jobs. A summary ratio and proportion of variance explained (the I2 index) were derived assuming a Gaussian random effect model for each exposure category. The meta-analysis of the published literature (n = 96 studies) showed large random variability between studies within each category (I2 > 90%), except where exposures were to a single carcinogenic substance (e.g. formaldehyde, silica) or similar jobs were performed (e.g. antineoplastic dispensing, gasoline attendants). The greatest summary frequency ratios were for silica (FR 9.02 95%CI 6.83-11.93), formaldehyde (FR 4.81 95%CI 2.19-10.60), and for hairdressers as an exposure category (FR 7.06 95%CI 3.96-12.57). The unexplained between-study variability can be related to exposures to mixtures of carcinogens with unknown mechanisms. If the latter had been measured, the between-study variability may have been explained. We conclude that better exposure assessments are needed to understand the relationship between occupational exposures and MN frequency responses in buccal cells. Nevertheless, our analysis indicates that the buccal cell MN assay is a promising tool for surveying workers exposed to genotoxic agents.


Assuntos
Carcinógenos/toxicidade , Mucosa Bucal/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Monitoramento Biológico/métodos , Biomarcadores/análise , Humanos , Testes para Micronúcleos/métodos
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