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1.
Bioorg Chem ; 146: 107247, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38493635

RESUMO

The current investigation encompasses the structural planning, synthesis, and evaluation of the urease inhibitory activity of a series of molecular hybrids of hydroxamic acids and Michael acceptors, delineated from the structure of cinnamic acids. The synthesized compounds exhibited potent urease inhibitory effects, with IC50 values ranging from 3.8 to 12.8 µM. Kinetic experiments unveiled that the majority of the synthesized hybrids display characteristics of mixed inhibitors. Generally, derivatives containing electron-withdrawing groups on the aromatic ring demonstrate heightened activity, indicating that the increased electrophilicity of the beta carbon in the Michael Acceptor moiety positively influences the antiureolytic properties of this compounds class. Biophysical and theoretical investigations further corroborated the findings obtained from kinetic assays. These studies suggest that the hydroxamic acid core interacts with the urease active site, while the Michael acceptor moiety binds to one or more allosteric sites adjacent to the active site.


Assuntos
Ácidos Hidroxâmicos , Urease , Sítio Alostérico , Domínio Catalítico , Inibidores Enzimáticos/química , Ácidos Hidroxâmicos/química , Cinética , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Cinamatos/química
2.
Head Neck Pathol ; 17(4): 1067-1070, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37768443

RESUMO

Squamous odontogenic tumor (SOT) is a rare benign but locally infiltrative tumor often misdiagnosed as other entities, such as ameloblastoma and squamous cell carcinoma, due to overlapping morphological findings. We document here the clinicopathological and imaging findings of an aggressive intraosseous SOT in the posterior left region of the maxilla in a 25-year-old male patient. On intraoral examination, the tumor extended from the region of the left lateral incisor to the upper left premolar and was covered by reddish mucosa, with discrete areas of ulceration. Imaging exams revealed an osteolytic lesion causing thinning, erosion, and buccal and lingual cortical plate perforation associated with an impacted canine. Microscopically, the tumor showed a proliferation of islands of well-differentiated squamous epithelium in a variably collagenized background. The peripheral cells of the islands were flat or slightly cuboidal and did not exhibit nuclei with peripheral palisade and reverse polarization. The diagnosis of SOT was rendered. The patient underwent surgical resection and has been under clinical follow-up for approximately 12 months with no signs of recurrence. A careful morphological evaluation is essential to avoid misdiagnosis and ensure a satisfactory treatment approach.


Assuntos
Ameloblastoma , Tumor Odontogênico Escamoso , Tumores Odontogênicos , Masculino , Humanos , Adulto , Tumor Odontogênico Escamoso/patologia , Maxila/patologia , Tumores Odontogênicos/patologia , Ameloblastoma/patologia , Epitélio/patologia
3.
Pharmaceutics ; 15(7)2023 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-37514094

RESUMO

The development of green synthesized polymeric nanoparticles with anticancer studies has been an emerging field in academia and the pharmaceutical and chemical industries. Vegetable oils are potential substitutes for petroleum derivatives, as they present a clean and environmentally friendly alternative and are available in abundance at relatively low prices. Biomass-derived chemicals can be converted into monomers with a unique structure, generating materials with new properties for the synthesis of sustainable monomers and polymers. The production of bio-based polymeric nanoparticles is a promising application of green chemistry for biomedical uses. There is an increasing demand for biocompatible and biodegradable materials for specific applications in the biomedical area, such as cancer therapy. This is encouraging scientists to work on research toward designing polymers with enhanced properties and clean processes, containing oncology active pharmaceutical ingredients (APIs). The nanoencapsulation of these APIs in bio-based polymeric nanoparticles can control the release of the substances, increase bioavailability, reduce problems of volatility and degradation, reduce side effects, and increase treatment efficiency. This review discusses the use of green chemistry for bio-based nanoparticle production and its application in anticancer medicine. The use of castor oil for the production of renewable monomers and polymers is proposed as an ideal candidate for such applications, as well as more suitable methods for the production of bio-based nanoparticles and some oncology APIs available for anticancer application.

4.
Curr Alzheimer Res ; 20(3): 131-148, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37309767

RESUMO

The accumulation of amyloid-ß (Aß) is the main event related to Alzheimer's disease (AD) progression. Over the years, several disease-modulating approaches have been reported, but without clinical success. The amyloid cascade hypothesis evolved and proposed essential targets such as tau protein aggregation and modulation of ß-secretase (ß-site amyloid precursor protein cleaving enzyme 1 - BACE-1) and γ-secretase proteases. BACE-1 cuts the amyloid precursor protein (APP) to release the C99 fragment, giving rise to several Aß peptide species during the subsequent γ-secretase cleavage. In this way, BACE-1 has emerged as a clinically validated and attractive target in medicinal chemistry, as it plays a crucial role in the rate of Aß generation. In this review, we report the main results of candidates in clinical trials such as E2609, MK8931, and AZD-3293, in addition to highlighting the pharmacokinetic and pharmacodynamic-related effects of the inhibitors already reported. The current status of developing new peptidomimetic, non-peptidomimetic, naturally occurring, and other class inhibitors are demonstrated, considering their main limitations and lessons learned. The goal is to provide a broad and complete approach to the subject, exploring new chemical classes and perspectives.


Assuntos
Doença de Alzheimer , Secretases da Proteína Precursora do Amiloide , Humanos , Secretases da Proteína Precursora do Amiloide/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Peptídeos beta-Amiloides/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico
5.
Head Neck Pathol ; 16(2): 407-415, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34414559

RESUMO

Juvenile xanthogranuloma (JXG) is the most common form of non-Langerhans cell histiocytosis and oral mucosal involvement is exceedingly rare. Histiocytic disorders harbor activating mutations in MAPK pathway, including the report of BRAF V600E in JXG of extracutaneous site. However, no information is available for oral JXG. Herein, the clinicopathological and immunohistochemical features of five new oral JXG were evaluated in conjunction with literature review. Also, we assessed the BRAF V600E in oral samples. Five oral JXG were retrieved from pathology archives. Morphological and immunohistochemical analyses were performed. The BRAF V600E status was determined with TaqMan allele-specific qPCR. The series comprised of three female and two male patients, most of them adults, with a median age of 39 years (range 13-68 years). Clinically, the lesions appeared as asymptomatic solitary nodules, measuring until 2.5 cm, with more incident to the buccal mucosa. Morphologically, most of the cases presented classical histological features of JXG, with histiocytic cells consistent with the non-Langerhans cell immunophenotype. BRAF V600E was not detected in the cases tested. This is the first and largest published series of oral JXG affecting adults and a Brazilian population. The molecular pathogenesis of oral JXG remains unknown. Clinicians and pathologists must recognize JXG to avoid misdiagnoses with oral benign or malignant lesions.


Assuntos
Xantogranuloma Juvenil , Adolescente , Adulto , Idoso , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Xantogranuloma Juvenil/diagnóstico , Xantogranuloma Juvenil/genética , Xantogranuloma Juvenil/metabolismo , Adulto Jovem
6.
Oral Dis ; 28(6): 1561-1572, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34263964

RESUMO

OBJECTIVE: To report the clinicopathologic features of acquired oral syphilis cases in South American countries. MATERIALS AND METHODS: Clinical data were retrospectively collected from the records of 18 oral diagnostic services in Argentina, Brazil, Chile, Colombia, Venezuela, Uruguay, and Peru. Serologies of nontreponemal and treponemal tests were used for diagnosis. RESULTS: The series comprised 339 cases of acquired oral syphilis. Secondary syphilis ranked as the most common stage (86.7%). Lesions were more frequent among males (58.0%) and young adults with a mean age of 33.3 years. Individuals aged 20-29 years were most affected (35.3%). The most commonly involved sites were the tongue (31.6%), lip/labial commissure (25.1%), and hard/soft palate (20.4%). Clinically, acquired oral syphilis usually presented as mucous patches (28.4%), papules (25.7%), and ulcers (18.1%). Skin manifestations occurred in 67.7% of individuals, while lymphadenopathy and fever were observed in 61.3% and 11.6% of all subjects, respectively. Most patients were treated with the benzathine penicillin G antibiotic. CONCLUSION: This report validates the spread of acquired oral syphilis infection among young adults in South America. Our directives include accessible diagnostic tools for proper disease screening, surveillance, and counselling of affected individuals, especially in low- and middle-income countries.


Assuntos
Doenças da Boca , Sífilis , Adulto , Brasil/epidemiologia , Humanos , Masculino , Doenças da Boca/diagnóstico , Doenças da Boca/tratamento farmacológico , Doenças da Boca/epidemiologia , Palato Duro , Estudos Retrospectivos , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Sífilis/epidemiologia , Adulto Jovem
7.
J Oral Pathol Med ; 50(6): 548-557, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34091947

RESUMO

BACKGROUND: The diagnosis of oral and maxillofacial mature T/NK-cell neoplasms is challenging because of their rarity, morphological heterogeneity and complex immunophenotype with scarce available data describing their clinical and microscopic aspects. Therefore, in this study, we investigated a series of mature T/NK-cell neoplasms affecting this anatomical region and provided an updated literature review. METHODS: Cases diagnosed as mature T/NK-cell lymphomas affecting the oral and maxillofacial region were retrospectively retrieved from six pathology files and their diagnoses were confirmed using haematoxylin and eosin-stained slides, immunohistochemical reactions and in situ hybridization for Epstein-Barr virus (EBV) detection. Patients' clinical data were collected from their pathology forms. RESULTS: A total of 22 cases were included in this study. Eleven (50%) consisted of extranodal NK/T-cell lymphomas, nasal type; eight (36.4%) were peripheral T-cell lymphomas, NOS; two (9.1%) were adult T-cell leukaemia/lymphomas, and one (4.5%) was an ALK-positive anaplastic large cell lymphoma. Overall, males predominated, with a mean age of 55.7 years. The palate was the most affected site (50%), and tumours usually presented as destructive and painful ulcers. EBV was present in all cases of extranodal NK/T-cell lymphoma nasal type but was absent in the other subtypes. CONCLUSION: Among mature T/NK-cell lymphomas of the oral and maxillofacial region, extranodal NK/T-cell lymphoma, nasal type and peripheral T-cell lymphoma, NOS predominated. Older men were the most affected patients, and this heterogeneous group of neoplasms has a very aggressive clinical behaviour.


Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Extranodal de Células T-NK , Linfoma de Células T Periférico , Adulto , Idoso , Herpesvirus Humano 4 , Humanos , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma de Células T Periférico/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Gerodontology ; 38(3): 317-320, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33590916

RESUMO

INTRODUCTION: Nasolabial Cyst (NC) or Klestadt's cyst is a relatively rare soft tissue developmental lesion of nasal alar region accounting for 0.7% of all non-odontogenic cysts. NC usually presents as an asymptomatic swelling located in the anterior region of the maxilla lateral to midline-resulting in obliteration of nasolabial sulcus, nasal vestibule and maxillary labial sulcus and facial asymmetry-often observed on early stages by most patients due to cosmetics issues. CASE REPORT: A 76-year-old woman was referred for evaluation of an asymptomatic facial swelling in the left upper lip region lasting 20 years. Extraoral clinical examination showed a left-sided swelling lateral to midline near to the alar base resulting in facial asymmetry. Intraoral clinical examination revealed the presence of a single painless well-defined nodular, sessile, non-tender swelling covered by normal oral mucosa, and located in the upper labial mucosa in the left incisor's region. An excisional biopsy was performed, and microscopic examination revealed a cystic cavity lined by cuboidal to columnar epithelium with mucous cells. The underlying connective tissue showed chronic inflammatory infiltrate close to muscular tissue. Patient recovery was uneventful, and there are no signs of local recurrence in a 2-year clinical follow-up. CONCLUSION: Clinicians should consider NC when evaluating an upper lip swelling extending to the nasolabial region of the elders.


Assuntos
Cistos , Doenças Nasais , Idoso , Cistos/diagnóstico por imagem , Feminino , Humanos , Mucosa Bucal , Recidiva Local de Neoplasia , Doenças Nasais/diagnóstico
9.
Rev. bras. odontol ; 77(1): 1-6, jan. 2020. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1103876

RESUMO

O objetivo do presente estudo foi avaliar a eficácia clínica e histopatológica da terapia fotodinâmica (TFD) associada à terapia a laser de baixa potência no tratamento de pacientes com queilite actínica (QA) após seis meses de acompanhamento. Material e Métodos: pacientes com QA ativa foram submetidos a duas sessões de TFD associadas à laserterapia de baixa potência, utilizando o 5-aminolevulinato de metila como droga fotossensibilizadora. Após seis meses de acompanhamento, uma nova biópsia incisional foi realizada para avaliar a resposta ao tratamento. Resultados: excelentes taxas de eficácia foram observadas na melhora dos sintomas neste estudo, no entanto, a análise histopatológica não foi tão promissora e apenas a melhora do grau de displasia só pode ser observada em 20% da amostra. Conclusão: de acordo com os resultados do presente estudo, pode-se concluir que a terapia fotodinâmica associada à laserterapia de baixa potência parece ser uma opção a ser considerada no tratamento da Queilite Actínica. No entanto, os pacientes devem ser acompanhados de perto clinicamente e, eventualmente, histopatologicamente


Objective: the aim of the present study was to evaluate the clinical and histopathological efficacy of photodynamic therapy (PDT) associated with the low-level laser therapy (LLLT) in the treatment of patients with Actinic Cheilitis (AC) after a six-month follow-up. Material and Methods: patients with active AC undergone through two sessions of PDT, associated with the low-level laser therapy using the Methyl 5-aminolevulinate as a photosensybilizer drug. After a six-month follow-up, a new incisional biopsy was performed in order to evaluate the response to treatment. Results: excellent efficacy rates were observed in the improvement of symptoms in this study, however, histopathological analysis was not so promising and the improvement of dysplasia degree could only be seen in 20% of the sample. Conclusion: according to the results of the present study, we concluded that the photodynamic therapy associated with low-level laser therapy is an option to be considered when treating Actinic Cheilits. However, patients should be clinically followed-up in a severing agenda and eventually, histopathologically


Assuntos
Fotoquimioterapia , Terapia com Luz de Baixa Intensidade , Queilite/terapia
10.
Rev Assoc Med Bras (1992) ; 65(2): 246-252, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30892451

RESUMO

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are drugs that act by maintaining glycosuria. Recent studies have shown promising effects of these in the treatment of type 2 diabetes mellitus (DM2). However, there may be an increased risk of developing urinary tract infections (UTIs) in patients treated with these. Our study aims to analyze the association between the risk of UTI in patients treated with SGLT2i. A systematic review of the literature was carried out by randomized clinical trials, totalizing at the end of the selection 23 articles that were statistically evaluated. The incidence of UTI was generally demonstrated in articles and in different subgroups: patients on SGLT2i monotherapy or on combination therapy; according to specific comorbidities of each sample or according to the drug used. They noticed an increase in the chance of UTI in the SGLT2i groups compared to the control groups on placebo or other oral antidiabetic agents. This increased chance was found predominantly with the use of Dapagliflozin, Canagliflozin, and Tofogliflozin, regardless of the dosing. Lastly, stands out that the dimension of UTI chances for DM2 patients who use SGLT2i remains to be more strictly determined.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Infecções Urinárias/etiologia , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Canagliflozina/efeitos adversos , Canagliflozina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Glucosídeos/efeitos adversos , Glucosídeos/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
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