RESUMO
This pilot study assessed the glycaemic control and the serum levels of inflammatory mediators in type 2 diabetes (T2DM) patients with apical periodontitis (AP). Thirty individuals were divided into four groups: Healthy (H); with AP (AP); with T2DM (T2DM); and with T2DM and AP (T2DM-AP). Demographic and pharmacological data were registered. The body mass index (BMI) and the levels of glycated haemoglobin (HbA1c) and IL-1ß, IL-6, IL-10, CCL3 and CCL4 were evaluated. AP areas were determined radiographically. Mean age was 64 ± 12 years, with 63% females. Most T2DM patients were under treatment with metformin and antihypertensives. BMI and H1bAc were significantly higher in T2DM patients in relation to H and AP groups. The AP areas were larger in the T2DM-AP group, compared with the AP group. These preliminary findings suggest no influence of AP on glycaemic control or inflammatory levels amongst T2DM patients, although T2DM increased the AP severity.
Assuntos
Diabetes Mellitus Tipo 2 , Periodontite Periapical , Idoso , Biomarcadores , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
Fibromyalgia is characterized by the amplification of central nervous system pain with concomitant fatigue, sleep, mood disorders, depression, and anxiety. It needs extensive pharmacological therapy. In the present study, Swiss mice were treated with reserpine (0.25 mg/kg, s.c.) over three consecutive days, in order to reproduce the pathogenic process of fibromyalgia. On day 4, the administrations of the Tx3-3 toxin produced significant antinociception in the mechanical allodynia (87.16% ±12.7%) and thermal hyperalgesia (49.46% ± 10.6%) tests when compared with the PBS group. The effects produced by the classical analgesics (duloxetine 30 mg/kg, pramipexole 1 mg/kg, and pregabalin 30 mg/kg, p.o., respectively) in both of the tests also demonstrated antinociception. The administrations were able to increase the levels of the biogenic amines (5-HTP and DE) in the brain. The treatments with pramipexole and pregabalin, but not duloxetine, decreased the immobility time in the FM-induced animals that were submitted to the forced swimming test; however, the Tx3-3 toxin (87.45% ± 4.3%) showed better results. Taken together, the data has provided novel evidence of the ability of the Tx3-3 toxin to reduce painful and depressive symptoms, indicating that it may have significant potential in the treatment of FM.
Assuntos
Analgésicos/administração & dosagem , Fibromialgia/tratamento farmacológico , Neuropeptídeos/administração & dosagem , Anestésicos/administração & dosagem , Animais , Modelos Animais de Doenças , Fibromialgia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Masculino , Camundongos , Reserpina/administração & dosagemRESUMO
Introduction: The tumors affecting salivary glands have a wide morphological diversity. Objective: This study aimed to examine the prevalence of salivary gland tumors in patients treated at São Lucas Teaching Hospital at the Pontifical Catholic University of Rio Grande do Sul (HSL-PUCRS), in Porto Alegre (RS), Brazil, from 2007 to 2016. Method: A retrospective study analyzing 201 files from the Department of Pathology at the HSL-PUCRS was carried out, by revising the medical records. Results: Seventy-three cases of salivary gland tumors were found, and their electronic and physical medical records were analyzed. Of the 73 cases, 56 (76.7%) were benign tumors and 17 (23.3%) were malignant tumors. The age group with the highest number of cases was between 41 and 60 years of age and the highest prevalence was found in females, with 54.8% of the cases. The parotid gland presented the highest prevalence, accounting for 72.6% of the cases. The predominant neoplasia was the pleomorphic adenoma, accounting for 53.4% of the tumors. The standard of distribution of neoplasms of salivary glands was similar to the encountered in other Brazilian regions. Conclusion: The largest salivary glands were the most affected by neoplastic processes. Pleomorphic adenoma and adenoid cystic carcinoma were the most frequent benign and malignant tumors, respectively, and parotid gland was the most affected site. In the light of previous literature data, the results allow to infer that some demographic characteristics (for example, sex and age) vary among the different geographic regions
Introducción: Los tumores que afectan a las glándulas salivales tienen una amplia diversidad morfológica. Objetivo: Identificar la prevalencia de neoplasias de glándulas salivales en pacientes atendidos en el Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (HSLPUCRS), en Porto Alegre (RS), desde 2007 hasta 2016. Método: Estudio retrospectivo mediante el análisis de 201 registros del Departamento de Patología de HSL-PUCRS. Resultados: Se encontraron 73 casos de neoplasias de glándulas salivales y se analizaron los registros electrónicos y físicos de los casos seleccionados. De los 73 casos, 56 (76,7%) fueron de neoplasias benignas y 17 (23,3%) de neoplasias malignas. El grupo de edad con mayor número de casos fue el de 41 a 60 años, y la mayor prevalencia en mujeres, con 54,8%. La glándula parótida tuvo una mayor prevalencia, constituyendo 72,6% de los casos. El tipo neoplásico más prevalente fue el adenoma pleomorfo, con 53,4%. El patrón de distribución de las neoplasias de glándulas salivales fue similar al encontrado en otras regiones de Brasil. Conclusión: Las glándulas salivales mayores fueron las glándulas más afectadas por procesos neoplásicos. El adenoma pleomórfico y el carcinoma adenoide quístico fueron los tumores benignos y malignos más frecuentes, respectivamente y el sitio más afectado fue la glándula parótida. Con base en la literatura previa, estos resultados permiten inferir que algunas características demográficas (por ejemplo, sexo y edad) varían entre las distintas regiones geográficas
Introdução: Os tumores que afetam as glândulas salivares apresentam vasta diversidade morfológica. Objetivo: Identificar a prevalência de neoplasias de glândulas salivares em pacientes atendidos no Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (HSL-PUCRS), em Porto Alegre (RS), no período de 2007 a 2016. Método: Estudo retrospectivo por meio da análise de 201 arquivos do Departamento de Patologia do HSL-PUCRS. Resultados: Foram encontrados 73 casos de neoplasias de glândulas salivares e os prontuários eletrônicos e físicos dos casos selecionados foram analisados. Dos 73 casos, 56 (76,7%) eram de neoplasias benignas e 17 (23,3%) de neoplasias malignas. A faixa etária com maior número de casos foi entre 41 e 60 anos e o sexo feminino apresentou a maior prevalência com 54,8%. A glândula parótida apresentou maior prevalência, perfazendo 72,6% dos casos. O tipo neoplásico mais prevalente foi o adenoma pleomórfico, com 53,4%. O padrão de distribuição das neoplasias de glândulas salivares foi semelhante ao encontrado em outras Regiões do Brasil. Conclusão: As glândulas salivares maiores foram as mais afetadas pelos processos neoplásicos. Adenoma pleomórfico e carcinoma adenoide cístico foram os tumores benignos e malignos mais frequentes, respectivamente, e a glândula parótida foi o local mais acometido. Com base na literatura prévia, esses resultados permitem inferir que algumas características demográficas (por exemplo, sexo e idade) variam entre as diferentes Regiões geográficas
Assuntos
Glândula Parótida , Glândulas Salivares Menores , Neoplasias das Glândulas Salivares , Adenoma Pleomorfo , Neoplasias de Cabeça e PescoçoRESUMO
The regenerative effects of stem cells derived from dental tissues have been previously investigated. This study assessed the potential of human tooth stem cells from apical papilla (SCAP) on nerve regeneration. The SCAP collected from nine individuals were characterized and polarized by exposure to interferon-γ (IFN-γ). IFN-γ increased kynurenine and interleukin-6 (IL-6) production by SCAP, without affecting the cell viability. IFN-γ-primed SCAP exhibited a decrease of brain-derived neurotrophic factor (BDNF) mRNA levels, followed by an upregulation of glial cell-derived neurotrophic factor mRNA. Ex vivo, the co-culture of SCAP with neurons isolated from the rat dorsal root ganglion induced neurite outgrowth, accompanied by increased BDNF secretion, irrespective of IFN-γ priming. In vivo, the local application of SCAP reduced the mechanical and thermal hypersensitivity in Wistar rats that had been submitted to sciatic chronic constriction injury. The SCAP also reduced the pain scores, according to the evaluation of the Grimace scale, partially restoring the myelin damage and BDNF immunopositivity secondary to nerve lesion. Altogether, our results provide novel evidence about the regenerative effects of human SCAP, indicating their potential to handle nerve injury-related complications.
Assuntos
Papila Dentária/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Regeneração Nervosa/fisiologia , Adolescente , Animais , Diferenciação Celular , Polaridade Celular/efeitos dos fármacos , Quimiocinas/metabolismo , Doença Crônica , Constrição Patológica , Modelos Animais de Doenças , Gânglios Espinais/metabolismo , Humanos , Inflamação/patologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interferon gama/farmacologia , Masculino , Neurônios/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Receptor 3 Toll-Like/agonistas , Receptor 3 Toll-Like/metabolismo , Receptor 4 Toll-Like/agonistas , Receptor 4 Toll-Like/metabolismo , Adulto JovemRESUMO
Taxane-derived drugs are antineoplastic agents used for the treatment of highly common malignancies. Paclitaxel and docetaxel are the most commonly used taxanes; however, other drugs and formulations have been used, such as cabazitaxel and nab-paclitaxel. Taxane treatment is associated with neurotoxicity, a well-known and relevant side effect, very prevalent amongst patients undergoing chemotherapy. Painful peripheral neuropathy is the most dose-limiting side effect of taxanes, affecting up to 97% of paclitaxel-treated patients. Central neurotoxicity is an emerging side effect of taxanes and it is characterized by cognitive impairment and encephalopathy. Besides impairing compliance to chemotherapy treatment, taxane-induced neurotoxicity (TIN) can adversely affect the patient's life quality on a long-term basis. Despite the clinical relevance, not many reviews have comprehensively addressed taxane-induced neurotoxicity when they are used therapeutically. This article provides an up-to-date review on the pathophysiology of TIN and the novel potential therapies to prevent or treat this side effect.
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Antineoplásicos , Taxoides , Antineoplásicos/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Docetaxel , Humanos , Paclitaxel , Taxoides/efeitos adversosRESUMO
Generalized pain and fatigue are both hallmarks of fibromyalgia, a syndrome with an indefinite etiology. The treatment options for fibromyalgia are currently limited, probably because of its intricate pathophysiology. Thus, further basic and clinical research on this condition is currently needed. This study investigated the effects of nociceptin/orphanin FQ (N/OFQ) receptor (NOPr) ligands and the modulation of the NOP system in the preclinical mouse model of reserpine-induced fibromyalgia. The effects of administration of the natural agonist N/OFQ and the selective NOPr antagonists (UFP-101 and SB-612111) were evaluated in fibromyalgia-related symptoms in reserpine-treated mice. The expression of prepronociceptin/orphanin FQ and NOPr was assessed in central and peripheral sites at different time points after reserpine administration. Nociceptin/orphanin FQ displayed dual effects in the behavioral changes in the reserpine-elicited fibromyalgia model. The peptide NOPr antagonist UFP-101 produced analgesic and antifatigue effects, by preventing alterations in brain activity and skeletal muscle metabolism, secondary to fibromyalgia induction. The nonpeptide NOPr antagonist SB-612111 mirrored the favorable effects of UFP-101 in painful and fatigue alterations induced by reserpine. A time-related up- or downregulation of prepronociceptin/orphanin FQ and NOPr was observed in supraspinal, spinal, and peripheral sites of reserpine-treated mice. Our data shed new lights on the mechanisms underlying the fibromyalgia pathogenesis, supporting a role for N/OFQ-NOP receptor system in this syndrome.
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Analgésicos/farmacologia , Fadiga/tratamento farmacológico , Fibromialgia/tratamento farmacológico , Peptídeos Opioides/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Antagonistas de Entorpecentes/farmacologia , Dor/tratamento farmacológico , Precursores de Proteínas/farmacologia , Receptores Opioides/efeitos dos fármacos , Receptor de Nociceptina , NociceptinaRESUMO
This study investigated the effects of smooth and microgrooved membrane blends, with different polycaprolactone (PCL)/ poly(lactic-co-glycolic acid) (PLGA) ratios on the viability, proliferation, and adhesion of different mammalian cell types. The polymer matrices with and without microgrooves, obtained by solvent casting, were characterized by field-emission scanning electron microscopy, atomic force microscopy, contact angle and Young's modulus. Blend characterization showed an increase in roughness and stiffness of membranes with 30% PLGA, without any effect on the contact angle value. Pure PCL significantly decreased the viability of Vero, HaCaT, RAW 264.7, and human fetal lung and gingival fibroblast cells, whereas addition of increasing concentrations of PLGA led to a reduced cytotoxicity. Increased proliferation rates were observed for all cell lines. Fibroblasts adhered efficiently to smooth membranes of the PCL70/PLGA30 blend and pure PLGA, compared to pure PCL and silicone. Microgrooved membranes promoted similar cell adhesion for all groups. Microstructured membranes (15 and 20-µm wide grooves) promoted suitable orientation of fibroblasts in both PCL70/PLGA30 and pure PLGA, as compared to pure PCL. Neuronal cells of the dorsal root ganglion exhibited an oriented adhesion to all the tested microgrooved membranes. Data suggest a satisfactory safety profile for the microgrooved PCL70/PLGA30 blend, pointing out this polymer combination as a promising biomaterial for peripheral nerve regeneration when cell orientation is required. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1522-1534, 2018.
Assuntos
Materiais Biocompatíveis/química , Poliésteres/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Alicerces Teciduais/química , Animais , Adesão Celular , Linhagem Celular , Células Cultivadas , Chlorocebus aethiops , Módulo de Elasticidade , Humanos , Masculino , Camundongos , Células RAW 264.7 , Ratos Wistar , Propriedades de Superfície , Engenharia Tecidual , Células VeroRESUMO
Background Breast cancer is highly prevalent among women worldwide. It is classified into three main subtypes: estrogen receptor positive (ER+), human epidermal growth factor receptor 2 positive (HER2+), and triple negative breast cancer (TNBC). This study has evaluated the effects of aspirin and metformin, isolated or in a combination, in breast cancer cells of the different subtypes. Methods The breast cancer cell lines MCF-7, MDA-MB-231, and SK-BR-3 were treated with aspirin and/or metformin (0.01 mM - 10 mM); functional in vitro assays were performed. The interactions with the estrogen receptors (ER) were evaluated in silico. Results Metformin (2.5, 5 and 10 mM) altered the morphology and reduced the viability and migration of the ER+ cell line MCF-7, whereas aspirin triggered this effect only at 10 mM. A synergistic effect for the combination of metformin and aspirin (2.5, 5 or 10 mM each) was observed in the TNBC cell subtype MDA-MB-231, according to the evaluation of its viability and colony formation. Partial inhibitory effects were observed for either of the drugs in the HER2+ cell subtype SK-BR-3. The effects of metformin and aspirin partly relied on cyclooxygenase-2 (COX-2) upregulation, without the production of lipoxins. In silico, metformin and aspirin bound to the ERα receptor with the same energy. Conclusion We have provided novel evidence on the mechanisms of action of aspirin and metformin in breast cancer cells, showing favorable outcomes for these drugs in the ER+ and TNBC subtypes.
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Antineoplásicos/farmacologia , Aspirina/farmacologia , Neoplasias da Mama/tratamento farmacológico , Metformina/farmacologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Receptores de Estrogênio/metabolismoRESUMO
OBJECTIVE: Nystatin and chlorhexidine are extensively used in oral medicine; however, there is some controversy about the possibility of these drugs showing antagonism. To clarify this issue, this study investigated the efficacy and stability of nystatin and chlorhexidine in combination. DESIGN: An in vitro study was conducted to analyze the effect of nystatin and chlorhexidine combined on Candida albicans ATCC 18804, using the drugs mixed as a single formulation and as independent formulations used sequentially with different time intervals between them. The minimum inhibitory concentration (MIC) and effects on C. albicans suspensions and biofilms were evaluated. Also, the stability of nystatin and chlorhexidine in a mixture was tested by high performance liquid chromatography (HPLC). RESULTS: When nystatin and chlorhexidine were mixed in a single formulation, there was no significant difference in MIC compared to that of the drugs used alone (as the only treatment). However, when these drugs were used as independent formulations, sequentially with time intervals in between, their MICs were higher than the respective MIC of the drug used alone, except for the MIC of chlorhexidine with a 10-min interval. Nystatin/chlorhexidine combinations showed lower activity against C. albicans biofilms, except for that with a 30-min interval. The drugs when combined showed high percentages of degradation at all the times evaluated. CONCLUSIONS: The combination of nystatin and chlorhexidine seems to interfere with the efficacy of the drugs and to increase their rate of degradation.