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In the context of neglected diseases, tegumentary leishmaniasis (TL) presents an emerging and re-emerging character in the national territory and in the world. The treatment of TL has limitations, such as intravenous administration route, high toxicity, and high treatment costs. Thus, several researchers work on new therapeutic strategies to improve the effectiveness of the treatment of leishmaniasis. In this light, the present study used a topical formulation, containing 8-hydroquinoline (8-HQN), for the treatment of Balb/c mice infected with L. amazonensis. After the treatment, the mean diameter of the lesion was measured, as well as the parasite load in organs and immunological parameters associated with the treatment. The results showed that the animals treated with 8-HQN 5%, when compared to controls, showed a reduction in the mean diameter of the lesion and in the parasite load. The animals treated with the ointment showed a type 1 cellular immune response profile associated with the production of cytokines such as INF-γ and TNF-α. In addition, the treatment did not demonstrate toxicity to mice. Therefore, the topical formulation containing 8-HQN 5% is a promising candidate in the topical treatment and could be considered, in the future, as an alternative for the treatment of TL.

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The application of computer-aided drug discovery (CADD) approaches has enabled the discovery of new antimicrobial therapeutic agents in the past. The high prevalence of methicillin-resistantStaphylococcus aureus(MRSA) strains promoted this pathogen to a high-priority pathogen for drug development. In this sense, modern CADD techniques can be valuable tools for the search for new antimicrobial agents. We employed a combination of a series of machine learning (ML) techniques to select and evaluate potential compounds with antibacterial activity against methicillin-susceptible S. aureus (MSSA) and MRSA strains. In the present study, we describe the antibacterial activity of six compounds against MSSA and MRSA reference (American Type Culture Collection (ATCC)) strains as well as two clinical strains of MRSA. These compounds showed minimal inhibitory concentrations (MIC) in the range from 12.5 to 200 µM against the different bacterial strains evaluated. Our results constitute relevant proven ML-workflow models to distinctively screen for novel MRSA antibiotics.

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Breast cancer prevails as the most common cancer in women, underscoring an urgent need for more effective therapies. This study explores the potential of our newly developed nanoemulsion containing a novel fucoside derivative of lapachol (NE-F-LapA) as an intravenous treatment strategy. We sought to overcome the solubility issues associated with fucoside with this improved drug delivery strategy that enhances tumor delivery and mitigates other dose-limiting toxicities. Nanoemulsion was prepared and characterized by DLS, zeta potential, encapsulation efficiency, and storage stability. Cytotoxicity against breast cancer cell lines (4T1 and MDA-MB-231) and non-tumor human fibroblasts (NTHF) were evaluated. In vivo assays included antitumoral activity performance and acute systemic toxicity in mice models. NE-F-LapA was synthesized and optimized to 200 nm size, - 20 mV zeta potential, and near-complete (>98%) drug encapsulation. Stability exceeded 6 months, and biological fluid exposure maintained suitable properties for administration. In vitro, NE-F-LapA showed high toxicity (3 µM) against 4T1 and MDA-MB-231, enhanced five times the breast cancer cell uptake and three times the selectivity when compared to normal cells. Systemic toxicity assessment in mice revealed no concerning hematological or biochemical changes. Finally, in a 4T1 breast tumor model, NE-F-LapA significantly inhibited growth by 50% of the subcutaneous 4T1 tumor and reduced lung metastases 5-fold versus control. Overall, tailored nanoemulsification of the lapachol derivative enabled effective intravenous administration and improved efficacy over the free drug, indicating promise for enhanced breast cancer therapy pending further optimization.

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The coating of liposomes with polyethyleneglycol (PEG) has been extensively discussed over the years as a strategy for enhancing the in vivo and in vitro stability of nanostructures, including doxorubicin-loaded liposomes. However, studies have shown some important disadvantages of the PEG molecule as a long-circulation agent, including the immunogenic role of PEG, which limits its clinical use in repeated doses. In this context, hydrophilic molecules as carbohydrates have been proposed as an alternative to coating liposomes. Thus, this work studied the cytotoxicity and preclinical antitumor activity of liposomes coated with a glycosyl triazole glucose (GlcL-DOX) derivative as a potential strategy against breast cancer. The glucose-coating of liposomes enhanced the storage stability compared to PEG-coated liposomes, with the suitable retention of DOX encapsulation. The antitumor activity, using a 4T1 breast cancer mouse model, shows that GlcL-DOX controlled the tumor growth in 58.5% versus 35.3% for PEG-coated liposomes (PegL-DOX). Additionally, in the preliminary analysis of the GlcL-DOX systemic toxicity, the glucose-coating liposomes reduced the body weight loss and hepatotoxicity compared to other DOX-treated groups. Therefore, GlcL-DOX could be a promising alternative for treating breast tumors. Further studies are required to elucidate the complete GlcL-DOX safety profile.

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A síndrome pós-COVID-19 afeta pacientes independentemente da gravidade da doença. Os sintomas mais comuns são fadiga, cefaleia, déficit de atenção, dispneia e depressão. Para ajudar na reabilitação dos pacientes, a intervenção fisioterapêutica tem sido utilizada como estratégia. Objetivo: Analisar os efeitos de um programa de reabilitação fisioterapêutica na qualidade de vida, capacidade funcional, percepção de esforço, percepção da dor e força muscular, em indivíduos com a síndrome pós-COVID-19. Métodos: Trata-se de um estudo quase experimental, com 33 indivíduos, divididos em dois grupos: intervenção (GI) que recebeu um programa de reabilitação fisioterapêutica e controle (GC) que não recebeu. Os participantes foram avaliados antes e após o período de intervenção para força, por meio de dinamometria de preensão palmar; nível de dor, pela escala visual analógica; capacidade funcional, pelo teste de caminhada de seis minutos; percepção de esforço, através da escala modificada de BORG e qualidade de vida pelo instrumento SF-36. Resultados: Observou-se no GI aumento significativo (p<0,05) da qualidade de vida nos domínios de capacidade funcional, aspectos físicos e redução da dor e aumento da força de preensão palmar. Houve diferença significativa (p<0,05) entre os grupos para percepção de esforço nos momentos antes e após as intervenções. Para as demais variáveis não foram evidenciadas diferenças significativas. Conclusão: O programa de intervenção fisioterapêutica promoveu melhora dos domínios de capacidade funcional, aspectos físicos e da dor da qualidade de vida, e aumento da força de preensão palmar de indivíduos com sintomas da síndrome pós-COVID-19.

Post-COVID-19 syndrome affects patients regardless of the severity of the disease. The most common symptoms are fatigue, migraine, attention deficit, dyspnea, and depression. Physiotherapeutic intervention has been used as a strategy to aid the rehabilitation of patients. Objective: To analyze the effects of a physiotherapeutic rehabilitation program on quality of life, functional capacity, perceived exertion, perception of pain, and muscle strength in patients with post-COVID-19 syndrome. Methods: This is a quasi-experimental study with 33 participants, divided into two groups: an intervention group (IG) who received the physiotherapeutic rehabilitation program and a control group (CG) who did not. Participants were assessed for strength before and after the intervention period, using handgrip dynamometry and being assessed with a visual analog scale (VAS) for pain, the six-minute walk test (6MWT) for functional capacity, the BORG scale for exertion perception, and the SF-36 scale for quality of life. Results: A significant increase (p<0.05) in quality of life was observed in the IG in the SF-36 domains of physical functioning, physical role limitations, bodily pain, and increased handgrip strength. There was a significant difference (p<0.05) between the groups for perceived exertion before and after the intervention. No significant differences were found among the other variables. Conclusion: The physiotherapeutic intervention program improved the quality of life assessed with the SF-36 domains of physical functioning, physical role limitations, and bodily pain, and increased handgrip strength of patients with symptoms of post-COVID-19 syndrome.

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BACKGROUND: Lung cancer is the deadliest type of cancer in the world and the search for compounds that can treat this disease is highly important. Lawsone (2-hydroxy-1,4-naphtoquinone) is a naphthoquinone found in plants from the Lawsone genus that show a high cytotoxic effect in cancer cell lines and its derivatives show an even higher cytotoxic effect. METHODS: Sulforhodamine B was used to evaluate the cytotoxic activity of compounds on tumor cells. Clonogenic assay was used to analyze the reduction of colonies and wound healing assay to the migratory capacity of A549 cells. Apoptosis and necrosis were analyzed by flow cytometer and Giemsa staining. Hemolysis assay to determine toxicity in human erythrocytes. RESULTS: Lawsone derivatives were evaluated and compound 1 (O-propargyllawsone) was the one with the highest cytotoxic effect, with IC50 below 2.5 µM in A549 cells. The compound was able to reduce colony formation and inhibit cell migration. Morphological changes and cytometry analysis show that the compound induces apoptosis and necrosis in A549 cells. CONCLUSIONS: These results show that O-propargyllawsone show a cytotoxic effect and may induce apoptosis in A549 cells.

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Objective: To analyze the effect of the Mobilization With Movement (MWM) of the Mulligan's concept in the perception of nociceptive and neuropathic pain, range of motion (ROM) and joint mobility of individuals with low back pain. Method: This is a randomized and controlled clinical trial, with 30 volunteers with nonspecific low back pain, divided into: Intervention Group (INTG), that received sustained natural apophyseal glides (SNAG) type MWM of the Mulligan's concept; Control Group (CONTG), which received a similar intervention to INTG. Volunteers were assessed using the Numeric Rating Scale for Pain (NRS Pain); the Modified Schober Test (MST) and ROM by goniometry for lumbar spine mobility and Douleur Neuropatique 4 (DN4) questionnaire for assessment of neuropathic and nociceptive pain. Results: INTG showed an increase in lumbar flexion (pre-intervention= 81.21±15.23°; post-intervention= 90.00±19.62°, p< 0.05), mobility of the lumbar spine in MST (pre= 15.33±1.05 post= 16.08±1.02, p< 0.05) and reduction of pain perception by NRS Pain (pre= 5.33±2.26; post= 1.47±2.61 p< 0.05) and in CONTG (pre= 4.07±2.34; post= 2.20±1.93, p< 0.05). Conclusion: The intervention with MWM - SNAGs promoted improved ROM and mobility in flexion of the lumbar spine, associated with reduction from the nociceptive pain in INTG and CONTG.

Objetivo: Analisar o efeito da Mobilization Whith Movement (MWM) do conceito Mulligan na percepção de dor nociceptiva e neuropática, na amplitude e na mobilidade articular de indivíduos com dor lombar. Métodos: Trata-se de um ensaio clínico randomizado e controlado, de 30 voluntários com dor lombar inespecífica, divididos em: Grupo Intervenção (GINT) que recebeu a mobilização articular com deslizamentos apofisários naturais mantidos (MWM - SNAGs); Grupo Controle (GCONT), que recebeu uma mobilização articular placebo. Os voluntários foram avaliados pela escala numérica de dor (EVN); pelo teste modificado de Schober (TMS) para a mobilidade da coluna lombar e pelo DN4 para avaliação da dor neuropática e nociceptiva. Resultados: GINT apresentou aumento da flexão lombar (pré intervenção= 81,21±15,23°; pós-intervenção= 90,00±19,62°, p= <0,05), da mobilidade da coluna lombar no TMS (pré= 15,33±1,05 pós= 16,08±1,02, p= <0,05) e redução da percepção de dor pela EVN (pré= 5,33±2,26; pós= 1,47±2,61= p< 0,05) e no GCONT (pré= 4,07±2,34; pós= 2,20±1,93, p < 0,05). Conclusão: A intervenção com MWM - SNAGs promoveu melhora da ADM e da mobilidade na flexão da coluna lombar, associada com redução da dor nociceptiva no GINT e no GCONT.

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Aim: Discovery of novel SARS-CoV-2 main protease (Mpro) inhibitors using a structure-based drug discovery strategy. Materials & methods: Virtual screening employing covalent and noncovalent docking was performed to discover Mpro inhibitors, which were subsequently evaluated in biochemical and cellular assays. Results: 91 virtual hits were selected for biochemical assays, and four were confirmed as reversible inhibitors of SARS CoV-2 Mpro with IC50 values of 0.4-3 µM. They were also shown to inhibit SARS-CoV-1 Mpro and human cathepsin L. Molecular dynamics simulations indicated the stability of the Mpro inhibitor complexes and the interaction of ligands at the subsites. Conclusion: This approach led to the discovery of novel thiosemicarbazones as potent SARS-CoV-2 Mpro inhibitors.

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Objective: To analyze the influence of exergaming (EXE) quality of life, cancer-related fatigue (CRF), electromyography, and strength and endurance muscle in a randomized crossover trial. Methods: We conducted a single-blinded, randomized, and crossover trial, which included 38 cancer volunteers undergoing chemotherapy (Age = 60.07 ± 12.10 years; body mass index = 26.79 ± 5.33 kg/m2). All volunteers were randomized into two intervention moments: EXE and without intervention (WI) and after 1-month washout period of crossing of the evaluated moments. The intervention was performed on an EXE protocol using Xbox 360 Kinect®, with the game "Your Shape Fitness Evolved 2012" two to three times per week for 20 sessions. All volunteers were assessed the CRF and quality-of-life levels through the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire, the median frequency (MDF) by surface electromyography, maximal voluntary isometric contraction (MVIC), and the muscle endurance time at 80% MVIC of the dorsiflexors and plantar flexors using dynamometer. Results: In the comparison between EXE and WI moments, were observed increase in the scores for quality of life (P < 0.001), subscale fatigue (P < 0.001), in the MDF values of right lateral gastrocnemius muscles: P = 0.017, muscle endurance time (left dorsiflexion [LDF]: P < 0.001; right dorsiflexion [RDF]: P < 0.001; left plantar flexion [LPF]: P < 0.001; RPF: P = 0.039), and muscle strength (LDF: P < 0.001; RDF: P < 0.001; LPF: P = 0.002). Conclusion: The crossover study, the EXE protocol promoted improvement in cancer-related fatigue (CRF) and quality of life, increased MVIC, endurance time, and MDF values of the dorsiflexor and plantar flexor muscles of cancer volunteers undergoing chemotherapy.

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ABSTRACT Introduction : The toothbrush is an important object for the hygiene of the oral cavity and an effective mechanism to remove the oral waste. Objective : To evaluate the perception of care, storage and parasitic contamination of toothbrushes in children with special health care needs (CSHCN) and children without special health care needs (CWSHCN) in Southern of Minas Gerais State. Material and Methods : This is an observational cross-sectional non-randomized study. The population consisted in 54 children, with age between 7 and 14 years. The questionnaire was distributed to patients to evaluate the perception of care and storage of children's toothbrushes. Investigation of toothbrushes contamination was performed by parasitological examination and real-time polymerase chain reactions. Results : Regarding the procedures performed after brushing, 50.0% of children with special health care needs (CSHCN) and 56.3% of children without special health care needs (CWSHCN) report washing their brush bristles with water (p <0.001). Both groups did not use an antiseptic solution on toothbrushes. 73.3% of (CSHCN) and 58.7% of (CWSHCN) answered that they use some protection (brush holder and bathroom cabinet) to avoid exposure of brushes to the environment (p <0.001). Conclusion : The children investigated by the study presented good conditions of care and storage of their toothbrushes. No contamination by pathogenic parasites was found during the study period.

RESUMEN Introducción : El cepillo de dientes es un objeto importante para la higiene de la cavidad bucal y un mecanismo eficaz para eliminar los residuos bucales. Objetivo : Evaluar la percepción del cuidado, almacenamiento y contaminación parasitaria de los cepillos dentales en niños con necesidades especiales de salud (CSHCN) y niños sin necesidades especiales de salud (CWSHCN) en el sur del estado de Minas Gerais. Material y Métodos : Se trata de un estudio observacional transversal no aleatorio. La población consistió en 54 niños, con edad entre 7 y 14 años. El cuestionario fue distribuido a los pacientes para evaluar la percepción del cuidado y almacenamiento de los cepillos dentales de los niños. La investigación de la contaminación de los cepillos dentales se realizó mediante un examen parasitológico y reacciones en cadena de la polimerasa en tiempo real. Resultados : En cuanto a los procedimientos realizados tras el cepillado, el 50,0% de los niños con necesidades especiales de atención sanitaria (NCNEAS) y el 56,3% de los niños sin necesidades especiales de atención sanitaria (NSNEAS) refieren lavar las cerdas del cepillo con agua (p <0,001). Ambos grupos no utilizaron una solución antiséptica en los cepillos de dientes. El 73,3% de los (NCNEAS) y el 58,7% de los (NSNEAS) contestaron que utilizan alguna protección (portacepillos y mueble de baño) para evitar la exposición de los cepillos al medio ambiente (p <0,001). Conclusiones : Los niños investigados por el estudio presentaron buenas condiciones de cuidado y almacenamiento de sus cepillos dentales. No se encontró contaminación por parásitos patógenos durante el período de estudio.

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Fusariosis has presented a significant increase in their incidence in the last years. This epidemiological panorama probably is due to the increasing profile of refractory susceptibility of Fusarium spp. to available drugs, especially in immunocompromised individuals. Thus, the development of new compounds with effectiveness on these organisms is a necessity. This study evaluated the antifungal potential of a chloroacetamide derivative (4-BFCA) against resistant Fusarium strains. As a result, the compound was effective against all strains (MIC range 12.5-50 µg/mL). The time kill assay demonstrated that 4-BFCA presents a concentration-dependent fungicidal action. Although its action mechanism has not yet been elucidated, it was possible to observe its efficacy through damages and alterations provoked along the hyphae of Fusarium spp. 4-BFCA maintained a high survival rate of Tenebrio molitor larvae, suggesting that it does not cause acute systemic toxicity on this host at the concentration evaluated. In addition, 4-BFCA was 83.33% effective in combating a fungal infection in vivo on the chorioallantoid membrane of embryonated eggs. Our results are very promising and arouse interest to investigate the action of 4-BFCA on Fusarium strains since it acts as a possible candidate for the development of new therapies for the treatment of fusariosis.

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PURPOSE: The aim of this research was to investigate the extent to which socioeconomic and regional differences in Brazil may influence the quality of life. To this end, we examined factors associated with health-related quality of life in two populations of oldest-old people, aged 80 and over: one from the Northeast of Brazil and the other from the Southeast. METHODS: 417 participants aged 80 and over were interviewed face-to-face, 179 from Brejo dos Santos, one of the poorest regions in the Northeast; and 238 from São Paulo, one of the largest urban metropolises in Southeast Brazil. Data, which included socioeconomic and demographic factors, health status, and health-related quality of life, were collected using a structured questionnaire. The dependent variable was determined by the completion rate of the 12-item Short Form Survey and analyzed using multiple logistic regression. RESULTS: Although the population of São Paulo had four times as many long-lived women than men, had better literacy levels, used more medications, and presented a greater prevalence of symptoms suggestive of depression in comparison to the Northeast's population, no difference was observed in the proportion of good physical components among the two populations, 54.3% in Brejo dos Santos' oldest-old and 50.4% in São Paulo's (P = .6272). Quality and quantity of sleep were factors that most affected the health-related quality of life among the oldest-old of Northeast. CONCLUSION: Factors associated with health-related quality of life were different among the oldest-old people of the two locations, thereby corroborating the heterogeneous nature of the longevous population.

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Canine prostate cancer (PC) is an aggressive disease, and dogs can be considered comparative models for human PC. In recent years, canine PC has been shown to resemble human castrate-resistant prostate cancer. The influx and efflux of testosterone in prostatic luminal cells are regulated by P-glycoprotein (P-gp). Therefore, human PC generally lacks P-gp expression and maintains the expression of androgen receptors (ARs). However, this co-expression has not previously been investigated in dogs. Therefore, this study aimed to evaluate AR and P-gp co-expression to elucidate these protein patterns in canine prostate samples. We identified AR/P-gp double immunofluorescence co-expression of both proteins in normal luminal cells. However, in canine PC, cells lack AR expression and exhibit increased P-gp expression. These results were confirmed by gene expression analyses. Overall, our results strongly suggest that normal canine prostate testosterone influx may be regulated by P-gp expression, and that during progression to PC, prostatic cells lack AR expression and P-gp overexpress. P-gp expression in canine PC may be related to a phenotype of multiple drug resistance.

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The Brazilian Compound Library (BraCoLi) is a novel open access and manually curated electronic library of compounds developed by Brazilian research groups to support further computer-aided drug design works, available on https://www.farmacia.ufmg.br/qf/downloads/ . Herein, the first version of the database is described comprising 1176 compounds. Also, the chemical diversity and drug-like profiles of BraCoLi were defined to analyze its chemical space. A significant amount of the compounds fitted Lipinski and Veber's rules, alongside other drug-likeness properties. A comparison using principal component analysis showed that BraCoLi is similar to other databases (FDA-approved drugs and NuBBEDB) regarding structural and physicochemical patterns. Furthermore, a scaffold analysis showed that BraCoLi presents several privileged chemical skeletons with great diversity. Despite the similar distribution in the structural and physicochemical spaces, Tanimoto coefficient values indicated that compounds present in the BraCoLi are generally different from the two other databases, where they showed different kernel distributions and low similarity. These facts show an interesting innovative aspect, which is a desirable feature for novel drug design purposes.

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Visceral leishmaniasis (VL) is a neglected tropical disease found in tropical and subtropical regions in the world. The therapeutics used for the treatment against disease presents problems, mainly related to drug toxicity, route of administration, high cost and/or by emergence of resistant strains. In this context, the search for alternative antileishmanial candidates is desirable. Recently, a naphthoquinone derivative namely 2-(2,3,4-tri-O-acetyl-6-deoxy-ß-L-galactopyranosyloxy)-1,4-naphthoquinone or Flau-A showed an effective in vitro biological action against Leishmania infantum. In the present study, the efficacy of this naphthoquinone derivative was evaluated in an in vivo infection model. BALB/c mice (n = 12 per group) were infected and later received saline or were treated with empty micelles (B/Mic), free Flau-A or it incorporated in Poloxamer 407-based micelles (Flau-A/Mic). The products were administered subcutaneously in the infected animals, which were then euthanized one (n = 6 per group) and 15 (n = 6 per group) days post-therapy, when immunological and parasitological evaluations were performed. Results showed that animals treated with Flau-A or Flau-A/Mic produced significantly higher levels of antileishmanial IFN-γ, IL-12, TNF-α, GM-CSF, nitrite and IgG2a isotype antibody, when compared to data found in the control (saline and B/Mic) groups; which showed significantly higher levels of parasite-specific IL-4, IL-10 and IgG1 antibody. In addition, animals receiving free Flau-A or Flau-A/Mic presented also significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes, when compared to the controls. A low hepatic and renal toxicity was also found. Overall, Flau-A/Mic showed better immunological and parasitological results, when compared to the use of free molecule. In conclusion, preliminary data suggest that this composition could be considered in future studies as promising therapeutic candidate against VL.

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Introdução: O preparo químico-mecânico representa uma etapa fundamental, pois promove a antissepsia do complexo sistema de canais radiculares, viabilizando um ambiente biológico favorável para o processo de cura e reparo dos tecidos periapicais. Porém, insucessos podem acontecer em dentes tratados e retratados endodonticamente, sendo a intervenção cirúrgica frequentemente indicada nesses casos. Relato do caso: Paciente do sexo masculino, 32 anos de idade, melanoderma, apresentou-se à clínica-escola de uma faculdade de Odontologia em um município baiano, com queixa principal de "aparecimento de bolha na gengiva e gosto amargo na boca". Ao exame clínico, visualizou-se presença de restauração de resina composta nas faces mesial e palatina, bem como fístula intrabucal ativa na região de fundo de vestíbulo, próximo ao ápice do elemento #22. Por meio de exames clínico e radiográfico, testes de sensibilidade pulpar e rastreamento da fístula, foi estabelecido diagnóstico de tratamento endodôntico concluído, e periapical de abscesso apical crônico. Em seguida, houve indicação de retratamento endodôntico e duas sessões de medicação intracanal com hidróxido de cálcio, seguidas de uma intervenção cirúrgica exploratória. Resultados: O protocolo de tratamento proposto foi eficaz. Constatou-se sucesso clínico, com cicatrização da fístula intrabucal ativa, e radiográfico, com reparação dos tecidos periapicais, além do restabelecimento da estética e função dentária, com acompanhamento de 26 meses. O paciente encontra-se sob acompanhamento semestral. Conclusão: é necessário salientar a relevância de efetuar com segurança um planejamento e prognóstico endodôntico confiável e, igualmente, o acompanhamento do caso, com supervisão clínica e radiográfica periódica (AU).

Introduction: Biological chemical preparation repre- sents a fundamental step, as it promotes asepsis of the complex root canal system, enabling a biological environment favorable to the process of healing and repair of the periapical tissues. However, failures can occur in endodontic treatment and retreatment teeth, where surgical intervention is often indicated in these cases. Description: The patient, a 32-year old man, melanoderma, presented at the school clinic of a School of Dentistry in a city in Bahia, with a chief complaint of "blistering of the gums and bitter taste in the mouth." Clinical examination revealed the presence of composite resin restoration on the mesial and palatine surfaces, and an active intraoral fistula in the vestibular region near the apex of tooth 22. By means of clinical, radiographic, pulp sensitivity tests and sinus tracking, a diagnosis of completed endodontic treatment was established, and periapical diagnosis of a chronic apical abscess. Afterwards, endodontic retreatment was indicated, consisting of two sessions of intracanal medication with calcium hydroxide, followed by an exploratory surgical intervention. Results: The proposed treatment protocol was effective. Clinical and radiographic success with healing of the active intrabuccal fistula and repair of the periapical tissues, as well as reestablishment of esthetics and dental function, was verified, in a period of twenty six months follow-up. At present, the patient is being followed-up semi-annually. Conclusion: it is necessary to emphasize the importance of safely performing reliable endodontic planning and prognosis, as well as follow up of the case, with periodic clinical and radiographic control (AU).

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Objective: To analyze the effect of the exergaming on muscular activity at rest and on maximum voluntary isometric contraction by electromyography (EMG) at peak torque, widespread pressure hyperalgesia identified using a tender point count, and static balance in fibromyalgia. Materials and Methods: Thirty-five women were divided into two groups: Wii™ (virtual rehabilitation, n = 16) and control (stretching exercises, n = 19), through simple randomization. The volunteers were evaluated by means of EMG, dynamometry by load cell, baropodometry, and algometry before interventions and reevaluated after the 10th and 20th sessions. The subjects participated fully in three 1-hour treatment sessions per week of 20 sessions. Results: The Wii group showed significant benefits for the peak torque of dorsiflexion movement after 20 sessions and for movement plantarflexion after 10 sessions. The control group showed bilateral improvement in muscular activity in the tibialis anterior muscle after 20 sessions. Both groups showed a significant decrease in tender point count, suggesting improved hyperalgesia after 10 sessions and 20 sessions. No significant improvement was found in static baropodometry in the two evaluated groups. Conclusion: Exergaming have the potential to increase the peak torque for dorsiflexion and plantarflexion movement in women with fibromyalgia. It also produces a decrease in tender point count equal to that with flexibility exercises and does not produce changes in the static balance.

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BACKGROUND: Melanoma is a malignant cancer that affects melanocytes and is considered the most aggressive skin-type cancer. The prevalence for melanoma cancer for the last five year is about one million cases. The impact caused of this and other types of cancer, revel the importance of research into potential active compounds. The natural products are an important source of compounds with biological activity and research with natural products may enable the discovery of compounds with potential activity in tumor cells. METHODS: The Sulforhodamine B was used to determine cell density after treatment with lawsone derivatives. Apoptosis and necrosis were analyzed by flow cytometer. Morphological changes were observed by fluorescence using the Phalloidin/FITC and DAPI stains. The clonogenic and wound healing assays were used to analyze reduction of colonies formation and migratory capacity of melanoma cells, respectability. RESULTS: In pharmacological screening, seven compounds derived from lawsone were considered to have high cytotoxic activity (GI > 75%). Three compounds were selected to assess the inhibitory concentration for 50% of cells (IC50), and the compound 9, that has IC50 5.3 µM in melanoma cells, was selected for further analyses in this cell line. The clonogenic assay showed that the compound is capable of reducing the formation of melanoma colonies at 10.6 µM concentration. The compound induced apoptotic morphological changes in melanoma cells and increased by 50% the cells dying from apoptosis. Also, this compound reduced the migratory capacity of melanoma cells. CONCLUSIONS: The results of this study showed that the evaluated lawsone derivatives have potential activity on tumor cells. The compound 9 is capable of inducing cell death by apoptosis in melanoma cells (B16F10).

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This paper describes a comparative analysis of the physicochemical and structural properties of prodrugs and their corresponding drugs with regard to drug-likeness rules. The dataset used in this work was obtained from the DrugBank. Sixty-five pairs of prodrugs/drugs were retrieved and divided into the following categories: carrier-linked to increase hydrophilic character, carrier-linked to increase absorption, and bioprecursors. We compared the physicochemical properties related to drug-likeness between prodrugs and drugs. Our results show that prodrugs do not always follow Lipinski's Rule of 5, especially as we observed 15 prodrugs with more than 10 hydrogen bond acceptors and 18 with a molecular weight greater than 500 Da. This fact highlights the importance of extending Lipinski's rules to encompass other parameters as both strategies (filtering of drug-like chemical libraries and prodrug design) aim to improve the bioavailability of compounds. Therefore, critical reasoning is fundamental to determine whether a structure has drug-like properties or could be considered a potential orally active compound in the drug-design pipeline.

Assuntos

RESUMO

The number of deaths due to systemic fungal infections is increasing alarmingly, which is aggravated by the limitations of traditional treatments and multidrug resistance. Therefore, the research and development of new therapeutic options against pathogenic fungi is an urgent need. To evaluate the fungicidal activity of a synthetic compound, 1,3-bis-(3,4-dichlorophenoxy)propan-2-aminium chloride (2j), through time-kill studies and pharmacokinetics/pharmacodynamics (PK/PD) modeling. The protective effect of the compound was also evaluated using the Drosophila melanogaster minihost model of candidiasis. Mathematical modeling of time-kill data of compound 2j was performed to obtain PD characteristics. Additionally, Toll-deficient D. melanogaster flies were infected with a Candida albicans strain and treated with 2j. We observed that compound 2j demonstrated a time- and dose-dependent fungicidal effect against Candida spp. and dermatophytes, even at low concentrations, and rapidly achieved kill rates reaching the maximum effect in less than one hour. The efficacy of the compound against systemic candidiasis in D. melanogaster flies was comparable to that achieved by fluconazole. These results support the potential of compound 2j as a systemic antifungal agent candidate and serve as a starting point for further studies involving mammalian animal models.

Assuntos