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Curcumin is a highly promising substance for treating burns, owing to its anti-inflammatory, antioxidant, antimicrobial, and wound-healing properties. However, its therapeutic use is restricted due to its hydrophobic nature and low bioavailability. This study was conducted to address these limitations; it developed and tested two types of lipid nanocarriers, namely nanoemulsions (NE-CUR) and nanostructured lipid carriers (NLC-CUR) loaded with curcumin, and aimed to identify the most suitable nanocarrier for skin burn treatment. The study evaluated various parameters, including physicochemical characteristics, stability, encapsulation efficiency, release, skin permeation, retention, cell viability, and antimicrobial activity. The results showed that both nanocarriers showed adequate size (~200 nm), polydispersity index (~0.25), and zeta potential (~>-20 mV). They also showed good encapsulation efficiency (>90%) and remained stable for 120 days at different temperatures. In the release test, NE-CUR and NCL-CUR released 57.14% and 51.64% of curcumin, respectively, in 72 h. NE-CUR demonstrated better cutaneous permeation/retention in intact or scalded skin epidermis and dermis than NLC-CUR. The cell viability test showed no toxicity after treatment with NE-CUR and NLC-CUR up to 125 µg/mL. Regarding microbial activity assays, free curcumin has activity against P. aeruginosa, reducing bacterial growth by 75% in 3 h. NE-CUR inhibited bacterial growth by 65% after 24 h, and the association with gentamicin had favorable results, while NLC-CUR showed a lower inhibition. The results demonstrated that NE-CUR is probably the most promising nanocarrier for treating burns.
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Due to several obstacles in treating tuberculosis (TB), the search for new therapeutic alternatives remains a global priority. The nitrogenous heterocyclic compounds are promising in searching for new anti-Mycobacterium tuberculosis molecules, and our previous results highlight the potential of tetrahydropyridines. After exploring the antimycobacterial potential and putative mechanism of action of a tetrahydropyridine derivative (NUNL02), we seek to measure the oxidative stress caused by NUNL02 inside the extracellular replicating M. tuberculosis since it could be the reason for the NUNL02 bactericidal effect against replicating and starved M. tuberculosis; and to evaluate the anti-M. tuberculosis activity of NUNL02 against the intracellular bacillus (even combined with an anti-TB drug) to explore the potential of this tetrahydropyridine as a promising adjuvant for TB therapy. Briefly, we assessed the activity of NUNL02 against the H37Rv strain and evaluated the combination of NUNL02 and rifampicin (RIF), at previously defined subinhibitory concentrations, against intramacrophage M. tuberculosis. NUNL02, in addition to promote the oxidative stress inside the extracellular replicating M. tuberculosis as a possible indirect mechanism of action, also presented bactericidal potential as promising as RIF against intracellular bacilli. Thus, our findings reinforce NUNL02 as a promising scaffold for the development of new options for TB.
Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Pirrolidinas/farmacologia , Rifampina/farmacologiaRESUMO
Monilinia fructicola (Wint.) Honey is a plant pathogenic fungus that infects stone fruits such as peach, nectarine and plum, which are high demand cultivars found in Brazil. This pathogen may remain latent in the host, showing no apparent signs of disease, and consequently may spread to different countries. The aim of this study was to evaluate the activity of hydroalcoholic extract (HydE) obtained from Lactarius deliciosus (L.) Sf. Gray a mushroom, against M. fructicola phytopathogenic-induced mycelial growth. In addition, the purpose of this study was to examine phytotoxicity attributed to HydE using Brassica oleracea seeds, as well as cytotoxic analysis of this extract on cells of mouse BALB/c monocyte macrophage cell line (J774A.1 cell line) (ATCC TIB-67). The L. deliciosus HydE inhibited fungal growth and reduced phytopathogen mycelial development at a concentration of 1.25 mg/ml. Our results demonstrated that the extract exhibited phytotoxicity as evidenced by (1) interference on germination percentage and rate index, (2) decreased root and initial growth measures, and (3) lower fresh weight of seedlings but no cytotoxicity in Vero cell lines. Data suggest that the use of the L. deliciosus extracts may be beneficial for fungal control without any apparent adverse actions on mouse BALB/c monocyte macrophage cell line (J774A.1 cell line) viability.
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Antifúngicos/farmacologia , Basidiomycota/química , Agentes de Controle Biológico/farmacologia , Animais , Antifúngicos/química , Ascomicetos/efeitos dos fármacos , Ascomicetos/crescimento & desenvolvimento , Agentes de Controle Biológico/química , Brasil , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Frutas/microbiologia , Germinação/efeitos dos fármacos , Camundongos , Micélio/efeitos dos fármacos , Micélio/crescimento & desenvolvimento , Fenol/análise , Doenças das Plantas/microbiologia , Sementes/crescimento & desenvolvimento , Sementes/microbiologiaRESUMO
Abstract Sporothrix spp. are the major dimorphic fungus associated with a type of subcutaneous mycosis, sporotrichosis. The limitation of antifungal availability and the past reports of in vitro resistance of Sporothrix spp. clinical isolates makes it important to search for new compounds with antifungal activities. In this study, we therefore evaluate the in vitro activities of complexes coordinated with Co(II) and cobalt chloride hexahydrate against clinical isolates of Sporothrix spp. Broth microdilution test was performed as per M38-A2 from CLSI (2008) in duplicate for 31 clinical isolates of Sporothrix spp. (27 S. brasiliensis e 04 S. schenckii stricto sensu). The antifungal activities of the complexes coordinated with Co(II) and cobalt chloride hexahydrate were detected at a concentration range of 32-128 µg/mL for all isolates. None of the compounds demonstrated any cytotoxicity (to macrophage cells) at the concentration of 200 µg/mL. The activity against Sporothrix spp. recorded in this study instigate the continuity of experimental studies with Co(II) to search for the mechanisms of antifungal action as well as to evaluate its interaction with the commercial antifungal drugs.
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Técnicas In Vitro/instrumentação , Macrófagos/classificação , Esporotricose/tratamento farmacológico , Sporothrix/classificação , Preparações Farmacêuticas/administração & dosagem , Cloretos/agonistas , FungosRESUMO
Although the administration of combined therapy is efficient to tuberculosis (TB) treatment caused by susceptible Mycobacterium tuberculosis strains, to overcome the multidrug resistance is still a challenge. Some studies have reported evidence about tetrahydropyridines as a putative efflux pump inhibitor, including in mycobacteria, being a promising strategy against M. tuberculosis. Thus, we investigated the biological potential of 2,2,2-trifluoro-1-(1,4,5,6-tetrahydropyridin-3-yl)ethanone derivative (NUNL02) against two strains of M. tuberculosis. NUNL02 was able to increase the susceptibility of the multidrug resistant strain to the anti-TB drugs, resulting in synergism with rifampicin. Still, we assume that this compound plays a role in the efflux mechanism in M. tuberculosis, besides, to be able to kill the bacillus under the deprivation of essential nutrients. Thus, our findings highlight NUNL02 as a promising prototype to develop a new adjuvant for TB treatment, mainly as EPI.
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Acetofenonas/farmacologia , Antibacterianos/farmacologia , Proteínas de Membrana Transportadoras/metabolismo , Mycobacterium tuberculosis/efeitos dos fármacos , Acetofenonas/síntese química , Acetofenonas/química , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mycobacterium tuberculosis/metabolismo , Relação Estrutura-AtividadeRESUMO
The continuous emergence of resistant Mycobacterium tuberculosis keeps tuberculosis (TB) treatment options still insufficient, and new therapeutic alternatives are urgently needed. Considering the antimycobacterial activity of phenazine derivatives previously reported by our research group, we aimed to explore possible applications to circumvent the resistance in M. tuberculosis. Firstly, we evaluated the antimicrobial activity of seven benzo[a]phenazine derivatives against eleven M. tuberculosis strains: ten resistant and one susceptible (H37 Rv). Then, we determined the cytotoxicity of benzo[a]phenazine derivatives and investigated the possible mechanism of action of the most promising compound. Among them, compound 10 was the only one active against all strains evaluated, with a minimum inhibitory concentration between 18.3 and 146.5 µM. For some resistant strains, this compound showed antimicrobial activity higher than rifampicin and it was also active against MDR strains, indicating an absence of cross-resistance with anti-TB drugs. Also, 10 showed a pharmacological safety for further in vivo studies and its mechanism of action seems to be related to oxidative stress. Thus, our findings indicate that benzo[a]phenazine derivatives are promising scaffolds for the development of new anti-TB drugs, mainly focusing on the treatment of resistant TB cases.
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Antituberculosos/química , Fenazinas/química , Animais , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Fenazinas/farmacologia , Fenazinas/uso terapêutico , Teoria Quântica , Espécies Reativas de Oxigênio/metabolismo , Rifampina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Células VeroRESUMO
BACKGROUND: Lipid nanocarriers have been widely tested as drug delivery systems to treat diseases due to their bioavailability, controlled release, and low toxicity. For the pulmonary route, the Food and Drug Administration favors the use of substances generally recognized as safe, as well as biodegradable and biocompatible to minimize the possibility of toxicity. Tuberculosis (TB) remains a public health threat worldwide, mainly due to the long treatment duration and adverse effects. Therefore, new drug delivery systems for treating TB are needed. OBJECTIVE: Physicochemical characterization of different lipid-based nanocarriers was used to optimize carrier properties. Optimized systems were incubated with Mycobacterium tuberculosis to assess whether lipid-based systems act as the energy source for the bacteria, which could be counterproductive to therapy. METHODS: Several excipients and surfactants were evaluated to prepare different types of nanocarriers using high-pressure homogenization. RESULTS: A mixture of trimyristin with castor oil was chosen as the lipid matrix after differential scanning calorimetry analysis. A mixture of egg lecithin and PEG-660 stearate was selected as an optimal surfactant system, as this mixture formed the most stable formulations. Three types of lipid nanocarriers, solid lipid nanoparticles, nanostructured lipid carriers (NLC), and nanoemulsions, were prepared, with the NLC systems showing the most suitable properties for further evaluation. It may provide the advantages of increasing the entrapment efficiency, drug release, and the ability to be lyophilized, producing powder for pulmonary administration as an alternative to entrap poor water-soluble molecules. CONCLUSION: Furthermore, the NLC system can be considered for use as a platform for the treatment of TB through the pulmonary route.
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Portadores de Fármacos , Nanopartículas , Tuberculose , Excipientes , Humanos , Lipídeos , Tamanho da Partícula , Tuberculose/tratamento farmacológicoRESUMO
This study aimed to use bioassays (single and multispecies) with organisms from different trophic levels to assess soil quality in reclaimed coal mining areas. Soil samples were collected from four sites: two sites with recent reclaim processes (one using topsoil and other using clayey soil), an natural attenuation site, and a control soil. The evaluated parameters were divided into (1) ecotoxicological tests (avoidance test with Eisenia andrei (earthworms) and Armadillidium vulgare (isopods); germination test with Sinapis alba seeds (mustard); reproduction tests with Folsomia candida (collembolans); bacterial toxicity test); (2) population and community assessments (a fungal count; microbial community analysis using Biolog EcoPlatesTM); (3) microcosms scale evaluation (the MS-3 multispecies system); and (4) chemical analysis (soil parameters, soil metal, and cations and anions in soil leachate). Results pointed to toxicity in the natural attenuation site that compromised of habitat function, probably due to low pH and low nutrient levels. The most recent reclaim process, using topsoil and clay soil, improved soil quality and fertility, with a further increase in habitat quality and heterogeneity. This study shows that some techniques used to reclaim degraded mining areas are effective in rebuilding habitats, sustaining soil biota, and reestablishing ecosystem services.
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Minas de Carvão , Oligoquetos , Poluentes do Solo , Animais , Bioensaio , Carvão Mineral , Ecossistema , Mineração , SoloRESUMO
In the last 15 years, Acinetobacter baumannii has received special attention, mainly due to several resistance mechanisms and high rates of morbimortality. The ability to form biofilms contributes to the persistence of this microorganism in the hospital environment and facilitates the occurrence of nosocomial infections. Several studies have highlighted the pharmacological relevance of pyridines in the treatment and control of infectious diseases and others have related the anti-A. baumannii potential of hydrazine derivatives. Considering this scenario, we aimed to evaluate the antimicrobial and antibiofilm activity of 10 pyridinylhydrazone compounds against A. baumannii. The minimum inhibitory concentration of the compounds was determined by broth microdilution method and the antibiofilm activity was evaluated by inhibition and destruction biofilm assays. In addition, the cytotoxicity of the compounds in the J774A.1 cell line was also evaluated, and the selectivity index was calculated. Among the 10 pyridine compounds, the compounds B and D were able to inhibit the formation of biofilms and destroy bacterial biofilms even in a concentration of 12.5 µg/mL. Thus, the pyridine compounds evaluated can be a scaffold for the development of new substances with antimicrobial and antibiofilm activity.
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Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Piridonas/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Background and Objectives: Helicobacter pylori is linked to gastroduodenal pathologies. To determine the frequency and potential risk factors of the H. pylori infection. Material and methods: A cross-sectional study was conducted, including 227 patients, submitted to upper gastrointestinal endoscopy. A questionnaire was applied to the patients, before endoscopy. The biopsy specimens were obtained from the antrum and gastric body for histology and PCR. The chi-square test was used for the categorical data analysis. P-values<0.05 were considered statistically significant.Results: 66.5% patients were positive for H. pylori. Based on the questionnaires applied to the patients, it was verified that marital status, smoking, alcohol consumption, toilet, education level and monthly family income had no significant association with the presence of H. pylori (p>0.05). However, we observed a significant association between the number of persons per household and presence of H. pylori (p=0.04). A statistically significant relation also was found between H. pylori and the patient's age (p=0.04) and between the histological and endoscopic diagnoses and the H. pylori infection (p≤0.01). Conclusions: We found a significant relation between household crowding and presence of H. pylori, which seems facilitate the person-to-person transmission H. pylori within families. Our results also suggest a cohort phenomenon. The increase in the frequency of H. pylori infection according to age may be due the acquisition of bacterium predominantly in childhood, when the sanitary conditions were deficient, and not during adulthood. Once acquired and untreated, the persistent H. pylori infection might have led to the development of severe gastroduodenal diseases.(AU)
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Humanos , Helicobacter pylori , InfecçõesRESUMO
Tuberculosis (TB) is considered an emergency global public health, mainly due to the TB-HIV co-infection, bacillus dormancy stage, and emergence of resistant strains. In addition, the therapeutic toxicity and its pharmacokinetic interactions with other drugs may influence treatment non-compliance, low serum concentration of drugs, and, consequently, treatment failure. Strategies using nanotechnology represent a new tool for the therapy, since they are effective delivery systems due to the possibility of solubilization of hydrophobic compounds, enable the production of formulations for oral use, and, in addition, increase bioavailability of drugs. This study aimed to develop a nanoemulsion (NE) containing rifampicin (RIF-NE) and evaluate its in vitro antimycobacterial activity using Resazurin Microtiter Assay against three Mycobacterium tuberculosis strains: two susceptible and a multidrug-resistant. Using the hot solvent diffusion method associated with phase inversion technique was possible to develop a liquid formulation containing 500 µg/mL rifampicin (RIF), which is a hydrophobic compound, of average size 25 nm. The results showed that the minimum inhibitory concentration of the encapsulated RIF was equal to the free form of RIF, indicating that the process of production of NEs did not affect the activity of the compound. Thus, RIF-NE could be a promising alternative for oral administration of RIF, being considered a child-friendly pharmaceutical formulation. Its application could avoid the administration of unknown and/or non-ideal concentrations, being functional in the regimes of prevention and treatment of TB and, in addition, in the fight against drug resistance.
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Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/química , Composição de Medicamentos/métodos , Mycobacterium tuberculosis/efeitos dos fármacos , Rifampina/administração & dosagem , Rifampina/química , Administração Oral , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Emulsões , Humanos , Testes de Sensibilidade Microbiana/métodos , Mycobacterium tuberculosis/fisiologia , Nanopartículas/administração & dosagem , Nanopartículas/químicaRESUMO
Tuberculosis (TB) is the cause of more than one million deaths worldwide, and despite being a curable disease, some factors can make therapy difficult, emphasizing the need for the development of new drugs that may potentiate the action of the classic anti-TB antimicrobials. Naphthoimidazoles show a broad spectrum of biological activities, including antimycobacterial activity. The aim of this study was to evaluate the anti-Mycobacterium tuberculosis activity of nine naphthoimidazoles, alone and combined with isoniazid (INH) and rifampicin (RIF). We evaluated the minimum inhibitory concentration (MIC) of the compounds, the fractional inhibitory concentration of the combinations of the naphthoimidazoles with INH or RIF, and the cytotoxicity of these compounds. Eight compounds showed MICs ranging from 1.56 to 25⯵g/mL and the presence of substituents on phenyl groups shown to be essential for antimycobacterial activity. Four compounds showed additivity with both INH and RIF and showed SI values higher than 10, indicating safety. Thus, considering the antimycobacterial activity and the absence of antagonism between naphthoimidazoles and the two main drugs for TB treatment, these compounds could be scaffolds for the development of new anti-TB drugs.
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Antituberculosos/farmacologia , Imidazóis/farmacologia , Isoniazida/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Naftoquinonas/farmacologia , Rifampina/farmacologia , Tuberculose/tratamento farmacológico , Antituberculosos/síntese química , Descoberta de Drogas , Farmacorresistência Bacteriana , Quimioterapia Combinada , Humanos , Imidazóis/síntese química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/patogenicidade , Naftoquinonas/síntese química , Relação Estrutura-Atividade , Tuberculose/microbiologiaRESUMO
INTRODUCTION: Helicobacter pylori infection is associated with gastritis, peptic ulcer disease and gastric carcinoma. The severity of damage is determined by the interplay between environmental/behavioral factors, bacterial pathogenicity genes and host genetic polymorphisms that can influence the secretion levels of inflammatory cytokines. Accordingly, this study aimed to identify polymorphisms in the IL-1B and IL-1RN genes and their associations with H. pylori infection, cagA gene of H. pylori, and gastroduodenal diseases. METHODOLOGY: Gastric biopsy samples from 151 patients infected with H. pylori and 76 uninfected individuals were analyzed. H. pylori infection was diagnosed by histology and PCR. Polymorphisms at positions -511, -31 and +3954 of the IL-1B gene were detected by PCR-RFLP, and an analysis of the VNTR polymorphism of the IL-1RN gene was performed by PCR. RESULTS: It was observed that the presence of the T/T genotype at position -511 and the C/C genotype at position -31 were associated with H. pylori infection and with an increased risk of gastritis in H. pylori-positive patients. Additionally, strains from patients H. pylori-positive carrying the cagA gene was significantly related with the T/T genotype at position -511 of IL-1B. No association of polymorphisms at position +3954 of IL-1B and in the IL-1RN with H. pylori infection and with risk of severe gastric diseases was found. CONCLUSIONS: We demonstrated that polymorphisms in the promoter region of the IL-1B gene (at positions -511 and -31) are associated with an enhanced risk of H. pylori infection as well as gastritis in H. pylori-positive patients.
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Gastrite/genética , Gastrite/imunologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Interleucina-1beta/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Biópsia , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Helicobacter pylori/imunologia , Helicobacter pylori/isolamento & purificação , Histocitoquímica , Humanos , Proteína Antagonista do Receptor de Interleucina 1/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
CagA of Helicobacter pylori undergoes tyrosine phosphorylation in a region containing differing numbers of repeat sequences (EPIYAs), which can result in a modulation of the inflammatory response. This study investigated whether the presence of CagA EPIYA variations in strains of H. pylori that are positive for this region contributes to differing degrees of disease severity in the gastric mucosa. In this study, 157 H. pylori-positive patients were included, and of those, 40.8% (64/157) were infected with cagA-positive strains, which were assayed for the presence of CagA EPIYA-ABC, EPIYA-ABCC, and EPIYA-ABCCC. Peptic ulcers were significantly more prevalent in patients infected with strains containing CagA EPIYA-ABCC/ABCCC than in those with CagA EPIYA ABC strains (P=0.044). This suggests that the number of repetitions of EPIYA-C influences the development of gastroduodenal lesions, highlighting the importance and usefulness of evaluating the cagA gene sequence when making therapeutic intervention decisions in patients infected with H. pylori.