RESUMEN

Aim: To evaluate the antifungal activity of amlodipine against strains of Candida spp. and to its possible mechanism of action.Methods: Broth microdilution tests were used to determine the minimum inhibitory concentration, while the synergistic activity was evaluated by calculating the fractional inhibitory concentration index. The action of amlodipine against biofilms was determined using the MTT assay and its possible mechanism of action was investigated through flow cytometry tests.Results: Amlodipine showed MICs ranging from 62.5 to 250 µg/ml, in addition to action against pre-formed and forming biofilms, with reductions between 50 and 90%. Amlodipine increases the externalization of phosphatidylserine and reduces the cell viability of fungal cells, suggesting apoptosis.Conclusion: Amlodipine had good antifungal activity against planktonic cells and biofilms of Candida spp., by leading the cells to apoptosis.

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Candida is a type of fungus that can cause diseases. This fungus became stronger over time and drugs can no longer kill them easily, so it is important to find new drugs. We decided to study whether amlodipine, a drug used for heart disease, has action against Candida. We discovered that amlodipine make fungi weaker. We still need to do more studies to find out if amlodipine can help prevent Candida diseases.

Asunto(s)

Amlodipino , Antifúngicos , Biopelículas , Candida , Pruebas de Sensibilidad Microbiana , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Antifúngicos/farmacología , Candida/efectos de los fármacos , Candida/fisiología , Candida/crecimiento & desarrollo , Amlodipino/farmacología , Viabilidad Microbiana/efectos de los fármacos , Apoptosis/efectos de los fármacos , Humanos , Citometría de Flujo , Plancton/efectos de los fármacos , Plancton/crecimiento & desarrollo

RESUMEN

Aim: Evaluate the anticandidal effect of Croton heliotropiifolius Kunth essential oil and its interaction with azoles and N-acetylcysteine (NAC) against planktonic cells and biofilms.Materials & methods: Broth microdilution and checkerboard methods were used to evaluate the individual and combined activity with fluconazole and itraconazole (ITRA). The antibiofilm effect of the oil was assessed in 96-well plates alone and combined with ITRA and NAC, and cytotoxicity determined by MTT.Results: The oil inhibited all Candida species growth. The activity was enhanced when associated with ITRA and NAC for planktonic cells and biofilms in formation. The effective concentrations were lower than the toxic ones to V79 cells.Conclusion: C. heliotropiifolius Kunth essential oil is an anticandidal alternative, and can be associated with ITRA and NAC.

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Candida is a type of fungus that can cause disease in people. In recent years, the number of available drugs to treat this disease have declined. It is important to search for new drugs. Plants are often used to improve health, so we tested the essential oil of a plant called Croton heliotropiifolius to see if it could kill the fungus. We found that the essential oil could kill the fungus, and could be used with other drugs to improve their effects.

Asunto(s)

Acetilcisteína , Antifúngicos , Biopelículas , Candida , Croton , Itraconazol , Pruebas de Sensibilidad Microbiana , Aceites Volátiles , Croton/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Itraconazol/farmacología , Antifúngicos/farmacología , Acetilcisteína/farmacología , Biopelículas/efectos de los fármacos , Candida/efectos de los fármacos , Sinergismo Farmacológico , Animales , Línea Celular , Fluconazol/farmacología , Cricetinae

RESUMEN

Candida species are among the priority pathogens in the area of research and development. Due to the problems associated with resistance to antifungals, new therapeutic alternatives are necessary. In this regard, drug repositioning has gained prominence. The objective of this study was to evaluate the activity of three tricyclic antidepressants (TCAs) - amitriptyline (AMT), nortriptyline (NOR) and clomipramine (CLO) - isolated or associated with antifungals against strains of Candida spp., as well as to analyze the possible mechanism of action. Among the methods used were broth microdilution tests, tolerance level assessment, checkerboard assays, flow cytometry and fluorescence microscopy. Furthermore, Candida cells were visualized after treatments by scanning electron microscopy (SEM). AMT presented MIC 50% in the range of 16 to 128 µg/mL, NOR from 8 to 128 µg/mL, and CLO from 8 to 64 µg/mL, with all three TCAs having a fungicidal inhibitory action profile. For these TCAs, there was synergism with amphotericin B (AMB) in 100% of the isolates. In association with fluconazole (FLC) and itraconazole (ITR), there were mostly indifferent interactions. TCAs isolated and associated with AMB reduced cell viability, promoted DNA fragmentation and damage, caused mitochondrial depolarization, externalization of phosphatidylserine, produced reactive oxygen species (ROS), decreased reduced glutathione (GSH) and increased carbonyl protein levels, causing morphological changes. The results suggest the antifungal mechanism of the TCAs works via the apoptotic pathway.

RESUMEN

The increase in fungal resistance is a major public health concern. In this context, Candida spp. is an important genus related to invasive diseases, especially in immunosuppressed patients. The relevance of alternative approaches to increasing fungal resistance stands out, in which products of natural origin demonstrate potential antifungal activity in vitro against Candida spp. In this sense, this work aimed to evaluate the in vitro activity of tannic acid against Candida spp. Minimum inhibitory concentration (MIC) was determined for tannic acid and the antifungals, and the checkerboard assay was performed to analyze the interactions between them. Furthermore, we evaluated the tannic acid antibiofilm activity and its possible mechanism of action. Tannic acid showed MIC ranging to 0.06 to 0.5 µg/ml and showed no loss of effectiveness when combined with antifungals. Also, is safe at the concentrations it exerts its antifungal activity in pre-formed biofilms, as demonstrated by IC50 in murine fibroblasts cells and the hemolytic assay. Additionally, its mechanisms of action can be related with induction of signals that lead to apoptosis in fungal cells.

RESUMEN

Introduction. The development of new antifungal drugs has become a global priority, given the increasing cases of fungal diseases together with the rising resistance to available antifungal drugs. In this scenario, drug repositioning has emerged as an alternative for such development, with advantages such as reduced research time and costs.Gap statement. Propafenone is an antiarrhythmic drug whose antifungal activity is poorly described, being a good candidate for further study.Aim. This study aims to evaluate propafenone activity against different species of Candida spp. to evaluate its combination with standard antifungals, as well as its possible action mechanism.Methodology. To this end, we carried out tests against strains of Candida albicans, Candida auris, Candida parapsilosis, Candida tropicalis, Candida glabrata and Candida krusei based on the evaluation of the MIC, minimum fungicidal concentration and tolerance level, along with checkerboard and flow cytometry tests with clinical strains and cell structure analysis by scanning electron microscopy (SEM).Results. The results showed that propafenone has a 50% MIC ranging from 32 to 256 µg ml-1, with fungicidal activity and positive interactions with itraconazole in 83.3% of the strains evaluated. The effects of the treatments observed by SEM were extensive damage to the cell structure, while flow cytometry revealed the apoptotic potential of propafenone against Candida spp.Conclusion. Taken together, these results indicate that propafenone has the potential for repositioning as an antifungal drug.

Asunto(s)

Antifúngicos , Candida , Pruebas de Sensibilidad Microbiana , Propafenona , Antifúngicos/farmacología , Candida/efectos de los fármacos , Candida/crecimiento & desarrollo , Propafenona/farmacología , Humanos , Itraconazol/farmacología , Sinergismo Farmacológico , Farmacorresistencia Fúngica/efectos de los fármacos , Candidiasis/microbiología , Candidiasis/tratamiento farmacológico , Reposicionamiento de Medicamentos

RESUMEN

Aim: The present study investigated the antimicrobial effectiveness of a rhamnolipid complexed with arginine (RLMIX_Arg) against planktonic cells and biofilms of methicillin-resistant Staphylococcus aureus (MRSA). Methodology: Susceptibility testing was performed using the Clinical & Laboratory Standards Institute protocol: M07-A10, checkerboard test, biofilm in plates and catheters and flow cytometry were used. Result: RLMIX_Arg has bactericidal and synergistic activity with oxacillin. RLMIX_Arg inhibits the formation of MRSA biofilms on plates at sub-inhibitory concentrations and has antibiofilm action against MRSA in peripheral venous catheters. Catheters impregnated with RLMIX_Arg reduce the formation of MRSA biofilms. Conclusion: RLMIX_Arg exhibits potential for application in preventing infections related to methicillin-resistant S. aureus biofilms.

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[Box: see text].

Asunto(s)

Antibacterianos , Arginina , Biopelículas , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Tensoactivos , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Arginina/farmacología , Arginina/química , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Tensoactivos/farmacología , Tensoactivos/química , Glucolípidos/farmacología , Glucolípidos/química , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/prevención & control , Infecciones Estafilocócicas/tratamiento farmacológico , Oxacilina/farmacología , Sinergismo Farmacológico

RESUMEN

Background: Staphylococcus aureus is a human pathogen responsible for high mortality rates. The development of new antimicrobials is urgent. Materials & methods: The authors evaluated the activity of hydralazine along with its synergism with other drugs and action on biofilms. With regard to action mechanisms, the authors evaluated cell viability, DNA damage and molecular docking. Results: MIC and minimum bactericidal concentration values ranged from 128 to 2048 µg/ml. There was synergism with oxacillin (50%) and vancomycin (25%). Hydralazine reduced the viability of biofilms by 50%. After exposure to hydralazine 2× MIC, 58.78% of the cells were unviable, 62.07% were TUNEL positive and 27.03% presented damage in the comet assay (p < 0.05). Hydralazine showed affinity for DNA gyrase and TyrRS. Conclusion: Hydralazine is a potential antibacterial.

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Staphylococcus aureus is a bacterium that can cause infection. Infections of S. aureus are becoming difficult to treat, but developing new drugs is a challenge. Repurposing them may be easier. This study looks at the possibility of using hydralazine, a type of medicine used to treat high blood pressure, against S. aureus. The authors found that hydralazine can kill S. aureus and can be used with other antibiotics, including oxacillin and vancomycin. Hydralazine interferes with important processes for the multiplication and survival of this bacterium. These results are preliminary but encouraging. Further studies are needed to confirm the use of hydralazine as a new treatment for S. aureus infections.

Asunto(s)

Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Staphylococcus aureus , Meticilina , Resistencia a la Meticilina , Simulación del Acoplamiento Molecular , Antibacterianos/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Pruebas de Sensibilidad Microbiana

RESUMEN

Croton heliotropiifolius Kunth, popularly known as "velame," is a shrub that resides in northeastern Brazil. The essential oil of C. heliotropiifolius contains high concentrations of volatile compounds in the leaves and is widely used in folk medicine for many purposes as an antiseptic, analgesic, sedative, and anti-inflammatory agent. Due to the apparent limited amount of information, the aim of this study was to determine the cytotoxic potential of essential oil extracted from leaves of C. heliotropiifolius, utilizing different human cancer cell lines (HL-60, leukemia; HCT-116, colon; MDA-MB435, melanoma; SF295, glioblastoma) and comparison to murine fibroblast L929 cell line. The chemical characterization of the essential oil revealed the presence of large amounts of monoterpenes and sesquiterpenes, the majority of which were aristolene (22.43%), germacrene D (11.38%), ɣ-terpinene (10.85%), and limonene (10.21%). The essential oil exerted significant cytotoxicity on all cancer cells, with low activity on murine L929 fibroblasts, independent of disruption of cell membranes evidenced by absence of hemolytic activity. The cytotoxicity identified was associated with oxidative stress, which culminated in mitochondrial respiration dysfunction and direct or indirect DNA damage (strand breaks and oxidative damage), triggering cell death via apoptosis. Our findings suggest that extracts of essential oil of C. Heliotropiifolius may be considered as agents to be used therapeutically in treatment of certain cancers.

Asunto(s)

Antineoplásicos , Croton , Aceites Volátiles , Sesquiterpenos , Humanos , Animales , Ratones , Aceites Volátiles/farmacología , Croton/química , Línea Celular Tumoral , Sesquiterpenos/análisis , Hojas de la Planta/química

RESUMEN

Species of the genus Candida, characterized as commensals of the human microbiota, are opportunistic pathogens capable of generating various types of infections with high associated costs. Considering the limited pharmacological arsenal and the emergence of antifungal-resistant strains, the repositioning of drugs is a strategy used to search for new therapeutic alternatives, in which minocycline and doxycycline have been evaluated as potential candidates. Thus, the objective was to evaluate the in vitro antifungal activity of two tetracyclines, minocycline and doxycycline, and their possible mechanism of action against fluconazole-resistant strains of Candida spp. The sensitivity test for antimicrobials was performed using the broth microdilution technique, and the pharmacological interaction with fluconazole was also analysed using the checkerboard method. To analyse the possible mechanisms of action, flow cytometry assays were performed. The minimum inhibitory concentration obtained was 4-427 µg ml-1 for minocycline and 128-512 µg ml-1 for doxycycline, and mostly indifferent and additive interactions with fluconazole were observed. These tetracyclines were found to promote cellular alterations that generated death by apoptosis, with concentration-dependent reactive oxygen species production and reduced cell viability. Therefore, minocycline and doxycycline present themselves as promising study molecules against Candida spp.

Asunto(s)

Antifúngicos , Fluconazol , Humanos , Fluconazol/farmacología , Antifúngicos/farmacología , Candida , Minociclina/farmacología , Doxiciclina/farmacología , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Fúngica

RESUMEN

Fungal infections caused by Cryptococcus spp. pose a threat to health, especially in immunocompromised individuals. The available arsenal of drugs against cryptococcosis is limited, due to their toxicity and/or lack of accessibility in low-income countries, requiring more therapeutic alternatives. Selective serotonin reuptake inhibitors (SSRIs), through drug repositioning, are a promising alternative to broaden the range of new antifungals against Cryptococcus spp. This study evaluates the antifungal activity of three SSRIs, sertraline, paroxetine, and fluoxetine, against Cryptococcus spp. strains, as well as assesses their possible mechanism of action. Seven strains of Cryptococcus spp. were used. Sensitivity to SSRIs, fluconazole, and itraconazole was evaluated using the broth microdilution assay. The interactions resulting from combinations of SSRIs and azoles were investigated using the checkerboard assay. The possible action mechanism of SSRIs against Cryptococcus spp. was evaluated through flow cytometry assays. The SSRIs exhibited in vitro antifungal activity against Cryptococcus spp. strains, with minimum inhibitory concentrations ranging from 2 to 32 µg/mL, and had synergistic and additive interactions with azoles. The mechanism of action of SSRIs against Cryptococcus spp. involved damage to the mitochondrial membrane and increasing the production of reactive oxygen species, resulting in loss of cellular viability and apoptotic cell death. Fluoxetine also was able to cause significant damage to yeast DNA. These findings demonstrate the in vitro antifungal potential of SSRIs against Cryptococcus spp. strains.

Asunto(s)

Cryptococcus neoformans , Cryptococcus , Humanos , Antifúngicos/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Fluoxetina/farmacología , Fluconazol/farmacología , Azoles , Pruebas de Sensibilidad Microbiana

RESUMEN

Introduction. Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant Staphylococcus aureus (MRSA) being a leading cause of antimicrobial resistance. To combat this problem, drug repurposing offers a promising solution for the discovery of new antibacterial agents.Hypothesis. Menadione exhibits antibacterial activity against methicillin-sensitive and methicillin-resistant S. aureus strains, both alone and in combination with oxacillin. Its primary mechanism of action involves inducing oxidative stress.Methodology. Sensitivity assays were performed using broth microdilution. The interaction between menadione, oxacillin, and antioxidants was assessed using checkerboard technique. Mechanism of action was evaluated using flow cytometry, fluorescence microscopy, and in silico analysis.Aim. The aim of this study was to evaluate the in vitro antibacterial potential of menadione against planktonic and biofilm forms of methicillin-sensitive and resistant S. aureus strains. It also examined its role as a modulator of oxacillin activity and investigated the mechanism of action involved in its activity.Results. Menadione showed antibacterial activity against planktonic cells at concentrations ranging from 2 to 32 µg ml-1, with bacteriostatic action. When combined with oxacillin, it exhibited an additive and synergistic effect against the tested strains. Menadione also demonstrated antibiofilm activity at subinhibitory concentrations and effectively combated biofilms with reduced sensitivity to oxacillin alone. Its mechanism of action involves the production of reactive oxygen species (ROS) and DNA damage. It also showed interactions with important targets, such as DNA gyrase and dehydroesqualene synthase. The presence of ascorbic acid reversed its effects.Conclusion. Menadione exhibited antibacterial and antibiofilm activity against MRSA strains, suggesting its potential as an adjunct in the treatment of S. aureus infections. The main mechanism of action involves the production of ROS, which subsequently leads to DNA damage. Additionally, the activity of menadione can be complemented by its interaction with important virulence targets.

Asunto(s)

Staphylococcus aureus Resistente a Meticilina , Oxacilina , Oxacilina/farmacología , Vitamina K 3/farmacología , Meticilina , Staphylococcus aureus , Especies Reactivas de Oxígeno , Antibacterianos/farmacología , Biopelículas

RESUMEN

Candida spp. infections are a serious health problem, especially in patients with risk factors. The acquisition of resistance, often associated with biofilm production, makes treatment more difficult due to the reduced effectiveness of available antifungals. Drug repurposing is a good alternative for the treatment of infections by Candida spp. biofilms. The present study evaluated the in vitro antibiofilm activity of sertraline in reducing the cell viability of forming and matured biofilms, in addition to elucidating whether effective concentrations are safe. Sertraline reduced biofilm cell viability by more than 80 % for all Candida species tested, acting at low and safe concentrations, both on mature biofilm and in preventing its formation, even the one with highest virulence. Its preventive mechanism seemed to be related to binding with ALS3. These data indicate that sertraline is a promising drug with anticandidal biofilm potential in safe doses. However, further studies are needed to elucidate the antibiofilm mechanism and possible application of pharmaceutical forms.

Asunto(s)

Candida , Candidiasis , Humanos , Sertralina/farmacología , Sertralina/uso terapéutico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candidiasis/tratamiento farmacológico , Biopelículas , Pruebas de Sensibilidad Microbiana , Candida albicans

RESUMEN

Introduction. Candida spp. are commensal fungal pathogens of humans, but when there is an imbalance in the microbiota, or weak host immunity, these yeasts can become pathogenic, generating high medical costs.Gap Statement. With the increase in resistance to conventional antifungals, the development of new therapeutic strategies is necessary. This study evaluated the in vitro antifungal activity of chlorogenic acid against fluconazole-resistant strains of Candida spp. Mechanism of action through flow cytometry and in silico analyses, as well as molecular docking assays with ALS3 and SAP5, important proteins in the pathogenesis of Candida albicans associated with the adhesion process and biofilm formation.Results. The chlorogenic acid showed in vitro antifungal activity against the strains tested, causing reduced cell viability, increased potential for mitochondrial depolarization and production of reactive oxygen species, DNA fragmentation and phosphatidylserine externalization, indicating an apoptotic process. Concerning the analysis through docking, the complexes formed between chlorogenic acid and the targets Thymidylate Kinase, CYP51, 1Yeast Cytochrome BC1 Complex e Exo-B-(1,3)-glucanase demonstrated more favourable binding energy. In addition, chlorogenic acid presented significant interactions with the ALS3 active site residues of C. albicans, important in the adhesion process and resistance to fluconazole. Regarding molecular docking with SAP5, no significant interactions were found between chlorogenic acid and the active site of the enzyme.Conclusion. We concluded that chlorogenic acid has potential use as an adjuvant in antifungal therapies, due to its anti-Candida activity and ability to interact with important drug targets.

Asunto(s)

Antifúngicos , Fluconazol , Antifúngicos/farmacología , Apoptosis , Biopelículas , Candida , Candida albicans , Ácido Clorogénico/farmacología , Farmacorresistencia Fúngica , Fluconazol/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular

RESUMEN

AIM: In the Roux-en-Y gastric bypass technique, classic laparoscopic surgical retractors are usually rigid, require an additional incision for its installation, or must be handled by an assistant during the surgical procedure, involving a risk of liver injury. The aim of this study was to evaluate and validate a technique of the esophagogastric junction exposure obtained by the flexible liver retractor in bariatric surgery, comparing its efficacy with the retractor classically used for this purpose. METHODS: This study was performed as a randomized, open, prospective, controlled, and comparative design in patients with medical indications of bariatric surgery. The subjects were distributed in the classic (control) and flexible (test) retractor groups. RESULTS: A total of 100 patients (n=50 control group, n=50 test group) were included. No statistically significant difference was observed in the mean duration of surgery. Regarding visibility, 100% of the patients in the flexible retractor group demonstrated an optimal visibility level, although without statistical significance concerning the classic retractor group (94%). Invariably, carrying a trocar was necessary when using the classic retractor. CONCLUSIONS: The flexible liver retractor is safe, effective, ergonomic, and inexpensive. Furthermore, it presented a satisfactory aesthetic profile, and the use of specific instruments, new adaptation curve, and training for its handling were not required.

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OBJETIVOS: Os afastadores clássicos de cirurgia laparoscópica são geralmente rígidos, necessitando de uma incisão adicional para sua instalação ou de um auxiliar para manuseio durante o ato cirúrgico e ainda, podem envolvem risco de injúria hepática. Avaliar e validar uma técnica de exposição da junção esofagogástrica obtida pelo afastador flexível de fígado em cirurgia bariátrica comparando sua eficácia com a de afastador classicamente utilizado para este fim. MÉTODOS: Tratou-se de um estudo prospectivo, aberto, controlado e comparativo em pacientes com indicação de cirurgia, distribuídos de forma randomizada em dois grupos: clássico (controle) e afastador flexível (teste). RESULTADOS: Foram incluídos 100 pacientes (n=50 grupo controle, n=50 grupo teste), sem diferença estatística na distribuição por idade e por morbidades, havendo diferença estatística somente no gênero (grupo controle obteve proporção maior de homens, p=0,020). Em relação ao tempo médio de realização das operações, não foi constatada diferença estatística. No quesito visibilidade, verificou-se que 100% dos pacientes do grupo afastador flexível obteve nível de visibilidade ótima, porém sem significância estatística com relação ao grupo clássico (94%). Invariavelmente, foi necessário um portal a mais de trocarte quando do uso do afastador clássico. CONCLUSÃO: O afastador flexível de fígado demonstrou-se seguro, eficaz, ergonômico, de baixo custo, de perfil estético satisfatório, não requerendo instrumental específico para uso ou nova curva de adaptação e aprendizado para manuseio.

Asunto(s)

Cirugía Bariátrica , Derivación Gástrica , Obesidad Mórbida , Unión Esofagogástrica/cirugía , Humanos , Estudios Prospectivos

RESUMEN

The current drug therapy for schizophrenia effectively treats acute psychosis and its recurrence; however, this mental disorder's cognitive and negative symptoms are still poorly controlled. Antipsychotics present important side effects, such as weight gain and extrapyramidal effects. The essential oil of Alpinia zerumbet (EOAZ) leaves presents potential antipsychotic properties that need further preclinical investigation. Here, we determined EAOZ effects in preventing and reversing schizophrenia-like symptoms (positive, negative, and cognitive) induced by ketamine (KET) repeated administration in mice and putative neurobiological mechanisms related to this effect. We conducted the behavioral evaluations of prepulse inhibition of the startle reflex (PPI), social interaction, and working memory (Y-maze task), and verified antioxidant (GSH, nitrite levels), anti-inflammatory [interleukin (IL)-6], and neurotrophic [brain-derived neurotrophic factor (BDNF)] effects of this oil in hippocampal tissue. The atypical antipsychotic olanzapine (OLZ) was used as standard drug therapy. EOAZ, similarly to OLZ, prevented and reversed most KET-induced schizophrenia-like behavioral alterations, i.e., sensorimotor gating deficits and social impairment. EOAZ had a modest effect on the prevention of KET-associated working memory deficit. Compared to OLZ, EOAZ showed a more favorable side effects profile, inducing less cataleptic and weight gain changes. EOAZ efficiently protected the hippocampus against KET-induced oxidative imbalance, IL-6 increments, and BDNF impairment. In conclusion, our data add more mechanistic evidence for the anti-schizophrenia effects of EOAZ, based on its antioxidant, anti-inflammatory, and BDNF up-regulating actions. The absence of significant side effects observed in current antipsychotic drug therapy seems to be an essential benefit of the oil.

Asunto(s)

Alpinia , Antipsicóticos , Aceites Volátiles , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo , Ratones , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Olanzapina

RESUMEN

Purpose: To evaluate the effect of topical instillation of pegaptanib sodium upon inflammatory angiogenesis induced in the rabbit cornea by alkaline cauterization. Methods: Inflammatory angiogenesis was induced by alkaline (sodium hydroxide) cauterization in the corneas of 29 male New Zealand rabbits. The animals were divided into 4 groups: a control group treated with 0.5% carboxymethylcellulose sodium eye drops, a group treated with 1.0% prednisolone acetate eye drops, a group treated with 0.5% pegaptanib sodium diluted in 15 mL 0.5% carboxymethylcellulose sodium, and a group treated with 1.0% pegaptanib sodium diluted in 15 mL 0.5% carboxymethylcellulose sodium. After cauterization, eye drops were administered every 12 hours for 21 days. The animals were evaluated every 3 days after cauterization, and the newly formed vessels were quantified from photographs. The treatment effectiveness was analyzed with 3 parameters of antiangiogenic response: neovascularization area (NA), total vascular length (TVL), and number of blood vessels (BVN). Results: Average NA, TVL, and BVN values were significantly higher in both pegaptanib groups than in the prednisolone group. A nonstatistically significant reduction in parameters on days 18 and 21 was the minimum achieved in both pegaptanib groups. The efficacy of the treatments in relation to the control was significantly greater in the prednisolone group than in the 0.5% pegaptanib group or the 1.0% pegaptanib group (P < 0.001). Conclusion: Topical instillation of 0.5% and 1.0% pegaptanib sodium diluted in 15 mL 0.5% carboxymethylcellulose sodium had no inhibitory effect on corneal neovascularization in this rabbit model.

Asunto(s)

Inhibidores de la Angiogénesis/farmacología , Aptámeros de Nucleótidos/farmacología , Inflamación/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Administración Tópica , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Aptámeros de Nucleótidos/administración & dosificación , Aptámeros de Nucleótidos/uso terapéutico , Cáusticos/administración & dosificación , Cáusticos/efectos adversos , Córnea/patología , Lesiones de la Cornea/inducido químicamente , Neovascularización de la Córnea/inducido químicamente , Modelos Animales de Enfermedad , Inflamación/diagnóstico , Instilación de Medicamentos , Masculino , Prednisolona/administración & dosificación , Prednisolona/farmacología , Conejos , Hidróxido de Sodio/administración & dosificación , Hidróxido de Sodio/efectos adversos , Resultado del Tratamiento

RESUMEN

The genus Candida spp. has been highlighted as one of the main etiological agents causing fungal infections, with Candida albicans being the most prominent, responsible for most cases of candidemia. Due to its capacity for invasion and tissue adhesion, it is associated with the formation of biofilms, mainly in the environment and hospital devices, decreasing the effectiveness of available treatments. The repositioning of drugs, which is characterized by the use of drugs already on the market for other purposes, together with molecular-docking methods can be used aiming at the faster development of new antifungals to combat micro-organisms. This study aimed to evaluate the antifungal effect of diazepam on mature C. albicans biofilms in vitro and its action on biofilm in formation, as well as its mechanism of action and interaction with structures related to the adhesion of C. albicans, ALS3 and SAP5. To determine the MIC, the broth microdilution test was used according to protocol M27-A3 (CLSI, 2008). In vitro biofilm formation tests were performed using 96-well plates, followed by molecular-docking protocols to analyse the binding agent interaction with ALS3 and SAP5 targets. The results indicate that diazepam has antimicrobial activity against planktonic cells of Candida spp. and C. albicans biofilms, interacting with important virulence factors related to biofilm formation (ALS3 and SAP5). In addition, treatment with diazepam triggered a series of events in C. albicans cells, such as loss of membrane integrity, mitochondrial depolarization and increased production of EROs, causing DNA damage and consequent cell apoptosis.

Asunto(s)

Antifúngicos/farmacología , Biopelículas/efectos de los fármacos , Candida/efectos de los fármacos , Diazepam/farmacología , Farmacorresistencia Fúngica/efectos de los fármacos , Ácido Aspártico Endopeptidasas/metabolismo , Candida/patogenicidad , Fluconazol/farmacología , Proteínas Fúngicas/metabolismo

RESUMEN

Two new diterpenoid derivatives 7α,12ß,17-triacetoxy-6ß,19-dihydroxy-13ß,16-spirocicloabiet-8-ene-11,14-dione ( 1: ) and 6ß-acetoxy-3ß,7α,12α-trihydroxy-13ß,16-spirocicloabiet-8-ene-11,14-dione ( 2: ) along with 11 ( 3: - 13: ) miscellaneous compounds were isolated from the leaves of Plectranthus ornatus Codd. Their structures were elucidated by spectroscopic analysis and gauge independent atomic orbitals 13C NMR calculations. The isolated compounds were screened for their effects on intestinal motility using guinea-pig ileum and duodenum and by their cytotoxicity against 4 human cancer cell lines (HCT-116, SF-295, PC-3, and HL-60). Compounds 6: and 9: were moderately cytotoxic against HL-60, whereas 6: and 13: were more active on SF-295 and HCT-116.

Asunto(s)

Plectranthus , Animales , Diterpenos/farmacología , Cobayas , Humanos , Estructura Molecular , Extractos Vegetales/farmacología , Hojas de la Planta

RESUMEN

RESUMO - RACIONAL: Os afastadores clássicos de cirurgia laparoscópica são geralmente rígidos, necessitando de uma incisão adicional para sua instalação ou de um auxiliar para manuseio durante o ato cirúrgico e ainda, podem envolvem risco de injúria hepática. OBJETIVOS: Avaliar e validar uma técnica de exposição da junção esofagogástrica obtida pelo afastador flexível de fígado em cirurgia bariátrica comparando sua eficácia com a de afastador classicamente utilizado para este fim. MÉTODOS: Tratou-se de um estudo prospectivo, aberto, controlado e comparativo em pacientes com indicação de cirurgia, distribuídos de forma randomizada em dois grupos: clássico (controle) e afastador flexível (teste). RESULTADOS: Foram incluídos 100 pacientes (n=50 grupo controle, n=50 grupo teste), sem diferença estatística na distribuição por idade e por morbidades, havendo diferença estatística somente no gênero (grupo controle obteve proporção maior de homens, p=0,020). Em relação ao tempo médio de realização das operações, não foi constatada diferença estatística. No quesito visibilidade, verificou-se que 100% dos pacientes do grupo afastador flexível obteve nível de visibilidade ótima, porém sem significância estatística com relação ao grupo clássico (94%). Invariavelmente, foi necessário um portal a mais de trocarte quando do uso do afastador clássico. CONCLUSÃO: O afastador flexível de fígado demonstrou-se seguro, eficaz, ergonômico, de baixo custo, de perfil estético satisfatório, não requerendo instrumental específico para uso ou nova curva de adaptação e aprendizado para manuseio.

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ABSTRACT - BACKGROUND: In the Roux-en-Y gastric bypass technique, classic laparoscopic surgical retractors are usually rigid, require an additional incision for its installation, or must be handled by an assistant during the surgical procedure, involving a risk of liver injury. Aim: The aim of this study was to evaluate and validate a technique of the esophagogastric junction exposure obtained by the flexible liver retractor in bariatric surgery, comparing its efficacy with the retractor classically used for this purpose. Methods: This study was performed as a randomized, open, prospective, controlled, and comparative design in patients with medical indications of bariatric surgery. The subjects were distributed in the classic (control) and flexible (test) retractor groups. Results: A total of 100 patients (n=50 control group, n=50 test group) were included. No statistically significant difference was observed in the mean duration of surgery. Regarding visibility, 100% of the patients in the flexible retractor group demonstrated an optimal visibility level, although without statistical significance concerning the classic retractor group (94%). Invariably, carrying a trocar was necessary when using the classic retractor. Conclusions: The flexible liver retractor is safe, effective, ergonomic, and inexpensive. Furthermore, it presented a satisfactory aesthetic profile, and the use of specific instruments, new adaptation curve, and training for its handling were not required.

Asunto(s)

Humanos , Obesidad Mórbida , Derivación Gástrica , Cirugía Bariátrica , Estudios Prospectivos , Unión Esofagogástrica/cirugía

RESUMEN

This study evaluated the effect of etomidate against biofilms of Candida spp. and analysed through molecular docking the interaction of this drug with ALS3, an important protein for fungal adhesion. Three fluconazole-resistant fungi were used: Candida albicans, Candida parapsilosis and Candida tropicalis. Growing biofilms were exposed to etomidate at 31.25-500 µg ml-1. Then, an ALS3 adhesive protein from C. albicans was analysed through a molecular mapping technique, composed of a sequence of algorithms to perform molecular mapping simulation based on classic force field theory. Etomidate showed antifungal activity against growing biofilms of resistant C. albicans, C. parapsilosis and C. tropicalis at all concentrations used in the study. The etomidate coupling analysis revealed three interactions with the residues of interest compared to hepta-threonine, which remained at the ALS3 site. In addition, etomidate decreased the expression of mannoproteins on the surface of C. albicans. These results revealed that etomidate inhibited the growth of biofilms.

Asunto(s)

Candida/efectos de los fármacos , Farmacorresistencia Fúngica/efectos de los fármacos , Etomidato/farmacología , Antifúngicos/metabolismo , Antifúngicos/farmacología , Biopelículas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Etomidato/metabolismo , Fluconazol/farmacología , Proteínas Fúngicas/metabolismo , Humanos , Glicoproteínas de Membrana/metabolismo , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular/métodos