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1.
Anal Bioanal Chem ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965103

RESUMEN

"Purple Drank", a soft drink containing promethazine (PMZ) and codeine (COD), has gained global popularity for its hallucinogenic effects. Consuming large amounts of this combination can lead to potentially fatal events. The binding of these drugs to plasma proteins can exacerbate the issue by increasing the risk of drug interactions, side effects, and/or toxicity. Herein, the binding affinity to human serum albumin (HSA) of PMZ and its primary metabolites [N-desmethyl promethazine (DMPMZ) and promethazine sulphoxide (PMZSO)], along with COD, was investigated by high-performance affinity chromatography (HPAC) though zonal approach. PMZ and its metabolites exhibited a notable binding affinity for HSA (%b values higher than 80%), while COD exhibited a %b value of 65%. To discern the specific sites of HSA to which these compounds were bound, displacement experiments were performed using warfarin and (S)-ibuprofen as probes for sites I and II, respectively, which revealed that all analytes were bound to both sites. Molecular docking studies corroborated the experimental results, reinforcing the insights gained from the empirical data. The in silico data also suggested that competition between PMZ and its metabolites with COD can occur in both sites of HSA, but mainly in site II. As the target compounds are chiral, the enantioselectivity for HSA binding was also explored, showing that the binding for these compounds was not enantioselective.

2.
J Bacteriol ; 204(11): e0017422, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36218351

RESUMEN

Pseudomonas aeruginosa inhibits or eradicates Staphylococcus aureus in most in vitro settings. Nonetheless, P. aeruginosa and S. aureus are commonly isolated from chronically infected, nonhealing wounds and lungs of people with cystic fibrosis (CF). Therefore, we hypothesized that S. aureus could protect itself from P. aeruginosa through glucose-derived metabolites, such as small organic acids, preventing it from being eradicated. This in vitro study demonstrated that S. aureus populations, in the presence of glucose, secrete one or more substances that efficiently eradicate P. aeruginosa in a concentration-dependent manner. These substances had a molecular mass lower than three kDa, were hydrophilic, heat- and proteinase-resistant, and demonstrated a pH-dependent effect. Nuclear magnetic resonance analysis identified acetoin, acetic acid, and oligopeptides or cyclic peptides in glucose-grown S. aureus supernatants. All the tested wild-type and clinical S. aureus strain inhibited P. aeruginosa growth. Thus, we proposed a model in which a cocktail of these compounds, produced by established S. aureus populations in glucose presence, facilitated these two species' coexistence in chronic infections. IMPORTANCE Chronic infections affect a growing part of the population and are associated with high societal and personal costs. Multiple bacterial species are often present in these infections, and multispecies infections are considered more severe than single-species infections. Staphylococcus aureus and Pseudomonas aeruginosa often coexist in chronic infections. However, the interactions between these two species and their coexistence in chronic infections are not fully understood. By exploring in vitro interactions, we found a novel S. aureus-mediated inhibition of P. aeruginosa, and we suggested a model of the coexistence of the two species in chronic infections. With this study, we enhanced our understanding of the pathogenesis of chronic multispecies infections, which is crucial to paving the way for developing improved treatment strategies.


Asunto(s)
Fibrosis Quística , Infecciones por Pseudomonas , Infecciones Estafilocócicas , Humanos , Pseudomonas aeruginosa/metabolismo , Staphylococcus aureus/metabolismo , Infecciones Estafilocócicas/microbiología , Fibrosis Quística/microbiología , Glucosa/metabolismo , Infecciones por Pseudomonas/microbiología , Biopelículas
3.
Behav Pharmacol ; 33(2&3): 213-221, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-34074811

RESUMEN

The endocannabinoid system modulates the stress coping strategies in the dorsolateral periaqueductal grey (dlPAG). The most relevant endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG) exert inhibitory control over defensive reactions mediated by the dlPAG. However, the protective role of anandamide is limited by its lack of effect in higher concentrations. Thus, the 2-AG emerges as a complementary target for developing new anxiolytic compounds. Nevertheless, the role of 2-AG on stress responsivity may vary according to the nature of the stimulus. In this study, we verified whether the dlPAG injection of 2-AG or inhibitors of its hydrolysis induce anxiolytic-like effects in male Wistar rats exposed to behavioral models in which physical stress (mild electric shock) is a critical component, namely the contextual fear conditioning test (CFC) and the Vogel conflict test (VCT). We also investigated the contribution of cannabinoid receptor type 1 (CB1) and type 2 (CB2) in such effects. The facilitation of 2-AG signaling in the dlPAG reduced contextual fear expression and exhibited an anxiolytic-like effect in the VCT in a mechanism dependent on activation of CB1 and CB2. However, the VCT required a higher dose than CFC. Further, the monoacylglycerol inhibitors, which inhibit the hydrolysis of 2-AG, were effective only in the CFC. In conclusion, we confirmed the anti-aversive properties of 2-AG in the dlPAG through CB1 and CB2 mechanisms. However, these effects could vary according to the type of stressor and the anxiety model employed.


Asunto(s)
Ansiolíticos , Endocannabinoides , Animales , Ansiolíticos/metabolismo , Ansiolíticos/farmacología , Ácidos Araquidónicos , Endocannabinoides/metabolismo , Endocannabinoides/farmacología , Miedo , Glicéridos , Masculino , Sustancia Gris Periacueductal/metabolismo , Piperidinas/farmacología , Pirazoles/farmacología , Ratas , Ratas Wistar , Receptor Cannabinoide CB1/metabolismo
4.
Chirality ; 34(9): 1166-1190, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35699356

RESUMEN

Polysaccharides arouse great interest due to their structure and unique properties, such as biocompatibility, biodegradability, and absence of toxicity. Polysaccharides from marine sources are particularly useful due to the wide variety of applications and biological activities. Chitosan, a deacetylated derivative of chitin, is an example of an interesting bioactive marine-derived polysaccharide. Moreover, a wide variety of chemical modifications and conjugation of chitosan with other bioactive molecules are responsible for improvements in physicochemical properties and biological activities, expanding the range of applications. An overview of the synthetic approaches for preparing chitosan, chitosan derivatives, and conjugates is described and discussed. A recent update of the biological activities and applications in different research fields, mainly focused on the last 5 years, is presented, highlighting current trends.


Asunto(s)
Quitosano , Quitina/química , Quitosano/química , Quitosano/farmacología , Polisacáridos/química , Polisacáridos/farmacología , Estereoisomerismo
5.
Drug Chem Toxicol ; 45(4): 1687-1697, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33334193

RESUMEN

The Triplaris gardneriana Wedd. seeds extract has great therapeutic potential due to numerous biological activities such as antioxidant, antibacterial and anti-inflammatory, which are associated with phenolic content. Although this herbal preparation has shown many benefits, recently their toxicity profile has begun to be explored. In this present study, the toxic effects of T. gardneriana seeds ethanolic extract (EETg) on biological systems of different taxonomical groups and levels of complexity (from cell culture to lower vertebrates) were assessed, through a variety of viability and toxicological assays. It was found that EETg did not impair the Saccharomyces cerevisiae growth at the highest tested concentration (200 µg/mL), and no toxicant evidence was observed in Aedes aegypti larvae or in Drosophila melanogaster adult stage. Contrarily, the extract reduced the viability of undifferentiated Caco-2 cells (250 µg/mL, 40% of viable cells), but did not affect differentiated ones. The embryotoxicity in Danio rerio model showed a LC50 of 7.41 mg/L (95% confidence interval, 4.78 - 11.49 mg/L). EETg did not show signs of toxicity in the majority of the models used, but lethality and malformations in zebrafish embryos occurred. Further analyses are needed to better understand the selective toxicity mechanism of EETg on zebrafish, as well as whether the toxic effects happen in higher vertebrates.


Asunto(s)
Polygonaceae , Pez Cebra , Animales , Células CACO-2 , Drosophila melanogaster , Embrión no Mamífero , Etanol , Humanos , Larva , Extractos Vegetales/toxicidad , Semillas/toxicidad
6.
Genomics ; 112(6): 5066-5071, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32898643

RESUMEN

Persistent infections by high-risk human papillomavirus (HR-HPV) are a necessary condition, but not sufficient for cervical cancer development. Genetic variants of HR-HPV appear to be related to the risk of persistent infections. The study performed a functional evaluation of variants of the HPV-31 promoter region (LCR). For this, cloning and subcloning of variants HPV-31/UFPE-21 HPV-31/UFPE-89, HPV-31/UFPE-66, E2 gene and prototype HPV-31 were performed. Transfection with different concentrations of E2 was done and the concentration of 25 ng was determined to be ideal for LCR activation. HPV-31/UFPE-21 and HPV-31/UFPE-89 have a greater ability to alter Nluc reporter gene expression levels and HPV-31/UFPE-66 showed decreased levels of gene expression of Nluc reporter gene compared to control. Statistical analysis showed a significant difference between the polymorphic LCR regions and the control (p < 0.0001). A more refined profile of variants of HPV-31 and its importance for the prognosis of cervical lesions begins to be drawn.


Asunto(s)
Papillomavirus Humano 31/genética , Regiones Promotoras Genéticas , Proteínas de Unión al ADN/metabolismo , Células HeLa , Humanos , Polimorfismo Genético , Transactivadores/metabolismo , Activación Transcripcional , Proteínas Virales/metabolismo
7.
Drug Dev Ind Pharm ; 46(6): 1026-1033, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32393135

RESUMEN

Objective: Considering the limited number of studies that analyze the behavior of plant preparations in human body, this study aimed to characterize the phenolic compounds from Triplaris gardneriana extract (EETg) in terms of antioxidant and metabolic aspects, integrating in vitro, in silico and in vivo strategies.Methods: EETg was analyzed in relation to polyphenols release from the plant matrix under in vitro digestion, as well as the pharmacokinetic prediction of their major compounds by in silico simulation and understanding of its in vivo antioxidant effect in an alternative animal model.Results: About 35.22% of polyphenols from EETg proved to be accessible after enzymatic hydrolysis. A kinetics study showed that 40% of the total content of these phytochemicals was released from the extract accompanied by increased antioxidant capacity after 180 min of gastrointestinal simulation. A computational approach revealed that 7 out of 9 major phenolic compounds of EETg showed good pharmacokinetic parameters such as intestinal absorption and bioavailability score. In addition, the extract showed a protective effect on copper-induced oxidative stress in Drosophila melanogaster, evidenced by the restoration of basal levels of thiol and malondialdehyde contents. These biochemical observations were supported by the examination of histological features of D. melanogaster brain.Conclusion: It was demonstrated that the oral administration of EETg would provide phenolic compounds partially absorbable by the human gut and capable of providing health benefits associated with the inhibition of oxidative stress. Additionally, the results highlight the need to implement new approaches for the rational development of plant-based medicines.


Asunto(s)
Drosophila melanogaster , Polygonaceae , Polifenoles/metabolismo , Animales , Antioxidantes , Estrés Oxidativo , Extractos Vegetales , Polifenoles/química , Semillas/química
8.
Cytokine ; 113: 99-104, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29935877

RESUMEN

Human papillomavirus (HPV) is responsible for high-grade cervical lesions and cervical cancer. The inflammation plays a key role in cervical cancer progression. In this context, studies propose an association between TNFα and IL10 SNPs and susceptibility to HPV infection. The present work aimed to investigate the possible association between IL10 and TNFα promoter polymorphisms and HPV infection in the cervical carcinogenesis risk in women from Brazil. A total of 654 samples was evaluated in this study. HPV detection was performed by PCR and HPV genotyping was performed by PCR and sequencing of positive MY09/11 PCR product. Genotyping of IL10 SNPs (rs1800871 and rs1800896) was performed by High Resolution Melt analysis. Genotyping of TNFα SNP (rs1800629) was performed by fluorogenic allele-specific probes. The distribution of TNF-308 (rs1800629) allelic (p = 0.03) and genotype (p = 0.03) frequencies and HPV-58 infection has showed a statistically significant difference between case and control groups for the assessed TNFα polymorphism. When it comes to TNFα (rs1800629) allelic and genotypic distribution and HPVs 18 and 31 infections, no statistically significant differences between case and control groups were observed for the studied TNFα polymorphism. The allelic and genotypic distribution of IL10-819 (rs1800871) and IL10-1082 (rs1800896) and HPV infection (HPVs 58, 18 and 31) has showed no statistically significant differences between case and control groups for the assessed IL10 polymorphisms. Furthermore, it was observed that haplotypes were associated with an increased cervical cancer risk in HPVs 16, 18 and 58-positive women. It was observed that women carrying the GTA and ATG haplotypes had 3.85 and 17.99-fold, respectively, increased cervical cancer susceptibility when infected by HPV-58. In women infected with HPV-16 and HPV-18, statistically significant results in women carrying the GTA and ATA haplotypes was observed. They had a 2.32 and 3.67-fold, respectively, increased cervical cancer susceptibility when infected by these two HPV types. The analysis of the haplotypes distribution in women infected with HPV-31 has showed no statistically significant results. Our study indicates that the association of genetic polymorphism in inflammation-related genes represents a risk to the susceptibility in the development of cervical cancer in women infected by HPVs 16, 18 and 58.


Asunto(s)
Carcinogénesis/genética , Haplotipos/genética , Interleucina-10/genética , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/genética , Factor de Necrosis Tumoral alfa/genética , Neoplasias del Cuello Uterino/genética , Adulto , Alelos , Brasil , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Infecciones por Papillomavirus/virología , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Neoplasias del Cuello Uterino/virología
9.
Curr Osteoporos Rep ; 16(5): 626-634, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30203250

RESUMEN

PURPOSE OF REVIEW: To identify the use of carbon nanomaterials in bone regeneration and present new data on the regenerative capacity of bone tissue in osteopenic rats treated with graphene nanoribbons (GNRs). RECENT FINDINGS: The results show that the physical and chemical properties of the nanomaterials are suitable for the fabrication of scaffolds intended for bone regeneration. The in vitro tests suggested a non-toxicity of the GNRs as well as improved biocompatibility and bone mineralization activity. Here, for the first time, we evaluated the potential of GNRs in remodeling and repairing bone defects in osteoporotic animal models in vivo. Interestingly, bone mineralization and the initiation of the remodeling cycle by osteoclasts/osteoblasts were observed after the implantation of GNRs, thus implying healthy bone remodeling when using GNRs. This study, therefore, has opened our perspectives and certainly calls for more attention to the use of carbon nanomaterials for a wide range of osteoporosis applications.


Asunto(s)
Regeneración Ósea , Grafito , Nanotubos de Carbono , Fracturas Osteoporóticas/terapia , Fracturas de la Columna Vertebral/terapia , Andamios del Tejido , Animales , Materiales Biocompatibles , Remodelación Ósea , Carbono , Humanos , Osteoblastos , Osteoclastos , Ratas
10.
Molecules ; 23(7)2018 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-30018269

RESUMEN

Protein tyrosine phosphatase 1B (PTP1B) is an intracellular enzyme responsible for deactivation of the insulin receptor, and consequently acts as a negative regulator of insulin signal transduction. In recent years, PTP1B has become an important target for controlling insulin resistance and type 2 diabetes. In the present study, the ethyl acetate extract of leaves of Miconia albicans (IC50 = 4.92 µg/mL) was assessed by high-resolution PTP1B inhibition profiling combined with HPLC-HRMS-SPE-NMR for identification of antidiabetic compounds. This disclosed eleven PTP1B inhibitors, including five polyphenolics: 1-O-(E)-caffeoyl-4,6-di-O-galloyl-ß-d-glucopyranose (2), myricetin 3-O-α-l-rhamnopyranoside (3), quercetin 3-O-(2″-galloyl)-α-l-rhamnopyranoside (5), mearnsetin 3-O-α-l-rhamnopyranoside (6), and kaempferol 3-O-α-l-arabinopyranoside (8) as well as eight triterpenoids: maslinic acid (13), 3-epi-sumaresinolic acid (14), sumaresinolic acid (15), 3-O-cis-p-coumaroyl maslinic acid (16), 3-O-trans-p-coumaroyl maslinic acid (17), 3-O-trans-p-coumaroyl 2α-hydroxydulcioic acid (18), oleanolic acid (19), and ursolic acid (20). These results support the use of M. albicans as a traditional medicine with antidiabetic properties and its potential as a source of PTP1B inhibitors.


Asunto(s)
Melastomataceae/química , Inhibidores de Fosfodiesterasa , Hojas de la Planta/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Cromatografía Líquida de Alta Presión , Humanos , Resonancia Magnética Nuclear Biomolecular , Inhibidores de Fosfodiesterasa/química , Inhibidores de Fosfodiesterasa/aislamiento & purificación , Proteína Tirosina Fosfatasa no Receptora Tipo 1/química
11.
J Nat Prod ; 80(4): 1020-1027, 2017 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-28248501

RESUMEN

A hyphenated procedure involving high-performance liquid chromatography, photodiode array detection, high-resolution mass spectrometry, solid-phase extraction, and nuclear magnetic resonance spectroscopy, i.e., HPLC-PDA-HRMS-SPE-NMR, has proven an effective technique for the identification of compounds in complex matrices. Most HPLC-PDA-HRMS-SPE-NMR investigations reported so far have relied on analytical-scale reversed-phase C18 columns for separation. Herein is reported the use of an analytical-scale pentafluorophenyl column as an orthogonal separation method following fractionation of a crude ethyl acetate extract of leaves of Coleonema album on a preparative-scale C18 column. This setup allowed the HPLC-PDA-HRMS-SPE-NMR analysis of 23 coumarins, including six new compounds, 8-O-ß-d-glucopyranosyloxy-6-(2,3-dihydroxy-3-methylbut-1-yl)-7-methoxycoumarin (4), (Z)-6-(4-ß-d-glucopyranosyloxy-3-methylbut-2-en-1-yl)-7-hydroxycoumarin (6), 6-(4-ß-d-glucopyranosyloxy-3-methylbut-1-yl)-7-hydroxycoumarin (8), (Z)-7-(4-ß-d-glucopyranosyloxy-3-methylbut-2-en-1-yloxy)coumarin (13), (S)-8-(3-chloro-2-hydroxy-3-methylbut-1-yloxy)-7-methoxycoumarin (19), and 7-(3-chloro-2-hydroxy-3-methylbut-1-yloxy)coumarin (20). The use of the pentafluorophenyl column even allowed separation of several regioisomers that are usually difficult to separate using reversed-phase C18 columns. The phytochemical investigation described for C. album in this report demonstrates the potential and wide applicability of HPLC-PDA-HRMS-SPE-NMR for accelerated structural identification of natural products in complex mixtures.


Asunto(s)
Cumarinas/análisis , Umbeliferonas/análisis , Cromatografía Líquida de Alta Presión/métodos , Cumarinas/química , Espectroscopía de Resonancia Magnética/métodos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Extractos Vegetales/química , Rutaceae/química , Extracción en Fase Sólida , Sudáfrica , Umbeliferonas/química , Umbeliferonas/aislamiento & purificación
12.
Curr Microbiol ; 73(3): 341-345, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27246500

RESUMEN

In the present work, we provide biological evidences supporting the participation of NCW2 gene in the mechanism responsible for cell tolerance to polyhexamethylene biguanide (PHMB), an antifungal agent. The growth rate of yeast cells exposed to this agent was significantly reduced in ∆ncw2 strain and the mRNA levels of NCW2 gene in the presence of PHMB showed a 7-fold up-regulation. Moreover, lack of NCW2 gene turns yeast cell more resistant to zymolyase treatment, indicating that alterations in the ß-glucan network do occur when Ncw2p is absent. Computational analysis of the translated protein indicated neither catalytic nor transmembrane sites and reinforced the hypothesis of secretion and anchoring to cell surface. Altogether, these results indicated that NCW2 gene codes for a protein which participates in the cell wall biogenesis in yeasts and that Ncw2p might play a role in the organisation of the ß-glucan assembly.


Asunto(s)
Antifúngicos/farmacología , Biguanidas/farmacología , Pared Celular/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , beta-Glucanos/metabolismo , Pared Celular/química , Pared Celular/genética , Farmacorresistencia Fúngica , Regulación Fúngica de la Expresión Génica , Proteínas de la Membrana/genética , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , beta-Glucanos/química
13.
Med Mycol ; 53(2): 93-8, 2015 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-25541558

RESUMEN

Sporotrichosis is a subacute or chronic subcutaneous infection, caused by the fungus Sporothrix schenkii complex, occurring in human and animal tissues. Potassium iodide and itraconazole have been used as effective therapy for first-choice treatment, while amphotericin B may be indicated for disseminated infection. However, the adverse effects of potassium iodide and amphotericin B or the long duration of therapy with itraconazole often weigh against their use, leading to the search for alternatives for the treatment of severe infections. Terpinen-4-ol and farnesol are components of essential oils present in many plant species and have been described to have antifungal activity against microorganisms. In this study, 40 strains of Sporothrix spp. were tested for the susceptibility to terpinen-4-ol and farnesol. Changes in cytoplasmic membrane permeability were also investigated. Terpenes inhibited all Sporothrix strains with MIC values ranging from 87.9 to 1,429.8 µg/ml for terpinen-4-ol and from 0.003 to 0.222 µg/ml for farnesol. The MFC values ranged from 177.8 to 5,722.6 µg/ml and from 0.027 to 0.88 µg/ml, respectively, for terpinen-4-ol and farnesol. Farnesol was the most active compound for the Sporothrix strains. Significant loss of 260 and 280 nm-absorbing material did not occur after treatment with concentrations equivalent to the MIC and sub-MIC of the tested terpenes, when compared to corresponding untreated samples. The failure of terpenes to lyse Sporothrix cells suggests that their primary mechanism of action is not by causing irreversible cell membrane damage. Thus, new studies are needed to better understand the mechanisms involved in the antifungal activity.


Asunto(s)
Antifúngicos/farmacología , Microbiología Ambiental , Farnesol/farmacología , Sporothrix/efectos de los fármacos , Esporotricosis/microbiología , Terpenos/farmacología , Membrana Celular/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Permeabilidad/efectos de los fármacos , Sporothrix/aislamiento & purificación
14.
Med Mycol ; 52(3): 320-5, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24662247

RESUMEN

Miltefosine (MIL), originally developed for use in cancer chemotherapy, has been shown to have important antifungal activity against several pathogenic fungi. Our aim in this study was to determine the in vitro activity of MIL against the dimorphic fungi Histoplasma capsulatum and Sporothrix spp. This was done using the broth microdilution method. MIL had an in vitro inhibitory effect against all strains of H. capsulatum var. capsulatum and Sporothrix spp. analyzed. The minimal inhibitory concentrations (MIC) varied from 0.25 µg/ml to 2 µg/ml for H. capsulatum var. capsulatum in the filamentous phase and from 0.125 µg/ml to 1 µg/ml in the yeast phase. The MIC interval for Sporothrix spp. in the filamentous phase was 0.25-2 µg/ml. The minimal fungicidal concentrations (MFCs) were ≤4 µg/ml for isolates of both analyzed species. This study demonstrates that MIL has an antifungal effect in vitro against two potentially pathogenic fungi and that more studies should be performed in order to evaluate its applicability in vivo.


Asunto(s)
Antifúngicos/farmacología , Histoplasma/efectos de los fármacos , Fosforilcolina/análogos & derivados , Sporothrix/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Fosforilcolina/farmacología
15.
Cureus ; 16(1): e52716, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38384604

RESUMEN

Malignant peritoneal mesothelioma (MPeM) is a rare cancer of the peritoneum with a poor prognosis and nonspecific clinical course. We discuss a case of MPeM in a 59-year-old male who presented with abdominal pain and distension, without any known previous asbestos exposure. The diagnosis was made after a second biopsy finally confirmed epithelioid MPeM in an advanced stage with pleural effusion. The patient underwent six cycles of chemotherapy with cisplatin and pemetrexed, experienced disease progression, and was then started on pembrolizumab as a second-line treatment. The patient achieved a complete response after two years of treatment with pembrolizumab and has been disease-free for almost four years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0. Despite the lack of evidence to support the treatment with immunotherapy for MPeM, our case report encourages its use, highlighting its ability to enable a complete response with pembrolizumab with an excellent quality of life.

16.
Antimicrob Agents Chemother ; 57(5): 2167-70, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23459491

RESUMEN

Coccidioidomycosis is a systemic mycosis caused by the dimorphic fungi Coccidioides spp. The treatment for chronic and/or disseminated coccidioidomycosis can be prolonged and complicated. Therefore, the search for new drugs is necessary. Farnesol is a precursor in the sterol biosynthesis pathway that has been shown to present antifungal activity. Thus, the objective of this study was to evaluate the in vitro antifungal activity of farnesol alone and in combination with antifungal agents against clinical and environmental strains of Coccidioides posadasii as well as to determine their effect on the synthesis of ergosterol and on cell permeability. This study employed the broth macrodilution method to determine the MIC of farnesol against 18 strains of C. posadasii. Quantification of ergosterol was performed with 10 strains of C. posadasii after exposure to subinhibitory concentrations of farnesol. Finally, the activity of farnesol was evaluated in the presence of osmotic stress, induced by the addition of NaCl to the culture medium, during the susceptibility tests. The results showed that farnesol exhibited low MICs (ranging from 0.00171 to 0.01369 mg/liter) against all tested strains. The combination of farnesol with the antifungals showed synergistic effects (fractional inhibitory concentration index [FICI] ≤ 0.5). As for the ergosterol quantification, it was observed that exposure to subinhibitory concentrations of farnesol decreased the amount of ergosterol extracted from the fungal cells. Furthermore, farnesol also showed lower MIC values when the strains were subjected to osmotic stress, indicating the action of this compound on the fungal membrane. Thus, due to the high in vitro antifungal activity, this work brings perspectives for the performance of in vivo studies to further elucidate the effects of farnesol on the host cells.


Asunto(s)
Antifúngicos/farmacología , Coccidioides/efectos de los fármacos , Ergosterol/antagonistas & inhibidores , Farnesol/farmacología , Fluconazol/farmacología , Permeabilidad de la Membrana Celular/efectos de los fármacos , Coccidioides/crecimiento & desarrollo , Coccidioides/metabolismo , Sinergismo Farmacológico , Quimioterapia Combinada , Ergosterol/biosíntesis , Pruebas de Sensibilidad Microbiana , Concentración Osmolar , Presión Osmótica , Cloruro de Sodio/química
17.
Med Mycol ; 51(4): 432-7, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23167705

RESUMEN

Studies of the genetic variation within populations of Coccidioides posadasii are scarce, especially for those recovered from South America. Understanding the distribution of genotypes among populations is important for epidemiological surveillance. This study evaluated the genetic diversity of 18 Brazilian strains of C. posadasii through the sequencing of the 18-28S region of nuclear rDNA, as well as through RAPD and M13-PCR fingerprinting techniques. The sequences obtained were compared to Coccidioides spp. previously deposited in GenBank. The MEGA5 program was used to perform phylogenetic analyses. Within the C. posadasii clade, a single cluster was observed, containing seven isolates from Ceará, which presented a single nucleotide polymorphism. These isolates were from the same geographical area. The strains of C. posadasii showed a lower rate of genetic diversity in the ITS1 and ITS2 regions. The results of M13 and RAPD-PCR fingerprinting indicated a similar electrophoretic profile. No differences between clinical and environmental isolates were detected. This was the first study assessing the genetic variability of a larger number of C. posadasii isolates from Brazil.


Asunto(s)
Coccidioides/genética , Coccidioidomicosis/microbiología , Variación Genética , Secuencia de Bases , Brasil/epidemiología , Coccidioides/clasificación , Coccidioides/aislamiento & purificación , Coccidioidomicosis/epidemiología , Dermatoglifia del ADN , ADN de Hongos/química , ADN de Hongos/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Genotipo , Datos de Secuencia Molecular , Filogenia , Polimorfismo de Nucleótido Simple , Técnica del ADN Polimorfo Amplificado Aleatorio , Análisis de Secuencia de ADN
18.
Can J Microbiol ; 59(11): 754-60, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24206358

RESUMEN

The objective of this study was to establish the phenotypical and molecular patterns of clinical isolates of Trichophyton tonsurans circulating in the state of Ceará, northeastern Brazil. For this purpose, 25 T. tonsurans strains isolated from independent cases of tinea capitis in children were phenotypically evaluated regarding their macro- and micro-morphological characteristics, vitamin requirements, urease production, and antifungal susceptibility. The molecular characterization was carried out with random amplified polymorphic DNA molecular markers and M13 fingerprinting. The presence of the genes CarbM14, Sub2, CER, URE, ASP, PBL, and LAC, which encode enzymes related to fungal virulence, was also evaluated. Finally, melanin production was assessed through specific staining. The data obtained demonstrated that these T. tonsurans strains have considerable phenotypical variation, although they showed a low degree of genetic polymorphism according to the markers used. The genes CarbM14, Sub2, CER, and URE were detected in all the analyzed strains. The gene LAC was also identified in all the strains, and melanin synthesis was phenotypically confirmed. The strains were susceptible to antifungals, especially itraconazole (GM = 0.06 µg/mL) and ketoconazole (GM = 0.24 µg/mL). Therefore, T. tonsurans strains can present great phenotypical heterogeneity, even in genetically similar isolates. Moreover, the presence of the LAC gene indicates the possible participation of melanin in the pathogenesis of these dermatophytes.


Asunto(s)
Tiña del Cuero Cabelludo/microbiología , Trichophyton/clasificación , Factores de Virulencia/genética , Antifúngicos/farmacología , Brasil/epidemiología , Niño , Dermatoglifia del ADN , Genotipo , Humanos , Fenotipo , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Técnica del ADN Polimorfo Amplificado Aleatorio , Mapeo Restrictivo , Cuero Cabelludo/microbiología , Tiña del Cuero Cabelludo/epidemiología , Tiña del Cuero Cabelludo/genética , Trichophyton/efectos de los fármacos , Trichophyton/genética , Trichophyton/patogenicidad , Virulencia/genética
19.
Biomed Phys Eng Express ; 9(5)2023 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-37207632

RESUMEN

Purpose.This study aimed to develop a computer system for automatic detection of thermographic changes indicating breast malignancy risk.Materials and methods. The database contained 233 thermograms of women, including 43 with malignant lesions and 190 with no malignant lesions. Five classifiers were evaluated (k-Nearest Neighbor, Support Vector Machine, Decision Tree, Discriminant Analysis, and Naive Bayes) in combination with oversampling techniques. An attribute selection approach using genetic algorithms was considered. Performance was assessed using accuracy, sensitivity, specificity, AUC, and Kappa statistics.Results. Support vector machines combined with attribute selection by genetic algorithm and ASUWO oversampling obtained the best performance. Attributes were reduced by 41.38%, and accuracy was 95.23%, sensitivity was 93.65%, and specificity was 96.81%. The Kappa index was 0.90, and AUC was 0.99.Conclusion. The feature selection process lowered computational costs and improved diagnostic accuracy. A high-performance system using a new breast imaging modality could positively aid breast cancer screening.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Teorema de Bayes , Detección Precoz del Cáncer , Algoritmos , Máquina de Vectores de Soporte
20.
Med Biol Eng Comput ; 61(2): 305-315, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36550236

RESUMEN

The present work shows a computational tool developed in the MATLAB platform. Its main functionality is to evaluate a thermal model of the breast. This computational infrastructure consists of modules in which manipulate the infrared images and calculate breast temperature profiles. It also allows the analysis of breast nodules. The different modules of the framework are interconnected through an interface which the major purpose is to automatize the whole process of the infrared image analysis, in a quick and organized way. The tool is initially supplied with a three-dimensional mesh that represents the substitute geometry of the patient's breast together with her infrared images which are transformed into temperature matrices. Through these matrices, the frontal and lateral mappings are performed by specified modules. This process generates an image and a text file with all the temperatures associated to the nodes of the surface mesh. The developed tool is also able to manage the use of a commercial mesh generation program and a computational fluid dynamics code, the FLUENT, in order to validate the technique by the use of a parametric analysis. In these analyses, the tumor may have several geometric shapes and different locations within the breast.


Asunto(s)
Mama , Procesamiento de Imagen Asistido por Computador , Humanos , Femenino , Mama/diagnóstico por imagen
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