RESUMEN
Faced with the emergence of multiresistant microorganisms that affect human health, microbial agents have become a serious global threat, affecting human health and plant crops. Antimicrobial peptides have attracted significant attention in research for the development of new microbial control agents. This work's goal was the structural characterization and analysis of antifungal activity of chitin-binding peptides from Capsicum baccatum and Capsicum frutescens seeds on the growth of Candida and Fusarium species. Proteins were initially submitted to extraction in phosphate buffer pH 5.4 and subjected to chitin column chromatography. Posteriorly, two fractions were obtained for each species, Cb-F1 and Cf-F1 and Cb-F2 and Cf-F2, respectively. The Cb-F1 (C. baccatum) and Cf-F1 (C. frutescens) fractions did not bind to the chitin column. The electrophoresis results obtained after chromatography showed two major protein bands between 3.4 and 14.2 kDa for Cb-F2. For Cf-F2, three major bands were identified between 6.5 and 14.2 kDa. One band from each species was subjected to mass spectrometry, and both bands showed similarity to nonspecific lipid transfer protein. Candida albicans and Candida tropicalis had their growth inhibited by Cb-F2. Cf-F2 inhibited the development of C. albicans but did not inhibit the growth of C. tropicalis. Both fractions were unable to inhibit the growth of Fusarium species. The toxicity of the fractions was tested in vivo on Galleria mellonella larvae, and both showed a low toxicity rate at high concentrations. As a result, the fractions have enormous promise for the creation of novel antifungal compounds.
Asunto(s)
Antifúngicos , Candida , Quitina , Fusarium , Simulación del Acoplamiento Molecular , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/metabolismo , Quitina/química , Quitina/metabolismo , Fusarium/efectos de los fármacos , Candida/efectos de los fármacos , Proteínas Portadoras/química , Proteínas Portadoras/metabolismo , Animales , Capsicum/química , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/farmacología , Pruebas de Sensibilidad Microbiana , Unión Proteica , Conformación ProteicaRESUMEN
There is a growing imperative for research into alternative compounds for the treatment of the fungal infections. Thus, many studies have focused on the analysis of antifungal proteins and peptides from different plant sources. Among these molecules are protease inhibitors (PIs). Previously, PIs present in the peptide-rich fractions called PEF1, PEF2 and PEF3 were identified from Capsicum chinense seeds, which have strong activity against phytopathogenic fungi. The aim of this study was to evaluate the mechanism of action and antimicrobial activity of PIs from PEF2 and PEF3 on the growth of yeasts of the genus Candida. In this work, analyses of their antimicrobial activity and cell viability were carried out. Subsequently, the mechanism of action by which the PIs cause the death of the yeasts was evaluated. Cytotoxicity was assessed in vitro by erythrocytes lysis and in vivo in Galleria mellonella larvae. PEF2 and PEF3 caused 100% of the growth inhibition of C. tropicalis and C. buinensis. For C. albicans inhibition was approximately 60% for both fractions. The PEF2 and PEF3 caused a reduction in mitochondrial functionality of 54% and 46% for C. albicans, 26% and 30% for C. tropicalis, and 71% and 68% for C. buinensis, respectively. These fractions induced morphological alterations, led to membrane permeabilization, elevated ROS levels, and resulted in necrotic cell death in C. tropicalis, whilst demonstrating low toxicity toward host cells. From the results obtained here, we intend to contribute to the understanding of the action of PIs in the control of fungal diseases of medical importance.
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Antifúngicos , Candida , Inhibidores de Proteasas , Antifúngicos/farmacología , Candida/efectos de los fármacos , Candida/crecimiento & desarrollo , Inhibidores de Proteasas/farmacología , Pruebas de Sensibilidad Microbiana , Animales , Capsicum/microbiología , Especies Reactivas de Oxígeno/metabolismo , Semillas/crecimiento & desarrollo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Eritrocitos/efectos de los fármacos , Larva/microbiología , Larva/crecimiento & desarrollo , Larva/efectos de los fármacosRESUMEN
With the emergence of multidrug-resistant microorganisms, microbial agents have become a serious global threat, affecting human health and various plants. Therefore, new therapeutic alternatives, such as chitin-binding proteins, are necessary. Chitin is an essential component of the fungal cell wall, and chitin-binding proteins exhibit antifungal activity. In the present study, chitin-binding peptides isolated from Capsicum chinense seeds were characterized and evaluated for their in vitro antimicrobial effect against the growth of Candida and Fusarium fungi. Proteins were extracted from the seeds and subsequently the chitin-binding proteins were separated by chitin affinity chromatography. After chromatography, two fractions, Cc-F1 (not retained on the column) and Cc-F2 (retained on the column), were obtained. Electrophoresis revealed major protein bands between 6.5 and 26.6 kDa for Cc-F1 and only a ~ 6.5 kDa protein band for Cc-F2, which was subsequently subjected to mass spectrometry. The protein showed similarity with hevein-like and endochitinase and was then named Cc-Hev. Data are available via ProteomeXchange with identifier PXD054607. Next, we predicted the three-dimensional structure of the peptides and performed a peptide docking with (NAG)3. Subsequently, growth inhibition assays were performed to evaluate the ability of the peptides to inhibit microorganism growth. Cc-Hev inhibited the growth of C. albicans (up to 75% inhibition) and C. tropicalis (100% inhibition) and induced a 65% decrease in cell viability for C. albicans and 100% for C. tropicalis. Based on these results, new techniques to combat fungal diseases could be developed through biotechnological applications; therefore, further studies are needed.
Asunto(s)
Antifúngicos , Candida , Capsicum , Quitina , Quitinasas , Fusarium , Semillas , Semillas/química , Antifúngicos/farmacología , Antifúngicos/aislamiento & purificación , Antifúngicos/química , Antifúngicos/metabolismo , Quitina/metabolismo , Quitina/farmacología , Fusarium/efectos de los fármacos , Quitinasas/farmacología , Quitinasas/metabolismo , Quitinasas/química , Quitinasas/aislamiento & purificación , Candida/efectos de los fármacos , Candida/enzimología , Lectinas de Plantas/farmacología , Lectinas de Plantas/química , Lectinas de Plantas/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Péptidos/farmacología , Péptidos/química , Péptidos/aislamiento & purificación , Péptidos/metabolismo , Simulación del Acoplamiento Molecular , Proteínas de Plantas/farmacología , Proteínas de Plantas/química , Proteínas de Plantas/aislamiento & purificación , Proteínas de Plantas/metabolismo , Péptidos Catiónicos AntimicrobianosRESUMEN
The abnormal hemodynamics in Fontan circulation due to persistently increased systemic venous pressure results in hepatic venous congestion and Fontan-associated liver disease. Combined assessment of cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in this context have not been fully explored. To evaluate cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in patients who have undergone Fontan procedures. Thirty-eight patients and 23 controls underwent cardiac and liver MRI examinations in a 3.0-T scanner. Mann-Whitney, Fisher exact test, and Spearman's correlation were applied to evaluate myocardial volumes, function, native cardiac and liver T1 mapping, ECVs and liver stiffness. The mean native cardiac T1 value (p = 0.018), cardiac ECV (p < 0.001), liver native T1 (p < 0.001), liver ECV (p < 0.001), and liver stiffness (p < 0.001) were higher in patients than controls. The indexed end-diastolic volume (EDVi) correlated with the myocardial ECV (r = 0.356; p = 0.033), native liver T1 (r = 0.571; p < 0.001), and with liver stiffness (r = 0.391; p = 0.015). In addition, liver stiffness correlated with liver ECV (r = 0.361; p = 0.031) and native liver T1 (r = 0.458; p = 0.004). An association between cardiac remodeling and cardiac and liver fibrosis were found in this population. The usefulness of MRI to follow cardiac and liver involvement in these patients is critical to improve treatment strategies and to prevent the need for combined liver and heart transplantation.
RESUMEN
OBJECTIVES: To evaluate MRI with gadoxetic acid to quantify liver function in cirrhotic patients using the relative enhancement index (REI) compared with Child-Pugh score (CPS), MELD score, and indocyanine green plasma disappearance rate (ICG-PDR) and to establish cutoffs for REI to stratify cirrhotic patients into good and poor liver function groups. METHODS: We prospectively evaluated 60 cirrhotic patients and calculated CPS, MELD score, ICG-PDR, and REI for each patient. Spearman's correlation coefficient was used to assess correlation between REI, CPS, MELD, and ICG-PDR. Good and poor liver function groups were created by k-means clustering algorithm using CPS, MELD, and ICG-PDR. ROC curve analysis was performed and optimal cutoff was identified for group differentiation. RESULTS: Good correlations were found between REI and other liver function biomarkers: REI and CPS (rho = - 0.816; p < 0.001); REI and MELD score (rho = - 0.755; p < 0.001); REI and ICG-PDR (rho = 0.745; p < 0.001)]. REI correlation was stronger for patients with Child-Pugh A (rho = 0.642, p = 0.002) and B (rho = 0.798, p < 0.001) than for those with Child-Pugh C (rho = 0.336, p = 0.148). REI is significantly lower in patients with poor liver function (p < 0.001). ROC curve showed an AUC 0.94 to discriminate patients with poor liver function (REI cutoff < 100; 100% sensitivity; 76% specificity). CONCLUSIONS: REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. REI can be easily calculated and can be used to estimate liver function in clinical practice in the routine evaluation of cirrhotic patients that undergo MR imaging with gadoxetic acid contrast. KEY POINTS: ⢠REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. ⢠REI can be easily calculated in the routine evaluation of cirrhotic patients that undergo gadoxetic acid-enhanced MRI. ⢠The REI enables stratification of cirrhotic patients into good and poor liver function groups and can be used as additional information, together with morphological and focal liver lesion evaluation.
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Medios de Contraste , Gadolinio DTPA , Humanos , Medios de Contraste/farmacología , Hígado/diagnóstico por imagen , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Verde de Indocianina/farmacología , Biomarcadores , Imagen por Resonancia Magnética/métodos , Estudios RetrospectivosRESUMEN
Quantitative computed tomography (QCT) has recently gained an important role in the functional assessment of chronic lung disease. Its capacity in diagnostic, staging, and prognostic evaluation in this setting is similar to that of traditional pulmonary function testing. Furthermore, it can demonstrate lung injury before the alteration of pulmonary function test parameters, and it enables the classification of disease phenotypes, contributing to the customization of therapy and performance of comparative studies without the intra- and inter-observer variation that occurs with qualitative analysis. In this review, we address technical issues with QCT analysis and demonstrate the ability of this modality to answer clinical questions encountered in daily practice in the management of patients with chronic lung disease.
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Enfermedades Pulmonares , Pulmón , Humanos , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico por imagen , Variaciones Dependientes del Observador , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Plant genomes are rich in repetitive sequences, and transposable elements (TEs) are the most accumulated of them. This mobile fraction can be distinguished as Class I (retrotransposons) and Class II (transposons). Retrotransposons that are transposed using an intermediate RNA and that accumulate in a "copy-and-paste" manner were screened in three genomes of peppers (Solanaceae). The present study aimed to understand the genome relationships among Capsicum annuum, C. chinense, and C. baccatum, based on a comparative analysis of the function, diversity and chromosome distribution of TE lineages in the Capsicum karyotypes. Due to the great commercial importance of pepper in natura, as a spice or as an ornamental plant, these genomes have been widely sequenced, and all of the assemblies are available in the SolGenomics group. These sequences were used to compare all repetitive fractions from a cytogenomic point of view. RESULTS: The qualification and quantification of LTR-retrotransposons (LTR-RT) families were contrasted with molecular cytogenetic data, and the results showed a strong genome similarity between C. annuum and C. chinense as compared to C. baccatum. The Gypsy superfamily is more abundant than Copia, especially for Tekay/Del lineage members, including a high representation in C. annuum and C. chinense. On the other hand, C. baccatum accumulates more Athila/Tat sequences. The FISH results showed retrotransposons differentially scattered along chromosomes, except for CRM lineage sequences, which mainly have a proximal accumulation associated with heterochromatin bands. CONCLUSIONS: The results confirm a close genomic relationship between C. annuum and C. chinense in comparison to C. baccatum. Centromeric GC-rich bands may be associated with the accumulation regions of CRM elements, whereas terminal and subterminal AT- and GC-rich bands do not correspond to the accumulation of the retrotransposons in the three Capsicum species tested.
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Capsicum/clasificación , Capsicum/genética , Variación Genética , Genoma de Planta , Secuencias Repetidas Terminales , Cromosomas de las Plantas/genética , Genómica , Filogenia , Secuencias Repetitivas de Ácidos Nucleicos , RetroelementosAsunto(s)
COVID-19 , Humanos , Activación Plaquetaria , SARS-CoV-2 , Sobrevivientes , Plaquetas/fisiologíaRESUMEN
BACKGROUND AND AIM: Fat distribution may have prognostic value in the evaluation of non-alcoholic fatty liver disease. This study was conducted to evaluate associations of magnetic resonance imaging-measured abdominal fat areas with steatosis, steatohepatitis, and fibrosis, assessed histopathologically, in patients with type 2 diabetes. METHODS: This prospective study included 66 patients with type 2 diabetes (12 males, 54 females, age 26-68 years), without chronic liver disease of other causes. Axial dual-echo magnetic resonance images were acquired. Visceral, subcutaneous, and preperitoneal fat areas were measured using Osirix software. Liver biopsy specimens were obtained from all patients and examined histopathologically to evaluate steatosis, steatohepatitis, and fibrosis. Linear (for steatosis) and logistic (for steatohepatitis and fibrosis) regression models were fitted for the outcomes. R2 was used as a measure of how much model variance the predictors explained and to compare different predictors of the same outcome. RESULTS: Visceral and preperitoneal fat areas correlated well with histopathologically determined liver steatosis grade (both P = 0.004) and liver fibrosis (P = 0.008 and P = 0.037, respectively). All fat areas correlated well with steatohepatitis (P ≤ 0.002). Preperitoneal and visceral fat areas were the best predictors of steatohepatitis (R2 = 0.379) and fibrosis (R2 = 0.181), respectively. CONCLUSIONS: Visceral fat area was the best predictor of fibrosis in patients with type 2 diabetes. Preperitoneal fat area was the best predictor of steatohepatitis and is a potential new non-invasive marker for use in the screening of these patients to detect more aggressive forms of non-alcoholic fatty liver disease.
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Diabetes Mellitus Tipo 2/complicaciones , Grasa Intraabdominal , Enfermedad del Hígado Graso no Alcohólico/etiología , Biomarcadores , Femenino , Humanos , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/patología , Cirrosis Hepática/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Pronóstico , RiesgoRESUMEN
Aspergilloma, also known as mycetoma or fungus ball, is characterized by a round or oval mass with soft-tissue attenuation within a preexisting lung cavity. The typical computed tomography (CT) aspect of an aspergilloma is a mass separated from the wall of the cavity by an airspace of variable size and shape, resulting in the air crescent sign, also known as the meniscus sign. This CT feature is non-specific and can be simulated by several other entities that result in intracavitary masses. This review describes the main clinical and imaging aspects of the infectious and non-infectious diseases that may present with fungus-ball appearance, including pulmonary hydatid cyst, Rasmussen aneurysm, pulmonary gangrene, intracavitary clot, textiloma, lung cancer, metastasis, and teratoma, focusing on the differential diagnosis.
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Aneurisma Falso/diagnóstico por imagen , Cuerpos Extraños/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Arteria Pulmonar/diagnóstico por imagen , Aspergilosis Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Aneurisma Falso/microbiología , Diagnóstico Diferencial , Equinococosis Pulmonar/diagnóstico por imagen , Gangrena/diagnóstico por imagen , Humanos , Aspergilosis Pulmonar Invasiva/diagnóstico por imagen , Teratoma/diagnóstico por imagen , Trombosis/diagnóstico por imagen , Tuberculosis Pulmonar/complicacionesRESUMEN
Many Fusarium species are able to cause severe infections in plants as well as in animals and humans. Therefore, the discovery of new antifungal agents is of paramount importance. CaThi belongs to the thionins, which are cationic peptides with low molecular weights (â¼5 kDa) that have toxic effects against various microorganisms. Herein, we study the mechanism of action of CaThi and its combinatory effect with fluconazole (FLC) against Fusarium solani. The mechanism of action of CaThi was studied by growth inhibition, viability, plasma membrane permeabilization, ROS induction, caspase activation, localization, and DNA binding capability, as assessed with Sytox green, DAB, FITC-VAD-FMK, CaThi-FITC, and gel shift assays. The combinatory effect of CaThi and FLC was assessed using a growth inhibition assay. Our results demonstrated that CaThi present a dose dependent activity and at the higher used concentration (50 µg mL-1 ) inhibits 83% of F. solani growth, prevents the formation of hyphae, permeabilizes membranes, induces endogenous H2 O2 , activates caspases, and localizes intracellularly. CaThi combined with FLC, at concentrations that alone do not inhibit F. solani, result in 100% death of F. solani when combined. The data presented in this study demonstrate that CaThi causes death of F. solani via apoptosis; an intracellular target may also be involved. Combined treatment using CaThi and FLC is a strong candidate for studies aimed at improved targeting of F. solani. This strategy is of particular interest because it minimizes selection of resistant microorganisms.
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Antifúngicos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Fluconazol/farmacología , Tioninas/farmacología , Antifúngicos/química , Péptidos Catiónicos Antimicrobianos/química , Capsicum/química , Membrana Celular/efectos de los fármacos , Permeabilidad de la Membrana Celular/efectos de los fármacos , Frutas/química , Fusarium/efectos de los fármacos , Fusarium/patogenicidad , Humanos , Hifa/efectos de los fármacos , Hifa/patogenicidad , Tioninas/químicaRESUMEN
Proteins extracted from Capsicum annuum L. fruits were initially subjected to reversed-phase chromatography on HPLC, resulting in eight peptide-rich fractions. All the fractions obtained were tested for their ability to inhibit porcine trypsin and amylase from both human saliva and from larval insect in vitro. All fractions were also tested for their ability to inhibit growth of the phytopathogenic fungi. Several fractions inhibited the activity of human salivary amylase and larval insect amylase, especially fraction Fa5. No fraction tested was found to inhibit trypsin activity, being Fa2 fraction an exception. Interestingly fraction Fa5 also displayed high antimicrobial activity against the species of the Fusarium genus. Fraction Fa5 was found to have two major protein bands of 17 and 6.5 kDa, and these were sequenced by mass spectrometry. Two peptides were obtained from the 6.5-kDa band, which showed similarity to antimicrobial peptides. Fraction Fa5 was also tested for its ability to permeabilize membranes and induce ROS. Fraction Fa5 was able to permeabilize the membranes of all the fungi tested. Fungi belonging to the genus Fusarium also showed an increase in the endogenous production of ROS when treated with this fraction. Antimicrobial peptides were also identified in the fruits from other Capsicum species.
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Antiinfecciosos , Capsicum/química , Inhibidores Enzimáticos , Frutas/química , Fusarium/crecimiento & desarrollo , Péptidos , Proteínas de Plantas , alfa-Amilasas/antagonistas & inhibidores , Animales , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificación , Antiinfecciosos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Humanos , Péptidos/química , Péptidos/aislamiento & purificación , Péptidos/farmacología , Proteínas de Plantas/química , Proteínas de Plantas/aislamiento & purificación , Proteínas de Plantas/farmacología , PorcinosRESUMEN
BACKGROUND: During the last few years, a growing number of antimicrobial peptides have been isolated from plants and particularly from seeds. Recent results from our laboratory have shown the purification of a new trypsin inhibitor, named CaTI, from chilli pepper (Capsicum annuum L.) seeds. This study aims to evaluate the antifungal activity and mechanism of action of CaTI on phytopathogenic fungi and detect the presence of protease inhibitors in other species of this genus. RESULTS: Our results show that CaTI can inhibit the growth of the phytopathogenic fungi Colletotrichum gloeosporioides and C. lindemuthianum. CaTI can also permeabilize the membrane of all tested fungi. When testing the inhibitor on its ability to induce reactive oxygen species, an induction of reactive oxygen species (ROS) and nitric oxide (NO) particularly in Fusarium species was observed. Using CaTI coupled to fluorescein isothiocyanate (FITC), it was possible to determine the presence of the inhibitor inside the hyphae of the Fusarium oxysporum fungus. The search for protease inhibitors in other Capsicum species revealed their presence in all tested species. CONCLUSION: This paper shows the antifungal activity of protease inhibitors such as CaTI against phytopathogenic fungi. Antimicrobial peptides, among which the trypsin protease inhibitor family stands out, are present in different species of the genus Capsicum and are part of the chemical arsenal that plants use to defend themselves against pathogens. © 2017 Society of Chemical Industry.
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Capsicum/química , Fungicidas Industriales/farmacología , Estrés Oxidativo/efectos de los fármacos , Enfermedades de las Plantas/microbiología , Extractos Vegetales/farmacología , Semillas/química , Inhibidores de Tripsina/farmacología , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Permeabilidad de la Membrana Celular/efectos de los fármacos , Colletotrichum/efectos de los fármacos , Colletotrichum/crecimiento & desarrollo , Colletotrichum/metabolismo , Fungicidas Industriales/química , Fungicidas Industriales/aislamiento & purificación , Fungicidas Industriales/metabolismo , Fusarium/efectos de los fármacos , Fusarium/crecimiento & desarrollo , Fusarium/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Inhibidores de Tripsina/química , Inhibidores de Tripsina/aislamiento & purificación , Inhibidores de Tripsina/metabolismoRESUMEN
BACKGROUND: Thionins are a family of plant antimicrobial peptides (AMPs), which participate in plant defense system against pathogens. Here we describe some aspects of the CaThi thionin-like action mechanism, previously isolated from Capsicum annuum fruits. Thionin-like peptide was submitted to antimicrobial activity assays against Candida species for IC50 determination and synergism with fluconazole evaluation. Viability and plasma membrane permeabilization assays, induction of intracellular ROS production analysis and CaThi localization in yeast cells were also investigated. RESULTS: CaThi had strong antimicrobial activity against six tested pathogenic Candida species, with IC50 ranging from 10 to 40 µg.mL(-1). CaThi antimicrobial activity on Candida species was candidacidal. Moreover, CaThi caused plasma membrane permeabilization in all yeasts tested and induces oxidative stresses only in Candida tropicalis. CaThi was intracellularly localized in C. albicans and C. tropicalis, however localized in nuclei in C. tropicalis, suggesting a possible nuclear target. CaThi performed synergistically with fluconazole inhibiting all tested yeasts, reaching 100% inhibition in C. parapsilosis. The inhibiting concentrations for the synergic pair ranged from 1.3 to 4.0 times below CaThi IC50 and from zero to 2.0 times below fluconazole IC50. CONCLUSION: The results reported herein may ultimately contribute to future efforts aiming to employ this plant-derived AMP as a new therapeutic substance against yeasts.
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Antifúngicos/farmacología , Candida/efectos de los fármacos , Capsicum/química , Fluconazol/farmacología , Tioninas/farmacología , Candida/crecimiento & desarrollo , Sinergismo Farmacológico , Frutas/química , Pruebas de Sensibilidad MicrobianaRESUMEN
Niemann-Pick disease is a rare autosomal recessive lysosomal storage disease with three subtypes. Types A and B result from a deficiency of acid sphingomyelinase activity, associated with the accumulation of lipid-laden macrophages (so-called Niemann-Pick cells) in various tissues, especially the liver and spleen. Type A is a fatal neurodegenerative disorder of infancy. Type B Niemann-Pick disease is a less severe form with milder neurological involvement, characterized by hepatosplenomegaly, hyperlipidemia, and pulmonary involvement; most patients live into adulthood. Type C Niemann-Pick disease is a complex lipid storage disorder caused by defects in cholesterol trafficking, resulting in a clinical presentation dominated by neurological involvement. Pulmonary involvement occurs in all three types of Niemann-Pick disease, but most frequently in type B. Respiratory manifestations range from a lack of symptoms to respiratory failure. Progression of respiratory disease is slow, but inexorable, due to the accumulation of Niemann-Pick cells in the alveolar septa, bronchial walls, and pleura, potentially leading to a progressively worsening restrictive pattern on pulmonary function testing. Bronchoalveolar lavage has important diagnostic value because it shows the presence of characteristic Niemann-Pick cells. Radiographic findings consist of a reticular or reticulonodular pattern and, eventually, honeycombing, involving mainly the lower lung zones. The most common changes identified by high-resolution computed tomography are ground-glass opacities, mild smooth interlobular septal thickening, and intralobular lines. The aim of this review is to describe the main clinical, imaging, and pathological aspects of Niemann-Pick disease, with a focus on pulmonary involvement.
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Enfermedad de Gaucher/diagnóstico , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/etiología , Enfermedades de Niemann-Pick/complicaciones , Enfermedades de Niemann-Pick/diagnóstico , Enfermedades Óseas/etiología , Tos/etiología , Diagnóstico Diferencial , Disnea/etiología , Humanos , Hepatopatías/etiología , Enfermedades de Niemann-Pick/terapia , Infecciones del Sistema Respiratorio/etiologíaRESUMEN
BACKGROUND: Ventilation with low tidal volume (VT) is well recognized as a protective approach to patients with acute respiratory distress syndrome (ARDS), but the optimal level of positive end-expiratory pressure (PEEP) remains uncertain. This study aims to evaluate two protective ventilatory strategies sequentially applied in patients with early ARDS. METHODS: In this prospective cohort study, fifteen patients were ventilated during 24 h with positive end-expiratory pressure (PEEP) adjusted according to the ARDSnet low-PEEP table (ARDSnet-24 h). During the next 24 h, nine patients with PaO2/FIO2 ratio below 350 mmHg were ventilated with PEEP titrated according to the Open Lung Concept protocol (ARDSnet + OLC). In the other six patients, regardless of their PaO2/FIO2 ratio, the ARDSnet remained for a further 24 h (ARDSnet-48 h). Ventilatory variables, arterial blood-gas and cytokine were obtained at baseline, 24 and 48 h. Additionally, whole-lung-computed tomography was acquired at 24 and 48 h. RESULTS: A sustained improvement in PaO2/FIO2 ratio (P = 0.008) with a decrease in collapsed regions (P = 0.008) was observed in the ARDSnet + OLC group compared with the ARDSnet-24 h group. A reduction in IL-6 in plasma (P < 0.02) was observed throughout the protocol in the ARDSnet + OLC group. Compared with the ARDSnet-48 h group, the ARDSnet + OLC presented smaller amounts of collapsed areas (P = 0.018) without significant differences in hyperinflated regions and in driving and plateau pressures. CONCLUSIONS: In this set of patients with early ARDS, mechanical ventilation with an individually tailored PEEP sustained improved pulmonary function with better aeration, without significant increase in hyperinflated areas". TRIAL REGISTRATION: Brazilian Clinical Trials Registry (ReBec). RBR-5zm9pr. 04th November 2015.
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Respiración con Presión Positiva/métodos , Atelectasia Pulmonar/prevención & control , Síndrome de Dificultad Respiratoria/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Análisis de los Gases de la Sangre , Femenino , Humanos , Interleucina-6/sangre , Interleucina-8/sangre , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores Protectores , Atelectasia Pulmonar/complicaciones , Atelectasia Pulmonar/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/complicaciones , Tomografía Computarizada Espiral , Adulto JovenRESUMEN
We report the case of a 45-year-old man who initially presented with chondrosarcoma of the left femur that was treated surgically. Follow-up chest computed tomography (CT) performed 3 years later showed multiple small nodules with a tree-in-bud branching pattern and larger elongated opacities with beaded contours. These findings raised the suspicion of intravascular tumor embolism. Pulmonary CT angiography demonstrated intravascular thrombosis and dilated and beaded peripheral pulmonary arteries. The tumoral origin of the thrombus was confirmed by lung biopsy.
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Condrosarcoma/secundario , Neoplasias Femorales/patología , Neoplasias Pulmonares/secundario , Nódulos Pulmonares Múltiples/secundario , Células Neoplásicas Circulantes/patología , Arteria Pulmonar/patología , Biopsia , Condrosarcoma/diagnóstico por imagen , Condrosarcoma/tratamiento farmacológico , Condrosarcoma/cirugía , Neoplasias Femorales/cirugía , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/tratamiento farmacológico , Arteria Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
The objective of this study was to isolate antimicrobial peptides from Capsicum baccatum seeds and evaluate their antimicrobial activity and inhibitory effects against α-amylase. Initially, proteins from the flour of C. baccatum seeds were extracted in sodium phosphate buffer, pH 5.4, and precipitated with ammonium sulfate at 90% saturation. The D1 and D2 fractions were subjected to antifungal tests against the yeasts Saccharomyces cerevisiae, Candida albicans, Candida tropicalis, and Kluyveromyces marxiannus, and tested against α-amylases from Callosobruchus maculates and human saliva. The D2 fraction presented higher antimicrobial activity and was subjected to further purification and seven new different fractions (H1-H7) were obtained. Peptides in the H4 fraction were sequenced and the N-terminal sequences revealed homology with previously reported storage vicilins from seeds. The H4 fraction exhibited strong antifungal activity and also promoted morphological changes in yeast, including pseudohyphae formation. All fractions, including H4, inhibited mammalian α-amylase activity but only the H4 fraction was able to inhibit C. maculatus α-amylase activity. These results suggest that the fractions isolated from the seeds of C. baccatum can act directly in plant defenses against pathogens and insects.
Asunto(s)
Antifúngicos/farmacología , Capsicum/química , Péptidos/farmacología , Proteínas de Almacenamiento de Semillas/farmacología , Semillas/química , Levaduras/efectos de los fármacos , alfa-Amilasas/antagonistas & inhibidores , Secuencia de Aminoácidos , Animales , Antifúngicos/aislamiento & purificación , Cromatografía por Intercambio Iónico , Inhibidores Enzimáticos/farmacología , Humanos , Insectos , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Micología , Péptidos/química , Péptidos/aislamiento & purificación , Proteínas de Almacenamiento de Semillas/química , Proteínas de Almacenamiento de Semillas/aislamiento & purificación , Alineación de Secuencia , Levaduras/crecimiento & desarrollo , alfa-Amilasas/metabolismoRESUMEN
Plants defend themselves against pathogens with production of antimicrobial peptides (AMPs). Herein we describe the discovery of a new antifungal and antibacterial peptide from fruits of Capsicum annuum that showed similarity to an already well characterized family of plant AMPs, thionins. Other fraction composed of two peptides, in which the major peptide also showed similarity to thionins. Among the obtained fractions, fraction 1, which is composed of a single peptide of 7 kDa, was sequenced by Edman method and its comparative sequence analysis in database (nr) showed similarity to thionin-like peptides. Tests against microorganisms, fraction 1 presented inhibitory activity to the cells of yeast Saccharomyces cerevisiae, Candida albicans, and Candida tropicalis and caused growth reduction to the bacteria species Escherichia coli and Pseudomonas aeruginosa. Fraction 3 caused inhibitory activity only for C. albicans and C. tropicalis. This fraction was composed of two peptides of â¼7 and 10 kDa, and the main protein band correspondent to the 7 kDa peptide, also showed similarity to thionins. This plasma membrane permeabilization assay demonstrates that the peptides present in the fractions 1 and 3 induced changes in the membranes of all yeast strains, leading to their permeabilization. Fraction 1 was capable of inhibiting acidification of the medium of glucose-induced S. cerevisiae cells 78% after an incubation time of 30 min, and opposite result was obtained for C. albicans. Experiments demonstrate that the fraction 1 and 3 were toxic and induced changes in the membranes of all yeast strains, leading to their permeabilization.