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Leprosy still represents a serious health problem in a number of countries, including Brazil. Although leprosy has been associated with poverty for a long time, it is still difficult to accurately define this relationship. Here, we evaluated in an endemic municipality the progress from 1995 to 2015 of epidemiological indicators to establish if there were any strong associations between social indicators and the occurrence of leprosy. An ecological study was conducted using the SINAN database (Brazilian leprosy-national notifiable diseases information system) in combination with georeferencing of leprosy cases. The georeferencing used the ArcGis programme and occurrence of cases was evaluated in relation to the Health Vulnerability Index (HVI), an indicator that categorises socio-economic and sanitation factors. The data identified a marked decrease in the overall prevalence of leprosy, a reduction in the new case-detection rate and a reduction in the number of cases with grade 2 disabilities (albeit with transient peaks in 2007 and 2015). Logistic regression analysis showed association of detection rates with elevated HVI. Thus, while the epidemiological indicators point to the elimination of leprosy, there is evidence of hidden cases and an association between higher rates of leprosy detection and greater social vulnerability remain.
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Enfermedades Endémicas , Lepra/epidemiología , Factores de Riesgo , Factores Socioeconómicos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Preescolar , Ciudades , Personas con Discapacidad/estadística & datos numéricos , Enfermedades Endémicas/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Prevalencia , Saneamiento/estadística & datos numéricos , Adulto JovenRESUMEN
It remains unknown whether or not a reduction in muscle sympathetic nerve activity in heart failure patients is associated over time with the effects of long- or short-term repeated exercise. 10 chronic heart failure patients, age 49±3 years old, functional class I-III NYHA, ejection fraction <40% were randomly submitted to either an acute bout of moderate continuous exercise OR high-intensity interval exercise. Muscle sympathetic nerve activity (microneurography) and forearm blood flow (venous occlusion plethysmography) were evaluated pre- and post-exercise sessions. The moderate exercise consisted of cycle exercise at an intensity corresponding to anaerobic threshold. The interval exercise consisted of a 2-min cycle exercise at intensity corresponding to anaerobic threshold, followed by a 1-min exercise set at respiratory compensation point. Exercise capacity was evaluated by cardiopulmonary exercise test. The caloric expenditure in both sessions was 100 kcal. Baseline muscle sympathetic nerve activity and forearm blood flow levels were not different between sessions. Moderate or high-intensity exercise caused no significant changes in muscle sympathetic nerve activity and forearm blood flow. These findings suggest that the reduction in muscle sympathetic nerve activity and the increase in forearm blood flow provoked by exercise training in chronic heart failure patients are due to cumulative effects over time.
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Ejercicio Físico/fisiología , Insuficiencia Cardíaca/fisiopatología , Músculo Esquelético/inervación , Sistema Nervioso Simpático/fisiopatología , Enfermedad Crónica , Prueba de Esfuerzo , Femenino , Antebrazo/irrigación sanguínea , Entrenamiento de Intervalos de Alta Intensidad , Humanos , Masculino , Microelectrodos , Persona de Mediana Edad , Pletismografía , Flujo Sanguíneo RegionalRESUMEN
AIMS: The effects of irradiation (gamma-rays and electron-beams), up to 10 kGy, in the antimicrobial activity of mushroom species (Boletus edulis, Hydnum repandum, Macrolepiota procera and Russula delica) differently processed (fresh, dried, freeze) were evaluated. METHODS AND RESULTS: Clinical isolates with different resistance profiles from hospitalized patients in Local Health Unit of Mirandela, Northeast of Portugal, were used as target micro-organisms. The mushrooms antimicrobial activity did not suffer significant changes that might compromise applying irradiation as a possible mushroom conservation technology. CONCLUSIONS: Two kGy dose (independently of using gamma-rays or electron-beams) seemed to be the most suitable choice to irradiate mushrooms. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides important results in antimicrobial activity of extracts prepared from irradiated mushroom species.
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Agaricales/efectos de la radiación , Antibacterianos/efectos de la radiación , Electrones , Rayos gamma , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Extractos Celulares/farmacología , HumanosRESUMEN
Trypanosoma cruzi trypomastigotes invade a great variety of mammalian cells, with several molecules being implicated in this complex event. Herein, the sequence GGIALAG present in prokineticin-2 receptor (PKR2), selected by phage display technology, is described as a new T. cruzi receptor for the Tc85 group of glycoproteins belonging to the gp85/TS superfamily and involved in cellular invasion of mammalian hosts. This finding is confirmed by the inhibitory activity of MCF10-A (human mammary) cell invasion by T. cruzi either by anti-PKR2 antibodies (77%) or GGIALAG-synthetic peptide (42%). Furthermore, interference RNA (iRNA) inhibition of PKR2 expression in MCF10-A cells reduces T. cruzi invasion by 50%. The binding site of Tc85 to PKR2 was localized at the C-terminal end of the molecule, upstream of the conserved FLY sequence, previously implicated in parasite cell invasion. PKR2, a receptor formed by seven membrane-spanning α-helical segments, is mainly present in the central nervous system, peripheral organs, and mature blood cells. Due to its wide distribution, PKR2 could be a suitable receptor for T. cruzi natural infection, contributing to the parasite dissemination throughout the mammalian organism. These findings augment the number and diversity of possible in vivo receptors for T. cruzi and reassure the multiplicity of Tc85 binding sites to mammalian hosts.
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Receptores Acoplados a Proteínas G/metabolismo , Receptores de Péptidos/metabolismo , Trypanosoma cruzi/fisiología , Animales , Bacteriófagos , Sitios de Unión , Línea Celular , Secuencia Conservada , Glicoproteínas/genética , Humanos , Receptores Acoplados a Proteínas G/genética , Receptores de Péptidos/genéticaRESUMEN
AIMS: The main objective of this study was to evaluate the capacity of wild mushroom extracts to potentiate the action of standard antibiotics, through synergisms that allow a decrease in their therapeutic doses and ultimately contribute to the reduction of resistances. METHODS AND RESULTS: Wild mushroom extracts were applied to different multiresistant micro-organisms (Escherichia coli, extended-spectrum beta-lactamase-producing (ESBL) E. coli and methicillin-resistant Staphylococcus aureus (MRSA), combined with commercial antibiotics (penicillin, ampicillin, amoxicillin/clavulanic acid, cefoxitin, ciprofloxacin, cotrimoxazol, levofloxacin). Microdilution method was used to determine minimum inhibitory concentrations (MICs). The results obtained showed higher synergistic effects against MRSA than against E. coli. Mycena rosea and Fistulina hepatica were the best extracts for synergistic effects against MRSA. The efficiency of Russula delica extract against E. coli 1 (resistant to ampicillin, ciprofloxacin and trimethoprim/sulfasoxazole) and E. coli 2 (resistant to amoxicillin/clavulanic acid and ampicillin) was higher than that of Leucopaxillus giganteus extract; nevertheless, the latter extract exhibited better synergistic effects against ESBL E. coli. CONCLUSIONS: This study shows that, similarly to plants, some mushroom extracts can potentiate the action of antibiotics extensively used in clinical practice for Gram-positive or Gram-negative bacteria, with positive action even against multiresistant bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Mushroom extracts could decrease therapeutic doses of standard antibiotics and reduce micro-organism's resistance to those drugs.
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Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Agaricales , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
Culex (Culex) pipiens (Diptera: Culicidae) has two recognized biotypes, pipiens and molestus, which differ in physiology and behaviour; this difference may influence vectorial capacity for West Nile virus (WNV). Our goal was first to determine the presence of Cx. pipiens populations in 31 locations in Portugal and to subsequently analyse their host-feeding preferences and habitat determinants. Molecular identification of Cx. pipiens forms and their hybrids was performed in 97 females; bloodmeal sources were identified in 59 engorged specimens. Overall, 61.9% of specimens were identified as Cx. pipiens f. pipiens, 20.6% as Cx. pipiens f. molestus, and 17.5% as hybrid forms. Culex pipiens f. pipiens fed preferentially on birds, and Cx. pipiens f. molestus on humans. Hybrid forms fed mostly on birds, but human bloodmeals were common. With reference to habitat, Cx. pipiens f. pipiens and hybrid forms were positively correlated with peri-urban habitats. Our results confirm the sympatric presence of different Cx. pipiens biotypes in 14 of the 31 locations studied. Peri-urban areas were a common habitat of all biotypes and may represent zones of hybridization. The feeding preferences and sympatric distribution of the Cx. pipiens biotypes observed in Portugal favour the epizootic circulation of WNV and the occurrence of disease outbreaks of WNV.
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Culex/fisiología , Ecosistema , Insectos Vectores/fisiología , Simpatría , Animales , Culex/genética , Conducta Alimentaria , Femenino , Humanos , Hibridación Genética , Insectos Vectores/genética , Masculino , Repeticiones de Microsatélite , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Portugal , Especificidad de la Especie , Fiebre del Nilo Occidental/transmisión , Fiebre del Nilo Occidental/virología , Virus del Nilo Occidental/fisiologíaRESUMEN
INTRODUCTION AND OBJECTIVES: Long-term use of an indwelling catheter is associated with complications such as catheter encrustation and infection. Canoxidin® is a novel oral treatment that can potentially prevent catheter encrustation, as it contains a urine acidifier and a combination of two crystallization inhibitors. This study aimed to evaluate the effects of Canoxidin® on catheter encrustation in patients with indwelling Foley catheters. PATIENTS AND METHODS: This was a single-center, double-blind, randomized, placebo-controlled study. Neuro-urology patients aged ≥18 years with an indwelling catheter (urethral or suprapubic) were randomized to treatment consisting of either Canoxidin® or placebo for one month. Foley catheters (two per patient, one before treatment and one after treatment) were removed for analysis of the presence and degree of encrustation. RESULTS: A total of 40 patients were enrolled and randomized, 28 of whom had analyzable catheters (13 assigned to Canoxidin® and 15 assigned to placebo). The patients had a mean age of 51.8 years, and eight (28.6%) were female. Two patients (13.3%) in the placebo group and eight patients (61.5%) in the Canoxidin® group experienced an improvement (less encrustation). There was a significant association between Canoxidin® and improvement (odds ratio: 10.4, 95% confidence interval: 1.6 to 66.9, Pâ¯=â¯0.016). No adverse effects attributable to the treatment were reported. CONCLUSIONS: The overall rate of catheter encrustation was high among those with indwelling Foley catheters. One-month treatment with Canoxidin® reduced the formation of these encrustations, with an excellent short-term safety profile.
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AIM AND METHODS: Although the antimicrobial activity of extracts from several mushroom species has been reported, studies with the individual compounds present in that extracts are scarce. Herein, the antimicrobial activity of different phenolic compounds identified and quantified in mushroom species from all over the world was evaluated. Furthermore, a structure-activity relationship (SAR) analysis and molecular docking studies were performed, in order to provide insights into the mechanism of action of potential antimicrobial drugs for resistant micro-organisms. RESULTS: 2,4-Dihydroxybenzoic and protocatechuic acids were the phenolic compounds with higher activity against the majority of Gram-negative and Gram-positive bacteria. Furthermore, phenolic compounds inhibited more MRSA than methicillin-susceptible Staphylococcus aureus. MRSA was inhibited by 2,4-dihydroxybenzoic, vanillic, syringic (MICs = 0.5 mg ml(-1) ) and p-coumaric (MIC = 1 mg ml(-1) ) acids, while these compounds at the same concentrations had no inhibitory effects against methicillin-susceptible Staph. aureus. CONCLUSIONS: The presence of carboxylic acid (COOH), two hydroxyl (OH) groups in para and ortho positions of the benzene ring and also a methoxyl (OCH3 ) group in the meta position seems to be important for anti-MRSA activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Phenolic compounds could be used as antimicrobial agents, namely against some micro-organisms resistant to commercial antibiotics.
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Agaricales/química , Antibacterianos/química , Antibacterianos/farmacología , Fenoles/química , Fenoles/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Proteínas de Unión a las Penicilinas/química , Relación Estructura-ActividadRESUMEN
Trypanosoma cruzi antioxidant enzymes are among the factors that guarantee parasite survival and maintain infection, enabling T. cruzi to cope with oxidative stress. Herein, the expression of cytosolic (TcCPx) and mitochondrial (TcMPx) tryparedoxin peroxidases was evaluated in tissue culture-derived trypomastigotes upon incubation with different concentrations of H(2)O(2). TcCPx expression slightly increased (5.4%) in cells submitted to 10 µM H(2)O(2) treatment when compared to the control, but decreased when higher H(2)O(2) concentrations (20-50 µM) were employed. Under these conditions, TcMPx expression increased (â¼53%) with 10 µM-treatment compared to the control, followed by a reduction that reached â¼46% of the control when using the highest concentration tested. Interestingly, in the supernatant of the incubations, TcCPx, but not TcMPx, was detected, and its levels increased concomitantly with its decreased expression in the intracellular compartment. Our data show that peroxiredoxins in the tissue culture-derived trypomastigote can be modulated under oxidative stress and are present in higher amounts when compared to the epimastigote stage of T. cruzi. Additionally, due to the different expression patterns observed upon H(2)O(2)-treatment, each peroxiredoxin may play a distinct role in protecting the parasite under oxidative stress conditions.
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Peróxido de Hidrógeno/farmacología , Estrés Oxidativo , Peroxidasas/metabolismo , Peroxirredoxinas/metabolismo , Proteínas Protozoarias/metabolismo , Trypanosoma cruzi/enzimología , Western Blotting , Línea Celular , Citosol/enzimología , Mitocondrias/enzimología , Trypanosoma cruzi/efectos de los fármacosRESUMEN
An outbreak of dengue fever in Madeira island was reported in 2012. Clinical and laboratory findings of the first two laboratory-confirmed autochthonous cases are reported. Both cases had fever (≥38 °C) and petechial rash. Symptoms also included myalgia, asthenia, nausea, vomiting, anorexia, diffuse abdominal pain, and diarrhoea. The two cases were confirmed by serology and one tested positive for a dengue viral sequence. Dengue virus serotype DEN-1 was identified with probable Central or South American origin.
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Virus del Dengue/genética , Virus del Dengue/aislamiento & purificación , Dengue/diagnóstico , Dengue/epidemiología , Brotes de Enfermedades , Adolescente , Adulto , Aedes/virología , Animales , Técnicas de Laboratorio Clínico , Dengue/transmisión , Dengue/virología , Virus del Dengue/clasificación , Femenino , Humanos , Masculino , Filogenia , Portugal/epidemiología , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia , SerotipificaciónRESUMEN
Previous study showed that muscle sympathetic nerve activity (MSNA) was augmented in anabolic steroids users (AASU). In the present study, we tested the hypothesis that the heart rate (HR) responses after maximal exercise testing would be reduced in AASU. 10 male AASU and 10 AAS nonusers (AASNU) were studied. Cardiopulmonary exercise was performed to assess the functional capacity and heart rate recovery. MSNA was recorded directly from the peroneal nerve by microneurography technique. Peak oxygen consumption (VO2) was lower in AASU compared to AASNU (43.66±2.24 vs. 52.70±1.68 ml/kg/min, P=0.005). HR recovery (HRR) at first and second minute was lower in AASU than AASNU (21±2 vs. 27±2 bpm, P=0.02 and 37±4 vs. 45±2 bpm, P=0.05, respectively). MSNA was higher in AASU than AASNU (29±3 vs. 20±1 bursts/min, P=0.01). Further analysis showed a correlation between HRR and MSNA (r=- 0.64, P=0.02), HRR at first minute and peak VO2 (r=0.70, P=0.01) and HRR at second minute and peak VO2 (r=0.62, P=0.02). The exacerbated sympathetic outflow associated with a lower parasympathetic activation after maximal exercise, which impairs heart rate recovery, strengthens the idea of autonomic imbalance in AASU.
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Anabolizantes/efectos adversos , Andrógenos/efectos adversos , Ejercicio Físico/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Adulto , Prueba de Esfuerzo , Tolerancia al Ejercicio/efectos de los fármacos , Tolerancia al Ejercicio/fisiología , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Consumo de Oxígeno/efectos de los fármacos , Entrenamiento de Fuerza , Autoadministración , Sistema Nervioso Simpático/efectos de los fármacosRESUMEN
Toscana virus (TOSV) is an emerging Phlebovirus of growing interest as a human pathogen in the Mediterranean Basin. In Portugal, however, little is known about the prevalence of TOSV infection. The aim of this work was to perform a seroprevalence study in patients with requests for laboratory diagnosis of vector-borne viruses. A total of 538 patients with and without neurological signs from 2004 to 2008 were studied by in-house indirect immunofluorescence assay and commercial enzyme-linked immunosorbent assays. A prevalence of 4.2% for IgG antibodies was found in the group of patients with neurological signs. Five (3%) of these had recent infections. In the group with no neurological signs, the IgG prevalence was 1.3%. Two samples, belonging to two patients, were also confirmed with plaque reduction neutralization tests with the TOSV ISS. Phl.3 Italian strain. This work showed that TOSV is present and causing disease from north to south in Portugal. The probable circulation of different phlebovirus serotypes in Portugal emphasizes the need for further studies.
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Anticuerpos Antivirales/sangre , Infecciones por Bunyaviridae/epidemiología , Infecciones por Bunyaviridae/virología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Infecciones por Bunyaviridae/sangre , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lactante , Masculino , Persona de Mediana Edad , Portugal/epidemiología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/aislamiento & purificación , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
AIMS: This work aimed to screen the antimicrobial activity of aqueous methanolic extracts of 13 mushroom species, collected in Bragança, against several clinical isolates obtained in Hospital Center of Trás-os-Montes and Alto Douro, Portugal. METHODS AND RESULTS: Microdilution method was used to determine the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). MIC results showed that Russula delica and Fistulina hepatica extracts inhibited the growth of gram-negative (Escherichia coli, Morganella morganni and Pasteurella multocida) and gram-positive (Staphylococcus aureus, MRSA, Enterococcus faecalis, Listeria monocytogenes, Streptococcus agalactiae and Streptococcus pyogenes) bacteria. A bactericide effect of both extracts was observed in Past. multocida, Strep. agalactiae and Strep. pyogenes with MBC of 20, 10 and 5 mg ml⻹, respectively. Lepista nuda extract exhibited a bactericide effect upon Past. multocida at 5 mg ml⻹ and inhibited Proteus mirabilis at 20 mg ml⻹. Ramaria botrytis extract showed activity against Enterococcus faecalis and L. monocytogenes, being bactericide for Past. multocida, Strep. agalactiae (MBCs 20 mg ml⻹) and Strep. pyogenes (MBC 10 mg ml⻹). Leucopaxillus giganteus extract inhibited the growth of E. coli and Pr. mirabilis, being bactericide for Past. multocida, Strep. pyogenes and Strep. agalactiae. CONCLUSIONS: Fistulina hepatica, R. botrytis and R. delica are the most promising species as antimicrobial agents. SIGNIFICANCE AND IMPACT OF THE STUDY: Mushroom extracts could be an alternative as antimicrobials against pathogenic micro-organisms resistant to conventional treatments.
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Agaricales/química , Antibacterianos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple , Materia Medica/farmacología , Pruebas de Sensibilidad Microbiana , PortugalRESUMEN
Trypanosoma cruzi is a protozoan parasite that infects vertebrates, causing in humans a pathological condition known as Chagas' disease. The infection of host cells by T. cruzi involves a vast collection of molecules, including a family of 85 kDa GPI-anchored glycoproteins belonging to the gp85/trans-sialidase superfamily, which contains a conserved cell-binding sequence (VTVXNVFLYNR) known as FLY, for short. Herein, it is shown that BALB/c mice administered with a single dose (1 µg/animal, intraperitoneally) of FLY-synthetic peptide are more susceptible to infection by T. cruzi, with increased systemic parasitaemia (2-fold) and mortality. Higher tissue parasitism was observed in bladder (7·6-fold), heart (3-fold) and small intestine (3·6-fold). Moreover, an intense inflammatory response and increment of CD4+ T cells (1·7-fold) were detected in the heart of FLY-primed and infected animals, with a 5-fold relative increase of CD4+CD25+FoxP3+ T (Treg) cells. Mice treated with anti-CD25 antibodies prior to infection, showed a decrease in parasitaemia in the FLY model employed. In conclusion, the results suggest that FLY facilitates in vivo infection by T. cruzi and concurs with other factors to improve parasite survival to such an extent that might influence the progression of pathology in Chagas' disease.
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Enfermedad de Chagas/inmunología , Glicoproteínas/química , Neuraminidasa/química , Péptidos/administración & dosificación , Trypanosoma cruzi/patogenicidad , Secuencia de Aminoácidos , Animales , Linfocitos T CD4-Positivos/inmunología , Enfermedad de Chagas/parasitología , Secuencia Conservada , Femenino , Factores de Transcripción Forkhead/inmunología , Glicoproteínas/inmunología , Humanos , Subunidad alfa del Receptor de Interleucina-2/inmunología , Ratones , Ratones Endogámicos BALB C , Neuraminidasa/inmunología , Parasitemia/inmunología , Parasitemia/parasitología , Péptidos/síntesis química , Péptidos/química , Peritoneo/citología , Linfocitos T Reguladores/inmunología , Trypanosoma cruzi/enzimología , Trypanosoma cruzi/inmunología , VirulenciaRESUMEN
Trypanosoma cruzi trypomastigotes adhere to extracellular matrix (ECM) to invade mammalian host cells regulating intracellular signaling pathways. Herein, resin-assisted enrichment of thiols combined with mass spectrometry were employed to map site-specific S-nitrosylated (SNO) proteins from T. cruzi trypomastigotes incubated (MTy) or not (Ty) with ECM. We confirmed the reduction of S-nitrosylation upon incubation with ECM, associated with a rewiring of the subcellular distribution and intracellular signaling pathways. Forty, 248 and 85 SNO-peptides were identified only in MTy, Ty or in both conditions, respectively. SNO proteins were enriched in ribosome, transport, carbohydrate and lipid metabolisms. Nitrosylation of histones H2B and H3 on Cys64 and Cys126, respectively, is described. Protein-protein interaction networks revealed ribosomal proteins, proteins involved in carbon and fatty acid metabolism to be among the enriched protein complexes. Kinases, phosphatases and enzymes involved in the metabolism of carbohydrates, lipids and amino acids were identified as nitrosylated and phosphorylated, suggesting a post-translational modifications crosstalk. In silico mapping of nitric oxide synthase (NOS) genes, previously uncharacterized, matched to four putative T. cruzi proteins expressing C-terminal NOS domain. Our results provide the first site-specific characterization of S-nitrosylated proteins in T. cruzi and their modulation upon ECM incubation before infection of the mammalian hosts. SIGNIFICANCE: Protein S-nitrosylation represents a major molecular mechanism for signal transduction by nitric oxide. We present for the first time a proteomic profile of S-nitrosylated proteins from infective forms of T. cruzi, showing a decrease in SNO proteins after incubation of the parasite with the extracellular matrix, a necessary step for the parasite invasion of the host mammalian cells. We also show for the first time nitrosylation of H2B (Cys64) and H3 (Cys126) histones, sites not conserved in higher eukaryotic cells, and suggest that some specific histone isoforms are sensitive to NO signaling. S-nitrosylation in H2B and H3 histones are more abundant in MTy. Moreover, proteins involved in translation, glycolytic pathway and fatty acid metabolism are enriched in the present dataset. Comparison of the SNO proteome and the phosphoproteome, obtained previously under the same experimental conditions, show that most of the proteins sharing both modifications are involved in metabolic pathways, transport and ribosome function. The data suggest that both PTMs are involved in reprogramming the metabolism of T. cruzi in response to environmental changes. Although NO synthesis was detected in T. cruzi, the identification of NOS remains elusive. Analysis in silico showed two genes similar in domains to NADPH-dependent cytochrome-P450 reductase and two putative oxidoreductases, but no oxygenase domain of NOS was mapped in the T. cruzi genome. It is tempting to speculate that NO synthase-like from T. cruzi and its early NO-mediated pathways triggered in response to host interaction constitute potential diagnostic and therapeutic targets.
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Enfermedad de Chagas , Trypanosoma cruzi , Animales , Matriz Extracelular , Proteoma , ProteómicaRESUMEN
Incubation of T. cruzi epimastigotes with the lectin Cramoll 1,4 in Ca(2+) containing medium led to agglutination and inhibition of cell proliferation. The lectin (50 microg/ml) induced plasma membrane permeabilization followed by Ca(2+) influx and mitochondrial Ca(2+) accumulation, a result that resembles the classical effect of digitonin. Cramoll 1,4 stimulated (five-fold) mitochondrial reactive oxygen species (ROS) production, significantly decreased the electrical mitochondrial membrane potential (Delta Psi(m)) and impaired ADP phosphorylation. The rate of uncoupled respiration in epimastigotes was not affected by Cramoll 1,4 plus Ca(2+) treatment, but oligomycin-induced resting respiration was 65% higher in treated cells than in controls. Experiments using T. cruzi mitochondrial fractions showed that, in contrast to digitonin, the lectin significantly decreased Delta Psi(m) by a mechanism sensitive to EGTA. In agreement with the results showing plasma membrane permeabilization and impairment of oxidative phosphorylation by the lectin, fluorescence microscopy experiments using propidium iodide revealed that Cramoll 1,4 induced epimastigotes death by necrosis.
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Fabaceae/química , Lectinas de Plantas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Señalización del Calcio/efectos de los fármacos , Permeabilidad de la Membrana Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Digitonina/farmacología , Glicoconjugados/metabolismo , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Necrosis , Fosforilación Oxidativa/efectos de los fármacos , Lectinas de Plantas/aislamiento & purificación , Especies Reactivas de Oxígeno/metabolismo , Trypanosoma cruzi/citología , Trypanosoma cruzi/metabolismoRESUMEN
SETTING: Burkitt's lymphoma is a rare form of cancer and is an extremely rare diagnosis during pregnancy. This form of lymphoma is a very fast growing B cell neoplasm and chemotherapy is the treatment of choice for the disease in all its stages. CASE REPORT: The authors describe the case of a Caucasian 40-year-old nulliparous woman, with previous known Epstein-Barr virus infection, that presents at 28 weeks gestation with supraclavicular adenopathy and multiple bilateral breast nodules, in which biopsy showed non-Hodgkin lymphoma, Burkitt's type. DISCUSSION: There are few described cases of Burkitt's lymphoma during pregnancy and in general the outcomes have been poor. In most of the cases, the patients were not treated by current standards or instead had a late diagnosis. This neoplasia is the most rapidly progressive human tumor, and any delay in initiating therapy can adversely affect patient's prognosis. The authors discuss treatment options in pregnancy and its perinatal implications.
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Linfoma de Burkitt/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Complicaciones Neoplásicas del Embarazo/virología , Adulto , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Burkitt/tratamiento farmacológico , Femenino , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológicoRESUMEN
The scientific publication landscape is changing quickly, with an enormous increase in options and models. Articles can be published in a complex variety of journals that differ in their presentation format (online-only or in-print), editorial organizations that maintain them (commercial and/or society-based), editorial handling (academic or professional editors), editorial board composition (academic or professional), payment options to cover editorial costs (open access or pay-to-read), indexation, visibility, branding, and other aspects. Additionally, online submissions of non-revised versions of manuscripts prior to seeking publication in a peer-reviewed journal (a practice known as pre-printing) are a growing trend in biological sciences. In this changing landscape, researchers in biochemistry and molecular biology must re-think their priorities in terms of scientific output dissemination. The evaluation processes and institutional funding for scientific publications should also be revised accordingly. This article presents the results of discussions within the Department of Biochemistry, University of São Paulo, on this subject.
Asunto(s)
Bioquímica , Biología Molecular , Publicaciones Periódicas como Asunto/estadística & datos numéricos , Edición/tendencias , Investigación , Brasil , Humanos , Publicaciones Periódicas como Asunto/normas , Publicaciones Periódicas como Asunto/tendenciasRESUMEN
The syndrome of cancer cachexia is accompanied by several alterations in lipid metabolism, and the liver is markedly affected. Previous studies showed that moderate exercise training may prevent liver fat accumulation through diminished delivery of lipids to the liver, increased hepatic oxidation and increased incorporation of triacylglycerol (TAG) into very low density lipoprotein (VLDL). Our aim was to examine the influence of moderate intensity training (8 weeks) upon TAG content, VLDL assembly and secretion, apolipoprotein B (apoB) and microsomal transfer protein (MTP) gene expression in the liver of cachectic tumour-bearing rats. Animals were randomly assigned to a sedentary control (SC), sedentary tumour-bearing (ST) or exercise-trained control (EC) or to an exercise trained tumour-bearing (ET) group. Trained rats ran on a treadmill (60% VO(2max)) for 60 min day(-1), 5 day week(-1), for 8 weeks. TAG content and the rate of VLDL secretion (followed for 3 h), as well as mRNA expression of apoB and MTP, and total cholesterol, VLDL-TAG, VLDL-cholesterol, high density lipoprotein cholesterol (HDL-cholesterol) and tumour weight were evaluated. VLDL-cholesterol showed a decrease in ST (p < 0.05) in relation to SC. Serum TAG, VLDL-TAG and tissue TAG content were all increased in ST (p < 0.01), when compared with SC. ST showed a lower rate of VLDL secretion (p < 0.05) and reduced expression of apoB (p < 0.001) and MTP (p < 0.001), when compared with SC. These parameters were restored to control values (p < 0.05) when the animals were submitted to the exercise training protocol. Tumour weight decreased 10-fold after training (p < 0.001). It is possible to affirm, therefore, that endurance training promoted the re-establishment of lipid metabolism in cachectic tumour-bearing animals, especially in relation to VLDL secretion and assembly.
Asunto(s)
Caquexia/metabolismo , Carcinoma 256 de Walker/complicaciones , Metabolismo de los Lípidos/fisiología , Hígado/metabolismo , Condicionamiento Físico Animal/fisiología , Animales , Apolipoproteínas B/genética , Peso Corporal , Caquexia/sangre , Caquexia/etiología , Carcinoma 256 de Walker/patología , Proteínas Portadoras/genética , Línea Celular Tumoral , Colesterol/sangre , HDL-Colesterol/sangre , VLDL-Colesterol/sangre , Expresión Génica , Lipoproteínas VLDL/sangre , Hígado/patología , Masculino , Proteínas/análisis , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Triglicéridos/sangre , Triglicéridos/metabolismoRESUMEN
This work explored a novel approach to enhance the antibacterial activity of commercial Gutta-percha (GP) cones, the most commonly used core filling materials used in endodontic treatment. The reported procedure involved an argon (Ar) plasma treatment (PT) of the GP cone surface, followed by the deposition of a ZnO thin film by magnetron sputtering. The resulting surfaces were evaluated for surface topography, antibacterial activity against Enterococcus faecalis and Staphylococcus aureus, and cytocompatibility with human osteoblastic cells. GP cones treated with NaOCl, a routine chair-side protocol, were also tested as reference. The deposition of a ZnO film on pristine GP cones increased its antibacterial activity. Cones pre-treated with Ar-plasma (PT) and coated with the ZnO thin film presented significantly higher antibacterial activity than that observed on the pristine and, also, compared to the ZnO coated cones. The higher antibacterial activity of PTâ¯+â¯ZnO cones appears related to the major effects induced by the PT pre-treatment on the cone surface endowing the deposited ZnO film with a homogeneous nanostructured topography that greatly improved surface reactivity. The modified GP cones maintained an appropriate cytocompatibility with human cells. This novel approach provides ready-to-use cones with enhanced antibacterial activity, improving a strict asepsis protocol during endodontic treatment and preventing secondary endodontic infections.