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Molecules ; 24(8)2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-31014025


Snakebite envenoming is a serious medical problem in different areas of the world. In Latin America, the major prevalence is due to snakes of the family Viperidae, where rattlesnakes (Crotalus) are included. They produce hemotoxic venom which causes bleeding, tissue degradation and necrosis. Each venom has several enzymatic activities, producing different effects in the envenoming, doing its clinical effects difficult to study. Comparison between venom molecules is also difficult when different techniques are used, and therefore, their identification/characterization using the same methodology is necessary. In this work, a general biochemical characterization in snake venom of serine proteases (SVSP), phospholipases A2 (PLA2), metalloproteases (SVMP) and hyaluronidases (SVH) of Crotalus aquilus (Ca), Crotalus polystictus (Cp) and Crotalus molossus nigrescens (Cmn) was done. Differences in protein pattern, enzyme content and enzymatic activities were observed. All the venoms showed high PLA2 activity, high molecular weight SVSP, and a wide variety of SVMP and SVH forms. Ca and Cp showed the highest enzymatic activities of SVMP and SVSP trypsin-like and chymotrypsin-like, whereas Cmn showed the highest SVH and similar PLA2 activity with Ca. All the venoms showed peptides with similar molecular weight to crotamine-like myotoxins. No previous biochemical characterization of C. aquilus has been reported and there are no previous analyses that include these four protein families in these Crotalus venoms.

Hidrolases/metabolismo , Hidrolases/toxicidade , Venenos de Serpentes/enzimologia , Animais , Crotalus , Metaloproteases/análise , México , Serina Proteases/análise , Especificidade da Espécie
Microbiologyopen ; 8(4): e00572, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30851083


The vast microbial diversity on the planet represents an invaluable source for identifying novel activities with potential industrial and therapeutic application. In this regard, metagenomics has emerged as a group of strategies that have significantly facilitated the analysis of DNA from multiple environments and has expanded the limits of known microbial diversity. However, the functional characterization of enzymes, metabolites, and products encoded by diverse microbial genomes is limited by the inefficient heterologous expression of foreign genes. We have implemented a pipeline that combines NGS and Sanger sequencing as a way to identify fosmids within metagenomic libraries. This strategy facilitated the identification of putative proteins, subcloning of targeted genes and preliminary characterization of selected proteins. Overall, the in silico approach followed by the experimental validation allowed us to efficiently recover the activity of previously hidden enzymes derived from agricultural soil samples. Therefore, the methodology workflow described herein can be applied to recover activities encoded by environmental DNA from multiple sources.

Bactérias/enzimologia , Proteínas de Bactérias/genética , Enzimas/genética , Biblioteca Gênica , Metagenômica/métodos , Solo/química , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Proteínas de Bactérias/metabolismo , Enzimas/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Microbiologia do Solo
Toxicon ; 163: 12-18, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30880186


Spider venoms are widely recognized as a new emerging source of potential research tools, pesticides, drug leads, and therapeutic agents. Some studies suggest that these venoms may contain interesting vasodilator compounds with potential therapeutic applications. In the present study, the vasodilator activity of the venom of Poecilotheria regalis was evaluated in isolated rat aortic rings. This venom induced an endothelium-dependent vasodilation [EC50 value was 5.52 (4.18-7.32) µg protein/ml with an Emax = 103.4 ±â€¯3.8%]. While the percentage of vasodilation induced by the venom was significantly diminished in the presence of a nitric oxide synthase inhibitor (L-NAME), it remained unaltered in the presence of suramin, a P2-purinergic receptor antagonist. Moreover, the vasodilator activity of the venom was not affected after boiling bath incubation, but was significantly decreased under reducing conditions. Additionally, venom composition was analyzed by reverse-phase chromatography and MALDI-TOF mass spectrometry, and two fractions were obtained, referred to as peptidic and non-peptidic fractions. Interestingly, both fractions induced vasodilation in isolated rat aortic rings. The results of this study showed that the venom of P. regalis induces a concentration-dependent vasodilation in rat aorta that was endothelium-dependent and involves the activation of NO/cGMP pathway. These results suggest that the venom contains a combination of both peptidic and non-peptidic vasodilator components. This study provides pharmacological data that suggest that P. regalis venom may be an important source of peptidic and non-peptidic vasodilator compounds.

Venenos de Aranha/farmacologia , Aranhas , Vasodilatação/efeitos dos fármacos , Animais , Aorta/efeitos dos fármacos , GMP Cíclico/metabolismo , Endotélio Vascular/efeitos dos fármacos , Feminino , Técnicas In Vitro , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Venenos de Aranha/química , Vasodilatadores/farmacologia
J Enzyme Inhib Med Chem ; 34(1): 451-458, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30734605


A series of organometallic acylhydrazones was prepared, incorporating Re(CO)3, Mn(CO)3 and ferrocenyl moieties, which were subsequently reacted with amino-sulfonamides in order to obtain carbonic anhydrase (CA, EC inhibitors possessing organometallic moieties in their molecules. The new derivatives were investigated as inhibitors of four human (h) CA isoforms with pharmaceutical applications, such as the cytosolic hCA I, II and VII and the mitochondrial hCA VA. An interesting inhibitory profile against these isoforms was obtained, with some of these metal complexes acting as subnanomolar or low nanomolar inhibitors. They were also thoroughly characterised from the chemical point of view, making them of interest for further developments in the field of metal complexes of sulfonamides with CA inhibitory action.

Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Hidrazonas/farmacologia , Compostos Organometálicos/farmacologia , Sulfonamidas/farmacologia , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Relação Dose-Resposta a Droga , Humanos , Hidrazonas/química , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Estrutura Molecular , Compostos Organometálicos/química , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química
Rev. medica electron ; 41(1): 90-103, ene.-feb. 2019. tab
Artigo em Espanhol | LILACS, CUMED | ID: biblio-991328


RESUMEN Introducción: las enfermedades cerebrovasculares son un problema de salud mundial, constituyen la tercera causa de muerte, la primera de discapacidad en el adulto y la segunda de demencia en el planeta Objetivo: caracterizar la hemorragia intracerebral en estos pacientes en relación con edad y sexo, factores de riesgo, letalidad según localización y extensión de la hemorragia. Materiales y métodos: se realizó un estudio observacional retrospectivo en pacientes ingresados con hemorragia intracerebral en el Hospital Faustino Pérez en los años 2012 y 2013. El universo del estudio fue de 86 pacientes ingresados con hemorragia intracerebral. Resultados: predominó el sexo masculino y el grupo de edades de 70-79 años con 54,65% y 34,88% respectivamente, la raza negra con 40,7% y el factor de riesgo más frecuente fue la hipertensión arterial con 82,55% seguido de la diabetes mellitus con 23.25. La letalidad fue más elevada en los pacientes mayores de 80 años con 41,66%. Según la localización la subcortical fue más frecuente con 34,88% y la más letal el tallo encefálico con 100%. Según la extensión predominó la intraparenquimatosa pura con 69,76% y fue más letal intraventricular con 55%. Conclusión: la hemorragia intracerebral fue más frecuente en pacientes del sexo masculino, del grupo de edades de 70-79 años y de raza negra. El factor de riesgo más frecuente fue la hipertensión arterial, la localización más frecuente fue la subcortical y la extensión la intraparenquimatosa pura. La letalidad fue más alta en pacientes mayores de 80 años, con localización en tronco encefálico y extensión intraventricular.

ABSTRACT Introduction: cerebrovascular diseases are a health problem around the world, being the third cause of death, the first one of disability in adults, and the second cause of dementia in the world. Objective: to characterize intracerebral hemorrhage in these patients in relation to age and sex, risk factors, lethality according to its location and hemorrhage extension. Materials and methods: an observational, retrospective study was carried out in patients admitted in the Hospital Faustino Perez with intracerebral hemorrhage in 2012 and 2013. The universe of the study was 86 patients admitted due to intracerebral hemorrhage. Results: male sex (54.65 %), 70-79-years-old age group (34.88 %) and black race (49.7 %) predominated. The most frequent risk factor was arterial hypertension (82.55 %), followed by diabetes mellitus (23.25 %). Lethality was higher in patients elder than 80 years old (41.66 %). According to location, the subcortical one was the most frequent (34.88 %), and the most lethal was the one of the brainstem (100 %). According for the extension, the pure intraparenchimatous one predominated (69.76 %), and the intraventricular one was the most lethal (55 %). Conclusion: the intracerebral hemorrhage was more frequent in male sex, 70-79-years-old age group and black race. The most frequent risk factor was arterial hypertension; the most frequent location was the subcortical one, and the one with larger extension was the pure intraparenchimatous one. Lethality was higher in patients aged more than 80 years, located in the brainstem and with intraventricular extension.

Humanos , Idoso , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/epidemiologia , Fatores de Risco , Estudos Retrospectivos , Estudo Observacional , Hipertensão
Artigo em Inglês | MEDLINE | ID: mdl-30710688


INTRODUCTION: Assaying venom toxicity in a suitable model system is often tricky, since normally the amount of venom is in short supply, and the assay subjects, i.e., typically mice, require large amounts. There is also no guarantee that the effects observed in the bioassay reflect the true nature of the venom's intended effects, as the animals used for assessment might not be the prey items to which the venom has evolved. METHODS: We harvested tarantula venoms from the Indian Poecilotheria regalis and the Mexican Bonnetina papalutlensis using light anesthesia and electrical stimulation. We follow the definition of venom as stated in (Nelsen et al., 2014). The recovered venom was lyophilized and reconstituted in sterile saline solution for injections. Drosophila melanogaster third instar larvae and adult flies were injected with 4.6 nanoliters of different concentrations of the venoms into the sixth abdominal segment, and scored for survival and development to adulthood. RESULTS: The injected venoms were very effective in provoking lethality of injected larvae and adults, with an LD50 of 1-5 nanomoles protein /gram wet weight. Comparison with other toxicity bioassays, i.e., mice and crickets -using the same P. regalis venom- renders the Drosophila bioassays three orders of magnitude more sensitive. The P. regalis and B. papalutlensis venoms have similar LD50. DISCUSSION: These bioassays use a small amount of venom compared to other bioassays, allowing characterization with far fewer starting material. As it uses insects, phylogenetically close to the intended prey victims, it also points to the efficiency of the tarantula venom for its preferred prey items, and thus, links as well to the tarantulas' ecology.

Drosophila melanogaster/efeitos dos fármacos , Venenos de Aranha/toxicidade , Animais , Bioensaio/métodos , Larva/efeitos dos fármacos , Dose Letal Mediana , Venenos de Aranha/isolamento & purificação
Artigo em Inglês | MEDLINE | ID: mdl-30335353


Cleaning and passivation of metal surfaces are necessary steps for selective film deposition processes that are attractive for some microelectronic applications (e.g., fully aligned vias or self-aligned contacts). For copper, there is limited knowledge about the mechanisms of the copper oxide reduction process and subsequent passivation layer formation reactions. We have investigated the in situ cleaning (i.e., oxidation and reduction by vapor-phase species) and passivation of chemical-mechanical polishing (CMP)-prepared Cu films in an effort to derive the mechanisms associated with selectively tailoring the surface chemistry. By monitoring the interaction of vapor-phase ethanol with the surface species generated after ozone cleaning at 300 °C, we find that the optimum procedure to remove these species and avoid byproduct redeposition is to use atomic layer deposition (ALD)-like binary cycles of ethanol and N2, with active pumping. We have further explored passivation of clean Cu using benzotriazole and 2,2'-bipyridine in an ALD environment. Both molecules chemisorb on clean Cu in an upright orientation, with respect to the metal surface at temperatures higher than the melting point of the organic inhibitors (100 ≤ T < 300 °C). Both molecules desorb without decomposition from clean Cu above 300 °C but not from Cu2O. Previous studies related to the passivation of Cu surfaces using heterocyclic amines have focused on solution-based or ultrahigh vacuum applications of the passivation molecules onto single crystalline Cu samples. The present work explores more industrially relevant vapor-phase passivation of CMP-cleaned, electroplated Cu samples using ALD-like processing conditions and in situ vapor-phase cleaning.

Arq. ciências saúde UNIPAR ; 22(3): 145-149, Set-Dez. 2018.
Artigo em Português | LILACS | ID: biblio-915520


O Rugby em cadeira de rodas (RCR) é um esporte paralímpico praticado por homens e mulheres com tetraplegia decorrente de lesão na medula espinhal (LME). Nos esportes de alto rendimento o desempenho do atleta depende de preparo físico, aspectos tático e técnico. Dentre as variáveis fisiológicas importantes no controle do treinamento e na resposta aos treinos encontra-se a frequência cardíaca (FC). O presente estudo teve como objetivo verificar a intensidade da FC durante jogos de RCR. Para isso, utilizou-se do frequencímetro FIRTSBEAT modelo SPORTS Team 4.6®, para o monitoramento da FC dos atletas de RCR durante os jogos. A amostra foi composta por nove atletas homens de RCR com LME com nível de lesão acima da vértebra T6. Os resultados obtidos demonstraram que a média das FC máximas foi de 138,55 ± 17,5 bpm. A intensidade variou cerca de 77% do tempo entre Zona aeróbia 1, Zona aeróbia 2 e Zona de limiar anaeróbio, indicando uma grande oscilação, o que é esperado por se tratar de um esporte que possui características de intermitência. Conclui-se que os atletas de RCR apresentaram uma FC máxima reduzida, correspondente às encontradas na literatura, e que esses apresentaram uma variação da intensidade da FC, com predominância entre 60% a 90% da FC máxima.

Wheelchair Rugby (WR) is a Paralympic sport modality practiced by men and women with spinal cord injury (SCI). In high performance sports, the performance of the athlete depends on his physical fitness, as well as tactical and technical aspects. Heart rate (HR) features among the several essential physiological variables in the control of the training and in response to training. This study aimed to determine the HR intensity during WR matches. In order to do so, FIRSTBEAT SPORTS Team 4.6® heart rate monitors were used to monitor the HR of the WR athletes during the games. The sample consisted of nine male WR athletes with SCI with impairment level above T6. The results showed that the average maximum HR was 138 ± 17.5 bpm. Intensity varied in approximately 77% of the time between the Aerobic Zone 1, Aerobic Zone 2 and the Anaerobic Threshold Zone, presenting great oscillation. This is expected, since rugby is a sport with intermittent characteristics. It was concluded that WR athletes showed reduced HR (max), similar to the results found in literature, and presented variation in the HR intensity, with a predominance between 60% to 90% of the HR(max).

Pessoas com Deficiência , Futebol Americano , Frequência Cardíaca
Rev. medica electron ; 40(2): 445-453, mar.-abr. 2018. ilus
Artigo em Espanhol | LILACS-Express | ID: biblio-902311


RESUMEN La Educación Médica de Postgrado ha estado involucrada en profundos cambios prometedores para el logro de mejores resultados en la formación integral de los claustros de profesores. En la pedagogía contemporánea constituye un reto la Pedagogía del cambio, eslabón necesario para superar factores de vulnerabilidad psicopedagógica. Con el objetivo de describir estos elementos dentro de las Ciencias Médicas en general y de la Oftalmología en particular se realizó un estudio descriptivo con métodos teóricos de análisis y síntesis de revisión bibliográfica del tema, para exponer sus propósitos dentro de la enseñanza de dichas ciencias, a partir de novedosos enfoques pedagógicos. Se realizó una búsqueda en las bases de datos SciELO Cuba, SciELO Regional, Pubmed, Cumed y Clinical Key, de todo lo relacionado con el tema en el período comprendido entre los años 2012-2016. Se utilizaron las siguientes palabras clave: educación de postgrado, pedagogía del cambio, liderazgo. Se expusieron los aspectos positivos que permiten argumentar las ventajas que aportan el escenario docente del taller así como el rol de liderazgo del docente.

ABSTRACT In recent years, high medical education has been involved in promising deep changes to achieve better results in the integral training of professorial staffs. In the contemporary pedagogy, the pedagogy of the change is a challenge, and a necessary link to overcome factors of psychopedagogical vulnerability. With the aim of describing these elements in Medical Sciences and particularly in Ophthalmology, the authors performed a descriptive study using theoretical methods of analysis and synthesis of the bibliographic review on the theme to expose their aims in teaching the before mentioned sciences from new pedagogical approaches. A bibliographic search was carried out in SciELO-Cuba, SciELO-regional, PubMed, CUMED and Clinical Key, looking for everything related to the theme in the period 2012-2016. The following key words were used: postgraduate education, pedagogy of the change, leadership. There they are exposed the positive aspects that allow arguing the advantages workshop's teaching stage as well as teacher´s leadership provide.

Cancer Genomics Proteomics ; 15(2): 115-120, 2018 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29496690


BACKGROUND: Cowden syndrome (CS) is a rare autosomal-dominant inherited disorder characterized by multiple hamartomas. While the hamartomas are benign, patients with CS have increased risk of osteosarcoma and of breast, thyroid, endometrial, soft-tissue and colonic neoplasms. Germline mutations of phosphatase and tensin homolog (PTEN) are implicated in CS and in the development of osteosarcoma. We report a patient with CS who presented with osteosarcoma, ganglioneuromatosis and a benign breast mass. Osteosarcoma, as presentation of CS, is rare (only one report in the English literature). Genomic DNA from the patient's peripheral blood was quantified by spectrophotometry, then underwent sequence enrichment, polymerase chain reaction and next-generation sequencing. Molecular analysis revealed a non-synonymous c.17_18delAA frameshift mutation in exon 1 of PTEN and a c.116G>T (p.R39L) missense mutation of serine/threonine kinase 11 (STK11) of unknown significance. CONCLUSION: We report a patient with CS presenting with ganglioneuromatosis, benign breast mass and osteosarcoma, harboring a novel molecular alteration in PTEN which to our knowledge has not been previously reported.

Neoplasias Ósseas/genética , Mutação em Linhagem Germinativa , Síndrome do Hamartoma Múltiplo/genética , Osteossarcoma/genética , PTEN Fosfo-Hidrolase/genética , Adulto , Neoplasias Ósseas/enzimologia , Feminino , Síndrome do Hamartoma Múltiplo/enzimologia , Síndrome do Hamartoma Múltiplo/patologia , Humanos , Osteossarcoma/enzimologia , Osteossarcoma/patologia
Langmuir ; 34(8): 2619-2629, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29381069


Despite the success of plasma-enhanced atomic layer deposition (PEALD) in depositing quality silicon nitride films, a fundamental understanding of the growth mechanism has been difficult to obtain because of lack of in situ characterization to probe the surface reactions noninvasively and the complexity of reactions induced/enhanced by the plasma. These challenges have hindered the direct observation of intermediate species formed during the reactions. We address this challenge by examining the interaction of Ar plasma using atomically flat, monohydride-terminated Si(111) as a well-defined model surface and focusing on the initial PEALD with aminosilanes. In situ infrared and X-ray photoelectron spectroscopy reveals that an Ar plasma induces desorption of H atoms from H-Si(111) surfaces, leaving Si dangling bonds, and that the reaction of di-sec-butylaminosilane (DSBAS) with Ar plasma-treated surfaces requires the presence of both active sites (Si dangling bonds) and Si-H; there is no reaction on fully H-terminated or activated surfaces. By contrast, high-quality hydrofluoric acid-etched Si3N4 surfaces readily react with DSBAS, resulting in the formation of O-SiH3. However, the presence of back-bonded oxygen in O-SiH3 inhibits H desorption by Ar or N2 plasma, presumably because of stabilization of H against ion-induced desorption. Consequently, there is no reaction of adsorbed aminosilanes even after extensive Ar or N2 plasma treatments; a thermal process is necessary to partially remove H, thereby promoting the formation of active sites. These observations are consistent with a mechanism requiring the presence of both undercoordinated nitrogen and/or dangling bonds and unreacted surface hydrogen. Because active sites are involved, the PEALD process is found to be sensitive to the duration of the plasma exposure treatment and the purge time, during which passivation of these sites can occur.

Cancer Control ; 24(3): 1073274817729240, 2017 Jul-Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28975833


Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Underlying chronic liver disease has been associated with an increased risk of developing HCC. This study is a review of the current literature regarding the diagnosis, prognostic significance, and role of treating underlying liver disease in patients who are at risk of primary liver cancer. Relevant peer review of the English literature between 1980 and 2017 within PubMed and the Cochrane library was conducted for scientific content on current advances in managing chronic liver diseases and the development of hepatocellular carcinoma. Hepatitis C virus, hepatitis B virus (HBV), nonalcoholic steatohepatitis, autoimmune hepatitis, hereditary hemochromatosis, Wilson disease, primary biliary cirrhosis, α 1-antitrypsin deficiency, and certain drugs lead to an increased risk of developing HCC. Patients with underlying liver disease have an increased incidence of HCC. Hepatitis C virus, HBV, and hemochromatosis can directly lead to HCC without the presence of cirrhosis, while HCC related to other underlying liver diseases occurs in patients with cirrhosis. Treating the underlying liver disease and reducing the progression to cirrhosis should lead to a decreased incidence of HCC.

Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco
Opt Lett ; 42(13): 2487-2490, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28957265


We unveil different regimes for the interaction between two orthogonally polarized soliton-like beams in a colloidal suspension of nanoparticles with positive polarizability. The interaction is always attractive. However, it noticeably changes as a function of the angle and the power distribution between the input beams. For small angles, both interacting solitons fuse into a single entity, whose propagation direction can be continuously steered. As the interaction angle increases, the resulting self-collimated beam can be practically switched between two positions when the power imbalance between the beams is changed. For interaction angles larger than ∼10°, the result is no longer a single emerging soliton when the input power is balanced between the two beams.