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1.
Infectio ; 23(supl.1): 97-106, dic. 2019. tab, graf
Artigo em Espanhol | LILACS-Express | ID: biblio-984513

RESUMO

Resumen Objetivo: Estimar las frecuencias de mutaciones y de polimorfismos adicionales asociados con resistencia a los fármacos inhibidores de la integrasa del virus de inmunodeficiencia humana tipo 1 (VIH-1). Metodología: Estudio descriptivo, de corte transversal, en individuos VIH-1 positivos de la ciudad de Medellín, quienes no habían recibido tratamiento antirretroviral. En ellos se determinó, a través del método de 2-dideoxinucleótidos y el sistema ABI3730XL, la secuencia del gen de la integrasa del VIH-1 a partir del ARN viral circulante, la cual fue analizada en la base de datos de resistencia a medicamentos antirretrovirales de la Universidad de Stanford y según reportes de literatura científica. Resultados: Se encontraron las siguientes mutaciones (con sus respectivas frecuencias): una mutación mayor, E138K (1/46), tres mutaciones accesorias G163E (3/46), L74I (3/50) y E157Q (2/48), una mutación no polimórfica A128T (1/49) y otras dos mutaciones potencialmente asociadas con resistencia a inhibidores de integrasa S230N (9/39) y S119P/R/T (4/47, 2/47 y 14/47, respectivamente). Conclusiones: En las secuencias analizadas, llama la atención la presencia de al menos una mutación asociada a resistencia a inhibidores de integrasa en el 14% de los individuos estudiados, sugiriendo una pobre presión selectiva de este tipo de fármacos en la población viral circulante en la zona.


Abstract Aim: To estimate the frequencies of major and accessory mutations, as well as additional polymorphisms associated with resistance to human immunodeficiency virus type 1 (VIH-1) integrase strand transfer inhibitors. Materials and methods: Descriptive cross-sectional study, focused on HIV-1 positive individuals from Medellín, recruited between 2013 and 2015, and that had not received antiretroviral therapy. In these patients, the sequence from HIV-1 integrase was determined from circulating viral RNA through Sanger chain termination method with the ABI3730XL system, and the sequences were analyzed using the HIV Drug Resistance Database from the University of Stanford, together with previous literature reports. Results: The following mutations associated with resistance to integrase strand transfer inhibitors, along with its respective frequencies, were found: one major mutation, E138K (1/46), three accessory mutations, G163E (3/46), L74I (3/50) and E157Q (2/48); one non-polymorphic mutation, A128T (1/49); and two mutations potentially associated with resistance to integrase strand transfer inhibitors, S230N (9/39) and S119P/R/T (4/47, 2/47 and 14/47, respectively). Conclusions: In the sequences analyzed, it is noteworthy the presence of at least one mutation related with resistance to integrase inhibitors in 14% of the studied patients, suggesting a poor selective pressure of this kind of drugs in the circulating viral population in our region.

2.
Eur. j. psychol. appl. legal context (Internet) ; 11(2): 61-69, jul.-dic. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-183600

RESUMO

Psychological intimate partner violence (IPV) is the most prevalent form of IPV and is often thought to precede physical IPV. However, psychological IPV often occurs independently of other forms of IPV, and it can often emerge during routine relationship interactions. Using data from imprisoned male offenders we investigate the effect of hostile and benevolent sexist attitudes on psychological IPV and the hypothesized mediating role of positive attitudes toward IPV and this effect when accounting for broader risk factors at the levels of community (social disorder), family-of-origin (conflictive climate in family of origin), and personality (antisocial personality traits) variables. The sample involved 196 male inmates of the Penitentiary Center of Villabona (Asturias, Spain). Structural equation models result showed significant total, direct and indirect effect of hostile sexism on psychological IPV, but not of benevolent sexism. When individual, family-of-origin, and community variables were considered, however, hostile sexism showed only an indirect effect on psychological IPV via positive attitudes toward abuse. These results are discussed in light of the debate of the role of sexist attitudes in the psychological IPV explanation when broader models are considered


La violencia de pareja (VP) psicológica es la forma más prevalente de VP y habitualmente suele preceder a la VP física. Sin embargo, la VP psicológica ocurre a menudo independientemente de otras formas de VP y puede darse en interacciones rutinarias con la pareja. Utilizando datos de hombres recluidos en prisión, hemos investigado el efecto del sexismo hostil y benevolente sobre la VP psicológica, así como el rol mediador de las actitudes positivas hacia el abuso de la pareja. Hemos investigado también ese efecto cuando están presentes otros factores de riesgo de VP psicológica señalados en la literatura reciente están presentes: comunidad (desorden social), familia de origen (clima conflictivo en la familia de origen) y factores individuales (rasgos de personalidad antisocial). Participaron en el estudio 196 hombres internos en el Centro Penitenciario de Villabona (Asturias, España). Los resultados de los modelos de ecuaciones estructurales estimados indican un efecto total, directo e indirecto significativo del sexismo hostil sobre la VP psicológica, pero no del sexismo benevolente. Cuando las variables de la comunidad, la familia de origen y factores individuales se incorporaron al modelo únicamente el efecto indirecto del sexismo hostil a través de las actitudes positivas hacia el abuso siguió siendo significativo. Los resultados se discuten en relación con el debate sobre el rol de las actitudes sexistas sobre la VP psicológica en el marco de modelos más generales de violencia


Assuntos
Humanos , Masculino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Violência por Parceiro Íntimo/psicologia , Sexismo/psicologia , Agressão/psicologia , Repressão Psicológica , Prisioneiros/psicologia , Esgotamento Psicológico/psicologia , Fatores de Risco , Violência contra a Mulher , Conflito (Psicologia) , Homicídio/psicologia
3.
Sci Rep ; 9(1): 15747, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673120

RESUMO

Canine distemper virus (CDV) is the cause of a multisystem disease in domestic dogs and wild animals, infecting more than 20 carnivore and non-carnivore families and even infecting human cell lines in in vitro conditions. Phylogenetic classification based on the hemagglutinin gene shows 17 lineages with a phylogeographic distribution pattern. In Medellín (Colombia), the lineage South America-3 is considered endemic. Phylogenetic studies conducted in Ecuador using fragment coding for the fusion protein signal peptide (Fsp) characterized a new strain belonging to a different lineage. For understanding the distribution of the South America-3 lineage in the north of the South American continent, we characterized CDV from three Colombian cities (Medellín, Bucaramanga, and Bogotá). Using phylogenetic analysis of the hemagglutinin gene and the Fsp region, we confirmed the circulation of CDV South America-3 in different areas of Colombia. We also described, for the first time to our knowledge, the circulation of a new lineage in Medellín that presents a group monophyletic with strains previously characterized in dogs in Ecuador and in wildlife and domestic dogs in the United States, for which we propose the name "South America/North America-4" due its intercontinental distribution. In conclusion, our results indicated that there are at least four different CDV lineages circulating in domestic dogs in South America: the Europe/South America-1 lineage circulating in Brazil, Uruguay, and Argentina; the South America-2 lineage restricted to Argentina; the South America-3 lineage, which has only been reported in Colombia; and lastly an intercontinental lineage present in Colombia, Ecuador, and the United States, referred to here as the "South America/North America-4" lineage.

4.
Rev. neurol. (Ed. impr.) ; 69(6): 249-254, 16 sept., 2019. tab, ilus
Artigo em Espanhol | LILACS-Express | ID: ibc-FGT-2185

RESUMO

Introducción. El seno cavernoso es una estructura de la base craneal que alberga varias estructuras nerviosas y vasculares. De su afectación se deriva el síndrome del seno cavernoso, una combinación de alteraciones oculomotoras y de las dos primeras ramas del trigémino, frecuentemente acompañadas de dolor o proptosis. La infiltración por un linfoma de Burkitt es una causa infrecuente de este síndrome. Caso clínico. Varón de 43 años, portador del virus de la inmunodeficiencia humana, con buen control de la enfermedad, que desarrolla un cuadro consistente en oftalmoplejía dolorosa progresiva en presencia de adenopatía laterocervical. Las pruebas complementarias permiten el diagnóstico de linfoma de Burkitt con extensión extranodal al seno cavernoso. También se realiza una revisión de los casos publicados en Medline: se recogen un total de 15 casos y se describen sus características epidemiológicas, forma de presentación, afectación extracraneal en el momento del diagnóstico y evolución clínica. Conclusiones. El linfoma de Burkitt es un síndrome linfoproliferativo de alto grado. Su forma asociada a inmunodeficiencia es una importante causa de morbimortalidad en este subgrupo de pacientes. En los casos analizados en la bibliografía, la edad de presentación fue variable y la forma de inicio fue una oftalmoplejía dolorosa progresiva o un síndrome de numb chin. Fue infrecuente una afectación exclusiva del seno cavernoso, pero en ese caso conllevaba un mal pronóstico. Es importante descartar un origen primario extracraneal y no confundirlo con un síndrome de Tolosa-Hunt idiopático que retrasaría el inicio del tratamiento antitumoral


Introduction. The cavernous sinus is a structure in the base of the skull that houses several nerve and vascular structures. Its compromise leads to cavernous sinus syndrome, which is a combination of oculomotor disorders and others affecting the first two trigeminal branches, often accompanied by pain or proptosis. Infiltration due to Burkitts lymphoma is a rare cause of this syndrome. CASE Report. A 43-year-old male, carrier of human immunodeficiency virus, with good control of the disease, who developed a clinical picture consisting of progressive painful ophthalmoplegia in the presence of a laterocervical adenopathy. Complementary tests allowed a diagnosis of Burkitts lymphoma with extranodal extension to the cavernous sinus. A review of the cases published in Medline was also carried out: a total of 15 cases were detected and their epidemiological characteristics, form of presentation, extracranial involvement at the time of diagnosis and clinical progression were described. Conclusions. Burkitts lymphoma is a high-grade lymphoproliferative syndrome. Its form associated with immunodeficiency is an important cause of morbidity and mortality in this subgroup of patients. In the cases analysed in the literature, the age of presentation varied and the form of onset was a progressive painful ophthalmoplegia or numb chin syndrome. Exclusive involvement of the cavernous sinus was infrequent, but in that case it entailed a poor prognosis. It is important to rule out a primary extracranial origin and not to confuse it with an idiopathic Tolosa-Hunt syndrome that would delay the beginning of antitumour treatment

6.
Ticks Tick Borne Dis ; 10(5): 995-996, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31151921

RESUMO

This report describes a new lethal case of Rickettsia rickettsii infection in a child from Northwestern Colombia, after ten years of the last outbreaks in the same region. Colombian public-health authorities should consider to include this severe rickettsiosis in the compulsory-reporting diseases, with the aim of knowing its burden in the country.


Assuntos
Rickettsia rickettsii/isolamento & purificação , Febre Maculosa das Montanhas Rochosas/microbiologia , Pré-Escolar , Colômbia , Evolução Fatal , Humanos , Masculino
7.
Sci Total Environ ; 688: 574-583, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31254823

RESUMO

Intensive use of agrochemicals is considered one of the major threats for soil quality. In an attempt to mitigate their side-effects on non-target organisms and soil functioning, many engineering and biological remediation methodologies are currently available. Among them, the use of biochar, a carbonaceous material produced from pyrolysing biomass, represents an attractive option enhancing both remediation and soil carbon storage potentials. Currently, activation of biochar with chemical or physical agents seeks for improving its remediation potential, but most of them have some undesirable drawbacks such as high costs and generation of chemical wastes. Alternatively, the use of biological procedures to activate biochar with extracellular enzymes is gaining acceptance mainly due to its eco-friendly nature and cost-effectiveness. In these strategies, microorganisms play a key role as a source of extracellular enzymes, which are retained on the biochar surface. Recently, several studies point out that soil macrofauna (earthworms) may act as a biological vector facilitating the adsorption of enzymes on biochar. This paper briefly introduces current biochar bioactivation methodologies and the mechanisms underlying the coating of biochar with enzymes. We then propose a new conceptual model using earthworms to activate biochar with extracellular enzymes. This new earthworm-biochar model can be used as a theoretical framework to produce a new product "vermichar", vermicompost produced from blended feedstock, earthworms, and biochar that can be used to improve soil quality and remove soil contaminants. This model can also be used to develop innovative in-situ "vermiremediation" technologies utilizing the beneficial effects of both earthworms and biochar. Since biochar may contain toxic chemicals generated during its production stages or later concentrated when applied to polluted soils, this paper also highlights the need for an ecotoxicological knowledge around earthworm-biochar interaction, promoting further discussion on suitable procedures for assessing the environmental risk of this conceptual model application in soil bioremediation.


Assuntos
Biodegradação Ambiental , Carvão Vegetal , Oligoquetos/fisiologia , Solo/química , Adsorção , Animais , Poluentes do Solo/análise , Poluentes do Solo/metabolismo
8.
Am J Trop Med Hyg ; 101(2): 336-342, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31162015

RESUMO

Rocky Mountain spotted fever (RMSF) has been reported in Colombia since 1937. Most recent outbreaks were in 2006-2008, followed by the absence of recognized cases. This report describes new clinical cases of RMSF and epidemiologic investigations. Medical records were reviewed, and fieldwork, serological and molecular diagnostic testing, and bacterial isolation were performed. Fever, hypotension, abdominal discomfort, and rash accompanied by thrombocytopenia and leukopenia were the most characteristic manifestations. Two convalescent sera from the index case and sera from two dogs revealed high anti-spotted fever group Rickettsia antibody titers. Rickettsia rickettsii was isolated from case 4. Cases 2 and 3 were identified by epidemiological connection with the index case. Thus, a new cluster of cases of RMSF was identified in Antioquia, Colombia, with the occurrence of fatal cases, which indicates the active circulation of the bacteria and a potential risk for the population.

9.
Acta Parasitol ; 64(2): 331-335, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30941664

RESUMO

INTRODUCTION: Saline groundwater desalination has recently emerged as an alternative source of irrigation water in arid and semiarid regions due to the gradual reduction in the quantity and quality of conventional water resources for agricultural use. In Fuerteventura Island (Spain), an extremely arid territory in the European Union, brackish water desalination is one of the few available water sources for agricultural production. Very little research has been conducted on the microbiological quality of this water mainly used for irrigation of vegetable crops. Free-living amoebae (FLA) are widely distributed protozoa in the environment and have been isolated from many environmental sources such as dust, soil and water. Among the pathogenic genera included in this group, Acanthamoeba spp., Naegleria fowleri and Balamuthia mandrillaris have been reported to be causative agents of lethal encephalitis, disseminated infections and keratitis. Particularly, Naegleria fowleri is a pathogenic FLA species which causes primary amoebic meningoencephalitis (PAM). MATERIALS AND METHODS: In the present study, the presence of pathogenic FLA strains on desalinated brackish water samples for irrigation has been evaluated during 7 months. RESULTS: From the analysed samples, only one was positive for Naegleria australiensis. This is the first report of Naegleria spp. in desalinated brackish water for irrigation in Spain.

10.
Infect Genet Evol ; 69: 267-278, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30808498

RESUMO

The introduction of highly active antiretroviral therapy (HAART) has significantly improved life expectancy of HIV-infected patients; nevertheless, it does not eliminate the virus from hosts, so a cure for this infection is crucial. Some strategies have employed the induction of anti-HIV CD8+ T cells. However, the high genetic variability of HIV-1 represents the biggest obstacle for these strategies, since immune escape mutations within epitopes restricted by Human Leukocyte Antigen class I molecules (HLA-I) abrogate the antiviral activity of these cells. We used a bioinformatics pipeline for the determination of such mutations, based on selection pressure and docking/refinement analyses. Fifty HIV-1 infected patients were recruited; HLA-A and HLA-B alleles were typified using sequence-specific oligonucleotide approach, and viral RNA was extracted for the amplification of HIV-1 gag, which was bulk sequenced and aligned to perform selection pressure analysis, using Single Likelihood Ancestor Counting (SLAC) and Fast Unconstrained Bayesian Approximation (FUBAR) algorithms. Positively selected sites were mapped into HLA-I-specific epitopes, and both mutated and wild type epitopes were modelled using PEP-FOLD. Molecular docking and refinement assays were carried out using AutoDock Vina 4 and FlexPepDock. Five positively selected sites were found: S54 at HLA-A*02 GC9, T84 at HLA-A*02 SL9, S125 at HLA-B*35 HY9, S173 at HLA-A*02/B*57 KS12 and I223 at HLA-B*35 HA9. Although some mutations have been previously described as immune escape mutations, the majority of them have not been reported. Molecular docking/refinement analysis showed that one combination of mutations at GC9, one at SL9, and eight at HY9 epitopes could act as immune escape mutations. Moreover, HLA-A*02-positive patients harbouring mutations at KS12, and HLA-B*35-positive patients with mutations at HY9 have significantly higher plasma viral loads than patients lacking such mutations. Thus, HLA-A and -B alleles could be shaping the genetic diversity of HIV-1 through the selection of potential immune escape mutations.

11.
Immunology ; 2018 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-30315653

RESUMO

Although dengue can progress to severe stages, the exact causes of this phenomenon are unknown; however, the possibility of monocyte participation is acknowledged. It has been suggested that monocyte subsets (classical, intermediate and non-classical) play differential roles in dengue immunopathology. Therefore, we determined the count of monocyte subsets and obtained the clinical information of patients with dengue. We noted a significant decrease in the count of non-classical monocytes in patients compared with controls. With this finding, we focused on studying the phenotype of non-classical monocytes in the present study. An increase in activation and differentiation markers, such as CD64, CD86, the percentage of tumor necrosis factor-α+ cells and exposure of phosphatidylserine, were recorded in the non-classical monocytes of patients compared with controls. Moreover, a significant decrease in the expression of CX3CR1 with a corresponding increase in the expressions of CCR2, CCR5, CD11b and CD54 was detected in the non-classical monocytes of patients in comparison with that of the controls. Significant increases in the frequency of microparticles from endothelium and in the concentrations of interleukin-6 (IL-6), IL-8 and IL-10 were noted in the plasma of patients. These findings demonstrate that in patients with dengue, non-classical monocytes are activated, exhibiting a phenotype associated with more differentiation, produces tumor necrosis factor-α and has a profile of less endothelial surveillance closer to the cellular migration. These changes were associated with hepatic compromise, endothelial alteration and high concentration of circulating cytokines. Hence, alterations of non-classical monocytes seem to be associated with the immunopathology of dengue infection.

12.
Arch Virol ; 163(12): 3291-3301, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30191374

RESUMO

Hantavirus cardiopulmonary syndrome (HPS) has gained importance in Latin America as an emerging disease, with reports of about 4000 HPS cases; however, this is probably an underestimate because of limited surveillance programs and diagnostic tools to confirm HPS. In order to address this issue and develop better serosurveillance capability, we evaluated three recombinant peptides from the Necoclí virus (NECV) nucleocapsid in antibody-capture ELISA. We cloned and expressed antigens representing the whole NECV nucleocapsid protein (NECV-rN), the immunodominant domain (NECV-rN100), and a serospecific domain (NECV-rN428), and then we compared these antigens in ELISA to detect IgG antibodies to NECV in human sera. We evaluated human sera collected during two epidemiological studies from the area where NECV was discovered. The first group included 609 sera from healthy individuals, and the second one included 89 samples from patients with undifferentiated febrile illness. In these two groups, hantavirus infection had previously been determined by the presence of IgG to Maciel virus (MCLV), a hantavirus closely related to NECV. The number of IgG-positive sera was higher using the Necoclí ELISA with the rN100 protein, which detected antibodies in a higher percentage of healthy individuals, 129/609 (21.2%), as well as in febrile patients, 11/89 (12.3%). In contrast, using MCLV ELISA, 8 of 609 (1.3%) and 4 of 89 (4.5%) samples from healthy and febrile patients, respectively, were seropositive. The agreement between the NECV and MCLV ELISA assays was ≥ 82.3%; however, the kappa indices were weak but statistically significant for rN (0.251 CI; 0.138-0.365) and rN100rN (0.153 CI; 0.084-0.223). The weak kappa indices were attributed to decreased MCLV ELISA assay sensitivity. These results suggest that NECV rN and rN100 have increased specificity and could be further validated for improved diagnosis of hantavirus infections.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Infecções por Hepadnaviridae/diagnóstico , Orthohepadnavirus/isolamento & purificação , Adolescente , Animais , Anticorpos Antivirais/sangue , Criança , Feminino , Infecções por Hepadnaviridae/sangue , Infecções por Hepadnaviridae/virologia , Humanos , Imunoglobulina G/sangue , Masculino , Proteínas do Nucleocapsídeo/imunologia , Orthohepadnavirus/classificação , Orthohepadnavirus/genética , Orthohepadnavirus/imunologia , Estudos Retrospectivos , Roedores/sangue , Roedores/virologia , Sensibilidade e Especificidade
13.
J Clin Psychopharmacol ; 38(5): 442-446, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30106876

RESUMO

PURPOSE/BACKGROUND: Some therapeutic drug monitoring studies suggest that increased weight is associated with small increases in clozapine concentrations. The goal of this study was to reanalyze a US double-blind study using a sophisticated statistical model to test whether weight gains from baseline or increases in percentage of body fat from baseline, computed from a published equation, are associated with increased total plasma clozapine concentrations after controlling for the effects of smoking and sex. METHODS/PROCEDURES: Using data from a multidosage randomized double-blind US clozapine trial previously published, a random intercept linear model of steady-state total plasma clozapine concentrations was fitted to 424 concentrations from 47 patients. FINDINGS/RESULTS: After adjusting for sex and smoking, (1) a 1-kg gain in body weight during clozapine treatment was significantly associated with a 1.4% increase in total plasma clozapine concentrations (95% confidence interval = 0.55 to 2.3) and (2) a 1-point increase in percentage of body fat during clozapine treatment was significantly associated with a 5.4% increase in total clozapine concentration (2.5 to 8.3) in females and 1.4% (-1.1 to 4.0) in males. IMPLICATIONS/CONCLUSIONS: As hypothesized, weight increases during clozapine treatment, which probably reflect increases in fat tissue, were associated with increases in total plasma concentrations. Pending further replication in other samples, it seems likely that clozapine may deposit in body fat and that this may decrease clozapine clearance. This change may be small in most patients but may be clinically relevant in females with major gains in body fat.

14.
Pharmacogenomics ; 19(10): 815-823, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29914302

RESUMO

AIM: The role of sex on the association of plasma prolactin levels with risperidone (R) and 9-hydroxyrisperidone (9-OHR) concentrations is investigated. METHODS: Plasma R and prolactin concentrations, CYP2D6 and exon 21 and 26 ABCB1 gene variants were studied in 110 patients. RESULTS: In females, a 1 ng/ml increase in R levels was associated with a significant 1.02% increase in prolactin levels. In males, a 1 ng/ml increase in 9-OHR levels was associated with a significant 1.18% increase in prolactin levels. ABCB1 haplotype 12 had significant but opposite effects in males and females. In the combined sample, 9-OHR, but not R levels had significant effects on prolactin levels. CONCLUSION: Genes had sex-specific effects on risperidone-associated prolactin elevations.

15.
Oncotarget ; 9(30): 21429-21443, 2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29765550

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the prognosis of HCC patients, especially those with metastasis, remains extremely poor. This is partly due to unclear molecular mechanisms underlying HCC metastasis. Our previous study indicates that MDM2 Binding Protein (MTBP) suppresses migration and metastasis of HCC cells. However, signaling pathways regulated by MTBP remain unknown. To identify metastasis-associated signaling pathways governed by MTBP, we have performed unbiased luciferase reporter-based signal array analyses and found that MTBP suppresses the activity of the ETS-domain transcription factor Elk-1, a downstream target of Erk1/2 MAP kinases. MTBP also inhibits phosphorylation of Elk-1 and decreases mRNA expression of Elk-1 target genes. Reduced Elk-1 activity is caused by inhibited nuclear translocation of phosphorylated Erk1/2 (p-Erk) by MTBP and subsequent inhibition of Elk-1 phosphorylation. We also reveal that MTBP inhibits the interaction of p-Erk with importin-7/RanBP7 (IPO7), an importin family member which shuttles p-Erk into the nucleus, by binding to IPO7. Moreover, high levels of MTBP in human HCC tissues are correlated with cytoplasmic localization of p-Erk1/2. Our study suggests that MTBP suppresses metastasis, at least partially, by down-modulating the Erk1/2-Elk-1 signaling pathway, thus identifying a novel regulatory mechanism of HCC metastasis by regulating the subcellular localization of p-Erk.

16.
BMC Cardiovasc Disord ; 18(1): 57, 2018 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-29606104

RESUMO

BACKGROUND: Heart failure (HF), the leading cause of morbidity and mortality in the US, affects 6.6 million adults with an estimated additional 3 million people by 2030. More than 50% of HF patients have heart failure with preserved left ventricular ejection fraction (HFpEF). These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. Patients with HFpEF experience symptoms of: (1) fatigue; (2) shortness of breath; and (3) swelling (edema) of the lower extremities. However, current HF guidelines offer no effective treatment to address these underlying pathophysiologic mechanisms. Thus, we propose a biobehavioral symptom science study using ubiquinol and D-ribose (therapeutic interventions) to target mitochondrial bioenergetics to reduce the complex symptoms experienced by patients with HFpEF. METHODS: Using a randomized, double-blind, placebo-controlled design, the overall objective is to determine if administering ubiquinol and/or D-ribose to HFpEF patients for 12 weeks would decrease the severity of their complex symptoms and improve their cardiac function. The measures used to assess patients' perceptions of their health status and level of vigor (energy) will be the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Vigor subscale of the Profile of Mood States. The 6-min walk test will be used to test exercise tolerance. Left ventricular diastolic function will be assessed using innovative advanced echocardiography software called speckle tracking. We will measure B-type natriuretic peptides (secreted from ventricles in HF) and lactate/ATP ratio (measure of cellular energetics). DISCUSSIONS: Ubiquinol (active form of Coenzyme Q10) and D-ribose are two potential treatments that can positively affect cellular energetic impairment, the major underlying mechanism of HFpEF. Ubiquinol, the reduced form of CoQ10, is more effective in adults over the age of 50. In patients with HFpEF, mitochondrial deficiency of ubiquinol results in decreased adenosine triphosphate (ATP) synthesis and reduced scavenging of reactive oxygen species. D-ribose is a substrate required for ATP synthesis and when administered has been shown to improve impaired myocardial bioenergetics. Therefore, if the biological underpinning of deficient mitochondrial ATP in HFpEF is not addressed, patients will suffer major symptoms including lack of energy, fatigue, exertional dyspnea, and exercise intolerance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03133793 ; Data of Registration: April 28, 2017.

17.
Genes (Basel) ; 9(3)2018 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-29495356

RESUMO

Colorectal cancer (CRC) is the third leading cause of cancer death for both men and women in the United States, yet it is treatable and preventable. African Americans have higher incidence of CRC than other racial/ethnic groups, however, it is unclear whether this disparity is primarily due to environmental or biological factors. Short chain fatty acids (SCFAs) are metabolites produced by bacteria in the colon and are known to be inversely related to CRC progression. The aim of this study is to investigate how stool SCFA levels, markers of inflammation in stool and dietary intake relate to colonoscopy findings in a diverse patient population. Stool samples from forty-eight participants were analyzed for SCFA levels and inflammatory markers (lysozyme, secretory IgA, lactoferrin). Additionally, participants completed the National Cancer Institute's Diet History Questionnaire II (DHQ II) to report dietary intake over the past year. Subsequently, the majority of participants underwent screening colonoscopy. Our results showed that African Americans had higher total levels of SCFAs in stool than other racial/ethnic groups, significantly lower intake of non-starchy vegetables and similar inflammatory marker expression and colonoscopy outcomes, compared to others. This work is an initial exploration into the biological and clinical factors that may ultimately inform personalized screening approaches and clinical decision-making to improve colorectal cancer disparities for African Americans.

18.
Iatreia ; 31(1): 36-50, ene.-mar. 2018. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-892686

RESUMO

RESUMEN Los virus transmitidos por garrapatas (VTG) pertenecen a las familias Flaviviridae, Bunyaviridae, Reoviridae, Asfarviridae y Orthomyxoviridae y son agentes causales de diferentes enfermedades en humanos y animales. Debido a la creciente importancia epidemiológica que están teniendo los VTG, esta revisión pretende englobar el conocimiento actual de estos agentes y las enfermedades que producen, así como exponer las estrategias abordadas en prevención y tratamiento que se han implementado hasta el momento en diferentes países. Es evidente que para la región Neotropical hacen falta estudios sobre los VTG presentes en la región, ya que la gran mayoría de los artículos, tanto revisiones de tema como trabajos originales, presentan datos de las regiones Neártica y Paleártica. Considerando el panorama actual de los estudios de VTG en la región Neotropical y las particularidades de la misma, es muy probable que existan otros VTG aún no identificados que podrían tener algún impacto en salud pública.


SUMMARY Tick-borne viruses (TBVs) belong to the Flaviviridae, Bunyaviridae, Reoviridae, Asfarviridae and Orthomyxoviridae families and cause different diseases in humans and animals. Due to the epidemiologic relevance of TBVs, this review highlights the actual knowledge of these agents and the diseases they cause, besides of the prevention and treatment strategies implemented so far. It is evident that studies that address the TBVs present in the Neotropical region are missing, since most of the studies, both reviews and original articles, present data from the Nearctic and Palearctic regions. Considering the current picture of the TBVs studies in the Neotropical area and its peculiarities, is probable that other not yet identified TBVs exist in this zone and have an impact in public health.


Assuntos
Humanos , Carrapatos , Viroses , Saúde Pública
19.
J Neurosci Res ; 96(6): 1080-1092, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29380912

RESUMO

Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over-the-counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra-arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline-TBI, (2) ubiquinol 30 minutes before TBI (UB-PreTBI), or (3) ubiquinol 30 minutes after TBI (UB-PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury-induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI.

20.
Methods Mol Biol ; 1604: 33-41, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28986823

RESUMO

An important aspect of virological surveillance is the identification of the detected viruses. Broad surveillance, that typically employs deep sequencing of collected tissue samples, provides the investigator with many sequence files constructed from overlapping stretches of DNA sequences. Directed surveillance for viruses of a specific taxonomic group provides the investigator with sequence files from cDNA amplified using specific primers to conserved viral regions. Here we will describe general approaches to identify hemorrhagic viral agents through phylogenetic analysis of cDNA sequences obtained during surveillance activities.


Assuntos
Vírus Hantaan/genética , Filogenia , Biologia Computacional , DNA Complementar/genética , Humanos
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