RESUMO
Spinal arachnoid webs are abnormal formations of arachnoid membranes that reside in the arachnoid space. Clinically, they may present as an incidental finding or in patients with progressively worsening myelopathy. Early detection and surgical intervention are recommended in patients with progressive symptoms. Several methods have been described for the surgical treatment of these web formations.1-4 The success of surgery and the ability to prevent recurrence is dependent on complete surgical resection of these lesions, which in some cases can appear complex and intricate in nature. A few reports have highlighted the use of intraoperative ultrasound to localize the lesion; however, none have highlighted its value in establishing successful web resection and restoration of normal cerebrospinal fluid flow.3,4 Herein, we demonstrate the use of intraoperative ultrasound as an effective adjunct to assessing and establishing complete resection of arachnoid webs. We illustrate how intraoperative ultrasound allows for real-time, direct visualization of arachnoid lysis with restoration of normal cerebrospinal fluid flow (Video 1). Our patient was symptomatic for 12 months with rapid progression of myelopathic symptoms in the 3 months before presentation. Following surgery, she remained asymptomatic at 4-year follow-up with no reoccurrence at 24-month magnetic resonance imaging. Intraoperative ultrasound is a useful adjunct to successfully performing dorsal arachnoid web surgery and ensuring improved surgical outcomes through complete web resection and decompression of the spinal cord.
Assuntos
Cistos Aracnóideos , Doenças da Medula Espinal , Feminino , Humanos , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/cirurgia , Imageamento por Ressonância Magnética , Aracnoide-Máter/diagnóstico por imagem , Aracnoide-Máter/cirurgia , Ultrassonografia , Cistos Aracnóideos/diagnóstico por imagem , Cistos Aracnóideos/cirurgiaRESUMO
Back pain is the single leading cause of disability worldwide. Despite the prevalence and morbidity of lower back pain, we still lack a gold-standard treatment that restores the physiological function of degenerated intervertebral discs. Recently, stem cells have emerged as a promising strategy for regenerative therapy for degenerative disc disease. In this study, we review the etiology, pathogenesis, and developing treatment strategies for disc degeneration in low back pain with a focus on regenerative stem cell therapies. A systematic search of PubMed/MEDLINE/Embase/Clinical Trials.gov databases was conducted for all human subject abstracts or studies. There was a total of 10 abstracts and 11 clinical studies (1 RCT) that met the inclusion criteria. The molecular mechanism, approach, and progress of the different stem cell strategies in all studies are discussed, including allogenic bone marrow, allogenic discogenic cells, autologous bone marrow, adipose mesenchymal stem cells (MSCs), human umbilical cord MSC, adult juvenile chondrocytes, autologous disc derived chondrocytes, and withdrawn studies. Clinical success with animal model studies is promising; however, the clinical outcomes of stem cell regenerative therapy remain poorly understood. In this systematic review, we found no evidence to support its use in humans. Further studies on efficacy, safety, and optimal patient selection will establish whether this becomes a viable, non-invasive therapeutic option for back pain.
Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Dor Lombar , Transplante de Células-Tronco Mesenquimais , Adulto , Animais , Humanos , Dor Lombar/terapia , Dor Lombar/etiologia , Degeneração do Disco Intervertebral/patologia , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Dor nas Costas/patologia , Disco Intervertebral/patologiaRESUMO
BACKGROUND: The clinical approach to upper and lower respiratory diseases from a joint perspective, known as united airways disease (UAD), is challenging for health care professionals owing to a paucity of specific studies. OBJECTIVE: This study reviews recent scientific evidence on the management of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) from a UAD perspective. METHODS: A systematic search of PubMed, Scopus, and Web of Science was conducted for 9 research questions, and studies published from January 2015 to July 2021 were included. Quality assessment was performed with the Critical Appraisal Skills Programme. RESULTS: In total, 32 publications met the inclusion criteria. Control of type 2 inflammation in UAD (reported in 9 studies) was associated with biologic therapies, for which an impact on asthma, CRSwNP, and/or aspirin/nonsteroidal anti-inflammatory drug-exacerbated respiratory disease outcomes was described in 9 studies. However, there was a lack of scientific evidence on clinical and/or biochemical markers associated with response to biologics in patients with UAD. The benefit on corticosteroid reduction in patients receiving biologics was reported in 9 studies. Three publications reported a positive impact of surgery on asthma and/or CRSwNP outcomes, and the effect of biologics on reducing the need of surgery was consistent across 6 studies. CONCLUSIONS: Our results underscore an overall scarcity of scientific evidence on the treatment strategies for these frequent coexisting entities from an UAD approach but also identify several research gaps and unmet needs that should be addressed to ensure optimal diagnosis, management, and follow-up of these patients.
Assuntos
Asma Induzida por Aspirina , Asma , Produtos Biológicos , Pólipos Nasais , Transtornos Respiratórios , Rinite , Sinusite , Asma/tratamento farmacológico , Asma/epidemiologia , Asma Induzida por Aspirina/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Doença Crônica , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/epidemiologia , Pólipos Nasais/terapia , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológicoRESUMO
BACKGROUND: MP-AzeFlu (Dymista®; spray of azelastine/fluticasone propionate) is the most effective allergic rhinitis (AR) treatment available. Its effect on asthma outcomes in patients with AR and asthma is unknown. METHODS: This pre-post historical cohort study, using the Optimum Patient Care Research Database, included patients aged ≥12 years, from UK general practice with active asthma (defined as a recorded diagnosis, with ≥1 prescription for reliever or controller inhaler) in the year before or at the initiation date. The primary study outcome was change in number of acute respiratory events (i.e. exacerbation or antibiotic course for a respiratory event) between baseline and outcome years. The effect size of MP-AzeFlu was quantified as the difference in % of patients that improved and worsened. RESULTS: Of the 1,188 patients with AR and asthma included, many had a record of irreversible obstruction (67%), and uncontrolled asthma (70.4%), despite high mean daily doses of reliever/controller therapy and acute oral corticosteroid use, in the year pre-MP-AzeFlu initiation. MP-AzeFlu initiation was associated with fewer acute respiratory events (effect size (e) = 5.8%, p = 0.0129) and a reduction in daily use of short-acting ß2-agonists, with fewer patients requiring >2 SABA puffs/week (e = 7.7% p < 0.0001). More patients had well-controlled asthma 1-year post-MP-AzeFlu initiation (e = 4.1%; p = 0.0037), despite a reduction in inhaled corticosteroids (e = 4.8%; p = 0.0078). CONCLUSIONS: This study provides the first direct evidence of the beneficial effect of MP-AzeFlu on asthma outcomes in co-morbid patients in primary care in the United Kingdom. TRIAL REGISTRATION: EUPAS30940. Registered August 13, 2019.
RESUMO
Anti-leucine-rich glioma-inactivated 1 (LGI1) limbic encephalitis (LE) has been classified as an autoimmune LE with a subacute course. Many patients with anti-LGI1 LE have normal or minimal cerebrospinal fluid (CSF) findings. Cerebrospinal fluid 14-3-3 protein or neuron specific enolase is usually seen in Creutzfeldt-Jakob disease (CJD) with high sensitivities, but can also be positive in other paraneoplastic and autoimmune encephalitides, which can make diagnosis challenging. The mainstay of treatment for anti-LGI1 LE generally focuses on steroids, intravenous immunoglobulin (IVIG), plasmapheresis, and/or rituximab. All the aforementioned modalities can be used in the treatment of anti-LGI1 LE and since this condition is highly responsive to treatment with steroids, prompt diagnosis can help stall the progression of this disease. Here, we present a case of anti-LGI1 LE that initially improved with empiric immunotherapy and showed definitive return to baseline with initiation of rituximab.
RESUMO
Neste estudo, investigaram-se as relações entre suporte social percebido, auto-regulação e comportamentos de consumo de álcool, tabaco e outras substâncias psicoactivas. A amostra foi constituída por 340 participantes. O suporte social correlacionou-se favoravelmente com a auto-regulação, mas somente na vertente de satisfação com o apoio social é que se observou esta tendência de forma evidente. O número de figuras de apoio diferenciou-se significativamente com o uso de tabaco, o que sugere o âmbito afiliativo de algumas substâncias psicoactivas. Nesse sentido, o uso de tabaco pode estar associado a uma rede social mais ampla, mas não com a qualidade do suporte social.
In this study the relationships between perceived social support, self-regulation and consuming behaviors of tobacco and other psychoactive substances we investigated. The sample consisted of 340 adult participants. Social support correlated positively with self-regulation, but was solely in the aspect of satisfaction with social support that this trend was noted clearly. The number of support providers differed considerably with the use of tobacco, which suggests the affiliative scope of some psychoactive substances. Accordingly, the use of tobacco may be associated with a larger social network, but not with the quality of social support.
RESUMO
ResumenLos pastos marinos son ambientes costeros que se han visto amenazados por el incremento de las actividades humanas. Alterando de forma negativa los procesos y servicios ambientales que presentan, así como la disminución de praderas. El objetivo es generar conocimiento de la distribución, estado de la estructura y nivel de fragmentación en dos arrecifes del Parque Nacional Sistema Arrecifal Veracruzano (PNSAV). Se eligieron dos praderas en arrecifes con características distintas: Sacrificios en el Norte que se encuentra cerca de la costa y Cabezo en el Sur que está alejado de la costa. Se determinaron las características específicas de haz y área de las praderas de macrófitas sumergidas presentes e identificaron cuatro grupos de cobertura morfofuncionales. Se comprobaron diferencias significativas entre coberturas (ANOVA no paramétrico, prueba de Kruskal-Wallis). Se realizó una clasificación supervisada de una imagen espacial de alta resolución verificada con datos de campo (55 Sacrificios y 290 Cabezo). El nivel de fragmentación se calculó usando métricas de paisaje a nivel de clase y se realizaron mapas temáticos en función de las cuatro coberturas. Las praderas se encuentran dominadas por Thalassia testudinum; se tuvieron densidades máximas de 208 haces/m2 para Cabezo y 176 haces/m2 en Sacrificios. Cabezo presentó pastos de hojas cortas (9 cm) y delgadas (0.55 cm) en promedio; Sacrificios tuvo hojas más largas (23.5 cm) y gruesas (1 cm). Sacrificios mostró menor grado de fragmentación que Cabezo; en ambos casos la fragmentación de la cobertura vegetal corresponde a menos del 50 %. Aunque el arrecife Cabezo presenta una mayor fragmentación, que crea un gran número de microambientes, siendo reconocido por su importancia como zona de reclutamiento. Este trabajo sirve como una línea de base para la creación de un plan de manejo adecuado (formación de una zona núcleo de Cabezo). Es necesario complementar este trabajo con nuevos esfuerzos del reconocimiento de las praderas de pastos marinos en todos los arrecifes del PNSAV, así como de monitoreos periódicos y reconocimiento de sus servicios ecosistémicos.
AbstractSeagrasses in coastal environments have been threatened by increased human activities; these have negatively altered processes and environmental services, and have decreased grassland areas. The aim of this study was to generate knowledge of Thalassia testudinum distribution, state of the structure and fragmentation level in two reefs of the Veracruz Reef System National Park (PNSAV). Two different reefs were selected: Sacrificios in the North and near the coast, and Cabezo in the South and away from the coast. Shoot-specific and area-specific characteristics of submerged macrophytes meadows present were determined, and four morpho-functional groups were identified. Significant differences between plant coverage were tested through nonparametric ANOVA, Kruskal-Wallis test. A supervised classification of spatial high-resolution image verified with field data was performed (55 Sacrificios and 290 Cabezo). The fragmentation level was calculated using landscape metrics, class level and thematic maps were made based on four covers. The meadows were dominated by Thalassia testudinum; maximum densities were 208 shoot/m2 in Cabezo, and 176 shoot/m2 in Sacrificios. Cabezo presented grasses with short (9 cm) and thin leaves (0.55 cm) on average; while Sacrificios showed longer (23.5 cm) and thicker (1 cm) leaves. Sacrificios showed lower fragmentation degree than Cabezo; in both cases, the vegetation cover fragmentation corresponded to less than 50 %. Although Cabezo reef presents further fragmentation, which creates a large number of microenvironments, being recognized for its importance as recruitment area. This work serves as a baseline for the creation of an adequate management plan (formation of a core area of Cabezo). It is necessary to complement this work with new efforts for the recognition of seagrass prairies in all PNSAV reefs, as well as periodic monitoring and recognition of ecosystem services. Rev. Biol. Trop. 64 (2): 427-448. Epub 2016 June 01.
Assuntos
Hydrocharitaceae/classificação , Dinâmica Populacional , Densidade Demográfica , Conservação dos Recursos Naturais , Recifes de Corais , MéxicoRESUMO
Phylogeographic studies inform about routes of pathogen dissemination and are instrumental for improving import/export controls. Genomes of 17 isolates of the bacterial wilt and potato brown rot pathogen Ralstonia solanacearum race 3 biovar 2 (R3bv2), a Select Agent in the United States, were thus analyzed to get insight into the phylogeography of this pathogen. Thirteen of fourteen isolates from Europe, Africa, and Asia were found to belong to a single clonal lineage while isolates from South America were genetically diverse and tended to carry ancestral alleles at the analyzed genomic loci consistent with a South American origin of R3bv2. The R3bv2 isolates share a core repertoire of 31 type III-secreted effector genes representing excellent candidates to be targeted with resistance genes in breeding programs to develop durable disease resistance. Toward this goal, 27 R3bv2 effectors were tested in eggplant, tomato, pepper, tobacco, and lettuce for induction of a hypersensitive-like response indicative of recognition by cognate resistance receptors. Fifteen effectors, eight of them core effectors, triggered a response in one or more plant species. These genotypes may harbor resistance genes that could be identified and mapped, cloned, and expressed in tomato or potato, for which sources of genetic resistance to R3bv2 are extremely limited.
Assuntos
Genômica , Doenças das Plantas/microbiologia , Ralstonia solanacearum/genética , Solanum tuberosum/microbiologia , África , Ásia , Capsicum/imunologia , Capsicum/microbiologia , Resistência à Doença , Europa (Continente) , Variação Genética , Lactuca/imunologia , Lactuca/microbiologia , Solanum lycopersicum/imunologia , Solanum lycopersicum/microbiologia , Filogeografia , Doenças das Plantas/imunologia , Ralstonia solanacearum/patogenicidade , Solanum melongena/genética , Solanum melongena/imunologia , Solanum tuberosum/imunologia , América do Sul , VirulênciaRESUMO
Currently, it is still unclear how to translate effectively programs validated in research for use in real-world contexts. Among the efforts being made to identify strategies which optimize the application of these programs in everyday practice are tests of the differential effectiveness of the programs depending on the application agent. Method: this study analyses the effects of two programs on alcohol use and its variables as a function of provider type. Two hundred students from the first year of secondary education were distributed among five experimental conditions: four treatment conditions, in which the two programs were applied by teachers at the school or external psychologists, and a control condition. Results: the results suggest that, for both programs, teachers obtain better outcomes in alcohol use and concern about addiction. Conclusions: it is concluded that teachers are the ideal application agents in terms of efficiency, and we discuss the implications for research and preventive practice.
En la actualidad no es claro cómo traducir efectivamente los programas validados en la investigación para su aplicación en contextos reales. Entre los esfuerzos que se han realizado está el de identificar estrategias que optimicen la aplicación de estos programas en la práctica cotidiana que tienen diferente efectividad dependiendo del agente que los aplique. Metodología: este estudio analiza los efectos de dos programas sobre el consumo de alcohol y sus variables en función del aplicador. Doscientos estudiantes de primer año de secundaria se distribuyeron en cinco condiciones experimentales: cuatro en condición de tratamiento, en que se aplicaron dos programas aplicados por profesores de la escuela o psicólogos externos, y un grupo control. Resultados: los hallazgos sugieren que en los dos programas los profesores obtienen mejores resultados sobre el consumo de alcohol y la preocupación por la adicción. Conclusiones: se concluye que los profesores son los agentes aplicadores ideales en términos de eficiencia y discutimos las implicaciones que esto tiene para la práctica investigativa y práctica.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Avaliação de Eficácia-Efetividade de Intervenções , Serviços Preventivos de Saúde , Avaliação de Resultado de Intervenções Terapêuticas , Alcoolismo/prevenção & controleRESUMO
INTRODUCCIÓN: la terapia con antirretrovirales ha tenido un gran impacto en la calidad de vida de las personas que viven con VIH/SIDA. Los pacientes tratados con estos fármacos necesitan una vigilancia estricta debido a sus efectos tóxicos. MÉTODOS: se realizó un estudio de 50 pacientes VIH/SIDA con tratamiento antirretroviral, atendidos en el hospital Dr. Juan Bruno Zayas entre mayo y septiembre del 2011. Se determinó la variación de parámetros hemato-bioquímicos que incluyeron estudios de perfil lipídico, hemático y renal. RESULTADOS: las mayores afectaciones de los lípidos estuvieron en los pacientes del esquema Rescate. Todos los esquemas mostraron alteraciones de las proteínas totales, la microalbuminuria y la mayoría de los pacientes de los esquemas 4, 1 y Rescate presentaron anemia. Los pacientes estudiados presentaron alteraciones discretas de los parámetros analizados, CONCLUSIONES: la toxicidad de los tratamientos aplicados está por debajo de la reportada en otras investigaciones.
INTRODUCTION: Antiretroviral therapy has had a great impact on the quality of life of people living with HIV/AIDS, but these drugs require strict surveillance due to their toxic effects. METHODS: A study was conducted of 50 HIV/AIDS patients under antiretroviral treatment cared for at Dr. Juan Bruno Zayas hospital from May to September 2011. Determination was performed of variations in hematochemical parameters, including lipid profiles and hematological and renal studies. RESULTS: Most alterations in lipids were found in patients from the Rescue scheme. All schemes showed alterations in total proteins and microalbuminuria, whereas most patients in Schemes 4, 1 and Rescue had anemia. The patients studied presented moderate alterations of the parameters analyzed. CONCLUSIONS: Toxicity of the treatments applied is below that reported by other studies.
Assuntos
Humanos , Síndrome da Imunodeficiência Adquirida , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Testes Hematológicos/métodosRESUMO
The aim of the present study was to analyze: (a) the relationship between alcohol and tobacco use and academic performance, and (b) the predictive role of psycho-educational factors and alcohol and tobacco abuse on academic performance in a sample of 352 Spanish adolescents from grades 8 to 10 of Compulsory Secondary Education. The Self-Description Questionnaire-II, the Sydney Attribution Scale, and the Achievement Goal Tendencies Questionnaire were administered in order to analyze cognitive-motivational variables. Alcohol and tobacco abuse, sex, and grade retention were also measured using self-reported questions. Academic performance was measured by school records. Frequency analyses and logistic regression analyses were used. Frequency analyses revealed that students who abuse of tobacco and alcohol show a higher rate of poor academic performance. Logistic regression analyses showed that health behaviours, and educational and cognitive-motivational variables exert a different effect on academic performance depending on the academic area analyzed. These results point out that not only academic, but also health variables should be address to improve academic performance in adolescence.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Cognição , Escolaridade , Motivação , Uso de Tabaco/epidemiologia , Uso de Tabaco/psicologia , Adolescente , Estudos Transversais , Feminino , Humanos , Masculino , Instituições Acadêmicas , Espanha/epidemiologia , Inquéritos e QuestionáriosRESUMO
New diagnostics are presented that use a digital camera to measure full-field soot temperatures and soot volume fractions in axisymmetric flames. The camera is a Nikon D700 with 12 megapixels and 14 bit depth in each color plane, which was modified by removing the infrared and anti-aliasing filters. The diagnostics were calibrated with a blackbody furnace. The flame considered here was an 88 mm long ethylene/air co-flowing laminar jet diffusion flame on a round 11.1 mm burner. The resolution in the flame plane is estimated at between 0.1 and 0.7 mm. Soot temperatures were measured from soot radiative emissions, using ratio pyrometry at 450, 650, and 900 nm following deconvolution. These had a range of 1600-1850 K, a temporal resolution of 125 ms, and an estimated uncertainty of ±50 K. Soot volume fractions were measured two ways: from soot radiative emissions and from soot laser extinction at 632.8 nm, both following deconvolution. Soot volume fractions determined from emissions had a range of 0.1-10 ppm, temporal resolutions of 125 ms, and an estimated uncertainty of ±30%. Soot volume fractions determined from laser extinction had a range of 0.2-10 ppm, similar temporal resolutions, and an estimated uncertainty of ±10%. The present measurements agree with past measurements in this flame using traversing optics and probes; however, they avoid the long test times and other complications of such traditional methods.
RESUMO
Poly(ethylene glycol) (PEG) side-chain functionalized lactide analogues have been synthesized in four steps from commercially available L-lactide. The key step in the synthesis is the 1,3-dipolar cycloaddition between PEG-azides and a highly strained spirolactide-heptene monomer, which proceeds in high conversions. The PEG-grafted lactides analogues were polymerized via ring-opening polymerization using triazacyclodecene as organocatalyst to give well-defined tri- and hepta-(ethylene glycol)-poly(lactide)s (PLA) with molecular weights above 10 kDa and polydispersity indices between 1.6 and 2.1. PEG-poly(lactide) (PLA) with PEG chain M(n) 2000 was also prepared but GPC analysis showed a bimodal profile indicating the presence of starting macromonomer. Cell adhesion assays were performed using MC3T3 E-1 osteoblast-like cells demonstrating that PEG-containing PLA reduces cell adhesion significantly when compared to unfunctionalized PLA.
RESUMO
O objetivo deste estudo é avaliar o papel da autorregulação desenvolvimental na adolescência como fator diferenciador do consumo de tabaco e álcool. Para isso, foi utilizada uma amostra de 407 alunos do Ensino Médio, avaliada com o recurso a um conjunto de questões sobre o consumo destas substâncias e ao Inventário de Autorregulação Adolescente (Moilanen, 2007), um instrumento baseado na teoria desenvolvimental sobre a autorregulação. Os resultados sugerem que a autorregulação é um fator diferenciador entre adolescentes que consomem, ou não, substâncias e a intensidade deste consumo. Adolescentes que consomem tendem a apresentar, consistentemente, pontuações mais baixas na autorregulação a curto e longo-prazo. As limitações e implicações dos resultados são apresentadas e discutidas.
The purpose of this study is to evaluate the role of developmental self-regulation in adolescence as a differentiating factor of tobacco and alcohol use. It was used a sample of 407 high school students, assessed with a number of questions about such substances use and the Adolescent Self-regulatory Inventory (Moilanen, 2007), a developmentally based measure about self-regulation. Results suggest that self-regulation is a differentiating factor between adolescents who use substances and those who not, and the intensity of consumption. Teenagers who use alcohol and tobacco seem to present consistently lower scores in short and long-term self-regulation. The limitations and implications of the results are presented and discussed.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Comportamento do Adolescente/psicologia , Consumo de Bebidas Alcoólicas/psicologia , Fumar/psicologia , Intenção , Desenvolvimento do Adolescente , Ensino Fundamental e MédioRESUMO
In silico simulation based on Markov chains is a powerful way to describe and predict the activity of many transport proteins including ion channels. However, modeling and simulation using realistic models of voltage- or ligand-gated ion channels exposed to a wide range of experimental conditions require building complex kinetic schemes and solving complicated differential equations. To circumvent these problems, we developed IonChannelLab a software tool that includes a user-friendly Graphical User Interface and a simulation library. This program supports channels with Ohmic or Goldman-Hodgkin-Katz behavior and can simulate the time-course of ionic and gating currents, single channel behavior and steady-state conditions. The program allows the simulation of experiments where voltage, ligand and ionic concentration are varied independently or simultaneously.
Assuntos
Simulação por Computador , Canais Iônicos/metabolismo , Modelos Moleculares , Software , Ativação do Canal Iônico , Cinética , Canais Iônicos de Abertura Ativada por Ligante/metabolismo , Cadeias de Markov , Interface Usuário-ComputadorRESUMO
Iminosugars are monosaccharide analogues that have been demonstrated to be specific inhibitors for glycosidases and are currently used therapeutically in several human disorders. N-alkylated derivatives of D-fagomine and (2R,3S,4R,5S)-2-(hydroxymethyl)-5-methylpyrrolidine-3,4-diol with aliphatic chains were tested in eight human cancer cell lines to analyze their cytotoxicity and the inhibitory effect in the activities of specific glycosidases. Results indicate that these compounds were more cytotoxic as the length of the alkyl chain increases. N-dodecyl-D-fagomine inhibited specifically the alpha-D-glucosidase activity in cell lysates, whereas no effect was detected in other glycosidases. The N-dodecyl derivative of (2R,3S,4R,5S)-2-(Hydroxymethyl)-5-methylpyrrolidine-3,4-diol induced specific inhibition against alpha-L-fucosidase in cell lysates. Our results indicated that the length of the alkyl chain linked to the iminosugars determine their cytotoxicity as well as the inhibitory effect on the enzymatic activities of specific glycosidases, in human cancer cell lines.
Assuntos
Glicosídeo Hidrolases/antagonistas & inibidores , Imino Piranoses/farmacologia , Pirrolidinas/farmacologia , Morte Celular/efeitos dos fármacos , Extratos Celulares , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glucosídeos/metabolismo , Glicosídeos/metabolismo , Humanos , Imino Piranoses/química , Fenótipo , Pirrolidinas/químicaAssuntos
Canais de Cloreto/química , Canais de Cloreto/metabolismo , Sítios de Ligação , Canais de Cloro CLC-2 , Canais de Cloreto/genética , Cistationina beta-Sintase/química , Humanos , Técnicas In Vitro , Ativação do Canal Iônico , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
Pseudomonas syringae causes plant diseases, and the main virulence mechanism is a type III secretion system (T3SS) that translocates dozens of effector proteins into plant cells. Here we report the existence of a subgroup of P. syringae isolates that do not cause disease on any plant species tested. This group is monophyletic and most likely evolved from a pathogenic P. syringae ancestor through loss of the T3SS. In the nonpathogenic isolate P. syringae 508 the genomic region that in pathogenic P. syringae strains contains the hrp-hrc cluster coding for the T3SS and flanking effector genes is absent. P. syringae 508 was also surveyed for the presence of effector orthologues from the closely related pathogenic strain P. syringae pv. syringae B728a, but none were detected. The absence of the hrp-hrc cluster and effector orthologues was confirmed for other nonpathogenic isolates. Using the AvrRpt2 effector as reporter revealed the inability of P. syringae 508 to translocate effectors into plant cells. Adding a plasmid-encoded T3SS and the P. syringae pv. syringae 61 effector gene hopA1 increased in planta growth almost 10-fold. This suggests that P. syringae 508 supplemented with a T3SS could be used to determine functions of individual effectors in the context of a plant infection, avoiding the confounding effect of other effectors with similar functions present in effector mutants of pathogenic isolates.
Assuntos
Proteínas de Bactérias/fisiologia , Proteínas de Transporte/fisiologia , DNA Bacteriano/genética , Pseudomonas syringae/patogenicidade , Fatores de Virulência/fisiologia , Arabidopsis/microbiologia , Proteínas de Bactérias/genética , Southern Blotting , Proteínas de Transporte/genética , Análise por Conglomerados , DNA Bacteriano/química , Deleção de Genes , Genoma Bacteriano , Dados de Sequência Molecular , Família Multigênica , Filogenia , Doenças das Plantas/microbiologia , Reação em Cadeia da Polimerase , Transporte Proteico , Pseudomonas syringae/crescimento & desenvolvimento , Pseudomonas syringae/isolamento & purificação , Pseudomonas syringae/metabolismo , Análise de Sequência de DNA , Nicotiana/microbiologia , Virulência , Fatores de Virulência/genéticaRESUMO
(-)-Epicatechin conjugates with sulfur-containing moieties are strong free radical scavengers with cell-protecting activities, which may be in part modulated by their capacity to bind to biological membranes. We present here a study of the interaction of these conjugates with membrane models such as multilamellar vesicles and a phospholipid-coated silica column (immobilized artificial membrane), monitored by differential scanning calorimetry and high-performance liquid chromatography, respectively. The nonpolyphenolic moiety significantly influenced the membrane behavior of the whole molecules. Bulky and hydrophobic conjugates clearly interacted with the phospholipids and may have a tendency to penetrate into the hydrophobic core of the vesicles. In contrast, the smaller cationic 4beta-(2-aminoethylthio)epicatechin may be located at the outer interface of the lipid membrane. The outcomes from both experimental set-ups were in good agreement. The differences detected in the biological activities of the conjugates may be explained in part by their tendency to penetrate the cell membrane.
Assuntos
Antioxidantes/metabolismo , Catequina/metabolismo , Membranas Artificiais , Varredura Diferencial de Calorimetria , Cromatografia Líquida de Alta Pressão , Lipossomos/metabolismo , Fosfolipídeos/metabolismoRESUMO
Se describe el caso de una paciente de 56 años de edad, que ingresó en el Servicio de Medicina Interna del Hospital Clinicoquirúrgico Juan Bruno Zayas por una emergencia hipertensiva (cefalea, vómitos, lenguaje disártrico, disminución de la fuerza muscular en hemicuerpo derecho y cifras de tensión arterial de 200/140 mm de Hg) y trastornos psicológicos; cuadro clínico que se inició días después de diagnosticarle el VIH/sida. A pesar de todos los esfuerzos realizados por mejorar su calidad de vida, fue remitida al Instituto de Medicina Tropical Pedro Kourí, donde falleció a causa de microsporidiosis renal, hepática, bronquial y vesical; enterocolitis inespecífica, gastritis aguda con ligera hemorragia difusa, hipertrofia concéntrica del ventrículo izquierdo por probable estenosis mitral y bronconeumonía focal