Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
1.
Pathogens ; 11(11)2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36364996

RESUMEN

Dynamic post-translational modifications allow the rapid, specific, and tunable regulation of protein functions in eukaryotic cells. S-acylation is the only reversible lipid modification of proteins, in which a fatty acid, usually palmitate, is covalently attached to a cysteine residue of a protein by a zDHHC palmitoyl acyltransferase enzyme. Depalmitoylation is required for acylation homeostasis and is catalyzed by an enzyme from the alpha/beta hydrolase family of proteins usually acyl-protein thioesterase (APT1). The enzyme responsible for depalmitoylation in Trypanosoma brucei parasites is currently unknown. We demonstrate depalmitoylation activity in live bloodstream and procyclic form trypanosomes sensitive to dose-dependent inhibition with the depalmitoylation inhibitor, palmostatin B. We identified a homologue of human APT1 in Trypanosoma brucei which we named TbAPT-like (TbAPT-L). Epitope-tagging of TbAPT-L at N- and C- termini indicated a cytoplasmic localization. Knockdown or over-expression of TbAPT-L in bloodstream forms led to robust changes in TbAPT-L mRNA and protein expression but had no effect on parasite growth in vitro, or cellular depalmitoylation activity. Esterase activity in cell lysates was also unchanged when TbAPT-L was modulated. Unexpectedly, recombinant TbAPT-L possesses esterase activity with specificity for short- and medium-chain fatty acid substrates, leading to the conclusion, TbAPT-L is a lipase, not a depalmitoylase.

2.
J Exp Clin Cancer Res ; 40(1): 321, 2021 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-34654437

RESUMEN

Chronic Lymphocytic Leukemia (CLL) is a hematological malignancy characterized by uncontrolled proliferation of B-cells and severe immune dysfunction. Chemo(immuno)therapies (CIT) have traditionally aimed to reduce tumor burden without fully understanding their effects on the immune system. As a consequence, CIT are usually associated with higher risk of infections, secondary neoplasms and autoimmune disorders. A better understanding of the biology of the disease has led to the development of therapeutic strategies which not only act against malignant B-cells but also reactivate and enhance the patient's own anti-tumor immune response. Here, we review the current understanding of the underlying interplay between the malignant cells and non-malignant immune cells that may promote tumor survival and proliferation. In addition, we review the available evidence on how different treatment options for CLL including CIT regimens, small molecular inhibitors (i.e, BTK inhibitors, PI3K inhibitors, BCL-2 inhibitors) and T-cell therapies, affect the immune system and their clinical consequences. Finally, we propose that a dual therapeutic approach, acting directly against malignant B-cells and restoring the immune function is clinically relevant and should be considered when developing future strategies to treat patients with CLL.


Asunto(s)
Inmunoterapia/métodos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Humanos
3.
Clin Lymphoma Myeloma Leuk ; 21(12): e985-e999, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34511320

RESUMEN

BACKGROUND: Ibrutinib demonstrated remarkable efficacy and favorable tolerability in patients with untreated or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including those with high-risk genetic alterations. The IBRORS-CLL study assessed the characteristics, clinical management and outcome of CLL patients receiving ibrutinib in routine clinical practice in Spain. PATIENTS: Observational, retrospective, multicenter study in CLL patients who started single-agent ibrutinib as first-line treatment or at first or second relapse between January 2016 and January 2019. RESULTS: A total of 269 patients were included (median age: 70.9 years; cardiovascular comorbidity: 55.4%, including hypertension [47.6%] and atrial fibrillation [AF] [7.1%]). Overall, 96.7% and 69% of patients underwent molecular testing for del(17p)/TP53 mutation and IGHV mutation status. High-risk genetic features included unmutated IGHV (79%) and del(17p)/TP53 mutation (first-line: 66.3%; second-line: 23.1%). Overall, 84 (31.2%) patients received ibrutinib as first-line treatment, and it was used as second- and third-line therapy in 121 (45.0%) and 64 (23.8%) patients. The median progression-free survival and overall survival were not reached irrespective of del(17p)/TP53, or unmutated IGHV. Common grade ≥3 adverse events were infections (12.2%) and bleeding (3%). Grade ≥3 AF occurred in 1.5% of patients. CONCLUSION: This real-world study shows that single-agent ibrutinib is an effective therapy for CLL, regardless of age and high-risk molecular features, consistent with clinical trials. Additionally, single-agent ibrutinib was well tolerated, with a low rate of cardiovascular events. This study also emphasized a high molecular testing rate of del(17p)/TP53 mutation and IGHV mutation status in clinical practice according to guideline recommendations.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Adenina/análogos & derivados , Anciano , Humanos , Piperidinas , Pirazoles/efectos adversos , Pirimidinas/efectos adversos , Estudios Retrospectivos , España/epidemiología
4.
Ann Hematol ; 100(3): 825-830, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33409623

RESUMEN

Among the different biomarkers predicting response in chronic lymphocytic leukemia (CLL), the most influential parameters are the mutational status of the IGHV genes and the presence of TP53 gene disruptions. Nevertheless, these important assessments are not readily available in most centers dealing with CLL patients. To provide this molecular testing across the country, the Spanish Cooperative Group on CLL (GELLC) established a network of four analytical reference centers. A total of 2153 samples from 256 centers were analyzed over a period of 30 months. In 9% of the patients, we found pathological mutations in the TP53 gene, whereas 48.96% were classified as IGHV unmutated. Results of the satisfaction survey of the program showed a Net Promoter Score of 85.15. Building a national network for molecular testing in CLL allowed the CLL population a broad access to complex biomarkers analysis that should translate into a more accurate and informed therapeutic decision-making.


Asunto(s)
Servicios de Laboratorio Clínico/organización & administración , Análisis Mutacional de ADN , Cadenas Pesadas de Inmunoglobulina/genética , Leucemia Linfocítica Crónica de Células B/genética , Derivación y Consulta/organización & administración , Proteína p53 Supresora de Tumor/genética , Biomarcadores de Tumor/genética , Servicios de Laboratorio Clínico/provisión & distribución , Estudios de Cohortes , Redes Comunitarias/organización & administración , Análisis Mutacional de ADN/métodos , Humanos , Ciencia de la Implementación , Colaboración Intersectorial , Satisfacción en el Trabajo , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/epidemiología , Técnicas de Diagnóstico Molecular/métodos , Mutación , Pronóstico , España/epidemiología , Encuestas y Cuestionarios
5.
Oecologia ; 190(3): 605-617, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31197480

RESUMEN

Indirect interactions among plant species mediated by frugivorous animals can be central to population and community dynamics, since the successful seed dispersal of species may depend on facilitative or competitive interactions with heterospecific plants. Yet, empirical evidence on these interactions is very scarce and mostly available at small spatial scales, within populations. Because lipid-rich fruits are known to be preferred by migratory birds, here we test our prediction of competitive inferiority of a carbohydrate-rich fruited species (the hawthorn Crataegus monogyna) compared to lipid-rich co-fruiting species in a Mediterranean region where the bulk of seed dispersal relies on migratory birds. We assessed avian seed dispersal in both relative (fruit removal rate) and absolute terms (seed dispersal magnitude) in seven hawthorn populations distributed across an altitudinal gradient encompassing three contrasting fruiting contexts: hawthorn is scarce in the lowlands, common in the midlands, and the dominant fruit species in the highlands. We found evidence of seed dispersal reduction due to interspecific competition in the lowland populations, where lipid-rich fruits dominate. Besides, DNA barcoding analysis of bird-dispersed seeds revealed that only a small subset of the local frugivore assemblages consumed hawthorn fruits in the lowland communities. Instead, the consumers of hawthorn fruits resembled the local frugivore assemblages where hawthorn fruits were more dominant and frugivore choices more limited. Our study suggests mechanisms by which the rarity or dominance of plant species might be jointly influenced by environmental constraints (here, precipitation along the altitudinal gradient) and frugivore-mediated indirect interactions among plants hindering or facilitating seed dispersal.


Asunto(s)
Dispersión de Semillas , Animales , Aves , Conducta Alimentaria , Frutas , Herbivoria
6.
Chembiochem ; 20(7): 886-890, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30561884

RESUMEN

Inverse-electron-demand Diels-Alder (iEDDA) cycloaddition between 1,2,4,5-tetrazines and strained dienophiles belongs among the most popular bioconjugation reactions. In addition to its fast kinetics, this cycloaddition can be tailored to produce fluorescent products from non-fluorescent starting materials. Here we show that even the reaction intermediates formed in iEDDA cycloaddition can lead to the formation of new types of fluorophores. The influence of various substituents on their photophysical properties and the generality of the approach with use of various trans-cyclooctene derivatives were studied. Model bioimaging experiments demonstrate the application potential of fluorogenic iEDDA cycloaddition.


Asunto(s)
Ciclooctanos/química , Colorantes Fluorescentes/química , Compuestos Heterocíclicos con 1 Anillo/química , Reacción de Cicloadición , Colorantes Fluorescentes/síntesis química , Células HeLa , Compuestos Heterocíclicos con 2 Anillos/síntesis química , Compuestos Heterocíclicos con 2 Anillos/química , Humanos , Microscopía Confocal/métodos , Microscopía Fluorescente/métodos
7.
Rev Bras Ter Intensiva ; 29(2): 213-221, 2017.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-28977261

RESUMEN

OBJECTIVE: The aim of this pilot study was to evaluate the feasibility of surface electromyographic signal derived indexes for the prediction of weaning outcomes among mechanically ventilated subjects after cardiac surgery. METHODS: A sample of 10 postsurgical adult subjects who received cardiovascular surgery that did not meet the criteria for early extubation were included. Surface electromyographic signals from diaphragm and ventilatory variables were recorded during the weaning process, with the moment determined by the medical staff according to their expertise. Several indexes of respiratory muscle expenditure from surface electromyography using linear and non-linear processing techniques were evaluated. Two groups were compared: successfully and unsuccessfully weaned patients. RESULTS: The obtained indexes allow estimation of the diaphragm activity of each subject, showing a correlation between high expenditure and weaning test failure. CONCLUSION: Surface electromyography is becoming a promising procedure for assessing the state of mechanically ventilated patients, even in complex situations such as those that involve a patient after cardiovascular surgery.


OBJETIVO: Avaliar a viabilidade do uso de índices derivados do sinal de eletromiografia de superfície para predizer desfechos do processo de desmame em pacientes mecanicamente ventilados após cirurgia cardíaca. MÉTODOS: Foram incluídos dez pacientes em pós-operatório de cirurgia cardiovascular que não cumpriram os critérios para extubação precoce. Os sinais da eletromiografia de superfície foram registrados, assim como as variáveis ventilatórias durante o processo de desmame, sendo o momento do procedimento determinado pela equipe médica, segundo sua experiência. Avaliaram-se diversos índices da atividade dos músculos respiratórios obtidos a partir da eletromiografia de superfície com uso de técnicas de processamento lineares e não lineares. Compararam-se dois grupos: pacientes com e sem sucesso no desmame. RESULTADOS: Os índices obtidos permitiram estimar a atividade diafragmática de cada paciente, demonstrando uma correlação entre atividade elevada e falha do teste de desmame. CONCLUSÃO: A eletromiografia de superfície está se tornando um procedimento promissor para avaliar as condições de pacientes ventilados mecanicamente, mesmo em condições complexas, como as que envolvem aqueles após cirurgia cardiovascular.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Electromiografía/métodos , Respiración Artificial/métodos , Desconexión del Ventilador/métodos , Adulto , Anciano , Extubación Traqueal , Diafragma/fisiología , Estudios de Factibilidad , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto
8.
Rev Bras Ter Intensiva ; 29(2): 253-258, 2017.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-28977266

RESUMEN

This study aimed to explore the usefulness of measuring respiratory muscle activity in mechanically ventilated patients suffering from acute organophosphate poisoning, with a view towards providing complementary information to determine the best time to suspend ventilatory support. Surface electromyography in respiratory muscles (diaphragm, external intercostal and sternocleidomastoid muscles) was recorded in a young man affected by self-poisoning with an unknown amount of parathion to determine the muscle activity level during several weaning attempts from mechanical ventilation. The energy distribution of each surface electromyography signal frequency, the synchronization between machine and patient and between muscles, acetylcholinesterase enzyme activity, and work of breathing and rapid shallow breathing indices were calculated in each weaning attempt. The work of breathing and rapid shallow breathing indices were not correlated with the failure/success of the weaning attempt. The diaphragm gradually increased its engagement with ventilation, achieving a maximal response that correlated with successful weaning and maximal acetylcholinesterase enzyme activity; in contrast, the activity of accessory respiratory muscles showed an opposite trend.


Este estudo teve como objetivo explorar a utilidade da avaliação da atividade muscular respiratória em pacientes em uso de ventilação mecânica após envenenamento agudo por organofosforados, para fornecer informações complementares para determinação do melhor momento para suspensão do suporte ventilatório. Foi registrada eletromiografia de superfície em músculos respiratórios (diafragma, intercostais externos e esternocleidomastóideos) em um homem jovem afetado por autoenvenenamento com quantidade desconhecida de paration, para determinar o nível de atividade muscular no decurso de diversas tentativas de desmame da ventilação mecânica. A distribuição de energia de cada frequência de sinal de eletromiografia de superfície; a sincronização entre máquina, paciente e músculos; a atividade da enzima acetilcolinesterase; o trabalho respiratório e os índices de respiração rápida e superficial foram calculados em cada uma das tentativas de desmame. O trabalho respiratório e o índice de respiração rápida e superficial não se correlacionaram com a falha ou o sucesso da tentativa de desmame. O diafragma aumentou gradualmente seu envolvimento com a ventilação, tendo alcançado resposta máxima, que se correlacionou com o sucesso do desmame e a atividade máxima da enzima acetilcolinesterase. Por outro lado, a atividade de músculos respiratórios acessórios mostrou tendência oposta.


Asunto(s)
Electromiografía/métodos , Intoxicación por Organofosfatos/terapia , Respiración Artificial/métodos , Desconexión del Ventilador , Acetilcolinesterasa/metabolismo , Adulto , Humanos , Masculino , Respiración , Músculos Respiratorios/fisiología
9.
J Crit Care ; 41: 260-267, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28599200

RESUMEN

PURPOSE: We present a new electromyographic index, named Engagement of Respiratory Muscle (ERM), for assessing the level of participation of respiratory muscles during spontaneous breathing test in patients poisoned with organophosphorus compound. METHODS: Diaphragm and sternocleidomastoid muscles activity was recorded by surface electromyography during spontaneous breathing test. A population of 23 patients poisoned with organophosphates and mechanically ventilated, and a control group of 28 healthy subjects were analyzed. RESULTS: All patients developed respiratory failure and 48% were diagnosed with intermediate syndrome by medical staff. The ERM index classified the patients in three clusters (p-value<0.005): Cluster I presented more engagement of the sternocleidomastoid compared to diaphragm, Cluster II had low muscle engagement of both muscles and also muscle weakness, Cluster III were characterized for the diaphragm recovery associated with higher engagement. The control group showed a similar muscle engagement to Cluster III. The capacity of ERM index for classifying patients with (sensitivity) and without (specificity) muscle weakness were 90.91% and 100% respectively. CONCLUSIONS: The ERM is a promising index to assess the level of participation of respiratory muscle on spontaneous breathing test in patients poisoned with organophosphorus compounds, which could improve the extubation prognosis for these patients.


Asunto(s)
Electromiografía , Organofosfatos/toxicidad , Plaguicidas/toxicidad , Insuficiencia Respiratoria/fisiopatología , Músculos Respiratorios/fisiopatología , Desconexión del Ventilador , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/terapia , Sensibilidad y Especificidad
10.
Rev. bras. ter. intensiva ; 29(2): 213-221, abr.-jun. 2017. tab, graf
Artículo en Portugués | LILACS | ID: biblio-899502

RESUMEN

RESUMO Objetivo: Avaliar a viabilidade do uso de índices derivados do sinal de eletromiografia de superfície para predizer desfechos do processo de desmame em pacientes mecanicamente ventilados após cirurgia cardíaca. Métodos: Foram incluídos dez pacientes em pós-operatório de cirurgia cardiovascular que não cumpriram os critérios para extubação precoce. Os sinais da eletromiografia de superfície foram registrados, assim como as variáveis ventilatórias durante o processo de desmame, sendo o momento do procedimento determinado pela equipe médica, segundo sua experiência. Avaliaram-se diversos índices da atividade dos músculos respiratórios obtidos a partir da eletromiografia de superfície com uso de técnicas de processamento lineares e não lineares. Compararam-se dois grupos: pacientes com e sem sucesso no desmame. Resultados: Os índices obtidos permitiram estimar a atividade diafragmática de cada paciente, demonstrando uma correlação entre atividade elevada e falha do teste de desmame. Conclusão: A eletromiografia de superfície está se tornando um procedimento promissor para avaliar as condições de pacientes ventilados mecanicamente, mesmo em condições complexas, como as que envolvem aqueles após cirurgia cardiovascular.


ABSTRACT Objective: The aim of this pilot study was to evaluate the feasibility of surface electromyographic signal derived indexes for the prediction of weaning outcomes among mechanically ventilated subjects after cardiac surgery. Methods: A sample of 10 postsurgical adult subjects who received cardiovascular surgery that did not meet the criteria for early extubation were included. Surface electromyographic signals from diaphragm and ventilatory variables were recorded during the weaning process, with the moment determined by the medical staff according to their expertise. Several indexes of respiratory muscle expenditure from surface electromyography using linear and non-linear processing techniques were evaluated. Two groups were compared: successfully and unsuccessfully weaned patients. Results: The obtained indexes allow estimation of the diaphragm activity of each subject, showing a correlation between high expenditure and weaning test failure. Conclusion: Surface electromyography is becoming a promising procedure for assessing the state of mechanically ventilated patients, even in complex situations such as those that involve a patient after cardiovascular surgery.


Asunto(s)
Humanos , Masculino , Adulto , Anciano , Respiración Artificial/métodos , Desconexión del Ventilador/métodos , Electromiografía/métodos , Procedimientos Quirúrgicos Cardíacos , Diafragma/fisiología , Proyectos Piloto , Estudios de Factibilidad , Extubación Traqueal , Persona de Mediana Edad
11.
Rev. bras. ter. intensiva ; 29(2): 253-258, abr.-jun. 2017. tab, graf
Artículo en Portugués | LILACS | ID: biblio-899506

RESUMEN

RESUMO Este estudo teve como objetivo explorar a utilidade da avaliação da atividade muscular respiratória em pacientes em uso de ventilação mecânica após envenenamento agudo por organofosforados, para fornecer informações complementares para determinação do melhor momento para suspensão do suporte ventilatório. Foi registrada eletromiografia de superfície em músculos respiratórios (diafragma, intercostais externos e esternocleidomastóideos) em um homem jovem afetado por autoenvenenamento com quantidade desconhecida de paration, para determinar o nível de atividade muscular no decurso de diversas tentativas de desmame da ventilação mecânica. A distribuição de energia de cada frequência de sinal de eletromiografia de superfície; a sincronização entre máquina, paciente e músculos; a atividade da enzima acetilcolinesterase; o trabalho respiratório e os índices de respiração rápida e superficial foram calculados em cada uma das tentativas de desmame. O trabalho respiratório e o índice de respiração rápida e superficial não se correlacionaram com a falha ou o sucesso da tentativa de desmame. O diafragma aumentou gradualmente seu envolvimento com a ventilação, tendo alcançado resposta máxima, que se correlacionou com o sucesso do desmame e a atividade máxima da enzima acetilcolinesterase. Por outro lado, a atividade de músculos respiratórios acessórios mostrou tendência oposta.


ABSTRACT This study aimed to explore the usefulness of measuring respiratory muscle activity in mechanically ventilated patients suffering from acute organophosphate poisoning, with a view towards providing complementary information to determine the best time to suspend ventilatory support. Surface electromyography in respiratory muscles (diaphragm, external intercostal and sternocleidomastoid muscles) was recorded in a young man affected by self-poisoning with an unknown amount of parathion to determine the muscle activity level during several weaning attempts from mechanical ventilation. The energy distribution of each surface electromyography signal frequency, the synchronization between machine and patient and between muscles, acetylcholinesterase enzyme activity, and work of breathing and rapid shallow breathing indices were calculated in each weaning attempt. The work of breathing and rapid shallow breathing indices were not correlated with the failure/success of the weaning attempt. The diaphragm gradually increased its engagement with ventilation, achieving a maximal response that correlated with successful weaning and maximal acetylcholinesterase enzyme activity; in contrast, the activity of accessory respiratory muscles showed an opposite trend.


Asunto(s)
Humanos , Masculino , Adulto , Respiración Artificial/métodos , Desconexión del Ventilador , Electromiografía/métodos , Intoxicación por Organofosfatos/terapia , Acetilcolinesterasa/metabolismo , Respiración , Músculos Respiratorios/fisiología
12.
Am J Trop Med Hyg ; 96(5): 1097-1106, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28167602

RESUMEN

AbstractIn Cusco, Peru, and South America in general, there is a dearth of travelers' diarrhea (TD) data concerning the clinical features associated with enteropathogen-specific infections and destination-specific risk behaviors. Understanding these factors would allow travel medicine providers to tailor interventions to patients' risk profiles and travel destination. To characterize TD etiology, evaluate region-specific TD risk factors, and examine relationships between preventive recommendations and risk-taking behaviors among medium- to long-term travelers' from high-income countries, we conducted this case-case analysis using 7 years of prospective surveillance data from adult travelers' presenting with TD to a physician in Cusco. At the time of enrollment, participants provided a stool sample and answered survey questions about demographics, risk behaviors, and the clinical features of illness. Stool samples were tested for norovirus (NV), bacteria, and parasites using conventional methods. Data obtained were then analyzed using case-case methods. NV (14%), enterotoxigenic Escherichia coli (11%), and Campylobacter (9%), notably ciprofloxacin-resistant Campylobacter, were the most frequently identified pathogens among adults with TD. Coinfection with multiple enteropathogens occurred in 5% of cases. NV caused severe disease relative to other TD-associated pathogens identified, confining over 90% of infected individuals to bed. Destination-specific risk factors include consumption of the local beverage "chicha," which was associated with Cryptosporidium infection. Preventive interventions, such as vaccines, directed against these pathogens could significantly reduce the burden of TD.


Asunto(s)
Infecciones por Campylobacter/epidemiología , Diarrea/epidemiología , Infecciones por Escherichia coli/epidemiología , Gastroenteritis/epidemiología , Vigilancia en Salud Pública , Medicina del Viajero , Adolescente , Adulto , Anciano , Campylobacter/aislamiento & purificación , Infecciones por Campylobacter/diagnóstico , Infecciones por Campylobacter/microbiología , Diarrea/diagnóstico , Diarrea/microbiología , Diarrea/virología , Escherichia coli Enterotoxigénica/aislamiento & purificación , Infecciones por Escherichia coli/diagnóstico , Infecciones por Escherichia coli/microbiología , Femenino , Gastroenteritis/diagnóstico , Gastroenteritis/virología , Humanos , Persona de Mediana Edad , Norovirus/aislamiento & purificación , Perú/epidemiología , Asunción de Riesgos , Viaje
13.
Microbiologyopen ; 2(3): 447-58, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23533111

RESUMEN

An increasing abundance of Aphanizomenon ovalisporum in water bodies from diverse world regions has been reported in the last few years, with the majority of the isolated strains producing the toxin cylindrospermopsin (CYN), leading to a rise in ecological and health risks. The understanding of CYN synthesis is crucial in the control of CYN production. An amidinotransferase (AMDT) seems to be the first enzyme involved in the synthesis of CYN. In this study, we have cloned and overexpressed the aoaA gene from the constitutive CYN producer A. ovalisporum UAM-MAO. The recombinant purified AoaA was characterized, confirming that it is an l-arginine:glycine AMDT. It shows an optimal activity between 32 and 37°C, at pH from 8 to 9. The activity exhibits a mixed (ping-pong/sequential) kinetic mechanism, and is inhibited by the reaction product guanidine acetate (GAA) in a noncompetitive manner. Mg(2+) stimulates AoaA activity while Co(2+) and Mn(2+) inhibit it. AoaA conserves the critical residues of the catalytic site and substrate specificity of AMDTs, as the previously reported AMDT from Cylindrospermopsis raciborskii Cyr. Both proteins can be included in a new group of prokaryotic AMDTs involved in CYN production.


Asunto(s)
Amidinotransferasas/genética , Amidinotransferasas/metabolismo , Aphanizomenon/enzimología , Uracilo/análogos & derivados , Alcaloides , Amidinotransferasas/química , Amidinotransferasas/aislamiento & purificación , Secuencia de Aminoácidos , Aphanizomenon/genética , Aphanizomenon/metabolismo , Toxinas Bacterianas , Clonación Molecular , Análisis por Conglomerados , Secuencia Conservada , Toxinas de Cianobacterias , Activadores de Enzimas/metabolismo , Inhibidores Enzimáticos/metabolismo , Estabilidad de Enzimas , Expresión Génica , Concentración de Iones de Hidrógeno , Cinética , Metales/metabolismo , Datos de Secuencia Molecular , Filogenia , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Homología de Secuencia de Aminoácido , Temperatura , Uracilo/biosíntesis
14.
Med Biol Eng Comput ; 50(1): 79-89, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21698432

RESUMEN

Recently developed techniques allow the analysis of surface EMG in multiple locations over the skin surface (high-density surface electromyography, HDsEMG). The detected signal includes information from a greater proportion of the muscle of interest than conventional clinical EMG. However, recording with many electrodes simultaneously often implies bad-contacts, which introduce large power-line interference in the corresponding channels, and short-circuits that cause near-zero single differential signals when using gel. Such signals are called 'outliers' in data mining. In this work, outlier detection (focusing on bad contacts) is discussed for monopolar HDsEMG signals and a new method is proposed to identify 'bad' channels. The overall performance of this method was tested using the agreement rate against three experts' opinions. Three other outlier detection methods were used for comparison. The training and test sets for such methods were selected from HDsEMG signals recorded in Triceps and Biceps Brachii in the upper arm and Brachioradialis, Anconeus, and Pronator Teres in the forearm. The sensitivity and specificity of this algorithm were, respectively, 96.9 ± 6.2 and 96.4 ± 2.5 in percent in the test set (signals registered with twenty 2D electrode arrays corresponding to a total of 2322 channels), showing that this method is promising.


Asunto(s)
Electromiografía/métodos , Procesamiento de Señales Asistido por Computador , Adulto , Algoritmos , Humanos , Masculino , Músculo Esquelético/fisiología , Sensibilidad y Especificidad , Adulto Joven
15.
PLoS One ; 4(7): e6118, 2009 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-19568433

RESUMEN

BACKGROUND: Acute respiratory illnesses and influenza-like illnesses (ILI) are a significant source of morbidity and mortality worldwide. Despite the public health importance, little is known about the etiology of these acute respiratory illnesses in many regions of South America. In 2006, the Peruvian Ministry of Health (MoH) and the US Naval Medical Research Center Detachment (NMRCD) initiated a collaboration to characterize the viral agents associated with ILI and to describe the clinical and epidemiological presentation of the affected population. METHODOLOGY/PRINCIPAL FINDINGS: Patients with ILI (fever > or =38 degrees C and cough or sore throat) were evaluated in clinics and hospitals in 13 Peruvian cities representative of the four main regions of the country. Nasal and oropharyngeal swabs, as well as epidemiological and demographic data, were collected from each patient. During the two years of this study (June 2006 through May 2008), a total of 6,835 patients, with a median age of 13 years, were recruited from 31 clinics and hospitals; 6,308 were enrolled by regular passive surveillance and 527 were enrolled as part of outbreak investigations. At least one respiratory virus was isolated from the specimens of 2,688 (42.6%) patients, with etiologies varying by age and geographical region. Overall the most common viral agents isolated were influenza A virus (25.1%), influenza B virus (9.7%), parainfluenza viruses 1, 2, and 3, (HPIV-1,-2,-3; 3.2%), herpes simplex virus (HSV; 2.6%), and adenoviruses (1.8%). Genetic analyses of influenza virus isolates demonstrated that three lineages of influenza A H1N1, one lineage of influenza A H3N2, and two lineages of influenza B were circulating in Peru during the course of this study. CONCLUSIONS: To our knowledge this is the most comprehensive study to date of the etiologic agents associated with ILI in Peru. These results demonstrate that a wide range of respiratory pathogens are circulating in Peru and this fact needs to be considered by clinicians when treating patients reporting with ILI. Furthermore, these data have implications for influenza vaccine design and implementation in South America.


Asunto(s)
Gripe Humana/epidemiología , Vigilancia de Guardia , Animales , Secuencia de Bases , Línea Celular , Cartilla de ADN , Brotes de Enfermedades , Humanos , Gripe Humana/virología , Personal Militar , Orthomyxoviridae/clasificación , Orthomyxoviridae/genética , Orthomyxoviridae/aislamiento & purificación , Perú/epidemiología , Filogenia , ARN Viral/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
16.
rev. viernes med ; 32(2): 7-23, jul. 2007. tab, graf
Artículo en Español | LIPECS | ID: biblio-1112564

RESUMEN

Se evaluaron las características clínicas y la escala económico funcional 8prolo) en un estudio retrospectivo de 207 pacientes con hernia de núcleo pulposo lumbar tratados quirúrgicamente (69 pacientes), comparándolos con los tratados médicamente (138 pacientes) y con seguimiento de dos años, en el Hospital de la Fuerza Aérea Peruana situado en Lima. No hubo diferencia estadísticamente significativa entre ambos grupos respecto a edad, sexo, ocupación, grado de esfuerzo habitual, obesidad, tabaquismo y trastornos psicosociales. Hubo diferencia estadística en la sintomatología presente en el tiempo del diagnóstico: lumbociatalgia, signo de Lasègue, trastorno moto y herniación del disco L4-L5 que fueron más frecuentes en los tratados quirúrgicamente; y la lumbalgia y herniación del disco L5-S1, que fueron más frecuentes en los tratados médicamente. Se empleó la técnica de Love modificada y las complicaciones posoperatorias sumaron 29%. Hubo mayor alivio sintomatológico en el primer año con la terapia cruenta, pero en el segundo año dicho alivio no fue estadísticamente diferente con ambas terapias. La mejoría en la escala económico-funcional de Prolo fue similar en el primer año con ambos tratamientos pero en el segundo año el tratamiento médico mostró mejor evolución que el quirúrgico. También se observó que los trastornos motores son de recuperación lenta y muy posteriores a la recuperación de los síntomas. La tendencia moderna es que el tratamiento quirúrgico no es un método curativo, no detiene el proceso patológico que permitió la herniación y solamente proporciona alivio sintomático y funcional. En nuestro medio no tenemos estudios comparativos de tratamiento quirúrgico vs. médico a corto plazo que nos muestre este tipo de evaluación. Recomendamos realizar estudios prospectivos para tal efecto.


The clinical characteristics and the economic-functional Prolo Scale were evaluated in a comparative and retrospective study of 207 patients with herniated lumbar nucleus pulpous, in which 69 patients underwent surgery and 138 patients had medical treatment for 2 years art he Fuerza Aerea Peruana Hospital, in Lima. There was significant statistical difference between both groups regarding age, sex, occupation, regular effort degree, obesity, smoking and psychosocial disorders. However, there were differences in the present symptomatology of the diagnostic: lumbosciatic pain, Lasègue’s sign, motor disorders and herniated L4-L5 disc, which were more often in those underwent surgery; and low back pain and herniated L5-S1 disc, which were more often in those who had medical treatment. The modified Love technique was employed in the surgery group and the postoperative complications were 29%. The surgical treatment gave more symptomatological relief in the first year, but in the second year that relief was not statically different with both treatments, but in the second year, the medical treatment had better evolution than the surgical treatment. In addition, it was observed that the motor disorders had, a slow recovery and very long after the recovery of the symptoms. The modern tendency is that the surgical treatment is not curative method, because it doesn’t stop the pathological process which allowed the origin of the hernia, it only gives symptomatic and functional relief. In our country there are not any studies about surgical versus medical treatment in short and long term which show us the kind of evaluation. For this reason, we recommend to make prospective studies.


Asunto(s)
Masculino , Femenino , Humanos , Desplazamiento del Disco Intervertebral , Desplazamiento del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/terapia , Región Lumbosacra , Epidemiología Descriptiva
17.
Am J Hypertens ; 18(3): 379-84, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15797657

RESUMEN

BACKGROUND: The objectives of this study were to characterize blood pressure (BP) in acute ischemic stroke and to determine its relationship with short-term functional outcome. METHODS: We examined 24-h BP recordings in 434 patients with ischemic stroke (lacunar stroke [LS], n = 205; non-lacunar stroke [NLS], n = 229) and in 178 normotensive subjects. Stroke severity was evaluated by the National Institutes of Health Stroke Scale (NIHSS). Patients found to be hypertensive on BP recordings on day 1 were given captopril or amlodipine. The primary outcome was both moderate-to-severe disability (Rankin scale scores 4 to 6) on day 7 or death during hospital stay. RESULTS: Patients with LS and NLS had significantly higher systolic BP (SBP) and diastolic BP levels than control subjects. On day 1, patients with NLS showed significantly higher NIHSS scores, SBP, and heart rate (HR) levels than LS patients. In the multivariate analysis, combined death or dependency was associated with NIHSS score (odds ratio [OR] = 1.08 per 1-point increase, 95% confidence interval [CI] = 1.04 to 1.13), 24-h SBP >160 mm Hg (OR = 2.35, 95% CI = 1.10 to 5.52), and plasma glucose levels >125 mg/dL on admission (OR = 1.88, 95% CI =1.03 to 3.57), whereas a decrease in SBP on day 7 (OR = 0.46, 95% CI = 0.24 to 0.88) was associated with better short-term outcome. CONCLUSIONS: At presentation, NLS patients showed higher BP levels than LS patients. Moderate reductions in BP during the first week after admission were associated with short-term functional improvement in patients with acute ischemic stroke.


Asunto(s)
Isquemia Encefálica/epidemiología , Hipertensión/diagnóstico , Hipertensión/epidemiología , Accidente Cerebrovascular/epidemiología , Enfermedad Aguda , Anciano , Presión Sanguínea , Monitores de Presión Sanguínea , Isquemia Encefálica/terapia , Femenino , Humanos , Hipertensión/terapia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/terapia
20.
J Stud Alcohol ; 63(2): 215-8, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12033698

RESUMEN

OBJECTIVE: Research indicates that Hispanic clients are less likely than non-Hispanic white (NHW) clients to attend Alcoholics Anonymous (AA) after treatment. This study examined how, if at all, the nature of commitment to prescribed AA-related behaviors after treatment differed between Hispanic and non-Hispanic whites, and how such behaviors were associated with drinking reductions. METHOD: This retrospective study was conducted using Project MATCH data collected at the Albuquerque clinical research unit. Study aims were investigated using the Form 90, the Alcoholics Anonymous Inventory and the Religious Background and Behavior measures. A total of 100 Hispanic and 105 non-Hispanic clients were randomized to receive either Cognitive Behavioral Therapy (CBT), Motivational Enhancement Therapy (MET) or Twelve-Step Facilitation (TSF) therapy, and findings were divided according to whether clients were encouraged to attend AA (TSF) or not (CBT and MET). RESULTS: Six months after treatment, Hispanic clients assigned to TSF reported significantly less AA attendance relative to NHW clients in TS, and no differences in AA attendance rates were found between Hispanics encouraged and not encouraged to attend AA (TSF vs CBT and MET). Among TSF clients, however, no ethnic differences were found in rates of specific AA-related behaviors. Controlling for intake beliefs, "God Consciousness" after treatment was significantly higher for Hispanic relative to NHW clients, and a main effect of treatment was also obtained (TSF vs CBT and MET). Specific AA-related practices were not associated with increased abstinence, in general. CONCLUSIONS: Despite less frequent AA attendance, Hispanic clients showed increase in AA commitment comparable to that of NHW clients. It thus appears that differential commitment to AA does not explain why Hispanic clients report less frequent AA attendance but equal benefit, relative to NHW clients.


Asunto(s)
Alcohólicos Anónimos , Hispánicos o Latinos/psicología , Centros de Tratamiento de Abuso de Sustancias , Población Blanca/psicología , Adulto , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Análisis de Varianza , Distribución de Chi-Cuadrado , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , Estudios Retrospectivos , Centros de Tratamiento de Abuso de Sustancias/estadística & datos numéricos , Encuestas y Cuestionarios , Población Blanca/estadística & datos numéricos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...