RESUMO
BACKGROUND: Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an excitatory neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid precursor proteins (APP), which are, in turn, relevant in the structural integrity of neurons. The present study provides preliminary evidence on the therapeutic potential of Phlogiellus bundokalbo venom against neurodegenerative diseases. METHODS: Spider venom was extracted by electrostimulation and fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was observed by a neurobehavioral response from Terebrio molitor larvae in vivo and fractions were screened for their inhibitory activities against AChE and BACE in vitro. RESULTS: The whole venom from P. bundokalbo demonstrated neuroactivity by inducing excitatory movements from T. molitor for 15 min. Sixteen fractions collected produced diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of sixteen fractions demonstrated AChE inhibitory activities with 14.34% (± 2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (± 3.90e-5) inhibition (p > 0.05), while none of the fractions were observed to exhibit BACE inhibition. Furthermore, three potent fractions against AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions compared to donepezil as the positive control. CONCLUSION: The venom of P. bundokalbo contains compounds that demonstrate neuroactivity and anti-AChE activities in vitro, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases.
RESUMO
Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an excitatory neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid precursor proteins (APP), which are, in turn, relevant in the structural integrity of neurons. The present study provides preliminary evidence on the therapeutic potential of Phlogiellus bundokalbo venom against neurodegenerative diseases. Methods Spider venom was extracted by electrostimulation and fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was observed by a neurobehavioral response from Terebrio molitor larvae in vivo and fractions were screened for their inhibitory activities against AChE and BACE in vitro. Results The whole venom from P. bundokalbo demonstrated neuroactivity by inducing excitatory movements from T. molitor for 15 min. Sixteen fractions collected produced diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of sixteen fractions demonstrated AChE inhibitory activities with 14.34% (± 2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (± 3.90e-5) inhibition (p > 0.05), while none of the fractions were observed to exhibit BACE inhibition. Furthermore, three potent fractions against AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions compared to donepezil as the positive control. Conclusion The venom of P. bundokalbo contains compounds that demonstrate neuroactivity and anti-AChE activities in vitro, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases.(AU)
Assuntos
Animais , Acetilcolinesterase , Venenos de Aranha/toxicidade , Neurotransmissores , Doenças Neurodegenerativas , Técnicas In VitroRESUMO
Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an excitatory neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid precursor proteins (APP), which are, in turn, relevant in the structural integrity of neurons. The present study provides preliminary evidence on the therapeutic potential of Phlogiellus bundokalbo venom against neurodegenerative diseases. Methods Spider venom was extracted by electrostimulation and fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was observed by a neurobehavioral response from Terebrio molitor larvae in vivo and fractions were screened for their inhibitory activities against AChE and BACE in vitro. Results The whole venom from P. bundokalbo demonstrated neuroactivity by inducing excitatory movements from T. molitor for 15 min. Sixteen fractions collected produced diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of sixteen fractions demonstrated AChE inhibitory activities with 14.34% (± 2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (± 3.90e-5) inhibition (p > 0.05), while none of the fractions were observed to exhibit BACE inhibition. Furthermore, three potent fractions against AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions compared to donepezil as the positive control. Conclusion The venom of P. bundokalbo contains compounds that demonstrate neuroactivity and anti-AChE activities in vitro, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases.(AU)
Assuntos
Animais , Acetilcolinesterase , Venenos de Aranha/toxicidade , Neurotransmissores , Doenças Neurodegenerativas , Técnicas In VitroRESUMO
In June 2009, the World Health Organization declared a novel influenza A, S-OIV (H1N1), pandemic. We observed 44 consecutive patients during the "first wave" of the pandemic. 70.5% of them showed co-morbidities (hypertension, obesity, chronic respiratory diseases, chronic renal disease, diabetes, pregnancy). Serious cases were admitted to the intensive care unit (ICU), particularly those with severe acute respiratory failure. Some of them developed acute kidney injury (AKI) and required renal replacement therapy (RRT). The average time between admission to the ICU and initiation of RRT was 3.16 ± 2.6 days. At initiation of RRT, most patients required mechanical ventilation. No relationship was found with creatinine-kinase levels. Seventy-five percent of the cases were observed during a 3-week period and mortality, related to respiratory failure, doubling of alanine amino transferase and use of inotropics was 81.8%. In conclusion, the H1N1-infected patients who developed RRT-requiring AKI, in the context of multi-organ failure, showed a high mortality rate. Thus, it is mandatory that elaborate strategies aimed at anticipating potential renal complications associated to future pandemics are implemented.
Assuntos
Injúria Renal Aguda/terapia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/epidemiologia , Influenza Humana/virologia , Pandemias , Diálise Renal , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/virologia , Adulto , Argentina/epidemiologia , Distribuição de Qui-Quadrado , Comorbidade , Cuidados Críticos , Feminino , Humanos , Influenza Humana/diagnóstico , Influenza Humana/mortalidade , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Respiração Artificial , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tempo para o Tratamento , Resultado do Tratamento , Adulto JovemRESUMO
En junio de 2009 la OMS declaró la pandemia por un nuevo virus de la Influenza A, S-OIV (H1N1). Casos severos fueron hospitalizados en UTI con falla respiratoria aguda. Alguno de estos casos desarrollaron injuria renal aguda y requirieron terapias de reemplazo renal (TRR). Durante el período de mayor incidencia observamos 44 casos consecutivos. 70,5% de estos presentaron comorbilidades (hipertensión, obesidad, enfermedades respiratorias crónicas, enfermedad renal crónica, diabetes, embarazo, otras). El tiempo promedio desde el ingreso a UTI y el comienzo de la TRR fue 3.16 +- 2.6 días. Al inicio de la TRR la mayoría de los pacientes presentaban SOFA score > - 10, presentando fallas cardiovascular y respiratoria. No hubo correlación con los niveles de CK. El 75% de los casos se observaron en un período de tres semanas de pandemia y un porcentaje alto presentaban aumento de enzimas hepáticas, necesidad de inotrópicos, ventilación mecánica y la mortalidad fue superior al 80%. En resumen, los pacientes infectados con S-OIV (H1N1) que requirieron TRR en contexto de falla multiparenquimatosa, presentaron una alta tasa de mortalidad. La experiencia dejada puede ayudarnos a desarrollar estrategias para anticipar potenciales complicaciones renales en futuras pandemias.
Assuntos
Injúria Renal Aguda , Vírus da Influenza A Subtipo H1N1RESUMO
The aim of this study was to evaluate the effects of electromyographic biofeedback training in chronically constipated patients with dyssynergic defecation. With this purpose, ten patients (4 males, 6 females) with dyssynergic defecation unresponsive to dietary corrections and fibre supplements were selected and enclosed in the study on the basis of fulfilled the Rome III criteria for this functional gastrointestinal disorder. The study was carried out following a series of defined phases: clinical and psychophysiological assessment prior to the treatment (4 weeks), EMG-biofeedback treatment (8 sessions, two per week) and follow-up (4 weeks) one month later. In all phases, four clinical variables were assessed through selfmonitoring (frequency of defecations per week, sensation of incomplete evacuation, difficulty evacuation level, and perianal pain at defecation); moreover, psychophysiological measures were obtained through electromyography (EMG) of the external anal sphincter. Results show significant improvements in psychophysiological measures (EMGactivity during straining to defecate and anismus index), as well as in clinical variables. Biofeedback's benefits were maintained at the follow-up period.
El objetivo de este estudio fue evaluar los efectos del entrenamiento en biofeedback-EMG en pacientes con estreñimiento crónico debido a defecación disinérgica. Con este propósito, 10 pacientes (4 varones, 6 mujeres) con defecación disinérgica que no respondían a correcciones dietéticas y suplementos de fibra, fueron seleccionados e incluidos en el estudio sobre la base de cumplir los criterios Roma III para el diagnóstico de este trastorno funcional gastrointestinal. El estudio se llevó a cabo a lo largo de una serie de fases definidas: evaluación psicofisiológica y clínica previa al tratamiento (4 semanas), tratamiento por medio de biofeedback-EMG (8 sesiones, a razón de dos sesiones semanales) y seguimiento (4 semanas) un mes más tarde. En todas las fases, cuatro variables clínicas fueron evaluadas a través de autorregistro (frecuencia de defecaciones semanales, sensación de evacuación incompleta, nivel de dificultad de la evacuación y dolor perianal en la defecación); además, se obtuvieron medidas psicofisiológicas a través de electromiografía (EMG) del esfínter anal externo. Los resultados muestran mejoras significativas en las medidas psicofisiológicas (actividad-EMG durante el esfuerzo para defecar e índice de anismus), así como en las variables clínicas. Los beneficios del biofeedback se mantuvieron en el período de seguimiento.
Assuntos
Falência Renal Crônica/terapia , Vacina contra Sarampo/administração & dosagem , Sarampo/epidemiologia , Diálise Renal/efeitos adversos , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Suscetibilidade a Doenças/epidemiologia , Feminino , Humanos , Incidência , Falência Renal Crônica/diagnóstico , Masculino , Sarampo/prevenção & controle , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Diálise Renal/métodos , Medição de Risco , Distribuição por Sexo , Vacinação/métodosAssuntos
Adulto , Humanos , Masculino , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Grupos de Risco , Injúria Renal Aguda/complicações , Hepatite B/prevenção & controle , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Rim/transplante , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome Nefrótica/complicaçõesAssuntos
Adulto , Humanos , Masculino , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome Nefrótica/complicações , Diálise/complicações , Insuficiência Renal Crônica/complicações , Rim/transplante , Diálise Renal/efeitos adversos , Hepatite B/prevenção & controle , Grupos de RiscoAssuntos
Adulto , Humanos , Masculino , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome Nefrótica/complicações , Injúria Renal Aguda/complicações , Insuficiência Renal Crônica/complicações , Rim , Diálise Renal/efeitos adversos , Hepatite B/prevenção & controle , Grupos de RiscoRESUMO
Se analizan 48 cánceres gástricos asistidos en el lapso comprendido entre los años 1979 y 1984 en el Servicio de Gastroenterología del Hospital Bartolomé Churruca. Se constata la mayor incidencia en la 6ª década de la vida y el sexo masculino. Se realiza un análisis de la sintomatología del lapso comprendido entre su aparición y la realización del diagnóstico. Se concluye que el método diagnóstico por excelencia es el endoscópico, tanto por sus posibilidades macroscópicas como también histológicas. Se destaca en lo que respecta a sobrevida y tratamiento, que en los pacientes sometidos a cirugía la expectativa de vida es mayor, más aún cuando la intervención quirúrgica es radical. Se destaca, por último, que la totalidad de los enfermos eran portadores de cánceres avanzados, siendo el adenocarcinoma el tipo histopatológico más frecuente
Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Neoplasias GástricasRESUMO
Se analizan 48 cánceres gástricos asistidos en el lapso comprendido entre los años 1979 y 1984 en el Servicio de Gastroenterología del Hospital Bartolomé Churruca. Se constata la mayor incidencia en la 6¬ década de la vida y el sexo masculino. Se realiza un análisis de la sintomatología del lapso comprendido entre su aparición y la realización del diagnóstico. Se concluye que el método diagnóstico por excelencia es el endoscópico, tanto por sus posibilidades macroscópicas como también histológicas. Se destaca en lo que respecta a sobrevida y tratamiento, que en los pacientes sometidos a cirugía la expectativa de vida es mayor, más aún cuando la intervención quirúrgica es radical. Se destaca, por último, que la totalidad de los enfermos eran portadores de cánceres avanzados, siendo el adenocarcinoma el tipo histopatológico más frecuente (AU)
Assuntos
Adulto , Pessoa de Meia-Idade , Idoso , Humanos , Neoplasias GástricasRESUMO
Con el objeto de investigar la incidencia y características de las infecciones en una sala de Clínica Médica de un hospital general se estudiaron prospectivamente 1.835 pacientes internados en forma consecutiva durante un año, de los cuales 923 mujeres y 912 varones, presentando 348 (19%) infecciones, el 15,9% infecciones extrahospitalarias y el 3,1% con infecciones hospitalarias. Se encontró una diferencia estadísticamente significativa en el promedio de edad de los enfermos no infectados e infectados. Las localizaciones fueron: aparato respiratorio 45,6%, infecciones urinarias 32,5% infecciones generalizadas 10,1% y de otras localizaciones 12,2%. Los gérmenes más comúnmente aislados fueron para las infecciones extrahospitalarias: E. coli, Klebsiella y estreptococos y en las infecciones hospitalarias: E. coli, proteus, Klebsiella y pseudomona. La incidencia de infecciones fue más frecuente en pacientes diabéticos, neoplásicos, mayores de 70 años y en accidentes vasculoencefálicos. El porcentaje alto de pacientes infectados y la gravedad de algunos de ellos, obligan a insistir sobre la necesidad de una correcta formación infectológica del internista
Assuntos
Humanos , Masculino , Feminino , Infecção Hospitalar/epidemiologia , Infecções Bacterianas/epidemiologia , Hospitais GeraisRESUMO
Con el objeto de investigar la incidencia y características de las infecciones en una sala de Clínica Médica de un hospital general se estudiaron prospectivamente 1.835 pacientes internados en forma consecutiva durante un año, de los cuales 923 mujeres y 912 varones, presentando 348 (19%) infecciones, el 15,9% infecciones extrahospitalarias y el 3,1% con infecciones hospitalarias. Se encontró una diferencia estadísticamente significativa en el promedio de edad de los enfermos no infectados e infectados. Las localizaciones fueron: aparato respiratorio 45,6%, infecciones urinarias 32,5% infecciones generalizadas 10,1% y de otras localizaciones 12,2%. Los gérmenes más comúnmente aislados fueron para las infecciones extrahospitalarias: E. coli, Klebsiella y estreptococos y en las infecciones hospitalarias: E. coli, proteus, Klebsiella y pseudomona. La incidencia de infecciones fue más frecuente en pacientes diabéticos, neoplásicos, mayores de 70 años y en accidentes vasculoencefálicos. El porcentaje alto de pacientes infectados y la gravedad de algunos de ellos, obligan a insistir sobre la necesidad de una correcta formación infectológica del internista (AU)