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1.
Int Arch Allergy Immunol ; 185(3): 253-259, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38035559

RESUMEN

INTRODUCTION: Asthma is one of the most common chronic diseases and affects around 334 million people worldwide. The estimated prevalence of severe asthma is 3-10% of the asthmatic population. Mepolizumab has demonstrated efficacy in reducing exacerbations, oral corticosteroid use, and improving quality of life, asthma control, and lung function in patients with severe eosinophilic asthma (SEA). Our study aimed to check the response to mepolizumab in a series of severe asthma patients regarding exacerbations, oral corticosteroid use, asthma control, quality of life, and lung function and to compare the response between patients with and without nasal polyps. METHOD: This is a retrospective, multicenter study of RE-ASGRAMUR (Register of Severe Asthma of the Region of Murcia) performed in eight hospitals of the Region of Murcia (Spain) under routine clinical practice conditions. We included patients diagnosed with SEA who completed at least 1 year of treatment with mepolizumab. We analyzed clinical characteristics, drug tolerance, and effectiveness: exacerbations, ACT, miniAQLQ, forced expiratory volume in 1 s (FEV1), and use of oral corticosteroids. We also compared the results between patients with and without nasal polyps. RESULTS: The median of exacerbations before treatment was 3 and decreased to 0 after treatment (mean decrease of 77.4%). The median diary oral prednisone intake was 15 mg before treatment and 5 mg after treatment (mean 56% reduction). We have obtained a significant improvement in other variables: ED visits and hospitalizations, asthma control (ACT), quality of life (miniAQLQ), and lung function (FEV1). Thirty-four out of 70 patients (48.57%) fulfilled the criteria of super-responder, and 17 out of 70 (24.29%) had a complete response. More patients in the group with nasal polyps fulfilled the criteria of super-responder and complete response to mepolizumab. CONCLUSIONS: Mepolizumab is a safe and effective treatment for SEA patients, improving exacerbations, oral corticosteroid intake, asthma control, quality of life, and lung function. In patients with associated nasal polyposis, there is a statistically significant higher proportion of super-responders and complete responders.


Asunto(s)
Antiasmáticos , Anticuerpos Monoclonales Humanizados , Asma , Pólipos Nasales , Eosinofilia Pulmonar , Humanos , Antiasmáticos/uso terapéutico , Calidad de Vida , Pólipos Nasales/complicaciones , Pólipos Nasales/tratamiento farmacológico , Estudios Retrospectivos , Asma/complicaciones , Asma/tratamiento farmacológico , Eosinofilia Pulmonar/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Resultado del Tratamiento , Respuesta Patológica Completa
2.
Allergol Immunopathol (Madr) ; 50(6): 163-168, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36335460

RESUMEN

INTRODUCTION: Clinical trials and real-life studies have been published showing effectiveness of benralizumab in severe eosinophilic asthmatic patients. The aim of the present study is to describe super-responders to benralizumab in a series of 79 patients who completed at least 1 year of treatment, and to compare super-responders with non super-responders. METHODS: This is a multicenter study of the Register of Severe Asthma of the Region of Murcia (RE-ASGRAMUR) Group performed in eight hospitals under the conditions of routine clinical practice. Patients with zero exacerbations and no oral corticosteroid therapy for asthma were considered super-responders. We analyzed clinical, functional, and inflammatory parameters of selected patients. RESULTS: In all, 50 of the 79 patients (63%) met the super-responder criteria. In addition, 36% of the patients (26/71) were considered as complete responders to treatment (super--responder + Asthma Control Test [ACT] ≥ 20 + forced expiratory volume in 1 s [FEV1] ≥ 80%). The super--responders were significantly older in age (P = 0.0029), had higher eosinophils count (P = 0.0423), higher proportion of nasal polyps (P = 0.036), and they had less severe disease at baseline. After 1 year of treatment, the super-responders had higher levels of ACT questionnaire (23 vs 19, P = 0.0007) and better percentage of FEV1 (83 vs 75, P = 0.0359). CONCLUSION: Almost two of the three patients treated with benralizumab were super--responders after 1 year of treatment and 36% had a complete response. Super-responders were associated with older age, higher eosinophils count, had nasal polyposis as comorbidity, and had less severe disease at baseline. This data illustrated the good real-life response of patients with severe eosinophilic asthma to the treatment with benralizumab.


Asunto(s)
Antiasmáticos , Asma , Pólipos Nasales , Eosinofilia Pulmonar , Humanos , Antiasmáticos/uso terapéutico , Eosinófilos , Asma/tratamiento farmacológico , Eosinofilia Pulmonar/tratamiento farmacológico , Progresión de la Enfermedad
3.
Eur J Clin Pharmacol ; 76(12): 1653-1658, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32886177

RESUMEN

PURPOSE: Feature films are increasingly being used in teaching health sciences. However, few publications address the effectiveness of this approach. We hypothesized that using feature films could help students learn. We aimed to assess the effectiveness of using a feature film to teach students about adverse drug reactions and pharmacovigilance. METHODS: The study population comprised third-, fifth-, and sixth-year undergraduate students of medicine, third-year undergraduate students of human biology, and graduate students in a master's degree program about the pharmaceutical and biotechnology industry. Students watched clips from the film 150 Miligrams (La fille de Brest) and discussed them afterward. To measure learning, we administered a 10-question multiple-choice test about pharmacovigilance concepts. We assessed students' satisfaction with the activity through a questionnaire. An exploratory comparative analysis was performed. RESULTS: A total of 237 students participated. Postintervention assessment scores were significantly higher than preintervention scores for the entire population and for all subgroups. The mean number of correct answers was 4.41 on the preintervention assessment and 5.78 on the postintervention assessment (mean gain: 1.37; 95% CI: 1.10-1.65). Similar results were found when analyzing groups of students from each group. Student satisfaction with this teaching activity was high in all groups. CONCLUSIONS: Cinemeducation is a useful tool for teaching about adverse drug reactions and pharmacovigilance processes. Most students were highly satisfied.


Asunto(s)
Instrucción por Computador/métodos , Educación de Pregrado en Medicina/métodos , Películas Cinematográficas , Farmacología Clínica/educación , Farmacovigilancia , Biología/educación , Biotecnología/educación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Evaluación Educacional/estadística & datos numéricos , Estudios de Factibilidad , Humanos , Aprendizaje , Satisfacción Personal , Proyectos Piloto , Estudios Prospectivos , Estudiantes de Medicina/psicología , Estudiantes de Medicina/estadística & datos numéricos , Estudiantes de Farmacia/psicología , Estudiantes de Farmacia/estadística & datos numéricos , Encuestas y Cuestionarios/estadística & datos numéricos
4.
J Cell Sci ; 127(Pt 23): 5105-14, 2014 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-25300794

RESUMEN

Knowledge of the distribution of mitochondria and endoplasmic reticulum (ER) in relation to the position of exocytotic sites is relevant to understanding the influence of these organelles in tuning Ca(2+) signals and secretion. Confocal images of probes tagged to mitochondria and the F-actin cytoskeleton revealed the existence of two populations of mitochondria, one that was cortical and one that was perinuclear. This mitochondrial distribution was also confirmed by using electron microscopy. In contrast, ER was sparse in the cortex and more abundant in deep cytoplasmic regions. The mitochondrial distribution might be due to organellar transport, which experiences increasing restrictions in the cell cortex. Further study of organelle distribution in relation to the position of SNARE microdomains and the granule fusion sites revealed that a third of the cortical mitochondria colocalized with exocytotic sites and another third located at a distance closer than two vesicle diameters. ER structures were also present in the vicinity of secretory sites but at a lower density. Therefore, mitochondria and ER have a spatial distribution that suggests a specialized role in modulation of exocytosis that fits with the role of cytosolic Ca(2+) microdomains described previously.


Asunto(s)
Células Cromafines/metabolismo , Células Cromafines/ultraestructura , Retículo Endoplásmico/ultraestructura , Exocitosis , Mitocondrias/ultraestructura , Animales , Señalización del Calcio , Bovinos , Células Cultivadas , Retículo Endoplásmico/metabolismo , Metabolismo Energético , Microscopía Confocal , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , Mitocondrias/metabolismo , Factores de Tiempo , Transfección
5.
J Neurophysiol ; 108(2): 453-66, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22514285

RESUMEN

Somatosensory afferents are represented within the cortical autonomic network (CAN). However, the representation of somatosensory afferents, and the consequent cardiovascular effects, may be modified by levels of baroreceptor input. Thus, we examined the cortical regions involved with processing somatosensory inputs during baroreceptor unloading. Neuroimaging sessions (functional magnetic resonance imaging [fMRI]) recorded brain activity during 30 mmHg lower-body negative pressure (LBNP) alone and combined with somatosensory stimulation (LBNP+SS) of the forearm (n = 14). Somatosensory processing was also assessed during increased sympathetic outflow via end-expiratory apnea. Heart rate (HR), blood pressure (BP), cardiac output (Q), and muscle sympathetic nerve activity (MSNA) were recorded during the same protocols in a separate laboratory session. SS alone had no effect on any cardiovascular or MSNA variable at rest. Measures of HR, BP, and Q during LBNP were not different compared with LBNP+SS. The rise in MSNA burst frequency was attenuated during LBNP+SS versus LBNP alone (8 vs. 12 bursts/min, respectively, P < 0.05). SS did not affect the change in MSNA during apnea. Activations within the insula and dorsal anterior cingulate cortex (ACC) observed during LBNP were not seen during LBNP+SS. Anterior insula and ACC activations occurring during apnea were not modified by SS. Thus, the absence of insular and dorsal ACC activity during LBNP+SS along with an attenuation of MSNA burst frequency suggest sympathoinhibitory effects of sensory stimulation during decreased baroreceptor input by a mechanism that includes conjoint insula-dorsal ACC regulation. These findings reveal that the level of baroreceptor input influences the forebrain organization of somatosensory afferents.


Asunto(s)
Sistema Nervioso Autónomo/fisiología , Barorreflejo/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Red Nerviosa/fisiología , Inhibición Neural/fisiología , Presorreceptores/fisiología , Prosencéfalo/fisiología , Adolescente , Adulto , Vías Aferentes , Presión Sanguínea/fisiología , Femenino , Humanos , Masculino , Adulto Joven
6.
Traffic ; 10(2): 172-85, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19054386

RESUMEN

The expression of SNAP-25 fused to green fluorescent protein (GFP) has been instrumental in demonstrating SNARE role in exocytosis. The wild-type GFP-SNAP-25 and a Delta9 form, product of botulinum neurotoxin A activity, the main ingredient in the BOTOX preparation, were employed here to study SNARE implication in vesicle mobility and fusion in cultured bovine chromaffin cells, a neuroendocrine exocytotic model. Using total internal reflection fluorescent microscopy, we have identified membrane microdomains of 500-600 nm diameter that contain both SNAP-25 and syntaxin-1 and associate with synaptobrevin-2. Interestingly, while the SNAP-25 Delta9 formed similar clusters, they displayed increased mobility both laterally and in the axis perpendicular to the plasmalemma, and this correlates with the enhanced dynamics of associated chromaffin granules. SNARE cluster-enhanced motion is reversed by elevation of the intracellular calcium level. Furthermore, single vesicle fusion was unlikely in the highly mobile vesicles present in the cells expressing SNAP-25 Delta9, which, in addition, displayed in average slower fusion kinetics. Consequently, SNARE cluster dynamics is a new aspect to consider when determining the factors contributing to the mobility of the vesicles in close vicinity to the plasma membrane and also the probability of exocytosis of this granule population.


Asunto(s)
Células Cromafines/metabolismo , Familia de Multigenes/genética , Proteínas SNARE/metabolismo , Vesículas Transportadoras/metabolismo , Animales , Calcio/metabolismo , Bovinos , Células Cultivadas , Exocitosis , Regulación de la Expresión Génica , Genes Reporteros/genética , Probabilidad , Unión Proteica
7.
Neuroimage ; 54(2): 1211-20, 2011 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-20884359

RESUMEN

Regions of the cortical autonomic network (CAN) are activated during muscle contraction. However, it is not known to what extent CAN activation patterns reflect muscle sensory inputs, top-down signals from the motor cortex, and/or motor drive to cardiovascular structures. The present study explored the functional representation of somatosensory afferent input within the CAN with an a priori interest in the insula and ventral medial prefrontal cortex (vMPFC) (n=12). Heart rate (HR) and functional MRI data were acquired during 1) 30s periods of electrical stimulation of the wrist flexors at sub-motor (SUB; Type I,II afferents) and 2) motor thresholds (MOT; Type I,II,III afferents), 3) volitional wrist flexion at 5% maximal voluntary contraction (MVC) to match the MOT tension (VOL5%), and 4) volitional handgrip at 35% MVC to elicit tachycardia (VOL35%). Compared with rest, HR did not change during SUB, MOT, or VOL5% but increased during VOL35% (p<0.001). High frequency HR variability was 29.42±18.87 ms(2) (mean±S.D.) at rest and 39.85±27.60 ms(2) during SUB (p=0.06). High frequency HR variability was decreased during VOL35% compared to rest (p≤0.005). SUB increased activity in the bilateral posterior insula, vMPFC, subgenual anterior cingulate cortex (ACC), mid-cingulate cortex (MCC), and posterior cingulate cortex. MOT increased activity in the left posterior insula and MCC. During VOL5%, activity increased in the right anterior-mid insula. VOL35% was associated with activity in the bilateral insula as well as vMPFC and subgenual ACC deactivation. These data suggest that the left posterior insula processes sensory input from muscle during passive conditions and specifically that Type I and/or II muscle afferent stimulation during SUB impacts the vMPFC and/or subgenual ACC, regions believed to be involved in brain default mode and parasympathetic activity.


Asunto(s)
Vías Aferentes/fisiología , Sistema Nervioso Autónomo/fisiología , Mapeo Encefálico , Corteza Cerebral/fisiología , Frecuencia Cardíaca/fisiología , Adulto , Estimulación Eléctrica , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Contracción Muscular/fisiología , Músculo Esquelético/inervación , Muñeca/inervación
8.
Exp Physiol ; 96(8): 718-35, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21602293

RESUMEN

The present study was designed to address the contribution of α-adrenergic modulation to the genesis of low-frequency (LF; 0.04-0.15 Hz) oscillations in R-R interval (RRi), blood pressure (BP) and muscle sympathetic nerve activity (MSNA) during different sympathetic stimuli. Blood pressure and RRi were measured continuously in 12 healthy subjects during 5 min periods each of lower body negative pressure (LBNP; -40 mmHg), static handgrip exercise (HG; 20% of maximal force) and postexercise forearm circulatory occlusion (PECO) with and without α-adrenergic blockade by phentolamine. Muscle sympathetic nerve activity was recorded in five subjects during LBNP and in six subjects during HG and PECO. Low-frequency powers and median frequencies of BP, RRi and MSNA were calculated from power spectra. Low-frequency power during LBNP was lower with phentolamine versus without for both BP and RRi oscillations (1.6 ± 0.6 versus 1.2 ± 0.7 ln mmHg(2), P = 0.049; and 6.9 ± 0.8 versus 5.4 ± 0.9 ln ms(2), P = 0.001, respectively). In contrast, the LBNP with phentolamine increased the power of high-frequency oscillations (0.15-0.4 Hz) in BP and MSNA (P < 0.01 for both), which was not observed during saline infusion. Phentolamine also blunted the increases in the LBNP-induced increase in frequency of LF oscillations in BP and RRi. Phentolamine decreased the LF power of RRi during HG (P = 0.015) but induced no other changes in LF powers or frequencies during HG. Phentolamine resulted in decreased frequency of LF oscillations in RRi (P = 0.004) during PECO, and a similar tendency was observed in BP and MSNA. The power of LF oscillation in MSNA did not change during any intervention. We conclude that α-adrenergic modulation contributes to LF oscillations in BP and RRi during baroreceptor unloading (LBNP) but not during static exercise. Also, α-adrenergic modulation partly explains the shift to a higher frequency of LF oscillations during baroreceptor unloading and muscle metaboreflex activation.


Asunto(s)
Neuronas Adrenérgicas/fisiología , Presión Sanguínea/fisiología , Corazón/inervación , Músculos/inervación , Receptores Adrenérgicos alfa/fisiología , Sistema Nervioso Simpático/fisiología , Antagonistas Adrenérgicos alfa/farmacología , Adulto , Barorreflejo/efectos de los fármacos , Barorreflejo/fisiología , Presión Sanguínea/efectos de los fármacos , Electrocardiografía/métodos , Ejercicio Físico/fisiología , Femenino , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Humanos , Presión Negativa de la Región Corporal Inferior/métodos , Masculino , Músculos/efectos de los fármacos , Fentolamina/farmacología , Presorreceptores/efectos de los fármacos , Presorreceptores/fisiología , Sistema Nervioso Simpático/efectos de los fármacos
9.
Am J Physiol Regul Integr Comp Physiol ; 299(5): R1407-14, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20826706

RESUMEN

The within-breath modulation of muscle sympathetic nerve activity (MSNA) is well established, with greater activity occurring during expiration and less during inspiration. Whether ventilation per se affects the longer-term (i.e., minute-to-minute) regulation of MSNA has not been determined. We sought to define the specific role of ventilation in regulating sympathetic activation during chemoreflex activation, where both ventilation and MSNA are increased. Ten young healthy subjects performed both asphyxic rebreathing and repeated, rebreathing apneas to cause the same magnitude of chemoreflex stress in the presence or absence of ventilation. Both protocols caused increases in sympathetic burst frequency, burst amplitude, and burst incidence. However, burst frequency was increased more during repeated apneas (12 ± 6 to 25 ± 7 bursts/min) compared with rebreathing (12 ± 5 to 17 ± 7 bursts/min; P < 0.001) due to a greater burst incidence during apneas (36 ± 11 bursts/100 heart beats) vs. rebreathing (26 ± 8 bursts/100 heart beats, P < 0.001). The sympathetic gain to chemoreflex stress was also larger during repeated apneas (2.29 ± 1.29 au/% desaturation) compared with rebreathing (1.44 ± 0.53 au/% desaturation, P < 0.05). The augmented sympathetic response during apneas was associated with a larger pressor response and total peripheral resistance compared with rebreathing. These data demonstrate that ventilation per se restrains sympathetic activation during chemoreflex activation. Further, the augmented sympathetic response during apneas was associated with greater cardiovascular stress and may be relevant to the cardiovascular pathology associated with sleep-disordered breathing.


Asunto(s)
Apnea/fisiopatología , Células Quimiorreceptoras/metabolismo , Inhibición Neural , Ventilación Pulmonar , Estrés Fisiológico , Sistema Nervioso Simpático/fisiopatología , Adulto , Apnea/metabolismo , Barorreflejo , Presión Sanguínea , Croacia , Frecuencia Cardíaca , Humanos , Masculino , Ontario , Nervio Peroneo/fisiopatología , Mecánica Respiratoria , Factores de Tiempo , Resistencia Vascular , Adulto Joven
10.
Adicciones ; 22(1): 59-64, 2010.
Artículo en Español | MEDLINE | ID: mdl-20300715

RESUMEN

The high rate of dropout from treatment programs is one of the most serious problems in the field of drug dependence. Early identification of predictors of dropout risk can provide useful information on the specific treatment needs of these types of patient. The aim of this study was to identify predictors of premature cessation of an outpatient treatment program for cocaine addicts. The study was carried out at public healthcare units in a Spanish city. Participants were 91 cocaine addicts admitted for treatment for their addiction, assessed by means of interview and various self-report measures. For identifying predictive variables the researchers used a factor analysis, a cluster analysis and a CHAID analysis. The variables that obtained predictive capacity were the MAST scores and the combined alcohol and drugs scores on the EuropASI. These three variables were grouped in a single factor which was called addictive severity. The predictive analysis showed that this factor had some degree of capacity for the prediction of dropout, but that it was not completely determinant. The results suggest the advantage of detecting at the admission stage those patients who might require more attention to their motivational aspects, greater treatment control and intensity, or the provision of complementary interventions.


Asunto(s)
Trastornos Relacionados con Cocaína , Cooperación del Paciente/estadística & datos numéricos , Adulto , Trastornos Relacionados con Cocaína/terapia , Femenino , Humanos , Masculino , Pacientes Desistentes del Tratamiento
11.
Adicciones ; 20(3): 295-304, 2008.
Artículo en Español | MEDLINE | ID: mdl-18813775

RESUMEN

Directly Observed Treatment (TOD-DOT) has been tested in different conditions. The objective of this work is to check whether a UCA-CAB (Centre for Addictive Behaviour) can achieve detox and reduce the risk of early relapse (up to 12 weeks) in alcoholic patients. All patients had an established organic addiction and serious withdrawal syndrome, and had undergone multiple previous treatments. Furthermore, they had not managed to abstain for a 3-month consecutive period over the previous 2 years. The aim of the Directly Observed Treatment was to attain detox and reduce relapse by following a multi-method approach: medical, psychological and personal care, based on a brief daily consultation and pharmacological supervision. The results were as follows: Of the 18 patients included in the study, after 12 weeks, 13 (72 %) were still abstinent and 4 (22 %) had relapsed. Thus, 17 (94 %) were still following the treatment, with just one drop-out. We analysed the profiles of the patients abstaining, of those who relapsed (4) and of the one who dropped out. The average CIWA-Ar was 27.05 (21-36). Any value over 20 is considered to indicate serious withdrawal syndrome, though there were no negative events leading to hospitalization. Level of adherence to the treatment (94 %) meant that the most seriously affected patients and those with fewest financial resources could benefit, not only from any auxiliary social schemes, but also from basic health services, permitting them to improve the quality of their everyday life.


Asunto(s)
Alcoholismo/rehabilitación , Atención Ambulatoria , Terapia por Observación Directa , Centros de Tratamiento de Abuso de Sustancias , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad
12.
Front Cell Neurosci ; 12: 344, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30356839

RESUMEN

Neuroendocrine chromaffin cells represent an excellent model to study the molecular mechanisms associated with the exo-endocytotic cycle of neurotransmitter release. In this study, EGFP-Lifeact and confocal microscopy has been used to analyze the re-organization of the cortical F-actin cytoskeleton associated to organelle transport during secretion with unprecedented detail. In these cells secretory events accumulate in temperature-sensitive and myosin II-dependent F-actin expansions and retractions affecting specific regions of the sub-membrane space. Interestingly, not only vesicles but also mitochondria are transported toward the plasmalemma during these expansions. Simultaneously, we found F-actin cytoskeletal retraction withdraws vesicles from the sub-plasmalemmal space, forming novel empty internal spaces into which organelles can be transported. In addition to these well-coordinated, F-actin-myosin II dependent processes that drive the transport of the majority of vesicles, fast transport of chromaffin vesicles was observed, albeit less frequently, which used F-actin comet tails nucleated from the granular membrane. Thus, upon cell stimulation F-actin structures use diverse mechanisms to transport organelles to and from the membrane during the exo-endocytotic cycle taking place in specific areas of cell periphery.

13.
Front Cell Neurosci ; 11: 135, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28522964

RESUMEN

Cultured bovine chromaffin cells have been used extensively as a neuroendocrine model to study regulated secretion. In order to extend such experimental findings to the physiological situation, it is necessary to study mayor cellular structures affecting secretion in cultured cells with their counterparts present in the adrenomedullary tissue. F-actin concentrates in a peripheral ring in cultured cells, as witnessed by phalloidin-rodhamine labeling, while extends throughout the cytoplasm in native cells. This result is also confirmed when studying the localization of α-fodrin, a F-actin-associated protein. Furthermore, as a consequence of this redistribution of F-actin, we observed that chromaffin granules and mitochondria located into two different cortical and internal populations in cultured cells, whereas they are homogeneously distributed throughout the cytoplasm in the adrenomedullary tissue. Nevertheless, secretion from isolated cells and adrenal gland pieces is remarkably similar when measured by amperometry. Finally, we generate mathematical models to consider how the distribution of organelles affects the secretory kinetics of intact and cultured cells. Our results imply that we have to consider F-actin structural changes to interpret functional data obtained in cultured neuroendocrine cells.

14.
An Pediatr (Barc) ; 65(1): 79-82, 2006 Jul.
Artículo en Español | MEDLINE | ID: mdl-16945294

RESUMEN

Shwachman-Diamond syndrome is a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal abnormalities, and short stature. We describe the clinical characteristics, laboratory data, and treatment in a 14-month-old boy diagnosed with this syndrome in our unit.


Asunto(s)
Enfermedades de la Médula Ósea/genética , Insuficiencia Pancreática Exocrina/genética , Anomalías Musculoesqueléticas/genética , Genes Recesivos , Humanos , Lactante , Masculino , Síndrome
15.
Appl Physiol Nutr Metab ; 39(5): 572-80, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24766240

RESUMEN

We tested the hypotheses that smoking-induced changes in vascular mechanics would be detected earlier in the lumped properties of peripheral vascular beds, which include the properties of microvasculature, than in the local properties of central conduits, and that such changes are reversible with lifestyle changes that include smoking cessation and exercise. Vascular measures were made in 53 young (18-40 years) female smokers and 25 age-matched non-smokers. Twenty-two of the smokers were tested before and after a 14-week smoking cessation program and, of these, 13 were tested again after 52 weeks of smoking cessation. Compared with non-smokers, lumped forearm vascular bed compliance (C: mL/mm Hg) was lower, while lumped viscoelasticity (K: mm Hg/(mL·min)) and resistance (R: mm Hg/(mL·min)) were higher in the smoker group. Neither the carotid-to-toe pulse wave velocity nor local carotid artery elasticity indices were different between groups. Compared with non-smokers, brachial artery distensibility was less, and other markers of stiffness higher, in the smoker group. At 14 and 52 weeks of smoking cessation, forearm vascular R was reduced and C was increased while K was unchanged. The changes in C and R occurred while maintaining a constant R×C value, which represents a dynamic time constant. Thus, early changes in K were observed in the forearm vascular bed of smokers, which were not reflected in the local properties of central conduit vessels. Forearm C, but not K, was reversed following smoking cessation, a finding that may represent a persistent effect of smoking on the intercellular matrix of the vessel wall.


Asunto(s)
Arterias/fisiología , Estilo de Vida , Cese del Hábito de Fumar , Adolescente , Adulto , Fenómenos Biomecánicos , Femenino , Humanos , Adulto Joven
16.
Pancreas ; 43(6): 895-902, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24897276

RESUMEN

OBJECTIVE: The objective of this study was to evaluate whether an uncontrolled activation of mast cells and macrophages through protease-activated receptor-2 (PAR-2) during acute pancreatitis could develop lung injury. METHODS: Pancreatitis was induced in rats by intraductal infusion of sodium taurocholate. In a group of animals, PAR-2 antagonist or trypsin (TRP) inhibitor was intravenously administered before the pancreatitis induction. In additional groups, the animals were treated with PAR-2-activating peptide or pancreatic TRP. The myeloperoxidase (MPO) activity was measured to evaluate the progression of inflammation. RESULTS: Plasma from the animals with pancreatitis and pancreatic TRP induced the secretion of mast cells and alveolar macrophages as well as increased the density of PAR-2 in the plasma membrane. The treatment of alveolar macrophages with TRP, tryptase, as well as PAR-1- and PAR-2-activating peptide led to an increase in calcium-triggered exocytosis. Similar results were obtained in acinar cells. The intravenous injection of PAR-2-activating peptide and TRP induced an increase in MPO activity in the lung. The intravenous injection of PAR-2 antagonist or TRP inhibitor before the pancreatitis induction could prevent the increase in MPO activity in the pancreas and the lung. CONCLUSIONS: The TRP generated during acute pancreatitis could be involved in the progression of lung injury through the activation of PAR-2 in alveolar macrophages.


Asunto(s)
Enfermedades Pulmonares/metabolismo , Pulmón/metabolismo , Pancreatitis/metabolismo , Receptor PAR-2/metabolismo , Células Acinares/efectos de los fármacos , Células Acinares/metabolismo , Enfermedad Aguda , Animales , Calcio/metabolismo , Calcio/farmacología , Línea Celular , Línea Celular Tumoral , Exocitosis/efectos de los fármacos , Inmunohistoquímica , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Enfermedades Pulmonares/fisiopatología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Microscopía Confocal , Oligopéptidos/farmacología , Pancreatitis/inducido químicamente , Pancreatitis/fisiopatología , Peroxidasa/metabolismo , Ratas Wistar , Receptor PAR-2/fisiología , Ácido Taurocólico , Tripsina/metabolismo , Tripsina/farmacología
17.
Int J Biochem Cell Biol ; 45(3): 583-92, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23220175

RESUMEN

It has been proposed recently that the F-actin cytoskeleton organizes the relative disposition of the SNARE proteins and calcium channels that form part of the secretory machinery in chromaffin cells, a neurosecretory model. To test this idea, we used confocal microscopy do determine if DsRed-SNAP-25 microdomains, which define the final sites of exocytosis along with syntaxin-1, preferentially remain in contact with F-actin cortical structures labelled by lifeact-EGFP. A quantitative analysis showed that in cells over-expressing these constructs there is a preferential colocalization, rather than a random distribution of SNAP-25 patches. To analyze the possible interactions between these proteins, we designed FRET experiments and tested whether treatment with agents that affect F-actin mobility would modify SNAP-25 movement. The significant FRET efficiencies detected suggest that direct molecular interactions occur, whereas dynamic experiments using TIRFM revealed that attenuation of cortical F-actin movement clearly diminishes the mobility of SNAP-25 clusters. Taken together, these data can be explained by a model that associates components of the secretory machinery to the F-actin cortex through flexible links.


Asunto(s)
Actinas/metabolismo , Células Cromafines/metabolismo , Exocitosis/genética , Proteína 25 Asociada a Sinaptosomas/metabolismo , Actinas/genética , Animales , Canales de Calcio/metabolismo , Bovinos , Células Cromafines/citología , Citoesqueleto/metabolismo , Exocitosis/fisiología , Microscopía Confocal , Proteínas Qa-SNARE/metabolismo , Proteínas SNARE/metabolismo , Proteína 25 Asociada a Sinaptosomas/genética
18.
J Mol Neurosci ; 48(2): 323-7, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22350991

RESUMEN

Chromaffin granules are restrained in a dense cortical cytoskeleton before releasing their complex mix of active substances in response to cell stimulation. In recent years, the complex organization and dynamics of the chromaffin cell cortex has been unveiled through its analysis with a range of techniques to visualize this structure, including confocal fluorescence, transmitted light, and evanescent field microscopy. Accordingly, it has become apparent that the cortex is a dense F-actin mesh that contains open polygonal spaces through which vesicles can access the submembrane space. In addition to its retentive role, this structure also influences vesicle motion in both the resting state and during cell stimulation with secretagogues. During secretion, the chromaffin cell cortex undergoes a complex reorganization, helping to replenish the empty fast releasable pool of vesicles. Such changes in the cortical cytoskeleton and in the vesicle motion are governed by the activity of molecular motors, such as myosins II and Va. Interestingly, the F-actin/myosin II network also affects the final stages of exocytosis, which involve the opening and expansion of the fusion pore, and the extrusion of the vesicles contents.


Asunto(s)
Actinas/fisiología , Células Cromafines/fisiología , Exocitosis/fisiología , Fusión de Membrana/fisiología , Vesículas Secretoras/fisiología , Animales , Células Cromafines/citología , Humanos , Miosinas/fisiología
19.
Artículo en Inglés | MEDLINE | ID: mdl-22255937

RESUMEN

Sympathetic nerve activity is an important regulator of blood pressure and blood flow in humans. Our understanding about how sympathetic neurons are recruited during baroreflex stress is limited. This paper investigates the sympathetic neural recruitment patterns during the Valsalva maneuver. Using microneurography, muscle sympathetic nerve activity was recorded in seven healthy subjects during baseline and the Valsalva maneuver. A new algorithm for detection and classification of action potentials was employed to study the differences between the recruitment of sympathetic neurons during baseline and the Valsalva maneuver. The data suggests that the Valsalva maneuver increases the number of spikes per sympathetic bursts and also recruits at least one additional new cluster of larger, faster conducting neurons. Also, action potential's latencies (i.e., inverse of conduction velocity) were shifted downward for all action potential clusters during this maneuver.


Asunto(s)
Músculos/fisiología , Neuronas/fisiología , Procesamiento de Señales Asistido por Computador , Maniobra de Valsalva/fisiología , Potenciales de Acción , Adulto , Algoritmos , Barorreflejo , Presión Sanguínea/fisiología , Análisis por Conglomerados , Femenino , Humanos , Masculino , Red Nerviosa , Redes Neurales de la Computación , Reproducibilidad de los Resultados , Sistema Nervioso Simpático/patología
20.
Int J Artif Organs ; 34(9): 766-70, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22094555

RESUMEN

Effectiveness of amphotericin B alone or in combination with rifampicin or clarithromycin on the killing of Candida species biofilms was investigated in vitro. Amphotericin B was assayed at 0.005 to 10 mg/ml. Rifampin and clarithromycin were assayed at 10 mg/ml. We studied 7 Candida albicans, 3 Candida parapsilosis, 3 Candida glabrata, 3 Candida krusei and 2 Candida tropicalis strains. Biofilms were developed in 96-well, flat-bottomed microtiter plates for 48 hours. A synergistic effect between amphotericin B and clarithromycin was demonstrated against 66.6% of C. parapsilosis, 66.6% of C. glabrata, and 42.8% of C. albicans biofilms. A synergistic effect between amphotericin B and rifampin was demonstrated against 66.6% of C. parapsilosis, 42.8% of C. albicans, and 33.3% of C. glabrata biofilms. No synergistic effect was observed against C. krusei or C. tropicalis biofilms with any of the combinations. Rifampin or clarithromycin alone did not exert any effect on Candida species biofilms. Rifampin or clarithromycin combinations with amphotericin B might be of interest in the treatment of Candida biofilm-related infections.


Asunto(s)
Anfotericina B/farmacología , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Candida/efectos de los fármacos , Claritromicina/farmacología , Rifampin/farmacología , Biopelículas/crecimiento & desarrollo , Candida/crecimiento & desarrollo , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada
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