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1.
Allergol. immunopatol ; 50(6): 47-52, 01 nov. 2022. tab
Artículo en Inglés | IBECS | ID: ibc-211523

RESUMEN

Although currently approved to treat severe asthma and chronic spontaneous urticaria, omalizumab has also been an effective and safe add-on treatment for other allergic diseases. Namely, omalizumab has been proposed to be used as add-on therapy in patients with allergic rhinitis and asthma and undergoing specific allergen immunotherapy (AIT). AIT is the only treatment that modifies the natural history of IgE-mediated diseases. This brief review summarizes the available evidence and controversies on the efficacy and safety of omalizumab combined with specific AIT (AU)


Asunto(s)
Humanos , Desensibilización Inmunológica/métodos , Antiasmáticos/uso terapéutico , Omalizumab/uso terapéutico , Alérgenos/uso terapéutico , Asma/terapia , Antialérgicos/uso terapéutico , Rinitis Alérgica/terapia
3.
Eur Ann Allergy Clin Immunol ; 51(1): 21-31, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30246512

RESUMEN

Summary: Background Allergy is characterized by allergen-specific IgE production. Molecular-based allergy diagnostic allows to define the precise sensitization profile. Bet v 1 is the major allergen of the PR-10 family. It has been reported that pan-allergens could affect the sensitization panel in adults. This study aimed to evaluate the impact of Bet v 1 sensitization on sensitization pattern in a large sample of children. Methods Serum IgE molecular components were assessed by ISAC method. Sera from 1,205 children, 708 males (58.76%) and 497 females (41.24%), median age 8.61 years (4.93 - 12.54 years) were analyzed. Results A total of 354 PR-10-positive subjects were detected out of 1,205 subjects. Bet v 1 positive children were significantly more frequently sensitized to other molecules belonging to PR-10 family and noteworthy also to other allergenic families than Bet v 1 negative children. Conclusions The present study demonstrates that Bet v 1 sensitization may significantly affect the sensitization pattern in children living in Genoa, a Mediterranean city located in a birch-free area.


Asunto(s)
Antígenos de Plantas/inmunología , Hipersensibilidad/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina E/sangre , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos
4.
Allergol. immunopatol ; 45(3): 265-271, mayo-jun. 2017. graf
Artículo en Inglés | IBECS | ID: ibc-162389

RESUMEN

BACKGROUND: Respiratory allergy is characterised by an IgE-mediated reaction. The immune system functions, including IgE production, progressively decline over time, such as growing up and ageing. Molecular-based allergy diagnostic defines sensitisation profile. This study aimed to evaluate the impact of age on serum allergen-specific IgE to molecular component levels in a large sample of subjects. METHODS: Serum IgE to: Phl p1, Bet v1, Ole e1, Cup a1, Par j2, Can f1, Der p2, and Fel d1 were assessed by ISAC method. Sera from 2788 patients, 1230 males (44.1%) and 1558 females (55.9%), median age 23 years (1st and 3rd quartiles: 9.7-49.7 years; age range: 1 month-103 years) were analysed. RESULTS: The number of positive tests (i.e. sensitisation) tended to increase between birth and school-age till young adulthood and then decreased (p < 0.0001) with the exception of Fel d 1 (p = 0.14). A similar age-dependent trend was observed considering the levels of each allergen components: the levels of each allergen component, with the exception of Fel d 1, tended to increase till early adulthood and then to decrease reaching the lowest levels in the elderly. CONCLUSIONS: Allergen-specific IgE production to inhaled molecular components trend to reduce with ageing, but with differences between allergens. This phenomenon should be adequately evaluated managing allergic patients


No disponible


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Inmunoglobulina E/análisis , Hipersensibilidad Inmediata/diagnóstico , Enfermedades Respiratorias/diagnóstico , Técnicas Inmunológicas , Alérgenos/análisis , Estudios Retrospectivos , 28599 , Análisis de Varianza
5.
Allergol Immunopathol (Madr) ; 45(3): 265-271, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28153352

RESUMEN

BACKGROUND: Respiratory allergy is characterised by an IgE-mediated reaction. The immune system functions, including IgE production, progressively decline over time, such as growing up and ageing. Molecular-based allergy diagnostic defines sensitisation profile. This study aimed to evaluate the impact of age on serum allergen-specific IgE to molecular component levels in a large sample of subjects. METHODS: Serum IgE to: Phl p1, Bet v1, Ole e1, Cup a1, Par j2, Can f1, Der p2, and Fel d1 were assessed by ISAC method. Sera from 2788 patients, 1230 males (44.1%) and 1558 females (55.9%), median age 23 years (1st and 3rd quartiles: 9.7-49.7 years; age range: 1 month-103 years) were analysed. RESULTS: The number of positive tests (i.e. sensitisation) tended to increase between birth and school-age till young adulthood and then decreased (p<0.0001) with the exception of Fel d 1 (p=0.14). A similar age-dependent trend was observed considering the levels of each allergen components: the levels of each allergen component, with the exception of Fel d 1, tended to increase till early adulthood and then to decrease reaching the lowest levels in the elderly. CONCLUSIONS: Allergen-specific IgE production to inhaled molecular components trend to reduce with ageing, but with differences between allergens. This phenomenon should be adequately evaluated managing allergic patients.


Asunto(s)
Inmunoglobulina E/inmunología , Rinitis Alérgica Estacional/epidemiología , Adolescente , Adulto , Factores de Edad , Envejecimiento/inmunología , Alérgenos/inmunología , Niño , Femenino , Humanos , Inmunoglobulina E/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rinitis Alérgica Estacional/inmunología , Adulto Joven
6.
Allergol. immunopatol ; 45(1): 87-92, ene.-feb. 2017. graf, tab
Artículo en Inglés | IBECS | ID: ibc-158980

RESUMEN

BACKGROUND: Respiratory allergy is characterised by an IgE-mediated reaction. The immune system functions, including IgE production, progressively decline over time with growing up and ageing. Molecular-based allergy diagnostic defines sensitisation profile. This study aimed to evaluate the impact of age on serum allergen-specific IgE to molecular component levels in a large sample of subjects. METHODS: Serum IgE to: rCor a11, rPru p3, nJug r3, rAra h8, rGly m4, rCor a8, nPen m1, nAct d8, Bos d 8, and nGal d2 were assessed by ISAC method. Sera from 2795 patients, 1234 males (44.1%) and 1561 females (55.9%), median age 23 years (1st and 3rd quartiles: 9.7-43.7 years; age range: 1 month-103 years) were analysed. RESULTS: The number of positive tests (i.e. sensitisation) tended to increase between birth and school-age until young adulthood and then decreased. A similar age-dependent trend was observed considering the levels of each allergen components: the levels of each allergen component tended to increase until early adulthood, but Gal d 2 and Bos d 8 (rapidly diminishing), and then to decrease over time. However, the pattern is significantly dependent on each single tested food. CONCLUSIONS: Allergen-specific IgE production to food molecular components tend to reduce with ageing, but with differences between allergens. This phenomenon should be adequately evaluated managing allergic patients


No disponible


Asunto(s)
Humanos , Niño , Adulto , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Inmediata/inmunología , Hipersensibilidad a los Alimentos/inmunología , 50293 , Alérgenos/inmunología , Estudios Retrospectivos
7.
Allergol Immunopathol (Madr) ; 45(1): 87-92, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27720248

RESUMEN

BACKGROUND: Respiratory allergy is characterised by an IgE-mediated reaction. The immune system functions, including IgE production, progressively decline over time with growing up and ageing. Molecular-based allergy diagnostic defines sensitisation profile. This study aimed to evaluate the impact of age on serum allergen-specific IgE to molecular component levels in a large sample of subjects. METHODS: Serum IgE to: rCor a11, rPru p3, nJug r3, rAra h8, rGly m4, rCor a8, nPen m1, nAct d8, Bos d 8, and nGal d2 were assessed by ISAC method. Sera from 2795 patients, 1234 males (44.1%) and 1561 females (55.9%), median age 23 years (1st and 3rd quartiles: 9.7-43.7 years; age range: 1 month-103 years) were analysed. RESULTS: The number of positive tests (i.e. sensitisation) tended to increase between birth and school-age until young adulthood and then decreased. A similar age-dependent trend was observed considering the levels of each allergen components: the levels of each allergen component tended to increase until early adulthood, but Gal d 2 and Bos d 8 (rapidly diminishing), and then to decrease over time. However, the pattern is significantly dependent on each single tested food. CONCLUSIONS: Allergen-specific IgE production to food molecular components tend to reduce with ageing, but with differences between allergens. This phenomenon should be adequately evaluated managing allergic patients.


Asunto(s)
Factores de Edad , Envejecimiento/inmunología , Alérgenos/inmunología , Hipersensibilidad a los Alimentos/inmunología , Inmunoglobulina E/sangre , Adolescente , Adulto , Niño , Femenino , Alimentos , Humanos , Inmunización , Masculino , Patología Molecular/métodos , Adulto Joven
8.
Int Rev Neurobiol ; 128: 1-49, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27238260

RESUMEN

BK channels are universal regulators of cell excitability, given their exceptional unitary conductance selective for K(+), joint activation mechanism by membrane depolarization and intracellular [Ca(2+)] elevation, and broad expression pattern. In this chapter, we discuss the structural basis and operational principles of their activation, or gating, by membrane potential and calcium. We also discuss how the two activation mechanisms interact to culminate in channel opening. As members of the voltage-gated potassium channel superfamily, BK channels are discussed in the context of archetypal family members, in terms of similarities that help us understand their function, but also seminal structural and biophysical differences that confer unique functional properties.


Asunto(s)
Biofisica , Activación del Canal Iónico/fisiología , Canales de Potasio de Gran Conductancia Activados por el Calcio/fisiología , Potenciales de la Membrana/fisiología , Animales , Sitios de Unión/fisiología , Calcio/metabolismo , Estimulación Eléctrica , Humanos , Canales de Potasio de Gran Conductancia Activados por el Calcio/química , Modelos Moleculares
9.
Allergy ; 71(8): 1181-91, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-26999633

RESUMEN

BACKGROUND: Pollen-food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens. METHODS: We examined 1271 Italian children (age 4-18 years) with seasonal allergic rhinoconjunctivitis (SAR). Foods triggering PFS were acquired by questionnaire. Skin prick tests were performed with commercial pollen extracts. IgE to panallergens Phl p 12 (profilin), Bet v 1 (PR-10), and Pru p 3 (nsLTP) were tested by ImmunoCAP FEIA. An unsupervised hierarchical agglomerative clustering method was applied within PFS population. RESULTS: PFS was observed in 300/1271 children (24%). Cluster analysis identified five PFS endotypes linked to panallergen IgE sensitization: (i) cosensitization to ≥2 panallergens ('multi-panallergen PFS'); (ii-iv) sensitization to either profilin, or nsLTP, or PR-10 ('mono-panallergen PFS'); (v) no sensitization to panallergens ('no-panallergen PFS'). These endotypes showed peculiar characteristics: (i) 'multi-panallergen PFS': severe disease with frequent allergic comorbidities and multiple offending foods; (ii) 'profilin PFS': oral allergy syndrome (OAS) triggered by Cucurbitaceae; (iii) 'LTP PFS': living in Southern Italy, OAS triggered by hazelnut and peanut; (iv) 'PR-10 PFS': OAS triggered by Rosaceae; and (v) 'no-panallergen PFS': mild disease and OAS triggered by kiwifruit. CONCLUSIONS: In a Mediterranean country characterized by multiple pollen exposures, PFS is a complex and frequent complication of childhood SAR, with five distinct endotypes marked by peculiar profiles of IgE sensitization to panallergens. Prospective studies in cohorts of patients with PFS are now required to test whether this novel classification may be useful for diagnostic and therapeutic purposes in the clinical practice.


Asunto(s)
Alérgenos/inmunología , Conjuntivitis Alérgica/diagnóstico , Hipersensibilidad a los Alimentos/diagnóstico , Alimentos/efectos adversos , Polen/inmunología , Rinitis Alérgica Estacional/diagnóstico , Adolescente , Edad de Inicio , Niño , Preescolar , Análisis por Conglomerados , Comorbilidad , Conjuntivitis Alérgica/epidemiología , Conjuntivitis Alérgica/inmunología , Femenino , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/inmunología , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Italia/epidemiología , Masculino , Vigilancia de la Población , Rinitis Alérgica Estacional/epidemiología , Rinitis Alérgica Estacional/inmunología , Factores de Riesgo , Estaciones del Año , Pruebas Cutáneas , Síndrome
12.
Physiology (Bethesda) ; 28(3): 172-89, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23636263

RESUMEN

Large-conductance Ca2+ -and voltage-gated K+ channels are activated by an increase in intracellular Ca2+ concentration and/or depolarization. The channel activation mechanism is well described by an allosteric model encompassing the gate, voltage sensors, and Ca2+ sensors, and the model is an excellent framework to understand the influences of auxiliary ß and γ subunits and regulatory factors such as Mg2+. Recent advances permit elucidation of structural correlates of the biophysical mechanism.


Asunto(s)
Señalización del Calcio , Activación del Canal Iónico , Subunidades alfa de los Canales de Potasio de Gran Conductancia Activados por Calcio/metabolismo , Animales , Sitios de Unión , Humanos , Subunidades alfa de los Canales de Potasio de Gran Conductancia Activados por Calcio/química , Potenciales de la Membrana , Modelos Biológicos , Modelos Moleculares , Unión Proteica , Conformación Proteica , Relación Estructura-Actividad
16.
J Membr Biol ; 188(1): 73-86, 2002 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-12172648

RESUMEN

Kv4 channels are thought to lack a C-type inactivation mechanism (collapse of the external pore) and to inactivate as a result of a concerted action of cytoplasmic regions of the channel. To investigate whether Kv4 channels have outer pore conformational changes during the inactivation process, the inactivation properties of Kv4.3 were characterized in 0 mM and in 2 mM external K+ in whole-cell voltage-clamp experiments. Removal of external K+ increased the inactivation rates and favored cumulative inactivation by repetitive stimulation. The reduction in current amplitude during repetitive stimulation and the faster inactivation rates in 0 mM external K+ were not due to changes in the voltage dependence of channel opening or to internal K+ depletion. The extent of the collapse of the K+ conductance upon removal of external K+ was more pronounced in NMG+-than in Na+-containing solutions. The reduction in the current amplitude during cumulative inactivation by repetitive stimulation is not associated with kinetic changes, suggesting that it is due to a diminished number of functional channels with unchanged gating properties. These observations meet the criteria for a typical C-type inactivation, as removal of external K+ destabilizes the conducting state, leading to the collapse of the pore. A tentative model is presented, in which K+ bound to high-affinity K+-binding sites in the selectivity filter destabilizes an outer neighboring K+ modulatory site that is saturated at approximately 2 mM external K+. We conclude that Kv4 channels have a C-type inactivation mechanism and that previously reported alterations in the inactivation rates after N- and C- termini mutagenesis may arise from secondary changes in the electrostatic interactions between K+-binding sites in the selectivity filter and the neighboring K+-modulatory site, that would result in changes in its K+ occupancy.


Asunto(s)
Activación del Canal Iónico/fisiología , Canales de Potasio con Entrada de Voltaje , Canales de Potasio/fisiología , Potasio/metabolismo , Línea Celular , Canales de Potasio de Tipo Rectificador Tardío , Conductividad Eléctrica , Humanos , Activación del Canal Iónico/efectos de los fármacos , Riñón/embriología , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Modelos Biológicos , Técnicas de Placa-Clamp , Potasio/farmacología , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio/efectos de los fármacos , Canales de Potasio Shal
17.
J Biol Chem ; 276(34): 31883-90, 2001 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-11427525

RESUMEN

Kv4.3 channels are important molecular components of transient K(+) currents (Ito currents) in brain and heart. They are involved in setting the frequency of neuronal firing and heart pacing. Altered Kv4.3 channel expression has been demonstrated under pathological conditions like heart failure indicating their critical role in heart function. Thyroid hormone studies suggest that their expression in the heart may be hormonally regulated. To explore the possibility that sex hormones control Kv4.3 expression, we investigated whether its expression changes in the pregnant uterus. This organ represents a unique model to study Ito currents, because it possesses this type of K(+) current and undergoes dramatic changes in function and excitability during pregnancy. We cloned Kv4.3 channel from myometrium and found that its protein and transcript expression is greatly diminished during pregnancy. Experiments in ovariectomized rats demonstrate that estrogen is one mechanism responsible for the dramatic reduction in Kv4.3 expression and function prior to parturition. Furthermore, the reduction of plasma membrane Kv4.3 protein is accompanied by a perinuclear localization suggesting that cell trafficking is also controlled by sex hormones. Thus, estrogen remodels the expression of Kv4.3 in myometrium by directly diminishing its transcription and, indirectly, by altering Kv4.3 delivery to the plasma membrane.


Asunto(s)
Regulación de la Expresión Génica/fisiología , Hormonas Esteroides Gonadales/fisiología , Canales de Potasio con Entrada de Voltaje , Canales de Potasio/genética , Isoformas de Proteínas/genética , Animales , Secuencia de Bases , Western Blotting , Clonación Molecular , Cartilla de ADN , Regulación hacia Abajo , Femenino , Inmunohistoquímica , Datos de Secuencia Molecular , Canales de Potasio/metabolismo , Embarazo , Preñez/metabolismo , Isoformas de Proteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Canales de Potasio Shal , Útero/metabolismo , Xenopus laevis
18.
J Gen Physiol ; 117(2): 149-63, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11158167

RESUMEN

In Shaker K(+) channel, the amino terminus deletion Delta6-46 removes fast inactivation (N-type) unmasking a slow inactivation process. In Shaker Delta6-46 (Sh-IR) background, two additional mutations (T449V-I470C) remove slow inactivation, producing a noninactivating channel. However, despite the fact that Sh-IR-T449V-I470C mutant channels remain conductive, prolonged depolarizations (1 min, 0 mV) produce a shift of the QV curve by about -30 mV, suggesting that the channels still undergo the conformational changes typical of slow inactivation. For depolarizations longer than 50 ms, the tail currents measured during repolarization to -90 mV display a slow component that increases in amplitude as the duration of the depolarizing pulse increases. We found that the slow development of the QV shift had a counterpart in the amplitude of the slow component of the ionic tail current that is not present in Sh-IR. During long depolarizations, the time course of both the increase in the slow component of the tail current and the change in voltage dependence of the charge movement could be well fitted by exponential functions with identical time constant of 459 ms. Single channel recordings revealed that after prolonged depolarizations, the channels remain conductive for long periods after membrane repolarization. Nonstationary autocovariance analysis performed on macroscopic current in the T449V-I470C mutant confirmed that a novel open state appears with increasing prepulse depolarization time. These observations suggest that in the mutant studied, a new open state becomes progressively populated during long depolarizations (>50 ms). An appealing interpretation of these results is that the new open state of the mutant channel corresponds to a slow inactivated state of Sh-IR that became conductive.


Asunto(s)
Activación del Canal Iónico/fisiología , Canales de Potasio/genética , Canales de Potasio/metabolismo , Animales , Artefactos , Conductividad Eléctrica , Cinética , Potenciales de la Membrana/fisiología , Mutagénesis/fisiología , Oocitos/fisiología , Técnicas de Placa-Clamp , Probabilidad , Canales de Potasio de la Superfamilia Shaker , Xenopus laevis
19.
Biophys J ; 78(6): 2959-72, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10827975

RESUMEN

We investigated the role of the accessory alpha(2)delta subunit on the voltage-dependent facilitation of cardiac L-type Ca(2+) channels (alpha(1C)). alpha(1C) Channels were coexpressed in Xenopus oocytes with beta(3) and alpha(2)delta calcium channel subunits. In alpha(1C) + beta(3), the amplitude of the ionic current (measured during pulses to 10 mV) was in average approximately 1.9-fold larger after the application of a 200-ms prepulse to +80 mV. This phenomenon, commonly referred to as voltage-dependent facilitation, was not observed when alpha(2)delta was coexpressed with alpha(1C) + beta(3). In alpha(1C) + beta(3), the prepulse produced a left shift ( approximately 40 mV) of the activation curve. Instead, the activation curve for alpha(1C) + beta(3) + alpha(2)delta was minimally affected by the prepulse and had a voltage dependence very similar to the G-V curve of the alpha(1C) + beta(3) channel facilitated by the prepulse. Coexpression of alpha(2)delta with alpha(1C) + beta(3) seems to mimic the prepulse effect by shifting the activation curve toward more negative potentials, leaving little room for facilitation. The facilitation of alpha(1C) + beta(3) was associated with an increase of the charge movement. In the presence of alpha(2)delta, the charge remained unaffected after the prepulse. Coexpression of alpha(2)delta seems to set all the channels in a conformational state from where the open state can be easily reached, even without prepulse.


Asunto(s)
Canales de Calcio Tipo L/química , Canales de Calcio Tipo L/fisiología , Corazón/fisiología , Animales , Membrana Celular/fisiología , Estimulación Eléctrica , Femenino , Sustancias Macromoleculares , Potenciales de la Membrana , Oocitos/fisiología , Técnicas de Placa-Clamp , Conejos , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Factores de Tiempo , Xenopus laevis
20.
FEBS Lett ; 460(3): 427-32, 1999 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-10556510

RESUMEN

Large conductance voltage-dependent and Ca(2+)-modulated K(+) channels play a crucial role in myometrium contractility. Western blots and immunocytochemistry of rat uterine sections or isolated cells show that MaxiK channel protein signals drastically decrease towards the end of pregnancy. Consistent with a transcriptional regulation of channel expression, mRNA levels quantified with the ribonuclease protection assay correlated well with MaxiK protein levels. As a control, Na(+)/K(+)-ATPase protein and RNA levels do not significantly change at different stages of pregnancy. The low numbers of MaxiK channels at the end of pregnancy may facilitate uterine contraction needed for parturition.


Asunto(s)
Miometrio/metabolismo , Hormonas Placentarias/fisiología , Canales de Potasio Calcio-Activados , Canales de Potasio/biosíntesis , Canales de Potasio/genética , ARN Mensajero/biosíntesis , Animales , Western Blotting , Células COS , Células Cultivadas , Femenino , Subunidades alfa de los Canales de Potasio de Gran Conductancia Activados por Calcio , Canales de Potasio de Gran Conductancia Activados por el Calcio , Potenciales de la Membrana , Miometrio/citología , Canales de Potasio/fisiología , Embarazo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Ribonucleasas/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Factores de Tiempo
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