ES2572976T3 - Sistema y método para el tratamiento fotodinámico de la piel - Google Patents

Sistema y método para el tratamiento fotodinámico de la piel Download PDF

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ES2572976T3
ES2572976T3 ES04779826.9T ES04779826T ES2572976T3 ES 2572976 T3 ES2572976 T3 ES 2572976T3 ES 04779826 T ES04779826 T ES 04779826T ES 2572976 T3 ES2572976 T3 ES 2572976T3
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David H. Mcdaniel
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GENTLEWAVES LLC
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/065—Light sources therefor
    • A61N2005/0651—Diodes
    • A61N2005/0652—Arrays of diodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0659—Radiation therapy using light characterised by the wavelength of light used infrared
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0662—Visible light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0662—Visible light
    • A61N2005/0663—Coloured light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0664—Details
    • A61N2005/0667—Filters

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Abstract

Un dispositivo, que consta de: más de una fuente de luz, en el que al menos una fuente de luz está adaptada para emitir radiación electromagnética multicromática de banda estrecha y en la que el dispositivo está adaptado para emitir radiación electromagnética multicromática de banda estrecha a una longitud de onda correspondiente a la luz amarilla de una primera fuente de luz y radiación correspondiente a luz infrarroja procedente de una segunda fuente de luz, en la que la proporción entre la intensidad de la luz amarilla y la luz infrarroja emitida por el dispositivo es de 4:1, y la radiación emitida tiene una fluencia de energía de menos de 4 J/cm2.

Description

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visibles y los 850 nm infrarrojos es bioactiva. También se puede añadir un filtro de IR especial para reducir el componente de IR de la radiación al que la piel o tejido objetivo está expuesto, ya que se cree que esto amortigua asimétricamente la forma de la curva IR/850. Ejemplos de tratamiento de un dispositivo de este tipo se muestran en las figuras de los dibujos adjuntos e ilustran que a 850 nm se cree que es un efecto ’dependiente de la dosis’ sobre
5 los fibroblastos. Además, a un nivel de potencia de aproximadamente 1 mW/cm2, se produce fotomodulación para el efecto de fenotipo de antienvejecimiento (aquellos especializados en el tema reconocerán que los medidores de energía no pueden medir esta con precisión, ya que puede haber cierta variación/error en los métodos del medidor). Generalmente, cuando se desea un tratamiento que no provoque lesión térmica, se aplica una fluencia de energía de menos de unos 4 J/cm2.
10 La proporción entre luz amarilla y radiación IR en la radiación utilizada para el tratamiento se ha descubierto que tiene un efecto sobre el rendimiento general del presente sistema. Se cree que cantidades relativas de cada tipo de radiación son importantes, más aún que el nivel de radiación real (siempre que no ocurra ablación). A unos 4 mW/cm2 para 590 nm y aproximadamente 1 mW/cm2 para los 850 nm (es decir, una relación de 4:1 de amarilla a IR)
15 se ha descubierto que produce buenos resultados. Otro factor a tener en cuenta es la forma de la amplitud frente a la curva de longitud de onda para el componente de IR del sistema.
El ’código’ se refiere al esquema de impulsos para diversos regímenes de tratamiento. Aquí se incluyen diversos factores, tales como longitud de impulso, retardo entre impulsos y repetición de impulsos. Por ejemplo, un 20 tratamiento puede abarcar un código de impulso de tiempo de "conexión" de 250 mseg, tiempo de "desconexión" de 100 mseg (o período oscuro), y 100 impulsos. Esto genera una fluencia de energía total, en J/cm2, de 25 segundos las veces del nivel de potencia de salida de los emisores. Esto permite una comparación de tratamiento de onda pulsada frente a onda continua (el "código" de tratamiento de onda continua sería 1 pulso, un tiempo de "conexión" de cualquier longitud de tratamiento que se elija, y un tiempo de "desconexión" de 0 seg.). En las tablas de datos y
25 figuras de dibujos adjuntas se muestran ejemplos que ilustran diversos códigos, proporciones y niveles de potencia, así como el efecto resultante sobre el efecto de fotoenvejecimiento en ciertos genes, y otros datos.
El descubrimiento actual también se relaciona con un método y dispositivo para tratar las quemaduras solares y otros fotoefectos relacionados con el sol sobre la piel humana o de mamíferos. Un enfoque es el uso de Retin A para
30 antes de la exposición al sol y se están realizando investigaciones utilizando vitaminas C, E y otros antioxidantes tópicamente. Otro enfoque que se está probando es el uso del antioxidante Licopeno, administrado oralmente, para calmar parte de la inflamación producida por quemaduras solares. No obstante, el descubrimiento actual muestra una gran mejora de dichos métodos de tratamiento.
35 Se puede pensar en arrugas, daños por el sol, y otros fotoefectos relacionados con el sol como ’cicatrices solares’. Son lesiones acumulativas que se derivan de la exposición repetida o a largo plazo al sol. El cuerpo humano utiliza un mecanismo de reparación de heridas imperfecto; así, el simulador solar del presente descubrimiento es, de alguna manera, un modelo para la curación de otras heridas. En el presente descubrimiento se utiliza un tratamiento que simula la luz solar desglosada en sus distintos componentes. La parte de UVA1 se utiliza en algunas
40 materializaciones, pero existe UVB y combinaciones de UVA y UVB que son más oncogénicas. Por ejemplo, UV, y en particular UVA1, provoca flacidez y fotoenvejecimiento de la piel, cambios en la matriz dérmica y proteínas estructurales, y aumenta los MPMs. La radiación UV también provoca el aumento de las vías inflamatorias, tales como IL1, IL6 y NFkB. Se sabe que estas vías afectan al envejecimiento y a otros trastornos de la piel relacionados con el sol y daños ambientales, tales como el tabaco, la contaminación, las drogas, enfermedades, lesiones térmicas
45 y otras heridas.
Se cree que el presente descubrimiento inhibe o revierte los efectos del fotoenvejecimiento y otros trastornos cutáneos mediante la inversión de la dirección del aumento/reducción génico desde las direcciones desfavorables y destructivas causadas por los efectos del simulador solar de UVA1 para cosas como colágeno, MPM1, cJun que es
50 importante en relación con MPM1, IL/interleucinas en vías inflamatorias y citocromos. Los ejemplos adjuntos describen el uso del sistema actual para tratamientos ilustrativos.
Los sistemas y métodos del presente descubrimiento se pueden utilizar en combinación con diversos vendajes para heridas como tiritas modificadas para tener una cubierta transparente, de forma que los espectros deseados de 55 fotomodulación mediante LED u otro tipo de luz se transmitan a la zona herida de la piel o tejido diana. Una materialización incluye una ’trampilla’ para permitir la inhibición periódica de la transmisión de la luz. La abertura o parte traslúcida/transparente del vendaje puede comprender también un filtro de IR. En aquellos casos en que no sea deseable incluir una abertura como parte del vendaje o apósito para heridas, el tamaño de los LED y otras fuentes luminosas hace posible incluir una fuente de luz dentro del vendaje. Dicha fuente se podría activar desde
11
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Antes 10% -5% Después 5%
WGW49 c-Fos % Tejido teñido 5 Antes 12% -6% Después 6%
WGW49 c-Jun % Tejido teñido Antes 35% -17% 10 Después 18%
WGW49 ERKI % Tejido teñido Antes 26% -24% Después 2%
15 WGW49 ERK2 % Tejido teñido Antes 13% -11% Después 2%
20 WGW49 TIMP1 % Tejido teñido Antes 15% -4% Después 11%
WGW49 EGFr % Tejido teñído 25 Antes 9% -2% Después 7%
El simulador solar tiene una lámpara de arco de xenón de 1000 vatios, provista de un filtro de agua y un espejo dicroico reflector de UV (280nm -400nm).
30 Se utiliza un filtro Schott WG-360 para similar radiación UVA1. Se ha añadido un filtro de I-Line centrado en 365 nm para eliminar la radiación visible e infrarroja, y se utiliza un filtro Hoya UV34 para filtrar cualquier radiación UVB y UVC restante. Se usa un radiómetro fotorresistente (International Light Inc., Newburyport, MA) para medir la irradiancia total.
35
Todos los resultados de la exposición a 590/810 nm LED(ZZ) o (DD) 250 ms conexión/100 ms desconexión/100 impulsos @ 3,6 mW/cm2
590/810 nm LED(DD) Genes relacionados con el envejecimiento de microarray de 24 hr
40
Proporc. Gen 2.1 HSPB1 proteína 1 de choque térmico 27kD
45 1.6 HSPB2 proteína 2 de choque térmico 27kD
-2.0 SAA1 suero amiloide A1
-1.1 GADD45A detención del crecimiento e inducible de daño de ADN, alfa 50
1.5 RAC1 sustrato 1 de toxina botulínica C3 relacionado con ras (familia rho, proteína de unión a GTP pequeña Rac1)
-1.1 RAC1 sustrato 1 de toxina botulínica C3 relacionado con ras (familia rho, proteína de unión a 55 GTP pequeña Rac1)
-1.1 DCTN1 dinactina 1 (p150, homólogo (Drosófila) pegado)
-1.4 CKMT2 creatina quinasa, mitocondrial 2 (sarcomérica)
13
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-1.3 EST, muy similar a PRECURSOR DE ANHIDRASA CARBÓNICA IV [H.sapiens]
1.0 PKLR piruvatocinasa, hígado y RBC 5
1.1 PSME2 subunidad 2 de activador del proteasoma (prosoma, macropaína) (PA28 beta)
1.1 PSME3 subunidad 3 de activador del proteasoma (prosoma, macropaína) (PA28 beta; Ki)
10 1.0 USA-CYP ciclofilina
1.1 SSR1 receptor de secuencias de señales, alfa (proteína alfa asociada con translocón)
-1.3 CYP3A3 citocromo P450, subfamilia IIIA (nifedipina oxidasa), polipéptido 3 15 -1.1 CYP3A3 citocromo P450, subfamilia IIIA (nifedipina oxidasa), polipéptido 3
1.2 CYP3A3 citocromo P450, subfamilia IIIA (nifedipina oxidasa), polipéptido 3
20 1.0 CYP3A7 citocromo P450, subfamilia IIIA, polipéptido 7
1.1 CYP3A7 citocromo P450, subfamilia IIIA, polipéptido 7
-1.1 CYP3A7 citocromo P450, subfamilia IIIA, polipéptido 7 25
1.2 CYP3A7 citocromo P450, subfamilia IIIA, polipéptido 7
1.3 CYP3A7 citocromo P450, subfamilia IIIA, polipéptido 7
30 1.0 CYP3A7 citocromo P450, subfamilia IIIA, polipéptido 7
1.0 ARNm de timidilato quinasa humana (CDC8), cds completos
1.1 CYP1B1 citocromo P450, subfamilia I, (inducible por dioxina), polipéptido 1, glaucoma 3, infantil 35 primario)
-1.3 CYP1B1 citocromo P450, subfamilia I, (inducible por dioxina), polipéptido 1, glaucoma 3, infantil primario)
40 1.5 CYP1B1 citocromo P450, subfamilia I, (inducible por dioxina), polipéptido 1, glaucoma 3, infantil primario)
1.0 THRA receptor de hormona tiroidea, alfa (homólogo de oncogén viral de la leucemia
eritroblástica aviar (v-erb-a))Todos los resultados de la exposición a 590/810 nm LED(ZZ) o (DD) 250 ms 45 conexión/100 ms desconexión/100 impulsos @ 3,6 mW/cm2
Genes de la vía de la glicólisis 590/810 nm LED (DD)@24 hrs
Proporción Expresión Gen Título
50
2.162361 2.18 TPI1 triosa fosfato isomerasa 1
1.552958 1.55 PGAM1 fosfogliceratomutasa 1 (cerebro) 55 1.448117 1.45 PDHA1 piruvato deshidrogenasa (lipoamida) alfa 1 1.424174 1.42 PGK1 fosfogliceratoquinasa 1
1.421996 1.42 DLD dihidrolipoamida deshidrogenasa (componente E3 de complejo de
17
piruvato deshidrogenasa, complejo 2-oxoglutarato, complejo de deshidrogenasa de ceto-ácido de cadena
ramificada)
5
1.371788 1.282148 miembro 4 1.37 1.26 PCK2 SLC2A4 fosfoenolpiruvato carboxilasa 2 (mitocondrial) familia 2 de transportadores de soluto (transportador de glucosa facilitado)
10
1.182199 1.179769 1.18 1.18 G6PD UGP2 glucosa 6 fosfato deshidrogenasa UDP-glucosa pirofosforilasa 2
1.176488
1.18 PC piruvato carboxilasa
15
1.171328 1.17 PFKP fosfofructocinasa, plaqueta
1.127554
1.13 ALDOA aldolasa A, fructose-bifosfato
20
1.11909 1.113097 1.12 1.11 GRP58 UGCG proteína regulada por glucosa, 58kD UDP-glucosa ceramida glucosiltransferasa
0.975606
-1.03 PGAM2 fosfoglicerato mutasa 2 (músculo)
25
0.968111 miembro 1 -1.03 SLC2A1 familia 2 de transportadores de soluto (transportador de glucosa facilitado)
0.986833
-1.03 GPD1 glicerol-3-fosfato deshidrogenasa 1 (soluble)
30
0.935412 -1.07 KHK ketohexokinasa (fructoquinasa)
0.928888
-1.08 G8PC glucosa-6-fosfatasa, catalítica (enfermedad por almacenamiento de
glucógeno tipo I, enfermedad de Von Gierke)
35 0.927444 -1.08 pseudogén de transportador de glucosa humano 0.923213 -1.08 GPD2 glicerol-3-fosfato deshidrogenasa 2 (mitocondrial) 0.90049 -1.11 PFKM fosfofructocinasa, músculo
40 0.89909 -1.11 PKLR piruvatocinasa, hígado y RBC 0.878266 -1.14 PDK2 piruvato deshidrogenasa quinasa, isoenzima 2 45 0.851629 -1.17 PCK1 fosfoenolpiruvato carboxilasa 1 (soluble) 0.846316 -1.18 ALDOC aldolasa C, fructosa-bifosfato 0.825748 -1.21 HK1 hexoquinasa 1
50 0.810006 -1.23 SLC2A5 familia 2 de transportadores de soluto (transportador de glucosa facilitado) miembro 5
0.800583 -1.25 PFKL fosfofructocinasa, hígado 55 0.785187 -1.27 G6PD glucosa-6-fosfato deshidrogenasa 0.774527 -1.29 G6PT1 glucosa-6-fosfatasa, proteína 1 de transporte (glucosa-6-fosfato)
18
0.763362 -1.31 ALDOB adolasa B, fructosa-bifosfato 0.741454 -1.35 BPGM 2,3-bisfosfoglicerato mutasa
5 0.741454 -1.35 BPGM 2,3-bisfosfoglicerato mutasa 0.729919 -1.37 GFPT1 glutamina fructosa-6-fosfato-transaminasa 1 0.69455 -1.44 AGXT alanina glioxilato aminotransferasa (oxalosis I; hiperoxaluria I; aciduria glicólica;
10 serina-piruvato aminotransferasa 0.65802 -1.52 SLC2A2 familia 2 de transportadores de soluto (transportador de glucosa facilitado) miembro 2
15 0.654048 -1.53 PDK4 piruvato deshidrogenasa quinasa, isoenzima 4 0.648789 -1.55 ARNm 3' de H.sapiens para enolasa específica de neuronas (EC 4.2.1.11) 0.621536 -1.61 FBP1 fructosa-bisfosfatasa 1
20 0.592292 -1.69 ALDOB aldolasa B, fructosa-bisfosfatasa
Genes de la vía de la glicólisis 590/810 nm LED (DD)@4 hrs
25 Proporción Expresión Gen Título 2.276179 2.28 GPD1 glicerol-3-fosfato deshidrogenasa 1 (soluble) 1.750555 1.75 PFKL fosfofructocinasa, hígado
30 1.698153 1.70 ALDOB aldolasa B, fructosa-bifosfato 1.690101 1.69 PFKM fosfofructocinasa, músculo 35 1.590717 1.59 PFKP fosfofructocinasa, plaqueta 1.418758 1.42 FBP1 fructosa-bisfosfatasa 1 1.218502 1.22 G8PC glucosa-6-fosfatasa, catalítica (enfermedad por almacenamiento de 40 glucógeno tipo I, enfermedad de Von Gierke) 1.19087 1.19 UGCG UDP-glucosa ceramida glucosiltransferasa 1.189572 1.19 PCK1 fosfoenolpiruvato carboxiquinasa 1 (soluble) 45 1.186725 1.19 HK1 hexoquinasa 1 1.187392 1.17 ALDOC adolasa C, fructosa-bifosfato
50 1.117239 1.12 ALDOA adolasa A, fructosa-bifosfato 1.09278 1.09 SLC2A2 familia 2 de transportadores de soluto (transportador de glucosa facilitado) miembro 2
55 1.081628 1.08 SLC2A4 familia 2 de transportadores de soluto (transportador de glucosa facilitado) miembro 4 1.03385 1.03 PKLR piruvatocinasa, hígado y RBC
19
imagen14
imagen15
1.0 IL1RAP proteína accesoria de receptor de interleucina 1
-1.1 IL1RAP proteína accesoria de receptor de interleucina 1 5
1.0 IL1A interleucina 1, alfa
1.0 IL1A interleucina 1, alfa 10 -1.1 IL1A interleucina 1, alfa
1.8 IL6 interleucina 6 (interferón, beta 2)
-1.7 IL6 interleucina 6 (interferón, beta 2) 15 -1.1 IL6 interleucina 6 (interferón, beta 2)
Todos los resultados de la exposición a 590/810 nm LED(ZZ) o (DD) 250 ms conexión/100 msdesconexión/100 impulsos @ 3,6 mW/cm2
20
JJ= 623 nm LED Array 250 ms conexión/100 ms desconexión/100 impulsos @ 3,6 mW/cm2
Resultados de microarray para LEDs de post-exposición de 24 hrs de marcadores de queratinocitos (en muestras de fibroblastos humanos)
25
590/810nm (DD) 590/810nm (ZZ) 623nm LED (JJ) 2.1 1.7 -1.3 ARNm de integrina beta-1D humana, dominio
citoplasmático, cds parciales 30
1.6 1.4 -1.3 ARNm de integrina beta-1D humana, dominio citoplasmático, cds parciales
1.5 1.6 -1.1 ARNm de integrina beta-1D humana, dominio 35 citoplasmático, cds parciales
1.3 -1.1 -1.4 ICAM1 Molécula 1 de adhesión intercelular (CD54), receptor de rinovirus humanos
40 1.3 1.0 -1.1 ICAM1 Molécula 1 de adhesión intercelular (CD54), receptor de rinovirus humanos
-1.1 -1.3 1.2 ICAM1 Molécula 1 de adhesión intercelular (CD54), receptor de rinovirus humanos 45
3.0 2.3 -1.7 KRT1 queratina 1 (hiperqueratosis epidermolítica)
1.9 1.1 -3.3 KRT1 queratina 1 (hiperqueratosis epidermolítica)
50 1.1 1.5 1.8 KRT1 queratina 1 (hiperqueratosis epidermolítica)
2.2 1.5 -1.4 KRT10 queratina 10 (hiperqueratosis epidermolítica, queratosis palmar y plantar)
55 1.2 -1.3 -1.3 KRT10 queratina 10 (hiperqueratosis epidermolítica, queratosis palmar y plantar)
1.3 1.0 -1.3 KRT10 queratina 10 (hiperqueratosis epidermolítica, queratosis palmar y plantar)
22
imagen16
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imagen18
imagen19
623 nm LED (JJ) Proporc. Gen Descripción
5 1.2 TGFB1 factor de crecimiento transformador, beta 1
2.0 TGFB3 factor de crecimiento transformador, beta 3
-1.4 TGFB1|1 factor de crecimiento transformador, beta 1 transcripción inducida 1 10
1.7 TGFA factor de crecimiento transformador, alfa
Microarray de 4 hr 15 590/810 nm LED (DD) Proporc. Gen Descripción
-1.4 TGFB1 factor de crecimiento transformador, beta 1 20
1.1 TGFB3 factor de crecimiento transformador, beta 3
-1.1 TGFB1|1 factor de crecimiento transformador, beta 1 transcripción inducida 1 25 1 TGFA factor de crecimiento transformador, alfa
Todos los resultados de la exposición a 590/810 nm LED(ZZ) o (DD) 250 ms conexión/100 msdesconexión/100 impulsos @ 3,6 mW/cm2 30 590/810 nm LED (DD) 24 hrs Proliferación: (funciones estimuladoras)
35 -1.1 CDK5 quinasa dependiente de ciclina 5
-1.4 PDGFA polipéptido alfa de factor de crecimiento derivado de plaquetas
40 1.9 BCRP1 proteína de región de rotura de conglomerados, leiomioma uterino, 1; barrera a factor de autointegración
1.1 MAPK1 proteína quinasa activada por mitógenos 1
45 -1.3 MAPK9 proteína quinasa activada por mitógenos 9 -1.9 MAPK4 proteína quinasa activada por mitógenos 4
1.2 MAPK14 proteína quinasa activada por mitógenos 14
50 -1.3 MAPK10 proteína quinasa activada por mitógenos 10
1 MAPK6 proteína quinasa activada por mitógenos 6
55 -1.1 CCNE1 ciclina E1
1.5 CCNI ciclina I -1.2 KNSL1 similar a quinesina 1
27
imagen20
1.4 APOC3 apolipoproteína C-III
(metabolismo energético y cadena respiratoria)
5 -1 NDUFB4 NADH deshidrogenasa (ubiquinona), 1 beta subcomplejo, 4 (15kD, B15)
1.2 NDUFB7 NADH deshidrogenasa (ubiquinona), 1 beta subcomplejo, 7 (18kD, B18)
1.6 NDUFB1 NADH deshidrogenasa (ubiquinona), 1 beta subcomplejo, 1 (7kD, MNLL)
10 1 ETFA flavoproteína de transferencia de electrones, polipéptido alfa (aciduria glutárica II)
-1.1 ATP5D ATP sintasa, transporte de H+, complejo F1 mitocondrial, subunidad delta
15 1.7 ATP5O ATP sintasa, transporte de H+, complejo F1 mitocondrial, subunidad O (proteína que confiere sensibilidad a la oligomicina)
1.3 ATP5G2 ATP sintasa, transporte de H+, complejo F0 mitocondrial, subunidad c (subunidad 9),
isoforma 2 20
1.7 ATP5F1 ATP sintasa, transporte de H+, complejo F0 mitocondrial, subunidad b, isoforma 1
1.9 ATP5C1 ATP sintasa, transporte de H+, complejo F1 mitocondrial, polipéptido gamma 1 25 Canal iónico, proteínas de transporte y potencial de membrana:
1.5 TAP1 transportador 1, ABC (cassette de unión a ATP)
-1.9 ABC3 cassette 3 de unión a ATP 30
1.8 ABC50 cassette 50 de unión a ATP (estimulado por TNF-alfa) -1.5 KCNJ13 canal de potasio de rectificación interna, subfamilia J, miembro 13
35 -1.1 KCNK1 canal de potasio, subfamilia K, miembro 1 (TWIK-1) -1.1 KCNQ1 canal de potasio, con entrada de voltaje, subfamilia similar a KQT, miembro 1
1.1 KCNAB1 canal de potasio, con entrada de voltaje, subfamilia relacionada con agitador, miembro 1 40 beta
-1 KCNA1 canal de potasio, con entrada de voltaje, subfamilia relacionada con agitador, miembro 1 (ataxia episódica con mioquimia)
45 1.2 KCNB1 canal de potasio, con entrada de voltaje, subfamilia relacionada con Shab, miembro 1
1.6 KCNMB1 canal de potasio activado por calcio de gran conductancia, subfamilia M, miembro 1 beta
-1.8 KCNJ8 canal de potasio de rectificación interna, subfamilia J, miembro 8
50 -1.1 KCNN4 canal de potasio activado por calcio de pequeña/media conductancia, subfamilia N, miembro 4
-1.4 KCNAB2 canal de potasio, con entrada de voltaje, subfamilia relacionada con agitador, miembro 2 55 beta
1.7 KCNK3 canal de potasio, subfamilia K, miembro 3 (TASK) -1.3 KCNJ15 canal de potasio de rectificación interna, subfamilia J, miembro 15
29
1 KCNQ2 canal de potasio, con entrada de voltaje, subfamilia similar a KQT, miembro 2
1.6 CLIC1 canal intracelular de cloruro 1
5
1.3 ASNA1 arsA transportadora de arsenito (bacterial), unión a ATP, homólogo 1
Citoesqueleto, motilidad celular y proteínas de matriz extracelular: 10 (citoesqueleto y motilidad) -2.2 MYH11 miosina, polipéptido pesado 11, músculo liso
1.9 RANBP7 proteína de unión a RAN 7
15
-1.6 ARPC2 complejo 2/3 de proteína relacionada con actina, subunidad 2 (34 kD) -1.2 LRRFIP1 proteína interaccionante 1 de repetición rica en leucina (en FLII) 20 -0.2 TPM1 tropomiosina 1 (alfa)
1.5 TPM2 tropomiosina 2 (beta)
(matriz extracelular)
25
1 FMOD fibromodulina
1.4 FBN1 fibrilina 1 (síndrome de Marfan) 30 -1.4 MMP10 metaloproteinasa de matriz 10 (estromelisina 2)
(migración, agregación y adhesión)
1 CDH13 cadherina 13, cadherina-H (corazón)
35
1.5 CDH11 cadherina 11, cadherina-OB (osteoblastos)
1.9 CDH2 cadherina 2, cadherina-N (neuronal)
40 1.3 CDH17 cadherina 17, cadherina LI (hígado-intestino)
1.1 CDH6 cadherina 6, cadherina-K (riñón fetal) -1.3 CDH3 cadherina 3, cadherina-P (placenta)
45
1 CDH13 cadherina 13, cadherina-H (corazón)
Síntesis y reparación de ADN:
50 -1.4 MPG N-metil purina-ADN glicosilasa 1 APRT adenina fosforribosiltransferasa -1 NUDT1 nudix tipo-(fracción X de unión a nucleósido difosfato) motivo 1
55
Factores de transcripción:
-1.4 GCN5L2 GCN5 similar a-(control general de síntesis de aminoácidos, levadura, homólogo) 2
30
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