Análisis retrospectivo de 23 años de necrólisis epidérmica tóxica en la Unidad de Quemados de Alicante, España / Retrospective analysis of 23 years of toxic epidermal necrolysis in the Burn Unit of Alicante, Spain

El Síndrome de Lyell o Necrólisis Epidérmica Tóxica (NET) se encuadra dentro del espectro de reacciones cutáneas adversas graves y se caracteriza por presentar una baja incidencia pero una elevada mortalidad. La mayoría de los casos de NET se relacionan con una reacción medicamentosa idiosincrática. El objetivo de este trabajo es reflejar la experiencia clínica con esta entidad en la Unidad de Quemados del Hospital General Universitario de Alicante, España, durante los últimos 23 años. Realizamos un estudio retrospectivo recogiendo los datos epidemiológicos, agentes causales probables, pruebas complementarias, patologías concomitantes, tratamiento y evolución clínica. En total recogimos 16 pacientes con una media de edad de 53,19 años, 68,75% mujeres y 31,25% varones. Los antibióticos fueron los fármacos más comúnmente implicados (31,25%), seguidos de los AINES (25%). Durante el ingreso hospitalario, el 43,75% de los pacientes recibió corticoides sistémicos, el 37,5% exclusivamente tratamiento de soporte y el 25% inmunoglobulinas intravenosas. El 56,25% sufrió algún tipo de secuela, siendo la afectación ocular la más frecuente (18,75%). Calculamos el SCORTEN (Severity of illness score for toxic epidermal necrolisys) para todos los pacientes en las primeras 24 horas de ingreso, siendo la suma de las probabilidades predichas de morir por NET de un 32%, cifra superior a los datos reales (mortalidad del 25%). La utilización de corticoides sistémicos sigue siendo controvertida, apareciendo en nuestro estudio un mayor número de infecciones y una mayor mortalidad asociada a dicho tratamiento. La retirada inmediata del fármaco sospechoso, el ingreso precoz en una Unidad de Quemados o de Cuidados Intensivos, el tratamiento de soporte y la reposición hidroelectrolítica, siguen siendo medidas cruciales y de primera línea en el tratamiento de estos pacientes. A pesar de que están descritos diferentes tipos de tratamiento farmacológico para el abordaje de la NET, ninguno ha logrado un rol convincente, por lo que consideramos que se necesitan más estudios prospectivos aleatorizados multicéntricos. Proponemos en este artículo un protocolo de actuación ante este tipo de pacientes (AU)

Lyell's syndrome or Toxic Epidermal Necrolysis (TEN) is considered within the spectrum of severe cutaneous adverse reactions; it's a rare disease but with a high mortality rate. Most of the cases are related to idiosyncratic drug reactions. The aim of this paper is to reflect the clinical experience with this pathology at the Burn Unit of the Universitary General Hospital of Alicante, Spain, for the past 23 years. We conduct a retrospective study, collecting epidemiological data, likely causative agents, additional tests, comorbidities, treatment and clinical evolution, including 16 patients with an average age of 53,19 years; 68,75% were females and 31,25% were males. Antibiotics were most commonly implicated drugs (31.25%), followed by nonsteroidal anti-inflammatory drugs (25%). During admission, 43,75% received systemic corticosteroids, 37,5% only supportive treatment and 25% intravenous immunoglobulin; 56.25% suffered some type of sequel, being the most frequent ocular involvement (18,75%). The SCORTEN (Severity of illness score for toxic epidermal necrolisys) was calculated for all patients in the first 24 hours of admission, the sum of the predicted probabilities of dying from NET it's 32%, higher than the actual data (mortality 25%). The use of systemic corticosteroids remains controversial, appearing in our study a greater number of infections and increased mortality associated with this treatment. Early admission in Burn or Intensive Care Unit, the prompt withdrawal of suspected drug, supportive treatment and fluid and electrolyte replacement, are considered crucial and first-line treatment in these patients. Different drug treatments have been described for the management of this condition without achieving a convincing role, so we considerer that new multicenter randomized prospective studies are required in the future. We propose in this paper a protocol for managing these patients (AU)

Water soluble fluorescent-magnetic perylenediimide-containing maghemite-nanoparticles for bimodal MRI/OI imaging.

The protein shell of apoferritin-encapsulated maghemite nanoparticles was functionalized with two different red-emitting perylenediimide fluorophores (PDI). One glycosacharide-PDI complex has been synthesized for the first time to be labeled to apoferritin-encapsulated maghemite nanoparticles. Bifunctionality of maghemite@perylenediimide was demonstrated by both magnetic-core and fluorescent-labeled shell properties. SQUID measurements confirmed superparamagnetic behavior above 35K. Fluorescence of perylenediimides is retained once attached to the magnetic nanoparticle. Moreover, fluorescence microscopy showed that one of these fluorescent-magnetic nanoparticles was specifically internalized in bifidobacteria without affecting cell viability. These results revealed that the dual-modal imaging probes of maghemite@perylenediimide nanoparticles have the potential to be used as optical/MR dual imaging agents.

Supramolecular zinc phthalocyanine-imidazolyl perylenediimide dyad and triad: synthesis, complexation, and photophysical studies.

Two new supramolecular architectures based on zinc phthalocyanine (Pc) and imidazolyl-substituted perylenediimide (PDI), ZnPc/DImPDI/ZnPc 1 and ZnPc/ImPDI 2, have been prepared. A strong electron-donor, ZnPc-8, which contained eight tert-octylphenoxy groups was synthesized to ensure high solubility, thereby reducing aggregation in solution and providing σ-donor features while avoiding regioisomeric mixtures. Also, PDI units were functionalized with tert-octylphenoxy groups at the bay positions, which provide solubility to avoid aggregation in solution, together with one and two imidazole moieties in the amide position, PDI-6 and PDI-4, respectively, to be able to strongly coordinate with the ZnPc complex. Supramolecular complexation studies by (1)H NMR spectroscopy and ESI-MS demonstrate a high coordinative binding constant between imidazole-substituted PDI-4 or PDI-6 and ZnPc-8. The same results were confirmed by UV/Vis and fluorescence titration studies. UV/Vis titration studies revealed the formation of a 1:1 complex ZnPc/ImPDI 2 for the systems ZnPc-8 and PDI-6 and a 2:1 complex ZnPc/DImPDI/ZnPc 1 for the interaction of ZnPc-8 and PDI-4. The binding constant in both cases was determined to be on the order of 10(5) M(-1). Femtosecond laser flash photolysis measurements provided a direct proof of the charge-separated state within both supramolecular assemblies by observing the transient absorption band at 820 nm due to the zinc phthalocyanine radical cation. The lifetimes of charge-separated states are (9.8±3) ns for triad 1 and (3±1) ns for dyad 2. As far as we know, this is the first time that a radical ion pair has been detected in a supramolecular assembled ZnPc-PDI system and has obtained the longest lifetime of a charge-separated state published for ZnPc-PDI assemblies.

Synthesis and photophysics of silicon phthalocyanine-perylenebisimide triads connected through rigid and flexible bridges.

Three new bisperylenebisimide-silicon phthalocyanine triads [(PBI)(2)-SiPcs 1, 2, and 3] connected with either rigid or flexible bridges were synthesized and characterized. A new synthetic approach to connect SiPc and PBI moieties through click chemistry produced triad 3 with an 80% yield. In (PBI)(2)-SiPc 1, PBI and SiPc are orthogonal and were connected with a rigid connector; triads 2 and 3 bear flexible aliphatic bridges, resulting in a tilted (2) or nearly parallel arrangement (3) of PBI and SiPc. Photoinduced intramolecular processes in these (PBI)(2)-SiPcs were studied and the results are compared with those of the reference compounds SiPc-ref and PBI-ref. The occurrence of electron-transfer processes between the SiPc and PBI units was confirmed by time-resolved emission and transient absorption techniques. Charge-separated (CS) states with lifetimes of 0.91, 1.3 and 2.0 ns for triads 1, 2, and 3, respectively, were detected using femtosecond laser flash photolysis. Upon the addition of Mg(ClO(4))(2), an increase in the lifetime of the CS states to 59, 110 and 200 µs was observed for triads (PBI)(2)-SiPcs 1, 2, and 3, respectively. The energy of the CS state (SiPc(·+)-PDI(·-)/Mg(2+)) is lower than the energy of both silicon phthalocyanine ((3)SiPc*-PDI) and perylenebisimide (SiPc-(3)PDI*) triplet excited states, which decelerates the metal ion-decoupled electron-transfer process for charge recombination to the ground state, thus increasing the lifetime of the CS state. The photophysics of the three triads demonstrate the importance of the rigidity of the spacer and the orientation between donor and acceptor units.

Synthesis and photoinduced electron transfer of phthalocyanine-perylenebisimide pentameric arrays.

Zinc phthalocyanine-perylenebisimide pentameric arrays, ZnPc(PDI)(4) 1 and 2, have been synthesized. ZnPc(PDI)(4) 1 has no substituents in the PDI bay positions, while ZnPc(PDI)(4) 2 presents four phenoxy groups in the bay positions of each perylene. In both cases, the PDI moieties are directly connected to the ZnPc. As a consequence of aggregation, photoexcitation of 1 affords the intermolecular exciplex rather than the charge-separated state. In contrast to 1, photoexcitation of 2, which contains sterically demanding substituents in the PDI moieties, affords the charge-separated (CS) state, which was clearly detected by its transient absorption spectrum in femtosecond laser flash photolysis measurements. The CS lifetime was determined to be 26 ps. The addition of Mg(ClO(4))(2) to a benzonitrile solution of 2 and the photoexcitation affords the long-lived CS state with the lifetime of 480 micros, whereas no such long-lived CS state was formed in the case of 1 under such conditions. The remarkable elongation of the CS lifetime results from the strong binding of Mg(2+) to the PDI(*-) moiety in the CS state.

Indium-mediated synthesis of heterobiaryls.

The palladium-mediated coupling reaction between triorganoindium reagents and organic electrophiles is extended to the synthesis of heteroaromatic compounds. Both electron-rich and electron-poor heterocycles can act as the organic electrophile or as the organoindium derivative.