Subdermal dissection technique for pure skin SCIA and ALT perforator flaps in burns and trauma defects: Clinical experience.

BACKGROUND: The pure skin perforator (PSP) flap is gaining popularity for its remarkable thinness. The subdermal dissection technique was recently introduced, allowing for a quicker elevation of a PSP flap. In this report, we present our two-year experience utilizing subdermal dissection for harvesting PSP flaps. METHODS: All patients who had undergone PSP flap reconstruction at our hospital from February 2021 to February 2023 were included. Demographic data, intraoperative variables, flap characteristics, and postoperative outcomes were collected. Surgical planning involved locating the perforator using ultrasound and harvesting the flap using the subdermal dissection technique. RESULTS: A total of 26 PSP flap reconstructions were conducted on 24 patients aged between 15 and 86 years. The flaps were based on perforators issuing from the superficial circumflex iliac artery in 24 cases, and from the descending branch of the lateral circumflex femoral artery in 2 cases. Flap sizes ranged from 3 × 1.5 cm to 19 × 6 cm, with a mean thickness of 3.48 mm. The average time for flap harvest was 131.92 min. Postoperatively, we observed four cases of partial necrosis, 1 total flap loss, and 2 instances of vascular thrombosis at the anastomosis site. The flaps exhibited good pliability without contracture, and no debulking procedures were required during the follow-up period (minimum 6 months, range 6-24; mean 9.4615). CONCLUSION: The subdermal dissection technique is a safe and efficient approach for elevating PSP flaps. Our initial experience with this technique has been encouraging, and it currently serves as our preferred reconstructive option for defects requiring thin reconstruction.

The redistributive effects of pandemics: Evidence on the Spanish flu.

Which are the effects of pandemics on the returns to factors of production? Are these effects persistent over time? These questions have received renewed interest after the out-burst of deaths caused by Covid-19. The Spanish Flu is the closest pandemic to Covid-19. In this paper, we analyze the impact of the Spanish Flu on the returns to labor and capital in Spain. Spain is an ideal country to perform this exercise. First, the "excess death rate" was one of the largest in Western Europe and it varied substantially across regions. Second, Spain was transitioning towards industrialization, with regions in different stages of development. Third, Spain was developed enough to have reliable data. We identify the effect of the Spanish Flu by exploiting within-country variation in "excess death rate". Our main result is that the effect of the Spanish Flu on daily real wages was large, negative, and broadly short-lived. The effects are heterogeneous across occupations and regions. The negative effects are exacerbated in (i) occupations producing non-essential goods like shoemakers and (ii) more urbanized provinces. Quantitatively, relative to pre-1918, the decline for the average region ranges from null to around 30 percent. In addition, we fail to find significant negative effects of the flu on returns to capital. Whereas the results for dividends are imprecisely estimated (we cannot reject a null effect), the effect on real estate prices (houses and land), driven by the post-1918 recovery, is positive. Experts on inequality have argued that pandemics have equalizing effects especially in a Malthusian setting, due to real wage increases. Our findings suggest that, at least, for a developing economy like Spain in the early 20th century, this result does not apply. Indeed, we document that the flu pandemic was conducive to a (short-run) reduction in real wages. In addition, we interpret our heterogeneous results as suggestive evidence that pandemics represent a demand shock.

Socioeconomic mortality differences during the Great Influenza in Spain.

Despite being one of the deadliest viruses in history, there is limited information on the socioeconomic factors that affected mortality rates during the Great Influenza Pandemic. In this study, we use occupation-province level data to investigate the relationship between influenza excess mortality rates and occupation-related status in Spain. We obtain three main results. Firstly, individuals in low-income occupations experienced the highest excess mortality, pointing to a notable income gradient. Secondly, professions that involved more social interaction were associated with a higher excess of mortality, regardless of income. Finally, we observe a substantial rural mortality penalty, even after controlling for income-related occupational groups. Based on this evidence, it seems that the high number of deaths was caused by not self-isolating. Some individuals did not quarantine themselves because they could not afford to miss work. In rural areas, home confinement was likely more limited because their inhabitants did not have immediate access to information about the pandemic or fully understand its impact due to their limited experience handling influenza outbreaks.

Enzymatic Debridement (Nexobrid) on Burned Hands: Retrospective Review from a Burn Referral Center in Spain.

Background: In deep burns, the gold standard of treatment is surgical debridement and coverage, but in hands, this may lead to poor aesthetic and functional results due to the complexity of this anatomical area. Enzymatic debridement (Nexobrid) allows for the preservation of the dermal remnant and reduces the number of skin grafts when compared with surgical excision. The study aimed to analyze the patients with intermediate second-degree or deeper burns in hands who required surgical treatment after Nexobrid and those who avoided it. Methods: A descriptive retrospective study of all patients who underwent Nexobrid following hand burns between May 2015 and April 2020 treated in Vall d'Hebrón University Hospital was conducted. After the enzymatic debridement, the burn unit team determined if the burn required conservative treatment or surgery, based on the characteristics of the wound bed. Results: A total of 202 hands were collected. Most hands included in this study had deep second-degree burns (122; 60.4%). Almost half of the hands underwent surgery (99; 49%), and most had deep second-degree burns (61; 61.62%). During follow-up, 24 hands required surgery for sequelae (11.88%) and 62 did not undergo follow-up (30.69%). In the group that needed sequelae surgery, 21 needed surgery after Nexobrid and three of them were healed with conservative treatment after Nexobrid (P < 0.001). Conclusions: Nexobrid decreases the number of surgical procedures in deep burns of the hand because more conservative attitudes are adopted. Also, it seems to reduce the need of surgery due to burn sequelae.

Sensory alteration patterns in burned patients.

INTRODUCTION: Burned patients may present with different type and severity of sensory dysfunction. Regenerative mechanisms in the peripheral nervous system are diminished after burn injury and thus unable to accurately regenerate somatosensitive skin receptors. The pattern by which neuronal regeneration occurs to regain this sensitivity in burn patients is still unclear. PATIENTS AND METHOD: This observational retrospective study focuses on determining the patterns of heat, heat-pain, cold, cold-pain, sympathetic skin response and touch following severe burns. Twenty-six burn patients with different type of burns were included in the study. The survey methods used included the Quantitative Sensory Test for termoalgesic measurement, electrical SSR and the Von Frey filaments for quantitative measurements of touch/pressure. RESULTS: The results showed that patients present with hypoesthesia to heat, cold, and touch in postburn skin areas compared with the contralateral healthy areas. However, in the heat-pain sensation, no hypoesthesia was noted. CONCLUSIONS: Our results suggest that burn patients have a sensitivity dysfunction in postburned skin areas. The use of QST could be considered the technique to determine the sensitivity of burned patients. Although, more high-quality studies should to be done.

Implementation and evaluation of telemedicine in burn care: Study of clinical safety and technical feasibility in a single burn center.

OBJECTIVE: The objective of this study is to review our experience in the implementation of an innovative Telemedicine Platform (the Teleburns Project) for the acute care of burned patients. METHODS: We developed and implemented a Teleburns Platform by the creation of a new medical software and hardware for High Definition medical videoconference, in order to assist distant burned patients. After the establishment of the system and revision of technical requirements, an internal validation of the project was done: we managed 40 consecutive burned patients via telemedicine videoconference within our own Center. Following the internal validation, a pilot test with the Verge de la Cinta Hospital (VCH) - located in Tortosa, 180km away from Barcelona - was conducted. A prospective review of 43 burn patients participating in tele-encounters was performed. The data collected were: patient and injury demographics, need for transfer to our hospital, need for surgical treatment, complications, readmissions and technical problems. RESULTS: No discrepancies were found between remote and face-to-face diagnosis and treatment during internal validation, obtaining a 100% reliability. No technical errors were reported. Concerning the pilot test with the VCH, 43 patients were assessed via telemedicine during a 48-month period. Mean age of the participants was 36.7 (0-85 years). The mean total burn surface area was 3.1% (range 0.5-15%). The more frequently affected areas were head and neck (27 patients) and hands (16 patients). As a result of the 43 televisits, 8 patients (18.6%) were immediately transferred to our Burn Center in Barcelona and 12 patients (27.9%) were asked to come a few days later, to be visited in our Day Care Unit. Thus 23 patients (53.5%) could avoid being transferred to the Burn Center. 5 of them were followed via Teleburns without complications and 17 patients were discharged after the first tele-encounter. All patients discharged presented an uneventful evolution and did not receive further care from our Burn Unit. Technical problems were reported in eleven occasions during this phase, none of which prevented completion of the visits. CONCLUSIONS: The use of Telemedicine for burn assessment can improve the accuracy of burn patients triage, resulting in enhanced resource utilization, time and cost saving for the health system and increased quality of care.

Comparative insight into the Zn(II)-, Cd(II)- and Cu(I)-binding features of the protozoan Tetrahymena pyriformis MT1 metallothionein.

Tetrahymena pyriformis MT1 (TpyMT1) is a model among ciliate metallothioneins (MTs). Here, we report on the analytic (ICP-AES, GC-FPD), spectroscopic (CD, UV-Vis, Raman) and spectrometric (ESI-MS) characterization of its recombinant Cd(II)-, Zn(II)- and Cu(I)-complexes, and of those formed during in vitro Zn/Cd and Zn/Cu replacement. In the presence of Cd(II), TpyMT1 renders a major Cd 11-TpyMT1 species, which is also the final step reached in the in vitro Zn/Cd exchange process in Zn 11-TpyMT1. Spectroscopic data supports a different folding of the isostoichiometric Cd 11- and Zn 11-TpyMT1 complexes. Unexpectedly, TpyMT1 biosynthesis in Zn(II)-rich cultures was sensitive to the aeration degree, so that high oxygenation rendered undermetalated, partially-oxidized, complexes (Zn9-TpyMT1). Biosynthesis in Cu(I)-rich media rendered extremely heterogeneous mixtures of CuxZny-species (x+y=8-20), where the higher the aeration, the higher the Zn(II) content. The complexity of these samples was reproduced during the Zn/Cu replacement, as the number of generated species increased gradually with the addition of copper to Zn(11)-TpyMT1. According to our results, a clear preference of TpyMT1 for Cd(II) binding, rather than for Zn(II), and especially Cu(I) can be postulated. This character is totally consistent with the induction pattern of the TpyMT1 gene and the postulated role of TpyMT1 in Cd-detoxification.

Zinc and cadmium complexes of a plant metallothionein under radical stress: desulfurisation reactions associated with the formation of trans-lipids in model membranes.

Metallothioneins (MTs) are sulfur-rich proteins capable of binding metal ions to give metal clusters. The metal-MT aggregates used in this work were Zn- and Cd-QsMT, where QsMT is an MT from the plant Quercus suber. Reactions of reductive reactive species (H(*) atoms and e(aq)(-)), produced by gamma irradiation of water, with Zn- and Cd-QsMT were carried out in both aqueous solutions and vesicle suspensions, and were characterized by different approaches. By using a biomimetic model based on unsaturated lipid vesicle suspensions, the occurrence of tandem protein/lipid damage was shown. The reactions of reductive reactive species with methionine residues and/or sulfur-containing ligands afford diffusible sulfur-centred radicals, which migrate from the aqueous phase to the lipid bilayer and transform the cis double bond of the oleate moiety into the trans isomer. Tailored experiments allowed the reaction mechanism to be elucidated in some detail. The formation of sulfur-centred radicals is accompanied by the modification of the metal-QsMT complexes, which were monitored by various spectroscopic and spectrometric techniques (Raman, CD, and ESI-MS). Attack of the H(*) atom and e(aq)(-) on the metal-QsMT aggregates can induce significant structural changes such as partial deconstruction and/or rearrangement of the metal clusters and breaking of the protein backbone. Substantial differences were observed in the behaviour of the Zn- and Cd-QsMT aggregates towards the reactive species, depending on the different folding of the polypeptide in these two cases.

Plant metallothionein domains: functional insight into physiological metal binding and protein folding.

Plant metallothioneins (MTs) differ from animal MTs by a peculiar sequence organization consisting of two short cysteine-rich terminal domains linked by a long cysteine-devoid spacer. The role of the plant MT domains in the protein structure and functionality is largely unknown. Here, we investigate the separate domain contribution to the in vivo binding of Zn and Cu and to confer metal tolerance to CUP1-null yeast cells of a plant type 2 MT (QsMT). For this purpose, we obtained three recombinant peptides that, respectively, correspond to the single N-terminal (N25) and C-terminal (C18) cysteine-rich domains of QsMT, and a chimera in which the spacer is replaced with a four-glycine bridge (N25-C18). The metal-peptide preparations recovered from Zn- or Cu-enriched cultures were characterized by ESI-MS, ICP-OES and CD and UV-vis spectroscopy and data compared to full length QsMT. Results are consistent with QsMT giving rise to homometallic Zn- or Cu-MT complexes according to a hairpin model in which the two Cys-rich domains interact to form a cluster. In this model the spacer region does not contribute to the metal coordination. However, our data from Zn-QsMT (but not from Cu-QsMT) support a fold of the spacer involving some interaction with the metal core. On the other hand, results from functional complementation assays in endogenous MT-defective yeast cells suggest that the spacer region may play a role in Cu-QsMT stability or subcellular localization. As a whole, our results provide the first insight into the structure/function relationship of plant MTs using the analysis of the separate domain abilities to bind physiological metals.

Organización de unidades de quemados durante la pandemia por COVID-19: experiencia de 5 unidades de quemados / Organization of burn units during the COVID-19 pandemic: experience of 5 burn units

El 11 de marzo de 2020, el brote del coronavirus SARS-Cov-2 fue declarado pandemia global, suponiendo un reto para todos los sistemas sanitarios del mundo. Por este motivo, desde los distintos estados se ha llevado a cabo una reorganización de los sistemas nacionales de salud para lidiar con esta enfermedad. En este contexto han surgido nuevas recomendaciones en el manejo del paciente quirúrgico, posponiéndose las cirugías electivas. No obstante, la naturaleza urgente del tratamiento del paciente gran quemado es un hecho que justifica su tratamiento quirúrgico, incluso en casos afectados por el virus. La coincidencia de la precocidad e intensidad con que la pandemia afectó a España con la existencia de una escasa evidencia en cuanto a la organización de las unidades de quemados en este nuevo contexto, propició que la organización de cada centro surgiera de novo en función de sus circunstancias particulares. En este trabajo, exponemos los esquemas organizativos y la experiencia de 5 unidades de quemados, 4 españolas y 1 chilena, en su adaptación al contexto de la pandemia por COVID-19

On March 11th, a pandemic situation caused by the virus SARS-Cov-2 was declared, challenging health-care systems all over the world. Therefore, a reorganization of national health-care systems had to be performed in order to deal with this disease. In this context, new recommendations have appeared for the management of surgical patients, postponing elective surgeries. However, urgency in the treatment of burn patients is justified, even in those cases affected by the virus. The coincidence of the precocity and intensity with which the pandemic affected Spain, with the existence of scarce evidence regarding burn unit organization, caused that reorganization of each center had to be performed from scratch, adapting their particular circumstances. In this article, we expose the organizational schemes and the experience of 5 burn units, 4 in Spain and 1 more in Chile, in their adaptation to the COVID-19 pandemic

Aplicación de la Microcirugía en el tratamiento del paciente quemado eléctrico / Application of Microsurgery in the treatment of the electric burned patient

INTRODUCCIÓN Y OBJETIVO: La Microcirugía como técnica dentro de la Cirugía Plástica no puede faltar en cualquier unidad de quemados para garantizar el tratamiento completo de sus pacientes. Sobre todo en los quemados eléctricos que presentan lesiones muy graves con exposición de tejidos nobles en los que es la primera opción reconstructiva. El objetivo de este artículo es mostrar la experiencia de la Unidad de Quemados del Hospital Universitario Vall d'Hebron de Barcelona, España, en los últimos 10 años en el uso de la Microcirugía en el paciente quemado agudo de etiología eléctrica. MATERIAL Y MÉTODO: Revisión retrospectiva de 19 colgajos realizados entre enero de 2010 y agosto de 2019 en 15 pacientes con quemaduras eléctricas, recogiendo datos de sexo, edad, localización del defecto, superficie corporal quemada (SCQ), colgajo empleado, días hasta la cobertura, tipo de anastomosis arterial, número de venas usadas, supervivencia de los colgajos y complicaciones. RESULTADOS: Destaca que los 15 pacientes fueron varones, con edad media de 36.5 años; SCQ media del 19.5%; el colgajo más usado fue el ántero-lateral de muslo con 9 casos (47.37%), seguido por el de dorsal ancho con 4 casos (21.05%), el colgajo inguinal y el de músculo recto femoral con 2 casos cada uno (10.53% en cada caso) y el de perforante tóraco-dorsal y de fascia temporal superficial con 1 caso cada uno (5.26% en cada caso). La localización más frecuente fue en extremidades inferiores con 12 casos (63.16%), seguida por las extremidades superiores con 5 casos (26.31%) y la cabeza con 2 casos (10.53%). La cirugía de cobertura con el colgajo libre se realizó de media a los 24 días. La anastomosis arterial fue término-terminal en 15 casos (79%). La anastomosis venosa fue término-terminal siempre, anastomosando 2 venas en 5 casos (26.31%) y solo 1 en el resto (73.69%). Dos colgajos fracasaron por congestión venosa (10.53%) y 2 colgajos se complicaron por infección (10.53%). CONCLUSIONES: La reconstrucción de defectos complejos tras quemadura eléctrica es un reto por el escaso número de casos que se presentan y por la propia idiosincrasia de la injuria eléctrica y del paciente quemado. El desbridamiento correcto, la selección del vaso receptor y decidir el momento óptimo para la reconstrucción son los puntos más importantes a tener en cuenta. Por estos motivos consideramos que esta patología debe ser abordada en unidades de quemados multidisciplinares con personal altamente entrenado

BACKGROUND AND OBJECTIVE: Microsurgery as a technique in Plastic Surgery cannot miss any burn ut for complete treatmeent of their patientes. Especially in electric burns that have very serious lesions with exposure of noble tissues where Microsurgery is the first reconstructive option. The objective of this paper is to show the experience of the Burn Unit of the Vall d'Hebron University Hospital in Barcelona, Spain, over the last 10 years in the application of Microsurgery in the burned patient of electrical etiology. METHODS: A total of 19 flaps performed between January 2010 and August 2019 in patients with electrical burn injury were reviewed retrospectively. The data collected were sex, age, location of the defect, total burned surface area (TBSA), flap used, days until coverage, type of arterial anastomosis, number of veins used, flap survival and complications. RESULTS: It is noteworthy that all the 15 patients treated were male, with an average age of 36.5 years; average TBSA was 19.5%; the most frequently flap used was the antero-lateral thigh in 9 cases (47.37%), followed by the latissimus dorsi muscle in 4 cases (21.05%), the inguinal and the rectus femoris muscle in 2 cases each (10.53% in each case) and the thoraco-dorsal artery perforator and the superficial temporal fascia on 1 occasion each of them (5.26% in each case). The most frequent location was in the lower extremities in 12 cases (63.16%), followed by the upper extremities in 5 cases (26.31%) and the head in 2 cases (10.53%). On average, coverage surgery with the free flap was performed at 24 days. Arterial anastomosis was performed end-to-end in 15 cases (79%). The venous anastomosis was always end-to-end anastomosing 2 veins in 5 cases (26.31%) and only 1 in the rest (76.69%). Two flaps failed due to venous congestion (10.53%) and 2 flaps were complicated with infection (10.53%). CONCLUSIONS: The reconstruction of complex defects associated with an electrical burn has been, is a challenge for plastic surgeons because of the small number of cases that occur and, because of the idiosyncrasy of the electrical injury and the burned patient. A correct debridement, the selection of the recipient vessel and deciding the optimal time for reconstruction are the most important points to consider. For these reasons we believe that this pathology should be addressed in multidisciplinary burn units with highly trained personnel

The sea urchin metallothionein system: Comparative evaluation of the SpMTA and SpMTB metal-binding preferences.

Metallothioneins (MTs) constitute a superfamily of ubiquitous metal-binding proteins of low molecular weight and high Cys content. They are involved in metal homeostasis and detoxification, amongst other proposed biological functions. Two MT isoforms (SpMTA and SpMTB) have been reported in the echinoderm Strongylocentrotus purpuratus (sea urchin), both containing 20 Cys residues and presenting extremely similar sequences, although showing distinct tissular and ontogenic expression patterns. Although exhaustive information is available for the Cd(II)-SpMTA complex, this including the full resolution of its 3D structure, no data has been reported concerning either SpMTA Zn(II) and Cu(I) binding properties, or the characterization of SpMTB at protein level. In this work, both the SpMTA and SpMTB isoforms, as well as their separate α and ß domains, have been recombinantly synthesized in the presence of Zn(II), Cd(II) or Cu(II), and the corresponding metal complexes have been analyzed using electrospray mass spectrometry, and CD, ICP-AES and UV-vis spectroscopies. The results clearly show a better performance of isoform A when binding Zn(II) and Cd(II), and of isoform B when coordinating Cu(I). Thus, our results confirm the differential metal binding preference of SpMTA and SpMTB, which, together with the reported induction pattern of the respective genes, highlights how also in Echinodermata the MT polymorphism may be linked to the evolution of different physiological roles.

Guía clínica de consenso en el uso de desbridamiento enzimático en quemaduras con NexoBrid(R) / Consensus guideline about the use of the enzymatic debridement in burn injuries with NexoBrid(R)

Introducción y Objetivo. El desbridamiento precoz es la base del tratamiento de las quemaduras. La retirada de la escara durante las primeras 72 horas es la mejor opción para reducir la estancia hospitalaria y los eventos infecciosos. Sin embargo, en muchas ocasiones se compromete la dermis viable necesaria para obtener los mejores resultados estéticos y funcionales, obligando a injertar el lecho. Hay numerosa evidencia acerca de la reducción de las tasas de injerto, la pérdida hemática y el número de intervenciones cuando se utiliza un desbridante enzimático, NexoBrid(R). El objetivo de esta publicación es establecer una guía clínica basada en la opinión de los expertos españoles. Material y Método. Se diseñó un panel de 7 expertos de las principales Unidades de Quemados españolas, con más de 350 pacientes tratados, que discutió las diferentes fases del tratamiento con NexoBrid(R) para obtener una guía clínica de consenso acerca de la indicación, uso y manejo del desbridamiento enzimático. Resultados. Se alcanzó un alto nivel de consenso, con más del 70% de acuerdo en cada una de las fases de tratamiento. Todos los aspectos del tratamiento con NexoBrid(R) fueron discutidos durante la reunión, así como las indicaciones y limitaciones de su uso, incluyendo todas las nuevas evidencias publicadas hasta el momento. También las diversas opciones utilizadas por los diferentes centros de quemados españoles, alcanzando una recomendación global sobre su uso. Conclusiones. Se redactó un documento como guía clínica preliminar sobre el uso de NexoBrid(R) hasta que se creen nuevas guías basadas en evidencia. No existe ningún otro consenso similar publicado hasta el momento (AU)

Background and Objective: Early debridement is considered the keystone of the burn injuries treatment. It is well known that the eschar removal during the first 72 hours is the best option to reduce the hospital stay and the infectious events. However this treatment compromise the preservation of viable dermis, needed to reach the best functional and aesthetic outcome, therefore grafting the wound bed is mandatory. There is increasing evidence that enzymatic debridement with NexoBrid(R) is showing a reduction in the grafting rate, the blood loss and the number of surgical excisions. The objective of this consensus meeting is providing guidelines based in Spanish experts experiences. Methods. A panel of 7 experts from the main Spanish Burn Units were design, with more than 350 patients treated by them, where the different statements were discussed, trying to get a consensus guideline of the indication, use and management of NexoBrid(R). Results. A high level agreement was stated. All the aspects of NexoBrid(R) treatment were discussed showing an agreement of 70%, as well as the indications and limitations of its use. All new evidence published so far this paper was included. Different treatment options used by the Spanish Burn Centers were discussed, showing a global recommendation in their use. Conclusions. A consensus document was created as a preliminary guideline for the NexoBrid(R) use until further guidelines are available. There is no other consensus guideline published so far this document (AU)

Técnica de Charles en elefantiasis de extremidad inferior. Caso clínico / Charles procedure in lower limb elephantiasis. A case report

La primera opción terapéutica para el linfedema consiste en medidas conservadoras conocidas como terapia descongestiva compleja, de la que se benefician muchos pacientes. Sin embargo, los casos refractarios severos requieren abordaje quirúrgico. Existen numerosas técnicas disponibles con tasas de recurrencia variables. La técnica de Charles es una alternativa apropiada para los casos más severos. Presentamos nuestra experiencia en un caso en varón de 21 años de edad con elefantiasis masiva de la extremidad inferior izquierda secundaria a linfedema congénito sin respuesta al tratamiento conservador. Tras una valoración clínica y radiológica exhaustiva se propone cirugía ablativa según la técnica de Charles, que llevamos a cabo en 3 tiempos quirúrgicos en 8 meses con resultados globalmente favorables. De paso revisamos la práctica actualmente aceptada para el tratamiento del linfedema de la extremidad inferior y las opciones terapéuticas disponibles (AU)

The first therapeutic option of lymphedema consists on a series of conservative measures known as complex descongestive therapy. Many patients benefit from this program. However, refractory severe cases require surgical management. Many techniques are available with different rates of recurrence. The Charles procedure is an appropriate alternative for severe cases. We present our experience with a 21 years old man with left lower limb massive elephantiasis secondary to congenital lymphedema refractory to conservative treatment. After clinical and radiological assessment, ablative surgery was proposed according to the Charles procedure, performed on 3 surgical times over 8 months, with favorable outcomes. By the way, we review the accepted practice to treat lymphedema in lower limb and the available therapeutic options (AU)

Caenorhabditis elegans metallothionein isoform specificity--metal binding abilities and the role of histidine in CeMT1 and CeMT2.

Two metallothionein (MT) isoforms have been identified in the model nematode Caenorhabditis elegans: CeMT1 and CeMT2, comprising two polypeptides that are 75 and 63 residues in length, respectively. Both isoforms encompass a conserved cysteine pattern (19 in CeMT1 and 18 in CeMT2) and, most significantly, as a result of their coordinative potential, CeMT1 includes four histidines, whereas CeMT2 has only one. In the present study, we present a comprehensive and comparative analysis of the metal [Zn(II), Cd(II) and Cu(I)] binding abilities of CeMT1 and CeMT2, performed through spectroscopic and spectrometric characterization of the recombinant metal-MT complexes synthesized for wild-type isoforms (CeMT1 and CeMT2), their separate N- and C-terminal moieties (NtCeMT1, CtCeMT1, NtCeMT2 and CtCeMT2) and a DeltaHisCeMT2 mutant. The corresponding in vitro Zn/Cd- and Zn/Cu-replacement and acidification/renaturalization processes have also been studied, as well as protein modification strategies that make it possible to identify and quantify the contribution of the histidine residues to metal coordination. Overall, the data obtained in the present study are consistent with a scenario where both isoforms exhibit a clear preference for divalent metal ion binding, rather than for Cu coordination, although this preference is more pronounced towards cadmium for CeMT2, whereas it is markedly clearer towards Zn for CeMT1. The presence of histidines in these MTs is revealed to be decisive for their coordination performance. In CeMT1, they contribute to the binding of a seventh Zn(II) ion in relation to the M(II)(6)-CeMT2 complexes, both when synthesized in the presence of supplemented Zn(II) or Cd(II). In CeMT2, the unique C-terminal histidine abolishes the Cu-thionein character that this isoform would otherwise exhibit.

Raman study of in vivo synthesized Zn(II)-metallothionein complexes: structural insight into metal clusters and protein folding.

Metallothioneins (MTs) are metal-chelating peptides that play an active role in zinc homeostasis. The participation of metal ligands other than cysteines and the presence of secondary structure elements in metal-MT complexes are fairly unknown, especially in nonvertebrate MTs. Here, four Zn(II) complexes of invertebrate MTs (mollusc, insect, nematode, and echinoderm) and the Zn(II)-MT complex of the mammalian MT1 isoform, heterologously synthesized in E. coli, were studied by analytic and spectroscopic techniques. By Raman and circular dichroism spectroscopy, new structural informations were obtained. The five analyzed MT isoforms consist largely of beta-turns with the near exclusion of alpha-helical segments. Raman spectroscopy was revealed as an useful tool, providing information about the state of the cysteine sulfur atoms (metal coordinated and oxidized), the participation of histidine in metal coordination, and the molecular environment of tyrosine residues. In all the five Zn(II)-MT studied samples, acid-labile sulfide anions were found as nonproteic ligands, since sulfide-containing and sulfide-devoid species coexisted in the corresponding preparations. Significantly, Raman bands useful as markers of sulfide bridging ligands were identified. Overall, this work illustrates how the combination of analytical and spectroscopic techniques can be a very informative approach for the analysis of in vivo-synthesized metal-MT complexes, providing new data on the metal binding behavior of MTs from the most diverse organisms.

The metal-binding features of the recombinant mussel Mytilus edulis MT-10-IV metallothionein.

In contrast with the paradigmatic mammalian metallothioneins (MTs), mollusc MT systems consist at least of a high-cadmium induced form, possibly involved in detoxification, and another isoform either constitutive or regulated by essential metals and probably associated with housekeeping metabolism. With the aim of providing a deeper characterization of the coordination features of a molluscan MT peptide of the latter kind, we have analyzed here the metal-binding abilities of the recombinant MeMT-10-IV isoform of Mytilus edulis (MeMT). Also, comparison with other MTs of this type has been undertaken. A synthetic complementary DNA was constructed, cloned and expressed into two Escherichia coli systems. Upon zinc coordination, MeMT folds in vivo into highly chiral and stable Zn(7) complexes, with an exceptional reluctance to fully substitute cadmium(II) and/or copper(I) for zinc(II). In vivo cadmium binding leads to homometallic Cd(7) complexes that structurally differ from any of the in vitro prepared Cd(7) complexes. Homometallic Cu-MeMT can only be obtained in vitro from Zn(7)-MeMT after a great molar excess of copper(I) has been added. In vivo, two different heterometallic Zn,Cu-MeMT complexes are recovered, which nicely correspond to two distinct stages of the in vitro zinc/copper replacement. These MeMT metal-binding features are consistent with a physiological role related to basal/housekeeping metal, mainly zinc, metabolism, and confirm the correspondence between the MeMT gene response pattern and the functional properties of the encoded protein.

Structural study of the zinc and cadmium complexes of a type 2 plant (Quercus suber) metallothionein: insights by vibrational spectroscopy.

Zn- and Cd-complexes of Quercus suber metallothionein (QsMT) were obtained by in vivo-synthesis, in order to obtain physiologically representative aggregates, and characterized by spectrometric and spectroscopic methods. The secondary structure elements and the coordination environments of the metal binding sites of the two aggregates were determined, as well as the main metal-containing species formed. The results obtained from the analysis of the Raman and IR spectra reveal that these metal-MT complexes predominantly contain beta-sheet elements (about 60%), whereas they lack alpha-helices. These structural features slightly depend on the divalent metal bound. In particular, Cd(II) binding to QsMT induces a slight increase of the beta-sheet percentage, as well as a decrease in beta-turn elements with respect to Zn(II) binding. Conversely, the in vivo capability of QsMT to inglobe metal and sulfide ions is metal-depending. Spectroscopic vibrational data also confirm the presence of sulfide ligands in the metal clusters of both Zn- and Cd-QsMT, while the participation of the spacer His residue in metal coordination was only found in Cd-QsMT, in agreement with the CD results. Overall data suggest different coordination environments for Zn(II) and Cd(II) ions in QsMT.

The Cd(II)-binding abilities of recombinant Quercus suber metallothionein: bridging the gap between phytochelatins and metallothioneins.

In this work, we have analyzed both at stoichiometric and at conformational level the Cd(II)-binding features of a type 2 plant metallothionein (MT) (the cork oak, Quercus suber, QsMT). To this end four peptides, the wild-type QsMT and three constructs previously engineered to characterize its Zn(II)- and Cu(I)-binding behaviour, were heterologously produced in Escherichia coli cultures supplemented with Cd(II), and the corresponding complexes were purified up to homogeneity. The Cd(II)-binding ability of these recombinant peptides was determined through the chemical, spectroscopic and spectrometric characterization of the recovered clusters. Recombinant synthesis of the four QsMT peptides in cadmium-rich media rendered complexes with a higher metal content than those obtained from zinc-supplemented cultures and, consequently, the recovered Cd(II) species are nonisostructural to those of Zn(II). Also of interest is the fact that three out of the four peptides yielded recombinant preparations that included S(2-)-containing Cd(II) complexes as major species. Subsequently, the in vitro Zn(II)/Cd(II) replacement reactions were studied, as well as the in vitro acid denaturation and S(2-) renaturation reactions. Finally, the capacity of the four peptides for preventing cadmium deleterious effects in yeast cells was tested through complementation assays. Consideration of all the results enables us to suggest a hairpin folding model for this typical type 2 plant Cd(II)-MT complex, as well as a nonnegligible role of the spacer in the detoxification function of QsMT towards cadmium.