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Catalytic reactions that use metal complexes as substrates, rather than catalysts, are nearly unknown. We recently demonstrated that certain flavins (FLs) are potent redox photocatalysts capable of converting PtIV anticancer prodrug complexes into PtII drugs in the biological environment. Herein, we investigate the mechanism of these artificial photocatalytic reactions employing four different free flavins, namely riboflavin (Rf), flavin mononucleotide (FMN), tetra-O-acetyl riboflavin (TARF) and lumiflavin (Lf), and the flavoprotein miniSOG (mini Singlet Oxygen Generator) together with a panel of PtIV substrates conveniently selected. NMR, steady-state and time-resolved optical spectroscopy studies highlight that light activation of FLs in the presence of NADH as electron donor (pH 7–7.5) eventually leads to the generation of the reduced FLH– species which catalyzes the PtIV-to- PtII conversion with turnover frequency (TOF) values ranging between 1.3 and 30 min–1, and turnover number (TON) values reaching 500. Comparable catalytic efficiency is also found for reactions performed in cell culture medium. Density functional theory suggests that activation via reduction of the PtIV substrates may be influenced by H-bonding interactions between the FL catalyst and the metal substrate and confirm that both the isoalloxazine and ribityl moieties of the FLs determine the catalytic efficiency of the process. The FMN-containing miniSOG is a less effective catalyst (TOFs < 5.6 min–1) since the formation of the doubly reduced FMNH– competes with an electron transfer reaction with the protein matrix which quenches the FMN triplet-excited state to give a singly-reduced FMN•–.

Background/objectives A high body mass index increases the risk of severe pancreatitis and associated mortality. Our aims were: (1) To determine whether obesity affects the release of extracellular nucleosomes in patients with pancreatitis; (2) To determine whether pancreatic ascites confers lipotoxicity and triggers the release of extracellular nucleosomes in lean and obese rats. Methods DNA and nucleosomes were determined in plasma from patients with mild or moderately severe acute pancreatitis either with normal or high body mass index (BMI). Lipids from pancreatic ascites from lean and obese rats were analyzed and the associated toxicity measured in vitro in RAW 264.7 macrophages. The inflammatory response, extracellular DNA and nucleosomes were determined in lean or obese rats with pancreatitis after peritoneal lavage. Results Nucleosome levels in plasma from obese patients with mild pancreatitis were higher than in normal BMI patients; these levels markedly increased in obese patients with moderately severe pancreatitis vs. those with normal BMI. Ascites from obese rats exhibited high levels of palmitic, oleic, stearic, and arachidonic acids. Necrosis and histone 4 citrullination-marker of extracellular traps-increased in macrophages incubated with ascites from obese rats but not with ascites from lean rats. Peritoneal lavage abrogated the increase in DNA and nucleosomes in plasma from lean or obese rats with pancreatitis. It prevented fat necrosis and induction of HIF-related genes in lung. Conclusions Extracellular nucleosomes are intensely released in obese patients with acute pancreatitis. Pancreatitis-associated ascitic fluid triggers the release of extracellular nucleosomes in rats with severe pancreatitis.

Chromatin remodeling seems to regulate the patterns of proinflammatory genes. Our aim was to provide new insights into the epigenetic mechanisms that control transcriptional activation of early-and late-response genes in initiation and development of severe acute pancreatitis as a model of acute inflammation. Chromatin changes were studied by chromatin immunoprecipitation analysis, nucleosome positioning, and determination of histone modifications in promoters of proinflammatory genes in vivo in the course of taurocholate-induced necrotizing pancreatitis in rats and in vitro in rat pancreatic AR42J acinar cells stimulated with taurocholate or TNF-alpha. Here we show that the upregulation of early and late inflammatory genes rely on histone acetylation associated with recruitment of histone acetyltransferase CBP. Chromatin remodeling of early genes during the inflammatory response in vivo is characterized by a rapid and transient increase in H3K14ac, H3K27ac, and H4K5ac as well as by recruitment of chromatin-remodeling complex containing BRG-1. Chromatin remodeling in late genes is characterized by a late and marked increase in histone methylation, particularly in H3K4. JNK and p38 MAPK drive the recruitment of transcription factors and the subsequent upregulation of early and late inflammatory genes, which is associated with nuclear translocation of the early gene Egr-1. In conclusion, specific and strictly ordered epigenetic markers such as histone acetylation and methylation, as well as recruitment of BRG-1-containing remodeling complex are associated with the upregulation of both early and late proinflammatory genes in acute pancreatitis. Our findings highlight the importance of epigenetic regulatory mechanisms in the control of the inflammatory cascade.

Summary The aim of the study was to compare the efficacy and tolerability of flutrimazole 1% powder vs. bifonazole 1% powder in treating tinea pedis. A multicentre, double blind, randomized, parallel and comparative study was conducted. Two hundred and twenty-two patients with clinically and mycologically confirmed tinea pedis were randomized to flutrimazole (n = 136) or bifonazole (n = 138) 1% powder applied twice daily for 4 weeks. The corresponding clinical cure rates were assessed at 2 and 4 weeks of treatment, and the global (clinical and mycological) cure rates were determined at the fourth week. Clinical cure rates were 83.5 and 82.4% for flutrimazole and bifonazole, respectively (95% CI: −0.0806 to 0.1009). Global cure rates were observed in 65.3 and 70.1% of patients treated with flutrimazole and bifonazole, respectively (95% CI: −0.0828 to 0.1779). Three non serious adverse events at the application site - itching (one patient per group) and dishydrotic eczema (one patient treated with flutrimazole) – were recorded during the study. These results support that flutrimazol 1% powder applied twice daily for a duration of 4 weeks is highly effective in the treatment of tinea pedis, showing a similar therapeutic profile with that of bifonazole 1% powder. Zusammenfassung Ziel der Studie war, Wirksamkeit und Vertraglichkeit von Flutrimazol-1%-Puder versus Bifonazol-1%-Puder in der Behandlung der Tinea pedis zu vergleichen. Es handelt sich um eine multizentrische, doppelblinde, randomisierte, parallele Vergleichsstudie. 222 Patienten mit klinisch und mykologisch bestatigter Tinea pedis wurden randomisiert zweimal taglich vier Wochen lang entweder mit Flutrimazol-1%-oder Bifonazol-1%-Puder behandelt. Die klinischen Heilungsraten wurden 2 und 4 Wochen, die globalen Heilungsraten (klinisch und mykologisch) 4 Wochen nach Behandlungsbeginn beurteilt. Die klinischen Heilungsraten betrugen 83.5% und 82.4% fur Flutrimazol bzw. Bifonazol, die globalen Heilungsraten 65.3% fur Flutrimazol und 70.1% fur Bifonazol. Drei leichtere Nebenwirkungsepisoden wurden beobachtet: Je eine pro Gruppe mit Juckreiz und ein Patient der Flutrimazol-Gruppe mit dishydrotischem Ekzem. Die Ergebnisse belegen. dass Flutrimazol-1%-Puder bei vierwochiger Anwendung zweimal taglich in der Behandlung von Tinea pedis hoch wirksam und im Therapieprofil der Bifonazol-1%-Puder-Behandlung gleichwertig ist.

El paso inexorable del tiempo y los condicionantes ambientales contribuyen al constante deterioro de los edificios. Si se trata de patrimonio cultural, su conservación y mantenimiento adquieren un cariz más relevante si cabe. En aquellos edificios en los que no se ha realizado conservación o ésta ha sido deficiente, el deterioro de la construcción obliga a una costosa rehabilitación, con una fase previa asociada al estudio de los procesos patológicos estructurales desarrollados. Se presenta una visión práctica sobre la integración de sistemas de instrumentación electrónica, adquisición de datos y desarrollo de software aplicados, de manera novedosa, al análisis de procesos patológicos estructurales, que permitan al investigador, entre otros: -monitorizar de manera remota, sin necesidad de desplazarse a la localización, la evolución en tiempo real de los datos recogidos por los sensores instalados, -realizar un histórico de los datos tomados, accesible tanto en forma de gráficas de evolución entre diferentes períodos de tiempo, como de fichero para su postprocesado, -establecer protocolos de actuación que evalúen sistemáticamente y de forma computerizada los factores que producen el deterioro en las edificaciones, definiendo alarmas automáticas en caso de que las magnitudes controladas excedan valores límites prefijados. Dicha integración se basa en la implantación de una arquitectura RTU sobre PC Industrial, junto a las tarjetas de adquisición de datos adecuadas al tipo de sensores dispuestos, que realiza ininterrumpidamente la recogida de los datos tomados, junto con la instalación de un servidor de aplicaciones, que periódicamente se comunica con el sistema, extrae los datos y les da persistencia en una base de datos, y finalmente un servidor web, que permite el acceso remoto a estos datos mediante una aplicación desarrollada en JavaFX que constituye una novedosa plataforma para el desarrollo de aplicaciones enriquecidas de Internet.

Glutathione oxidation and protein glutathionylation are considered hallmarks of oxidative stress in cells because they reflect thiol redox status in proteins. Our aims were to analyze the redox status of thiols and to identify mixed disulfides and targets of redox signaling in pancreas in experimental acute pancreatitis as a model of acute inflammation associated with glutathione depletion. Glutathione depletion in pancreas in acute pancreatitis is not associated with any increase in oxidized glutathione levels or protein glutathionylation. Cystine and homocystine levels as well as protein cysteinylation and gamma-glutamyl cysteinylation markedly rose in pancreas after induction of pancreatitis. Protein cysteinylation was undetectable in pancreas under basal conditions. Targets of disulfide stress were identified by Western blotting, diagonal electrophoresis, and proteomic methods. Cysteinylated albumin was detected. Redox-sensitive PP2A and tyrosine protein phosphatase activities diminished in pancreatitis and this loss was abrogated by N-acetylcysteine. According to our findings, disulfide stress may be considered a specific type of oxidative stress in acute inflammation associated with protein cysteinylation and gamma-glutamylcysteinylation and oxidation of the pair cysteine/cystine, but without glutathione oxidation or changes in protein glutathionylation. Two types of targets of disulfide stress were identified: redox buffers, such as ribonuclease inhibitor or albumin, and redox-signaling thiols, which include thioredoxin 1, APE1/Ref1, Keap1, tyrosine and serine/threonine phosphatases, and protein disulfide isomerase. These targets exhibit great relevance in DNA repair, cell proliferation, apoptosis, endoplasmic reticulum stress, and inflammatory response. Disulfide stress would be a specific mechanism of redox signaling independent of glutathione redox status involved in inflammation. (C) 2014 Elsevier Inc. All rights reserved.

Mitogen-activated protein kinases (MAPKs) are considered major signal transducers early during the development of acute pancreatitis. Pentoxifylline is a phosphodiesterase inhibitor with marked anti-inflammatory properties through blockade of extracellular signal regulated kinase (ERK) phosphorylation and tumor necrosis factor alpha production. Our aim was to elucidate the mechanism of action of pentoxifylline as an anti-inflammatory agent in acute pancreatitis. Necrotizing pancreatitis induced by taurocholate in rats and taurocholate-treated AR42J acinar cells were studied. Phosphorylation of ERK and ERK kinase (MEK1/2), as well as PP2A, PP2B, and PP2C serine/threonine phosphatase activities, up-regulation of proinflammatory genes (by reverse transcription-polymerase chain reaction and chromatin immunoprecipitation), and recruitment of transcription factors and histone acetyltransferases/deacetylases to promoters of proinflammatory genes (egr-1, atf-3, inos, icam, il-6, and tnf-alpha) were determined in the pancreas during pancreatitis. Pentoxifylline did not reduce MEK1/2 phosphorylation but prevented the marked loss of serine/threonine phosphatase PP2A activity induced by taurocholate in vivo without affecting PP2B and PP2C activities. The rapid loss in PP2A activity induced by taurocholate in acinar cells was due to a decrease in cAMP levels that was prevented by pentoxifylline. Pentoxifylline also reduced the induction of early (egr-1, atf-3) responsive genes and abrogated the up-regulation of late (inos, icam, il-6, tnf-alpha) responsive genes and recruitment of transcription factors (nuclear factor kappaB and C/EBPbeta) and histone acetyltransferases to their gene promoters during pancreatitis. In conclusion, the beneficial effects of pentoxifylline--and presumably of other phosphodiesterase inhibitors--in this disease seem to be mediated by abrogating the loss of cAMP levels and PP2A activity as well as chromatin-modifying complexes very early during acute pancreatitis.

Acute pancreatitis is an acute inflammatory process localized in the pancreatic gland that frequently involves peripancreatic tissues. It is still under investigation why an episode of acute pancreatitis remains mild affecting only the pancreas or progresses to a severe form leading to multiple organ failure and death. Proinflammatory cytokines and oxidative stress play a pivotal role in the early pathophysiological events of the disease. Cytokines such as interleukin 1beta and tumor necrosis factor alpha initiate and propagate almost all consequences of the systemic inflammatory response syndrome. On the other hand, depletion of pancreatic glutathione is an early hallmark of acute pancreatitis and reactive oxygen species are also associated with the inflammatory process. Changes in thiol homestasis and redox signaling decisively contribute to amplification of the inflammatory cascade through mitogen activated protein kinase (MAP kinase) pathways. This review focuses on the relationship between oxidative stress, pro-inflammatory cytokines and MAP kinase/protein phosphatase pathways as major modulators of the inflammatory response in acute pancreatitis. Redox sensitive signal transduction mediated by inactivation of protein phosphatases, particularly protein tyrosin phosphatases, is highlighted.

This paper presents 2D finite difference time domain (FDTD) and finite element (FE) modeling of liquid crystal (LC) devices. The enhancements to standard FDTD required for fully non-diagonal tensor materials such as LCs are outlined and they have been implemented in an in-house code. The results have been validated against a commercial FE package and good agreement is observed. The codes are then used to study in-filling of photonic crystal devices, in particular a benchmark structure being used a part of the COST P11 activity is used. Results are shown for transmission through the device and the effects of LC in-filling and director field rotation are seen

Acute pancreatitis is an inflammation initially localized in the pancreatic gland which may lead to local and systemic complications. The development of severe acute pancreatitis is mediated by pathophysiological mechanisms involved in the systemic inflammatory response, cytokines and oxidative stress being their components of major importance. Nevertheless, it is still unknown why an episode of acute pancreatitis remains mild or progresses to a severe form. Activated leukocytes are the main source of cytokines. Interleukin 1beta and tumor necrosis factor alpha (TNF-alpha) initiate and propagate almost all the consequences of the systemic inflammatory response syndrome, leading to amplification of the inflammatory response. It is noteworthy that the systemic inflammatory response is restrained and the rate of mortality decreased in acute pancreatitis when TNF-alpha is blocked with specific antibodies or in knock-out mice deficient in its receptors. A synergy between pro-inflammatory cytokines and oxidative stress occurs in the development of the inflammatory response in acute pancreatitis. Pro-inflammatory cytokines and oxidative stress trigger common signal transduction pathways that lead to amplification of the inflammatory cascade, mainly through activation of mitogen-activated protein kinases (MAPK) and nuclear factor kappaB (NF-kappaB). Furthermore, pro-inflammatory cytokines, particularly TNF-alpha, and oxidative stress promote each other generating a vicious circle in acute pancreatitis. This cross-talk that arises between pro-inflammatory cytokines and oxidative stress greatly contributes to amplification of the uncontrolled inflammatory cascade through MAPK and NF-kappaB.

[EN]: The best conditions for the refining of shea butter usedin cosmetic industries are defined. The objective is to obtain a bleached, deodorized fat, with a 3% maximun free acidity and a high amount of unsaponifiable matter having minimal losses with respect to the initial sample. The following variables have been studied: phosphoric acid proportion in degumming, bleaching clays and active carbon percentages in bleaching, and temperature/time in the stage of deodorization. The results demonstrate that good quality shea butter can be obtained by physical refining if the level of free fatty acid in the initial sample is lower than 5%. Otherwise, a neutralization is necessary, which should be partial in order to reduce the loss of unsapbliifable matter., [ES]: Se estudian las condiciones más adecuadas en la refinación de la manteca de karité para su uso en cosmética. El objetivo es conseguir un producto decolorado, desodorizado con acidez libre inferior al 3% e insaponificable elevado, con pérdidas mínimas sobre el existente en la muestra inicial. Se han estudiado las siguientes variables: proporción de ácido fosfórico en la fase de desgomado, cantidad de tierras decolorantes y carbón activo en la decoloración y temperatura/tiempo en la desodorización. Los resultados demuestran que puede obtenerse una grasa de buena calidad mediante refinación física cuando las muestras contienen menos de un 5% de acidez. En caso contrario es necesario una neutralización previa que debe ser parcial para disminuir al mínimo las pérdidas de compuestos del insaponificable.

In the last years, new technologies such as the brain-machine interfaces (BMI) have been incorporated in the rehabilitation process of subjects with stroke. These systems are able to detect motion intention, analyzing the cortical signals using different techniques such as the electroencephalography (EEG). This information could guide different interfaces such as robotic devices, electrical stimulation or virtual reality.A 40 years-old man with stroke with two months from the injury participated in this study. We used a BMI based on EEG. The subject's motion intention was analyzed calculating the event-related desynchronization. The upper limb motor function was evaluated with the Fugl-Meyer Assessment and the participant's satisfaction was evaluated using the QUEST 2.0. The intervention using a physical therapist as an interface was carried out without difficulty.The BMI systems detect cortical changes in a subacute stroke subject. These changes are coherent with the evolution observed using the Fugl-Meyer Assessment.Entrenamiento de las señales corticales a traves de un sistema BMI-EEG, evolucion e intervencion. A proposito de un caso.Introduccion. En los ultimos años estan incorporandose nuevas tecnologias en el tratamiento fisioterapeutico de pacientes con ictus, como las interfaces cerebro-maquina –brain-machine interface (BMI)–, capaces de detectar la intencion de movimiento analizando las señales corticales por medio de diferentes tecnicas, como la electroencefalografia (EEG). Estas señales se traducen en comandos con el fin de realizar una funcion. Caso clinico. Varon de 40 años con ictus de dos meses de evolucion, en el cual se empleo un dispositivo BMI-EEG. La intencion de movimiento del sujeto se analizo calculando la desincronizacion relacionada con el evento. La funcion motora del miembro superior fue evaluada con la escala de Fugl-Meyer, y el nivel de satisfaccion del paciente, mediante el cuestionario QUEST 2.0. La intervencion se llevo a cabo sin dificultad siendo el fisioterapeuta la interfaz. Conclusiones. Los sistemas BMI-EEG detectan cambios corticales en un sujeto con ictus subagudo. Estos cambios son coherentes con los cambios observados en escalas clinicas.

Hepatic gamma-cystathionase, a rate-limiting enzyme for the synthesis of L-cysteine from L-methionine in the trans-sulphuration pathway, exhibits significantly higher activity in the newly born infant as compared to the fetus. The aim of this work was: 1) To determine whether the increase in gamma-cystathionase activity occurring in the fetal-to-neonatal transition is due to up-regulation of its mRNA and protein, 2) To elucidate the mechanisms responsible for this increase in gamma-cystathionase activity. Our results show that expression of gamma-cystathionase at both the mRNA and protein levels was higher in newborn than in fetal liver. gamma-Cystathionase activity in fetal hepatocytes in vitro increased when incubated with tert-butyl-hydroperoxide at low concentration (0.01 mM). Hence, moderate oxidative stress would act as a signal to up-regulate gamma-cystathionase in the fetal to neonatal transition. Stress hormones, such as phenylephrine or glucagon also increased gamma-cystathionase activity in fetal hepatocytes. We also report a competitive inhibition of purified gamma-cystathionase by L-cysteine, which would help to maintain physiological low L-cysteine levels in hepatocytes. In conclusion, our results show that increased hepatic gamma-cystathionase activity in the fetal-to-neonatal transition is due to up-regulation of its gene expression mediated by stress hormones together with the physiological oxidative stress that occurs at birth.

This article discusses how new technologies and research areas such as interaction design and new resources such as conductive materials can challenge the current perception and reach of prints. As part of the Design Lab and Print Lab at Liverpool John Moores University School of Art and Design, since …. we have been running a series of experiments and workshops with a wide range of artists, printmakers, designers and makers. We began by questioning the role of the print as part of an interactive system that uses functional materials. We started our exploration from an interdisciplinary perspective, where printmaking and digital technologies co-exist, thus the engagement with the print shares many of the properties and affordances1 of a wide range of user interfaces. Our research tested the role of functional materials and the ways in which they might be used in a printmaking environment for interactive outputs.

El artículo tiene como objetivo presentar la metodología seguida para la puesta en marcha de la monitorización remota de la Iglesia del Seminario Mayor de Comillas. En primer lugar, se exponen los trabajos desarrollados referentes al registro de los daños existentes en la Iglesia. La finalidad fue la de disponer de datos de entrada para elegir las zonas en las que instalar los dispositivos de seguimiento, haciendo coincidir éstas con las áreas en las que los daños eran mayores. Así, el levantamiento de grietas fue elaborado a partir de la toma de datos realizada in situ, procediendo en gabinete a confeccionar planos en los que se representaron los daños registrados en arcos, contrafuertes, bóvedas, muros interiores y muros de fachada. En la toma de datos llevada a cabo, además de registrar el trazado de las distintas grietas se realizó una evaluación cualitativa de las mismas, clasificando éstas visualmente de forma aproximada por su espesor. Además, se realizó un reportaje fotográfico detallado con el fin de complementar la información recogida en los planos. Una vez localizadas las zonas de mayor concentración de daño, se dispusieron en las mismas una serie de puntos de control manual y sensores en continuo. De forma discreta se controlaron un total de 22 variables: 16 puntos de control para evaluar la apertura/cierre de grietas y 6 placas inclinométricas para detectar posibles desplomes de los muros. Por su parte, para poder realizar el control de forma continua se tiene planificado instalar en el edificio un total de 18 sensores: 7 LVDTs a modo de fisurómetros, 4 servoinclinómetros, 3 cintas de convergencia, 2 termohigrómetros, 1 veleta y 1 anemómetro. Dichos sensores se agruparon en tres estaciones de adquisición de datos que, a su vez, se encuentran conectadas a un PC Industrial en el que se almacenan las mediciones, equipado con dos baterías que garantizan el funcionamiento ininterrumpido del sistema durante aproximadamente una semana en caso de cese de la corriente eléctrica. Fue desarrollada una aplicación basada en JavaFX que, además de permitir la gestión remota de los datos almacenados en el servidor, posibilita la definición de alarmas y otra serie de funcionalidades interesantes, todo ello en un entorno gráfico muy intuitivo. El sistema remoto de monitorización instalado ha posibilitado disponer de un control centralizado de los parámetros objeto de seguimiento. A modo de ejemplo, se presentan alguna de las mediciones registradas hasta la fecha.

The neoliberal model that has permeated higher education, has instrumentalised and commodified knowledge. This has forced academics to participate in the production of research to attract funding in the search of institutional stability. This paper problematizes the limited opportunities of integration of young Latin-American researchers in academic institutions. The purpose of this study is to explore the factors that hinder access to academia and unveil the weaknesses behind governmental policies for the development of employment programmes in both industry and academia. The methodology employed, is a critical discourse analysis of five biographies of Chilean and Mexican doctors. Results uncovered the use of discursive strategies that aim to legitimise reasons behind work fragility and the discursive construction of these actors. This article contributes to acknowledge similar patterns amongst Latin-American young researchers.

Cyclooxygenase-2, a key regulatory enzyme in the synthesis of the antifibrotic agent prostaglandin E2, is downregulated in lung tissue from patients with idiopathic pulmonary fibrosis.To investigate the association between COX2.3050 (G --C), COX2.8473 (C --T) and COX2.926 (G --C) single nucleotide polymorphisms (SNP) and the susceptibility to idiopathic pulmonary fibrosis and the progression of the disease.Genetic polymorphisms were analyzed in 121 out of 225 available control subjects and in all of 174 patients with idiopathic pulmonary fibrosis by real time polymerase chain reaction. Logistic regression analysis of covariance and chi-squares test were used for statistical analysis.While analysis of disease development did not find any significant association with single SNP genotype, a haplotype analysis revealed a strong association between the disease development and one haplotype [GC] at loci COX2.3050 and COX2.8473, and suggested a recessive genetic effect of this haplotype. Further analysis concluded that subjects having two copies of [GC] haplotype, or equivalently (GG/CC) genotype at the two SNPs, had an increased risk after adjusting for age and sex. Due to the interaction, this elevated risk increased slowly with age, and the estimated odds ratio (OR) decreased with age from OR = 1.4 at age 30 to OR = 1 at age 74 and OR = 0.96 at age SO. The OR was significantly greater than 1 up to age 66, and not significant for age older than 66. Therefore, the recessive effect of [GC] haplotype increased the risk of IPF of subjects younger than 66 years, but its effect diminished for seniors older than 66. One hundred and forty-nine patients with idiopathic pulmonary fibrosis were followed up for 33.7 +/- 2.1 months. Further analysis of disease progressions, defined by the changes in pulmonary function tests, did not reveal any association with either SNP genotypes or haplotypes.The carriage of double homozygote (GG/CC) at the SNP loci of COX2.3050 and COX2.8473 polymorphisms may increase the susceptibility to idiopathic pulmonary fibrosis, by approximately 1.4 folds at age 30 and by a smaller fold greater than 1 up to age 66 years, but not the progression of the disease. These findings may help to improve our understanding of idiopathic pulmonary fibrosis pathogenesis and may lead to the development of new therapeutic strategies.

Catalysis has strongly emerged in the field of medicinal inorganic chemistry as a suitable tool to deliver new drug candidates and to overcome drawbacks associated to metallodrugs. In this Concept article, we discuss representative examples of how catalysis has been applied in combination with metal complexes to deliver new therapy approaches. In particular, we explain key achievements in the design of catalytic metallodrugs that damage biomolecular targets and in the development of metal catalysis schemes for the activation of exogenous organic prodrugs. Moreover, we discuss our recent discoveries on the flavin-mediated bioorthogonal catalytic activation of metal-based prodrugs; a new catalysis strategy in which metal complexes are unconventionally employed as substrates rather than catalysts.

Since the discovery of cisplatin, light activation has been employed as a strategy to switch and improve the anticancer effects of platinum compounds. This contribution highlights some of the most representative discoveries obtained in the field of platinum-based photochemotherapy over the years.