Photodynamic therapy of cutaneous T-cell lymphoma cell lines mediated by 5-aminolevulinic acid and derivatives

The delta-amino acid 5-aminolevulinic acid (ALA), is the precursor of the endogenous photosensitiser Protoporphyrin IX (PpIX), and is currently approved for Photodynamic Therapy (PDT) of certain superficial cancers. However, ALA-PDT is not very effective in diseases in which T-cells play a significant role. Cutaneous T-cell lymphomas (CTCL) is a group of non-Hodgkin malignant diseases, which includes mycosis fungoides (MF) and Sézary syndrome (SS). In previous work, we have designed new ALA esters synthesised by three-component Passerini reactions, and some of them showed higher performance as compared to ALA. This work aimed to determine the efficacy as pro-photosensitisers of five new ALA esters of 2-hydroxy-N-arylacetamides (1f, 1 g, 1 h, 1i and 1 k) of higher lipophilicity than ALA in Myla cells of MF and HuT-78 cells of SS. We have also tested its effectiveness against ALA and the already marketed ALA methyl ester (Me-ALA) and ALA hexyl ester (He-ALA). Both cell Myla and SS cells were effectively and equally photoinactivated by ALA-PDT. Besides, the concentration of ALA required to induce half the maximal porphyrin synthesis was 209 μM for Myla and 169 μM for HuT-78 cells. As a criterion of efficacy, we calculated the concentration of the ALA derivatives necessary to induce half the plateau porphyrin values obtained from ALA. These values were achieved at concentrations 4 and 12 times lower compared to ALA, according to the derivative used. For He-ALA, concentrations were 24 to 25 times lower than required for ALA for inducing comparable porphyrin synthesis in both CTCL cells. The light doses for inducing 50% of cell death (LD50) for He-ALA, 1f, 1 g, 1 h and 1i were around 18 and 25 J/cm2 for Myla and HuT-78 cells respectively, after exposure to 0.05 mM concentrations of the compounds. On the other hand, the LD50s for the compound 1 k were 40 and 57 J/cm2 for Myla and HuT-78, respectively. In contrast, 0.05 mM of ALA and Me-ALA did not provoke photokilling since the concentration employed was far below the porphyrin saturation point for these compounds. Our results suggest the potential use of ALA derivatives for topical application in PDT treatment of MF and extracorporeal PDT for the depletion of activated T-cells in SS

Identifying non-destructive growth and maturity indexes of Prickly pear (Opuntia albicarpa S. Var. Burrona) and evaluation of freeze-drying conditions

Around the world, prickly pear fruits are valued as a source of dietary functional compounds and ingredients for innovative foods. Growth and physicochemical changes of Opuntia albicarpa S. fruits were recorded from 0 to 132 days-after-flowering (DAF) to identify non-destructive maturity-indices. Optimum-ripened fruits were freeze-dried to study physicochemical and functional characteristics of dried and rehydrated pulp. Principal component analysis confirmed growth turned into fruit ripening in DAF 99, and it lasted until DAF 132. Changes in color parameters of the peel correlated with fruit texture and pulp sugar content and taste index (P < 0.01). During freeze-drying, plate temperature had more significant effects than the thickness (P < 0.05). At 30°C, color ΔE between dried and fresh slices augmented, but, texture Δ´s (medium force) between rehydrated and fresh pulp was lower. Color tests could be used to harvest commercially-ripened fruits. Freeze-drying at 30°C improves the rehydrated slices texture regarding thickness maintaining rehydration coefficients.Las tunas son apreciadas en todo el mundo como fuente de compuestos funcionales dietarios e ingredientes para alimentos innovadores. Para identificar índices de maduración no destructivos, se registraron cambios en el crecimiento y en los parámetros fisicoquímicos de frutos de Opuntia albicarpa S. entre los días después de la floración (DAF) 0 al 132. Frutos con maduración óptima fueron liofilizados para evaluar características fisicoquímicas y funcionales de pulpa seca y rehidratada. El análisis de componentes principales confirmo que el crecimiento dio lugar a la maduración en el DAF 99 y ésta prosiguió hasta el DAF 132. Los cambios en parámetros de color en cáscara correlacionaron con la textura del fruto, y en pulpa, con el contenido de azúcares y el índice de sabor (P< 0.01). Durante la liofilización, la temperatura de placa tiene más efectos significativos que el espesor (P≤ 0.05). A 30°C, el ΔE de color entre la pulpa seca y fresca aumentó, pero, el Δ de textura (fuerza media) fue menor entre la rehidratada y la fresca. Se pueden emplear evaluaciones de color para cosechar frutos en su madurez comercial, y liofilizar estos frutos a 30°C mejora la textura sin importar el espesor, manteniendo los coeficientes de rehidratación.This work was supported by the SIMORELOS program of CONACyT

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Amazon tree dominance across forest strata

The forests of Amazonia are among the most biodiverse plant communities on Earth. Given the immediate threats posed by climate and land-use change, an improved understanding of how this extraordinary biodiversity is spatially organized is urgently required to develop effective conservation strategies. Most Amazonian tree species are extremely rare but a few are common across the region. Indeed, just 227 ‘hyperdominant’ species account for >50% of all individuals >10 cm diameter at 1.3 m in height. Yet, the degree to which the phenomenon of hyperdominance is sensitive to tree size, the extent to which the composition of dominant species changes with size class and how evolutionary history constrains tree hyperdominance, all remain unknown. Here, we use a large floristic dataset to show that, while hyperdominance is a universal phenomenon across forest strata, different species dominate the forest understory, midstory and canopy. We further find that, although species belonging to a range of phylogenetically dispersed lineages have become hyperdominant in small size classes, hyperdominants in large size classes are restricted to a few lineages. Our results demonstrate that it is essential to consider all forest strata to understand regional patterns of dominance and composition in Amazonia. More generally, through the lens of 654 hyperdominant species, we outline a tractable pathway for understanding the functioning of half of Amazonian forests across vertical strata and geographical locations

Tormenta eléctrica después de infarto agudo de miocardio en paciente con trombo apical de ventrículo izquierdo de formación reciente

La tormenta eléctrica postinfarto agudo de miocardio es una entidad amenazante de la vida y puede estar desencadenada por la isquemia activa secundaria a enfermedad no revascularizada. Adicionalmente la injuria miocárdica y sobre el sistema de conducción puede desencadenar la aparición de extrasístoles ventriculares, las cuales pueden participar como desencadenantes de arritmias ventriculares complejas. La adecuada identificación de las extrasístoles y otros posibles desencadenantes de la taquicardia ventricular son importantes para establecer las acciones terapéuticas que lleven a un adecuado control de la tormenta. Se presenta un caso de un paciente con tormenta arrítmica desencadenada por extrasístole ventricular frecuente con acoplamiento corto, la cual presentaba fenómeno de R en T, y era refractaria a manejo farmacológico, por lo que fue tratada exitosamente con ablación con catéter de radiofrecuencia

Aspergillus fumigatus en cardiodesfibrilador implantado cinco años antes

Las infecciones por hongos en dispositivos cardiacos son excepcionales y los casos reportados por Aspergillus son aún más escasos. Su diagnóstico requiere de un alto índice de sospecha, además de la extracción completa del dispositivo con el fin de documentarla. Se describe un caso raro de infección por Aspergillus fumigatus cinco años después de haber sido implantado un cardiodesfibrilador, se hace una revisión de la literatura y se repasan las principales características de la serie más amplia reportada