Biopharmaceutical optimization in neglected diseases for paediatric patients by applying the provisional paediatric biopharmaceutical classification system

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146268/1/bcp13650.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146268/2/bcp13650_am.pd

Reduced Salivary Lactoferrin Levels in Early-Onset Alzheimer's Disease

Grants from Instituto de Salud Carlos III (PI22CIII/00042), CIBERNED (CB07/502, CB06/05/1111, PI2021/03), the Spanish Ministry of Economy and Competitiveness (PID2020-119978RB-I00) and the Andalucía-FEDER Program (UPO-1380913).S

Non-canonical NFκB activation promotes chemokine expression in podocytes

TNF-like weak inducer of apoptosis (TWEAK) receptor Fn14 is expressed by podocytes and Fn14 deficiency protects from experimental proteinuric kidney disease. However, the downstream effectors of TWEAK/Fn14 in podocytes are poorly characterized. We have explored TWEAK activation of non-canonical NFκB signaling in cultured podocytes. In cultured podocytes, TWEAK increased the expression of the chemokines CCL21, CCL19 and RANTES in a time-dependent manner. The inhibitor of canonical NFκB activation parthenolide inhibited the CCL19 and the early RANTES responses, but not the CCL21 or late RANTES responses. In this regard, TWEAK induced non-canonical NFκB activation in podocytes, characterized by NFκB2/p100 processing to NFκB2/p52 and nuclear migration of RelB/p52. Silencing by a specific siRNA of NIK, the upstream kinase of the non-canonical NFκB pathway, prevented CCL21 upregulation but did not modulate CCL19 or RANTES expression in response to TWEAK, thus establishing CCL21 as a non-canonical NFκB target in podocytes. Increased kidney Fn14 and CCL21 expression was also observed in rat proteinuric kidney disease induced by puromycin, and was localized to podocytes. In conclusion, TWEAK activates the non-canonical NFκB pathway in podocytes, leading to upregulation of CCL21 expression. The non-canonical NFκB pathway should be explored as a potential therapeutic target in proteinuric kidney disease.Grants support: FEDER funds and FIS ISCIII-RETIC REDinREN RD12/0021, PI15/00298, PI13/00047, CP14/00133, CP12/03262, Spanish Society of Nephrology, FRIAT-IRSIN, Comunidad de Madrid (CIFRA S2010/ BMD-2378), CYTED IBERERC, Programa Intensificación Actividad Investigadora (ISCIII) to AO, Miguel Servet to MDSN and ABS and FIS to LVR and LG

Influence of different organoclays on the curing, morphology, and dynamic mechanical properties of an epoxy adhesive

The thermal, mechanical, and adhesive properties of nanoclay-modified adhesives were investigated. Two organically modified montmorillonites: Cloisite 93A (C93A) and Nanomer I.30E (I.30E) were used as reinforcement of an epoxy adhesive. C93A and I.30E are modified with tertiary and primary alkyl ammonium cations, respectively. The aim was to study the influence of the organoclays on the curing, and on the mechanical and adhesive properties of the nanocomposites. A specific goal was to compare their behavior with that of Cloisite30B/epoxy and Cloisite15A/ epoxy nanocomposites that we have previously studied. Both C30B and C15A are modified with quaternary alkyl ammonium cations. Differential scanning calorimetry results showed that the clays accelerate the curing reaction, an effect that is related to the chemical structure of the ammonium cations. The three Cloisite/nanocomposites showed intercalated clay structures,the interlayer distance was independent of the clay content. The I.30E/epoxy nanocomposites presented exfoliated structure due to the catalytic effect of the organic modifier. Clay-epoxy nanocompo-sites showed lower glass transition temperature (Tg) and higher values of storage modulus than neat epoxy thermoset, with no significant differences between exfoliated or intercalated nanocom-posites. The shear strength of aluminum joints using clay/epoxy adhesives was lower than with the neat epoxy adhesive. The wáter aging was less damaging for joints with I.30E/epoxy adhesive

Betunes modificados con azufre: aditivos estabilizadores

En el presente trabajo se estudia la influencia de aditivos encaminados a conseguir la estabilidad de dichos betunes modificados. Mediante medidas de viscosidad y penetración se ha comprobado que la presencia combinada de diciclopentadieno + aminas, favorece la interacción del azufre con el betún por formación de polisulfuros. Asimismo, se ha analizado la influencia de inhibidores de radicales libre

Ternary nanocomposites: curing, morphology and mechanical properties of epoxy/thermoplastic/organoclay systems

The influence of two organically modified montmorillonites on the curing, morphology and mechanical properties of epoxy/poly(vinyl acetate)/organoclay ternary nanocomposites was studied. The organoclays and poly(vinyl acetate) (PVAc) provoked contrary effects on the epoxy curing reaction. Ternary nanocomposites developed different morphologies depending on the PVAc content, that were similar to those observed in the epoxy/PVAc binary blends. The organoclays were only located in the epoxy phase independently of the morphology. All nanocomposites showed intercalated structures with similar clay interlayer distances. Both PVAC and organoclays lowered the Tg of the epoxy phase, the presence of clays did not influence the Tg of the PVAc phase. The addition of the organoclays to the epoxy improved stiffness but lowered ductility while the adition of PVAc improved toughness although reduced stiffness of epoxy thermoset. Ternary nanocomposites exhibited optimal properties that combine the favourable effects of the clay and the thermoplastic

Influence of graphene nanoplatelets on curing and mechanical properties of graphene/epoxy nanocomposites.

The influence of graphene nanoplatelets (GNPs) on the curing of an epoxy resin based on diglycidyl ether of bisphenol A (DGEBA) and cross-linked with 4,4′ diaminodiphenylmethane (DDM) was studied. Dynamic mechanical properties and tensile properties of the corresponding graphene/epoxy nanocomposites were obtained. Two compositions 1 and 5 mass% of GNPs were studied. The cross-linking reaction of the epoxy resin is accelerated in dispersions with 5 mass% GNPs. In the presence of GNPs, the curing reaction becomes less exothermic, obtaining less perfect epoxy networks compared to neat epoxy (DGEBA–DDM) thermoset. Accordingly, the glass transition temperatures (Tg) of the nanocomposites are lower than that of the neat epoxy thermoset. This effect is not detected for low content of graphene (1 mass%). Protocol of curing having two isothermal steps leads to more perfect networks than the dynamic curing in the DSC. The Tg reduction is minimized in the samples cured through two isothermal steps. The storage moduli of the nanocomposite containing 5 mass% graphene, both in the glassy (T Tg) states, are higher than the ones of neat epoxy thermoset, being most pronounced this effect at T > Tg. Tensile tests confirmed the higher elastic moduli of the nanocomposites; however, a decrease in strain at break and tensile strength was observed for the nanocomposite containing 5 mass% of GNPs. This brittle behavior is consistent with the morphology of the samples studied by scanning electron microscopy

Cure behavior and mechanical properties of graphene/epoxy nanocomposites

In this work we study the curing process of an epoxy resin reinforced with graphene nanoplatelets and the thermal and mechanical properties of the obtained nanocomposites, in order to clarify the effect of GNPs on these properties