Proto-Aggregation studies in supramolecular hydrogels derived from succinic acid

Treball de Final de Grau en Química. Codi: QU0943. Curs acadèmic: 2015-201

Precious metal complexes of bis(pyridyl)allenes: synthesis and catalytic and medicinal applications

The incorporation of donor-type substituents on the allene core opens up the possibility of coordination complexes in which the metal is bonded to the donor groups, with or without interaction with the double bond system. Despite the challenges in the synthesis of such allene-containing metal complexes, their unique 3D environments and dual functionality (allene and metal) could facilitate catalysis and interaction with chemical and biological systems. Bis(pyridyl)allenes are presented here as robust ligands for novel Pd(II), Pt(IV) and Au(III) complexes. Their synthesis, characterisation and first application as catalysts of benchmark reactions for Pd, Pt and Au are presented with interesting reactivity and selectivities. The complexes have also been probed as antimicrobial and anticancer agents with promising activities, and the first studies on their unusual interaction with several DNA structures will open new avenues for research in the area of metallodrugs with new mechanisms of action

Recent advances in near infrared upconverting nanomaterials for targeted photodynamic therapy of cancer

Photodynamic therapy (PDT) is a well-established treatment of cancer that uses the toxic reactive oxygen species, including singlet oxygen (1O2), generated by photosensitiser drugs following irradiation of a specific wavelength to destroy the cancerous cells and tumours. Visible light is commonly used as the excitation source in PDT, which is not ideal for cancer treatment due to its reduced tissue penetration, and thus inefficiency to treat deep-lying tumours. Additionally, these wavelengths exhibit elevated autofluorescence background from the biological tissues which hinders optical biomedical imaging. An alternative to UV-Vis irradiation is the use of near infrared (NIR) excitation for PDT. This can be achieved using upconverting nanoparticles (UCNPs) functionalised with photosensitiser (PS) drugs where UCNPs can be used as an indirect excitation source for the activation of PS drugs yielding to the production of singlet 1O2 following NIR excitation. The use of nanoparticles for PDT is also beneficial due to their tumour targeting capability, either passively via the enhanced permeability and retention (EPR) effect or actively via stimuli-responsive targeting and ligand-mediated targeting (ie. using recognition units that can bind specific receptors only present or overexpressed on tumour cells). Here, we review recent advances in NIR upconverting nanomaterials for PDT of cancer with a clear distinction between those reported nanoparticles that could potentially target the tumour due to accumulation via the EPR effect (passive targeting) and nanoparticle-based systems that contain targeting agents with the aim of actively target the tumour via a molecular recognition process

Bilayer-coating strategy for hydrophobic nanoparticles providing colloidal stability, functionality, and surface protection in biological media

The surface chemistry of nanoparticles is a key step on the pathway from particle design towards applications in biologically relevant environments. Here, a bilayer-based strategy for the surface modification of hydrophobic nanoparticles is introduced that leads to excellent colloidal stability in aqueous environments and good protection against disintegration, while permitting surface functionalization via simple carbodiimide chemistry. We have demonstrated the excellent potential of this strategy using upconversion nanoparticles (UCNPs), initially coated with oleate and therefore dispersible only in organic solvents. The hydrophobic oleate capping is maintained and a bilayer is formed upon addition of excess oleate. The bilayer approach renders protection towards luminescence loss by water quenching, while the incorporation of additional molecules containing amino functions yields colloidal stability and facilitates the introduction of functionality. The biological relevance of the approach was confirmed with the use of two model dyes, a photosensitizer and a nitric oxide (NO) probe that, when attached to the surface of the UCNPs, retained their functionality to produce singlet oxygen and detect intracellular NO, respectively. We present a simple and fast strategy to protect and functionalize inorganic nanoparticles in biological media, which is important for controlled surface engineering of nanosized materials for theranostic applications

Recent advances in nanoparticle‑based targeting tactics for antibacterial photodynamic therapy

The rise of antibacterial drug resistance means treatment options are becoming increasingly limited. We must find ways to tackle these hard-to-treat drug-resistant and biofilm infections. With the lack of new antibacterial drugs (such as antibiotics) reaching the clinics, research has switched focus to exploring alternative strategies. One such strategy is antibacterial photodynamic therapy (aPDT), a system that relies on light, oxygen, and a non-toxic dye (photosensitiser) to generate cytotoxic reactive oxygen species. This technique has already been shown capable of handling both drug-resistant and biofilm infections but has limited clinical approval to date, which is in part due to the low bioavailability and selectivity of hydrophobic photosensitisers. Nanotechnology-based techniques have the potential to address the limitations of current aPDT, as already well-documented in anti-cancer PDT. Here, we review recent advances in nanoparticle-based targeting tactics for aPDT

Gold nanoparticle-based two-photon fluorescent nanoprobe for monitoring intracellular nitric oxide levels

Significance Nitric oxide (NO) is involved in the regulation of physiological and pathological mechanisms of the cardiovascular, nervous and immune systems; and plays an important role in cancer being involved in tumor growth and suppressing processes depending on its concentration. Approach The development of a near-infrared excitable nanoprobe, consisting of gold nanoparticles functionalized with a two-photon excitable NO probe, for the detection of intracellular NO is reported. Results The nanoprobe showed good selectivity towards NO over cellular interferences and excellent stability in aqueous-medium over time. The nanoprobe was able to selectively detect endogenous and exogenous NO in different cell lines and it accumulated in the acidic organelles showing negligible toxicity. Importantly, the nanoprobe showed potential to quantify intracellular NO concentrations in breast cancer cells. Conclusions The novel gold-based two-photon nanoprobe showed an excellent performance and versatility and could potentially be applied for the spatiotemporal monitoring of in vivo NO levels

Broad-spectrum photo-antimicrobial polymers based on cationic polystyrene and Rose Bengal

New strategies to fight bacteria and fungi are necessary in view of the problem of iatrogenic and nosocomial infections combined with the growing threat of increased antimicrobial resistance. Recently, our group has prepared and described two new readily available materials based on the combination of Rose Bengal (singlet oxygen photosensitizer) and commercially available cationic polystyrene (macroporous resin Amberlite® IRA 900 or gel-type resin IRA 400). These materials showed high efficacy in the antimicrobial photodynamic inactivation (aPDI) of Pseudomonas aeruginosa. Here, we present the photobactericidal effect of these polymers against an extended group of pathogens like Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, and the opportunistic yeast Candida albicans using green light. The most interesting finding is that the studied materials are able to reduce the population of both Gram-positive and Gram-negative bacteria with good activity, although, for C. albicans, in a moderate manner. In view of the results achieved and especially considering the inexpensiveness of these two types of photoactive polymers, we believe that they could be used as the starting point for the development of coatings for self-disinfecting surfaces

Check-List sistemático a pie de cama del paciente crítico

La transmisión de información sobre el paciente entre los médicos que dejan y asumen la responsabilidad de los pacientes (“handover”, “handoff” o “sign-out” en la literatura anglosajona) tiene lugar cientos de veces cada día en los hospitales de todo el mundo. Los errores en la transferencia de información son frecuentes: según la Joint Comission on Accreditation of Healthcare Organizations (JCAHO 2.003) casi el 70% de los incidentes críticos que ponen en riesgo la seguridad del paciente están causados por errores de comunicación. En el año 2.006 la US Joint Commision publicó unos objetivos de seguridad para el paciente (Joint Commission National Patient Safety Goal Requirement 2E 2.006) en los que recomienda: – Mejorar la comunicación eficaz entre el personal sanitario. – Poner en marcha (implementar) un “handoff” estandarizado que dé la oportunidad de preguntar y responder, y crear discusiones. Existen numerosos estudios en los que se proponen “reglas nemotécnicas” en forma de listas de verificación o checklist como herramienta de ayuda durante el pase o “handoff” de los paciente en las unidades de Reanimación

Genetic Screening for TLR7 Variants in Young and Previously Healthy Men With Severe COVID-19

Introduction: Loss-of-function TLR7 variants have been recently reported in a small number of males to underlie strong predisposition to severe COVID-19. We aimed to determine the presence of these rare variants in young men with severe COVID-19. Methods: We prospectively studied males between 18 and 50 years-old without predisposing comorbidities that required at least high-flow nasal oxygen to treat COVID-19. The coding region of TLR7 was sequenced to assess the presence of potentially deleterious variants. Results: TLR7 missense variants were identified in two out of 14 patients (14.3%). Overall, the median age was 38 (IQR 30-45) years. Both variants were not previously reported in population control databases and were predicted to be damaging by in silico predictors. In a 30-year-old patient a maternally inherited variant [c.644A>G; p.(Asn215Ser)] was identified, co-segregating in his 27-year-old brother who also contracted severe COVID-19. A second variant [c.2797T>C; p.(Trp933Arg)] was found in a 28-year-old patient, co-segregating in his 24-year-old brother who developed mild COVID-19. Functional testing of this variant revealed decreased type I and II interferon responses in peripheral mononuclear blood cells upon stimulation with the TLR7 agonist imiquimod, confirming a loss-of-function effect. Conclusions: This study supports a rationale for the genetic screening for TLR7 variants in young men with severe COVID-19 in the absence of other relevant risk factors. A diagnosis of TLR7 deficiency could not only inform on treatment options for the patient, but also enables pre-symptomatic testing of at-risk male relatives with the possibility of instituting early preventive and therapeutic interventions

IgG4-related disease: results from a multicenter Spanish registry

IgG4-related disease (IgG4-RD) is a rare entity consisting of inflammation and fibrosis that has been described in multiple organs. Concrete diagnostic criteria have been established recently and there is a lack of large series of patients.To describe the clinical presentation, histopathological characteristics, treatment and evolution of a series of IgG4-RD Spanish patients.A retrospective multicenter study was performed. Twelve hospitals across Spain included patients meeting the current 2012 consensus criteria on IgG4-RD diagnosis.Fifty-five patients were included in the study, 38 of whom (69.1%) were male. Median age at diagnosis was 53 years. Thirty (54.5%) patients were included in the Histologically Highly Suggestive IgG4-RD group and 25 (45.5%) in the probable IgG4-RD group. Twenty-six (47.3%) patients had more than 1 organ affected at presentation. The most frequently affected organs were: retroperitoneum, orbital pseudotumor, pancreas, salivary and lachrymal glands, and maxillary sinuses.Corticosteroids were the mainstay of treatment (46 patients, 83.6%). Eighteen patients (32.7%) required additional immunosuppressive agents. Twenty-four (43.6%) patients achieved a complete response and 26 (43.7%) presented a partial response (<50% of regression) after 22 months of follow-up. No deaths were attributed directly to IgG4-RD and malignancy was infrequent.This is the largest IgG4-RD series reported in Europe. Patients were middle-aged males, with histologically probable IgG4-RD. The systemic form of the disease was frequent, involving mainly sites of the head and abdomen. Corticosteroids were an effective first line treatment, sometimes combined with immunosuppressive agents. Neither fatalities nor malignancies were attributed to IgG4-RD